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'An underutilized tool: ' UV-LED lights can kill coronaviruses and HIV with the flip of a switch, study finds -- ScienceDaily | Researchers killed both viruses using UV-LED lights, which can alternate between white light and decontaminating ultraviolet ( UV) light. With a cheap retrofit, they could also be used in many standard lighting fixtures, giving them a `` unique appeal '' for public spaces, says Christina Guzzo, senior author of the study.
`` We're at a critical time where we need to use every single possible stop to get us out of this pandemic, '' says Guzzo, an assistant professor in the department of biological sciences. `` Every mitigation strategy that can be easily implemented should be used. ''
UV lights kill viruses through radiation. Guzzo, alongside PhD students Arvin T. Persaud and Jonathan Burnie, first tested the lights on bacterial spores notorious for their resistance to this radiation ( known as Bacillus pumilus spores).
`` If you're able to kill these spores, then you can reasonably say you should be able to kill most other viruses that you would commonly encounter in the environment, '' says Guzzo, principal investigator at the Guzzo Lab.
Within 20 seconds of UV exposure, the spores ' growth dropped by 99 per cent.
The researchers then created droplets containing coronaviruses or HIV, to mimic typical ways people encounter viruses in public, such as from coughing, sneezing and bleeding. The droplets were then exposed to UV light and placed in a culture to see if any of the virus remained active. With just 30 seconds of exposure, the virus ' ability to infect dropped by 93 per cent.
Upon testing the viruses at different concentrations, they found samples with more viral particles were more resistant to the UV lights. But even with a viral load so high Guzzo calls it `` the worst-case scenario, '' infectivity dropped 88 per cent.
Though it wasn't included in the study, Guzzo and her students also compared UV light to two heavy duty disinfectants used in lab research. They found the lights were similarly effective in their ability to deactivate viruses.
`` I was really surprised that UV could perform on the same level of those commonly used lab chemicals, which we regard as the gold standard, '' she says. `` That made me think, 'Oh, my gosh, this is a legitimate tool that's really underutilized. ' ''
Balance UV's pros and cons with clever use, researchers say
While the lights still left a small percentage of the virus viable, Guzzo references the `` Swiss cheese model '' of defence against COVID. Every strategy to fight the spread has its holes, but every layer is another chance to stop straggling virus particles.
Repeated exposure to UV light is key to catching those missed particles -- fortunately, it's as easy as flipping a switch. It's also simpler to change a light bulb than an air filtration system. Guzzo notes that UV-LEDs are cheap and could be easy to retrofit in existing light fixtures, and that the bulbs are long-lasting and simple to maintain.
`` You could disinfect in a way that wouldn't be infringing on people's enjoyment of that everyday 'normal ' life that they long for, '' Guzzo says.
The lights also benefit from automation. A standardized, germicidal dose of light can be delivered each time, while the process of wiping down spaces with disinfectants leaves room for human error. Chemicals and waste from these disinfectants also end up in watersheds and landfills as hands are washed and wipes thrown away.
But the lights aren't harmless, and there's a reason for wearing sunscreen and sunglasses -- UV radiation damages nucleic acid, and repeated, prolonged exposure is harmful. That's why Guzzo says the lights should be used when public spaces are empty, such as vacated buses that have finished their routes, or empty elevators travelling between floors. Escalator handrails could be continuously disinfected by putting UV lights in the underground part of the track, cleaning it with each rotation.
Safe Antivirus Technologies, Inc., a Toronto-based start-up company that partnered with Guzzo for the study, is developing unique UV-LED lighting modules. With motion sensors, the lights automatically switch to UV light when a room is empty, then turn back to regular light with movement.
Funded by the Natural Sciences and Engineering Research Council ( NSERC) Alliance COVID-19 Grant and published in the Virology Journal, this study highlights UV-LEDs as a tool that could be used beyond the pandemic, ideally to help prevent another.
`` Worldwide events like the COVID-19 pandemic, as terrible as they are, hopefully can still be learned from, '' Guzzo says. `` One thing we learned is that this is an underutilized tool we should think more about implementing. '' | science |
Rehabilitation psychologists: Specialists you may not yet know, but might one day need -- ScienceDaily | On a wet morning, an avid mountain biker loses control and is knocked out. They're hospitalized and initially make great strides in recovery. Months later, however, physical therapy hasn't fully resolved their feeling of being off-balance. They 've been avoiding biking, and even walking or running, because they're terrified of falling again.
Physical rehabilitation alone isn't working for these patients, and it's beginning to feel like recovery either won't come or won't end. These are circumstances in which a rehabilitation psychologist may be useful to guide them through the process of rehab and recovery, says Brigid Waldron-Perrine, Ph.D., a rehabilitation psychologist at Michigan Medicine.
`` You don't get a manual that comes with your injury that tells you how to navigate returning to your usual pattern of functioning, '' said Waldron-Perrine, who is also an associate professor of physical medicine and rehabilitation at U-M Medical School. `` In many cases, there are cognitive, behavioral or emotional barriers to progress that patients may not understand or know how to manage. As experts in human functioning, that's where we can be useful guides. ''
What is rehabilitation psychology?
Around 25% of Americans -- more than 60 million people -- have some type of disability. And millions of people are evaluated each year for traumatic brain injury, stroke, heart attacks and other conditions that can affect a person's mobility, cognition or other forms of functioning.
Many conditions don't have one straightforward treatment or `` answer '' that will result in certain success. There may not be a surgery to receive or pill to take that returns someone to optimal functioning. This uncertainty, Waldron-Perrine says, makes many patients very uncomfortable.
`` There is this sort of internalized belief in society that medicine is certain, but when you actually find yourself in the health care system, you realize very quickly that there is a great deal more uncertainty in medicine that anyone would have ever guessed, '' she said. `` Physicians often do not have the skill set or tools to respond to your discomfort with uncertainty. ''
Rehabilitation psychology addresses that uncertainty directly and encourages maximizing meaningful engagement in individually relevant ways. The field developed after World War II as soldiers were treated and was further advanced by Beatrice Wright in the 1970s and beyond. Wright notably expresses that coping with or adjusting to disability can not be fully understood without examining social and environmental factors that contribute to success in living or, alternately, distress.
Rehabilitation psychologists assess and treat cognitive, emotional and functional difficulties. Often working in multidisciplinary treatment teams, they help people to identify and overcome barriers to participation in life activities. If a patient who had a stroke because of high blood pressure or diabetes is not effectively managing their condition and continually ends up back in the hospital because they don't understand the physician's instructions or can't follow them, a rehab psychologist could be consulted.
`` We encourage the patient to understand their own needs and to assert those needs within the system, while assisting the system in meeting the care needs of the patient, '' Waldron-Perrine said. `` Oftentimes, addressing issues of communication or identifying problems to be addressed proactively can cut downstream costs of rehospitalization or redundant treatment because of lack of an integrated treatment plan. ''
Rehabilitation psychologists are integral members of the rehabilitation team at U-M Health, says Ted Claflin, M.D., associate director of the Michigan Medicine Inpatient Rehabilitation Facility.
`` Their understanding of human behavior allows them to better understand and treat psychological issues that confront our patients after a significant medical issue has happened, '' Claflin said. `` They can help people adjust to a new diagnosis, stay motivated during their recovery or deal with the emotional aftermath of hospitalization and/or treatment. ''
Where is the field of rehabilitation psychology heading?
During the COVID-19 pandemic, several studies have shown increasing demand for therapy after people experience long hospitalizations. While it may seem to be solely a growing demand for rehabilitation and psychologists dedicated to it, Waldron-Perrine says, it's just a need that has consistently not been met.
`` The need is being met in some places where the system recognizes the impact we can have not just at the patient level but at the clinician, therapy team and system level, '' she said. `` But the traditional medical model does not necessarily include rehabilitation psychology as a universally available resource, which means our services and reach are often limited. ''
Over several decades, as rehab psychologists have seen a need for more of their services, reimbursement margins for the care provided have dipped. The costs of tests and technology used to assist patients continue to rise, while services for patients are met with less coverage by insurance providers. Additionally, categorization by insurance panels can provide an additional barrier to accessing care, with separate coverage and authorizations often the only option for patients seeking what is considered `` mental health '' treatment, no matter the medical context.
In a recent `` state of the field '' study, Waldron-Perrine and several experts concluded that rehab psychologists need to be more active in promoting their unique contributions to health care, with the ultimate goal of being seen as `` go-to '' experts for the many roles they serve. The results are published in Rehabilitation Psychology.
In addition to cost savings from decreased hospitalization and redundant care, researchers say rehab psychologists can demonstrate their ability to assess the likelihood of successful outcomes for surgical intervention, such as bariatric surgery for obesity and spinal cord stimulator placement for back pain.
Ultimately, Waldron-Perrine says, there are simply not enough people in the field to optimize the care of the many and diverse patients seen in rehabilitation settings. The researchers noted that professional recruitment outreach needs to happen `` broadly and simultaneously '' at the high school, college and graduate school levels.
`` A rehabilitation psychologist recognizes that individuals have unique needs, and function within a complex system, '' Waldron-Perrine said. `` The goal is to maximize function and adaptation of every person in every aspect of life. With increased public awareness of this profession and increased recruitment from a relatively early level of education, we will hopefully see payoff in future research and public policy advocacy that contributes to meeting the needs of all patients and, ultimately, a more equitable world. ''
Additional authors include: Laurie N. Baker, Ph.D., Mark Barisa, Ph.D., Mark Sweatman, Ph.D., all of the Shepherd Center, and Robert L. Karol, Karol Neuro+Rehab Consulting, Greg A. Stern, PsyD, Courage Kenny Rehabilitation Institute | science |
Universal flu vaccine candidate -- ScienceDaily | Influenza, commonly referred to as `` flu, '' is a major global public health concern and a huge economic burden to societies. Seasonal influenza epidemics afflict between 13 to 100 million individuals annually, including three to five million cases of severe illness and 300,000 to 600,000 deaths worldwide. This represents a top global public health concern and an extraordinary economic burden to all societies. Pandemics are less frequent, but are generally more severe and pose a greater threat. Over the past century, there have been at least four devastating pandemics caused by the Influenza A virus which took the lives of hundreds of millions of individuals.
Although vaccination arguably represents the most effective way to prevent influenza, current vaccination strategies suffer from certain limitations, chief of which require current influenza vaccines to be updated annually to match circulating strains. This results in low vaccination take-up rates and poor coverage due to inaccurate prediction of circulating strains. Broadly protective, `` universal '' flu vaccines that do not need to be updated annually have therefore been pursued.
The highly conserved M2e peptide is a leading universal flu candidate; this peptide shares a conserved sequence with nearly all known human Influenza A strains. However, its limited ability to trigger a strong and long-lasting immune response has represented a major roadblock in its clinical development.
Researchers from the Yong Loo Lin School of Medicine at the National University of Singapore and Monash University in Melbourne have published a paper in the latest issue of Proceedings of the National Academy of Sciences of the United States of America where they successfully leveraged on a novel vaccine platform to deliver M2e to immune cells. This allowed them to prove that a single shot immunisation containing M2e was able to trigger long-lasting immune responses that could protect effectively against multiple strains of the flu.
The team was also able to demonstrate that this vaccination approach significantly enhanced protective immune responses in the context of pre-existing flu immunity. This scenario is particularly relevant in adult and elderly populations, where individuals have been exposed to flu viruses multiple times in the past and have low levels of M2e-specific antibodies in their blood circulation.
This vaccine approach has the potential to minimise the amount of M2e vaccine antigen ( substance that triggers the body's immune response against that itself) and the number of injections required for effective and long-lasting protection. It also removes the need for strong adjuvants ( a substance which enhances the body's immune response to an antigen), reducing potential side-effects, particularly in more vulnerable populations.
Beyond the flu, this vaccine platform could be employed to tackle a multitude of diseases, including infectious diseases such as COVID-19. The current COVID-19 pandemic has highlighted the importance of developing versatile, powerful platforms for the rapid deployment of vaccines against any highly virulent diseases. This new finding could lend itself to further development of vaccines for this, or any future, novel diseases. The team is currently working on a COVID-19 vaccine candidate using the same strategy. | science |
Hong Kong faces 'tough balancing act ' in easing border rules, official says | Hong Kong faces a tough balancing act as the city aims to lift some border restrictions for international travelers starting next month, according to a government official.
The Chinese territory intends to ease a travel ban on flights from nine countries, including the U.S., U.K. and Australia, and allow those travelers to quarantine in a hotel for seven days rather than 14. The changes will take effect on April 1.
`` It's very important that we have to cater to the needs of the international businessmen, but equally we also have a very large population in Hong Kong that needs the relaxation of the border restriction to the mainland of China, because that's also a very important part of Hong Kong for family reunion and businesses as well, '' Bernard Chan, convenor of the Executive Council, told CNBC's `` Squawk Box Asia '' on Monday.
`` So it's a very tough balancing act, '' he said, especially as China continues to see pockets of Covid outbreaks.
Hong Kong's executive council is a cabinet-like body that advises the city's chief executive.
China has been battling its worst Covid outbreak since early 2020, with local governments blaming the new omicron BA.2 variant for the current wave sweeping across the country. The biggest city Shanghai began a two-stage lockdown Monday.
Read CNBC's latest global coverage of the Covid pandemic:
Hong Kong has stuck firmly to a `` dynamic zero '' coronavirus policy, like in mainland China, seeking to stamp out all outbreaks with sweeping restrictions and quarantine.
The city reported 7,685 new Covid infections on Monday and 168 deaths, according to official data, as the latest wave of omicron infections continues to abate.
Between March 22 and 28, an average of 4,217.4 cases were reported per day, a decline from the average of 8,704.4 cases per day reported in the previous 7-day period, according to government data.
Still, Hong Kong lags behind regional peers — especially rival financial hub Singapore, which said last Thursday it will lift nearly all border restrictions for vaccinated travelers starting next month.
`` As the rest of the world is opening up, we need to try to figure a way out, '' said Chan. `` Starting from April 1, we start to reduce the hotel quarantine time from 14 days to 7 days. Obviously, it's not good enough, but still it's a big improvement, '' he added.
According to a recent report from the European Chamber of Commerce in Hong Kong, the city's zero- Covid strategy `` has come at a very high cost for Hong Kong's business community. ''
The survey found 49% of the companies polled said they are considering relocating their offices fully or partially in the next 12 months.
Moreover, existing restrictions have hampered the corporate strategy or hiring plans for 2 out of 3 companies in Hong Kong, the report added.
Acknowledging `` these are trying times '' for Hong Kong, Chan said he remains confident the city will regain its status as a global business hub when the pandemic ends.
`` I do believe Covid will be over. It's a matter of when it's over, '' he said. `` Hong Kong still is very attractive being a center of the Greater Bay of China and the economy of China continues to grow. I think people will come back. '' | business |
Autoantibodies against interleukin-1 receptor antagonist in multisystem inflammatory syndrome in children: a multicentre, retrospective, cohort study | BackgroundMultisystem inflammatory syndrome in children ( MIS-C) is a rare but serious complication of infection with SARS-CoV-2. A possible involvement of pathogenetically relevant autoantibodies has been discussed. Recently, neutralising autoantibodies against inflammatory receptor antagonists progranulin and interleukin-1 receptor antagonist ( IL-1Ra) were found in adult patients with critical COVID-19. The aim of this study was to investigate the role of such autoantibodies in MIS-C.MethodsIn this multicentre, retrospective, cohort study, plasma and serum samples were collected from patients ( 0–18 years) with MIS-C ( as per WHO criteria) treated at five clinical centres in Germany and Spain. As controls, we included plasma or serum samples from children with Kawasaki disease, children with inactive systemic juvenile idiopathic arthritis, and children with suspected growth retardation ( non-inflammatory control) across four clinical centres in Germany and Spain ( all aged ≤18 years). Serum samples from the CoKiBa trial were used as two further control groups, from healthy children ( negative for SARS-CoV-2 antibodies) and children with previous mild or asymptomatic COVID-19 ( aged ≤17 years). MIS-C and control samples were analysed for autoantibodies against IL-1Ra and progranulin, and for IL-1Ra concentrations, by ELISA. Biochemical analysis of plasma IL-1Ra was performed with native Western blots and isoelectric focusing. Functional activity of the autoantibodies was examined by an in vitro IL-1β-signalling reporter assay.FindingsSerum and plasma samples were collected between March 6, 2011, and June 2, 2021. Autoantibodies against IL-1Ra could be detected in 13 ( 62%) of 21 patients with MIS-C ( 11 girls and ten boys), but not in children with Kawasaki disease ( n=24; nine girls and 15 boys), asymptomatic or mild COVID-19 ( n=146; 72 girls and 74 boys), inactive systemic juvenile idiopathic arthritis ( n=10; five girls and five boys), suspected growth retardation ( n=33; 13 girls and 20 boys), or in healthy controls ( n=462; 230 girls and 232 boys). Anti-IL-1Ra antibodies in patients with MIS-C belonged exclusively to the IgG1 subclass, except in one patient who had additional IL-1Ra-specific IgM antibodies. Autoantibodies against progranulin were only detected in one ( 5%) patient with MIS-C. In patients with MIS-C who were positive for anti-IL-1Ra antibodies, free plasma IL-1Ra concentrations were reduced, and immune-complexes of IL-1Ra were detected. Notably, an additional, hyperphosphorylated, transiently occurring atypical isoform of IL-1Ra was observed in all patients with MIS-C who were positive for anti-IL-1Ra antibodies. Anti-IL-1Ra antibodies impaired IL-1Ra function in reporter cell assays, resulting in amplified IL-1β signalling.InterpretationAnti-IL-1Ra autoantibodies were observed in a high proportion of patients with MIS-C and were specific to these patients. Generation of these autoantibodies might be triggered by an atypical, hyperphosphorylated isoform of IL-1Ra. These autoantibodies impair IL-1Ra bioactivity and might thus contribute to increased IL-1β-signalling in MIS-C.FundingNanoBioMed fund of the University of Saarland, José Carreras Center for Immuno and Gene Therapy, Dr Rolf M Schwiete Stiftung, Staatskanzlei Saarland, German Heart Foundation, Charity of the Blue Sisters, Bavarian Ministry of Health, the Center for Interdisciplinary Clinical Research at University Hospital Münster, EU Horizon 2020.
Multisystem inflammatory syndrome in children ( MIS-C) is a rare but serious complication of infection with SARS-CoV-2. A possible involvement of pathogenetically relevant autoantibodies has been discussed. Recently, neutralising autoantibodies against inflammatory receptor antagonists progranulin and interleukin-1 receptor antagonist ( IL-1Ra) were found in adult patients with critical COVID-19. The aim of this study was to investigate the role of such autoantibodies in MIS-C.
In this multicentre, retrospective, cohort study, plasma and serum samples were collected from patients ( 0–18 years) with MIS-C ( as per WHO criteria) treated at five clinical centres in Germany and Spain. As controls, we included plasma or serum samples from children with Kawasaki disease, children with inactive systemic juvenile idiopathic arthritis, and children with suspected growth retardation ( non-inflammatory control) across four clinical centres in Germany and Spain ( all aged ≤18 years). Serum samples from the CoKiBa trial were used as two further control groups, from healthy children ( negative for SARS-CoV-2 antibodies) and children with previous mild or asymptomatic COVID-19 ( aged ≤17 years). MIS-C and control samples were analysed for autoantibodies against IL-1Ra and progranulin, and for IL-1Ra concentrations, by ELISA. Biochemical analysis of plasma IL-1Ra was performed with native Western blots and isoelectric focusing. Functional activity of the autoantibodies was examined by an in vitro IL-1β-signalling reporter assay.
Serum and plasma samples were collected between March 6, 2011, and June 2, 2021. Autoantibodies against IL-1Ra could be detected in 13 ( 62%) of 21 patients with MIS-C ( 11 girls and ten boys), but not in children with Kawasaki disease ( n=24; nine girls and 15 boys), asymptomatic or mild COVID-19 ( n=146; 72 girls and 74 boys), inactive systemic juvenile idiopathic arthritis ( n=10; five girls and five boys), suspected growth retardation ( n=33; 13 girls and 20 boys), or in healthy controls ( n=462; 230 girls and 232 boys). Anti-IL-1Ra antibodies in patients with MIS-C belonged exclusively to the IgG1 subclass, except in one patient who had additional IL-1Ra-specific IgM antibodies. Autoantibodies against progranulin were only detected in one ( 5%) patient with MIS-C. In patients with MIS-C who were positive for anti-IL-1Ra antibodies, free plasma IL-1Ra concentrations were reduced, and immune-complexes of IL-1Ra were detected. Notably, an additional, hyperphosphorylated, transiently occurring atypical isoform of IL-1Ra was observed in all patients with MIS-C who were positive for anti-IL-1Ra antibodies. Anti-IL-1Ra antibodies impaired IL-1Ra function in reporter cell assays, resulting in amplified IL-1β signalling.
Anti-IL-1Ra autoantibodies were observed in a high proportion of patients with MIS-C and were specific to these patients. Generation of these autoantibodies might be triggered by an atypical, hyperphosphorylated isoform of IL-1Ra. These autoantibodies impair IL-1Ra bioactivity and might thus contribute to increased IL-1β-signalling in MIS-C.
NanoBioMed fund of the University of Saarland, José Carreras Center for Immuno and Gene Therapy, Dr Rolf M Schwiete Stiftung, Staatskanzlei Saarland, German Heart Foundation, Charity of the Blue Sisters, Bavarian Ministry of Health, the Center for Interdisciplinary Clinical Research at University Hospital Münster, EU Horizon 2020.
The course of SARS-CoV-2 infection is typically mild or asymptomatic in children.1Ludvigsson JF Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults.Acta Paediatr. 2020; 109: 1088-1095Google Scholar, 2Liguoro I Pilotto C Bonanni M et al.SARS-COV-2 infection in children and newborns: a systematic review.Eur J Pediatr. 2020; 179: 1029-1046Google Scholar, 3O'Driscoll M Ribeiro Dos Santos G Wang L et al.Age-specific mortality and immunity patterns of SARS-CoV-2.Nature. 2021; 590: 140-145Google Scholar Multisystem inflammatory syndrome in children ( MIS-C; also known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2) is a rare but serious complication that usually occurs after SARS-CoV-2 infection following a latency period ( approximately 2–6 weeks).4Viner RM Whittaker E Kawasaki-like disease: emerging complication during the COVID-19 pandemic.Lancet. 2020; 395: 1741-1743Google Scholar, 5Verdoni L Mazza A Gervasoni A et al.An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.Lancet. 2020; 395: 1771-1778Google Scholar, 6Whittaker E Bamford A Kenny J et al.Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.JAMA. 2020; 324: 259-269Google Scholar, 7Dufort EM Koumans EH Chow EJ et al.Multisystem inflammatory syndrome in children in New York State.N Engl J Med. 2020; 383: 347-358Google Scholar, 8Feldstein LR Rose EB Horwitz SM et al.Multisystem inflammatory syndrome in US children and adolescents.N Engl J Med. 2020; 383: 334-346Google Scholar, 9Fernández-Sarmiento J De Souza D Jabornisky R Gonzalez GA Arias López MDP Palacio G Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 ( PIMS-TS): a narrative review and the viewpoint of the Latin American Society of Pediatric Intensive Care ( SLACIP) Sepsis Committee.BMJ Paediatr Open. 2021; 5e000894Google Scholar All affected children present with persistent fever while other clinical features might vary. Acute abdominal pain, diarrhoea or vomiting, muscle pain, headache, and fatigue have been reported.6Whittaker E Bamford A Kenny J et al.Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.JAMA. 2020; 324: 259-269Google Scholar Initial descriptions have highlighted overlapping features with those observed in Kawasaki disease, including bilateral conjunctival injection ( hyperaemia) and exanthema, swollen hands and feet, and so-called strawberry tongue, as well as cardiovascular features such as myocardial dysfunction, arterial hypotension, myocarditis, pericarditis, and involvement of the valves and coronary arteries ( dilatation or aneurysma) or systemic shock.4Viner RM Whittaker E Kawasaki-like disease: emerging complication during the COVID-19 pandemic.Lancet. 2020; 395: 1741-1743Google Scholar, 5Verdoni L Mazza A Gervasoni A et al.An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.Lancet. 2020; 395: 1771-1778Google Scholar Laboratory data have revealed excessive inflammation with highly elevated serum concentrations of C-reactive protein, procalcitonin, and ferritin, and elevated troponin and N-terminal pro-B-type natriuretic peptide reflecting cardiac involvement.6Whittaker E Bamford A Kenny J et al.Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.JAMA. 2020; 324: 259-269Google Scholar Furthermore, hyponatraemia, markers of coagulopathy ( elevated D-dimers and prolonged prothrombin time and partial thromboplastin time) and haematological abnormalities ( anaemia, lymphocytopenia, and thrombocytopenia or thrombocytosis) have been reported.10Rodriguez-Smith JJ Verweyen EL Clay GM et al.Inflammatory biomarkers in COVID-19-associated multisystem inflammatory syndrome in children, Kawasaki disease, and macrophage activation syndrome: a cohort study.Lancet Rheumatol. 2021; 3: e574-e584Google Scholar Most affected children need intensive care due to multiorgan failure and shock.7Dufort EM Koumans EH Chow EJ et al.Multisystem inflammatory syndrome in children in New York State.N Engl J Med. 2020; 383: 347-358Google Scholar, 8Feldstein LR Rose EB Horwitz SM et al.Multisystem inflammatory syndrome in US children and adolescents.N Engl J Med. 2020; 383: 334-346Google Scholar, 9Fernández-Sarmiento J De Souza D Jabornisky R Gonzalez GA Arias López MDP Palacio G Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 ( PIMS-TS): a narrative review and the viewpoint of the Latin American Society of Pediatric Intensive Care ( SLACIP) Sepsis Committee.BMJ Paediatr Open. 2021; 5e000894Google Scholar, 11Harwood R Allin B Jones CE A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 ( PIMS-TS): results of a national Delphi process.Lancet Child Adolesc Health. 2021; 5: 133-141Google Scholar, 12WHOMultisystem inflammatory syndrome in children and adolescents temporally related to COVID-19. Scientific brief.https: //www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19Date: May 15, 2020Date accessed: May 1, 2021Google Scholar, 13Esteve-Sole A Anton J Pino-Ramirez RM et al.Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease.J Clin Invest. 2021; 131144554Google Scholar
Research in contextEvidence before this studyBefore starting our analyses, we searched PubMed ( May 1, 2021) using the search terms “ MIS-C ”, “ PIMS ”, “ COVID-19 ”, and “ autoantibodies ” OR “ anti-IL-1Ra ” OR “ anti- progranulin ” for articles with these terms appearing in publication titles and abstracts of English language articles. Multisystem inflammatory syndrome in children ( MIS-C; also called paediatric inflammatory multisystem syndrome paediatric inflammatory temporally associated with SARS-CoV-2) has emerged as a rare but serious complication after infection with SARS-CoV-2 in children and adolescents. Published work has already described different autoantibody responses in COVID-19 and MIS-C and a possible pathogenetic involvement has been discussed, particularly in the context of type I interferon-targeting autoantibodies. Recently, neutralising autoantibodies against anti-inflammatory receptor antagonists progranulin and interleukin-1 receptor antagonist ( IL-1Ra) were identified in adult patients with critical COVID-19. Neutralising antibodies against IL-1Ra have also been reported in IgG4-associated disease. However, we found no published studies that have investigated the occurrence of antibodies against IL-1Ra or progranulin in MIS-C.Added value of this studyOur retrospective multicentre cohort study identified IL-1Ra-specific autoantibodies in a high proportion of patients with MIS-C, but not in healthy or disease controls. Generation of the anti-IL-1Ra antibodies might be triggered by an atypical, hyperphosphorylated isoform of IL-1Ra, which we observed in all autoantibody-positive patients with MIS-C. IL-1Ra-specific antibodies were also associated with decreased IL-1Ra plasma concentration and impaired IL-1Ra bioactivity. In contrast to critical COVID-19 in adults, in MIS-C, antibodies against IL-1Ra belonged predominantly to the IgG1 subclass and antibodies against progranulin were infrequent.Implications of all the available evidenceFunctional neutralising autoantibodies directed against IL-1Ra can contribute to excessive IL-1 signalling in MIS-C.
Before starting our analyses, we searched PubMed ( May 1, 2021) using the search terms “ MIS-C ”, “ PIMS ”, “ COVID-19 ”, and “ autoantibodies ” OR “ anti-IL-1Ra ” OR “ anti- progranulin ” for articles with these terms appearing in publication titles and abstracts of English language articles. Multisystem inflammatory syndrome in children ( MIS-C; also called paediatric inflammatory multisystem syndrome paediatric inflammatory temporally associated with SARS-CoV-2) has emerged as a rare but serious complication after infection with SARS-CoV-2 in children and adolescents. Published work has already described different autoantibody responses in COVID-19 and MIS-C and a possible pathogenetic involvement has been discussed, particularly in the context of type I interferon-targeting autoantibodies. Recently, neutralising autoantibodies against anti-inflammatory receptor antagonists progranulin and interleukin-1 receptor antagonist ( IL-1Ra) were identified in adult patients with critical COVID-19. Neutralising antibodies against IL-1Ra have also been reported in IgG4-associated disease. However, we found no published studies that have investigated the occurrence of antibodies against IL-1Ra or progranulin in MIS-C.
Our retrospective multicentre cohort study identified IL-1Ra-specific autoantibodies in a high proportion of patients with MIS-C, but not in healthy or disease controls. Generation of the anti-IL-1Ra antibodies might be triggered by an atypical, hyperphosphorylated isoform of IL-1Ra, which we observed in all autoantibody-positive patients with MIS-C. IL-1Ra-specific antibodies were also associated with decreased IL-1Ra plasma concentration and impaired IL-1Ra bioactivity. In contrast to critical COVID-19 in adults, in MIS-C, antibodies against IL-1Ra belonged predominantly to the IgG1 subclass and antibodies against progranulin were infrequent.
Functional neutralising autoantibodies directed against IL-1Ra can contribute to excessive IL-1 signalling in MIS-C.
Despite numerous published studies since its initial description, understanding of MIS-C pathogenesis remains limited. The formation of pathogenetically relevant autoantibodies has been suggested to contribute to a hyperinflammatory state.14Consiglio CR Cotugno N Sardh F et al.The immunology of multisystem inflammatory syndrome in children with COVID-19.Cell. 2020; 183: 968-981.e7Google Scholar, 15Gruber CN Patel RS Trachtman R et al.Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children ( MIS-C).Cell. 2020; 183 ( 95.e14): 982Google Scholar The autoantibody hypothesis is supported by, firstly, the observation of a latency period between SARS-CoV-2 infection and MIS-C onset, during which priming and activation of adaptive immune mechanisms might occur; and, secondly, the favourable clinical response of patients to intravenous immunoglobulins ( IVIGs) and glucocorticoids. Furthermore, the American College of Rheumatology recommends treatment with a high dose of the recombinant interleukin-1 receptor antagonist ( IL-1Ra) anakinra for IVIG-refractory patients with MIS-C.16Wikén M Hallén B Kullenberg T Koskinen LO Development and effect of antibodies to anakinra during treatment of severe CAPS: sub-analysis of a long-term safety and efficacy study.Clin Rheumatol. 2018; 37: 3381-3386Google Scholar, 17Henderson LA Canna SW Friedman KG et al.American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: version 1.Arthritis Rheumatol. 2020; 72: 1791-1805Google Scholar, 18Henderson LA Canna SW Friedman KG et al.American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: version 2.Arthritis Rheumatol. 2021; 73: e13-e29Google Scholar
Recently, in adult patients with critical COVID-19, we identified neutralising autoantibodies against progranulin,19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar an anti-inflammatory ligand of the pro-inflammatory receptors tumour necrosis factor receptor 1 ( TNFR1), TNFR2, and DR3 ( also known as TNF receptor superfamily members 1A, 1B, and 25),20Kessenbrock K Fröhlich L Sixt M et al.Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin.J Clin Invest. 2008; 118: 2438-2447Google Scholar, 21Zhu J Nathan C Jin W et al.Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair.Cell. 2002; 111: 867-878Google Scholar, 22Tang W Lu Y Tian QY et al.The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice.Science. 2011; 332: 478-484Google Scholar, 23Liu C Li XX Gao W Liu W Liu DS Progranulin-derived atsttrin directly binds to TNFRSF25 ( DR3) and inhibits TNF-like ligand 1A ( TL1A) activity.PLoS One. 2014; 9e92743Google Scholar that acts as direct receptor antagonist of TNFα and TL1A ( also known as TNF ligand superfamily member 15).22Tang W Lu Y Tian QY et al.The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice.Science. 2011; 332: 478-484Google Scholar, 23Liu C Li XX Gao W Liu W Liu DS Progranulin-derived atsttrin directly binds to TNFRSF25 ( DR3) and inhibits TNF-like ligand 1A ( TL1A) activity.PLoS One. 2014; 9e92743Google Scholar In these adult patients we also detected autoantibodies against IL-1Ra,19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar a ligand of the pro-inflammatory IL-1 receptor and antagonist of IL-1α and IL-1β binding and signalling. 24Dinarello CA Rosenwasser LJ Wolff SM Demonstration of a circulating suppressor factor of thymocyte proliferation during endotoxin fever in humans.J Immunol. 1981; 127: 2517-2519Google Scholar, 25Arend WP Joslin FG Massoni RJ Stimulation of production of interleukin-1 and an interleukin-1 inhibitor in human monocytes.Rheumatology. 1985; 24: 175-178Google Scholar, 26Arend WP Interleukin-1 receptor antagonist: discovery, structure and properties.Prog Growth Factor Res. 1990; 2: 193-205Google Scholar, 27Arend WP Interleukin 1 receptor antagonist. A new member of the interleukin 1 family.J Clin Invest. 1991; 88: 1445-1451Google Scholar, 28Dinarello CA Thompson RC Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro.Immunol Today. 1991; 12: 404-410Google Scholar The aim of this study was to investigate the role of such autoantibodies in MIS-C.
In this multicentre, retrospective, cohort study, serum and plasma samples were collected from patients ( ≤18 years) with MIS-C treated at five clinical centres in Germany and Spain. Blood samples of patients with MIS-C were drawn in the Department of Pediatric Cardiology ( Saarland University Hospital, Homburg, Germany), the Department of Pediatrics ( Klinikum Saarbrücken, Saarbrücken, Germany), the Department of Pediatric Rheumatology and Immunology ( University Children's Hospital Münster, Münster, Germany), the Department of Pediatrics ( Klinikum Kempten, Kempten, Germany), and the Department of Pediatrics ( Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain). All patients with MIS-C fulfilled the WHO criteria.12WHOMultisystem inflammatory syndrome in children and adolescents temporally related to COVID-19. Scientific brief.https: //www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19Date: May 15, 2020Date accessed: May 1, 2021Google Scholar As a control group, we collected plasma samples from patients with Kawasaki disease at the Hospital Sant Joan de Déu ( Universitat de Barcelona) and at the Department of Paediatric Cardiology ( Ludwig Maximilians University, Munich, Germany). Furthermore, we included plasma samples from children with inactive systemic juvenile idiopathic arthritis at the Department of Pediatric Rheumatology and Immunology ( University Children's Hospital Münster). As a non-inflammatory control group, serum samples were collected from children with suspected growth retardation at the Department of Pediatrics ( Saarland University, Homburg, Germany). We also included serum samples negative for SARS-CoV-2 antibodies from healthy paediatric control patients, referred to as healthy controls herein, and serum samples from children with a history of asymptomatic or mild COVID-19, from the CoKiBa study.29Laub O Leipold G Toncheva AA et al.Symptoms, SARS-CoV-2 antibodies, and neutralization capacity in a cross sectional-population of German children.Front Pediatr. 2021; 9678937Google Scholar Healthy controls were age and sex-matched with the MIS-C group ( multiple matched cases for each MIS-C group). Samples in the CoKiBa study were obtained 1–3 months after the peak of the first pandemic wave ( spring 2020) in Bavaria. Most control groups were aged 0–18 years apart from groups from the CoKiBa trial ( aged ≤17 years). Plasma samples of adult patients ( > 18 years) with critical COVID-19 were obtained from the Department of Internal Medicine V, Saarland University Medical School ( Homburg, Germany).
This study was approved by the Ethics Committee of the Saarland Medical Association ( reference number 41/21) and conducted according to the Declaration of Helsinki. All parents or guardians and adult patients signed written informed consent.
Baseline data including demographic characteristics, clinical manifestations, laboratory parameters, and current drug therapies at the time of blood sampling were collected by study staff with the exception of the CoKiBa study samples. In the CoKiBa trial, data were collected by questionnaire at the time of blood sampling. We were not able to obtain follow-up samples systematically but had access to longitudinal samples for two patients in the MIS-C group.
Product details of all kits and antibodies used are listed in the appendix ( p 38). ELISA for autoantibodies was performed as described previously.30Thurner L Preuss KD Fadle N et al.Progranulin antibodies in autoimmune diseases.J Autoimmun. 2013; 42: 29-38Google Scholar In brief, the antigens were obtained with use of the coding sequences of the GRN gene encoding progranulin and isoform 1 precursor of IL1RN, and were recombinantly expressed with a C-terminal FLAG tag in HEK293 cells under the control of a cytomegalovirus promoter ( pSFI).31Bornkamm GW Berens C Kuklik-Roos C et al.Stringent doxycycline-dependent control of gene activities using an episomal one-vector system.Nucleic Acids Res. 2005; 33: e137Google Scholar Total cell extracts were prepared and bound to Nunc MaxiSorp plates ( eBioscience, Frankfurt, Germany) precoated with murine anti-FLAG monoclonal antibody at a dilution of 1:2500 ( volume/volume; Sigma-Aldrich, Munich, Germany) at 4°C overnight. After blocking with 1·5% ( weight/volume) gelatin in Tris-buffered saline ( TBS) for 1 h at room temperature and washing steps with TBS with Triton X-100, the individual plasma samples were diluted 1:100. ELISA was performed according to standard manufacturer protocols with the antibodies: biotinylated goat antihuman heavy and light chain IgG at a dilution of 1:2500 ( Dianova, Hamburg, Germany); subclass-specific sheep antihuman IgG1, IgG2, IgG3, and IgG4 ( Binding Site Group, Birmingham, UK) at a dilution of 1:5000; goat antihuman IgM ( Dianova) at a dilution of 1:2500; or goat antihuman IgA ( Dianova) at a dilution of 1:2500. Following this step, corresponding biotinylated secondary antibodies were used for immunoassays performed to detect IgG subclasses and IgM. Peroxidase-labelled streptavidin ( Roche Applied Science, Indianapolis, IN, USA) was used at a dilution of 1:50 000. As a cutoff for positivity, the average of the optical density ( OD) of the negative samples plus three SDs was applied. To determine the epitope region of the anti-IL-1Ra antibodies, we expressed fragments of full-length IL-1Ra ( amino acids 59–75, 98–116, 125–143, and 161–177), and, as a control antigen, full-length IL-36Ra, with a C-terminal FLAG tag in HEK293 cells under the control of a cytomegalovirus promoter ( pSFI).31Bornkamm GW Berens C Kuklik-Roos C et al.Stringent doxycycline-dependent control of gene activities using an episomal one-vector system.Nucleic Acids Res. 2005; 33: e137Google Scholar As a control for possible bystander humoral immune responses, IgG antibodies directed against Clostridium tetani tetanus toxin ( Argio Biolaboratories, Hsinchu City, Taiwan) were analysed by ELISA.
Isoelectric focusing and western blotting ( including native western blotting with non-reducing sample pretreatment and gradient gels without SDS) were performed. Blocking was done overnight at 4°C in 10% non-fat dry milk ( weight/volume). Plasma samples were analysed for IL-1Ra isoforms. Plasma from anti-IL-1Ra antibody-positive patients was treated with alkaline phosphatase as previously described with FastAP Thermosensitive Alkaline Phosphatase ( Fermentas, Darmstadt, Germany).32Grass S Preuss KD Ahlgrimm M et al.Association of a dominantly inherited hyperphosphorylated paraprotein target with sporadic and familial multiple myeloma and monoclonal gammopathy of undetermined significance: a case-control study.Lancet Oncol. 2009; 10: 950-956Google Scholar
IL-1Ra plasma concentrations were measured with an IL1RA Human ELISA Kit ( Thermo Fisher Scientific, Waltham, MA USA) according to the manufacturer's instructions. The accuracy of IL-1Ra plasma concentrations measured by ELISA has been validated previously by a dilution series with recombinant human IL-1Ra in the presence of recombinant anti-IL-1Ra antibodies or anti-IL-1Ra antibodies purified from patient plasma.19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar Progranulin plasma concentrations were determined with a Progranulin ( human) ELISA Kit ( AdipoGen, Incheon, South Korea) according to the manufacturer's instructions.
For an IL-1β signalling reporter assay, HEK-Blue IL-1β Cells ( Invivogen, San Diego, CA, USA) were used, which react specifically to IL-1β and IL-1α by induction of nuclear factor-κB and activator protein 1, leading to expression of secreted embryonic alkaline phosphatase reporter. Recombinant IL-1Ra at 40 ng/mL ( Biozol, Eching, Germany) alone or with either rabbit antihuman IL-1Ra antibody at 5 μg/mL ( antibodies-online, Aachen, Germany), recombinant anti-SLP2 antibody at 5 μg/mL ( Abcam, Cambridge, UK), diluted plasma ( 1:20) from a patient with acute MIS-C and high-titred ( 1:800) anti-IL-1Ra antibodies, or diluted plasma ( 1:20) from the same patient 7 months after onset of MIS-C but without detectable anti-IL-1Ra antibodies, were preincubated for 2 h at room temperature. Subsequently, these compounds were added with either 2 ng/mL IL-1β ( Biozol) or 2 ng/mL TNF ( Biozol) in 100 μl Dulbecco's Modified Eagle Medium to HEK-Blue IL-1β reporter cells ( 2 × 104 cells per well) and incubated overnight at 37°C. Thereafter, 180 μL of each supernatant was collected, 20 μl QUANTI-Blue ( Invivogen) was added, and secreted embryonic alkaline phosphatase activity was measured at an OD of 655 nm. Experiments were performed in triplicate. Diluted plasma ( 1:20) from adult patients with critical COVID-19 with and without anti-IL-1Ra antibodies served as controls.
Differences in proportions of Anti-IL-1Ra autoantibody positivity between the MIS-C and control groups were compared by Fisher's exact test, not corrected for multiple testing. Associations between two categorical variables were tested with two-tailed Fisher's exact test. IL-1Ra plasma concentrations measured by ELISA were analysed for normality distribution with Shapiro–Wilk and Kolmogorov–Smirnov tests. Mean IL-1Ra plasma concentration in autoantibody-positive patients with MIS-C was compared with mean concentration in seronegative patients with MIS-C, and with mean values in the control groups, via Brown–Forsythe and Welch ANOVA and Dunnett's T3 multiple comparisons test. All analyses were repeated excluding two MIS-C cases that had received IVIGs before the blood sampling.
A p value less than 0·05 was regarded to indicate statistical significance. GraphPad Prism ( version 9.3.0) was used for analysis.
The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Serum and plasma samples analysed in this study were collected between March 6, 2011, and June 2, 2021. We analysed 21 patients ( 11 girls and ten boys) with MIS-C, with a median age of 7·0 years ( range 1·5–17·0 years), and a mean weight of 31·6 kg ( SD 19·2; range 9·8–71·8; table, appendix pp 1–2). All patients with MIS-C were seropositive or PCR positive ( or both seropositive and PCR positive) for SARS-CoV-2, with the exception of one patient who had only reported contact with SARS-CoV-2. The control groups comprised 146 children with asymptomatic or mild COVID-19 ( 72 girls and 74 boys, median age 8 years [ range 0–16 ]), 24 children with Kawasaki disease ( nine girls and 15 boys; median age 3·0 years [ 0·1–7·5 ]), ten children with systemic juvenile idiopathic arthritis in remission ( five girls and five boys; median age 15·5 [ 9·0–18·0 ]), 33 non-inflammatory patients with suspected growth retardation ( 13 girls and 20 boys; median age 10·6 years [ 3·0–15·3 ]), and 462 healthy controls ( 230 girls and 232 boys; median age 8 years [ 0–16 years ]). All samples from patients with MIS-C, with the exception of two patients, and all patients with Kawasaki disease were collected before administration of IVIGs. Further baseline characteristics of the MIS-C and control groups are presented in the table.TableStudy populationHealthy controls ( n=462) Non-inflammatory controls * Children with suspected growth retardation. ( n=33) MIS-C ( n=21) Kawasaki disease ( n=24) Inactive systemic juvenile idiopathic arthritis ( n=10) Asymptomatic or mild COVID-19 ( n=146) Demographic characteristicsAge, years8 ( 0–16) 10·6 ( 3·0–15·3) 7·0 ( 1·5–17·0) 3·0 ( 0·1–7·5) 15·5 ( 9·0–18·0) 8 ( 0–16) SexFemale230 ( 50%) 13 ( 39%) 11 ( 52%) 9 ( 38%) 5 ( 50%) 72 ( 49%) Male232 ( 50%) 20 ( 61%) 10 ( 48%) 15 ( 63%) 5 ( 50%) 74 ( 51%) Clinical manifestationsFever > 3 days163 ( 35%) †Parent report of fever > 38·5°C.021 ( 100%) 24 ( 100%) 057 ( 39%) †Parent report of fever > 38·5°C.Rash23 ( 5%) 014 ( 67%) 17 ( 71%) 03 ( 2%) Bilateral conjunctivitis20 ( 4%) ‡Parent report of conjunctivitis.015 ( 71%) 21 ( 88%) 05 ( 3%) ‡Parent report of conjunctivitis.Gastrointestinal symptoms108 ( 23%) §Parent report of diarrhoea or nausea.018 ( 86%) 4 ( 17%) 029 ( 20%) §Parent report of diarrhoea or nausea.Cardiac involvementNA013 ( 62%) 24 ( 100%) 0NACoronary artery aneurysmsNA0ND4 ( 17%) 0NAArthritisNA002 ( 8%) 1 ( 10%) NALaboratory parametersC-reactive protein, mg/LNDND214 ( 74–440) 95 ( 3–382) < 0·5 ( not detectable–13) NDFerritin, ng/mLNDND565 ( 67–40 006) ND35 ( 24–226) NDNatrium, mmol/LNDND133 ( 124–141) 135 ( 126–138) 140 ( 138–142) NDLeukocyte count, ×109 cells/LNDND17·8 ( 10·3–30·6) 15·9 ( 7·9–37·3) 6·4 ( 4·4–32·5) NDNeutrophils,% NDNDNA82 ( 53–86) 55 ( 36–85) NDPlatelet count, ×103 cells/mLNDND151 ( 78–1248) 547 ( 135–974) 296 ( 214–339) NDSARS-CoV-2, serology positive0ND¶Collected before 2019.19/20 ( 95%) ND¶Collected before 2019.ND‖Collected before 2020.146 ( 100%) SARS-CoV-2, PCR positive * * PCR at admission to hospital.NDND‖Collected before 2020.4/20 ( 20%) ND‖Collected before 2020.ND‖Collected before 2020.NDTreatmentIVIGThe analysed serum or plasma study samples were all collected from IVIG-naive patients ( except two MIS-C cases); patients were subsequently treated during the disease course as medically indicated.0019 ( 90%) 24 ( 100%) 00Steroids0020 ( 95%) 1 ( 4%) 3 ( 30%) 0Anakinra0015 ( 71%) 21 ( 88%) 5 ( 50%) 0Ventilation009 ( 43%) 000Data are median ( range), n (%), or n/N (%) where N is patients with available data. Body weight is reported for the MIS-C group in the appendix ( pp 1-2); weight data were not collected or unavailable for all other groups. MIS-C=multisystem inflammatory syndrome in children. NA=not available. ND=not determined. IVIG=intravenous immunoglobulin. * Children with suspected growth retardation.† Parent report of fever > 38·5°C.‡ Parent report of conjunctivitis.§ Parent report of diarrhoea or nausea.¶ Collected before 2019.‖ Collected before 2020. * * PCR at admission to hospital.†† The analysed serum or plasma study samples were all collected from IVIG-naive patients ( except two MIS-C cases); patients were subsequently treated during the disease course as medically indicated. Open table in a new tab
Data are median ( range), n (%), or n/N (%) where N is patients with available data. Body weight is reported for the MIS-C group in the appendix ( pp 1-2); weight data were not collected or unavailable for all other groups. MIS-C=multisystem inflammatory syndrome in children. NA=not available. ND=not determined. IVIG=intravenous immunoglobulin.
Anti-IL-1Ra antibodies were detected in 13 ( 62%) of 21 patients with MIS-C, with titres ranging between 1:200 to 1:800 ( figure 1A and 1D, appendix pp 3–5, 19–20). All anti-IL-1Ra antibodies in patients with MIS-C belonged exclusively to the IgG1 subclass, with the exception of one patient, who additionally had anti-IL-1Ra antibodies of the IgM subclass ( figure 1C, appendix p 19). Anti-IL-1Ra antibodies bound to a region spanning from amino acid 98 to 143 ( figure 1E). Autoantibodies against progranulin were only detected in one ( 5%) patient with MIS-C at a titre of 1:200 ( appendix p 5).Figure 1ELISA of IL-1Ra antibodies in patients with MIS-C and control participants.Show full caption ( A) ELISA data for anti-IL-1Ra antibodies in plasma from an exemplary 13 patients with MIS-C. Data for the other eight patients with MIS-C are shown in the appendix ( pp 5, 19). Anti-IL-1Ra antibody subclasses in follow-up samples ( initial presentation and 3-month and 7-month follow-up) of a single patient ( B) and in samples collected at presentation of acute inflammation ( C). ( D) Titres of anti-IL-1Ra antibodies in patients with MIS-C at presentation. ( E) Epitope mapping of anti-IL-1Ra antibodies in MIS-C. ( F) ELISA of anti-IL-1Ra antibodies in plasma of intravenous immunoglobulin-naive patients with Kawasaki disease at presentation ( n=6) and serum samples obtained from patients with systemic juvenile idiopathic arthritis ( in remission; n=10). Positive control was anti-FLAG antibody; negative control was healthy paediatric control plasma. MIS-C=multisystem inflammatory syndrome in children. IL-1Ra=interleukin-1 receptor antagonist. OD=optical density. IL-36Ra=interleukin-36 receptor antagonist. AA=amino acid. sJIA=systemic juvenile idiopathic arthritis. KD=Kawasaki disease.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) ELISA data for anti-IL-1Ra antibodies in plasma from an exemplary 13 patients with MIS-C. Data for the other eight patients with MIS-C are shown in the appendix ( pp 5, 19). Anti-IL-1Ra antibody subclasses in follow-up samples ( initial presentation and 3-month and 7-month follow-up) of a single patient ( B) and in samples collected at presentation of acute inflammation ( C). ( D) Titres of anti-IL-1Ra antibodies in patients with MIS-C at presentation. ( E) Epitope mapping of anti-IL-1Ra antibodies in MIS-C. ( F) ELISA of anti-IL-1Ra antibodies in plasma of intravenous immunoglobulin-naive patients with Kawasaki disease at presentation ( n=6) and serum samples obtained from patients with systemic juvenile idiopathic arthritis ( in remission; n=10). Positive control was anti-FLAG antibody; negative control was healthy paediatric control plasma. MIS-C=multisystem inflammatory syndrome in children. IL-1Ra=interleukin-1 receptor antagonist. OD=optical density. IL-36Ra=interleukin-36 receptor antagonist. AA=amino acid. sJIA=systemic juvenile idiopathic arthritis. KD=Kawasaki disease.
Anti-IL-1Ra antibodies were not detectable in children with asymptomatic or mild COVID-19 ( vs MIS-C group, Fisher's exact test p < 0·0001; appendix pp 23–26), Kawasaki disease ( p < 0·0001; figure 1F, appendix p 22), or inactive systemic juvenile idiopathic arthritis ( p=0·0013; figure 1F). Anti-IL-1Ra antibodies were also not detectable in the non-inflammatory group ( p < 0·0001; appendix p 20) or healthy control group ( p < 0·0001, appendix pp 23–26). Progranulin autoantibodies were undetectable in all control groups ( appendix pp 6–18, 20–22, 27–30).
Clostridium tetanus toxin IgG antibody concentrations in patients MIS-C did not differ from the concentrations measured in patients with Kawasaki disease or healthy controls ( appendix p 31).
IL-1Ra typically produces two bands on isoelectric focusing.19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar Isoelectric focusing of total protein from plasma of one patient with MIS-C with several follow-up samples revealed the presence of an additional, more negatively charged third band of IL-1Ra ( appendix p 33) at the time of initial presentation. Pretreatment with alkaline phosphatase before isoelectric focusing resulted in disappearance of protein bands resembling both the normally occurring second IL-1Ra isoform as well as the atypical additional third, indicating a hyperphosphorylation. In the disease course of this patient, hyperphosphorylated IL-1Ra was no longer detectable at 3 or 7 months after initial MIS-C onset ( appendix p 33).
Hyperphosphorylated IL-1Ra was observed in all 13 MIS-C patients with anti-IL-1Ra antibodies but not in the patients with MIS-C who were autoantibody negative ( appendix pp 33–34), healthy controls ( appendix p 35), or control patients with Kawasaki disease ( appendix p 36), inactive systemic juvenile idiopathic arthritis, or non-inflammatory conditions ( n=49 negative samples) analysed by isoelectric focusing, resulting in a significant association ( Fisher's exact test, two-tailed p < 0·0001), which was maintained when excluding the two patients with MIS-C who had received IVIGs before blood sampling ( p < 0·0001).
In MIS-C patients positive for anti-IL-1Ra antibody, we observed that free IL-1Ra plasma concentrations were significantly decreased ( figure 2A, appendix 3–5) at presentation of acute inflammation ( n=13, mean 279·4 pg/mL [ SD 58·2 ]; or excluding the two MIS-C patients who received IVIGs before blood sampling, n=11, mean 275·0 pg/mL [ 62·6 ]), compared with MIS-C patients negative for anti-IL-1Ra antibody ( n=8; mean 1746·0 pg/mL [ 200·4 ], p < 0·0001). A significant decrease was also observed compared with patients with Kawasaki disease ( n=6 with available data; mean 1038·0 pg/mL [ SD 312·8 ], p=0·0094; or versus 11 MIS-C cases, p=0·0093) or patients with inactive systemic juvenile idiopathic arthritis ( n=10; mean 1278·0 [ 323·1 ], p < 0·0001; figure 2A).Figure 2Neutralising and functional effect of anti-IL-1Ra antibodies in MIS-CShow full caption ( A) Free IL-1Ra plasma concentrations as measured by ELISA in patients with MIS-C ( n=21), Kawasaki disease ( n=6) and systemic juvenile idiopathic arthritis ( n=10). Horizontal lines represent the mean and SD. Data were analysed by Brown–Forsythe and Welch ANOVA with Dunnett's T3 multiple comparisons. ( B) IL-1β-signalling reporter assay on selected MIS-C plasma compared with an adult critical COVID-19 plasma sample ( both 1:20 dilution) as well as commercially available anti-IL-1Ra antibody or control ( anti-SLP2) antibody. The absorbance of secreted embryonic alkaline phosphatase, as a marker for IL-1β pathway activation in HEK IL-1β reporter cells, was detected at 650 nm. Error bars show mean ( SD). MIS-C=multisystem inflammatory syndrome in children. IL-1Ra=interleukin-1 receptor antagonist. KD=Kawasaki disease. sJIA=systemic juvenile idiopathic arthritis. TNF=tumour necrosis factor. IL-1β=interleukin-1β.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) Free IL-1Ra plasma concentrations as measured by ELISA in patients with MIS-C ( n=21), Kawasaki disease ( n=6) and systemic juvenile idiopathic arthritis ( n=10). Horizontal lines represent the mean and SD. Data were analysed by Brown–Forsythe and Welch ANOVA with Dunnett's T3 multiple comparisons. ( B) IL-1β-signalling reporter assay on selected MIS-C plasma compared with an adult critical COVID-19 plasma sample ( both 1:20 dilution) as well as commercially available anti-IL-1Ra antibody or control ( anti-SLP2) antibody. The absorbance of secreted embryonic alkaline phosphatase, as a marker for IL-1β pathway activation in HEK IL-1β reporter cells, was detected at 650 nm. Error bars show mean ( SD). MIS-C=multisystem inflammatory syndrome in children. IL-1Ra=interleukin-1 receptor antagonist. KD=Kawasaki disease. sJIA=systemic juvenile idiopathic arthritis. TNF=tumour necrosis factor. IL-1β=interleukin-1β.
Similar to the absolute concentrations of free IL-1Ra as measured by ELISA, native western blots of total plasma protein also revealed weakened protein bands resembling IL-1Ra in all patients with MIS-C who were positive for anti-IL-1Ra antibodies. However, all autoantibody-positive patients had an additional protein band representing IgG-bound IL-1Ra ( appendix pp 33–34). In the only patient ( MIS-C-21) presenting with IgM antibodies in addition to IgG1, we observed an additional protein band representing IgM-bound IL-1Ra.
We further analysed the two MIS-C patients with longitudinal samples available. In one patient ( MIS-C-1), free IL-1Ra plasma concentration was strongly reduced at the time of MIS-C presentation ( 172·0 pg/mL) compared with values at 3 months ( 1297·1 pg/mL) and 7 months ( 847·5 pg/mL). Native western blot of total plasma protein at initial presentation and the 3-month follow-up produced a weakened free IL-1Ra signal and revealed the presence of IgG-bound IL-1Ra, which was absent at 7 months when the patient was seronegative for anti-IL-1Ra antibodies ( appendix p 32). In the other patient ( MIS-C-6), the initial plasma sample was positive for anti-IL-1Ra antibodies, which coincided with hyperphosphorylated IL-1Ra ( appendix p 33) and reduced free IL-1Ra plasma concentration ( 323·5 pg/mL). At a 5-week follow-up visit, anti-IL-1Ra antibodies and hyperphosphorylated IL-1Ra were no longer detectable ( data not shown), whereas IL-1Ra plasma concentration had increased to 1642·0 pg/mL.
To investigate a possible functional effect of the observed anti-IL-1Ra antibodies, we performed an in vitro IL-1β signalling reporter assay. Addition of plasma from a patient with MIS-C who was positive for anti-IL-1Ra antibodies significantly weakened the antagonism by recombinant IL-1Ra, resulting in a stronger stimulatory effect of IL-1β ( figure 2B). We observed similar impairment of IL-1Ra bioactivity when adding commercially available antihuman IL-1Ra antibody or plasma obtained from an adult patient with critical COVID-19 who had tested positive for IL-1Ra antibodies. By contrast, IL-1Ra function was not affected when adding plasma from the MIS-C patient when the sample was obtained at the 7-month follow-up and negative for anti-IL-1Ra antibodies ( figure 2B). IL-1Ra function was also not affected when adding plasma from an adult patient with critical COVID-19 who had tested negative for anti-IL1-Ra antibodies.
In this study we report on neutralising autoantibodies against the anti-inflammatory molecule IL-1Ra as an exclusive phenomenon in patients with MIS-C, when compared with Kawasaki disease and other inflammatory and non-inflammatory paediatric conditions, including asymptomatic and mild courses of SARS-CoV-2 infection. Although we did not observe anti-IL-1Ra antibodies in any of the control conditions enrolled in this study, our findings are in accordance with those in our preprint paper on adults with critical COVID-19,19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar in whom anti-IL-1Ra antibodies were detected in a high proportion of patients ( about 50%).
In contrast to MIS-C, in adult patients with critical COVID-19 we observed autoantibodies against progranulin in about 40% of patients.19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar However, we only detected anti-progranulin antibodies in one of 21 patients with MIS-C in the present study. Compared with critical COVID-19 in adults, anti-IL-1Ra antibodies were found in a higher proportion in patients with MIS-C ( 13 [ 62% ] of 21). Notably, the plasma concentrations of free IL-1Ra were significantly reduced in all patients with MIS-C who had anti-IL-1Ra antibodies, compared with patients with Kawasaki disease or systemic juvenile idiopathic arthritis, which coincided with detection of immune-complexed IL-1Ra. Anti-IL-1Ra antibodies in patients with MIS-C belonged exclusively to the IgG1 subclass, apart from one patient who had additional antibodies of the IgM class, which is in contrast to adults with critical COVID-19, in whom anti-IL-1Ra antibodies of the IgM class and several IgG subclasses were universally detectable in all investigated patients.19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar These findings might suggest that a class switch of the anti-IL-1Ra antibodies from IgM to IgG might have already occurred within the latency period between infection and manifestation of hyperinflammation, or that the children might have had a clinically inapparent previous autoimmune response against IL-1Ra and consequently already established respective immunological memory. IL-1Ra-specific autoantibodies were also recently reported in IgG4-associated diseases,33Jarrell JA Baker MC Perugino CA et al.Neutralizing anti-IL-1 receptor antagonist autoantibodies induce inflammatory and fibrotic mediators in IgG4-related disease.J Allergy Clin Immunol. 2022; 149: 358-368Google Scholar which might support the idea of IL-1Ra-specific immunity outside of a SARS-CoV-2 infection context. Furthermore, our epitope mapping data indicated that anti-IL-1Ra antibodies in patients with MIS-C recognise a more confined epitope ( amino acids 98–143) compared with respective antibodies in adult COVID-19,19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar which might argue for at least a partly distinct immunological mechanism and origin of this immune response.
However, in both critical COVID-19 and MIS-C, we observed a hyperphosphorylated isoform of the IL-1Ra antigen, which coincided with the presence of anti-IL-1Ra antibodies. In patient follow-up samples, we observed the disappearance of hyperphosphorylated IL-1Ra, which preceded the disappearance of anti-IL-1Ra antibodies. Conversely, data from longitudinal samples of adult patients with severe or critical COVID-19 has shown that hyperphosphorylation of IL-1Ra preceded the formation of respective autoantibodies. Collectively, data from both COVID-19 and MIS-C suggest that atypical post-translational modifications are associated with SARS-CoV-2-infection itself or the resulting inflammatory environment,19Thurner L Fadle N Bewarder M et al.Autoantibodies against progranulin and IL-1 receptor antagonist due to immunogenic posttranslational isoforms contribute to hyperinflammation in critically ill COVID-19.bioRxiv. 2021; ( published online Oct 20.) ( preprint).https: //doi.org/10.1101/2021.04.23.441188Google Scholar and that these modifications are likely to be immunogenic.
Collectively, the findings of our study need to be discussed in view of three main limitations. First, we do not have a detailed molecular understanding of the circumstances and mechanism of the IL-1Ra hyperphosphorylation, and we can not delineate particular HLA associations with the reported autoantibody phenotypes, even though specific HLA haplotypes have been reported to associate with the general immunopathology in patients with MIS-C and COVID-19.34Porritt RA Paschold L Rivas MN et al.HLA class I-associated expansion of TRBV11–2 T cells in multisystem inflammatory syndrome in children.J Clin Invest. 2021; 131146614Google Scholar, 35Moreews M Le Gouge K Khaldi-Plassart S et al.Polyclonal expansion of TCR Vbeta 21·3+ CD4+ and CD8+ T cells is a hallmark of multisystem inflammatory syndrome in children.Sci Immunol. 2021; 6eabh1516Google Scholar, 36Weiner 3rd, J Suwalski P Holtgrewe M et al.Increased risk of severe clinical course of COVID-19 in carriers of HLA-C * 04:01.EClinicalMedicine. 2021; 40101099Google Scholar Importantly, however, the coinciding autoantibodies proved to be functional and impaired IL-1Ra bioactivity, and this might thus offer an additional explanation for the hyperinflammatory phenotype in patients with MIS-C. Second, due to the small number of predominantly White patients with MIS-C included in our study, we did not observe differences in the clinical presentation or severity of MIS-C between patients with or without autoantibodies against IL-1Ra. Further studies with larger cohorts and mixed ethnicity are necessary to address this question. Third, based on our data we can not provide specific treatment recommendations for autoantibody-positive patients. IVIG treatment has recently been suggested to selectively deplete IL-1-producing neutrophils in both Kawasaki disease and MIS-C.37Zhu YP Shamie I Lee JC et al.Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C.J Clin Invest. 2021; 131e147076Google Scholar In case of non-response to IVIG, this effect could support application of selective IL-1 targeting therapies,17Henderson LA Canna SW Friedman KG et al.American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: version 1.Arthritis Rheumatol. 2020; 72: 1791-1805Google Scholar, 18Henderson LA Canna SW Friedman KG et al.American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: version 2.Arthritis Rheumatol. 2021; 73: e13-e29Google Scholar, 38Koné-Paut I Tellier S Belot A et al.Phase II open label study of anakinra in intravenous immunoglobulin-resistant Kawasaki disease.Arthritis Rheumatol. 2021; 73: 151-161Google Scholar which might also help to override temporarily imbalanced IL-1 signalling due to IL-1Ra-neutralising autoantibodies in patients with MIS-C. However, we can not make predictions about the in vivo concentrations of anakinra that would potentially be required to override anti-IL-1Ra immunity in MIS-C or whether use of the anti-IL-1β monoclonal antibody canakinumab might offer an adequate alternative treatment particularly in this scenario.
In summary, autoantibodies against IL-1Ra together with a hyperphosphorylated isoform of IL-1Ra were observed in a high proportion of children with MIS-C. Although the small number of patients with MIS-C enrolled in this study might pose a limitation, the high numbers of controls ( both inflammatory and non-inflammatory) highlight our findings as unique rather than an epiphenomenon. Our data suggest that anti-IL-1Ra autoantibodies are pathogenetically relevant and potentially contribute to hyperinflammation in patients with MIS-C.
LT, BT, JP, NF, ER, and CK planned the study, reviewed and verified the data, and wrote the manuscript. NF, ER, M-CH, and LT performed experiments. KR, YF, K-DP, IAK, SLB, PK, SG, KH, TR, SM, SS, AJ, MBe, MBö, HA-K, CK, EB, AK, DF, and MK reviewed the data and manuscript. SM, SL, SS, M-CD, RB, MF, HJ, HS, TR, HA-K, HW, SG, PK, KM, AJ, JA, and RMP-R provided patient and control samples and clinical data. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
All data required to evaluate the conclusions in the paper are present in the manuscript or its appendix. Further information on the study protocol or de-identified datasets generated and analysed within this publication are available from the corresponding author on reasonable request.
LT has received research grants from Wilhelm Sander-Stiftung, BioNanoMed, and the Homburger Forschungsförderung programme of the University of Saarland; travel grants for meeting attendance from AbbVie, Janssen, and EUSA-Pharm; and has participated in advisory boards for Takeda, AstraZeneca, Merck, and EUSA Pharma. LT and K-DP were listed among inventors of a patent on progranulin antibodies as marker for autoimmune diseases filed by University of Saarland, which expired in 2017. CK has received consulting fees from Novartis and Swedish Orphan Biovitrum ( SOBI) and receives research support from Novartis. MBö has received speakers honoraria from or participated in advisory boards for Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cyotkinetics, Medtronic, Novartis, Servier, and Vifor. HW has received honoraria ( lecture fees) from Novartis and Takeda, and travel support from Octapharma and CSL-Behring. DF has received speaker fees or honoraria from Chugai-Roche, Novartis, and SOBI, and research support from Novartis, Pfizer, and SOBI. JA has received grants and travel grants for meeting attendance from SOBI and Novartis, and participated in advisory boards for SOBI and Novartis. BT has received honoraria for lectures from Nutricia Milupa and is a private shareholder of BioNTech. MK has received research support for the CoKiBa trial from Roche, who provided the diagnostic antibodies at a time when they were not yet commercially available. In addition, MK has received honoraria for lectures from Pädnetz Bayern, Ärztlicher Kreisverband, and Bayerischer Berufsverband der Kinder- und Jugendärzte, and participated in the advisory board for COVID-19 in children of the Bavarian Ministry of Health. SLB has participated in advisory boards and received honoraria for lectures from Shinogi and Pfizer. RB has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Novartis; personal fees from GlaxoSmithKline, Grifols, and CSL Behring; grants from the German Ministry of Education and Research, Competence Network on Asthma and COPD, Sander Stiftung, Schwiete Stiftung, Krebshilfe, and Mukosviszidose; and has a leadership role at the Alpha-1-Center in Bad Lippspringe, Germany. All other authors declare no competing interests.
We thank the patients and their parents, who supported this research project. We also want to thank all physicians, nurses, and other staff not mentioned here, who cared for the patients. We thank Susanne Brandstetter for compiling the symptoms of the control groups obtained from the CoKiBa trial. This work was supported by a young investigator NanoBioMed fund of the University of Saarland ( to LT); by funding from the Dr Rolf M Schwiete Stiftung and the Staatskanzlei of the Federal State of Saarland ( to SS); and by funding from the German Heart Foundation ( to AJ). CK and DF were supported by the Center for Interdisciplinary Clinical Research at University Hospital Muenster ( grant number Fo2/018/20) and the EU's Horizon 2020 research and innovation programme ( grant agreement number 779295; via the ImmunAID consortium). The CoKiBa trial was funded by the Charity of the Blue Sisters and the project Post-COVID Kids Bavaria of the Bavarian Ministry of Health.
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IL-1 receptor antagonist, MIS-C, and the peculiar autoimmunity of SARS-CoV-2For years, rheumatologists have sought to make sense of autoantibodies that are identified in patients with inflammation following acute infections. Often, it is unclear whether these autoantibodies are directly triggered by infection, and furthermore whether they might be contributing to the patient's immunopathology. Full-Text PDF | tech |
Availability of oral antivirals against SARS-CoV-2 infection and the requirement for an ethical prescribing approach - The Lancet Infectious Diseases | The first two oral antivirals, molnupiravir and nirmatrelvir–ritonavir, are now becoming available in many countries. These medicines will be indicated to treat mild-to-moderate COVID-19 in non-hospitalised patients who are at high risk of progressing to severe COVID-19. These antivirals should be prescribed within 5 days of symptom onset, and after SARS-CoV-2 infection has been confirmed. However, the availability of these antivirals will be scarce for some time due to manufacturing constraints. Each country should establish a policy on the conditions under which these antivirals can be prescribed. Such a policy should be based on the fulfilment of five ethical elements: transparency, relevance, appeals, enforcement, and fairness. Following the principles of distributive justice, molnupiravir and nirmatrelvir–ritonavir should be prescribed according to a hierarchy of predicted efficacy, ideally on the basis of an evidence-based scoring system. The placebo-controlled randomised trials that supported the temporary authorisation of these two antivirals were conducted in unvaccinated patients with COVID-19, so an evidence-based prescription practice would only use these drugs for unvaccinated patients until further data become available. However, in the countries that authorised these antivirals in 2021 ( the UK and the USA), both vaccinated and unvaccinated patients meeting particular requirements have access to these antivirals. Due to the complexity of prioritisation, national health authorities should start issuing their draft policies as soon as possible and these policies should be regularly updated. The effectiveness of these antivirals against the omicron variant of SARS-CoV-2 must be urgently assessed. Once implemented, molnupiravir and nirmatrelvir–ritonavir must show their effectiveness and safety in the real world, and health systems must be adequately adapted for the correct use of these antivirals.
The first two oral antivirals, molnupiravir and nirmatrelvir–ritonavir, are now becoming available in many countries. These medicines will be indicated to treat mild-to-moderate COVID-19 in non-hospitalised patients who are at high risk of progressing to severe COVID-19. These antivirals should be prescribed within 5 days of symptom onset, and after SARS-CoV-2 infection has been confirmed. However, the availability of these antivirals will be scarce for some time due to manufacturing constraints. Each country should establish a policy on the conditions under which these antivirals can be prescribed. Such a policy should be based on the fulfilment of five ethical elements: transparency, relevance, appeals, enforcement, and fairness. Following the principles of distributive justice, molnupiravir and nirmatrelvir–ritonavir should be prescribed according to a hierarchy of predicted efficacy, ideally on the basis of an evidence-based scoring system. The placebo-controlled randomised trials that supported the temporary authorisation of these two antivirals were conducted in unvaccinated patients with COVID-19, so an evidence-based prescription practice would only use these drugs for unvaccinated patients until further data become available. However, in the countries that authorised these antivirals in 2021 ( the UK and the USA), both vaccinated and unvaccinated patients meeting particular requirements have access to these antivirals. Due to the complexity of prioritisation, national health authorities should start issuing their draft policies as soon as possible and these policies should be regularly updated. The effectiveness of these antivirals against the omicron variant of SARS-CoV-2 must be urgently assessed. Once implemented, molnupiravir and nirmatrelvir–ritonavir must show their effectiveness and safety in the real world, and health systems must be adequately adapted for the correct use of these antivirals.
There is a substantial unmet medical need for safe and efficacious oral medications for non-hospitalised patients with COVID-19. Currently there are five medicinal products authorised for treating patients with COVID-19 who do not require supplemental oxygen—four monoclonal antibodies ( bamlanivimab–etesevimab, casirivimab–imdevimab, regdanvimab, and sotrovimab) and one antiviral ( remdesivir). However, these products require parenteral administration and should be given in health-care facilities with trained staff to manage potential severe hypersensitivity reactions.1European Medicines AgencyRegkirona ( regdanvimab).https: //www.ema.europa.eu/en/documents/overview/regkirona-epar-medicine-overview en.pdfDate: Nov, 2021Date accessed: January 3, 2022Google Scholar, 2European Medicines AgencyRonapreve ( casirivimab and imdevimab).https: //www.ema.europa.eu/en/documents/product-information/ronapreve-epar-product-information en.pdfDate: Nov, 2021Date accessed: January 3, 2022Google Scholar, 3GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory Agency. Ronapreve.https: //www.gov.uk/government/publications/regulatory-approval-of-ronapreve/summary-of-the-public-assessment-report-for-ronapreveDate: Nov 19, 2021Date accessed: January 3, 2022Google Scholar, 4GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory Agency. Summary of products characteristics for xevudy.https: //www.gov.uk/government/publications/regulatory-approval-of-xevudy-sotrovimab/summary-of-product-characteristics-for-xevudyDate: Dec 2, 2021Date accessed: January 3, 2022Google Scholar, 5US Food and Drug AdministrationEmergency use authorization for casirivimab and imdevimab.https: //www.fda.gov/media/143891/downloadDate: Nov 21, 2021Date accessed: January 3, 2022Google Scholar, 6US Food and Drug AdministrationEmergency use authorization for bamlanivimab and etesevimab.https: //www.fda.gov/media/145611/downloadDate: Dec 3, 2021Date accessed: January 3, 2022Google Scholar, 7European Medicines AgencyVeklury. Summary of product characteristics.https: //www.ema.europa.eu/en/medicines/human/EPAR/vekluryDate: Dec 22, 2021Date accessed: January 3, 2022Google Scholar It is expected that in a few months, two oral antivirals, molnupiravir and nirmatrelvir–ritonavir, will become available in many countries. These oral antivirals have shown their clinical efficacy against COVID-19 in placebo-controlled, double-blind, randomised controlled trials ( RCTs). However, using these antivirals in the real world will be challenging since their availability will be low across almost all countries for some time.
On Nov 4, 2021, molnupiravir was temporarily authorised in the UK for the treatment of mild-to-moderate COVID-19 in adults, provided they meet particular requirements.8GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory Agency. Summary of products characteristics for Lagevrio.https: //www.gov.uk/government/publications/regulatory-approval-of-lagevrio-molnupiravir/summary-of-product-characteristics-for-lagevrioDate: Dec 20, 2021Date accessed: January 3, 2022Google Scholar 2 weeks later, the European Medicines Agency ( EMA) issued advice on the use of molnupiravir and started evaluating the application for marketing authorisation of molnupiravir in the EU ( table 1).9European Medicines AgencyAssessment report. Procedure under article 5 ( 3) of regulation ( EC) No 726/2004 use of molnupiravir for the treatment of COVID-19.https: //www.ema.europa.eu/en/documents/referral/lagevrio-also-known-molnupiravir-mk-4482-covid-19-article-53-procedure-assessment-report en.pdfDate: Nov 19, 2021Date accessed: January 3, 2022Google Scholar, 30European Medicines AgencyEMA receives application for marketing authorisation for Lagevrio ( molnupiravir) for treating patients with COVID 19.https: //www.ema.europa.eu/en/news/ema-receives-application-marketing-authorisation-lagevrio-molnupiravir-treating-patients-covid-19Date: Nov 23, 2021Date accessed: January 3, 2022Google Scholar On Dec 23, 2021, the US Food and Drug Administration ( FDA) granted emergency use authorisation for molnupiravir. At the planned interim analysis ( n=775, for efficacy) of the pivotal RCT ( MOVe-OUT), the external data monitoring committee recommended stopping enrolment due to efficacy with regard to the primary endpoint. Following the assessment of the full study population ( n=1433) of this trial, molnupiravir treatment resulted in a 3 percentage point absolute risk reduction in hospitalisation or death when compared with the placebo.12US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for molnupiravir.https: //www.fda.gov/media/155054/downloadDate: Dec 23, 2021Date accessed: January 3, 2022Google Scholar, 13Jayk Bernal A Gomes da Silva MM Musungaie DB et al.Molnupiravir for oral treatment of COVID-19 in non-hospitalized patients.N Engl J Med. 2021; 386: 509-520Google Scholar This finding means that 35 patients must be treated to prevent one patient from being hospitalised or dying.Table 1Main characteristics of molnupiravir and nirmatrelvir–ritonavir as of Dec 31, 2021MolnupiravirNirmatrelvir–ritonavirMechanism of action8GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory Agency. Summary of products characteristics for Lagevrio.https: //www.gov.uk/government/publications/regulatory-approval-of-lagevrio-molnupiravir/summary-of-product-characteristics-for-lagevrioDate: Dec 20, 2021Date accessed: January 3, 2022Google Scholar, 9European Medicines AgencyAssessment report. Procedure under article 5 ( 3) of regulation ( EC) No 726/2004 use of molnupiravir for the treatment of COVID-19.https: //www.ema.europa.eu/en/documents/referral/lagevrio-also-known-molnupiravir-mk-4482-covid-19-article-53-procedure-assessment-report en.pdfDate: Nov 19, 2021Date accessed: January 3, 2022Google Scholar, 10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar, 11GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory AgencyRegulatory approval of Paxlovid. Summary of products characteristics.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1044405/Paxlovid SmPC.pdfDate: Dec 31, 2021Date accessed: January 3, 2022Google ScholarMolnupiravir is a prodrug that is metabolised to the ribonucleoside analogue NHC; NHC distributes into cells where it is phosphorylated to form the pharmacologically active ribonucleoside triphosphate ( NHC-TP); NHC-TP incorporation into viral RNA by the viral RNA polymerase results in an accumulation of errors ( error catastrophe) in the viral genome leading to inhibition of replicationNirmatrelvir ( PF-07321332) is a 3C-like protease inhibitor, preventing viral replication; ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, resulting in increased plasma concentrations of nirmatrelvirIndicationEU9European Medicines AgencyAssessment report. Procedure under article 5 ( 3) of regulation ( EC) No 726/2004 use of molnupiravir for the treatment of COVID-19.https: //www.ema.europa.eu/en/documents/referral/lagevrio-also-known-molnupiravir-mk-4482-covid-19-article-53-procedure-assessment-report en.pdfDate: Nov 19, 2021Date accessed: January 3, 2022Google Scholar and UK8GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory Agency. Summary of products characteristics for Lagevrio.https: //www.gov.uk/government/publications/regulatory-approval-of-lagevrio-molnupiravir/summary-of-product-characteristics-for-lagevrioDate: Dec 20, 2021Date accessed: January 3, 2022Google ScholarAdult patients ( aged ≥18 years) with mild-to-moderate COVID-19 diagnosis ( not requiring supplemental oxygen) with a duration of symptoms of ≤5 days and positive SARS-CoV-2 diagnostic test; patients at increased risk of progressing to severe COVID-19; patients having at least one risk factor for developing severe COVID-19; not recommended during pregnancy or breastfeeding with a 4-day post-treatment window for use of effective contraception and interruption of breastfeeding.. UK11GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory AgencyRegulatory approval of Paxlovid. Summary of products characteristics.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1044405/Paxlovid SmPC.pdfDate: Dec 31, 2021Date accessed: January 3, 2022Google Scholar.. Adults who do not require supplemental oxygen and who are at increased risk of progression to severe COVID-19USA10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar, 12US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for molnupiravir.https: //www.fda.gov/media/155054/downloadDate: Dec 23, 2021Date accessed: January 3, 2022Google ScholarAdult patients ( aged ≥18 years), with mild-to-moderate COVID-19 diagnosis with a duration of symptoms of ≤5 days, positive SARS-CoV-2 diagnostic test, and for whom alternative COVID-19 treatment options are not accessible or clinically appropriate; patients should be at high risk for progressing to severe COVID-19, including hospitalisation or death; according to animal studies, molnupiravir might cause fetal harm during pregnancy; is not recommended for use in pregnancyAdult and adolescent patients ( aged ≥12 years, weighing ≥40 kgs), with mild-to-moderate COVID-19 diagnosis with a duration of symptoms of ≤5 days, with positive SARS-CoV-2 diagnostic test; patients should be at high risk for progressing to severe COVID-19, including hospitalisation or deathContraindications10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar, 11GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory AgencyRegulatory approval of Paxlovid. Summary of products characteristics.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1044405/Paxlovid SmPC.pdfDate: Dec 31, 2021Date accessed: January 3, 2022Google Scholar, 12US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for molnupiravir.https: //www.fda.gov/media/155054/downloadDate: Dec 23, 2021Date accessed: January 3, 2022Google ScholarNone identified so farCo-administration with medicines highly dependent on CYP3A for clearance or with potent CYP3A inducers; patients with severe hepatic or severe renal impairment; patients with a history of clinically significant hypersensitivity to the active substancesAdverse events8GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory Agency. Summary of products characteristics for Lagevrio.https: //www.gov.uk/government/publications/regulatory-approval-of-lagevrio-molnupiravir/summary-of-product-characteristics-for-lagevrioDate: Dec 20, 2021Date accessed: January 3, 2022Google Scholar, 9European Medicines AgencyAssessment report. Procedure under article 5 ( 3) of regulation ( EC) No 726/2004 use of molnupiravir for the treatment of COVID-19.https: //www.ema.europa.eu/en/documents/referral/lagevrio-also-known-molnupiravir-mk-4482-covid-19-article-53-procedure-assessment-report en.pdfDate: Nov 19, 2021Date accessed: January 3, 2022Google Scholar, 10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar, 11GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory AgencyRegulatory approval of Paxlovid. Summary of products characteristics.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1044405/Paxlovid SmPC.pdfDate: Dec 31, 2021Date accessed: January 3, 2022Google Scholar, 12US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for molnupiravir.https: //www.fda.gov/media/155054/downloadDate: Dec 23, 2021Date accessed: January 3, 2022Google ScholarCommon: dizziness, headache, diarrhoea, nausea; uncommon: vomiting, rash, urticariaWith incidence of ≥1% and a difference in number of participants affected of five or more versus the comparator group were dysgeusia, diarrhoea, hypertension, myalgia; common adverse reactions: dysgeusia, diarrhoea, vomitingPhase 2 and 3 clinical trial data—primary outcome measureMOVe-OUT ( NCT04575597):12US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for molnupiravir.https: //www.fda.gov/media/155054/downloadDate: Dec 23, 2021Date accessed: January 3, 2022Google Scholar, 13Jayk Bernal A Gomes da Silva MM Musungaie DB et al.Molnupiravir for oral treatment of COVID-19 in non-hospitalized patients.N Engl J Med. 2021; 386: 509-520Google Scholar at enrolment, patients should be unvaccinated and should present at least one of the following risk factors for disease progression: aged ≥60 years, diabetes, obesity ( body-mass index > 30 kg/m2), chronic kidney disease, serious heart condition, chronic obstructive pulmonary disease, or active cancer; all-cause hospitalisation or death until day 29 ( primary endpoint): molnupiravir, 6·8% ( 48/709); placebo, 9·7% ( 68/699); absolute risk reduction: 3·0 ( 95% CI 0·1–5·9) percentage points; relative risk reduction: 30%; number of deaths by day 29: molnupiravir, 0·14% ( 1/709); placebo, 1·3% ( 9/699); patients with baseline positive antibodies ( recent infection): molnupiravir, 19·1% ( 137/678); placebo, 20·5% ( 147/666); total, 19·8% ( 284/1346); recruiting sites in Africa, Asia, Europe, North America, and South AmericaEPIC-HR ( NCT04960202):10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar all-cause hospitalisation or death through day 28 ( primary endpoint): nirmatrelvir–ritonavir, 0·8% ( 8/1039); placebo, 6·3% ( 66/1046); absolute risk reduction: 5·6 ( 95% CI 4·0–7·2) percentage points; relative risk reduction: 88%; number of deaths by day 28: nirmatrelvir–ritonavir, 0% ( 0/1039); placebo, 1·1% ( 12/1046); having received or expecting to receive any dose of a SARS-CoV-2 vaccine before the day 34 visit was an exclusion criterion; recruiting sites in Africa, Asia, Europe, Latin America, and the USANumber of patients needed to treat to prevent one hospitalisation or death35 ( 95% CI 17–1000) 19 ( 95% CI 14–25) Posology8GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory Agency. Summary of products characteristics for Lagevrio.https: //www.gov.uk/government/publications/regulatory-approval-of-lagevrio-molnupiravir/summary-of-product-characteristics-for-lagevrioDate: Dec 20, 2021Date accessed: January 3, 2022Google Scholar, 9European Medicines AgencyAssessment report. Procedure under article 5 ( 3) of regulation ( EC) No 726/2004 use of molnupiravir for the treatment of COVID-19.https: //www.ema.europa.eu/en/documents/referral/lagevrio-also-known-molnupiravir-mk-4482-covid-19-article-53-procedure-assessment-report en.pdfDate: Nov 19, 2021Date accessed: January 3, 2022Google Scholar, 10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar, 11GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory AgencyRegulatory approval of Paxlovid. Summary of products characteristics.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1044405/Paxlovid SmPC.pdfDate: Dec 31, 2021Date accessed: January 3, 2022Google Scholar, 12US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for molnupiravir.https: //www.fda.gov/media/155054/downloadDate: Dec 23, 2021Date accessed: January 3, 2022Google Scholar800 mg every 12 h for 5 days; oral route300 mg ( nirmatrelvir) + 100 mg ( ritonavir) every 12 h for 5 days; oral routePrice and manufacturingUS $ 700 in the USA,14Willyard C How antiviral pill molnupiravir shot ahead in the COVID drug hunt.https: //www.nature.com/articles/d41586-021-02783-1Date: Oct 8, 2021Date accessed: January 3, 2022Google Scholar $ 750 in Japan,15The Japan TimesJapan to pay $ 1·2 billion for 1·6 million courses of Merck's COVID-19 pill.https: //www.japantimes.co.jp/news/2021/11/10/national/science-health/japan-covid-pill/Date: Nov 10, 2021Date accessed: January 3, 2022Google Scholar per treatment course; estimated cost-based generic price: $ 17·74; 16Barber M Gotham D Estimated cost-based generic prices for molnupiravir for the treatment of COVID-19 infection.https: //scholar.harvard.edu/files/melissabarber/files/estimated cost-based generic prices for molnupiravir for the treatment of covid-19 infection.pdfDate: Oct 1, 2021Date accessed: January 3, 2022Google Scholar Merck signed a license agreement with The Medicines Patent Pool to facilitate affordable access of the product in 105 low-income and middle-income countries; 17Medicines Patent PoolThe Medicines Patent Pool ( MPP) and MSD enter into licence agreement for molnupiravir, an investigational oral antiviral COVID-19 medicine, to increase broad access in low- and middle- income countries.https: //medicinespatentpool.org/news-publications-post/mpp-msd-new-licence-announcement-molnupiravirDate: Oct 27, 2021Date accessed: January 3, 2022Google Scholar although in this agreement 100% of south Asian and sub-Saharan African populations are covered, only 5% of European and central Asian populations and 18% of Latin American and Caribbean populations are covered; 18Newton W Vaidya M Most of Latin America, Caribbean left behind in Merck's oral Covid-19 antiviral deal. Clinical Trials Arena, Nov 2, 2021https: //www.clinicaltrialsarena.com/analysis/molnupiravir-access-latin-america-caribbean/Date accessed: January 3, 2022Google Scholar Merck manufacturing capacity: 10 million courses by the end of 2021; 19Dyer O Covid-19: FDA expert panel recommends authorising molnupiravir but also voices concerns.BMJ. 2021; 375n2984Google Scholar the manufacturing capacity of licensee companies must also be taken into account; 13 Indian companies will roll out molnupiravir at a price of Rs2000–3000 ( $ 26·9–40·4) per treatment course20Pilla V A full molnupiravir treatment likely to cost up to Rs 3,000.https: //economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/a-full-molnupiravir-treatment-likely-to-cost-up-to-rs-3000/articleshow/88578681.cmsDate: Dec 30, 2021Date accessed: January 3, 2022Google Scholar $ 530 ( USA) 21Mishra M U.S. to buy 10 mln courses of Pfizer's COVID-19 pill for $ 5·3 bln.https: //www.reuters.com/business/healthcare-pharmaceuticals/us-govt-buy-10-mln-courses-pfizers-covid-19-pill-529-bln-2021-11-18/Date: Nov 18, 2021Date accessed: January 3, 2022Google Scholar per treatment course; Pfizer signed a license agreement with The Medicines Patent Pool to facilitate affordable access of the product in 105 low-income and middle-income countries,22Medicines Patent PoolPfizer and The Medicines Patent Pool ( MPP) sign licensing agreement for COVID-19 oral antiviral treatment candidate to expand access in low- and middle-income countries.https: //medicinespatentpool.org/news-publications-post/pfizer-and-the-medicines-patent-pool-mpp-sign-licensing-agreement-for-covid-19-oral-antiviral-treatment-candidate-to-expand-access-in-low-and-middle-income-countriesDate: Nov 16, 2021Date accessed: January 3, 2022Google Scholar although some countries ( eg, Brazil, Iraq, Kazakhstan, Lebanon, Peru) are excluded; 23Amnesty International Public StatementAmnesty International's reaction to Pfizer's license agreement for Paxlovid with the Medicines Patent Pool.https: //www.amnesty.org/en/wp-content/uploads/2021/11/POL4050102021ENGLISH.pdfDate: Nov 18, 2021Date accessed: January 3, 2022Google Scholar Pfizer manufacturing capacity: 180 000 treatment courses by the end of 2021, and 120 million by the end of 2022; 24Nadeem D O'donnell C US authorizes Pfizer oral COVID-19 treatment, first for at-home use.https: //www.reuters.com/business/healthcare-pharmaceuticals/pfizer-oral-covid-19-pill-gets-us-authorization-at-home-use-2021-12-22/Date: Dec 23, 2021Date accessed: January 3, 2022Google Scholar the manufacturing capacity of licensee companies must also be taken into accountCountries where it is authorisedTemporary authorisation granted in India,25Hindustan TimesGovt gives emergency approval to Covid-19 vaccines Covovax, Corbevax and anti-viral molnupiravir.https: //www.hindustantimes.com/india-news/breaking-news-live-december-28-2021-101640651613288.htmlDate: Dec 28, 2021Date accessed: January 3, 2022Google Scholar Israel,26Jaffe-Hofman M Merck's COVID-19 pill to arrive in Israel within two weeks.https: //www.jpost.com/breaking-news/article-689649Date: Dec 25, 2021Date accessed: January 3, 2022Google Scholar Japan,27The Pharma LetterJapan approves molnupiravir for SARS-CoV-2 infection.https: //www.thepharmaletter.com/in-brief/brief-japan-latest-to-approve-molnupiravir-for-sars-cov-2-infectionDate: Dec 25, 2021Date accessed: January 3, 2022Google Scholar the UK,8GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory Agency. Summary of products characteristics for Lagevrio.https: //www.gov.uk/government/publications/regulatory-approval-of-lagevrio-molnupiravir/summary-of-product-characteristics-for-lagevrioDate: Dec 20, 2021Date accessed: January 3, 2022Google Scholar and the USA12US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for molnupiravir.https: //www.fda.gov/media/155054/downloadDate: Dec 23, 2021Date accessed: January 3, 2022Google ScholarTemporary authorisation granted in Israel,28Efrati I Israel authorized use of Pfizer antiviral COVID pill Paxlovid.https: //www.haaretz.com/israel-news/israel-authorizes-use-of-pfizer-antiviral-covid-pill-paxlovid-1.10495082Date: Dec 26, 2021Date accessed: January 3, 2022Google Scholar South Korea,29Kumar A South Korea approves of Pfizer's Paxlovid antiviral pill for emergency use to fight COVID.https: //www.republicworld.com/world-news/rest-of-the-world-news/south-korea-approves-of-pfizers-paxlovid-antiviral-pill-for-emergency-use-to-fight-covid.htmlDate: Dec 27, 2021Date accessed: January 3, 2022Google Scholar the UK,11GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory AgencyRegulatory approval of Paxlovid. Summary of products characteristics.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1044405/Paxlovid SmPC.pdfDate: Dec 31, 2021Date accessed: January 3, 2022Google Scholar and the USA10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google ScholarNHC=N-hydroxycytidine. NHC-TP=N-hydroxycytidine triphosphate. Open table in a new tab
NHC=N-hydroxycytidine. NHC-TP=N-hydroxycytidine triphosphate.
There are concerns over whether molnupiravir could speed up emergence of SARS-CoV-2 mutants19Dyer O Covid-19: FDA expert panel recommends authorising molnupiravir but also voices concerns.BMJ. 2021; 375n2984Google Scholar because this prodrug causes multiple viral mutations, which leads to impaired viral fitness and ultimately viral extinction.31Painter WP Holman W Bush JA et al.Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2.Antimicrob Agents Chemother. 2021; 65: e02428-e02520Google Scholar Zhou and colleagues have shown that N-hydroxycytidine ( NHC), the initial metabolite of molnupiravir, displays host mutational activity in an animal cell culture assay.32Zhou S Hill CS Sarkar S et al.β-d-N4-hydroxycytidine inhibits SARS-CoV-2 through lethal mutagenesis but is also mutagenic to mammalian cells.J Infect Dis. 2021; 224: 415-419Google Scholar Theoretically, NHC might cause birth defects or long-term damage to patients ' DNA, but according to the UK regulatory agency, it is of low risk for genotoxicity and mutagenicity in clinical use.33Harrison C COVID-19 antiviral pills raise hopes for curbing pandemic.https: //www.nature.com/articles/d41587-021-00024-4Date: Nov 25, 2021Date accessed: January 3, 2022Google Scholar
Although all participants in the pivotal RCT were unvaccinated, the indication comprises all patients with mild-to-moderate COVID-19, regardless of patients ' vaccine status. It is noteworthy that the USA emergency use authorisation requires that to prescribe molnupiravir, no other alternative treatment options ( nirmatrelvir–ritonavir or even remdesivir or monoclonal antibodies) should be accessible or clinically appropriate,12US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for molnupiravir.https: //www.fda.gov/media/155054/downloadDate: Dec 23, 2021Date accessed: January 3, 2022Google Scholar which will restrict use of molnupiravir.
The second oral antiviral, nirmatrelvir ( PF-07321332), is a 3C-like protease inhibitor developed by Pfizer that inhibits SARS-CoV-2 replication ( table 1). Nirmatrelvir is administered with a low dose of ritonavir. The FDA granted emergency use authorisation for this medicine on Dec 22, 2021, whereas the UK Medicines and Healthcare products Regulatory Agency ( MHRA) granted conditional authorisation for nirmatrelvir 9 days later. Nirmatrelvir is under evaluation by the EMA, who have issued advice on its use based on interim results of the pivotal phase 3 RCT ( EPIC-HR).34European Medicines AgencyConditions of use, conditions for distribution and patients targeted and conditions for safety monitoring addressed to member states. For unauthorized product. Paxlovid ( PF-07321332 150 mg and ritonavir 100 mg).https: //www.ema.europa.eu/en/documents/referral/paxlovid-pf-07321332-ritonavir-covid-19-article-53-procedure-conditions-use-conditions-distribution en.pdfDate: Dec 22, 2021Date accessed: January 3, 2022Google Scholar At the planned interim analysis ( n=1219, for efficacy) of this RCT, the external data monitoring committee recommended stopping enrolment due to efficacy with regard to the primary endpoint. Nirmatrelvir–ritonavir provided a 5·6 percentage point absolute risk reduction in hospitalisation or death when compared with the placebo.10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar Therefore, 19 patients must be treated to prevent one patient from being hospitalised or dying.
As a protease inhibitor, nirmatrelvir–ritonavir has no risk of displaying host mutational activity. Although this medicinal product will be given for a short period of time ( 5 days), prescribing physicians should bear in mind that ritonavir ( given at 100 mg every 12 h) can interact with various medicines.35Foisy MM Yakiwchuk EM Hughes CA Induction effects of ritonavir: implications for drug interactions.Ann Pharmacother. 2008; 42: 1048-1059Google Scholar Both the FDA and the MHRA provided lists of medicinal products that are contraindicated for concomitant use with nirmatrelvir–ritonavir and lists of established and potential clinically significant drug interactions.10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar
It is noteworthy that, although only unvaccinated adults were included in the pivotal RCT, the use of nirmatrelvir–ritonavir in the USA is temporarily authorised in both adolescent and adult patients, regardless of their vaccination status.10US Food and Drug AdministrationFact sheet for healthcare providers: emergency use authorization for Paxlovid.https: //www.fda.gov/media/155050/downloadDate: Dec 22, 2021Date accessed: March 11, 2022Google Scholar In the UK, only vaccinated and unvaccinated adults can receive this antiviral.11GOV.UKGoogle ScholarMedicines and Healthcare products Regulatory AgencyRegulatory approval of Paxlovid. Summary of products characteristics.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/1044405/Paxlovid SmPC.pdfDate: Dec 31, 2021Date accessed: January 3, 2022Google Scholar
Interim results of an additional phase 3 trial ( NCT05011513), which included both fully vaccinated adults who are at risk of progression to severe COVID-19 and unvaccinated adults at low risk of hospitalisation or death, showed that 0·6% ( two of 333) of the antiviral group were hospitalised versus 2·4% ( eight of 329) of the placebo group, an absolute difference of 1·8 percentage points. No deaths have been reported and the trial is ongoing.36PfizerPfizer announces additional phase 2/3 study results confirming robust efficacy of novel COVID-19 oral antiviral treatment candidate in reducing risk of hospitalization or death.https: //www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-additional-phase-23-study-resultsDate: Dec 14, 2021Date accessed: January 3, 2022Google Scholar
Molnupiravir and nirmatrelvir–ritonavir will initially be available in many countries under temporary authorisation schemes ( as has already happened in the UK and the USA), so many months will elapse before a full marketing authorisation might be granted. In this Personal View, we assume that both medicines will be available—although in small quantities for some time—in many countries. The actual availability depends on the agreements reached by each country and the manufacturing companies ( table 2).Table 2Number of molnupiravir and nirmatrelvir–ritonavir orders by country, and percentage of fully vaccinated individuals as of Dec 31, 2021Number of treatment coursesPercentage of the total population who are fully vaccinated * Data are from Our World in Data.38MolnupiravirNirmatrelvir–ritonavirAustralia300 000500 00077% Belgium10 000.. 76% Canada500 0001 000 00077% Germany.. 1 000 000†Data are from Deutsche Welle.3971% Indonesia600 000–1 000 000.. 41% Israel.. 100 00064% Italy50 00050 00074% Japan1 600 000.. 78% Malaysia150 000.. 78% Philippines300 000.. 34% South Korea200 00070 00083% Switzerland864050 000‡Data are from Südwestrundfunk.4067% Thailand200 000.. 65% UK2 230 0002 750 00070% USA3 100 00010 000 00062% Data are from Reuters,37ReutersFactbox: countries rush to buy experimental antiviral COVID-19 pills.https: //www.reuters.com/business/healthcare-pharmaceuticals/countries-rush-buy-merck-experimental-covid-19-pill-2021-11-03/Date: Dec 30, 2021Date accessed: January 3, 2022Google Scholar except where noted. * Data are from Our World in Data.38Our World in DataStatistics and Research. Coronavirus ( COVID-19) vaccinations.https: //ourworldindata.org/covid-vaccinationsDate: Dec 10, 2021Date accessed: January 3, 2022Google Scholar† Data are from Deutsche Welle.39Deutsche WelleGermany buys 1 million doses of anti-COVID pill Paxlovid.https: //www.dw.com/en/germany-buys-1-million-doses-of-anti-covid-pill-paxlovid/a-60276666Date: Dec 28, 2021Date accessed: January 3, 2022Google Scholar‡ Data are from Südwestrundfunk.40Südwestrundfunk “ Paxlovid ” —das sollte man über das anti-corona-medikament wissen.https: //www.swr.de/swraktuell/rheinland-pfalz/medikament-paxlovid-wissenswertes-rlp-100.htmlDate: Dec 28, 2021Date accessed: January 3, 2022Google Scholar Open table in a new tab
Data are from Reuters,37ReutersFactbox: countries rush to buy experimental antiviral COVID-19 pills.https: //www.reuters.com/business/healthcare-pharmaceuticals/countries-rush-buy-merck-experimental-covid-19-pill-2021-11-03/Date: Dec 30, 2021Date accessed: January 3, 2022Google Scholar except where noted.
The first decision to be made by the health authorities of each country is whether molnupiravir and nirmatrelvir–ritonavir should be provided under research protocols, or whether these oral antivirals should be available without prospectively registering any type of scientific data from patients. This decision is relevant because clinical trial protocols will need approval from research ethics committees and regulatory agencies, and investigators must seek informed consent from all participants. Trial protocols of these ideally large and simple trials will describe in detail the selection criteria of participants and how to assess clinical outcomes. In December, 2021, this approach is being used in a UK-wide adaptive platform trial, PANORAMIC ( ISRCTN30448031).41University of OxfordPANORAMIC. Help find effective early treatment for COVID-19.https: //www.panoramictrial.org/Date accessed: January 3, 2022Google Scholar This trial aims to assess novel treatments for COVID-19 in the community. In addition, the UK National Health Service has established the prescription requirements for molnupiravir ( panel). Only people at the highest risk of getting seriously ill have been included in the list of eligible patients with COVID-19, regardless of the patient's vaccination status.42UK National Health ServiceTreatments for coronavirus ( COVID-19).https: //www.nhs.uk/conditions/coronavirus-covid-19/treatments-for-coronavirus/Date accessed: January 3, 2022Google Scholar The approach taken by other countries remains to be seen. Large differences in initial availability of both antivirals are expected between countries on the basis of antiviral orders made so far ( table 2).PanelTreatment guidance pertaining to molnupiravir for patients with COVID-19, as issued by the UK NHS * 42UK National Health ServiceTreatments for coronavirus ( COVID-19).https: //www.nhs.uk/conditions/coronavirus-covid-19/treatments-for-coronavirus/Date accessed: January 3, 2022Google ScholarIndicationPatients who have tested positive for the virus and are at highest risk of getting seriously ill. This includes patients who have: •Down syndrome•A rare condition affecting the brain or nerves ( including multiple sclerosis, motor neuron disease, Huntington's disease, or myasthenia gravis) •Sickle cell disease•Some types of cancer•HIV or AIDS•A severe liver condition ( such as cirrhosis) •Chronic kidney disease, stage 5•Had an organ, bone marrow, or stem cell transplant recently•Had chemotherapy grades B and C in the previous 12 months•Had chemotherapy in the previous 6 monthsHow to get molnupiravirPatients with one of the main symptoms of COVID-19 ( high temperature, a new continuous cough, or loss of or change to the sense of smell or taste) will be sent a free PCR test kit at home.The NHS will contact the patient ( by text, email, or phone call) within 24 h of a positive PCR test result to check if the antiviral is right for the patient. The treatment is free of charge. Molnupiravir will be delivered to the patient through a hospital pharmacy, or can be collected by a friend, relative, or NHS volunteer responder.NHS=National Health Service. * These requirements are also applicable to sotrovimab. On Dec 16, 2021, casirivimab–imdevimab was the monoclonal antibody chosen by the NHS. The change to sotrovimab a few days later was probably due to the lack of in-vitro activity of casirivimab–imdevimab against the SARS-CoV-2 omicron variant.
Patients who have tested positive for the virus and are at highest risk of getting seriously ill. This includes patients who have: •Down syndrome•A rare condition affecting the brain or nerves ( including multiple sclerosis, motor neuron disease, Huntington's disease, or myasthenia gravis) •Sickle cell disease•Some types of cancer•HIV or AIDS•A severe liver condition ( such as cirrhosis) •Chronic kidney disease, stage 5•Had an organ, bone marrow, or stem cell transplant recently•Had chemotherapy grades B and C in the previous 12 months•Had chemotherapy in the previous 6 months
Patients with one of the main symptoms of COVID-19 ( high temperature, a new continuous cough, or loss of or change to the sense of smell or taste) will be sent a free PCR test kit at home.
The NHS will contact the patient ( by text, email, or phone call) within 24 h of a positive PCR test result to check if the antiviral is right for the patient. The treatment is free of charge. Molnupiravir will be delivered to the patient through a hospital pharmacy, or can be collected by a friend, relative, or NHS volunteer responder.
NHS=National Health Service. * These requirements are also applicable to sotrovimab. On Dec 16, 2021, casirivimab–imdevimab was the monoclonal antibody chosen by the NHS. The change to sotrovimab a few days later was probably due to the lack of in-vitro activity of casirivimab–imdevimab against the SARS-CoV-2 omicron variant.
The main advantage of molnupiravir and nirmatrelvir–ritonavir is the option to dispense them at community pharmacies. However, this mode of distribution is unlikely to happen in many countries because, as mentioned previously, molnupiravir and nirmatrelvir–ritonavir will only be temporarily authorised, meaning that access to them will be controlled by the local health authorities rather than the normal channels of marketed pharmaceutical products. In some countries, available supplies might also be so low that dispensing the stock to community pharmacies could be inefficient. We presume that in almost all countries, molnupiravir and nirmatrelvir–ritonavir will primarily be prescribed outside of any research study, and could be dispensed at primary care centres, hospital pharmacies ( or similar health-care facilities), or even in nursing homes with appropriate health-care professional resources, after the prescription has been filled out by a physician. In many settings and for most patients with COVID-19, mandatory rapid testing of SARS-CoV-2 infection by certified laboratories or health-care providers will not be followed by an in-person visit with their physician—telemedicine will be the norm.43Monaghesh E Hajizadeh A The role of telehealth during COVID-19 outbreak: a systematic review based on current evidence.BMC Public Health. 2020; 201193Google Scholar, 44Hollander JE Carr BG Virtually perfect? Telemedicine for Covid-19.N Engl J Med. 2020; 382: 1679-1681Google Scholar Some health systems could try to implement a circuit that includes at-home diagnostic tests, telemedicine, and rapid turnaround of definitive laboratory testing.45Gottlieb S FDA's policy changes for COVID-19 at-home diagnostics—implications for addressing other infectious diseases and future pandemics.JAMA Health Forum. 2021; 2e215190Google Scholar In any case, withdrawal of the medication after the prescription will require a visit to the point of care.
Assuming that both oral antivirals are authorised ( as a result of having enough scientific evidence to support their positive benefit–risk assessment), the principles of distributive justice should be followed such that these medicines are prescribed according to a hierarchy of predicted efficacy, since all clinically similar patients deserve the same consideration. In other words, patients with COVID-19 who are most likely to benefit from these antivirals should be prioritised. This prioritisation should ideally be based on an evidence-based scoring system—as has been used with monoclonal antibody treatment for patients with mild-to-moderate COVID-19 who are at high risk of progressing to severe COVID-19.46Razonable RR Ganesh R Bierle DM Clinical prioritization of anti-spike antibody treatment of mild to moderate COVID-19.Mayo Clin Proc. 2022; 97: 26-30Google Scholar This scoring system is based on the FDA eligibility criteria for monoclonal antibody therapy, and a direct correlation between the number of comorbidities and the rate of hospitalisations in this type of patient was shown; therefore, patients with higher scores should have higher priority.46Razonable RR Ganesh R Bierle DM Clinical prioritization of anti-spike antibody treatment of mild to moderate COVID-19.Mayo Clin Proc. 2022; 97: 26-30Google Scholar
With limited availability of these antivirals, rationing is mandatory—as was the case with N-95 masks, ventilators, and other interventions in previous phases of this pandemic.47Emanuel EJ Persad G Upshur R et al.Fair allocation of scarce medical resources in the time of Covid-19.N Engl J Med. 2020; 382: 2049-2055Google Scholar Consequently, it is necessary that each country establish a policy on the conditions under which these oral antivirals can be prescribed. Policies that set limits on health care in hospitals must meet five ethical elements48Rosoff PM Patel KR Scates A Rhea G Bush PW Govert JA Coping with critical drug shortages: an ethical approach for allocating scarce resources in hospitals.Arch Intern Med. 2012; 172: 1494-1499Google Scholar to be considered fair. These ethical elements are derived from the Accountability and Reasonableness framework,49Daniels N Accountability for reasonableness.BMJ. 2000; 321: 1300-1301Google Scholar, 50Daniels N Sabin JE Setting limits fairly: can we learn to share medical resources?. Oxford University Press, New York, NY2002Google Scholar and are applicable to the case we are addressing. The five elements are: transparency ( the policy should be open to all stakeholders for review), relevance ( the policy must be clinically relevant to the patient population), appeals ( patients must have the opportunity to appeal a decision), enforcement ( health authorities must guarantee the implementation of the policy), and fairness ( clinically similar patients should be treated similarly across the country).48Rosoff PM Patel KR Scates A Rhea G Bush PW Govert JA Coping with critical drug shortages: an ethical approach for allocating scarce resources in hospitals.Arch Intern Med. 2012; 172: 1494-1499Google Scholar
Appeals and fairness, the third and fifth of these elements, deserve special reflections. Patients must be informed of the availability of SARS-CoV-2 antivirals and ( if applicable) be told why they were not prescribed the antiviral by their physician. Since these antivirals must be prescribed and taken within 5 days of the onset of COVID-19 symptoms, appeals must be implemented and the final decision must be made in a very short period of time ( ideally < 12 h), following the decision not to prescribe an antiviral to a patient. This need for an effective and quick appeals process creates specific logistical challenges in health systems where seeking second ( and definitive) opinions is not common.
Regarding fairness, health authorities will have to distribute the limited number of available packages of these antivirals to point-of-care sites according to pre-established criteria ( eg, adult population at risk of severe COVID-19 served by each primary care centre, or percentage of fully vaccinated adults). Physicians should have clear guidance on how to prioritise the prescription of these products, since a first come, first served approach is inefficient and inequitable. While access to these oral antivirals is limited, health authorities must help prescribers with their decision-making process by issuing a guidance document with a list of characteristics—and absence of contraindications—that priority patients must present. For example, should patients with two risk factors ( eg, obesity and diabetes) be prioritised over those with one risk factor ( eg, aged ≥60 years)? Should patients at highest risk of progression to severe COVID-19 always be prioritised, and who are those patients? Should immunocompromised patients always have priority over any other non-immunocompromised patients eligible for any of these antivirals? As mentioned previously, an evidence-based scoring system will be of crucial value. Furthermore, with substantial differences in efficacy and varying safety profiles, should a distinction be made between the patients who are prescribed one or the other antiviral according to the risk criteria of progression to severe COVID-19 presented by each patient? Prioritising nirmatrelvir–ritonavir over molnupiravir, as the FDA has done, does not appear to completely solve the problem of to whom these antivirals should be prescribed first when availability is limited.
A debate has emerged in the USA over which patients should be treated with molnupiravir and nirmatrelvir–ritonavir. If, as we believe, predicted efficacy is the most crucial factor to consider, unvaccinated patients should be prioritised over vaccinated patients, even if the temporary authorisations include both vaccinated and unvaccinated patients with COVID-19 ( as was the case with both antivirals in the UK and the USA). If there is a shortage of treatment courses available for these two antivirals, it seems reasonable to prioritise unvaccinated patients over vaccinated patients, since vaccinated individuals have a substantially lower risk of developing severe COVID-19 than unvaccinated individuals.51Centers for Disease Control and PreventionThe possibility of COVID-19 after vaccination: breakthrough infections.https: //www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/why-measure-effectiveness/breakthrough-cases.htmlDate: Dec 17, 2021Date accessed: January 3, 2022Google Scholar This approach has been rejected by some US bioethicists, who argue that “ refusing a medicine to a vaccinated person with a breakthrough infection while giving it to a vaccine refuser … was impossible to justify ”, and that this approach will reward people “ who ignored public health advice and penalise those who heeded it ”.52Dyer O Covid-19: doctors will refuse to limit use of antiviral drug to unvaccinated patients, say ethicists.BMJ. 2021; 375n2855Google Scholar There are two problems with this line of argument. First, when scarcity is the norm, predicted efficacy should be a key factor to consider, and since these two antivirals have been tested solely in unvaccinated patients, there is reason to prioritise unvaccinated over vaccinated patients. The efficacy ( and the effect size) of these antivirals in vaccinated patients with COVID-19 should not be taken for granted and should be demonstrated in double-blind, placebo-controlled RCTs. In a few months ' time, Pfizer will show the final results of a trial ( NCT05011513) that, as mentioned previously, recruited fully vaccinated participants. Second, research has shown that vaccine hesitancy is much more prevalent in some ethnic groups than others, in groups with low levels of education, and in socioeconomically deprived groups and areas.53Robertson E Reeve KS Niedzwiedz CL et al.Predictors of COVID-19 vaccine hesitancy in the UK household longitudinal study.Brain Behav Immun. 2021; 94: 41-50Google Scholar, 54Agarwal R Dugas M Ramaprasad J Luo J Li G Gao GG Socioeconomic privilege and political ideology are associated with racial disparity in COVID-19 vaccination.Proc Natl Acad Sci USA. 2021; 118e2107873118Google Scholar, 55Saban M Myers V Ben-Shetrit S Wilf-Miron R Socioeconomic gradient in COVID-19 vaccination: evidence from Israel.Int J Equity Health. 2021; 20: 242Google Scholar Some of the unvaccinated groups might have dismissed public health advice, but many others will either not have been reached by the advice, or not have fully processed the information.
Since these oral antivirals are expected to be less effective in vaccinated individuals with breakthrough SARS-CoV-2 infections than in unvaccinated individuals, the therapeutic use of these medicines in all patients regardless of vaccination status might reduce the positive benefit–risk assessment of these antivirals. From a cost-effectiveness perspective, this reduction in the positive benefit–risk assessment will result in the need to treat more patients to prevent a hospitalisation or death.
The appearance of the SARS-CoV-2 omicron variant ( and other variants that could arise in the near future) might change the clinical effectiveness of nirmatrelvir–ritonavir and molnupiravir. Actual clinical effectiveness must be urgently assessed to ensure that the prescription of these medicines is indicated regardless of the SARS-CoV-2 variant causing the infection. This assessment is especially relevant after observing that—with the likely exception of sotrovimab—the monoclonal antibodies mentioned previously have little or no in-vitro activity against omicron; 56National Institutes of HealthOpenData Portal: SARS-CoV-2 variants and therapeutics. Therapeutic activity explorer. B.1.1529. Reported in vitro therapeutic activity.https: //opendata.ncats.nih.gov/variant/activityDate accessed: January 3, 2022Google Scholar although, this lack of in-vitro activity does not necessarily mean an absence of clinical effectiveness. In the USA, four treatment options are recommended in the following order of preference: nirmatrelvir–ritonavir, sotrovimab ( single intravenous infusion), remdesivir ( intravenous infusion for 3 consecutive days as off-label use, but backed by a placebo-controlled RCT57Early remdesivir to prevent progression to severe Covid-19 in outpatients.N Engl J Med. 2021; 386: 305-315Google Scholar), and molnupiravir ( only when none of the others can be used). These options are recommended to treat non-hospitalised patients with mild-to-moderate COVID-19 who are at high risk of clinical progression.58National Institutes of HealthCOVID-19 treatment guidelines. The COVID-19 treatment guidelines panel's statement on the use of anti-SARS-CoV-2 monoclonal antibodies or remdesivir for the treatment of COVID-19 in nonhospitalized patients when omicron is the predominant circulating variant.https: //files.covid19treatmentguidelines.nih.gov/guidelines/archive/statement-on-anti-sars-cov-2 -- 12-23-2021.pdfDate: Dec 30, 2021Date accessed: January 3, 2022Google Scholar All of these medications have shown in-vitro activity against the omicron variant of SARS-CoV-2.56National Institutes of HealthOpenData Portal: SARS-CoV-2 variants and therapeutics. Therapeutic activity explorer. B.1.1529. Reported in vitro therapeutic activity.https: //opendata.ncats.nih.gov/variant/activityDate accessed: January 3, 2022Google Scholar
Most patients with COVID-19 who begin treatment with a SARS-CoV-2 oral antiviral in the upcoming months will not be included in any research protocol. Although it would be expected that international organisations ( eg, WHO59WHOTherapeutics and COVID-19: living guideline.https: //app.magicapp.org/ # /guideline/nBkO1EDate: Dec 7, 2021Date accessed: January 3, 2022Google Scholar and the European Centre for Disease Prevention and Control60European Centre for Disease Prevention and ControlTreatment and pharmaceutical prophylaxis of COVID-19.https: //www.ecdc.europa.eu/en/covid-19/latest-evidence/treatmentDate accessed: January 3, 2022Google Scholar) and professional infectious diseases associations ( eg, the European Society of Clinical Microbiology and Infectious Diseases61Bartoletti M Azap O Barac A et al.ESCMID COVID-19 living guidelines: drug treatment and clinical management.Clin Microbiol Infect. 2021; 28: 222-238Google Scholar and Infectious Diseases Society of America62Infectious Diseases Society of AmericaIDSA guidelines on the treatment and management of patients with COVID-19.https: //www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/Date: Dec 30, 2021Date accessed: January 3, 2022Google Scholar) would be diligent in including these antivirals in their guidelines on the treatment of patients with COVID-19, this guidance is unlikely to address the issue discussed. All countries aiming to make nirmatrelvir–ritonavir and molnupiravir available for their patients should prepare a policy that ensures the fair prescription of these medicines to all eligible patients. Some countries might decide not to use one of these antivirals ( as France did with molnupiravir) 63Cottineau J Pourquoi le molnupiravir, traitement du Covid-19 de Merck, a été retoqué par la HAS. L'Usine Nouvelle.https: //www.usinenouvelle.com/article/pourquoi-le-molnupiravir-traitement-du-covid-19-de-merck-a-ete-retoque-par-la-has.N1168562Date: Dec 13, 2021Date accessed: January 3, 2022Google Scholar or to restrict the use of one antiviral to a very specific list of eligible patients ( as the UK did with molnupiravir).42UK National Health ServiceTreatments for coronavirus ( COVID-19).https: //www.nhs.uk/conditions/coronavirus-covid-19/treatments-for-coronavirus/Date accessed: January 3, 2022Google Scholar Due to the complexity of prioritisation, national health authorities should start issuing their draft policies as soon as possible, so that all stakeholders can provide their input. Ideally, the final consensus policy should be ready before these products arrive in each country. This timeline should enable health systems to prepare, thereby maximising the benefits these antivirals can provide. The policy should be regularly updated, taking into account the availability of the two antivirals over time, the inclusion of novel treatments for non-hospitalised patients with mild-to-moderate COVID-19 who are at high risk of clinical progression, and the emergence of new SARS-CoV-2 variants. Health systems ' point-of-care managers and prescribing physicians should have clear guidance on how to manage the number of treatment courses received and how to proceed with any eligible patient with COVID-19. The population should be appropriately informed about what to expect from their health system with regards to these two oral antivirals, which should be fundamental tools to fight the pandemic.
Research studies should assess the effect of different SARS-CoV-2 variants in conjunction with the number of patients with COVID-19 ( clinically diagnosed and who have tested positive) who, as per each country's policy, fulfil the requirements for a prescription of nirmatrelvir–ritonavir or molnupiravir in the 5-day period from symptom onset. Any factor preventing proper process compliance in eligible patients must be identified and addressed.64McDonald SA Soetens LC Schipper CMA et al.Testing behaviour and positivity for SARS-CoV-2 infection: insights from web-based participatory surveillance in the Netherlands.BMJ Open. 2021; 11e056077Google Scholar The effectiveness of nirmatrelvir–ritonavir and molnupiravir needs to be shown in the real world, and health systems must show that they are properly adapted to prescribe and use these antivirals correctly. Health systems in high-income countries might find it challenging to show they are properly adapted, whereas this task could be insurmountable for health systems in low-income and middle-income countries, which could increase inequity in access to these medications.
To appropriately address the need for an ethical prescribing approach for these oral antivirals, each health system will need to decide upon a scoring system that prioritises eligible patients ( this scoring system might differ between health systems), and, closely related, the most appropriate location from which to provide available oral antivirals and other treatments for non-hospitalised patients with mild-to-moderate COVID-19 who are at high risk of clinical progression to severe COVID-19.
RD-R conceived the idea and wrote the first draft of the manuscript. All authors provided comments and edits throughout the drafting process for important intellectual content. All authors approved the final version of the manuscript and are accountable for all aspects included in it.
SLB declared speaker fees from Pfizer and Shionogi as well as advisory board fees from Pfizer ( for ceftazidime with avibactam) and Shionogi ( for cefiderocol), outside the submitted work. All other authors declare no competing interests. | tech |
Temporal changes in factors associated with COVID-19 vaccine hesitancy and uptake among adults in Hong Kong: Serial cross-sectional surveys - The Lancet Regional Health – Western Pacific | BackgroundCOVID-19 vaccine hesitancy can lead to reduced vaccine uptake and hinder the safe relaxation of other public health measures. This study aims to explore the factors associated with vaccine hesitancy and uptake among adults before and after the implementation of the COVID-19 vaccination program in Hong Kong.MethodsCross-sectional telephone surveys were conducted every four weeks over a nine-month period from November 2020 through July 2021. Target respondents were Hong Kong resident aged 18 or above and recruited by random-digit dialling. In each survey, responses on COVID-19 vaccine hesitancy and COVID-19 vaccine uptake were collected as primary and secondary outcomes, respectively. Data of potentially associated factors, including socio-demographics, chronic medical conditions, perceived risk of COVID-19, perceived personal efficacy in self-protection, confidence in the government's ability to control the pandemic, compliance with social distancing measures, and confidence in COVID-19 vaccines, were also collected. Multivariable logistic regression models were used to examine the factors associated with COVID-19 vaccine hesitancy at different time points.FindingsTen cross-sectional surveys were conducted, including 7411 respondents. The levels of vaccine hesitancy fluctuated over time. From December 2020 to May 2021, the age group with the highest vaccine hesitancy was young adults 18–34y, while the vaccine hesitancy was highest among adults ≥ 65y in June-July 2021 ( Fig. 2C). Our regression analyses ( Fig. 3) showed that before and at the beginning of the rollout of the mass vaccination program, there was no statistically significant association between chronic medical conditions and vaccine hesitancy. However, two-five months after the program implementation respondents with chronic medical conditions were more likely to be hesitant. From January to June 2021, higher confidence in the government was associated with lower vaccine hesitancy ( Fig. 3). Confidence in COVID-19 vaccines was consistently associated with lower vaccine hesitancy at different stages of the program.InterpretationThe factors associated with COVID-19 vaccine hesitancy changed over time. This study highlighted the importance to monitor temporal changes in COVID-19 vaccine hesitancy and associated factors, and adjust promotion strategies correspondingly to boost vaccination uptake.FundingHealth and Medical Research Fund, Hong Kong.
COVID-19 vaccine hesitancy can lead to reduced vaccine uptake and hinder the safe relaxation of other public health measures. This study aims to explore the factors associated with vaccine hesitancy and uptake among adults before and after the implementation of the COVID-19 vaccination program in Hong Kong.
Cross-sectional telephone surveys were conducted every four weeks over a nine-month period from November 2020 through July 2021. Target respondents were Hong Kong resident aged 18 or above and recruited by random-digit dialling. In each survey, responses on COVID-19 vaccine hesitancy and COVID-19 vaccine uptake were collected as primary and secondary outcomes, respectively. Data of potentially associated factors, including socio-demographics, chronic medical conditions, perceived risk of COVID-19, perceived personal efficacy in self-protection, confidence in the government's ability to control the pandemic, compliance with social distancing measures, and confidence in COVID-19 vaccines, were also collected. Multivariable logistic regression models were used to examine the factors associated with COVID-19 vaccine hesitancy at different time points.
Ten cross-sectional surveys were conducted, including 7411 respondents. The levels of vaccine hesitancy fluctuated over time. From December 2020 to May 2021, the age group with the highest vaccine hesitancy was young adults 18–34y, while the vaccine hesitancy was highest among adults ≥ 65y in June-July 2021 ( Fig. 2C). Our regression analyses ( Fig. 3) showed that before and at the beginning of the rollout of the mass vaccination program, there was no statistically significant association between chronic medical conditions and vaccine hesitancy. However, two-five months after the program implementation respondents with chronic medical conditions were more likely to be hesitant. From January to June 2021, higher confidence in the government was associated with lower vaccine hesitancy ( Fig. 3). Confidence in COVID-19 vaccines was consistently associated with lower vaccine hesitancy at different stages of the program.
The factors associated with COVID-19 vaccine hesitancy changed over time. This study highlighted the importance to monitor temporal changes in COVID-19 vaccine hesitancy and associated factors, and adjust promotion strategies correspondingly to boost vaccination uptake.
Health and Medical Research Fund, Hong Kong.
Research in context Evidence before this studyVaccine hesitancy is one of the 10 threats to global health according to the World Health Organization. In the era of COVID-19, vaccine hesitancy affects vaccination coverage in many parts of the world. Some studies have explored the factors associated with COVID-19 vaccine hesitancy at single points in time, but relatively few studies have explored factors associated with changing hesitancy over time at different phases of the COVID-19 pandemic and different stages of COVID-19 vaccination programs. We searched PubMed on 4 December 2021 for cross-sectional studies assessing the temporal changes of potential factors associated with COVID-19 vaccination intention and vaccine hesitancy with the following search terms ( ( COVID-19 OR SARS-CoV-2) AND ( vaccine hesitancy OR vaccine uptake OR vaccination intention) AND ( factors OR predictors OR determinants OR reasons OR drivers OR barriers) AND ( changes OR change OR trend OR overtime OR over time OR temporal)). We found two studies examining the potential factors associated with the changing vaccination intention or vaccine hesitancy at different time points before the rollout of the mass COVID-19 vaccination programs and five studies examining the potential factors at different time points at the beginning and after the program rollout. None of them comprehensively studied the temporal changes of potential factors associated with COVID-19 vaccination intention or vaccine hesitancy before and after the rollout of the mass COVID-19 vaccination program. Added value of this studyFrom ten monthly cross-sectional surveys before and after the implementation of the mass COVID-19 vaccination program in Hong Kong, we found that the age group with the highest vaccine hesitancy has changed from young adults aged 18-34 years before and at the beginning of the vaccination program ( December 2020-May 2021) to older adults aged ≥65 years 4-5 months after the program implementation ( June-July 2021). Before and at the beginning of the rollout of the mass vaccination program ( November 2020-March 2021), the association between chronic medical conditions and vaccine hesitancy was insignificant, however, 2-5 months after the program implementation ( April-July 2021) respondents with chronic medical conditions were more likely to be hesitant. Higher confidence in the government was not significantly associated with vaccine hesitancy in November-December 2020, but was associated with a lower risk of vaccine hesitancy from January to June 2021. We also discussed how the temporal changes in the factors associated with vaccine hesitancy could be associated with a set of contextual changes, including changes in risk of COVID-19, widespread reports about potential vaccine adverse effects from the media, and changes in vaccine-related policy. Implications of the available evidenceOur study suggests that vaccine hesitant groups and the factors associated with vaccine hesitancy could change during the implementation of the COVID-19 vaccination programs. Continuous monitoring of COVID-19 vaccine hesitancy and its associated factors, and evaluating and adjusting the vaccination program are essential for the success of the vaccination program.
Vaccine hesitancy is one of the 10 threats to global health according to the World Health Organization. In the era of COVID-19, vaccine hesitancy affects vaccination coverage in many parts of the world. Some studies have explored the factors associated with COVID-19 vaccine hesitancy at single points in time, but relatively few studies have explored factors associated with changing hesitancy over time at different phases of the COVID-19 pandemic and different stages of COVID-19 vaccination programs. We searched PubMed on 4 December 2021 for cross-sectional studies assessing the temporal changes of potential factors associated with COVID-19 vaccination intention and vaccine hesitancy with the following search terms ( ( COVID-19 OR SARS-CoV-2) AND ( vaccine hesitancy OR vaccine uptake OR vaccination intention) AND ( factors OR predictors OR determinants OR reasons OR drivers OR barriers) AND ( changes OR change OR trend OR overtime OR over time OR temporal)). We found two studies examining the potential factors associated with the changing vaccination intention or vaccine hesitancy at different time points before the rollout of the mass COVID-19 vaccination programs and five studies examining the potential factors at different time points at the beginning and after the program rollout. None of them comprehensively studied the temporal changes of potential factors associated with COVID-19 vaccination intention or vaccine hesitancy before and after the rollout of the mass COVID-19 vaccination program.
From ten monthly cross-sectional surveys before and after the implementation of the mass COVID-19 vaccination program in Hong Kong, we found that the age group with the highest vaccine hesitancy has changed from young adults aged 18-34 years before and at the beginning of the vaccination program ( December 2020-May 2021) to older adults aged ≥65 years 4-5 months after the program implementation ( June-July 2021). Before and at the beginning of the rollout of the mass vaccination program ( November 2020-March 2021), the association between chronic medical conditions and vaccine hesitancy was insignificant, however, 2-5 months after the program implementation ( April-July 2021) respondents with chronic medical conditions were more likely to be hesitant. Higher confidence in the government was not significantly associated with vaccine hesitancy in November-December 2020, but was associated with a lower risk of vaccine hesitancy from January to June 2021. We also discussed how the temporal changes in the factors associated with vaccine hesitancy could be associated with a set of contextual changes, including changes in risk of COVID-19, widespread reports about potential vaccine adverse effects from the media, and changes in vaccine-related policy.
Our study suggests that vaccine hesitant groups and the factors associated with vaccine hesitancy could change during the implementation of the COVID-19 vaccination programs. Continuous monitoring of COVID-19 vaccine hesitancy and its associated factors, and evaluating and adjusting the vaccination program are essential for the success of the vaccination program.
There is strong evidence that COVID-19 vaccines are effective for preventing symptomatic SARS-CoV-2 infections and reducing COVID-19-related hospitalizations and complications,1Al Kaabi N. Zhang Y. Xia S. et al.Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial.JAMA. 2021; 326: 35-45Google Scholar, 2Thomas S.J. Moreira E.D. Kitchin N. et al.Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine through 6 months.N Engl J Med. 2021; 385: 1761-1773Google Scholar, 3Tartof S.Y. Slezak J.M. Fischer H. et al.Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study.Lancet. 2021; 398: 1407-1416Google Scholar despite having lower efficacy against mild-to-moderate infections and disease transmission.4Madhi S.A. Baillie V. Cutland C.L. et al.Efficacy of the ChAdOx1 nCoV-19 COVID-19 vaccine against the B. 1.351 variant.N Engl J Med. 2021; 384: 1885-1898Google Scholar,5Singanayagam A. Hakki S. Dunning J. et al.Community transmission and viral load kinetics of the SARS-CoV-2 delta ( B. 1.617. 2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study.Lancet Infect Dis. 2022; 22: 183-195Google Scholar Therefore, high population uptake rates of COVID-19 vaccination can provide protection against severe disease for vaccinated individuals and limit the public health impact of COVID-19 epidemics. COVID-19 vaccination campaigns have been launched in many countries since late 2020 and early 2021. However, a major challenge to reaching high vaccination coverage is vaccine hesitancy.
Vaccine hesitancy refers to delaying or refusing a vaccine even if the vaccination services are available.6MacDonald N.E. Vaccine hesitancy: definition, scope and determinants.Vaccine. 2015; 33: 4161-4164Google Scholar Despite the increasing availability of COVID-19 vaccines worldwide, COVID-19 vaccine hesitancy was widely reported.7Tram K.H. Saeed S. Bradley C. et al.Deliberation, dissent, and distrust: understanding distinct drivers of COVID-19 vaccine hesitancy in the United States.Clin Infect Dis. 2021; https: //doi.org/10.1093/cid/ciab633Google Scholar, 8Razai M.S. Chaudhry U.A. Doerholt K. Bauld L. Majeed A. COVID-19 vaccination hesitancy.BMJ. 2021; 373: n1138Google Scholar, 9Machingaidze S. Wiysonge CS. Understanding COVID-19 vaccine hesitancy.Nat Med. 2021; 27: 1338-1339Google Scholar Some studies reported that the prevalence of vaccine hesitancy would change from time to time before and after the rollout of the mass COVID-19 vaccination campaigns.7Tram K.H. Saeed S. Bradley C. et al.Deliberation, dissent, and distrust: understanding distinct drivers of COVID-19 vaccine hesitancy in the United States.Clin Infect Dis. 2021; https: //doi.org/10.1093/cid/ciab633Google Scholar,10Daly M. Jones A. Robinson E. Public trust and willingness to vaccinate against COVID-19 in the US from October 14, 2020, to March 29, 2021.JAMA. 2021; 325: 2397-2399Google Scholar,11Wang K. Wong E.L.Y. Ho K.F. et al.Change of willingness to accept COVID-19 vaccine and reasons of vaccine hesitancy of working people at different waves of local epidemic in Hong Kong, China: repeated cross-sectional surveys.Vaccines. 2021; 9: 62Google Scholar Understanding the factor associated with vaccine hesitancy is essential to identify major hesitant groups and design effective vaccine risk communication strategies for promoting vaccination acceptance at different stages of a vaccination program. Vaccine hesitancy could be influenced by a set of individual psychological and contextual factors as well as their interactions. Contextual factors may involve increasing availability of COVID-19 vaccines, changes in risk of COVID-19, widespread reports about potential vaccine adverse effects from the media, and changes in vaccine-related policy. These contextual changes would influence individual perceptions of COVID-19 risk and confidence in COVID-19 vaccines and hence affect their vaccination intention.12Loomba S. de Figueiredo A. Piatek S.J. de Graaf K. Larson H.J. Measuring the impact of COVID-19 vaccine misinformation on vaccination intent in the UK and USA.Nat Hum Behav. 2021; 5: 337-348Google Scholar,13Solís Arce J.S. Warren S.S. Meriggi N.F. et al.COVID-19 vaccine acceptance and hesitancy in low- and middle-income countries.Nat Med. 2021; 27: 1385-1394Google Scholar In view of the unstable situation of the global pandemic, the emerge of SARS-CoV-2 Variants of Concern, and the development of new COVID-19 vaccines, the major vaccine hesitant groups and factors associated with vaccine hesitancy could also change over time. However, few studies monitored the temporal changes of the factors associated with COVID-19 vaccine hesitancy and uptake at different stages before and after the implementation of a vaccination program.
Based on repeated cross-sectional population-based surveys, this study aimed ( i) to monitor the changes of COVID-19 vaccine hesitancy over time, ( ii) to examine the potential factors associated with COVID-19 vaccine hesitancy among adults before and after the launch of the COVID-19 vaccination program in Hong Kong and ( iii) to examine the differences in sociodemographic characteristics and other factors between vaccinated and unvaccinated respondents over the five months after the implementation of the program. The potential influencing factors included in our study were sociodemographic factors, such as gender, age, education level, and occupation, and perception factors, e.g., perceived risks of COVID-19, perceived benefits and risks of COVID-19 vaccines, confidence in the authorities proving the vaccines, etc., which were potential factors associated with COVID-19 vaccine hesitancy and/or vaccination intention reported in previous studies.7Tram K.H. Saeed S. Bradley C. et al.Deliberation, dissent, and distrust: understanding distinct drivers of COVID-19 vaccine hesitancy in the United States.Clin Infect Dis. 2021; https: //doi.org/10.1093/cid/ciab633Google Scholar,14Nomura S. Eguchi A. Yoneoka D. et al.Reasons for being unsure or unwilling regarding intention to take COVID-19 vaccine among Japanese people: a large cross-sectional national survey.Lancet Reg Health West Pac. 2021; 14100223Google Scholar, 15Wiysonge C.S. Ndwandwe D. Ryan J. et al.Vaccine hesitancy in the era of COVID-19: could lessons from the past help in divining the future?.Hum Vaccin Immunother. 2022; 18: 1-3Google Scholar, 16Wong M.C. Wong E.L. Huang J. et al.Acceptance of the COVID-19 vaccine based on the health belief model: a population-based survey in Hong Kong.Vaccine. 2021; 39: 1148-1156Google Scholar, 17Woolf K. McManus I.C. Martin C.A. et al.Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: results from the UK-REACH prospective nationwide cohort study.Lancet Reg Health Eur. 2021; 9100180Google Scholar
This was a repeated cross-sectional survey conducted using random-digit dialling of both land-based telephone and mobile numbers roughly in the ratio of 1:1. The telephone numbers were randomly generated using known prefixes assigned to telecommunication services providers. The surveys were implemented by a survey company and all the phone calls were scheduled at different times of a day covering both working hours and non-working hours in order to recruit a more representative sample. Experienced interviewers were deployed by the survey company to conduct the telephone interviews. The interviewers were trained prior to the fieldwork and monitored by experienced supervisors. Each sampled telephone number were called up to five times at different times and on different days before being dropped. For land-based samples, if there was more than one eligible and available members, “ next birthday rule ” was adopted. The one who will have his/her birthday next was invited to participate in the survey. All survey data were collected by a Web-based Computer Assisted Telephone Interviewing system which allows real-time data entry by interviewers and consolidation.
A total of ten survey rounds were involved in this study. Four rounds were conducted before the implementation of the COVID-19 vaccination program in Hong Kong from early November 2020 to late January 2021, while the remaining six rounds were conducted from the first week of the program rollout ( 22–26 February 2021) and thereafter once every month till the fifth months after the COVID-19 vaccination program was launched. The sample size of each survey round was around 500 for the first five rounds and increased to approximately 1000 for the other rounds. For each survey round, a sample size of around 500 ( n) was sufficient to estimate population characteristics ( p = 0.5) with a margin of error 0.04 ( m = 0.04) and 95% confidence interval ( t = 1.96) using the following formula.n=t2×p ( 1−p) m2
Using the same formula, a sample size of around 1000 ( n) was sufficient to estimate population characteristics ( p = 0.5) with a margin of error 0.03 ( m = 0.03) and 95% confidence interval ( t = 1.96). Target respondents were Cantonese-speaking Hong Kong resident aged 18 or above and have land-based or mobile telephone lines. Visitors who travel to Hong Kong were excluded. Each telephone interview lasted for ∼ten minutes based on a standardized questionnaire. Major study measures were described below.
Before the COVID-19 vaccination program, we assessed respondents’ intention to receive a COVID-19 vaccine if it was available. The response scale was 7-point categorical ranging from “ never ” to “ certain ”. Respondents were classified as having vaccine hesitancy if they responded “ never ”, “ very unlikely ”, “ unlikely ”, or “ evens ” to take a COVID-19 vaccine, while the respondents answered “ likely ”, “ very likely ”, or “ certain ” were classified as having no/low vaccine hesitancy. From February 2021 after COVID-19 vaccines were provided in Hong Kong, respondents were first asked about their actual uptake of COVID-19 vaccination. For those who were yet to take the COVID-19 vaccines, we assessed their vaccination intention. The primary outcome of this study is vaccine hesitancy defined as never, very unlikely, unlikely, or evens to get vaccinated, rather than likely, very likely, or certain to vaccinate or already vaccinated in all survey rounds ( Fig. S1a). The secondary outcome is self-reported COVID-19 vaccine uptake in the six rounds of surveys from February to July 2021 ( Fig. S1b).
In each survey round, we collected data on socio-demographics, perceived risk of COVID-19, perceived internal, and external control over COVID-19 pandemic, compliance to social distancing measures and confidence in COVID-19 vaccines ( see Supplementary Table S1 for details). For socio-demographics, we recorded age, gender, educational attainment, and occupation of the respondents. Their chronic medical conditions were also recorded. Measures of the perceived risk of COVID-19 included perceived susceptibility to COVID-19, perceived severity of COVID-19, and worry about being infected with COVID-19. Perceived internal and external controls were perceived personal efficacy in self-protection and confidence in the government's ability to control the pandemic, respectively. We assessed compliance to social distancing measures by the compliance to avoiding crowded places, avoiding going out, and avoiding social gathering. Noting the high collinearity of these three factors, and given that compliance with avoiding social gathering was found to be a better predictor for modeling local COVID-19 transmission in our previous study,18Du Z. Wang L. Shan S. et al.Pandemic fatigue impedes mitigation of COVID-19 in Hong Kong.Res Sq. 2021; https: //doi.org/10.21203/rs.3.rs-591241/v1Google Scholar we only included the measure of compliance with avoiding social gathering in the analysis. These measures were similar to those used in our previous surveys in 2003 SARS outbreak and 2009–10 influenza A ( H1N1) pandemic.19Cowling B.J. Ng D.M. Ip D.K. et al.Community psychological and behavioral responses through the first wave of the 2009 influenza A ( H1N1) pandemic in Hong Kong.J Infect Dis. 2010; 202: 867-876Google Scholar,20Leung G.M. Ho L.M. Chan S.K.K. et al.Longitudinal assessment of community psychobehavioral responses during and after the 2003 outbreak of severe acute respiratory syndrome in Hong Kong.Clin Infect Dis. 2005; 40: 1713-1720Google Scholar All respondents were also assessed on their confidence in COVID-19 vaccines with a standard vaccine confidence scale in vaccination importance, effectiveness, safety, and religious and personal belief compatibility.21de Figueiredo A. Simas C. Karafillakis E. Paterson P. Larson HJ. Mapping global trends in vaccine confidence and investigating barriers to vaccine uptake: a large-scale retrospective temporal modelling study.Lancet. 2020; 396: 898-908Google Scholar
To demonstrate the temporal changes of COVID-19 vaccine hesitancy along with changes in the local epidemic situation, we collected official data on the number of daily reported laboratory-confirmed COVID-19 cases in Hong Kong to draw the epidemic curve from 18 January 2020 to 31 August 2021. The data were classified as numbers of local ( infected in Hong Kong) or imported ( infected outside Hong Kong) cases and the data were obtained from the Hong Kong Centre for Health Protection.22Centre for Health Protection. Coronavirus disease ( COVID-19) in HK. 2021. https: //chp-dashboard.geodata.gov.hk/covid-19/en.html. Accessed 13 Sep 2021.Google Scholar
The data analysis mainly included three parts. First, the temporal changes of COVID-19 vaccine hesitancy were assessed. The proportion of COVID-19 vaccine hesitancy in each survey was calculated as the number of respondents reported never, very unlikely, unlikely, or evens to the COVID-19 vaccination intention question over the number of respondents, and the proportions were rim-weighted by age, sex, education level, and occupation status distributions to the adult population in Hong Kong ( census data in 2019) and the 95% confidence intervals ( CIs) were also calculated with the normal approximation. The temporal changes of COVID-19 vaccine confidence against vaccine hesitancy were assessed. The weighted proportions of COVID-19 vaccine confidence and the corresponding 95% CIs for each item were calculated for each survey. Second, the unweighted factor-stratified proportions of vaccine hesitancy in each survey were calculated. Vaccine hesitancy and its associated factors were compared with chi-square tests. Multivariable logistic regression models were used to examine the factors that may have an impact on COVID-19 vaccine hesitancy at different time points. Third, factors potentially associated with COVID-19 vaccine uptake ( self-report vaccine uptake from the surveys) were assessed by running multivariable logistic regression models using data from each survey round conducted from March to July 2021. Multiple imputation was used to replace a small proportion of missing values ( no more than 6% on any factor) in the regression models. Multiple imputation was done with R package mice ( Multivariate Imputation by Chained Equations) version 3.13.0, using predictive mean matching for included variables, with 20 imputations for five iterations. Additional data analyses were conducted to explore the temporal changes of COVID-19 vaccine hesitancy by factors. Please see Supplementary Table S9 for details. All data analyses were done with R version 4.0.2 ( R Foundation for Statistical Computing, Vienna, Austria).
This study was approved by the Institutional Review Board of The University of Hong Kong ( Reference No.: UW 20-095). Verbal informed consents were provided by respondents before data collection. All data were anonymised when entered into the electronic database. Original identities ( landline phone numbers or mobile numbers) were kept in a separate file accessible only to authorised persons. No incentive was provided for the participation in the cross-sectional surveys.
The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
In total, 7411 respondents were recruited for the ten rounds of telephone surveys. The recruitment process is shown in Figure 1 and the detail recruitment process for each survey is shown in Supplementary Fig. S2. The detailed implementation date, sample size in each round, and distributions of gender, age, educational attainment, occupation, chronic medical conditions, and trust in the government of respondents in each round of surveys are shown in Table 1.Figure 1Flow chart of respondent recruitment and interview. There were 1004, 1004 and 1010 respondents in the first three rounds of surveys ( 2–5 November 2020, 30 November -3 December 2020 and 28–30 December 2020), respectively. But only 504, 537 and 329 respondents in these surveys were invited to answer the vaccination intention question. Therefore, there were 7,411 respondents included in the analysis.View Large Image Figure ViewerDownload Hi-res image Download ( PPT) Table 1Respondent characteristics.CharacteristicsTotal3–4 months before the vaccination program1–2 months before the vaccination program0–1 months after the vaccination program was implemented2–3 months after the vaccination program was implemented4–5 months after the vaccination program was implemented2–5 Nov 2020N (%) 30 Nov–3 Dec 2020N (%) 28–30 Dec 2020N (%) 25–27 Jan 2021N (%) 22–23 Feb 2021N (%) 29–31 Mar 2021N (%) 27–30 Apr 2021N (%) 24–28 May 2021N (%) 21–25 Jun 2021N (%) 19–24 Jul 2021N (%) Total number of respondents741150453732950950910011010100310041005Received at least 1st dose -- -- 0 ( 0) 106 ( 10.6) 170 ( 16.8) 234 ( 23.3) 381 ( 37.9) 516 ( 51.3) SexMale3017 ( 40.7) 212 ( 42.1) 252 ( 46.9) 137 ( 41.6) 207 ( 40.7) 235 ( 46.2) 439 ( 43.9) 422 ( 41.8) 397 ( 39.6) 368 ( 36.7) 348 ( 34.6) Female4394 ( 59.3) 292 ( 57.9) 285 ( 53.1) 192 ( 58.4) 302 ( 59.3) 274 ( 53.8) 562 ( 56.1) 588 ( 58.2) 606 ( 60.4) 636 ( 63.3) 657 ( 65.4) Age, median ( interquartile range) 52 ( 36-68) 50 ( 33-67) 51 ( 35-67) 54 ( 38-70) 49 ( 34-65) 52 ( 38-67) 55 ( 35-70) 52 ( 35-69) 52 ( 36-67) 53 ( 37-68) 55 ( 39-70) Age group18–24588 ( 7.9) 59 ( 11.7) 35 ( 6.5) 23 ( 7.0) 49 ( 9.6) 45 ( 8.8) 84 ( 8.4) 77 ( 7.6) 75 ( 7.5) 72 ( 7.2) 69 ( 6.9) 25–34968 ( 13.1) 69 ( 13.7) 85 ( 15.8) 41 ( 12.5) 64 ( 12.6) 55 ( 10.8) 128 ( 12.8) 156 ( 15.4) 133 ( 13.3) 126 ( 12.5) 111 ( 11.0) 35–441109 ( 15.0) 73 ( 14.5) 87 ( 16.2) 55 ( 16.7) 90 ( 17.7) 80 ( 15.7) 137 ( 13.7) 152 ( 15.0) 141 ( 14.1) 158 ( 15.7) 136 ( 13.5) 45–541134 ( 15.3) 58 ( 11.5) 81 ( 15.1) 56 ( 17.0) 87 ( 17.1) 83 ( 16.3) 128 ( 12.8) 144 ( 14.3) 167 ( 16.7) 161 ( 16.0) 169 ( 16.8) 55–641222 ( 16.5) 77 ( 15.3) 96 ( 17.9) 54 ( 16.4) 83 ( 16.3) 88 ( 17.3) 180 ( 18.0) 148 ( 14.7) 177 ( 17.6) 161 ( 16.0) 158 ( 15.7) 65 or above2245 ( 30.3) 157 ( 31.2) 145 ( 27.0) 96 ( 29.2) 128 ( 25.1) 147 ( 28.9) 325 ( 32.5) 309 ( 30.6) 292 ( 29.1) 310 ( 30.9) 336 ( 33.4) EducationPrimary or below1255 ( 16.9) 76 ( 15.1) 86 ( 16.0) 67 ( 20.4) 65 ( 12.8) 61 ( 12.0) 169 ( 16.9) 179 ( 17.7) 188 ( 18.7) 181 ( 18.0) 183 ( 18.2) Secondary3285 ( 44.3) 221 ( 43.8) 228 ( 42.5) 140 ( 42.6) 243 ( 47.7) 244 ( 47.9) 438 ( 43.8) 425 ( 42.1) 442 ( 44.1) 440 ( 43.8) 464 ( 46.2) Tertiary or above2777 ( 37.5) 202 ( 40.1) 220 ( 41.0) 112 ( 34.0) 195 ( 38.3) 194 ( 38.1) 387 ( 38.7) 393 ( 38.9) 356 ( 35.5) 370 ( 36.9) 348 ( 34.6) OccupationProfessional1148 ( 15.5) 77 ( 15.3) 79 ( 14.7) 56 ( 17.0) 80 ( 15.7) 95 ( 18.7) 156 ( 15.6) 159 ( 15.7) 163 ( 16.3) 128 ( 12.7) 155 ( 15.4) Clerical and service worker1369 ( 18.5) 90 ( 17.9) 113 ( 21.0) 68 ( 20.7) 132 ( 25.9) 86 ( 16.9) 166 ( 16.6) 176 ( 17.4) 174 ( 17.3) 181 ( 18.0) 183 ( 18.2) Production worker717 ( 9.7) 53 ( 10.5) 46 ( 8.6) 36 ( 10.9) 40 ( 7.9) 58 ( 11.4) 104 ( 10.4) 85 ( 8.4) 109 ( 10.9) 99 ( 9.9) 87 ( 8.7) Schooling359 ( 4.8) 37 ( 7.3) 24 ( 4.5) 10 ( 3.0) 22 ( 4.3) 26 ( 5.1) 59 ( 5.9) 48 ( 4.8) 47 ( 4.7) 47 ( 4.7) 39 ( 3.9) Home maker1341 ( 18.1) 79 ( 15.7) 77 ( 14.3) 57 ( 17.3) 80 ( 15.7) 70 ( 13.8) 154 ( 15.4) 200 ( 19.8) 199 ( 19.8) 227 ( 22.6) 198 ( 19.7) Retired2052 ( 27.7) 141 ( 28.0) 166 ( 30.9) 79 ( 24.0) 116 ( 22.8) 142 ( 27.9) 318 ( 31.8) 284 ( 28.1) 253 ( 25.2) 266 ( 26.5) 287 ( 28.6) Not employed nor schooling308 ( 4.2) 17 ( 3.4) 22 ( 4.1) 11 ( 3.3) 30 ( 5.9) 23 ( 4.5) 30 ( 3.0) 43 ( 4.3) 42 ( 4.2) 44 ( 4.4) 46 ( 4.6) With chronic medical condition2361 ( 31.9) 166 ( 32.9) 168 ( 31.3) 104 ( 31.6) 138 ( 27.1) 142 ( 27.9) 337 ( 33.7) 324 ( 32.1) 326 ( 32.5) 318 ( 31.7) 338 ( 33.6) Higher trust in the government2730 ( 36.8) 178 ( 35.3) 159 ( 29.6) 101 ( 30.7) 144 ( 28.3) 170 ( 33.4) 364 ( 36.4) 346 ( 34.3) 371 ( 37.0) 416 ( 41.4) 481 ( 47.9) Open table in a new tab
Hong Kong had experienced four epidemic waves of COVID-19 and we categorised the first wave from 23 January to 29 February 2020, the second wave from 1 March to 30 April 2020, the third wave from 1 May to 31 October 2020, and the fourth wave from 1 November 2020 to 31 May 2021 ( Figure 2A). The survey timeline covered the fourth wave and post-fourth wave periods from November 2020 to July 2021. From early November to early December 2020, around 34–41% of the respondents reported that they were having COVID-19 vaccine hesitancy, but the rate increased to 51.5% ( 95% CI: 46.6–56.3%) in late January 2021 ( Figure 2B and Supplementary Table S4). Since the launch of the program, the vaccine hesitancy rate declined to 43.0% ( 95% CI: 38.0–48.0%) in late February, but the rate increased again to around 49–55% 1–3 months later ( late March to late May 2021). Then, the vaccine hesitancy rate decreased significantly in June and July 2021 to 26.5% ( 95% CI: 23.4–29.6%). Figure 2C shows the unweighted vaccine hesitancy rate by age groups. The rates ( 58–83%) were highest among young adults aged 18–34 years old from December 2020 to May 2021. Nonetheless, the vaccine hesitancy rates decreased to around 22–30% in this age group in July 2021. For older adults aged 65 or above, the proportions of COVID-19 vaccine hesitancy were around 31–40% from early November 2020 to late February 2021. But the rates remained at higher levels ( 45–54%) from March to June 2021. In the last survey conducted in July 2021, the vaccine hesitancy rate was highest in the age group 65 years or above.Figure 2Panel A. COVID-19 cases by date of reporting. The reporting period is from 18 January 2020 to 31 August 2021. Panel B. COVID-19 vaccine hesitancy. COVID‐19 vaccine hesitancy was defined as never, very unlikely, unlikely, or evens to get vaccinated, rather than likely, very likely or certain to vaccinate or already vaccinated. The proportions of COVID-19 vaccine hesitancy were weighted to the Hong Kong census data in 2019, with 95% CI +/- about 3%. Panel C. COVID-19 vaccine hesitancy stratified by age. Proportions shown in Panel C are unweighted age-stratified vaccine hesitancy rates. Panel D. COVID-19 vaccine confidence. Vaccine confidence was defined as agree or strongly agree to statements rather than neutral, disagree or strongly disagree. The proportions of vaccine confidence were weighted to the Hong Kong census data in 2019, with 95% CI +/- about 3%.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
The temporal changes in COVID-19 vaccine confidence are shown in Figure 2D and Supplementary Table S4. The confidence in vaccine safety and efficacy decreased from November 2020 to January 2021 and increased gradually in the subsequent months from February to July 2021. The confidence in vaccine safety and efficacy reached the highest levels of 54.6% ( 95% CI: 50.9–58.3%) and 63.7% ( 95% CI: 59.9–67.4%), respectively in late July 2021. Most respondents ( 70.6%) believed that COVID-19 vaccines would be important for children to have in late November to early December 2020. However, this proportion dropped significantly to 38.2% ( 95% CI: 34.6–41.8%) in April and May 2021 and remained at around 50% in June and July 2021. The proportions of respondents who reported COVID-19 vaccines were compatible with their religious beliefs and personal values were higher from early November to early December 2020 ( 33–36% and 59–64%, respectively) and remained at low levels of around 22–28% and 45–55% separately from late December 2020 to late July 2021. The reliability coefficient of the five items for measuring COVID-19 confidence was 0.82 ( 95% CI: 0.81–0.83) ( value of Cronbach's alpha). Thus, we calculated the mean of respondents’ answers to the five items on COVID-19 vaccine confidence which was then categorized into low vaccine confidence ( mean score≤ 3) and high vaccine confidence ( mean score > 3) for subsequent logistic regression analyses.
Supplementary Table S5 shows the unweighted factor-stratified COVID-19 vaccine hesitancy in each survey and Figure 3 shows the adjusted odds ratios of factors of multivariable regression analyses. Females were more likely to be hesitant to take the vaccines before and at the beginning of the vaccination program ( November-December 2020 and March 2021), but three months after the implementation ( May-July 2021) of the program, gender was no longer a statistically significant factor associated with vaccine hesitancy. The analyses showed that age group was not a statistically significant factor associated with vaccine hesitancy from December 2020 to February 2021. However, younger adults and older adults were statistically significantly more hesitant to take the vaccine compared to mid-aged adults from March to July 2021. There was no obvious pattern in vaccine hesitancy in respondents with different occupations or educational attainment. Before the launch of the vaccination program, having chronic medical conditions was not statistically significantly associated with vaccine hesitancy but was associated with a greater risk of vaccine hesitancy after the vaccination program started from April to July 2021, with the adjusted odds ratios ranging from 1.57 ( 95% CI: 1.10–2.23) to 2.15 ( 95% CI: 1.50–3.08) ( Table S6). Higher confidence in the government was not statistically significantly associated with vaccine hesitancy in November-December 2020, but was associated with a lower risk of vaccine hesitancy from January to June 2021. Worry about being infected with SARS-CoV-2 and belief in self-efficacy in preventing COVID-19 were not statistically significantly associated with vaccine hesitancy throughout the ten survey rounds. In addition, greater confidence in COVID-19 vaccines was associated with lower vaccine hesitancy in all survey rounds.Figure 3Multivariable logistic regression analysis of potential factors associated with COVID-19 vaccine hesitancy. Numbers in the boxes are odds ratios. Numbers in black and with “ * ” indicate statistically significant. Green color indicates less likely to be hesitant and orange indicates more likely to be hesitant.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
The self-reported COVID-19 vaccine uptake rate was 0% ( 0/509) in February 2021, 10.6% ( 106/1001) in March 2021, 16.8% ( 170/1010) in April 2021, 23.3% ( 234/1003) in May 2021, 37.9% ( 381/1004) in June 2021 and 51.3% ( 516/1005) in July 2021 ( Table 1). Supplementary Table S7 shows the unweighted factor-stratified COVID-19 vaccine uptake in each survey and Figure 4 presents the adjusted odds ratios of potential factors that were associated with COVID-19 vaccine uptake from March to July 2021. Vaccinated respondents were less likely to be female ( adjusted odds ratios > 1) in late March 2021, but the gender difference was not statistically significant from April to July 2021. In the last survey, vaccinated respondents were more likely to be mid-aged adults and attended secondary, tertiary or above education ( adjusted odds ratios < 1). People with chronic medical conditions were less likely to report having received COVID-19 vaccines from April to July 2021. Vaccinated respondents tended to trust in their ability to prevent themselves from SARS-CoV-2 infections and have confidence in the government to control the pandemic in March/April 2021. In addition, vaccinated respondents reported lower compliance to social distancing measures compared to unvaccinated respondents in May and July 2021. Higher confidence in COVID-19 vaccines was statistically significantly associated with vaccine uptake in all survey rounds.Figure 4Multivariable logistic regression analysis of potential factors associated with COVID-19 vaccine uptake. Numbers in the boxes are odds ratios. Numbers in black and with “ * ” indicate statistically significant. Green color indicates more likely to be already vaccinated and orange indicates less likely to be already vaccinated.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Our study was conducted from November 2020 to July 2021 to monitor the changes in COVID-19 vaccine hesitancy before and after the implementation of the mass COVID-19 vaccination program in Hong Kong covering the fourth wave and post-fourth wave period. When COVID-19 vaccines were under development and testing, Wang and colleagues conducted two cross-sectional online surveys in February 2020 ( the first wave) and August–September 2020 ( the third wave), respectively, among the working population in Hong Kong.11Wang K. Wong E.L.Y. Ho K.F. et al.Change of willingness to accept COVID-19 vaccine and reasons of vaccine hesitancy of working people at different waves of local epidemic in Hong Kong, China: repeated cross-sectional surveys.Vaccines. 2021; 9: 62Google Scholar Their study found that rates of COVID-19 vaccine hesitancy ( defined as refuse or undecided rather than accept COVID-19 vaccines) increased from 55.8% in the first wave to 65.2% in the third wave.11Wang K. Wong E.L.Y. Ho K.F. et al.Change of willingness to accept COVID-19 vaccine and reasons of vaccine hesitancy of working people at different waves of local epidemic in Hong Kong, China: repeated cross-sectional surveys.Vaccines. 2021; 9: 62Google Scholar Our study found that vaccine hesitancy during the fourth wave and post-fourth wave period was generally lower compared to the vaccine hesitancy rates in the first and third waves reported by Wang et al.11Wang K. Wong E.L.Y. Ho K.F. et al.Change of willingness to accept COVID-19 vaccine and reasons of vaccine hesitancy of working people at different waves of local epidemic in Hong Kong, China: repeated cross-sectional surveys.Vaccines. 2021; 9: 62Google Scholar Our study findings were somewhat different from that conducted in the United States which reported that COVID-19 vaccine hesitancy ( similar definition to ours) decreased from 46.0% in October 2020 before the implementation of COVID-19 vaccination campaign there to 35.2% in March 2021 after the program had been implemented for three months.10Daly M. Jones A. Robinson E. Public trust and willingness to vaccinate against COVID-19 in the US from October 14, 2020, to March 29, 2021.JAMA. 2021; 325: 2397-2399Google Scholar Our study provides important insights into the changes in factors that influenced COVID-19 vaccine hesitancy as the vaccines became increasingly available for the population.
First, we found that the vaccine hesitancy increased one month before the start of the mass COVID-19 vaccination program. Many contextual changes could possibly contribute to the increase, e.g. recent reports about the potential adverse effects following COVID-19 vaccination in the countries where mass COVID-19 vaccination campaigns started in December 2020 and January 2021. In late February 2021, COVID-19 vaccines were primarily provided for five priority groups in Hong Kong, including adults aged 60 years old or above, healthcare workers, residents and staff of residential care homes, personnel maintaining critical public services, and personnel performing cross-boundary related work.23The Government of the Hong Kong SAR. Government announces 2019 COVID-19 vaccination programme. 2021. https: //www.info.gov.hk/gia/general/202102/18/P2021021800767.htm. Accessed 2 Nov 2021.Google Scholar And the top government officials took the lead to receive the first few doses of COVID-19 vaccines in Hong Kong. Our survey conducted in the first week of the program showed that the rate of COVID-19 vaccine hesitancy nevertheless decreased to 43.0%. From 16 March 2021, the priority groups of COVID-19 vaccination were expanded to all adults aged 30 or above in Hong Kong. However, Comirnaty vaccination services were suspended from 24 March to 5 April 2021 due to the packaging defects of the Comirnaty vaccine, one of the two types of COVID-19 vaccines available in Hong Kong.24The Government of the Hong Kong SAR. Suspension of BioNTech vaccination. 2021. https: //www.info.gov.hk/gia/general/202103/24/P2021032400357.htm ( accessed 10 Nov 2021).Google Scholar This could be a potential major contributor to the temporary increase in COVID-19 vaccine hesitancy detected in the survey round conducted in late March 2021. Starting from 23 April 2021, the COVID-19 vaccination program was expanded to cover all Hong Kong residence aged 16 years or above. In May 2021, incentives such as paid leaves due to COVID-19 vaccination and some relaxation of social distancing measures for vaccinated individuals were announced by the government of Hong Kong to encourage COVID-19 vaccine uptake. In addition, some private sectors in Hong Kong also introduced tangible incentives such as lotteries to encourage people to take the vaccines. These contextual changes might have contributed to the decrease in COVID-19 vaccine hesitancy since May 2021 which reached a rate of 26.5% in late July 2021.
The temporal changes in associations of age and chronic medical condition with COVID-19 vaccine hesitancy and uptake also provided important insights. We found that young adults aged 18–34 had the highest COVID-19 vaccine hesitancy in late 2020 – early 2021 but their vaccine hesitancy became comparable to that of the mid-age group in July 2021. The incentives from the government and private sectors and the exemption from frequent compulsory COVID-19 testing among certain working groups might possibly contribute to the change among young adults. Older adults aged 65 or above who had the least vaccine hesitancy in late 2020 became the most hesitant age group in mid-2021 and the COVID-19 vaccine uptake rate was lowest among older adults in June-July 2021. The results from the regression analyses suggested that chronic disease was not associated with COVID-19 vaccine hesitancy from late 2020 to early 2021. However, the chronic medical condition became a statistically significant factor associated with vaccine hesitancy and uptake from April to July 2021. The temporal changes of these associations of older age and chronic medical condition with COVID-19 vaccine hesitancy and uptake could possibly be explained by the changes of risk and benefit perception of COVID-19 vaccination. There were also several reports of fatalities in older adults following COVID-19 vaccination and the changes in medical recommendations for the COVID-19 vaccination of people with underlying medical conditions.25The Government of the Hong Kong SAR. LCQ17: COVID-19 vaccination programme. 2021. https: //www.info.gov.hk/gia/general/202104/21/P2021042000643.htm? fontSize=1. Accessed 5 Dec 2021.Google Scholar These contextual changes have greatly influenced vaccine hesitancy among older people and people with underlying medical conditions. In addition, Hong Kong adopts the “ zero-COVID ” strategy and COVID-19 local transmission has been maintained at a low level since April 2021. This has contributed to low perceived risks from infections with SARS-CoV-2, which means that perceived risks from the adverse events associated with the vaccination could outweigh the perceived risk from the disease.
Compared to other countries/territories following the “ zero-COVID ” strategy, the prevalence of vaccine hesitancy was higher among the Hong Kong population compared to that in Mainland China and New Zealand.26Wang J. Lu X. Lai X. et al.The changing acceptance of COVID-19 vaccination in different epidemic phases in China: a longitudinal study.Vaccines. 2021; 9: 191Google Scholar,27Prickett K.C. Habibi H. Carr PA. COVID-19 vaccine hesitancy and acceptance in a cohort of diverse New Zealanders.Lancet Reg Health West Pac. 2021; 14100241Google Scholar As the natural infection rate of COVID-19 is low in Hong Kong, a high uptake rate is crucial to achieve a high level of population immunity. Hong Kong's current COVID-19 first dose vaccine uptake rate was only 61.4% among the population aged 12 or above by 31 August 2021. Older adults and individuals with chronic diseases who are at high risk of severe consequences after SARS-CoV-2 infection28Zheng Z. Peng F. Xu B. et al.Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis.J Infect. 2020; 81: e16-e25Google Scholar,29Bajgain K.T. Badal S. Bajgain B.B. Santana M.J. Prevalence of comorbidities among individuals with COVID-19: a rapid review of current literature.Am J Infect Control. 2021; 49: 238-246Google Scholar had the highest hesitancy to take COVID-19 vaccines. This can be a potential challenge to the healthcare system if the pandemic resurges in Hong Kong. Public communication on the safety profile of COVID-19 vaccines among older adults and people with chronic medical conditions2Thomas S.J. Moreira E.D. Kitchin N. et al.Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine through 6 months.N Engl J Med. 2021; 385: 1761-1773Google Scholar is critical to dispel their misconceptions and promote population-wide vaccination uptake.
Trust in the government's ability to control the pandemic could be used as a proxy of confidence in the government. From January to June 2021, those having confidence in the government were less likely to be vaccine hesitant. Other studies also found that greater vaccine hesitancy was associated with lower confidence in the government or lower public trust in authorities who provided the vaccination services.7Tram K.H. Saeed S. Bradley C. et al.Deliberation, dissent, and distrust: understanding distinct drivers of COVID-19 vaccine hesitancy in the United States.Clin Infect Dis. 2021; https: //doi.org/10.1093/cid/ciab633Google Scholar,14Nomura S. Eguchi A. Yoneoka D. et al.Reasons for being unsure or unwilling regarding intention to take COVID-19 vaccine among Japanese people: a large cross-sectional national survey.Lancet Reg Health West Pac. 2021; 14100223Google Scholar,30Dodd RH, Pickles K, Cvejic E, et al. Perceived public health threat a key factor for willingness to get the COVID-19 vaccine in Australia. medRxiv 2021 Aug 5; S0264-410X ( 21) 01008-2. doi: 10.1016/j.vaccine.2021.08.007. Online ahead of print.Google Scholar Since the social unrest in 2019 in Hong Kong,31Ni M.Y. Yao X.I. Leung K.S. et al.Depression and post-traumatic stress during major social unrest in Hong Kong: a 10-year prospective cohort study.Lancet. 2020; 395: 273-284Google Scholar the trust in the government among people of different political orientations has become extremely low, which can be a challenge to encourage their uptake of COVID-19 vaccines in Hong Kong.
There were some limitations in this study. First, the data were collected using telephone surveys. Although efforts were made to improve the representativeness of samples to the population including making phone calls during and beyond working hours and generating phone numbers for landline and mobile at a 1:1 ratio, volunteer bias was unavoidable. Self-reported vaccination uptake rates were generally higher compared to the actual uptake rates during the survey periods ( the actual COVID-19 first dose uptake rates among adults aged 18 or above on the end dates of the last 5 surveys were 7.2%, 14.3%, 20.5%, 32.6%, and 46.8%, respectively). This may possibly because vaccinated individuals were more willing to participate in the telephone surveys. Second, the vaccine hesitancy responses were self-reported. Respondents reported having vaccine hesitancy may not necessarily translate to no vaccine uptake, while respondents reported likely, very likely, or certain to take COVID-19 vaccines may still delay taking the vaccines.6MacDonald N.E. Vaccine hesitancy: definition, scope and determinants.Vaccine. 2015; 33: 4161-4164Google Scholar Third, we did not record the reasons for vaccine hesitancy in the surveys. Fourth, we could not provide evidence about the causal associations between contextual changes including changes in the news reports about COVID-19 vaccines and policies and the changes in public risk perceptions and their vaccine hesitancy. It limited us from providing more specific recommendations to boost vaccine uptake among hesitant groups. In addition, the findings of this study were limited by the cross-sectional design. No causal relationship could be inferred.
In conclusion, the prevalence of COVID-19 vaccine hesitancy, and the associated factors would change over time. As the COVID-19 pandemic transitioning to the endemicity phase, high vaccination coverage is essential to ensure the sustainability of that transition. In addition, the third dose has been administered in some countries and booster shots might be administered to the general population ultimately.32Krause P.R. Fleming T.R. Peto R. et al.Considerations in boosting COVID-19 vaccine immune responses.Lancet. 2021; 398: 1377-1380Google Scholar Regular monitoring of vaccine hesitancy and its predictors should be implemented to guide policy-making to boost vaccine uptake.
BJC consults for AstraZeneca, GSK, Moderna, Pfizer, Roche and Sanofi Pasteur. The authors report no other potential conflicts of interest.
The study was designed by JX, BJC and QL. The survey tools were developed by JX, BJC and QL. Funding was obtained by MYN, BJC and QL. Data analyses were done by JX and JC. JX wrote the first draft of the manuscript and all authors interpreted data, provided critical review and revision of the text and approved the submitted manuscript.
We thank the Government of the Hong Kong Special Administrative Region and the Food and Health Bureau of the Hong Kong SAR Government ( Grant No.: COVID19F04).
Survey data are available from the corresponding author on request.
The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations.
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Citizen science data are crucial to understand wildlife roadkill, demonstrates a study in Flanders -- ScienceDaily | Making roads safer for both animals and people starts with a simple first step: understanding when, where, and how many animals get run over. This knowledge can help protect specific species, for example by using warning signs, preventing access to the roads for animals, creating overpasses and underpasses, or closing roads. Wildlife roadkill data can also help monitor other trends, such as population dynamics, species distribution, and animal behavior.
Thanks to citizen science platforms, obtaining this kind of data is no longer a task reserved for scientists. There are now dozens of free, easy-to-use online systems, where anyone can record wildlife collision accidents or roadkill, contributing to a fuller picture that might later be used to inform policy measures.
One such project is the Flemish Animals under wheels, where users can register the roadkill they saw, adding date, time and geolocation online or by using the apps. The data is stored in the online biodiversity database Waarnemingen.be, the Flemish version of the international platform Observation.org.
Between 2008 and 2020, the project collected almost 90,000 roadkill records from Flanders, Belgium, registered by over 4,000 citizen scientists. Roadkill recording is just a small part of their nature recording activities -- the multi-purpose platform which also allows the registration of living organisms. This is probably why the volunteers have remained engaged with the project for over 6 years now.
In a first for science, researchers from Natuurpunt Studie, the scientific institute linked to the largest Nature NGO in Flanders, with support from the Department of Environmental and Spatial Development, set out to analyze over 10 years of roadkill records in the region, using data provided by citizen scientists. In their study, published in the peer-reviewed journal Nature Conservation, they focused on 17 key species of mammals and their fate on the roads of Flanders.
The researchers analyzed data on 145,000 km of transects monitored, which resulted in records of 1,726 mammal and 2,041 bird victims. However, the majority of the data -- over 60,000 bird and mammal roadkill records -- were collected opportunistically, where opportunistic data sampling favors larger or more `` enigmatic '' species. Hedgehogs, red foxes and red squirrels were the most frequently registered mammal roadkill victims.
In the last decade, roadkill incidents in Flanders have diminished, the study found, even though search effort increased. This might be the result of effective road collision mitigation, such as fencing, crossing structures, or animal detection systems. On the other hand, it could be a sign of declining populations among those animals that are most prone to being killed by vehicles. More research is needed to understand the exact reason. Over the last 11 years, roadkill records of the European polecat showed a significant relative decrease, while seven species, including the roe deer and wild boar, show a relative increase in recorded incidents.
There seems to be a clear influence of the COVID-19 pandemic on roadkill patterns for some species. Restrictions in movement that followed likely led simultaneously to fewer casualties and a decrease in the search effort.
The number of new observations submitted to Waarnemingen.be continues to increase year after year, with data for 2021 pointing to about 9 million. Even so, the scientists warn that those recorded observations `` are only the tip of the iceberg. ''
`` Citizen scientists are a very valuable asset in investigating wildlife roadkill, '' the researchers conclude. `` Without your contributions, roadkill in Flanders would be a black box. '' | science |
Are Children Really Learning? Exploring foundational skills in the midst of a learning crisis | Even before the onset of the COVID-19 pandemic, there were serious questions about whether children were actually learning. With widespread school closures and other disruptions to the education system brought about by the pandemic, the learning crisis has escalated to new heights. As the pandemic enters its third year, 23 countries – home to around 405 million schoolchildren – are yet to fully open schools, with many schoolchildren at risk of dropping out. Over the past two years nearly 147 million children missed more than half of their in-person schooling, amounting to 2 trillion hours of lost learning. Children have to get back to the classroom, but changes are needed to ensure that they really learn, starting with the foundational basics of reading and numeracy.
This report offers unique insight into the extent of the learning crisis by providing an in-depth picture of which children are most at risk of not acquiring foundational learning skills. The analysis of 32 low- and middle-income countries and territories uses newly released data to examine the equity perspectives of the crisis, exploring learning outcomes among different subgroups of children, with a focus on the most vulnerable.
Children are expected to have acquired foundational reading and numeracy skills at the end of Grade 2. But in half of the countries analyzed, only 30 per cent of children attending Grade 3 have foundational reading skills and a mere 18 per cent have foundational numeracy skills. Among many countries in sub-Saharan Africa, fewer than one in 10 children have foundational learning skills on time.
When looking at the factors that impede the attainment of foundational learning skills, poverty is the most striking, particularly with regard to reading skills. The likelihood that a child in the lowest wealth quintile has foundational reading skills is 16 percentage points lower than for a child from the highest wealth quintile. For foundational numeracy, the difference is 9 percentage points. Other factors that influence foundational reading skills include gender, urban-rural location, functional difficulty status, parental involvement in their children’ s education and the home environment.
In some countries, the percentage of out-of-school children is particularly alarming, most notably in Chad, where half of all children aged 8-14 are out-of-school. Even more striking, the data reveal that in the Central African Republic, Chad, Guinea-Bissau, Sao Tome and Principe, and Sierra Leone the children who are out of school do not have any foundational reading skills.
Data emerging from several countries indicate that COVID-19 -related hardships and shuttered schools have led to a worsening of the numbers of out-of-school children. For example, in South Africa, the number of out-of-school children tripled from 250,000 to 750,000 between March 2020 and July 2021, and in Malawi, the dropout rate among girls in secondary education increased by 48 per cent between 2020 and 2021. In Kenya, a survey of 4,000 adolescents aged 10-19 years found that 16 per cent of girls and 8 per cent of boys did not return when schools reopened. Further evidence also points to substantial numbers of children not returning to school following reopening: in Liberia, 43 per cent of students reportedly did not return to the classroom when schools reopened; and in Uganda about one in 10 students at the primary and secondary levels did not report back to school at reopening.
In the countries analyzed, the current pace of learning is so slow that it would take an average of seven years for most schoolchildren to learn foundational reading skills that should have been grasped in two years, and 11 years to learn foundational numeracy skills.
The prolonged school closures and other major disruptions to the education system brought on by the pandemic have led to substantial learning loss. Simulations comparing the impact of a year of school closures on different age cohorts of children ( Grade 1 and Grade 6) reveal that younger children are at risk for more substantial and sustained learning loss than older children. A child currently enrolled in Grade 1 could suffer a 27 percentage point reduction in reading mastery by Grade 9. This signifies the urgent need to redouble efforts to make up for this period of learning loss. If effective learning recovery strategies are introduced, both younger and older children can be expected to regain nearly all of their lost learning by the time they reach Grade 9.
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The dataset you are about to download is licensed under a Creative Commons Attribution 3.0 IGO license. | general |
What a day! Fix Emea 2022 in London | What a day last Thursday! 2 years and 2 weeks elapsed since the last FIX EMEA trading conference in London! An absolute eternity! I felt excited like a schoolboy leaving home for the first day of the new school year… Who will be there again? Who switched classes? How did things go over the last 2 years? How well did it feel, getting on the Eurostar to London! It used to be a routine…now it was an experience again! Arriving in St-Pancras, jumping on the Thameslink, jumping off in The City and 5 minutes walking to the venue….the return of the salesman’ s life…I almost forgot the excitement of it it! Finally, I arrived at Leonardo Royal and entered the already well crowded exposition area. Before I could even reach the cloakroom I bumped into Alex and Ty, shook hands with James and noticed a bunch of former colleagues, clients and friends who I hadn’ t seen live for years! I caught up with Eric, learning about the latest evolutions in the bank’ s dealing room, had coffee with my Scandinavian friends from Nasdaq, Sequitor, London Stock Exchange and wherever they were working now. How nice to see my Italian friends from List and exchanging old memories with Kumalin, Simon and Stewart! Nick from Traderserve, it must have been 4-5 years since we last met! As much fun it was to meet “ old “ friends, as enjoyable it was to meet people I did not know… In one way or another the atmosphere just led to new acquaintances. I met with Pippa, senior director in a big bank, who got into finance after a career in the Royal Navy. With Monica, born and raised in Costa Rica, I chatted about her wonderful country which I visited a couple of times as a mariner myself. And there was Robert, Arsiane, Yuhang, Dan…and so many more. The price for the funniest company name certainly went to my new Dutch friends of “ BOTS ”, “ bots ” meaning “ bump ” in English. Of course, one would forget, we talked about business as well, exchanging more information and news than in a month of on-line covid times. I had a great strategy discussion with Richard and John and a technical one with Paul. New opportunities popped up, next actions got agreed, plans made, ….summarized: we’ re back in business! As a cherry on the conference cake I met with Karen, whose name strongly suggested Flemish ancestors. And yes, we had a lively chat about the origins of the “ Biebuyck ” name. After the conference a lot of people gathered at the pub around the corner and discussions and exchanges of ideas just went on in this friendly atmosphere that I also hardly remembered. I had a fantastic day and evening thanks to this fantastic FIX Global event team! Thank you FIX Global and all sponsors and participants! We are so happy and proud to be part of this lively and exciting community! I can’ t wait to see you again very soon, in Stockholm!
1538 | tech |
Home prices rose 19.2% in January from last year | Home prices continued to surge higher in January.
Prices rose 19.2% in January from the year before, up from an 18.9% annual increase in December, according to the S & P CoreLogic Case-Shiller US National Home Price Index.
Phoenix, Tampa and Miami reported the highest annual gains among the 20 cities in the index in January. Phoenix led the way for the 32nd consecutive month with prices 32.6% higher than the year before. It was followed by Tampa with a 30.8% increase, and Miami with a 28.1% gain.
Sixteen of the 20 cities saw higher year-over-year price increases in January than in December. Price growth was strongest in the South, but every region continued to see gains.
`` Home price changes in January 2022 continued the strength we had observed for much of the prior year, '' said Craig J. Lazzara, managing director at S & P Dow Jones Indices.
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How much house can I afford?
Last fall, price increases began to slow. But that trend reversed in January, with the year-over-year jump in prices being the fourth largest in the 35 years of data.
`` The macroeconomic environment is evolving rapidly. Declining Covid cases and a resumption of general economic activity has stoked inflation, and the Federal Reserve has begun to increase interest rates in response, '' said Lazzara. `` We may soon begin to see the impact of increasing mortgage rates on home prices. ''
Choppier waters ahead
The numbers showed a strong start to the 2022 housing market, as buyers rushed to snag a home before mortgage rates climbed too high, but many factors have changed since January, said George Ratiu, senior economist and manager of economic research at Realtor.com.
`` The world has changed considerably since the start of the year, with a host of events shuffling the economic and real estate landscape, '' Ratiu said. `` Globally, Russia's invasion in Ukraine destroyed human lives, along with a long stretch of relative stability in Europe. The continuing war is impacting global trade and leading to renewed disruptions in supply chains. ''
In the US, inflation surged to levels
not seen since the 1980s
, prompting the Federal Reserve to
increase the federal funds rate
and signal much more aggressive monetary tightening in the coming months, he said.
These factors seem to indicate a significant shift for the real estate market, Ratiu added.
`` While buyers remain interested and willing to purchase homes,
mortgage rates
are already moving toward 5% and starting to cap their ability to qualify for a loan, '' he said.
The monthly payment for a median-priced home has jumped 30% in the past year, far outpacing even fast-rising consumer prices, which are up almost 8% from a year ago, he said.
Rent jumped 17% since last year, hitting a new record
Other indicators show that both sales of new and
existing homes
in February were slower as inventory remains near record lows and costs to own a home continue to rise.
Even as the small number of homes for sale will continue to push prices higher throughout the spring buying season, Ratiu said, he expects real estate conditions to adjust in the months ahead.
`` For sellers, April offers the ideal combination of higher prices and still-limited competition from other homeowners that typically ensure a successful close, '' he said. `` For buyers, local market conditions and personal circumstances will determine if there's more value in securing a fixed mortgage rate now versus holding out for more inventory and better prices later in the year. '' | general |
Dollar declines, euro jumps on hopes in Ukraine peace talks | In this article
The dollar fell against a basket of peer currencies on Tuesday following reports of progress in peace talks between Russia and Ukraine, giving a lift to the euro and reducing the safe-haven appeal of the greenback.
Russia promised at peace talks in Istanbul on Tuesday to scale down its military operations around Kyiv and northern Ukraine, while Ukraine proposed adopting a neutral status but with international guarantees that it would be protected from attack.
The dollar, which had risen as much as 3.4% since Russia invaded Ukraine, declined 0.914% to 98.181, as traders looked to currencies deemed riskier.
`` Risk appetite is back and I think you're seeing potentially a major turning point in the war in Ukraine as Russia signals talks have been constructive and there's hope that there could be a ceasefire, '' said Edward Moya, senior analyst at Oanda.
The euro was up 1.13% at $ 1.111, having earlier hit its highest level since March 17.
Any step toward a ceasefire or potential peace deal in Ukraine would support the euro as Europe is seen suffering a significant economic blow from the conflict, which began with Russia's invasion on Feb. 24.
The greenback tumbled 1.19% against the yen, which is set for its biggest monthly rise since November 2016, to 122.45 yen. The Japanese currency had fallen to its lowest level since 2015 on Monday.
Japanese Finance Minister Shunichi Suzuki said the government would closely watch currency moves to prevent a `` bad '' weak yen that hurts the economy.
`` While the comments from Japanese officials overnight are unlikely to reverse the yen weakening trend on their own, they should at least help to slow the recent fast pace of yen selling, '' Lee Hardman, currency and emerging market analyst at MUFG, said in a note to clients.
The Bank of Japan on Tuesday continued to defend a key yield cap by offering to buy unlimited amounts of 10-year government bonds, which will likely keep the yen on its back foot.
`` The divergence between the U.S. and Japan's monetary policy will continue to weigh on the yen, which we expect to stabilize at around 125 versus the dollar and probably even beyond that level, '' said Roberto Mialich, a forex strategist at Unicredit.
`` Our view on the greenback remains positive due to the Federal Reserve's hawkish stance, '' he said.
China's offshore yuan dipped 0.18% to 6.3745 against the greenback after new pandemic restrictions in Shanghai. It hit its lowest since October 2021 at 6.4106 in mid-March.
Shanghai, China's most populous city, tightened the first phase of a two-stage COVID-19 lockdown, asking residents to stay indoors.
In cryptocurrencies, bitcoin was up 1.49% at $ 48,013 after hitting its highest level since late December on Monday.
Ether, the world's second-largest cryptocurrency, was up 3.66% at $ 3,456. | business |
Smart Phone, Smart Business | ITU data from 2020 show that 93.1% of the world’ s population is now within reach of a 3G mobile network. Consumer pricing of mobile voice and data packages continue to decline. All of this is encouraging but the near universal coverage does not mean people are connected. ITU data from 2020 also indicate that 3.7 billion people have never gone online and of the 4 billion who are online many find that the cost of connecting limits their engagement in the digital economy. The connectivity gap has shifted from the need to build more infrastructure to one of affordability and digital skills.
Africa continues to be the most expensive region to purchase mobile voice and bundled with 1.5 G of data1. In many developing countries achieving the Broadband Commission on Sustainable Development’ s target goal of internet access falling below 2% of GNI is an unrealized vision. This is especially true for those in the lower 40% of their country’ s income strata.
For women, the cost of exclusion is high. In 2021, GSMA again reported affordability and literacy as the top two barriers contributing to the 7% gap in women’ s ownership of mobile phones and 15% gap between women and men’ s use of mobile internet services. Outside of Asia, GSMA reports the level of smartphone ownership by women in low and middle income countries stagnated between 2019 and 2020. When women do own a phone they are more likely than men to own a basic phone, rather than a smartphone. In Sub-Saharan Africa 37% fewer women than men use the mobile internet.
We need to find ways to support women in building their economic livelihoods especially after the COVID-19 pandemic which has disproportionately affected women. For women entrepreneurs developing strategies to ease their way to smartphone ownership and mobile internet use is one way we can keep gender at the center of our recovery work. We want to understand and test solutions for addressing the affordability and skills gap - so we have designed the Smart Phone, Smart Business project.
We will also look to see if women used the incorporated digital literacy content to build their digital skills and confidence in evaluating digital financial service offerings.
Working with four local partners in Ghana we will support women entrepreneurs in acquiring smartphones supported by data plans. | general |
First ICC Trial on Darfur Crimes: Ali Mohammed Ali, Known as Ali Kosheib or Kushayb, Janjaweed Leader | Help us continue to fight human rights abuses. Please give now to support our work
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Ali Kosheib, or Kushayb, is the nom de guerre of Ali Mohammed Ali, identified by the International Criminal Court ( ICC) as Ali Mohammed Ali Abd–Al-Rahman. Kosheib is believed to have been the principal leader of the Janjaweed militias in the Wadi Saleh area of West Darfur. He also held commanding positions in Sudanese government auxiliary forces, the Popular Defense Forces and Central Reserve Police.
In early 2003, the Janjaweed worked alongside the Sudanese government forces during its armed conflict with rebel groups to carry out a systematic campaign of “ ethnic cleansing. ” The campaign targeted civilians from African Fur, Masalit, and Zaghawa ethnic groups, from which the members of the rebel groups were drawn. Attacking from the air and land, Sudanese government forces and allied militias killed, raped, and forcibly displaced more than 2 million people from their homes and land. The Sudanese government recruited, armed, and trained the Janjaweed forces.
Kosheib is implicated as a key leader in attacks on villages around Mukjar, Bindisi, and Garsila in 2003-2004. Kosheib is also implicated in leading or participating in deadly attacks on ethnic Salamat communities in Central Darfur in April 2013.
Ali Kosheib is charged with 31 counts of war crimes and crimes against humanity committed in in 2003 and 2004 in four villages, Kodoom, Bindisi, Mukjar, and Deleig, in West Darfur. Murder, attempted murder, pillaging, rape, torture, intentionally directing attacks against the civilian population, forcible transfer, destruction of property, outrages upon personal dignity, persecution, and cruel and other inhumane treatment are among the charges. Kosheib is charged both with directing attacks, and also mobilizing, recruiting, arming, and providing supplies to Janjaweed militia under his command.
Human Rights Watch identified Kosheib more than 15 years ago as an individual who should be investigated by the ICC for his alleged crimes in Darfur.
The International Criminal Court issued the first arrest warrant for Ali Kosheib on April 27, 2007. A second warrant, issued in 2018, was made public in 2020. These warrants included just over 50 charges of war crimes and crimes against humanity. The charges were consolidated into 31 charges ahead of what is known as the confirmation of charges hearings, which took place in May 2021. Following those hearings, ICC judges confirmed all charges and sent the case for trial.
Ali Kosheib voluntarily surrendered to the ICC in the Central African Republic. On June 9, 2020, the ICC announced he was in court custody.
The court indicated that the Central African Republic, Chad, France, the Netherlands, and the United Nations-African Union hybrid peacekeeping forces provided cooperation and assistance in his surrender. Kosheib’ s first appearance before the ICC was on June 15, 2020.
This trial is the first time a leader will be held to account for serious crimes allegedly committed in Darfur, albeit 18 years after the crimes began. The trial is a rare, long-awaited chance for the victims and communities the Janjaweed terrorized to see an alleged leader face justice. The trial is also the first by the ICC on crimes committed by state forces and allied militias in Darfur, and shows that those who commit crimes can still face justice, even over a decade later.
One Darfuri man who works with Darfuri refugees and internally displaced people said about the Kosheib trial: “ We appreciate the role of the ICC, not in a vindictive way, but for justice, for people all over the world, to know that no one is above justice, and for every dictator who wishes to exterminate and kill his people or his neighbors to know he will face the law. ”
Darfuris and activists in Sudan and across Africa have long campaigned for the surrender of Kosheib and other ICC suspects. Local communities and displaced Darfuris in Sudan demonstrated in support of Kosheib facing justice and held vigils for victims of attacks for which he is allegedly responsible.
A Khartoum-based activist who works with Darfuri victims told Human Rights Watch, “ When we sat down with the victims [ in the past two years in Darfur ], we asked them what they need and they said, ‘ We need justice.’ … We can not express our feeling, how happy we are that … justice is being prevailed. ”
Four other people, including former Sudanese president Omar al-Bashir, are facing ICC charges. All are fugitives of the court:
Two other Sudanese rebel leaders were charged with crimes related to the attack on an African Union base, but one of them, Saleh Mohammed Jerbo Jamus, died, and the ICC judges declined to confirm charges against the other, Bahar Idriss Abu Garda.
Human Rights Watch found that Sudanese government forces and allied militias committed crimes against humanity and war crimes, but due to the limitations of its research did not reach a conclusion on whether the crimes met the intent required for the crime of genocide. Human Rights Watch also found that rebel groups are also implicated in serious crimes including attacks on civilians, killings, abductions, and looting.
The ICC needs greater cooperation from Sudanese authorities. Sudanese authorities need to transfer the ICC’ s other suspects, including former president Omar al-Bashir, to the ICC without further delay. One Darfuri activist told Human Rights Watch in March 2022: “ The Kosheib trial is a good step. But achieving full justice in Darfur relies on the surrender of Omar al-Bashir, Ahmed Haroun and Abdulraheem Mohammed Hussein and others. ”
The cooperation required from Sudanese authorities includes both executing arrest warrants and responding positively to requests from the ICC prosecutor. The ICC needs access to documents, archives, crime scenes, witnesses, and other evidence relevant to Darfur cases, as well as the ability to travel to all parts of Sudan and work independently.
Though Sudan is not a party to the ICC, the UN Security Council Resolution 1593, which referred the situation in Darfur to the ICC, requires the government of Sudan to cooperate with the court.
Under former president al-Bashir, Sudan blatantly withheld cooperation with the ICC, and the ICC referred several instances of noncooperation to the Security Council, including the government’ s failure to enforce arrest warrants against Ali Kosheib and Ahmad Haroun.
Sudan’ s transitional government, which took office in 2019, promised to cooperate with the ICC and the transitional government welcomed former ICC prosecutor Fatou Bensouda to Sudan for the first time in October 2020. The authorities also signed a cooperation agreement with the ICC on the Kosheib case in February 2021.
In June 2021, the Council of Ministers approved the transfer of the three people in Sudanese custody to the ICC, but it is yet to happen. In October 2021, just prior to the coup by military leaders that ousted the transitional government, the ICC prosecutor, Karim Khan, who took up his position in June 2021, visited Sudan and discussed cooperation.
Khan returned to Sudan in December 2021, at which time Sudanese authorities indicated that a memorandum of understanding relating to cooperation signed between the Sudanese government and the ICC prior to the coup remained in effect.
Khan emphasized in a January briefing to the UN Security Council that Sudan’ s accelerated cooperation with the ICC is the “ only viable path to ensuring long-delayed justice for the survivors of crimes against humanity in Darfur. ”
The trial is scheduled to start on April 5, 2022 and should begin with a reading of the charges to the accused and opening statements from the Office of the Prosecutor and then the Defense. This will be followed by the presentation of evidence, especially questioning of witnesses. There is no preset length for the trial, but trials of this nature tend to last at least a couple of years.
The ICC has an innovative system of victim participation, which allows victims of alleged crimes to make their views and concerns known to the judges in the trial through their legal representatives. This is separate from any role as witnesses. Victim participation is one way to enhance the ICC’ s resonance in affected communities.
On October 19, 2021, the Trial Chamber issued a decision allowing 151 victims to participate in the pretrial and confirmation of charges phases of the proceedings. In a decision on January 14, 2022, ICC judges authorized 142 victims to participate in the trial phase of the proceedings. These include 130 of the same victims who participated in the earlier phases of the proceedings ( decisions related to the other 21 victims are pending based on available information), and 12 new victims.
The representatives can make an opening statement, oral submissions, present arguments on the merits, question witnesses, and present evidence at the trial. In the event of conviction, victims also may apply to the court for reparations, which may be individual or collective, symbolic or monetary, and are determined on a case-by-case basis.
Ali Kosheib is entitled to a fair and expeditious trial, conducted impartially, as provided under articles 66 and 67 of the ICC’ s founding Rome Statute and international fair trial standards. They include the following protections:
Kosheib will be required to be in the courtroom during the duration of the trial in accordance with article 63 the Rome Statute.
Penalties in the event of conviction are imprisonment for a maximum term of 30 years or for life in accordance with article 77 of the Rome Statute. Additional penalties include “ forfeiture of proceeds, property and assets derived directly or indirectly from that crime. ” The death penalty – which Human Rights Watch opposes due to its inherent cruelty – is not an available punishment at the ICC.
Outreach by the ICC about the trial to the communities most affected by the crimes will be important to maximize the ICC’ s accessibility and impact locally.
The ICC is planning a series of outreach events before the trial’ s opening, although the court has been forced to limit some of its activities, due to the more difficult logistical and security environment caused by the October 2021 coup.
Events are slated to include hybrid information sessions with diaspora, media, and civil society based in Khartoum, and security permitting, in Nyala, the capital of South Darfur, and with community leaders living in internally displaced camps in Darfur. Participants will receive information and have the chance to see videos about the trial, and to ask questions to ICC staff, likely through a virtual connection from The Hague.
The ICC is preparing videos and radio programs that will include interviews with key players in the trial and “ public service messages ” about it. These programs, and video and audio summaries of the trial, will be broadcast by Radio Dabanga in Darfur, networks of radio and TV stations based in Sudan, and several radio stations that are accessible to refugee communities in eastern Chad.
The Outreach Unit has a WhatsApp group for media, which journalists can access by emailing Outreachhq @ icc-cpi.int and a drop box folder for updated information on the trial in addition to information posted on the ICC’ s website.
Due to competing resource and logistical demands along with security considerations, the ICC is not organizing a local delegation to travel from Sudan to attend the opening in The Hague, but such a delegation, which might include local activists, community leaders, and media, might be considered at later points in the trial.
Longer term, the ICC intends to set up screening and listening clubs to ensure continued accessibility to the proceedings. There will be regular discussions and updates regarding the trial in camps for displaced people, local communities living elsewhere in Darfur, and in refugee camps in eastern Chad, with the opportunity to ask questions. The Outreach Unit has indicated that it will also plan to resume staff outreach visits to Sudan and Chad as soon as practicable.
The ICC opened an investigation into the situation Darfur crimes in 2005 following a referral by the UN Security Council in Resolution 1593. As Sudan is not an ICC member, the referral was needed for the ICC to investigate crimes committed in Darfur. This was the first such referral by the UN Security Council.
The council has referred only one other situation to the ICC to date: the situation in Libya. Despite a vital need for other referrals given the gravity of crimes committed in countries that have yet to join the ICC, such as regarding crimes in Syria and Myanmar, the council has failed to act due to political considerations.
Serious crimes in Darfur by government and government-allied forces have persisted over the years, fueled by massive impunity, including rewarding some of those implicated in crimes.
As recently as 2016, forces continued to attack Darfuris by air and ground, and crimes between 2010 and 2015 included significant killings of civilians, and rape and assault of women and girls. Two counterinsurgency campaigns in Darfur between 2014 and 2015, led by the government’ s Rapid Support Forces ( RSF), included repeated attacks on villages, burning and looting of homes, beatings, rapes, and executions of villagers. The RSF has included some former members of the Janjaweed, which also increasingly has become referred to simply as government-backed militias. Some of the RSF attacks were conducted with the support of the Sudanese Armed Forces and government-backed militias.
An extended ceasefire that began in 2017 helped reduced violence, but government forces and their proxy militias continued to carry out some attacks against civilians. Abuses again intensified in 2019, largely by local armed groups, in some cases implicating state security forces, in the wake of the withdrawal of a hybrid UN/AU peacekeeping force and again with the October 2021 coup.
While various factors, often localized ones, have played a role in the recent uptick in violence, the failure of the authorities over the last two years to provide meaningful civilian protection and justice for past and ongoing abuses has contributed to the escalation in violence and civilian harm. West Darfur in particular has experienced several serious bouts of violence since the beginning of 2021, with hundreds of people killed, tens of thousands displaced, and significant civilian property destroyed.
Sudan’ s first year of a three-year transition to democratic rule following the dramatic ouster of President Omar al-Bashir in 2019 was marked by a failing economy, political tensions, and continuing popular protests in support of quicker and more far-reaching justice and reforms. The Covid-19 pandemic compounded these problems. The government introduced some reforms but has not yet carried out most of the institutional and law reforms called for in the August 2019 constitutional charter. The second year of the pandemic was marred by political instability that slowed the pace of rights and rule of law reforms, and a dire economic situation that compounded public discontent.
On October 25, 2021, the military leaders of the transitional government carried out a coup, arresting civilian officials and dissolving the transitional government. Protesters took to the streets rejecting the coup, and security forces responded violently with lethal force, detaining protesters and political leaders, as well cutting off internet for almost three weeks.
On November 21, a deal was signed between the then-reinstated prime minister Dr. Abdalla Hamdok and the military, allowing the prime minister to be released from house arrest and to form a new technocratic government. Protesters and other political groups have rejected the deal. Hamdok resigned in January 2022. The security forces have continued to detain protesters, political opponents, and others in Khartoum and beyond.
Security forces in Sudan have repeatedly attacked or otherwise used excessive force, including lethal force, against peaceful demonstrators in Khartoum. Calls from regional and international officials for the military to halt the crackdown have not been heeded.
The current situation threatens the important, though limited, gains of the transition government on accountability, including cooperation with the ICC. While military leaders have not reversed early commitments, the current climate of crackdown and lack of accountability remains a threat to victims of crimes in Darfur and across Sudan.
Closing Gaps in the Selection of ICC Cases | general |
Le jour où l’ Ukraine et la Russie ont fait un pas en avant dans les pourparlers de paix à Istanbul | ► Le site de la rédaction russe de RFI diffuse la radio publique ukrainienne ( en langue ukrainienne) depuis la page d'accueil.
Les points essentiels:
►Un nouveau round de pourparlers a eu lieu mardi à Istanbul, « significatifs » selon Moscou, qui s'est engagé à réduire « radicalement » son activité militaire dans les régions de Kiev et Tchernihiv. De son côté, l'Ukraine demande un accord international garantissant sa sécurité. Le prochain cycle de négociations ne reprendra pas ce mercredi. Les Occidentaux déclarent qu'il ne doit pas y avoir de relâchement dans leur position vis-à-vis de la guerre en Ukraine. De son côté, le président Volodymyr Zelensky a salué des « signaux positifs ».
► Au moins 5 000 personnes sont mortes à Marioupol, ville assiégée par la Russie depuis plusieurs semaines, selon une responsable ukrainienne. L'ONU cherche à mettre en place un « cessez-le-feu humanitaire ». Les évacuations de civils ont repris. Un immeuble administratif a été bombardé à Mykolaïv, neuf personnes au moins ont été tuées.
► Les autorités ukrainiennes ont affirmé lundi avoir repris la ville d'Irpin, dans la banlieue de Kiev. Les forces ukrainiennes ont également repoussé les attaques russes vers Brovary, à l'est de Kiev, au cours des dernières 24 heures.
►Des mercenaires du groupe Wagner se sont déployés dans l'est de l'Ukraine, a indiqué lundi le ministère britannique de la Défense, qui estime que plus de 1 000 combattants de la sulfureuse société paramilitaire pourraient être amenés à combattre dans le pays.
Les horaires sont donnés en temps universel ( TU)
22h20: À l'ONU, la Russie accusée d'avoir provoqué une « crise alimentaire mondiale »
Devant le Conseil de sécurité de l'ONU, la Russie a été accusée mardi d'avoir provoqué une « crise alimentaire mondiale » voire de faire courir un risque de « famine » en ayant déclenché une guerre contre l'Ukraine, le « grenier à blé de l'Europe ». Le président russe « Vladimir Poutine a commencé cette guerre. Il a créé cette crise alimentaire mondiale. Et il est celui qui peut l'arrêter », a martelé la numéro deux de la diplomatie américaine Wendy Sherman lors d'une réunion du Conseil de sécurité consacrée à la situation humanitaire en Ukraine.
L'ambassadeur de France à l'ONU Nicolas de Rivière a enfoncé le clou: « L'agression de la Russie contre l'Ukraine accroît le risque de famine à travers le monde. Les populations des pays en voie de développement sont les premières touchées ».
Leur homologue russe Vassily Nebenzia a rétorqué que « les véritables raisons des graves turbulences sur les marchés mondiaux de l'alimentation ne sont en aucun cas dues aux agissements de la Russie, mais plutôt à l'hystérie incontrôlée des sanctions lancées par l'Occident contre » Moscou.
21h45: La guerre en Ukraine en images
21h17: Alors que les négociations se poursuivent entre l’ Ukraine et la Russie, Moscou a annoncé une réduction « radicale » de ses opérations autour de Kiev et au nord du pays. Ces déclarations sont accueillies avec scepticisme en Occident. Mais du côté des réfugiés ukrainiens, le retour est tout de même dans de nombreux esprits comme le constate notre envoyé spécial à Korczowa en Pologne, Simon Rozé.
►Reportage - Dans le camp polonais de Korczowa, les réfugiés ukrainiens espèrent un retour au pays
20h45: Des milliers de civils possiblement tués en un mois à Marioupol, selon l'ONU
Des milliers de civils pourraient avoir été tués à Marioupol depuis que l'armée russe a lancé il y a plus d'un mois son offensive contre la ville du sud de l'Ukraine, a déclaré à Reuters la cheffe de la mission locale de l'Onu pour les droits de l'homme, fournissant ses premières estimations.
Près de 5 000 personnes, dont environ 210, ont été tués à Marioupol depuis le début du siège de l'armée russe contre la ville portuaire, avait déclaré lundi un porte-parole du maire. Selon la mairie, 90% des bâtiments de la ville ont été endommagés, 40% d'entre eux détruits, dont des hôpitaux, des écoles, des crèches et des usines.
19h50: Des signaux « positifs » lors des pourparlers russo-ukrainiens de mardi, selon Volodymyr Zelensky
Les signaux en provenance des négociations russo-ukrainiennes de mardi en Turquie sont « positifs, mais ils ne taisent pas les explosions ou les obus russes », a déclaré Volodymyr Zelensky. L'Ukraine n ' a pas pour autant « l'intention de relâcher » ses efforts militaires, car « l'armée russe a toujours un potentiel important pour poursuivre les attaques contre notre État », a-t-il relevé.
« Il ne faut pas s'attendre à ce que les négociations [ entre Kiev et Moscou ] entraînent la levée des sanctions contre la Fédération de Russie. Cette question-là ne peut être envisagée qu'une fois la guerre terminée et que nous aurons récupéré ce qui est à nous », a ajouté Volodymyr Zelensky dans une vidéo postée sur Telegram.
19h20: Les forces russes se repositionne près de Kiev, cen'est « pas un vrai retrait », pour le Pentagone
Les forces russes autour de Kiev ont entamé un « repositionnement » mais « pas un vrai retrait », a affirmé mardi le porte-parole du ministère américain de la Défense, John Kirby. « Nous pouvons confirmer que nous avons vu un petit nombre » de troupes « commencer à se repositionner », a-t-il dit devant la presse. Mais « nous devons être prêts à voir une offensive majeure contre d'autres zones d'Ukraine » et « cela ne signifie pas que la menace contre Kiev est terminée », a-t-il prévenu.
18h58: L'étau russe semblait se desserrer autour de Mykolaïv au sud-est du pays, lorsqu'une frappe russe a touché le bâtiment de l'administration régionale, ce mardi. L'attaque a fait neuf morts et 28 blessés. Alyona, 51 ans, directrice d'une usine qui fabrique du pain dans la ville nous raconte que malgré ces attaques, elle et son équipe ne comptent pas arrêter leur travail.
Ce mardi, pour la première fois, on nous a prévenu que l'électricité sera coupée pendant quelques heures alors qu'avant on travaillait et d'un coup on se retrouvait dans le noir et toute notre production de pain est arrêtée. Mais heureusement qu'on a encore de l'eau, des médicaments et du réseau ici. Nos livreurs continuent à distribuer du pain partout dans la ville et dans la région même sous les bombes et les tirs. On ne va pas arrêter de travailler, on ne peut pas laisser les gens sans pain....
Témoignage d'Alyona, directrice d'une usine de fabrique de pain
Sophia Khatsenkova
18h33: Premier Conseil des ministres « public » depuis le début de la guerre
Pour la première fois depuis le déclenchement de l'invasion russe, le Conseil des ministres ukrainien s'est déroulé en public mardi, a annoncé le Premier ministre Denys Chmygal. « La plupart de nos collègues ministres travaillent à Kiev. Les autres sont en mission dans différentes régions », a-t-il ajouté, sans donner d'autres précisions. « Le pays se remet au travail », a-t-il conclu. D'autres réunions entre les membres du gouvernement auront lieu « de temps à autre » pour « que les gens voient que nous agissons au quotidien pour se rapprocher de la victoire tous ensemble », peut-on encore lire sur le site du gouvernement ukrainien.
18h05: Joe Biden attend de voir si la Russie « tient parole » sur une désescalade
Joe Biden a déclaré mardi que les Occidentaux attendaient de voir si la Russie « tenait parole » sur la réduction de son activité militaire en direction de Kiev et Tchernihiv, en Ukraine. « Il semble y avoir un consensus sur le fait qu'il faut voir ce qu'ils ont à offrir », a-t-il ajouté.
Nous verrons bien ce qu’ ils feront, mais en attendant, nous allons maintenir de fortes sanctions, nous allons continuer à fournir à l’ armée ukrainienne des moyens de défense et nous allons continuer à surveiller de près ce qu’ il se passe.
Joe Biden: « Je n’ interprète rien du tout avant de voir leurs actes »
Guillaume Naudin
17h53: Près de sept millions d'Ukrainiens sont des déplacés internes. Des gens démunis qui ont principalement fui les villes de l’ est de l’ Ukraine, écrasées par les bombes russes. À Dnipro, ils sont accueillis dans des centres d’ aide sociale. Certaines églises leur ouvrent également leurs portes, comme celle du père Vassili. Il est interrogé par nos envoyés spéciaux en Ukraine, Vincent Souriau et Sami Boukhelifa.
Ce sont les pays européens et l’ Union européenne qui nous envoient l’ aide humanitaire. Je suis heureux qu’ on ait pu créer des structures de distribution de ces aides ici à Dnipro. Dans notre ville, les gens sont à l’ abri. Ceux qui fuient la guerre, trouvent ici le soutien nécessaire, que ce soit via la municipalité, la population ou via les organisations religieuses comme la nôtre.
Père Vassili: à Dnipro, « ceux qui fuient la guerre trouvent ici le soutien nécessaire »
Sami BoukhelifaVincent Souriau
17h14: Les « nationalistes » ukrainiens à Marioupol doivent déposer les armes, déclare Vladimir Poutine
Le président russe Vladimir Poutine a affirmé mardi que les forces ukrainiennes défendant le port stratégique de Marioupol, assiégé depuis des semaines par les troupes de Moscou, doivent se rendre pour permettre de venir en aide aux civils sur place. « Pour trouver une solution à la situation humanitaire difficile dans cette ville, les combattants nationalistes ukrainiens doivent arrêter de résister et déposer les armes », a indiqué Vladimir Poutine, selon un communiqué du Kremlin résumant un échange téléphonique avec son homologue français Emmanuel Macron.
17h10: Une opération humanitaire à Marioupoln'est pas possible « à ce stade », annonce l'Élysée
Les conditions pour lancer dans les prochains jours une opération humanitaire au secours des habitants de la ville ukrainienne de Marioupol, assiégée par l'armée russe, ne « sont pas réunies à ce stade », a annoncé l'Élysée après un entretien entre les présidents Emmanuel Macron et Vladimir Poutine. Le chef de l'État français a présenté cette opération d'évacuation – proposée par la France, la Turquie et la Grèce – à son homologue russe qui a dit « qu'il allait y réfléchir » avant de donner une réponse, a ajouté la présidence.
16h47: Londres, Washington, Paris, Rome et Berlin mettent en garde contre tout « relâchement de la détermination occidentale », pour Downing Street
Le Premier ministre britannique Boris Johnson, le président américain Joe Biden, le président français Emmanuel Macron, le chancelier allemand Olaf Scholz et le président du Conseil italien Mario Draghi sont convenus qu'il ne pouvait pas y avoir de détente des Occidentaux dans leur position à propos de la guerre en Ukraine, a rapporté Downing Street. Par ailleurs, « les dirigeants ont discuté de la nécessité de travailler ensemble pour redessiner l'architecture énergétique internationale et réduire la dépendance aux hydrocarbures russes », ont déclaré les services de Boris Johnson dans un communiqué.
16h24: Au premier jour de la guerre en Ukraine, l'arsenal militaire déployé par les Russes faisait frémir. Malgré tout, les soldats ukrainiens opposent une forte résistance à la 2e armée du monde. Face à l'enlisement de ses troupes, Vladimir Poutine a annoncé qu'il recentrait ses objectifs sur l'est du pays. Franck Alexandre, spécialiste des questions de défense à RFI, revient dans un nouvel épisode du podcast Témoins d'actu sur les difficultés de l'armée russe
►Témoins d'actu - Russie: la 2e armée du monde a-t-elle encore les moyens de ses ambitions en Ukraine?
15h52: les Bourses européennes finissent en forte hausse après les avancées lors des pourparlers
Les Bourses européennes ont terminé en hausse, renouant avec l'optimisme après des avancées dans les négociations entre l'Ukraine et la Russie, qui fait espérer une détente du conflit. La Bourse de Paris a pris 3,08% à 6 792,16 points, tirée par les valeurs du luxe. La place de Francfort a gagné 2,79%, Milan 2,41% et l'Euro Stoxx 50, indice européen de référence, 2,96%. Londres a grapillé 0,86%, lestée par le secteur des matières premières.
15h40: Une nouvelle session de pourparlers entre Kiev et Moscou s'est ouverte ce matin à Istanbul. Recep Tayyip Erdogan se livre à un délicat exercice d'équilibriste entre les 2 belligérants. Membre de l'Otan, la Turquie partage des frontières maritimes en mer Noire aussi bien avec l'Ukraine qu'avec la Russie et elle entretient de bonnes relations avec les deux pays, ce qui l ' a amenée à être un « facilitateur » dans la recherche d'une issue à la guerre, selon la présidence. Le décryptage de Marc Pierini, ancien ambassadeur de l’ Union européenne à Ankara.
►Invité International - Positionnement de la Turquie dans les pourparlers russo-ukrainiens: « Un pied dans chaque camp »
15h14: Le Royaume-Uni jugera la Russie « sur ses actes, pas ses paroles »
Le gouvernement britannique a averti mardi la Russie qu'il la jugerait « sur ses actes, pas ses paroles » après l'annonce par Moscou d'une réduction « radicale » de ses activités militaires en direction de Kiev et Tchernihiv, dans le nord-est de l'Ukraine.
15h02: Les États-Unis ne voient pas de signes de « réel sérieux » de la Russie dans les négociations
Les États-Unis doutent encore du « réel sérieux » de la Russie dans les négociations avec l'Ukraine, a affirmé mardi le secrétaire d'État américain Antony Blinken après l'annonce d'avancées dans les discussions entre Kiev et Moscou à Istanbul. « Jen'ai rien vu qui puisse suggérer qu'il y a un véritable mouvement parce que nousn'avons pas vu de signes de réel sérieux de la part de la Russie », a déclaré Antony Blinken, en visite au Maroc, lors d'une conférence de presse.
14h43: La Pologne s'apprête à interdire les importations du charbon russe
Le gouvernement polonais a annoncé un projet de loi comprenant notamment l'interdiction des importations de charbon en provenance de Russie, première sanction européenne de ce type sur les sources de l'énergie. La Pologne se prononce d'ailleurs pour le renforcement des sanctions contre Moscou suite à l'invasion de l'Ukraine, et notamment pour l'interdiction des importations des carburants.
14h34: L'Irlande et la Belgique expulsent aussi des diplomate russes
Plusieurs pays de l'ouest de l'Europe ont annoncé l'expulsion de diplomates russes ce mardi après-midi. L'Irlande a annoncé expulser quatre diplomates russes au motif que leurs activités « ne correspondent pas aux standards internationaux du comportement diplomatique » en précisant vouloir « garder ouverts les canaux diplomatiques » avec Moscou dans le contexte de l'invasion russe en Ukraine. La Belgique a décidé d'expulser aussi 21 personnes travaillant pour l'ambassade et le consulat de Russie qui sont soupçonnées d'implication « dans des opérations d'espionnage et d'influence menaçant la sécurité nationale ».
14h18: Dans le camp de réfugiés à Bezimenne, les réfugiés sont « évacués de force vers la Russie », selon le conseiller du maire de Marioupol
La ville martyre de Marioupol abrite encore entre 140 000 et 160 000 civils. Plusieurs dizaines de milliers ont pu fuir depuis le début du siège de la ville par les forces russes et rejoindre certains camps de réfugiés. Celui de la ville de Bezimenne, situé à une trentaine de kilomètres à l'est de Marioupol, est sous le contrôle des forces russes. Plusieurs témoignages font état d'évacuations forcées de ces civils vers la Russie et les territoires sous le contrôle des forces russes à l'est. Une information que nous confirme le conseiller du maire de Marioupol, Petro Andrushenko.
Le camp de réfugiés de Bezimenne est le premier camp de ce type, dans lequel les Russes procèdent à une sorte de triage. Ils séparent les gens en trois groupes. Dans un premier groupe il y a les personnes âgées et les retraités. Ces gens sont évacués vers des territoires occupés par la Russie en Ukraine, c'est à dire vers les régions de Donetsk et Lougansk. Le deuxième groupe, moins important, sont les habitants de Marioupol qui ont de la famille en Russie et qui peuvent les rejoindre. Et le troisième groupe, qui est le plus important sont des adultes qu'on évacue vers la Russie. Tous ces gens sont évacués de force, on ne leur pose aucune question pour savoir ce qu'ils veulent, et où ils veulent aller. Tous ces gens sont sans exception évacués de force. Dans un camp de réfugiés comme celui de Bezimenne, les gensn'ont eu aucune chance de s'exprimer sur ce qu'ils voulaient, ils ont été transportés de force en Russie.
Dans le camp de réfugiés à Bezimenne, les réfugiés sont « triés » puis « évacués de force vers la Russie », selon le conseiller du Maire de Marioupol, Petro Andrushenko
Jelena Tomic
14h05: Les Pays-Bas expulsent 17 Russes accusés d'espionnage
Les Pays-Bas vont expulser 17 officiers de renseignement russes qui s'adonnaient « secrètement » à des activités d'espionnage, a indiqué mardi le ministère des Affaires étrangères néerlandais. La Haye a pris cette décision sur la base d'informations des services de renseignement néerlandais selon lesquelles les personnes concernées, « accréditées en tant que diplomates auprès des représentations russes aux Pays-Bas, sont secrètement actives en tant qu'officiers de renseignement », a déclaré le ministère dans un communiqué.
13h48: Le patriarche de Constantinople dénonce l'agression russe en Ukraine
Le patriarche orthodoxe de Constantinople Bartholomée a rencontré ce mardi 29 mars à Varsovie des réfugiés ukrainiens pour leur témoigner sa solidarité et dénoncer l'agression russe contre leur pays. Lors d'un discours à l'université catholique Stefan Wyszynski, il a qualifié « d'inimaginables » les destructions causées « par cette invasion horrible, dans la nation ukrainienne et dans le monde entier ». Arrivé en Pologne à l'invitation du président Andrzej Duda, qu'il a rencontré lundi, il avait dénoncé le même jour la guerre en Ukraine « injuste » et « infondée ».
13h17: La Turquie salue les « progrès » des négociations
Le ministre turc des Affaires étrangères Mevlüt Cavusoglu a salué mardi les « progrès les plus significatifs » depuis le début de la guerre, lors des pourparlers entre la Russie et l'Ukraine à Istanbul, précisant qu'ils ne reprendraient pas ce mercredi 30 mars. « Désormais il reviendra aux ministres des Affaires étrangères des deux pays de se réunir pour résoudre les questions les plus difficiles », a estimé le ministre au terme de trois heures de discussions. Retrouvez le compte-rendu de notre correspondante à Istanbul, Anne Andlauer.
►Des pourparlers russo-ukrainiens « substantiels » à Istanbul
12h56: L'Ukraine veut que la Russie ne s'oppose pas à son adhésion à l'UE, selon le négociateur russe
L'Ukraine réclame, dans le cadre de ses propositions de sortie de crise, que la Russie ne s'oppose pas à son éventuelle adhésion à l'Union européenne, a déclaré mardi le principal négociateur russe Vladimir Medinski, cité par l'agence RIA.
12h54: L'euro et le rouble grimpent avec l'avancée des négociations
La monnaie unique européenne, en berne depuis plusieurs semaines alors que le conflit pèse sur les perspectives économiques du Vieux Continent, prenait 1,2% à 1,1121 dollar, tandis que le rouble grimpait en flèche de 10,5% à 85,42 roubles pour un dollar vers 12H45 TU.
12h50: L'Ukraine acceptera d'être neutre si elle obtient un « accord international » pour garantir sa sécurité
« Nous insistons pour qu'il s'agisse d'un accord international qui sera signé par tous les garants de la sécurité », a déclaré David Arakhamia. « Nous voulons un mécanisme international de garanties de sécurité où les pays garants agiront de façon analogue à l'article 5 de l'Otan et même de façon plus ferme », a-t-il ajouté.
L'article 5 du traité de l'Alliance atlantique stipule qu'une attaque contre l'un de ses membres est une attaque contre tous.
David Arakhamia a cité, parmi les pays que l'Ukraine voudrait avoir comme garants, les Etats-Unis, la Chine, la France et la Grande-Bretagne - membres du Conseil de sécurité de l'ONU - mais aussi la Turquie, l'Allemagne, la Pologne et Israël.
« L'Ukraine acceptera un statut neutre si le système de garantie de sécurité fonctionne », a-t-il ajouté.
Pour que ces garanties puissent prendre effet dans les plus brefs délais, la Crimée et les territoires du Donbass sous contrôle des séparatistes pro-russes - seraient « temporairement exclues », de l'accord, a encore précisé le négociateur.
12h48: Joe Biden va s'entretenir de l'Ukraine avec des dirigeants européens
L'appel téléphonique est prévu à 9h15 ( 13h15 TU) avec les dirigeants français, britannique, allemand et italien.
12h31: Le nombre de réfugiés s'approche inexorablement de la barre des 4 millions
Depuis le 22 mars, le flux de réfugiés s'est nettement ralenti, aux alentours de 40 000 passages quotidiens, et la barre des quatre millions qu'avait projetée le Haut-commissariat des Nations unies pour les réfugiés ( HCR) au début du conflit pourrait être franchie dès le milieu de cette semaine.
12h30: Le pétrole brut perd 5% à Londres et New York
Les deux références du pétrole perdaient plus de 5% mardi, en réaction aux progrès annoncés dans les négociations entre l'Ukraine et la Russie, mais aussi un confinement en Chine qui pèse sur la demande. Le baril de Brent de la mer du Nord pour livraison en mai cédait 5,95% à 105,79 dollars le baril, et le WTI américain dévissait de 6,14%, à 99,45 dollars, retombant sous de la barre symbolique des 100 dollars le baril.
12h28: Les conditions sont « suffisantes » pour une rencontre Zelensky-Poutine, dit le négociateur ukrainien
« Les résultats de la réunion d'aujourd'hui [ à Istanbul ndlr ] sont suffisants pour une rencontre au niveau des chefs d'État », a déclaré David Arakhamia. Depuis le début du conflit, Moscou a toujours refusé une telle proposition de Kiev.
12h02: Kiev veut un « accord international » garantissant sa sécurité, déclare le négociateur ukrainien
« Nous insistons pour qu'il s'agisse d'un accord international qui sera signé par tous les garants de la sécurité, a déclaré David Arakhamia. Nous voulons un mécanisme international de garanties de sécurité où les pays garants agiront de façon analogue au chapitre 5 de l'Otan et même de façon plus ferme », a-t-il ajouté
12h01: La Russie annonce réduire « radicalement » son activité militaire dans les régions de Kiev et Tcherniguiv en Ukraine
« Les négociations sur un accord sur la neutralité et le statut non-nucléaire de l'Ukraine entrant dans une dimension pratique [... ], il a été décidé, pour accroître la confiance, de réduire radicalement l'activité militaire en direction de Kiev et Tcherniguiv », a déclaré à Istanbul le vice-ministre russe de la Défense, Alexandre Fomine, à l'issue des discussions.
Le chef de la délégation russe et représentant du Kremlin, Vladimir Medinski, a fait état de « discussions substantielles » et dit que les propositions « claires » de l'Ukraine en vue d'un accord allaient être « étudiées très prochainement et soumises au président » Vladimir Poutine.
Selon lui, une rencontre des dirigeants ukrainien Volodymyr Zelensky et russe Vladimir Poutine, et de représentants d'États garants, serait possible en cas d'accord pour mettre fin aux hostilités.
« En ce qui concerne une rencontre des deux présidents, nous avons dit depuis le début qu'elle sera possible lorsqu'il y aura un accord [... ] La rencontre pourrait être multilatérale, avec la participation d'États garants », a-t-il dit.
« Après la discussion substantielle d'aujourd'hui, nous nous sommes entendus et proposons que la rencontre se fasse pour parapher l'accord », a-t-il dit.
« À condition d ' ( effectuer) un travail rapide sur l'accord, et de trouver les compromis nécessaires, la possibilité de conclure la paix se rapprochera », a dit Vladimir Medinski.
11h45: Fin de la réunion entre Russes et Ukrainiens à Istanbul
Les discussions ont duré quatre heures, entrecoupées de plusieurs pauses. On ignore encore si elles reprendront mercredi.
11h41: La Russie expulse 10 diplomates des pays baltes
Les accréditations de quatre diplomates de l'ambassade de Lituanie, trois de celle de Lettonie et trois des missions estoniennes ont été retirées, a annoncé le ministère russe des Affaires étrangères dans un communiqué.
Cette mesure a été prise « selon le principe de réciprocité » après l'expulsion « injustifiée » de 10 diplomates russes annoncée le 18 mars par ces trois pays membres de l'Union européenne et de l'Otan, a ajouté le ministère.
11h40: Au moins sept morts et 22 blessés dans la frappe russe à Mykolaïv, selon Zelensky
« Il n ' y avait pas de visées militaires à Mykolaïv, les habitants de Mykolaïv ne présentaient aucune menace contre la Russie. Et malgré cela, comme tous les Ukrainiens, ils sont devenus les cibles des troupes russes », a-t-il affirmé lors d'une adresse au Parlement danois.
11h37: Budapest annule une réunion après des divergences avec Prague et Varsovie
Une réunion prévue mercredi à Budapest du groupe de Visegrad a été annulée après la décision des ministres polonais et tchèque de la Défense de ne pas y participer en raison des liens de la Hongrie avec le Kremlin.
« Une rencontre des ministres de la Défense du groupe dit V4 se tiendra à une date ultérieure », a indiqué à l'AFP mardi le ministère hongrois de la Défense, sans plus de précisions.
Plus tôt, le ministre polonais Mariusz Blaszczak avait annoncé qu'il «n'irait pas » à Budapest. Son homologue tchèque Jana Cernochova avait également déclaré la semaine dernière qu'elle ne s ' y rendrait pas.
« Ils ont des élections et iln'est pas juste que je participe à la campagne », a-t-elle expliqué, en référence aux législatives organisées le 3 avril en Hongrie.
« J'ai toujours soutenu le V4 et je suis vraiment désolée que les hommes politiques hongrois trouvent maintenant que le pétrole russe bon marché est plus important que le sang ukrainien », a dit la ministre.
11h34: Les attaques russes contre Marioupol sont un « crime contre l'humanité », déclare Zelensky
« Ce que les troupes russes font à Marioupol est un crime contre l'humanité, qui se déroule en direct sous les yeux de la planète », a dit Volodymyr Zelensky devant le Parlement danois lors d'une intervention en visioconférence, les accusant de bombarder volontairement les abris des civils dans cette ville assiégée
10h53: L'enseigne de sports française Decathlon « suspend » ses activités en Russie
« Respectant scrupuleusement les sanctions internationales, Decathlon constate que les conditions d'approvisionnement ne sont plus réunies pour poursuivre son activité en Russie. Decathlon est amené à suspendre l'exploitation de ses magasins », écrit dans son communiqué l'enseigne de la galaxie Mulliez, qui a jusque-là maintenu en Russie les activités de ses marques Auchan et Leroy-Merlin
10h41: En Amérique latine, la gauche critique « l'impérialisme américain » face à la guerre en Ukraine
S’ il fallait une preuve de l’ antiaméricanisme latent sur le continent latino-américain, les réactions de nombreuses personnalités et présidents de gauche à la guerre en Ukraine en sont une. Ils sont en effet nombreux à blâmer les États-Unis, l’ Otan et l’ Occident en général, et à ne pas croire aux informations des principaux médias des États-Unis et d’ Europe.
►Les explications de notre correspondant à Quito, Éric Samson
10h40: Le Japon interdit les exportations de produits de luxe vers la Russie
La nouvelle liste de produits interdits à l'exportation comprend 19 catégories, des voitures d'une valeur supérieure à 6 millions de yens ( environ 44 000 euros) aux bijoux, montres, cosmétiques, alcools et objets d'art d'un prix supérieur à 40 000 yens, a précisé le ministère dans un communiqué.
10h38: Le Kremlin insiste sur le paiement du gaz russe en roubles, après des critiques du G7
Le Kremlin a insisté mardi sur le paiement en roubles du gaz russe livré à l'Europe, rejetant les critiques du G7, alors que les Occidentaux et les Russes multiplient les sanctions et contre-sanctions depuis l'offensive russe en Ukraine.
« Personne ne va livrer de gaz gratuitement. C'est tout simplement impossible. Et on ne peut le payer qu'en roubles », a déclaré le porte-parole du Kremlin, Dmitri Peskov.
« La situation a changé dans le contexte d'une guerre économique menée contre la Russie », a-t-il souligné, « les entreprises [ commandant du gaz russe ] doivent [ le ] comprendre ».
10h21: La Finlande s'inquiète d'une ingérence russe dans son débat sur l'Otan
La Finlande doit se préparer à des actions d'ingérence russe et à des attaques hybrides liées au débat en cours sur l'adhésion du pays nordique à l'Otan, a affirmé son service de renseignement.
« L'ensemble de la société finlandaise doit être vigilant sur des tentatives russes d'influencer le processus de décision de la Finlande sur la question de l'Otan », a déclaré le directeur du Service de sûreté ( Supo).
10h13: Le Kremlin confirme que l'oligarque Abramovitch est un médiateur avec l'Ukraine
« Abramovitch joue un rôle pour établir des contacts entre les parties russe et ukrainienne », a dit le porte-parole de la présidence russe Dmitri Peskov lors d'un briefing.
« Il est présent à Istanbul », bien qu'il ne soit pas un membre officiel de la délégation russe, a-t-il ajouté.
10h12: Les chaînes d'approvisionnement russes, prochaine cible des sanctions américaines
Les États-Unis et leurs alliés envisagent de sanctionner de nouveaux secteurs de l'économie russe et de perturber ses chaînes d'approvisionnement, en raison de la poursuite de la guerre en Ukraine, a déclaré le secrétaire adjoint au Trésor américain, Wally Adeyemo.
L'objectif de cet élargissement des mesures punitives contre Moscou est de saper davantage « la machine de guerre du Kremlin », a-t-il dit lors d'une conférence organisée par l'institut d'études Chatham House à l'occasion d'une visite à Londres.
10h10: La Croix-Rouge demande à Moscou et Kiev de s'entendre sur les évacuations
Le Comité international de la Croix-Rouge ( CICR) a appelé la Russie et l'Ukraine à tout faire pour parvenir à un accord sur une évacuation sécurisée des civils de Marioupol et d'autres villes assiégées par l'armée russe, lors des négociations qui ont débuté entre les deux parties en Turquie.
10h02: « une guerre de l'information », 3 000 journalistes sur place
L'invasion russe de l'Ukraine caractérisée par « une grande concentration de journalistes sur le terrain » dont le nombre est évalué « entre 3 000 et 3 500 » constitue « une guerre de l'information », relève une enquête de l'ONG grecque iMedD, centrée sur la transparence et l'indépendance du journalisme.
« Plateformes, réseaux sociaux, propagande, provocation, fausses nouvelles, concurrence, interdictions de circulation, embargos [... ] sont les armes `` nucléaires '' d'une guerre de l'information - non seulement en termes de manipulation de l'opinion publique, mais aussi dans un contexte des stratégies et tactiques de l'Est et de l'Occident sur le terrain », estime cette enquête.
09h47: Le président français Emmanuel Macron et son homologue russe Vladimir Poutine s'entretiendront par téléphone cet après-midi
Emmanuel Macron et Vladimir Poutine vont de nouveau se parler au téléphone mardi à 16h30 heure de Paris ( 14H30 TU), a annoncé l'Élysée, notamment au sujet d'une opération humanitaire d'évacuation dans la ville ukrainienne assiégée de Marioupol organisée avec la France, la Grèce et la Turquie.
09h41: La France se prépare à d'éventuelles coupures ciblées de gaz
La France se prépare à de possibles coupures ciblées de gaz chez d'importants consommateurs pour faire face à une éventuelle interruption de l'approvisionnement russe l'hiver prochain, ont indiqué mardi le gouvernement et le gestionnaire du réseau de distribution.
« On attend la sortie d'un décret délestage, que le gouvernement doit sortir ces prochains jours », a indiqué lors d'une conférence de presse Laurence Poirier-Dietz, directrice générale de GRDF, le réseau de distribution de gaz.
Si les particuliers ne sont pas concernés par ces éventuelles mesures, la responsable de GRDF a rappelé qu'ils pouvaient aussi facilement économiser de l'énergie.
Le candidat communiste Fabien Roussel a invité mardi Bernard Arnault, le PDG de LVMH, à « baisser son chauffage », comme le recommande le réseau de distribution de gaz GRDF, mais pas les plus précaires, qui « ont déjà du mal à se chauffer ».
09h12: Malgré l'interruption de certaines liaisons aériennes ou ferroviaires, la Russien'est pas coupée du monde
Les liaisons aériennes directes entre les États-Unis, l'Union européenne et la Suisse, c'était déjà fini. Dimanche 27 mars, la dernière ligne ferroviaire encore active entre la Russie et l'UE s’ est aussi arrêtée: le train Allegro entre la gare centrale de la capitale finlandaise Helsinki et Saint-Pétersbourg a fait son dernier trajet. Mais certains pays maintiennent des liaisons directes avec la Russie. ►Nos explications
09h09: Au moins deux morts dans la frappe russe sur l'administration de Mykolaïv
Deux corps sans vie ont été sortis des gravats après une frappe russe sur le bâtiment de l'administration régionale de Mykolaïv, touchée par une frappe russe, ont constaté des journalistes de l'AFP.
⚡️Russia destroys Mykolaiv's Regional Administration with a Kalibr missile this morningNew armoured vehicle assault on Mykolaiv expected. `` Donbass focus '' was another lie. pic.twitter.com/1tUxV7FSkz
09h05: Le chef de l'AIEA en Ukraine pour discuter de la sécurité des sites nucléaires
« Le conflit militaire pose un danger sans précédent pour les centrales et autres sites du pays. Nous devons prendre des mesures urgentes pour nous assurer qu'elles continuent à fonctionner en toute sûreté et réduire le risque d'un accident », a déclaré Rafael Grossi, directeur général de l'Agence internationale de l'énergie atomique, cité par le communiqué.
IAEA @ RafaelMGrossi is in # Ukraine to start delivery of urgent technical assistance to ensure safety and security of country’ s nuclear facilities and help avert the risk of an accident that could endanger people and the environment. https: //t.co/DKTR6u2Axz pic.twitter.com/M3fnMUgN1l
08h12: La Russie accorde un sursis de service militaires au jeunes travaillant dans les hautes technologies
Pour faire face à une fuite des cerveaux provoquée par l'offensive russe en Ukraine, les entreprises du secteur des hautes technologies ont jusqu'au 1er mai 2022 pour établir la liste de leurs collaborateurs de moins de 27 ans pour lesquels elles veulent obtenir une telle dispense, selon un communiqué du gouvernement russe.
Les étudiants dans une soixantaine de spécialités universitaires sont concernés aussi, ces matières couvrant des domaines aussi variés que les mathématiques, la cartographie, la robotique, l'aéronautique, les chantiers navals ou encore les nanotechnologies.
07h44: L'administration régionale de Mykolaïv dans le sud touchée par une frappe russe, annonce le gouverneur
« Le bâtiment de l'administration régionale touché », a écrit le gouverneur Vitaly Kim, assurant que la plupart des personnes se trouvant à l'intérieur étaient indemnes. « On cherche huit civils et trois militaires », a précisé le responsable.
07h42: Les pourparlers sont officiellement ouverts en Turquie
Les pourparlers entre les délégations russe et ukrainienne à Istanbul ont commencé aujourd'hui peu après 10h30 ( 07h30 TU), a rapporté l'agence officielle turque Anadolu.
C'est la première fois que les délégations des deux pays, arrivées la veille en Turquie, se retrouvent en présence après plusieurs rounds de pourparlers en visioconférence.
La ville turque d’ Antalya avait accueilli le 10 mars une rencontre des chefs de la diplomatie russe et ukrainienne, qui n’ avait abouti à rien, rappelle notre correspondante à Istanbul, Anne Andlauer.
Comme Recep Tayyip Erdogan l’ a rappelé à Istanbul, la Turquie joue pour l’ instant un rôle de facilitateur et non de médiateur à proprement parler. Kiev s’ est dit favorable dès le début à une médiation turque. Mais Ankara a très peu de leviers sur Moscou.
Tout en soutenant l’ Ukraine, à laquelle elle fournit des drones de combat, la Turquie ménage donc la Russie, en refusant notamment de se joindre aux sanctions occidentales.
La Turquie espère jouer un rôle clé dans la résolution du conflit, à la fois pour limiter les dommages déjà perceptibles sur sa fragile économie, pour préserver ses liens avec l’ Ukraine et la Russie et pour redorer le blason de sa diplomatie.
L'oligarque russe Roman Abramovitch, qui tente de jouer les médiateurs entre Moscou et Kiev, était également présent à l'ouverture de la rencontre, selon une photo diffusée par la présidence turque, qui le montre assistant à l'allocution de Recep Tayyip Erdogan.
07h39: Reprise des évacuations par les couloirs humanitaires après une suspension
« Trois couloirs humanitaires ont été validés pour aujourd'hui », a déclaré la vice-Première ministre ukrainienne Iryna Verechtchouk dans une vidéo diffusée sur Telegram.
Selon elle, le premier couloir sera mis en place entre Marioupol et Zaporojie plus au nord par voiture, et de Berdiansk, où avaient déjà été évacués des civils au cours des jours précédents, vers Zaporojie.
►À lire: un couloir humanitaire en suspens à Marioupol
Le deuxième couloir va de la ville de Melitopol, sous le contrôle des forces russes dans le sud du pays, à Zaporojie, et le troisième rejoint Zaporojie depuis Energodar, localité également entre les mains de Moscou, où est située une centrale nucléaire.
07h25: L'Ukraine dit espérer trois couloirs humanitaires, dont un à Marioupol
Les autorités ukrainiennes espèrent pouvoir ouvrir trois couloirs humanitaires aujourd'hui afin de permettre l'évacuation de civils de villes assiégées par les troupes russes, a déclaré la vice-Première ministre ukrainienne Irina Verechtchouk.
06h49: « Les deux parties ont des préoccupations légitimes », affirme Erdogan devant les délégations à Istanbul
Le président turc a appelé les deux parties à « mettre un terme à cette tragédie ».
Les pourparlers entre les deux délégations doivent commencer après cette réception, dans le palais de Dolmabahçe à Istanbul où la présidence turque dispose de bureaux.
06h45: Le moral des consommateurs allemands devrait fortement reculer en avril, pour le deuxième mois consécutif, plombé par la guerre en Ukraine qui aggrave l'inflation, selon le baromètre GfK.
06h23: Des « couacs » dans la stratégie de communication des autorités ukrainiennes?
Vidéos montrant des soldats supposément ukrainiens torturer des prisonniers, tribune de journalistes dénonçant le manque de liberté de la presse, diffusion des identités de 620 personnes accusées d'appartenir au FSB... Les autorités ukrainiennes, pourtant remarquées pour leurs efforts de communication vis-à-vis des Occidentaux, sont confrontées à un certain nombre de « couacs ».
Notre envoyé spécial, Vincent Souriau, fait le point ici.
La profusion d'informations et d'images concernant l'invasion russe de l'Ukraine met les médias au défi de ne pas devenir des relais partisans de la guerre de l'information qui se déroule en parallèle et à déployer de nouvelles méthodes de travail.
« Ce fut un déluge ( d'images et d'informations) dès la première heure du conflit », raconte Shayan Sardarizadeh, journaliste au sein de l'équipe de la BBC chargée de la désinformation.Il cite deux moments comparables en termes de volumes d'éléments à trier: la pandémie mondiale de Covid-19 et les deux semaines ayant entouré le vote de l'élection présidentielle américaine en novembre 2020.Le bombardement du théâtre de Marioupol, ville assiégée par les forces russes, illustre la difficulté pour les médias à rendre compte eux-mêmes d'événements se produisant sur un terrain à l'accès rendu presque impossible.C'est ainsi la mairie de cette cité portuaire qui a en premier publié sur la messagerie Telegram une photo du théâtre montrant sa partie centrale complètement détruite, et encore la municipalité qui a depuis dit redouter environ 300 morts dans cette frappe, en citant des témoins.Dès les premiers jours du conflit, un autre épisode survenu sur l'île aux Serpents avait été relayé par de nombreuses publications, sans autre source que des responsables ukrainiens.Après avoir présenté des soldats ukrainiens comme morts « en héros », ces autorités avaient finalement indiqué quelques jours plus tard être « très heureuses » que ces derniers soient « vivants », après que l'armée russe avait largement communiqué sur le retour de ces soldats ukrainiens sur la terre ferme.Ces revirements illustrent « le brouillard d'informations dû à la guerre » et « le désir de propagande » des deux camps, analyse Arnaud Mercier, professeur en communication à l'Université Paris-II Panthéon-Assas, et auteur d'Armes de communication massive, qui analyse la communication politique pendant la guerre d'Irak.
04h22: L'effort humanitaire se déploie depuis Dnipro, la plus grande ville de l'est ukrainien encore intacte
Quasiment tout l’ est de l’ Ukraine essuie les feux de l’ artillerie russe et l’ accueil des déplacés s'organise désormais à partir de la plus grande ville régionale encore intacte, Dnipro, où se sont rendus nos envoyés spéciaux, Vincent Souriau et Sami Boukhelifa.
Au moins ici, il y a quelques arbres. Il y a aussi une église et ces deux petits bâtiments, des bureaux que l’ ONG Caritas a transformés en centre d’ accueil pour les déplacés « Ils savent que c’ est un voyage sans retour. Dans la moitié des cas, leur maison a été rasée par les bombardements, ils ont passé des semaines dans un abri sans rien à manger, décrit une femme. Ils ont tenu bon pour arriver jusqu’ ici, et quand ils sont là, ils lâchent tout, ils commencent à pleurer… Et l’ émotion prend toute la place » Ces gens qui ont tout perdu, on leur propose du pain, des paquets des céréales, de la farine, et quelques vêtements. Le minimum vital… Aleskandr Yeliseiev vient de Roubijnie, dans la région de Lougansk. Il parle quelques mots de français, il adore les chansons de Joe Dassin et il est passé tout près de la mort « Vers le 13 mars, les obus sont tombés deux étages en dessous de chez nous, quatre obus de mortier. ça m’ a projeté par terre, je me suis cassé la gueule. Quand je me suis relevé, j’ avais plus de chaussures, j’ étais blessé… Et je me suis précipité au sous-sol, ça a duré quatre jours. Mon rêve, c’ est de retrouver mes enfants, mes petits-enfants, de serrer mes petites-filles dans mes bras et de jamais lâcher. Ça me fout le cafard, j’ ai envie de chialer, je les veux dans mes bras et je veux pas les lâcher. » Encore 15 heures de train au départ de Dnipro… Et si tout va bien, Aleksandr et sa femme Irina devraient retrouver leurs proches d’ ici la fin de la semaine dans l’ ouest de l’ Ukraine.
Accueil des déplacés à Dnipro
Vincent SouriauSami Boukhelifa
01h00: Témoignage « La situation à Marioupol n ' a pas changé ces derniers jours »
Le président français Emmanuel Macron a déclaré ce dimanche qu'il parlerait à son homologue russe Vladimir Poutine pour organiser une opération d'évacuation de la ville de Marioupol, où environ 170 000 civils seraient toujours prisonniers des bombardements russes et des combats entre les forces russe et ukrainienne.
Emmanuel Macron a annoncé une opération humanitaire exceptionnelle pour évacuer les habitants de Marioupol. Cette opération serait en cours de préparation, en lien avec la Turquie et la Grèce. Le conseiller du maire de Marioupol, Petro Andrushenko, revient sur la situation de la ville, au micro de Jelena Tomic.
La situation à Marioupol n ' a pas changé ces derniers jours. La situation humanitaire est catastrophique et les combats de rues, les bombardements et pilonnages continuent. Nous estimons qu ' à l'intérieur de la ville il y a 150 000 personnes, qu'entre 160 et 180 000 ont pu être évacuées de Marioupol. Officiellement, près de 5 000 civils ont été tuées, dont plus de 300 enfants. Les combats ont lieu dans les 4 districts que compte la ville. Certaines zones sont sous le contrôle des Russes, mais vous savez en temps de guerre, la situation change d'heure en heure, il est donc très difficile de dire quelle zone est sous le contrôle des Russes, mais si l'on observe la situation dans sa globalité, notre armée ukrainienne contrôle la plus grande partie de la ville
Petro Andrushenko, conseiller du maire de Marioupol
Jelena Tomic
00h30: L’ invasion russe en Ukraine est une « répétition » de la guerre en Syrie, selon Amnesty
L'invasion russe en Ukraine est une « répétition » de la Syrie avec une « multiplication des crimes de guerre » depuis plus d'un mois de conflit, a alerté Amnesty international lors de la présentation mardi à Johannesburg de son rapport 2021-2022.
« Ce qui se passe en Ukraine est la répétition de ce qu'on a pu voir en Syrie », a déclaré à l'AFP la secrétaire générale de l'ONG, Agnès Callamard. « Nous sommes dans des attaques intentionnelles d'infrastructures civiles, d'habitations », des bombardements d'écoles, a-t-elle fustigé, accusant la Russie de permettre des couloirs humanitaires pour les transformer en un « piège mortel ».
« Nos chercheurs sur place pendant dix jours ont documenté l'emploi des mêmes tactiques qu'en Syrie et Tchétchénie », dont des attaques visant des civils et l'emploi de munitions interdites par le droit international, a renchéri lors d'une conférence de presse parallèle à Paris, Marie Struthers, directrice d'Amnesty Europe de l'Est et Asie centrale.
00h00: Volodymyr Zelensky estime nécessaire des sanctions plus fortes contre la Russie
Le président ukrainien Volodymyr Zelensky a exhorté lundi les pays occidentaux à renforcer rapidement leurs sanctions contre la Russie, notamment en imposant un embargo sur le pétrole russe, afin d'empêcher Moscou d'avoir les coudées franches pour accentuer ses mesures contre l'Ukraine.
Dans un message vidéo quotidien, Volodymyr Zelensky, visiblement irrité, a déclaré que l'Occident avait fait une erreur de calcul l'an dernier en retardant l'imposition de sanctions contre la Russie, avec pour conséquence le début de l'invasion russe.
« Une guerre à grande échelle a commencé. Il y a maintenant de nombreuses indications et avertissements sur de présumées sanctions plus fortes, comme un embargo sur les livraisons russes de pétrole vers l'Europe, qui seront mises en place si la Russie utilise des armes chimiques », a dit le dirigeant ukrainien, tapant plusieurs fois du poing sur la table. | general |
Hari Prasad Sure, et al., Civ. Act. ( Release No. LR-25350; Mar. 29, 2022) | The Securities and Exchange Commission today announced insider trading charges against three software engineers employed at Twilio, Inc., a San Francisco-based cloud computing communications company, and four family members and friends for allegedly generating more than $ 1 million in collective profits by insider trading ahead of the company's positive first quarter 2020 earnings announcement on May 6, 2020.
According to the SEC's complaint, friends Hari Sure, Lokesh Lagudu and Chotu Pulagam were software engineers at Twilio and had access to various databases relevant to the company's reporting of revenue. As alleged, around March 2020, they learned through the databases that Twilio's customers had increased their usage of the company's products and services in response to health measures taken in light of the Covid-19 pandemic, and concluded in a joint chat that Twilio's stock price would `` rise for sure. ''
The SEC's complaint alleges that despite receiving a company policy that prohibited them from insider trading, Sure, Lagudu and Chotu Pulagam knowingly tipped off, or used the brokerage accounts of, their family and close friends - Dileep Kamujula, Sai Nekkalapudi, Abhishek Dharmapurikar and Chetan Pulagam - to trade Twilio options and stock in advance of its May 6, 2020 earnings announcement while in possession of the confidential information concerning customer usage. According to the complaint, the scheme generated more than $ 1 million in illegal trading profits.
The SEC's complaint, filed in the Northern District of California, charges each of the defendants with violating the antifraud provisions of Section 10 ( b) of the Securities Exchange Act of 1934 and Rule 10b-5 thereunder.
Today, the U.S. Attorney's Office for the Northern District of California announced criminal charges against Dileep Kamujula.
The SEC's investigation, which is continuing, was conducted by Erin Wilk and Elena Ro of the San Francisco Regional Office, with assistance from Jan Jindra of the SEC's Division of Economic and Risk Analysis, as well as John Rymas of the Market Abuse Unit's Analysis and Detection Center. The case was supervised by Jennifer J. Lee of the San Francisco Regional Office. The litigation will be led by Susan LaMarca, Ms. Wilk and Ms. Ro.
The SEC appreciates the assistance of the U.S. Attorney's Office for the Northern District of California, the Federal Bureau of Investigation, and the Financial Industry Regulatory Authority ( FINRA). | tech |
Preparation Preconditions: What measures are needed to combat another pandemic? | Could we have foreseen the damage caused by the COVID-19 pandemic? This is a central question that has plagued biopharma companies, healthcare systems, and governments alike in the last two years. A recent peer-reviewed study published in the Lancet suggests that the global number of fatalities may stand at a staggering number in excess of 18 million, although many of these could have gone unreported. How could we have braced ourselves for the COVID-19 pandemic, and what measures could have been taken to prevent it?
March 2020 saw the introduction of the first lockdown in the UK, and the beginning of mass restrictions that have become all too familiar in our social landscape. Since then, questions have been raised surrounding failures in the country’ s leadership, and how the NHS can be better funded to prevent mass chaos and better support its staff.
The 100 Days Mission to Respond to Future Pandemic Threats is an initiative kickstarted by the government, building on the target set by the Coalition for Epidemic Preparedness Innovations ( CEPI) to have effective vaccines within 100 days of a pathogen being sequenced. The government has pledged £160 million towards this cause, but what more is needed to make this a reality?
COVID-19 has evidently driven growth for pharma, and has prompted greater funding into pandemic-related research. However, the strain it has placed on healthcare systems and pharma companies can not be understated.
The past two years has seen as a drastic surge in demand for personal protective equipment ( PPE) and over-the-counter ( OTC) medications, which has led to worldwide shortages. China and India, the two main global suppliers of active pharmaceutical ingredients ( APIs) and generics, implemented export bans at the beginning of the pandemic, which caused shortages of both products in most countries. This in turn slowed the manufacture of finished products, causing certain medicines to become scarce, with a knock-on impact on patients’ quality of life.2 Pharmaceutical retailers have also experienced fewer walk-ins, causing a loss in profit and greater redundancies. The magnitude of the economic damage caused is undeniable.
As mentioned previously, the 100 Day Mission has potential to stave off the threat of another pandemic. Pharmafocus spoke to RD Therapeutics CEO, Ailene Thiel, who shared with us: “ CEPI’ s mission to cut vaccine development to 100 days is a truly momentous goal. COVID-19 will not be the last pandemic. It is critical for the world to come together to develop and distribute vaccines, diagnostics and therapeutics. CEPI’ s plan will reduce the risk posed by epidemics and pandemics by developing a library of vaccines for known disease threats, such as Lassa fever, MERS and Nipah virus, and build on the scientific advances made during COVID-19 to prepare in advance for ‘ Disease X’ - the threat of an unknown pathogen with pandemic potential. CEPI is also working to develop the next generation of globally accessible COVID-19 vaccines, including ‘ variant-proof’ COVID-19 vaccines, as well as vaccines that provide broad protection against all Betacoronaviruses.
“ If we can work with CEPI to speed up vaccine distribution and ensure broader geographic reach, we can significantly reduce the spread and impact of future viruses, potentially saving millions of lives and reducing the economic impact on communities around the world. The 100 Days Mission has recognised the need to compress vaccine development timelines in an effort to save lives and prevent trillions of dollars of economic damage. ”
Needle-free vaccines are also currently being explored as a tool to combat against future pandemics. Ailene Thiel enlightened Pharmafocus on the potential of this: “ Innovation is needed in efficient vaccine platforms that can be manufactured in regional hubs and easily and quickly distributed to every corner of the globe. A very large part of the world is still currently struggling to obtain and distribute needle-based therapies. In Africa alone, 83% of the population has not received their first dose of a COVID vaccine. How can we, as a society that claims to be working to address inequalities, let this happen? An alternative that provides huge advantages is oral vaccination. Oral vaccination via the sublingual route can be achieved through self-administration, is non-invasive, and avoids the requirements for cold-chain transportation and storage. Moreover, it does not require administration by healthcare professionals, individuals who are in short supply during a pandemic. ”
Clinical trials are instrumental in mitigating the risk of future pandemics. In a 2021 article in EBR January, titled Amplified Needs Accelerate Innovation During a Pandemic, Dr Patrick Schneider, PhD, shared: “ The clinical trial process and pharmaceutical value chain as a whole are notoriously slow and expensive – that is, they were until COVID-19’ s impact and unprecedented need for speed created an opportunity. Randomised clinical trials, while a classic approach and important for collecting data broadly across vaccine candidates, can be coupled with newer approaches like real-world trials or Bayesian statistics to accelerate vaccine development.3 This monumental shift has the potential to revolutionise a process that can drastically improve how critical vaccines and therapies successfully reach patients. ”
Pharmafocus also spoke to Dr Gerald Pfeifer from SUSE, who articulated the increasingly instrumental role that open-source technologies play in driving research: “ Open source technology is a very collaborative way of developing software and driving innovation together. It’ s very similar to academia; you share the base, you jointly cooperate on base research on base components. In the pandemic, companies conducted research and shared the samples with others. You sequence the virus, you share the study results for everyone to benefit from it, so you combine forces. The open source approach is about collaborating on something and making the blueprint readily available. You make the code available, and then people can build and distribute it. ”
Artificial intelligence supported the response to COVID-19, and will play an increasingly pivotal role in preparing against future pandemics. Ailene Thiel shared: “ The COVID-19 pandemic has propelled the adoption of technologies that are improving the clinical trial process. Artificial Intelligence ( AI) and Machine Learning ( ML) will play an increasing role in improving the efficacy and reducing the costs of clinical trials. Patients will also benefit, as AI/ML will enable learning from trials which can lead to improved patient satisfaction rates. AI algorithms, combined with wearable technology, will facilitate monitoring of patients real-time, providing continuous monitoring of safety and efficacy which will help retain patients in clinical trials. Shared analytics platforms will improve predictions and support collaboration. Innovative data visualisation tools are changing the level of insights that can be shared with users and facilitate decision making. Natural Language Processing ( NLP) adds a new dimension and can capture clinical trial feedback which previously was often lost. All these more recent technologies will help tremendously with the 100 Days Mission aims – to reduce the impact of future pandemics by making diagnostics, therapeutics and vaccines available within 100 days. ”
Preventing another pandemic means guaranteeing access to vaccines not only in wealthier countries, but also low and middle-income regions. Over the past two years, global health authorities have consistently raised the issue of unfair access to vaccines, as well as other tools to help combat the pandemic. However, the first shipment of vaccines – 600,000 doses of the Oxford-AstraZeneca jab – delivered by Covax, the WHO-backed access programme, only arrived in the Ghanaian capital, Accra, in late February 2021. More than three-quarters of people in low-income countries aged 12 and over are yet to receive a single-dose, compared with 10% in high-income countries, according to the research group, Our World in Data.4
Dr Pfeifer offered his perspective on how this can be combatted: “ Companies such as Biotech, Pfizer, and Moderna can make the code or the instructions readily available. It’ s a political question, a business question. It doesn’ t have to be completely free. Open source can be applied to hardware, or medicine, and there are many skilled developers that can contribute to collaboration online, despite being on the other side of the globe. ”
Open-source vaccines are also notable tools that offer potential to bridge the inequality gap. Afrigen Biologics and Vaccines, a South African start-up, has successfully formulated a replica of Moderna’ s COVID-19 vaccine, and the first human trials of the copycat drug could commence in November. Researchers have embraced the concept of ‘ open-source pharma’, which is an idea modelled on the free software movement that encourages collaboration and sharing to improve coding for software.4 The aim of the initiative is to make this technology accessible to poorer nations, and also to train qualified staff to produce vaccines locally, without breaking any intellectual property rules.
Ailene shared how vaccines can be distributed equally across borders: “ In spite of the spectacular success to date in developing vaccines at record speed to address the current pandemic, the response to date has demonstrated clear inequities, as seen by the significant proportion of the world that continues to be under-vaccinated against COVID-19, most notably low- and lower-middle income countries. There are multiple factors at play that perpetuate the inequity of global vaccination, and success is significantly constrained by challenges in the governmental and health systems of many developing countries. Within the health systems themselves, challenges include a lack of trained medical personnel, inadequate health infrastructure, such as vaccine storage facilities, and limited tracking mechanisms.
“ The only way to address this issue is to deliver vaccines equitably to all corners of the world by removing current barriers to global vaccination. There is a clear opportunity for new vaccine delivery technologies to help facilitate more equitable access to vaccines. Oral vaccination can remove most of the existing barriers and can be easily delivered to remote populations. It can be delivered in schools, places of worship and town halls, without trained medical professionals in attendance. As such, it is well positioned to address unmet medical needs in developing countries – a critical element in increasing equitable access to vaccines and hereby controlling or preventing a global pandemic. ”
The COVID-19 pandemic have steered pharma companies in the right direction, as the industry as a whole now has a clearer idea of what went wrong, and where to go from here. Global access to vaccines can be achieved by taking advantage of tools such as open-source pharma, and through exploring alternative options to needle-vaccines that can be distributed broadly with more ease. | tech |
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As Europe seeks replacements for Russian oil, the Canadian government has withheld approval of a $ 12 billion supply project led by Norwegian producer Equinor ASA offshore of Newfoundland.
A week after the Russian invasion of Ukraine began on Feb. 24, the Liberal federal cabinet in Ottawa announced its second 40-day postponement of a decision on the 200,000 b/d platform planned for an Atlantic discovery known as Bay du Nord.
The announcement said the cabinet needs more study of potential “ significant adverse environmental effects ” despite a favorable verdict rendered last August by the national government’ s own watchdog, the Impact Assessment Agency of Canada ( IAAC).
A 337-page report on a three-year IAAC review said, “ The Agency concludes that the Bay du Nord development project is not likely to cause significant adverse environmental effects, taking into account the implementation of mitigation measures. ”
The IAAC found Equinor’ s new Atlantic supply platform would have slight effects on greenhouse gas emissions, the prime reduction target of federal climate change policy: increases by 0.04% for Canada’ s total and by 2.5% for Newfoundland.
The cabinet review of Bay du Nord is shrouded in official secrecy that covers politically sensitive work on consensus decisions by the Canadian government’ s executive branch. But differences among current member ministers are well known.
Environment Minister Steven Guilbeault, a Member of Parliament ( MP) from Montreal, is a declared fossil fuel opponent.
Guilbeault is a former Greenpeace campaign manager and a founder of a French Canadian counterpart, Equiterre, that backed the Quebec government’ s 2021 rejection of the Energie Saguenay liquefied natural gas ( LNG) export project and adoption of a provincial ban against oil and gas drilling. Both groups oppose the Bay du Nord plan.
Global demand for oil will take “ a huge drop ” of 75% by 2050, Guilbeault told a March 24 meeting of the Canadian Senate’ s energy committee. He described his policy goal for Canada as “ a more sustainable, nature-positive, net-zero [ emissions ] country. ”
As for the Newfoundland offshore supply plan, Guilbeault said, “ It must be understood that if the Bay du Nord project goes ahead, it could not produce oil before 2028. I doubt that our European friends and colleagues will wait until 2028 for Canadian oil. ”
On the other side of the Liberal spectrum, Labor Minister Seamus O’ Regan, a St. John’ s MP and former television personality, stood out as a champion of his home Newfoundland’ s fossil fuel industry before the cabinet review of Bay du Nord.
“ There will be no economic recovery without our oil and gas sector, ” O’ Regan told the Canadian Gas Association’ s Energy Magazine during the industry slump inflicted by the COVID-19 virus pandemic.
“ We [ Canada ] are the fourth largest producer of gas in the world. We are the sixth largest exporter of natural gas. Energy is our family business. It’ s what we do, ” said O’ Regan.
As Minister of Natural Resources until last fall, he presided over a CDN $ 320-million ( US $ 256-million) Newfoundland oil industry aid package and regulatory reform to accelerate offshore exploration drilling approvals. He backed the western Canadian industry’ s carbon capture and storage ( CCS) route towards hitting the government net-zero emissions target.
Suspense over the fate of Bay du Nord heightened in Newfoundland after a March 22 announcement of an alliance between the Liberals and the New Democratic Party ( NDP), a Canadian version of the Democrats’ “ progressives ” left wing in the United States.
The deal created a 184-MP voting majority – of 159 Liberals plus 25 New Democrats – to dominate Canada’ s 335-seat Parliament after no clear winner emerged among five political parties that contested a 2021 national election.
In trade for cabinet commitments to enforce climate change policy, and to top up Canada’ s Medicare system with dentistry and prescription drug programs, the NDP pledged to support the Liberal administration until the next mandatory election in 2025.
Offshore oil development fuels deep community divisions in Newfoundland.
“ Newfoundland and Labrador needs the Bay du Nord project, ” said an open letter by Charlene Johnson, head of the St. John’ s Energy NL group with an international membership roster of 460 organizations. “ The world needs the Bay du Nord Project. ”
Johnson wrote, “ Bay du Nord is a generational project, led by a company committed to ESG [ environment, society and governance ] principles and producing energy to meet global demand via those principles. They are committed to doing so by the lowest carbon means possible. ”
[ Want today’ s Henry Hub, Houston Ship Channel and Chicago Citygate prices? Check out NGI’ s daily natural gas price snapshot now. ]
Project opponents, an environmentalist coalition led by the Sierra Club’ s Canadian branch and including Greenpeace and Equiterre, were no less forceful in an open letter that called on the cabinet to veto Bay du Nord.
The opposition said, “ This project is incompatible with Canada’ s domestic and global climate commitments, contradicts Canada’ s commitment to capping emissions from the oil and gas sector, is based on a seriously flawed Environmental Impact Statement, and does not provide Newfoundland and Labrador the support needed to transition workers to a prosperous, clean economy. ”
The next target date for a decision on Equinor’ s Newfoundland project is April 13. But the Canadian regulatory structure gives the federal cabinet power to vary the agenda.
As the Bay du Nord debate heated up, the cabinet made changes on two other fossil fuel regulatory fronts. An offshore drilling rights sale has been suspended for up to 90 days. Guilbeault announced accelerated enforcement of a 75% methane emissions cut.
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Tesla stock surges after plans to enable stock split were disclosed | Shares of Tesla shot up Monday after the electric vehicle giant disclosed plans to enable a stock split, which would be the second in two years.
The company ( TSLA) said in an 8-K filing with the Securities and Exchange Commission that it will ask shareholders to approve an increase in the number of shares outstanding. The request will be made at its 2022 annual shareholders ' meeting expected in October.
The company said the stock split would be enacted in the form of a stock dividend. `` Tesla's Board of Directors... has approved the management proposal, but the stock dividend will be contingent on final Board approval, '' the company stated.
The stock jumped 8.0% to $ 1,091.84, the highest closing price since Jan. 12. It had slipped 0.3% on Friday to snap an eight-day winning streak. Monday's rally comes even after a report that Tesla will pause production in China amid new COVID-19 lockdowns.
Tesla had 1.033 billion shares outstanding as of Jan. 31. In the 2021 proxy statement, the company said it is authorized to have 2.00 billion shares outstanding.
The company's only other stock split, a 5-to-1 split, took effect on Aug. 31, 2020. At that time, the stock was trading at a pre-split-adjusted price of about $ 2,213. The stock closed Aug. 31 at split-adjusted $ 498.32.
To lower the stock price to around that level, Tesla would have to increase number of shares it is authorized to have outstanding by more than 1 billion, so it could enact a 2-for-1 split. To match the previous 5-for-1 split, the number of authorized shares outstanding would have to increase by more than 3 billion.
Although a stock split doesn't change anything about a company's fundamentals, it has historically helped boost the stock price, as it is viewed as a sign of management's confidence that the stock will continue to perform well, as Mark Hulbert has written for MarketWatch.
Also read: Tesla is one of only 11 stocks in the S & P 500, excluding energy, that enjoys this critical support.
Tesla's stock had soared 78% from the time the company said after the Aug. 11 close that it approved a 5-for-1 stock split through Aug. 31, but then fell 33.7% over the next week. The stock didn't close back above the Aug. 31 closing price until Nov. 19.
Wedbush analyst Dan Ives said he believes a stock split would be a `` smart strategic move '' for Tesla, as it follows similar moves announced this year by Alphabet Inc. ( GOOGL) ( GOOGL) and Amazon.com Inc. ( AMZN) He believes a split will be a positive catalyst for Tesla's stock going forward.
Read more: The stock split from Google's parent may spark a wave, Bank of America analysts say.
Ives reiterated his outperform rating, which he's had on Tesla's stock since April 2021, and kept his price target at $ 1,400.
Tesla's stock has gained 3.3% year-to-date through Monday, and has soared 78.6% over the past 12 months. In comparison, the S & P 500 index has gained 15.2% over the past year.
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Ruxolitinib in addition to standard of care for the treatment of patients admitted to hospital with COVID-19 ( RUXCOVID): a randomised, double-blind, placebo-controlled, phase 3 trial | BackgroundCOVID-19 is associated with acute respiratory distress and cytokine release syndrome. The Janus kinase ( JAK) 1/JAK2 inhibitor ruxolitinib reduces inflammatory cytokine concentrations in disorders characterised by cytokine dysregulation, including graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis. We assessed whether treatment with the JAK1/JAK2 inhibitor ruxolitinib would be beneficial in patients with COVID-19 admitted to hospital.MethodsRUXCOVID was an international, randomised, double-blind, phase 3 trial of ruxolitinib plus standard of care versus placebo plus standard of care in patients with COVID-19. Patients who were hospitalised but not on mechanical ventilation or in the intensive care unit [ ICU ] were randomly assigned ( 2:1) to oral ruxolitinib 5 mg twice per day or placebo for 14 days ( 14 additional days were allowed if no improvement). The primary endpoint was a composite of death, respiratory failure ( invasive ventilation), or ICU care by day 29, analysed by logistic regression including region, treatment, baseline clinical status, age, and sex as covariates. This trial is registered with ClinicalTrials.gov, NCT04362137.FindingsBetween May 4 and Sept 19, 2020, 432 patients were randomly assigned to ruxolitinib ( n=287) or placebo ( n=145) plus standard of care; the mean age was 56·5 years ( SD 13·3), 197 ( 46%) were female, and 235 ( 54%) were male. The primary objective was not met: the composite endpoint occurred in 34 ( 12%) of 284 ruxolitinib-treated patients versus 17 ( 12%) of 144 placebo-treated patients ( odds ratio 0·91, 95% CI 0·48–1·73; p=0·77). By day 29, nine ( 3%) of 286 ruxolitinib-treated patients had died compared with three ( 2%) of 145 placebo-treated patients; 22 ( 8%) of 286 ruxolitinib-treated patients had received invasive ventilation compared with ten ( 7%) of 145 placebo-treated patients; and 30 ( 11%) of 284 ruxolitinib-treated patients had received ICU care compared with 17 ( 12%) of 144 placebo-treated patients. In an exploratory analysis, median time to recovery was 1 day faster with ruxolitinib versus placebo ( 8 days vs 9 days; hazard ratio 1·10, 95% CI 0·89–1·36). Adverse events included headache ( 23 [ 8% ] of 281 on ruxolitinib vs 11 [ 8% ] of 143 on placebo) and diarrhoea ( 21 [ 7% ] vs 12 [ 8% ]).InterpretationRuxolitinib 5 mg twice per day showed no benefit in the overall study population. A larger sample is required to determine the clinical importance of trends for increased efficacy in patient subgroups.FundingNovartis and Incyte.
COVID-19 is associated with acute respiratory distress and cytokine release syndrome. The Janus kinase ( JAK) 1/JAK2 inhibitor ruxolitinib reduces inflammatory cytokine concentrations in disorders characterised by cytokine dysregulation, including graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis. We assessed whether treatment with the JAK1/JAK2 inhibitor ruxolitinib would be beneficial in patients with COVID-19 admitted to hospital.
RUXCOVID was an international, randomised, double-blind, phase 3 trial of ruxolitinib plus standard of care versus placebo plus standard of care in patients with COVID-19. Patients who were hospitalised but not on mechanical ventilation or in the intensive care unit [ ICU ] were randomly assigned ( 2:1) to oral ruxolitinib 5 mg twice per day or placebo for 14 days ( 14 additional days were allowed if no improvement). The primary endpoint was a composite of death, respiratory failure ( invasive ventilation), or ICU care by day 29, analysed by logistic regression including region, treatment, baseline clinical status, age, and sex as covariates. This trial is registered with ClinicalTrials.gov, NCT04362137.
Between May 4 and Sept 19, 2020, 432 patients were randomly assigned to ruxolitinib ( n=287) or placebo ( n=145) plus standard of care; the mean age was 56·5 years ( SD 13·3), 197 ( 46%) were female, and 235 ( 54%) were male. The primary objective was not met: the composite endpoint occurred in 34 ( 12%) of 284 ruxolitinib-treated patients versus 17 ( 12%) of 144 placebo-treated patients ( odds ratio 0·91, 95% CI 0·48–1·73; p=0·77). By day 29, nine ( 3%) of 286 ruxolitinib-treated patients had died compared with three ( 2%) of 145 placebo-treated patients; 22 ( 8%) of 286 ruxolitinib-treated patients had received invasive ventilation compared with ten ( 7%) of 145 placebo-treated patients; and 30 ( 11%) of 284 ruxolitinib-treated patients had received ICU care compared with 17 ( 12%) of 144 placebo-treated patients. In an exploratory analysis, median time to recovery was 1 day faster with ruxolitinib versus placebo ( 8 days vs 9 days; hazard ratio 1·10, 95% CI 0·89–1·36). Adverse events included headache ( 23 [ 8% ] of 281 on ruxolitinib vs 11 [ 8% ] of 143 on placebo) and diarrhoea ( 21 [ 7% ] vs 12 [ 8% ]).
Ruxolitinib 5 mg twice per day showed no benefit in the overall study population. A larger sample is required to determine the clinical importance of trends for increased efficacy in patient subgroups.
COVID-19 was declared a global pandemic on March 11, 2020, by WHO.1Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Google Scholar As of March 1, 2022, more than 437 million cases of COVID-19 had been reported, with 5·96 million deaths worldwide.2Johns Hopkins UniversityCOVID-19 Dashboard by the Center for Systems Science and Engineering ( CSSE).https: //coronavirus.jhu.edu/map.htmlDate: 2020Date accessed: March 1, 2022Google Scholar Although most people with COVID-19 develop mild or uncomplicated illness, many have some form of respiratory involvement.3Siddiqi HK Mehra MR COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal.J Heart Lung Transplant. 2020; 39: 405-407Google Scholar, 4The Novel Coronavirus Pneumonia Emergency Response Epidemiology TeamThe epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases ( COVID-19) —China, 2020.China CDC Wkly. 2020; 2: 113-122Google Scholar, 5Carsana L Sonzogni A Nasr A et al.Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study.Lancet Infect Dis. 2020; 20: 1135-1140Google Scholar Approximately 20% of people develop severe disease resulting in pneumonia, hospitalisation, and oxygen support; 5% require admission to the intensive care unit ( ICU) and invasive mechanical ventilation.3Siddiqi HK Mehra MR COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal.J Heart Lung Transplant. 2020; 39: 405-407Google Scholar, 4The Novel Coronavirus Pneumonia Emergency Response Epidemiology TeamThe epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases ( COVID-19) —China, 2020.China CDC Wkly. 2020; 2: 113-122Google Scholar, 5Carsana L Sonzogni A Nasr A et al.Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study.Lancet Infect Dis. 2020; 20: 1135-1140Google Scholar
On infection, the virus activates the innate and adaptive immune systems, resulting in the release of pro-inflammatory cytokines in an attempt to eliminate the virus.6Ackermann M Verleden SE Kuehnel M et al.Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19.N Engl J Med. 2020; 383: 120-128Google Scholar As the disease progresses, the innate immune system response contributes to oxidative injury and alveolar membrane damage, resulting in hypoxia.6Ackermann M Verleden SE Kuehnel M et al.Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19.N Engl J Med. 2020; 383: 120-128Google Scholar Hypoxemia is further exacerbated by pulmonary microthromboses and macrothromboses.7Moores LK Tritschler T Brosnahan S et al.Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel report.Chest. 2020; 158: 1143-1163Google Scholar, 8Goker Bagca B Biray Avci C The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19.Cytokine Growth Factor Rev. 2020; 54: 51-62Google Scholar
Severe disease can be complicated by acute respiratory distress syndrome ( the primary cause of death in 70% of COVID-19 fatalities), sepsis and septic shock, or multiorgan failure, or a combination of these, which have all been linked to the host inflammatory response.9Yang X Yu Y Xu J et al.Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.Lancet Respir Med. 2020; 8: 475-481Google Scholar, 10Khadke S Ahmed N Ahmed N et al.Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.Virol J. 2020; 17: 154Google Scholar, 11Shimabukuro-Vornhagen A Gödel P Subklewe M et al.Cytokine release syndrome.J Immunother Cancer. 2018; 6: 56Google Scholar, 12Hojyo S Uchida M Tanaka K et al.How COVID-19 induces cytokine storm with high mortality.Inflamm Regen. 2020; 40: 37Google Scholar The marked increase in immune cells and pro-inflammatory chemokines and cytokines, including interleukin ( IL) -1, IL-6, IL-8, and tumour necrosis factor ( TNF), drives lung injury and the activation of additional pro-inflammatory pathways via the Janus kinase/signal transducer and activator of transcription ( JAK/STAT) pathway, resulting in further lung inflammation, lung lesions, respiratory dysfunction and failure, and in some cases, death.8Goker Bagca B Biray Avci C The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19.Cytokine Growth Factor Rev. 2020; 54: 51-62Google Scholar, 10Khadke S Ahmed N Ahmed N et al.Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.Virol J. 2020; 17: 154Google Scholar
Research in contextEvidence before this studyWe searched PubMed for articles published between Jan 1 and May 1, 2020, that evaluated treatments for COVID-19 using the search terms `` ( COVID-19 OR SARS-COV-2) AND ( therap * OR treatment OR drug) ''. The search focused on clinical studies, clinical trials, meta-analyses, and systematic reviews. Before the start of this study ( May, 2020), evidence regarding pharmacotherapy in severe COVID-19 was scarce. There were indications that severe disease and death might be related to hyperinflammation, with similarities to cytokine release syndrome. Studies suggested that agents that block inflammatory pathways, including the Janus kinase/signal transducer and activator of transcription ( JAK/STAT) pathway, should be evaluated as treatment for severe COVID-19. Because ruxolitinib, a potent and selective inhibitor of JAK1 and JAK2, had previously shown efficacy in controlling inflammatory cytokine dysregulation in other disorders, such as graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis, it was considered a candidate for the treatment of severe COVID-19 disease.During the conduct of this trial, the North American ACTT-2 study of baricitinib ( a JAK1/JAK2 inhibitor) combined with remdesivir in COVID-19 found that addition of the JAK inhibitor to antiviral treatment reduced time to recovery, in particular in hospitalised patients requiring high-flow oxygen support. A trial of tofacitinib ( a JAK1/JAK3 inhibitor) in Brazil found that tofacitinib plus standard care reduced mortality or respiratory failure in a population consisting mainly of patients with severe COVID-19. However, in another study in patients with mild-to-moderate COVID-19, tofacitinib treatment showed a reduction in inflammatory markers, but no clinical benefits. Trials of tocilizumab in COVID-19 also found that patients with more severe disease were more likely to benefit from immunosuppressive therapy, and in the large RECOVERY trial ( n=4116), tocilizumab improved outcomes in patients with hypoxia and substantial inflammation.Added value of this studyTo our knowledge, this was the first randomised, controlled, phase 3 study to evaluate ruxolitinib plus standard of care ( according to local practice) for patients with COVID-19. This study showed that, in a broad, international population of patients admitted to hospital for COVID-19 who were not on invasive mechanical ventilation or in the intensive care unit, a low dose of ruxolitinib ( 5 mg twice per day) plus standard-of-care treatment did not significantly improve outcomes or slow progression of severe disease in an international population compared with placebo plus standard-of-care treatment. Hence our data suggest that JAK1/JAK2 inhibitor therapy in COVID-19 needs to be considered with caution.Implications of all the available evidenceRUXCOVID was compatible with previous studies of JAK inhibitors in COVID-19: although the proportion of patients on high-flow oxygen was small ( 22 [ 5% ] of 432), a trend toward greater efficacy of ruxolitinib versus placebo was noted in this subgroup. No benefit was observed in patients with no or low-flow oxygen requirements. Substantial inflammation was not an inclusion criterion. Taken together, studies suggest that JAK inhibitor treatment might improve outcomes in patients with COVID-19, especially in a certain subset; however, our findings do not support the use of ruxolitinib as a treatment option for patients with mild-to-moderate COVID-19 who are admitted to hospital. Much is still being learned about COVID-19, and a need exists to identify patient subsets that would benefit from specific treatments. In novel global health crises, robust a priori sample-size estimates are not always possible. Therefore, we suggest that adaptive designs, including futility analyses and sample-size reestimation, be built into future studies conducted under these conditions. When all the evidence is viewed in context, JAK1/JAK2 inhibitor therapy in general is not effective in all subsets of hospitalised patient populations. More research is needed to better understand what inhibitors are beneficial in which subpopulations.
We searched PubMed for articles published between Jan 1 and May 1, 2020, that evaluated treatments for COVID-19 using the search terms `` ( COVID-19 OR SARS-COV-2) AND ( therap * OR treatment OR drug) ''. The search focused on clinical studies, clinical trials, meta-analyses, and systematic reviews. Before the start of this study ( May, 2020), evidence regarding pharmacotherapy in severe COVID-19 was scarce. There were indications that severe disease and death might be related to hyperinflammation, with similarities to cytokine release syndrome. Studies suggested that agents that block inflammatory pathways, including the Janus kinase/signal transducer and activator of transcription ( JAK/STAT) pathway, should be evaluated as treatment for severe COVID-19. Because ruxolitinib, a potent and selective inhibitor of JAK1 and JAK2, had previously shown efficacy in controlling inflammatory cytokine dysregulation in other disorders, such as graft-versus-host disease, myelofibrosis, and secondary hemophagocytic lymphohistiocytosis, it was considered a candidate for the treatment of severe COVID-19 disease.
During the conduct of this trial, the North American ACTT-2 study of baricitinib ( a JAK1/JAK2 inhibitor) combined with remdesivir in COVID-19 found that addition of the JAK inhibitor to antiviral treatment reduced time to recovery, in particular in hospitalised patients requiring high-flow oxygen support. A trial of tofacitinib ( a JAK1/JAK3 inhibitor) in Brazil found that tofacitinib plus standard care reduced mortality or respiratory failure in a population consisting mainly of patients with severe COVID-19. However, in another study in patients with mild-to-moderate COVID-19, tofacitinib treatment showed a reduction in inflammatory markers, but no clinical benefits. Trials of tocilizumab in COVID-19 also found that patients with more severe disease were more likely to benefit from immunosuppressive therapy, and in the large RECOVERY trial ( n=4116), tocilizumab improved outcomes in patients with hypoxia and substantial inflammation.
To our knowledge, this was the first randomised, controlled, phase 3 study to evaluate ruxolitinib plus standard of care ( according to local practice) for patients with COVID-19. This study showed that, in a broad, international population of patients admitted to hospital for COVID-19 who were not on invasive mechanical ventilation or in the intensive care unit, a low dose of ruxolitinib ( 5 mg twice per day) plus standard-of-care treatment did not significantly improve outcomes or slow progression of severe disease in an international population compared with placebo plus standard-of-care treatment. Hence our data suggest that JAK1/JAK2 inhibitor therapy in COVID-19 needs to be considered with caution.
RUXCOVID was compatible with previous studies of JAK inhibitors in COVID-19: although the proportion of patients on high-flow oxygen was small ( 22 [ 5% ] of 432), a trend toward greater efficacy of ruxolitinib versus placebo was noted in this subgroup. No benefit was observed in patients with no or low-flow oxygen requirements. Substantial inflammation was not an inclusion criterion. Taken together, studies suggest that JAK inhibitor treatment might improve outcomes in patients with COVID-19, especially in a certain subset; however, our findings do not support the use of ruxolitinib as a treatment option for patients with mild-to-moderate COVID-19 who are admitted to hospital. Much is still being learned about COVID-19, and a need exists to identify patient subsets that would benefit from specific treatments. In novel global health crises, robust a priori sample-size estimates are not always possible. Therefore, we suggest that adaptive designs, including futility analyses and sample-size reestimation, be built into future studies conducted under these conditions. When all the evidence is viewed in context, JAK1/JAK2 inhibitor therapy in general is not effective in all subsets of hospitalised patient populations. More research is needed to better understand what inhibitors are beneficial in which subpopulations.
Many patients with severe respiratory disease due to COVID-19 have features consistent with cytokine release syndrome ( CRS),13Wang W Liu X Wu S et al.Definition and risks of cytokine release syndrome in 11 critically ill COVID-19 patients with pneumonia: analysis of disease characteristics.J Infect Dis. 2020; 222: 1444-1451Google Scholar also referred to as cytokine storm, which is related to increased activation of the JAK/STAT pathway.11Shimabukuro-Vornhagen A Gödel P Subklewe M et al.Cytokine release syndrome.J Immunother Cancer. 2018; 6: 56Google Scholar Unlike the systemic CRS that can be caused by chimeric antigen receptor T-cell therapy, CRS-like cytokine storm in COVID-19 predominantly occurs within the lungs.12Hojyo S Uchida M Tanaka K et al.How COVID-19 induces cytokine storm with high mortality.Inflamm Regen. 2020; 40: 37Google Scholar Predictive criteria for cytokine storm risk in COVID-19 were recently proposed, with potential to enable a tailored preventive approach by identifying patients at high risk.14Caricchio R Gallucci M Dass C et al.Preliminary predictive criteria for COVID-19 cytokine storm.Ann Rheum Dis. 2021; 80: 88-95Google Scholar In the early stages of the development of treatment strategies for severe COVID-19 disease, it was suggested that host-directed therapies, including JAK inhibition and other immunotherapies, might be of benefit to patients with cytokine storm.15Mehta P McAuley DF Brown M Sanchez E Tattersall RS Manson JJ COVID-19: consider cytokine storm syndromes and immunosuppression.Lancet. 2020; 395: 1033-1034Google Scholar, 16Zumla A Hui DS Azhar EI Memish ZA Maeurer M Reducing mortality from 2019-nCoV: host-directed therapies should be an option.Lancet. 2020; 395: e35-e36Google Scholar, 17Stebbing J Phelan A Griffin I et al.COVID-19: combining antiviral and anti-inflammatory treatments.Lancet Infect Dis. 2020; 20: 400-402Google Scholar
Ruxolitinib is a potent and selective inhibitor of JAK1 and JAK2, approved for the treatment of myelofibrosis, polycythemia vera, and steroid-refractory acute graft-versus-host disease ( USA only).18Jakafi ( ruxolitinib) Prescribing information. Incyte, Wilmington, DE2020Google Scholar Ruxolitinib reduces concentrations of inflammatory cytokines in disorders in which cytokine dysregulation plays a role, including graft-versus-host disease19Zeiser R Burchert A Lengerke C et al.Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey.Leukemia. 2015; 29: 2062-2068Google Scholar and hemophagocytic lymphohistiocytosis.20Ahmed A Merrill SA Alsawah F et al.Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: an open-label, single-centre, pilot trial.Lancet Haematol. 2019; 6: e630-e637Google Scholar, 21Goldsmith SR Saif Ur Rehman S Shirai CL Vij K DiPersio JF Resolution of secondary hemophagocytic lymphohistiocytosis after treatment with the JAK1/2 inhibitor ruxolitinib.Blood Adv. 2019; 3: 4131-4135Google Scholar, 22Keenan C Nichols KE Albeituni S Use of the JAK inhibitor ruxolitinib in the treatment of hemophagocytic lymphohistiocytosis.Front Immunol. 2021; 12614704Google Scholar
The activity of ruxolitinib in CRS-related diseases warranted investigation of its use in patients with severe COVID-19 with clear symptoms and a positive test for SARS-CoV-2 without progression to intubation or need for ICU care. Furthermore, independent investigator-initiated studies revealed potential clinical benefit from the addition of ruxolitinib to best available therapy.23La Rosée F Bremer HC Gehrke I et al.The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation.Leukemia. 2020; 34: 1805-1815Google Scholar, 24Cao Y Wei J Zou L et al.Ruxolitinib in treatment of severe coronavirus disease 2019 ( COVID-19): A multicenter, single-blind, randomized controlled trial.J Allergy Clin Immunol. 2020; 146: 137-146Google Scholar Here we report the primary analysis of RUXCOVID ( NCT04362137), a global phase 3 study evaluating ruxolitinib plus standard of care versus placebo plus standard of care in hospitalised patients with COVID-19 not requiring invasive ventilation.
RUXCOVID was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study ( appendix p 13) evaluating the efficacy and safety of ruxolitinib plus standard of care versus placebo plus standard of care in patients with COVID-19.25Langmuir P Yeleswaram S Smith P Knorr B Squier P Design of clinical trials evaluating ruxolitinib, a JAK1/JAK2 inhibitor, for treatment of COVID-19-associated cytokine storm.Del J Public Health. 2020; 6: 50-54Google Scholar The study was conducted in 61 centres across 12 countries ( Russia, USA, Brazil, Spain, Argentina, Peru, Turkey, Mexico, UK, Colombia, France, and Germany; appendix p 5). The study was approved by the institutional review board or central ethics committee at each participating institution and conducted in accordance with the Declaration of Helsinki.
Patients were required to be aged 12 years or older and hospitalised for confirmed COVID-19 ( by PCR test or another rapid test from the respiratory tract). Additionally, patients had to meet at least one of: pulmonary infiltrates ( chest x-ray or chest CT scan); respiratory frequency of at least 30 breaths per min; requiring supplementary oxygen; oxygen saturation of 94% or less on room air; or arterial oxygen partial pressure ( PaO2) /fraction of inspired oxygen ( FiO2) of less than 300 mm Hg ( 40 kPa). Patients were excluded due to any of the following conditions: uncontrolled infection besides COVID-19; currently intubated or intubated between screening and randomisation; in ICU at time of randomisation; on antirejection, immunosuppressant, or immunomodulatory drugs ( ie, tocilizumab, ruxolitinib, canakinumab, sarilumab, or anakinra); unable to ingest tablets at randomisation; pregnant or nursing. Full inclusion and exclusion criteria can be found in the appendix ( p 3). As per other studies early in the pandemic,26Kalil AC Patterson TF Mehta AK et al.Baricitinib plus remdesivir for hospitalized adults with COVID-19.N Engl J Med. 2021; 384: 795-807Google Scholar, 27Beigel JH Tomashek KM Dodd LE et al.Remdesivir for the treatment of COVID-19—final report.N Engl J Med. 2020; 383: 1813-1826Google Scholar inclusion was based on clinical criteria rather than hyperinflammation or cytokine storm because, at the time of study initiation, there were no clear cytokine-related criteria associated with COVID-19 that could have reliably been used. Eligible participants were only included in the study after informed consent was obtained, as approved by each institutional review board or independent ethics committee.
Patients were randomly assigned ( 2:1) to receive oral ruxolitinib or oral matching-image placebo. Block randomisation, with a block size of 3, was used to decrease the risk of imbalance. Randomisation was stratified by geographical region ( North America, western Europe, eastern Europe, Latin America, and other). Randomisation was done by interactive response technology. The investigator contacted the interactive response technology system, which assigned a randomisation number to each participant, linking them to their unique medication number. Medication numbers were automatically assigned to medication packs. Study treatments were identical in packaging, appearance, taste, and odour.
Participants, investigator staff, persons performing the assessments, and the clinical trial team remained masked throughout the trial. Unmasking occurred in the case of participant emergencies and at the conclusion of the study.
Patients received oral ruxolitinib ( Novartis Pharma AG, Stein, Switzerland) 5 mg twice per day or oral placebo twice per day, for 14 days. An additional 14 days of study drug was allowed if, in the opinion of the investigator, the patient's clinical signs and symptoms were not improving or worsened, and the potential benefit outweighed the risk.
Ruxolitinib 5 mg twice per day is the approved starting dose in the USA for treatment of steroid-refractory acute graft-versus-host disease with demonstrated anti-inflammatory effect.28Jagasia M Perales MA Schroeder MA et al.Ruxolitinib for the treatment of steroid-refractory acute GVHD ( REACH1): a multicenter, open-label phase 2 trial.Blood. 2020; 135: 1739-1749Google Scholar It is also the starting dose recommended for patients with myelofibrosis with a platelet count of 50 × 109 per L to less than 100 × 109 per L.18Jakafi ( ruxolitinib) Prescribing information. Incyte, Wilmington, DE2020Google Scholar Therefore, ruxolitinib 5 mg twice per day was included in this study.
Study treatment was given in combination with standard-of-care therapy according to the investigator's clinical judgment, with appropriate monitoring of potential drug–drug interactions. Permitted concomitant therapies included antivirals ( including remdesivir), corticosteroids ( including dexamethasone), heparin, anticoagulants, antiemetics, calcineurin inhibitors, azole fungal prophylaxis, broad-spectrum antibiotics, narcotics, and sedatives. Prohibited medications were other JAK inhibitors, aspirin ( > 150 mg/day), and fluconazole ( > 200 mg/day).
Dose reductions or interruptions were allowed in the case of drug toxicities ( appendix p 2). If the patient became intubated during the study, an aqueous suspension of the study medication could be delivered via nasogastric tube. Hospitalised patients were assessed daily up to day 29 ( end of study) for vital signs, oxygen saturation ( SpO2), fraction of inspired oxygen ( FiO2), consciousness, haematology ( every other day), clinical chemistry ( every other day), in-hospital outcomes, and biomarkers ( day 7). Patients who were discharged during the study period were subsequently assessed daily up to day 29, via telephone, for clinical status, ventilatory status, adverse events, and previous or concomitant nondrug therapies. On the date of discharge, patients on oxygen by nasal cannula ( ≤2 L/min) were assessed for SpO2 on room air, based on investigator medical judgement. On days 15 and 29, discharged patients had all assessments performed in clinic.
The primary endpoint was a composite of death, respiratory failure ( requiring invasive mechanical ventilation), or ICU care, by day 29.
Secondary efficacy endpoints included mortality rate by day 29, respiratory failure by day 29, ICU care by day 29 ( post hoc), duration of hospitalisation, changes in clinical status, and changes in the National Early Warning Score 2 ( NEWS2; appendix p 14). Changes in clinical status were measured using the COVID-19-specific 9-point ( 0–8) ordinal scale proposed by the WHO in February, 2020 ( appendix pp 2, 6). Assessments included the proportion of patients with improved or deteriorated clinical status scores at day 29; time to 1 or more points of improvement from baseline; and mean change in the score from baseline at days 15 and 29. Changes in NEWS2 included time to discharge or NEWS2 score of 2 or less for 24 h, whichever came first; and change from baseline in NEWS2 score.
Exploratory efficacy endpoints included time to recovery ( a post-hoc measure to allow comparison with the ACTT-2 study), independence from non-invasive ventilation, and oxygen therapy; duration of ICU stay, supplementary oxygen, and invasive mechanical ventilation; and ratio to baseline in concentrations of exploratory biomarkers, including C-reactive protein ( CRP), ferritin, and D-dimer. Biomarker samples were analysed in central ( for post-hoc measures of TNF, interferon [ IFN ] -γ, IL-10, IL-2RA, IL-6, IL-8) and local ( ferritin, CRP, procalcitonin, IL-6 [ if available ], D-dimer) laboratories.
Treatment-emergent adverse events were defined as those occurring, or increasing in severity, between the first dose of study medication and the last study visit and were assessed and graded according to the Common Terminology Criteria for Adverse Events ( version 5.0). The safety population included all patients who received at least one dose of study medication.
The study was designed to have at least 80% power to detect an absolute difference of 15% between the treatment groups in the proportion of patients meeting the primary endpoint ( based on multiple sample size calculations assuming the rate of the primary outcome in the control group to be in the range of 30–80%) —the required sample size was 402 patients.
The primary endpoint was analysed by a logistic regression model with treatment group, region, baseline WHO ( 0–8) clinical status ( ≤3 or ≥4), age, and sex as covariates. The estimated odds ratio ( OR; < 1 favours ruxolitinib), p values, and 95% CIs were calculated. Retrieved dropout data after study treatment discontinuation were collected. If retrieved dropout data were available up to day 29, those were used for analysis. If no retrieved dropout data were collected after study treatment discontinuation, the retrieved dropout data were not complete to day 29, or patients withdrew from the study before day 29, then the patient was considered to meet the primary endpoint, unless they were in one of the following scenarios: there was no occurrence of death, mechanical ventilation, or ICU care in all the available data and patients were discharged from the hospital; or, the last available data ( either on treatment or off treatment) were from day 15 or later and there was no occurrence of death, mechanical ventilation, or ICU care in all the available data.
A post-hoc analysis of the primary endpoint examined subgroups defined by baseline demographic and disease state parameters. The subgroup analyses were explored using the same logistic regression model as described for the primary analysis with the additional term of subgroup factor ( if not already included in the model) and the interaction term of subgroup and treatment. No adjustment was made for multiplicity. Secondary and exploratory endpoints were similarly analysed without adjustments for multiplicity. Time to discharge or recovery was analysed using a proportional hazards model for competing risk analysis, which included treatment, region, age, sex, baseline WHO ( 0–8) clinical status, and the interaction term of baseline WHO ( 0-8) clinical status and treatment as covariates. Patients who were not discharged and did not die were censored at their last assessment date. Median ( 95% CI) times to discharge or recovery were estimated by the Kaplan-Meier method stratified by baseline clinical status, with dead patients being censored at the maximum follow-up time in the study. For both time to discharge and time to recovery, hazard ratio ( HR) and 95% CIs were calculated. An HR of more than 1 favours ruxolitinib. This study was registered with ClinicalTrials.gov, NCT04362137.
The study was funded and designed by Novartis and Incyte. Data were analysed and interpreted by the funder in collaboration with all the authors; the funder was unaware of the treatment group assignments until database lock.
Between May 4 and Sept 19, 2020, 432 patients were randomly assigned ( 2:1) to receive ruxolitinib ( n=287) plus standard of care or placebo ( n=145) plus standard of care ( randomised analysis set; figure 1). The greatest proportion of the 432 patients were from Russia ( 171 [ 40% ]), followed by the USA ( 48 [ 11% ]), Brazil ( 41 [ 9% ]), and Spain ( 39 [ 9% ]; appendix p 5 for all study sites). Patients who developed respiratory failure or required ICU care, or both, at randomisation ( ruxolitinib n=2 and placebo n=1) were excluded from the primary efficacy analyses. The safety set comprised 424 patients who received at least one dose of study drug ( ruxolitinib n=281 and placebo n=143).Figure 1Trial profileShow full captionICU=intensive care unit. * Eight patients were randomly assigned but did not receive treatment due to consent withdrawal ( n=4), patient decision ( n=3), and misrandomisation ( n=1). †Includes patients who completed first course of 14-day treatment, but discontinued from second course of 14-day treatment.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
ICU=intensive care unit. * Eight patients were randomly assigned but did not receive treatment due to consent withdrawal ( n=4), patient decision ( n=3), and misrandomisation ( n=1). †Includes patients who completed first course of 14-day treatment, but discontinued from second course of 14-day treatment.
Baseline demographics and disease characteristics were balanced between the two treatment groups ( table 1). Mean patient age was 56·5 years ( SD 13·3); 122 ( 28%) of 432 were aged 65 years or older and none were younger than 18 years ( range 20–90). Most patients were White ( 351 [ 81% ]), and nearly half ( 201 [ 47% ] of 426) had a body-mass index ( BMI) of more than 30 kg/m2. The median time between the onset of COVID-19 symptoms and randomisation was 11 days ( IQR 8–14). Most patients had mild disease ( WHO [ 0–8 ] clinical status of 3 [ hospitalised, no oxygen support ], 141 [ 33% ] patients; WHO [ 0–8 ] clinical status of 4 [ low-flow oxygen support ], 268 [ 62% ]); only 22 [ 5% ] patients had severe disease ( WHO [ 0–8 ] clinical status of 5 [ non-invasive ventilation or high-flow oxygen support ]). Most patients had pneumonia ( 428 [ 99% ]). At baseline, 249 ( 58%) patients were receiving steroids and 28 ( 6%) were receiving remdesivir. Rates of concomitant therapy use at baseline by region ( eg, antithrombotics, systemic steroids, remdesivir) are shown in the appendix ( p 7). Concomitant therapy used at any time during the study is shown in the appendix ( p 8).Table 1Baseline patient demographics and disease characteristicsRuxolitinib ( n=287) Placebo ( n=145) Total ( N=432) Age, years56·4 ( 13·7; 22–90) 56·9 ( 12·5; 20–84) 56·5 ( 13·3; 20–90) Age category, ≥65 years83 ( 29%) 39 ( 27%) 122 ( 28%) SexFemale125 ( 44%) 72 ( 50%) 197 ( 46%) Male162 ( 56%) 73 ( 50%) 235 ( 54%) RaceWhite242 ( 84%) 109 ( 75%) 351 ( 81%) American Indian or Alaska Native26 ( 9%) 13 ( 9%) 39 ( 9%) Black or African American6 ( 2%) 9 ( 6%) 15 ( 3%) Asian5 ( 2%) 5 ( 3%) 10 ( 2%) Multiple3 ( 1%) 2 ( 1%) 5 ( 1%) Unknown5 ( 2%) 7 ( 5%) 12 ( 3%) EthnicityHispanic or Latino93 ( 32%) 39 ( 27%) 132 ( 31%) Not Hispanic or Latino184 ( 64%) 93 ( 64%) 277 ( 64%) Not reported2 ( 1%) 6 ( 4%) 8 ( 2%) Unknown8 ( 3%) 7 ( 5%) 15 ( 3%) Weight, kg85·2 ( 18·8) 87·2 ( 18·7) 85·9 ( 18·8) n283145428Body-mass index, kg/m2n282144426Mean ( SD) 29·9 ( 5·6) 31·0 ( 6·5) 30·3 ( 5·9) > 30 kg/m2129 ( 46%) 72 ( 50%) 201 ( 47%) CountryRussia114 ( 40%) 57 ( 39%) 171 ( 40%) USA32 ( 11%) 16 ( 11%) 48 ( 11%) Brazil28 ( 10%) 13 ( 9%) 41 ( 9%) Spain29 ( 10%) 10 ( 7%) 39 ( 9%) Argentina16 ( 6%) 11 ( 8%) 27 ( 6%) Peru15 ( 5%) 10 ( 7%) 25 ( 6%) Turkey13 ( 5%) 7 ( 5%) 20 ( 5%) Mexico14 ( 5%) 4 ( 3%) 18 ( 4%) UK10 ( 3%) 4 ( 3%) 14 ( 3%) Colombia7 ( 2%) 3 ( 2%) 10 ( 2%) France4 ( 1%) 6 ( 4%) 10 ( 2%) Germany5 ( 2%) 4 ( 3%) 9 ( 2%) Time between onset of symptoms and randomisation, days11·0 ( 8·0–14·0) 11·0 ( 8·0–13·5) 11·0 ( 8·0–14·0) Time between diagnosis and randomisation, days5·0 ( 3·0–8·0) 5·0 ( 3·0–7·0) 5·0 ( 3·0–8·0) WHO ( 0–8) clinical status3, hospitalised with mild disease ( no oxygen therapy [ defined as SpO2 ≥94% on room air ]) 94 ( 33%) 47 ( 32%) 141 ( 33%) 4, hospitalised with mild disease ( oxygen by mask or nasal prongs) 175 ( 61%) 93 ( 64%) 268 ( 62%) 5, hospitalised with severe disease ( noninvasive ventilation or high-flow oxygen) 17 ( 6%) 5 ( 3%) 22 ( 5%) Missing baseline clinical status1 ( < 1%) 01 ( < 1%) Pneumonia284 ( 99%) 144 ( 99%) 428 ( 99%) Steroid use170 ( 59%) 79 ( 54%) 249 ( 58%) Remdesivir use21 ( 7%) 7 ( 5%) 28 ( 6%) Data are mean ( SD; range); n (%); mean ( SD); n; or median ( IQR). SpO2=oxygen saturation. WHO ( 0–8) =COVID-19-specific 9-point ordinal scale for clinical status proposed by WHO ( appendix p 6). Open table in a new tab
Data are mean ( SD; range); n (%); mean ( SD); n; or median ( IQR). SpO2=oxygen saturation. WHO ( 0–8) =COVID-19-specific 9-point ordinal scale for clinical status proposed by WHO ( appendix p 6).
The study failed to meet the primary objective ( table 2). The composite endpoint of death, respiratory failure requiring invasive mechanical ventilation, or ICU care by day 29 occurred in 34 ( 12%) of 284 patients in the ruxolitinib group versus 17 ( 12%) of 144 patients in the placebo group ( OR 0·91, 95% CI 0·48–1·73; p=0·77).Table 2Primary, selected secondary, and exploratory efficacy outcomesRuxolitinib ( n=287) Placebo ( n=145) Comparison ( 95% CI) Primary endpointComposite endpoint of death, respiratory failure requiring mechanical ventilation, or ICU care by day 29 * Patients who developed respiratory failure or required ICU care, or both at randomisation are excluded from the analysis.34/284 ( 12%) 17/144 ( 12%) OR 0·91 ( 0·48–1·73); p=0·77Secondary endpointsMortality rate by day 299/286 ( 3%) 3/145 ( 2%) OR 1·21 ( 0·35–5·11) Respiratory failure by day 29 * Patients who developed respiratory failure or required ICU care, or both at randomisation are excluded from the analysis.22/286 ( 8%) 10/145 ( 7%) OR 0·99 ( 0·45–2·21) ICU care by day 29 * Patients who developed respiratory failure or required ICU care, or both at randomisation are excluded from the analysis.†Post hoc.30/284 ( 11%) 17/144 ( 12%) OR 0·81 ( 0·42–1·55) Change in WHO ( 0–8) clinical status at day 29‡Patients with missing data at day 29 were treated as non-responders.≥1-point improvement261/286 ( 91%) 136/145 ( 94%) OR 0·79 ( 0·35–1·79) ≥2-point improvement252/286 ( 88%) 129/145 ( 89%) OR 1·00 ( 0·52–1·92) ≥1-point deterioration14/286 ( 5%) 5/145 ( 3%) OR 1·18 ( 0·40–3·49) Death by baseline clinical status by day 29†Post hoc.§There were no deaths in the ruxolitinib and placebo groups in patients with a baseline WHO ( 0–8) clinical status of 5.WHO ( 0–8) clinical status of 32/94 ( 2%) 1/47 ( 2%) OR 0·80 ( 0·10–9·53) WHO ( 0–8) clinical status of 47/175 ( 4%) 2/93 ( 2%) OR 1·35 ( 0·32–7·89) Duration of hospitalisation, days¶Patients who did not have the event and did not die were censored at their last assessment date. Median is estimated by Kaplan-Meier method, with deaths being censored at the maximum follow-up time in the study.9·0 ( 8·0–10·0) 9·0 ( 8·0–12·0) HR 1·04 ( 0·84–1·28) Time to hospital discharge or NEWS2 of ≤2 maintained for 24 h, days¶Patients who did not have the event and did not die were censored at their last assessment date. Median is estimated by Kaplan-Meier method, with deaths being censored at the maximum follow-up time in the study.4·0 ( 3·0–4·0) 4·0 ( 3·0–5·0) HR 1·02 ( 0·84–1·23) Exploratory endpointsTime to recovery ( no longer infected, or ambulatory with no or minimal limitations), days†Post hoc. ¶Patients who did not have the event and did not die were censored at their last assessment date. Median is estimated by Kaplan-Meier method, with deaths being censored at the maximum follow-up time in the study.8·0 ( 8·0–9·0) 9·0 ( 7·0–11·0) HR 1·10 ( 0·89–1·36) Time to independence from non-invasive ventilation, days19·0 ( 11·5–25·0) 12·0 ( 9·0–22·0) NA‖Only summary statistics were conducted for these exploratory outcomes; all were evaluated on subsets of patients defined by post-baseline events, which could be confounded with treatment effect.Time to independence from supplementary oxygen, days5·5 ( 3·0–10·5) 6·0 ( 3·0–10·0) NA‖Only summary statistics were conducted for these exploratory outcomes; all were evaluated on subsets of patients defined by post-baseline events, which could be confounded with treatment effect.Duration of ICU care, days9·0 ( 7·0–13·0) 9·0 ( 4·0–21·0) NA‖Only summary statistics were conducted for these exploratory outcomes; all were evaluated on subsets of patients defined by post-baseline events, which could be confounded with treatment effect.Duration of supplementary oxygen, days5·0 ( 2·0–10·0) 6·0 ( 3·0–10·0) NA‖Only summary statistics were conducted for these exploratory outcomes; all were evaluated on subsets of patients defined by post-baseline events, which could be confounded with treatment effect.Duration of invasive mechanical ventilation, days7·5 ( 5·0–16·0) 12·0 ( 5·0–28·0) NA‖Only summary statistics were conducted for these exploratory outcomes; all were evaluated on subsets of patients defined by post-baseline events, which could be confounded with treatment effect.Data are n/total number of patients included in the analysis ( M [ not model based ]; [% ]), median ( 95% CI), or median ( IQR), unless otherwise specified. ORs are based on logistic regression models incorporating treatment group, region, baseline WHO ( 0–8) clinical status ( ≤3, ≥4), age, and sex as covariates. An OR of less than 1 means an event was less likely in the ruxolitinib group ( which favoured ruxolitinib for all except the positive outcome events assessing ≥1-point or ≥2-point improvements in WHO ( 0–8) clinical status, in which an OR > 1 favoured ruxolitinib). An HR of more than 1, representing higher instantaneous rates of discharge or recovery, favoured ruxolitinib. HR=hazard ratio. ICU=intensive care unit. NA=not analysed. NEWS2=National Early Warning Score 2. OR=odds ratio. WHO ( 0–8) =COVID-19-specific 9-point ordinal scale for clinical status proposed by WHO ( appendix p 6). * Patients who developed respiratory failure or required ICU care, or both at randomisation are excluded from the analysis.† Post hoc.‡ Patients with missing data at day 29 were treated as non-responders.§ There were no deaths in the ruxolitinib and placebo groups in patients with a baseline WHO ( 0–8) clinical status of 5.¶ Patients who did not have the event and did not die were censored at their last assessment date. Median is estimated by Kaplan-Meier method, with deaths being censored at the maximum follow-up time in the study.‖ Only summary statistics were conducted for these exploratory outcomes; all were evaluated on subsets of patients defined by post-baseline events, which could be confounded with treatment effect. Open table in a new tab
Data are n/total number of patients included in the analysis ( M [ not model based ]; [% ]), median ( 95% CI), or median ( IQR), unless otherwise specified. ORs are based on logistic regression models incorporating treatment group, region, baseline WHO ( 0–8) clinical status ( ≤3, ≥4), age, and sex as covariates. An OR of less than 1 means an event was less likely in the ruxolitinib group ( which favoured ruxolitinib for all except the positive outcome events assessing ≥1-point or ≥2-point improvements in WHO ( 0–8) clinical status, in which an OR > 1 favoured ruxolitinib). An HR of more than 1, representing higher instantaneous rates of discharge or recovery, favoured ruxolitinib. HR=hazard ratio. ICU=intensive care unit. NA=not analysed. NEWS2=National Early Warning Score 2. OR=odds ratio. WHO ( 0–8) =COVID-19-specific 9-point ordinal scale for clinical status proposed by WHO ( appendix p 6).
The subgroup analysis for the primary outcome ( figure 2) revealed that for most subgroups, the proportions of patients who met the primary endpoint were similar between ruxolitinib and placebo. The strongest interaction between subgroup and primary endpoint in ruxolitinib versus placebo was for BMI ( > 30 kg/m2 vs ≤30 kg/m2; unadjusted p=0·034). Patients with a BMI of more than 30 kg/m2 had a better response with ruxolitinib versus placebo ( OR 0·41, 95% CI 0·15–1·08); however, since the analysis was not adjusted for multiplicity, it should be interpreted with caution. Patients in North America had a better response with ruxolitinib versus placebo than patients in other regions ( OR 0·19; 95% CI 0·04–1·01); however, this was driven by a high proportion of patients meeting the primary endpoint in the small placebo subgroup ( five [ 31% ] of 16). When assessed by baseline WHO ( 0–8) clinical status ( 3, 4, and 5), findings suggested that patients with a higher clinical status score ( ie, more-severe disease) had a better response to ruxolitinib than those with a lower baseline clinical status ( status 3 OR 1·16 [ 95% CI 0·20–6·66 ]; status 4 OR 0·90 [ 0·43–1·90 ]; status 5 OR 0·28 [ 0·03–2·78 ]). However, the sample size for patients with the most severe clinical status ( score of 5) at baseline was small ( n=20). Lower ORs were observed ( which favoured ruxolitinib over placebo, with wide and overlapping CIs) in patients who were aged younger than 65 years ( OR 0·69, 95% CI 0·31–1·53); used corticosteroids at baseline ( OR 0·77, 0·33–1·80); had no hypertension at baseline ( OR 0·64, 0·25–1·66); and had more than 10 days between onset of symptoms and randomisation ( OR 0·65, 0·28–1·54). No subgroup analysis was done by remdesivir use because the proportion of patients receiving remdesivir was small ( 28 [ 6% ] of 432 with baseline use and 49 [ 12% ] of 424 with use at any time). An additional post-hoc analysis examined the effect of steroid treatment at any time during the study on the proportion of patients meeting the primary endpoint: among patients with any steroid use, 28 ( 14%) of 203 in the ruxolitinib group and 13 ( 13%) of 100 in the placebo group met the primary endpoint; among patients with no steroid use, seven ( 9%) of 82 in the ruxolitinib group and four ( 9%) of 44 in the placebo group met the primary endpoint. Note that these steroid use subgroups were defined partly by post-randomisation variables, and the subgroup memberships were influenced by treatments the patients received during the study. Thus, we can not attribute any observed effect ( or lack thereof) in this subgroup analysis to the investigational treatment since it could be due to differences in patient population.Figure 2Primary endpoint ( death, respiratory failure, or ICU care by day 29) according to subgroup analysisShow full captionICU=intensive care unit. M=total number of patients included in the analysis. CRP=C-reactive protein. FEU=fibrinogen equivalent units.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
ICU=intensive care unit. M=total number of patients included in the analysis. CRP=C-reactive protein. FEU=fibrinogen equivalent units.
The proportions of patients meeting the individual components of the primary endpoint were similar between the treatment groups ( table 2). Change in WHO ( 0–8) clinical status over time was similar across treatment groups ( appendix p 15) as were the median times to discharge and NEWS2 value of 2 or less maintained for 24 h ( table 2). The median time to recovery was numerically shorter in the ruxolitinib group versus placebo group ( 8 days [ 95% CI 8–9 ] vs 9 days [ 7–11 ]; HR 1·10, 95% CI 0·89–1·36 ]; table 2). The difference in median time to recovery between ruxolitinib and placebo groups was numerically larger in patients with higher baseline WHO ( 0–8) clinical status scores ( WHO [ 0–8 ] clinical status 3, 9 days vs 7 days; WHO [ 0–8 ] clinical status 4, 8 days vs 10 days; WHO [ 0–8 ] clinical status 5, 11 days vs 15 days; appendix p 9). Additional secondary endpoints are reported in the appendix ( p 10).
The effect of treatment on inflammatory biomarkers ( CRP, ferritin, D-dimer, procalcitonin, TNF, IFN-γ, IL-10, IL-2RA, IL-6, and IL-8) was also assessed. Over the 29 days of study, decreases were observed in the median concentrations of CRP ( 42·4 mg/L [ IQR 16·6–93·2 ] to 3·1 mg/L [ 1·3–7·2 ] with ruxolitinib vs 45·0 mg/L [ 16·7–81·6 ] to 2·6 mg/L [ 1·0–5·7 ] with placebo), ferritin ( 628 μg/L [ 301–1276 ] to 254 μg/L [ 113–513 ] with ruxolitinib and 462 μg/L [ 264·5–999·5 ] to 200 μg/L [ 91–464 ] with placebo), and D-dimer ( 0·735 mg/L FEU [ 0·400–1·335 ] to 0·540 mg/L FEU [ 0·300–1·000 ] with ruxolitinib and 0·700 mg/L FEU [ 0·440–1·260 ] to 0·520 mg/L FEU [ 0·320–1·020 ] with placebo). Concentrations of IFN-γ, IL-10, IL-2RA ( marker of T-cell activation), and IL-6 decreased ( ie, improved) over time while IL-8, procalcitonin, and TNF concentrations did not. However, no appreciable difference in biomarker levels was observed between ruxolitinib and placebo groups.
Overall, 266 ( 63%) of 424 patients had an adverse event ( appendix p 11). The most common treatment-emergent adverse events in the ruxolitinib versus placebo groups were headache ( 23 [ 8% ] of 281 vs 11 [ 8% ] of 143) and diarrhoea ( 21 [ 7% ] of 281 vs 12 [ 8% ] of 143; table 3). No meaningful differences in rates of adverse events were observed between treatment groups ( any adverse events 173 [ 62% ] of 281 with ruxolitinib vs 93 ( 65%) of 143 with placebo; and grade 3 or more adverse events, 35 ( 12%) of 281 with ruxolitinib vs 23 ( 16%) of 143 with placebo). Rates of infection and cytopenia, which were adverse events of special interest, were similar between the ruxolitinib and placebo treatment groups: infection ( excluding tuberculosis), 24 ( 9%) of 281 versus 13 ( 9%) of 143; leukopenia, seven ( 2%) of 281 versus five [ 3% ] of 143; anaemia, six ( 2%) of 281 versus one ( 1%) of 143; thrombocytopenia, three ( 1%) of 281 versus two ( 1%) of 143, respectively.Table 3Frequent treatment-emergent adverse events ( ≥2% in any treatment group) by preferred termRuxolitinib ( n=281) * Preferred terms are presented in descending order of frequency in the RUX group.Placebo ( n=143) Number of patients with ≥1 adverse event†A patient with multiple adverse events is counted only once.173 ( 62%) 93 ( 65%) Headache23 ( 8%) 11 ( 8%) Diarrhoea21 ( 7%) 12 ( 8%) Alanine aminotransferase increased17 ( 6%) 6 ( 4%) COVID-19‡COVID-19 relates to adverse events of worsening disease.12 ( 4%) 3 ( 2%) Cough12 ( 4%) 3 ( 2%) Fatigue10 ( 4%) 2 ( 1%) Constipation9 ( 3%) 7 ( 5%) Hypokalaemia8 ( 3%) 7 ( 5%) Transaminases increased7 ( 2%) 3 ( 2%) Anxiety6 ( 2%) 1 ( 1%) Asthenia6 ( 2%) 0 ( 0%) Hyperkalaemia6 ( 2%) 6 ( 4%) Nausea6 ( 2%) 11 ( 8%) Neutropenia6 ( 2%) 4 ( 3%) Pyrexia6 ( 2%) 2 ( 1%) Thrombocytosis6 ( 2%) 3 ( 2%) Aspartate aminotransferase increased5 ( 2%) 3 ( 2%) Hypoxia5 ( 2%) 5 ( 3%) Abdominal pain4 ( 1%) 4 ( 3%) Dyspnoea4 ( 1%) 3 ( 2%) Hyperglycaemia4 ( 1%) 5 ( 3%) Hypertension4 ( 1%) 3 ( 2%) Hypoproteinaemia4 ( 1%) 3 ( 2%) Leukocytosis4 ( 1%) 4 ( 3%) Insomnia3 ( 1%) 4 ( 3%) Urinary tract infection3 ( 1%) 5 ( 3%) Dizziness2 ( 1%) 4 ( 3%) Hyponatremia1 ( < 1%) 3 ( 2%) A patient with multiple adverse events within a preferred term is counted only once for that preferred term. * Preferred terms are presented in descending order of frequency in the RUX group.† A patient with multiple adverse events is counted only once.‡ COVID-19 relates to adverse events of worsening disease. Open table in a new tab
A patient with multiple adverse events within a preferred term is counted only once for that preferred term.
There were 46 ( 11%) of 424 patients who had serious adverse events ( appendix p 12), with 45 ( 11%) of 424 patients having a serious adverse event with a grade 3 or more ( 31 [ 11% ] of 281 in the ruxolitinib group, and 14 [ 10% ] of 143 in the placebo group). 12 patients died during the study ( nine [ 3% ] of 281 patients in the ruxolitinib group and three [ 2% ] of 143 patients in the placebo group); no deaths were considered related to treatment.
RUXCOVID was a randomised, phase 3 study evaluating the safety and efficacy of ruxolitinib plus standard of care compared with placebo plus standard of care in patients with COVID-19. The study did not meet its primary objective, and ruxolitinib was not associated with clinically meaningful improvements versus placebo in the secondary or exploratory endpoints. Overall, clinical status and inflammatory biomarker levels improved over time and were similar in both treatment groups. Ruxolitinib was well tolerated, and rates of treatment-emergent adverse events and serious adverse events were comparable between groups. Findings suggested that patients with more severe disease and those with a high BMI had a better response to ruxolitinib.
It should be noted that the study was designed at a very early stage of the COVID-19 pandemic. The standard of care evolved rapidly, and current knowledge might have led to differences in the timing of dosing and in the inclusion and exclusion criteria for choosing patients most likely to benefit from immunomodulatory treatment of the COVID-19 cytokine storm.
The results from our study differ from those reported in the ACTT-2 study of baricitinib ( a JAK1/JAK2 inhibitor) plus remdesivir.26Kalil AC Patterson TF Mehta AK et al.Baricitinib plus remdesivir for hospitalized adults with COVID-19.N Engl J Med. 2021; 384: 795-807Google Scholar Several possible factors could account for these differences. Ruxolitinib and baricitinib inhibit JAK1 and JAK2 with similar potency,17Stebbing J Phelan A Griffin I et al.COVID-19: combining antiviral and anti-inflammatory treatments.Lancet Infect Dis. 2020; 20: 400-402Google Scholar but potential differences in how downstream proteins such as STAT3 are impacted, especially in the presence of an antiviral drug, can not be discounted. Levels of phosphorylated STAT3—which has an immunomodulatory role—were significantly greater in various immune cell types isolated from patients with COVID-19-related pneumonia and decreased after treatment with baricitinib in ACTT-2.26Kalil AC Patterson TF Mehta AK et al.Baricitinib plus remdesivir for hospitalized adults with COVID-19.N Engl J Med. 2021; 384: 795-807Google Scholar Although ruxolitinib can also inhibit STAT3 phosphorylation,29Verstovsek S Kantarjian H Mesa RA et al.Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis.N Engl J Med. 2010; 363: 1117-1127Google Scholar this was not specifically examined in the present study and could contribute to the observed differences. Study designs were different: the RUXCOVID study had a composite primary endpoint that included mortality, respiratory failure, and ICU care, whereas ACTT-2 had a primary endpoint of time to recovery. Differences in regions might also have affected outcomes. Most patients ( 953 [ 92% ] of 1033) in the ACTT-2 study were treated in North America compared with only 11% ( 48/432) in the present study ( in which the small North American subgroup appeared to do better with ruxolitinib). The variability in clinical settings, standards of care, and outcomes ( such as variation in how patients are triaged to ICUs, with ICU care being a component of the composite endpoint) was probably higher in our study, and thus the sensitivity to detect a clinical effect of ruxolitinib might have been lower, even with the inclusion of region in the logistic regression model.
More patients had severe COVID-19 ( eg, more patients requiring high-flow oxygen or non-invasive mechanical ventilation) in ACTT-2 than in the RUXCOVID study. In the present study, median time to recovery for ruxolitinib was 11 days versus 15 days with placebo ( HR 1·51, 95% CI 0·44–5·19) in patients with more severe disease ( WHO [ 0–8 ] score 5; non-invasive ventilation or high-flow oxygen); median time to recovery was lower for patients treated with baricitinib plus remdesivir than placebo plus remdesivir in this subgroup of the ACTT-2 study ( 10 days vs 18 days; rate ratio for recovery 1·51 [ 95% CI 1·10–2·08 ]). Median time to recovery was 8 days with ruxolitinib vs 9 days with placebo in the overall study ( HR 1·10, 95% CI 0·89–1·36), similar to what was seen in the ACTT-2 study ( 7 days with baricitinib plus remdesivir vs 8 days with placebo plus remdesivir; rate ratio for recovery 1·16, 95% CI 1·01–1·32).
Findings from tocilizumab studies also suggested that patients with more severe disease are the most likely to benefit from treatment with immunomodulatory agents.30Stone JH Frigault MJ Serling-Boyd NJ et al.Efficacy of tocilizumab in patients hospitalized with COVID-19.N Engl J Med. 2020; 383: 2333-2344Google Scholar, 31Salama C Han J Yau L et al.Tocilizumab in patients hospitalized with COVID-19 pneumonia.N Engl J Med. 2021; 384: 20-30Google Scholar It is possible that patients with COVID-19 require treatment with an immunomodulatory agent in combination with antiviral medication. In ACTT-2, all patients received remdesivir in combination with baricitinib; however, in RUXCOVID, only 49 ( 12%) of 424 patients received remdesivir at any time during the study ( appendix p 8). Additionally, baricitinib has been found to prevent viral entry through inhibition of numb-associated kinases ( NAKs),32Stebbing J Sánchez Nievas G Falcone M et al.JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.Sci Adv. 2021; 7eabe4724Google Scholar which suggests that the mechanism of action in COVID-19 might be different from that of ruxolitinib, which does not substantially inhibit NAKs at tolerated doses.17Stebbing J Phelan A Griffin I et al.COVID-19: combining antiviral and anti-inflammatory treatments.Lancet Infect Dis. 2020; 20: 400-402Google Scholar
A further difference between the ACTT-2 study and RUXCOVID was the dose: the dose of ruxolitinib used in RUXCOVID ( 5 mg twice per day) was at the low end of the dosing range ( 5–25 mg twice per day), while that of baricitinib in ACTT-2 ( 4 mg per day) was at the high end of the dosing range ( 1–4 mg daily).18Jakafi ( ruxolitinib) Prescribing information. Incyte, Wilmington, DE2020Google Scholar, 26Kalil AC Patterson TF Mehta AK et al.Baricitinib plus remdesivir for hospitalized adults with COVID-19.N Engl J Med. 2021; 384: 795-807Google Scholar Ruxolitinib at a dose of 5 mg twice per day showed benefit in a phase 2 study of ruxolitinib in COVID-1924Cao Y Wei J Zou L et al.Ruxolitinib in treatment of severe coronavirus disease 2019 ( COVID-19): A multicenter, single-blind, randomized controlled trial.J Allergy Clin Immunol. 2020; 146: 137-146Google Scholar and demonstrated efficacy in graft-versus-host disease.28Jagasia M Perales MA Schroeder MA et al.Ruxolitinib for the treatment of steroid-refractory acute GVHD ( REACH1): a multicenter, open-label phase 2 trial.Blood. 2020; 135: 1739-1749Google Scholar A further motivation for using this dose for the present study was to minimise the risk of cytopenia and infection ( ultimately, these adverse events were not more prevalent in the ruxolitinib group in this study). Nevertheless, higher initial doses ( ≥10 mg twice per day) are routinely used in treating myelofibrosis and graft-versus-host disease,18Jakafi ( ruxolitinib) Prescribing information. Incyte, Wilmington, DE2020Google Scholar with a pronounced decrease in inflammatory cytokines observed.29Verstovsek S Kantarjian H Mesa RA et al.Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis.N Engl J Med. 2010; 363: 1117-1127Google Scholar
Although the design of our study was scientifically sound ( a randomised, double-blind, placebo-controlled study), some limitations and weaknesses could not have been predicted at the time of the study design. The overall therapeutic landscape and standard of care changed substantially during the study, and this change might have impacted the proportion of patients meeting the primary endpoint in the control group. Remdesivir became the standard of care in the USA, but not in all countries where our study took place. More recent studies, like ACTT-2, demonstrated the benefit of combination therapy in this setting. Therefore, although the large geographical diversity of our study was a potential strength, making more generalisable conclusions possible, it might be a limitation due to geographical variation in standard of care.
Although no other studies have used ICU care as an outcome measure, the possibility of exceeding local ICU capacities was of urgent concern at the time of the study design. However, the timing and use of ICU care varied according to medical practice among centres, which might have impacted our results both by reducing the numbers of eligible patients on high-flow oxygen, who may or may not have been in ICU care, and by introducing variation in the determination of the primary endpoint. Given the inevitable uncertainty in designing studies in a global health crisis caused by a novel disease, futility analysis or sample-size re-estimation, or both, could be considered, especially when no earlier-phase trials have been done and it is not clear whether a drug will demonstrate clinical benefit or what the treatment effect could be.
Additionally, at the inception of the study, it was not known which patient groups might benefit the most from treatment. In RUXCOVID, patients were not screened for cytokine storm, and it was assumed that this was the major mechanism of pulmonary hyperinflammation. Patients with COVID-associated hyperinflammation have since been defined as those with a CRP of more than 150 mg/L or a ferritin level of more than 1500 μg/L, or both.33Manson JJ Crooks C Naja M et al.COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study.Lancet Rheumatol. 2020; 2: e594-e602Google Scholar In RUXCOVID, fewer than one-quarter of the patients met this criterion ( based on the IQRs of CRP and ferritin). Recent studies suggest that patients with more-severe disease, including people with signs of hyperinflammation, might be the ones who benefit most from treatment with immunomodulatory agents. The DEVENT study evaluated ruxolitinib 5 mg twice per day and 15 mg twice per day versus placebo in patients with COVID-19 who required mechanical ventilation.25Langmuir P Yeleswaram S Smith P Knorr B Squier P Design of clinical trials evaluating ruxolitinib, a JAK1/JAK2 inhibitor, for treatment of COVID-19-associated cytokine storm.Del J Public Health. 2020; 6: 50-54Google Scholar The DEVENT study did not meet its primary endpoint: mortality up to day 29 in the two treatment groups versus placebo was 55% versus 74% ( OR 0·42, 95% CI 0·171–1·023; p=0·028) in the 5-mg group and 52% versus 70% ( OR 0·46, 95% CI 0·201–1·028; p=0·029) in the 15-mg group.34IncytePress Release.https: //www.businesswire.com/news/home/20210318005781/en/Incyte-Announces-Results-from-the-Phase-3-DEVENT-Study-Evaluating-Ruxolitinib-Jakafi% C2% AE-as-a-Treatment-for-Patients-with-COVID-19-Associated-Acute-Respiratory-Distress-Syndrome-ARDS-on-Mechanical-VentilationDate: March 18, 2021Date accessed: June 21, 2021Google Scholar These findings should be considered in the design of future studies. Moreover, there is a need to identify the subset of patients who would benefit the most from specific treatments, including treatment with immunomodulatory agents. Finally, because robust a priori sample-size estimates are unlikely to be possible in novel global health crises, we suggest that adaptive designs, including futility analyses and sample-size re-estimation, be built into future studies conducted under these conditions.
All authors contributed to the design of the study, or to the collection, analysis, or interpretation of study data, or to both. MKH and WC had full access to the raw data and verified it. All authors contributed to the drafting and revising of the manuscript and have approved the final version of the manuscript for publication. All authors are accountable for the content and integrity of the manuscript.
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided are anonymised to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
IG, AG, ALB, AR, JS-O, FT, RT, and SS have no competing interests. MKH reports personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, Regeneron, United Therapeutics, UpToDate, Altesa Biopharma, Medscape, and Integrity. MKH has received either in kind research support or funds paid to the institution from the National Institutes of Health, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation, and the American Lung Association. MKH has participated in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to their institution. MKH has received stock options from Meissa Vaccines and Altesa Biopharma. MA has participated in clinical studies funded by AbbVie, AstraZeneca, EMS, Eurofarma, GSK, Humanigen, Janssen, Novartis, Sanofi Genzyme, Angion Biomedica Corporation, and Beigene; has received honoraria from Aché, AstraZeneca, Chiesi, Eurofarma, IPI ASAC Brasil, and Sanofi; has received meeting or travel support from AstraZeneca, GSK, Novartis, and Sanofi Genzyme; and has participated in data safety monitor boards or advisory boards, or both, for Sanofi Genzyme, Chiesi, AstraZeneca, Abbott, and Zambom. JHF has received research funding from Novartis; grants from Boehringer Ingelheim and CSL-Behring; consulting fees from Novartis, Boehringer Ingelheim, and CSL-Behring; honoraria from AstraZeneca, Boehringer Ingelheim, CSL-Behring, GSK, MSD, and Novartis; meeting or travel support from AstraZeneca, Boehringer Ingelheim, CSL-Behring, and Novartis; and materials from CSL-Behring; and has participated in data safety monitor boards or advisory boards, or both, for Boehringer Ingelheim and AstraZeneca. LB, DSB, JMF, BK, WC, TL, and ML are employees and stockholders of Novartis. XS was an employee of Novartis during the conduct of the study. PL is an employee of Incyte.
We thank the patients and their families, investigators, and study site staff for their dedicated efforts contributing to the successful completion of this study, despite the challenges faced during the COVID-19 pandemic. This study was funded by Novartis and Incyte. The first draft of the manuscript was prepared by medical writers funded by Novartis, with guidance from the authors. The authors thank Amos Race and Karen Chinchilla ( ArticulateScience, Hamilton, NJ, USA) for providing medical writing support, which was funded by Novartis, in accordance with Good Publication Practice guidelines.
Download.pdf ( 2.83 MB) Help with pdf files Supplementary appendix
No perfect therapy for the imperfect COVID-19 cytokine stormMore than 2 years into the pandemic, almost 6 million people have died from COVID-19 worldwide. Many people who succumbed to the virus had cytokine storm syndrome, a dysregulated immune response to the pathogen.1 Progress toward treating COVID-19 has been substantial on several fronts, including rapidly developed safe and effective vaccines, and various antiviral therapies ( eg, monoclonal antibody therapies, protease inhibitors, and nucleoside analogues). Antiviral approaches are particularly effective early during infection, but cytokine targeted therapies have shown benefit during later stages of illness, when hyperinflammation is present. Full-Text PDF | tech |
Oil drops on positive signals from Russia-Ukraine peace talks | In this article
Oil prices dropped on Tuesday, extending losses from the previous day after Russia called peace talks with Ukraine constructive and China's new lockdowns to curb the spread of the coronavirus hit fuel demand.
Brent crude fell 2%, or $ 2.25, to end the day at $ 110.23 a barrel. U.S. West Texas Intermediate ( WTI) crude settled 1.62%, or $ 1.72, lower at $ 104.24 per barrel. Both benchmarks lost about 7% on Monday.
Ukrainian and Russian negotiators met in Turkey for the first face-to-face talks in nearly three weeks. The top Russian negotiator said the talks were `` constructive ''.
Ukraine proposed adopting neutral status in exchange for security guarantees at the talks, meaning it would not join military alliances or host military bases, Ukrainian negotiators said.
`` Oil prices are under pressure again on expectations about peace talks between Ukraine and Russia, which could lead to an easing of sanctions... '' said Hiroyuki Kikukawa, general manager of research at Nissan Securities.
Sanctions imposed on Russia over its invasion of Ukraine have disrupted oil supplies, driving prices higher.
Prices also came under pressure after new lockdowns in Shanghai to curb rising coronavirus cases hit fuel demand in China, the world's biggest importer.
Shanghai accounts for about 4% of China's oil consumption, ANZ Research analysts said.
Lockdowns have dampened consumption of transportation fuels in China to a point where some independent refiners are trying to resell crude purchased for delivery over the next two months, traders and analysts said.
`` China's zero-COVID policy is bringing some relief to the oil market, albeit involuntarily, which is very tight due to the supply outages from Russia, '' said Commerzbank analyst Carsten Fritsch.
Oil prices rose almost $ 2 earlier in the day as Kazakhstan's supplies continued to be disrupted and major producers showed no sign of being in a hurry to boost output significantly.
Kazakhstan is set to lose at least a fifth of its oil production for a month after storm damage to mooring points used to export crude from the Caspian Pipeline Consortium ( CPC), the energy ministry said.
The producer group OPEC+ was also expected to stick to its plan for a modest rise in May at this week's meeting, despite a surge in prices due to the Ukraine crisis and calls from the United States and other consumers for more supply.
The energy ministers of Saudi Arabia and the United Arab Emirates, key members of OPEC+, said the producers ' group should not engage in politics as pressure mounted on them to take action against Russia over its invasion of Ukraine. | business |
Peace Talks, Covid Concerns Push Oil Prices Lower | Oil futures settled lower on Tuesday but recovered most of their early-session losses as the market focused on developments in eastern Europe. | general |
Call the midwife! Giving birth during a pandemic – in pictures | As the US went into lockdown, Maggie Shannon began photographing parents and midwives as they navigated unfamiliar new Covid protocols
Mee-Lai Stone
Tue 29 Mar 2022 07.00 BST | general |
More contagious omicron BA.2 Covid subvariant dominant in the U.S., CDC says | The more contagious omicron subvariant, BA.2, is now the dominant version of Covid-19 in the U.S., according to data released by the Centers for Disease Control and Prevention this week.
The subvariant accounts for nearly 55% of Covid infection samples that have undergone genetic sequencing. Even so, the spread of a more contagious strain does not guarantee the U.S. will endure a new wave of cases.
BA.2 has doubled as a proportion of circulating variants of the virus in the U.S. about every two weeks. At the beginning of February, the omicron subvariant made up just 1% of sequenced Covid cases in the U.S.
The BA.2 subvariant spreads about 75% faster than the earlier version of omicron, BA.1, according to the latest update from the U.K. Health Security Agency. BA.2 has caused a spike in infections in the U.K. and Germany in recent weeks, though cases have started to decline again there.
China has been battling its worst outbreak since 2020, which is also driven by BA.2
Though BA.2 spreads faster, it does not make people sicker than the earlier version of omicron, according to data from South Africa and the U.K., among other countries. Omicron and its subvariants generally result in less severe illness than the delta variant. Scientists in Qatar have found that Covid vaccines are as effective against BA.2 as they were against BA.1, though omicron has caused more breakthrough infections.
White House chief medical advisor Dr. Anthony Fauci said earlier this month that BA.2 could cause an uptick in cases in the U.S. But he does not expect another surge. Fauci said the country does not yet need to reintroduce Covid restrictions in response to the subvariant.
In New England, BA.2 now makes up about 73% of all Covid cases that have undergone genetic sequencing, according to the CDC. In New York and New Jersey, BA.2 represents more than 70% of sequenced cases. Throughout the pandemic, the Northeast has often been an epicenter of new variants and a harbinger of what the rest of the nation will face.
Read CNBC's latest global coverage of the Covid pandemic:
New infections have plummeted 96% since the peak of the unprecedented wave of omicron cases in January, according to a CNBC analysis of data from Johns Hopkins University. Hospital admissions from Covid have plunged 92% from the peak of the winter spike, according to data from the CDC.
The CDC has shifted its focus to hospitalizations, an indicator of how much severe illness the virus is causing, when issuing public health guidance on Covid. Earlier this month, the CDC said 98% of the U.S. population lives in areas where they can go without face masks.
Ali Mokdad, a leading epidemiologist at the Institute for Health Metrics and Evaluation at the University of Washington, said Covid cases will continue to decline through the spring and summer due to built up immunity from vaccines and the winter omicron wave. Mokdad said another surge is possible in the winter as protection from the vaccines wanes.
However, Michael Osterholm — a top epidemiologist at the Center for Infectious Disease Research and Policy at the University of Minnesota — said it is unclear how BA.2 will affect the U.S. It is difficult to predict what the variant's spread in one country means for another nation, because previous strains have affected parts of the world differently, he added.
Osterholm said the U.S. has had high levels of immunity before, only to see a major surge. In December, about 95% of the U.S. population ages 16 and older had antibodies against the virus either through vaccination or infection, according to a CDC survey of blood donor samples.
However, omicron still managed to cause the most infections of the entire pandemic weeks later. | business |
BA.2 is now the dominant covid-19 sub-variant in the US — Quartz | The omicron sub-variant BA.2 accounted for most new coronavirus infections in the US last week, according to new data from the Centers for Disease Control and Prevention ( CDC). In the week ending March 26, BA.2 accounted for nearly 55% of new cases, while the previously dominant strain BA.1.1 accounted for 40.4% of cases.
While covid-19 cases in the US have been declining since hitting an all-time high due in January, a surge of BA.2 cases in Europe and Asia has put US health officials on alert even as most states have dropped restrictions. Meanwhile, the Food and Drug Administration ( FDA) approved an additional covid-19 booster shot today ( March 29) for older and immunocompromised people in the US.
BA.2 has been around since the omicron variant first emerged last fall, but it didn’ t account for a meaningful proportion of US covid-19 cases until early this year. Between the week ending Jan. 29 and Feb. 26 the proportion of BA.2 covid cases grew nearly 10-fold, and has gradually eclipsed BA.1 cases over the past month.
The now-dominant sub-variant is believed to be more transmissible than previous variants of the virus, in part because its spike protein has several mutations that are not present in other omicron strains.
But so far BA.2 doesn’ t appear to cause more severe illness than the previously dominant omicron strain, and US-approved vaccines should provide sufficient protection against severe disease. People who were previously infected with BA.1 should also have good immunity against BA.2, according to Joshua Sharfstein, a professor at the Johns Hopkins Bloomberg School of Public Health.
While other parts of the world are locking down in response to surging BA.2 cases, the US is largely open, with few pandemic restrictions still in place.
Today the FDA approved a second booster dose of the Pfizer and Moderna vaccines for anyone over 50 years old, as well as some immunocompromised patients. While the US hasn’ t yet recommended a fourth covid-19 vaccine for all Americans, an FDA official said last month this would likely happen in the fall.
Even as the US continues to document thousands of coronavirus cases each week, the money to pay for covid testing, treatment, and vaccines may soon run out due to an impasse in Washington. The White House recently asked Congress for an additional $ 22.5 billion to support domestic and global covid-19 efforts, but the funding was stripped from a final government spending bill. | tech |
March U.S. auto sales: Toyota, GM, Nissan, Hyundai, Kia slip | U.S. sales fell again at Toyota Motor Corp., Ford Motor Co., Honda Motor Co., Hyundai, Kia and Subaru last month as tight inventories caused by supply-chain bottlenecks continue to undermine the auto industry's recovery from the pandemic.
Lean new-vehicle inventories, along with rising inflation and gasoline prices that have clouded the economic outlook, resulted in sharply lower March and first-quarter U.S. car and light-truck sales across the industry.
LMC Automotive said the market dropped 22 percent to 1.25 million cars and light trucks in March, with retail sales at just under 1.1 million.
The seasonally adjusted, annualized rate of sales came in at 13.4 million for March, Motor Intelligence and LMC said, the slowest pace of the quarter, and down from 17.8 million in March 2021, which kicked off the industry's hottest three-month stretch on record.
March is typically one of the strongest months of the year, a bellwether of the spring selling season and fueled by heavy promotions. But last month was the fifth-weakest March for volume since 2000, LMC said.
LMC noted one positive development with March: the daily selling rate increased to 46,400 units a day, the highest average in the last seven months, on slightly improved inventories.
First-quarter U.S. sales fell 16 percent to 3.29 million, LMC Automotive said. It was the second-worst quarter for volume in a decade, behind only 2020's second quarter, at the height of the COVID-19 pandemic, Cox Automotive said.
Toyota Motor, with one of the industry's leanest new-vehicle stockpiles, said first-quarter sales skidded 15 percent to 514,592. It was still enough to edge past General Motors by 5,484 deliveries, which reported first-quarter volume slid 20 percent to 509,108.
GM's four brands all posted declines in the latest quarter: 20 percent at Chevrolet, 7.5 percent at GMC, 58 percent at Buick and 24 percent at Cadillac.
Toyota overtook GM as the bestselling U.S. automaker in 2021. GM sales have now dropped three straight quarters.
Toyota said March deliveries slid 24 percent behind declines of 23 percent at the Toyota division and 29 percent at Lexus. It was the eighth consecutive monthly decline at the Toyota brand and second straight dip at Lexus.
Ford Motor deliveries slid 26 percent, with the Ford division down 26 percent and Lincoln off 25 percent. The automaker's pickup sales skidded 34 percent behind a 47 percent drop in F series volume. The new Maverick compact pickup, one of the company's fastest-churning models, helped buoy Ford's truck sales with 8,695 deliveries in March.
Ford said it ended March with 268,00 light vehicles in inventory, up from 199,000 at the end of February but down from 370,000 at the close of March 2021.
Stellantis sold 405,221 vehicles in the first quarter. Overall, total U.S. and retail sales during the period declined 14 percent and 13 percent, respectively, the company said. Volume dropped 2 percent at Jeep and 15 percent at Ram.
Honda Motor Co. sales skidded for the eighth consecutive month, with March deliveries down 27 percent at the Honda brand and 26 percent at Acura. Company officials cited unprecedented low levels of new-vehicle inventory for the latest results.
`` We’ re riding a bit of a roller coaster due to fluctuating parts supply issues, '' said Dave Gardner, executive vice president at American Honda. “ We aren’ t out of the woods yet, but we will continue to manage the supply issues to maximize production and help our dealers meet the needs of our customers. ”
First-quarter volume at Nissan plunged 30 percent compared to last year, with the Nissan division falling 29 percent and Infiniti down 41 percent. | general |
Murphy Oil Corporation Schedules First Quarter 2022 Earnings Release and Conference Call | Murphy Oil Corporation ( NYSE: MUR) will host a conference call and webcast beginning at 9:00 a.m. Eastern Daylight Time ( EDT) on Wednesday, May 4, 2022 to discuss first quarter 2022 earnings. The company plans to release its financial and operating results before the market opens that morning.
A webcast link and related presentation material will be included on the Investors page of the company’ s website at http: //ir.murphyoilcorp.com.
Date: Wednesday, May 4, 2022 Time: 9:00 a.m. EDT Toll Free Dial-in: 888-886-7786 Conference ID: 86484903
ABOUT MURPHY OIL CORPORATION As an independent oil and natural gas exploration and production company, Murphy Oil Corporation believes in providing energy that empowers people by doing right always, staying with it and thinking beyond possible. Murphy challenges the norm, taps into its strong legacy and uses its foresight and financial discipline to deliver inspired energy solutions. Murphy sees a future where it is an industry leader who is positively impacting lives for the next 100 years and beyond. Additional information can be found on the company’ s website at www.murphyoilcorp.com.
FORWARD-LOOKING STATEMENTS This news release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are generally identified through the inclusion of words such as “ aim ”, “ anticipate ”, “ believe ”, “ drive ”, “ estimate ”, “ expect ”, “ expressed confidence ”, “ forecast ”, “ future ”, “ goal ”, “ guidance ”, “ intend ”, “ may ”, “ objective ”, “ outlook ”, “ plan ”, “ position ”, “ potential ”, “ project ”, “ seek ”, “ should ”, “ strategy ”, “ target ”, “ will ” or variations of such words and other similar expressions. These statements, which express management’ s current views concerning future events or results, are subject to inherent risks and uncertainties. Factors that could cause one or more of these future events or results not to occur as implied by any forward-looking statement include, but are not limited to: macro conditions in the oil and natural gas industry, including supply/demand levels, actions taken by major oil exporters and the resulting impacts on commodity prices; increased volatility or deterioration in the success rate of our exploration programs or in our ability to maintain production rates and replace reserves; reduced customer demand for our products due to environmental, regulatory, technological or other reasons; adverse foreign exchange movements; political and regulatory instability in the markets where we do business; the impact on our operations or market of health pandemics such as COVID-19 and related government responses; other natural hazards impacting our operations or markets; any other deterioration in our business, markets or prospects; any failure to obtain necessary regulatory approvals; any inability to service or refinance our outstanding debt or to access debt markets at acceptable prices; or adverse developments in the US or global capital markets, credit markets or economies in general. For further discussion of factors that could cause one or more of these future events or results not to occur as implied by any forward-looking statement, see “ Risk Factors ” in our most recent Annual Report on Form 10-K filed with the US Securities and Exchange Commission ( “ SEC ”) and any subsequent Quarterly Report on Form 10-Q or Current Report on Form 8-K that we file, available from the SEC’ s website and from Murphy Oil Corporation’ s website at http: //ir.murphyoilcorp.com. Murphy Oil Corporation undertakes no duty to publicly update or revise any forward-looking statements.
Investor Contacts: Kelly Whitley, kelly whitley @ murphyoilcorp.com, 281-675-9107 Megan Larson, megan larson @ murphyoilcorp.com, 281-675-9470
View source version on businesswire.com: https: //www.businesswire.com/news/home/20220329005831/en/
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To further protect the integrity of our editorial content, we keep a strict separation between our sales teams and authors to remove any pressure or influence on our analyses and research.
Read our editorial policy to learn more about our process. | business |
( OFFICIAL) -UPDATE 3-Auto manufacturers scramble as Shanghai locks down | ( Corrects Thyssenkrupp statement in fourth paragraph after company clarifies that the facility assembles production lines for powertrains and other products rather than producing powertrains)
SHANGHAI, March 29 ( Reuters) - Shanghai's COVID-19 lockdown roiled auto production on Tuesday as two major suppliers joined Tesla in shutting plants to comply with measures to control the spread of the coronavirus.
General Motors Co's joint venture in Shanghai maintained production by asking workers to sleep on factory floors and getting passes for trucks to continue deliveries, two people familiar with the matter said.
A key auto supplier, Aptiv PLC, told workers at one of its Shanghai facilities that supplies Tesla and GM's Shanghai joint venture to head home on Tuesday because of the need to enforce COVID controls, people briefed on the measure said.
Thyssenkrupp said it had closed a facility in Shanghai where it assembles production lines for automotive components, including powertrains and batteries, until April 6 to comply with local coronavirus regulations.
The Aptiv and Thyssenkrupp closures came on the second day of a lockdown in Shanghai, home to 26 million people and a major hub for manufacturing of vehicles and other goods. The city has instituted tough controls on movements of people to try to control the spread of the highly infectious Omicron variant.
The lockdown, one of the biggest tests for China's '' zero-COVID '' strategy, has forced automakers and suppliers to either try to adapt with extreme measures to keep factories running or to shut down and risk delayed shipments at a time when demand for vehicles is strong.
German auto supplier Bosch on Tuesday said its two plants in Shanghai are working with reduced personnel. `` We are doing everything we can to maintain the supply chains as much as possible and to serve the demands of our customers, '' the company said in a statement.
For global automakers and suppliers, the latest coronavirus-related disruptions in China, the world's largest market, are piling on top of problems created by the war in Ukraine.
The measures GM took to keep its Shanghai plant open equate to a `` closed-loop '' management process, which China's financial hub has asked companies to adopt to stay open during a two-stage lockdown to battle its outbreak.
In the bubble-like arrangement, workers sleep, live and work in isolation from the rest of the world to prevent virus transmission. A similar system was used at the Winter Olympics in Beijing to seal event personnel off from the public.
The facilities, which GM runs as part of a joint venture with Chinese state-owned automaker SAIC Motor Corp, produce Buick, Chevrolet and Cadillac vehicles. The facilities are in areas east of Shanghai's Huangpu River that have been locked down from Monday to Friday.
CONTINGENCY PLANS
GM, which said on Monday that its Shanghai joint venture was producing normally, declined to comment on the arrangements at its factory. A spokesperson said the company and its joint ventures had developed and were executing contingency plans with their suppliers to mitigate uncertainty related to COVID-19. SAIC did not have immediate comment.
SAIC-GM's ability to keep its Shanghai production lines running contrasts with that of Tesla Inc, which Reuters reported has suspended production for the four-day period. It was unable to secure sufficient provisions for its workers to achieve closed-loop management, one source said.
The workers at the affected Aptiv site were told to stay home on Wednesday and await further notice, the four sources told Reuters. Two of the sources said the affected compound produces for Tesla and GM's Shanghai joint venture with SAIC.
Aptiv's Shanghai facilities are in the west of the city and had not been affected by the city's lockdown, which started in eastern districts. The sources said the workers at the affected facility had been told that it had to shut due to COVID-19 issues.
Aptiv declined to comment on the production suspension. `` I can confirm that we are following all government orders and not impacting customers ' production, '' an Aptiv spokesperson said. Tesla, GM and SAIC did not have immediate comment.
TCL Corp and Apple suppliers Foxconn and Shenzhen Deren Electronic Co Ltd managed to keep production going in southern China this month with closed-loop management after manufacturing hubs such as Shenzhen and Dongguan were hit by similar lockdown measures. ( Reporting by Zhang Yan and Norihiko Shirouzu; Additional reporting by Christoph Steitz and Ilona Wissenbach in Frankfurt, writing by Brenda Goh; editing by Paul Simao, Jonathan Oatis and Sam Holmes) | business |
Less than half of countries are implementing learning recovery strategies at scale to help children catch up | NEW YORK/PARIS/WASHINGTON D.C., 30 March 2022 - “ More than two years into the COVID-19 pandemic, we are witnessing a colossal loss to children’ s learning. Less than half of countries are implementing learning recovery strategies at scale to help children catch up. Unless all countries implement and expand programmes in the coming months, they risk losing a generation.
“ With a combined 2 trillion hours of in-person schooling lost due to school closures since March 2020, students in more than 4 in 5 countries have fallen behind in their learning. Less well-off children have seen their learning falling back. In particular, the most marginalised – those living in poverty and rural areas, children with disabilities, and the youngest students – have fallen the furthest behind.
“ Basic, foundational skills upon which every aspect of education is built have been erased in many countries. Children have forgotten how to read and write; some are unable to recognise letters. Children who were poised to start school for the first time never got the chance to learn these skills in the first place, as early childhood education disappeared in most countries. Without urgent remedial action, this could carry serious lifelong consequences in terms of health and well-being, future learning and employment.
“ And yet, our March 2022 data show that less than half of countries featured in a new analysis published today are implementing learning recovery strategies at scale to help children catch up on what they’ ve missed. Only half of low-income countries have a plan in place to assess where those who have returned are at in their learning.
“ While we have seen pockets of data that point to a staggering number of children not returning to school once their classrooms reopened, some countries are not collecting or not able to collect information on how many children have or have not returned to school, so we are flying blind. A quarter of low-income countries – already with high out-of-school populations – do not have the data to show how many students have returned to school.
“ The alarm was sounded many times. Six months into the pandemic, with a lack of access to remote learning, we already knew that at least a third of schoolchildren globally were completely cut off from their education. We knew that some 24 million children and youth were at risk of dropping out altogether. We knew child labour and child marriage would rise. And yet, not enough is being done to help children recover what they’ ve lost.
“ At a time when it’ s needed the most, education funding has and continues to fall desperately short. Countries allocated on average 3 per cent of their COVID-19 stimulus packages to education. In low- and lower-middle-income countries, the allocation was less than 1 per cent.
“ While countries scramble to recover, they are overlooking the single, most-effective long-term recovery and sustainability tool – education.
“ Governments must double down efforts get every child into school. Education is a fundamental human right. The multiple and intersecting barriers – including poverty, cultural norms, and poor quality teaching – preventing children from accessing their education must be broken down. Every child needs to be assessed on their learning and based on the results, they must have access to quality, tailored, catch-up classes to recover what they’ ve lost and beyond. Teaching should be adjusted to the level they currently are at in their learning. Teachers must be given the training, support and resources they need. And finally, schools must go beyond places of learning and support children’ s well-being and safety.
“ This is a now-or-never moment to act and transform education in order to save this generation. ”
A joint report issued today by UNESCO, UNICEF and the World Bank highlights staggering levels of learning loss globally and takes stock of the measures being taken by countries to mitigate learning losses as schools reopen. The Where are we on education recovery? report is based on a survey of 122 UNICEF country and fundraising offices administered in early March 2022. The data presented in this statement is noted in the new report which presents the importance of and progress made in five key actions for education recovery:
UNICEF works in some of the world’ s toughest places, to reach the world’ s most disadvantaged children. Across more than 190 countries and territories, we work for every child, everywhere, to build a better world for everyone.
`` We must take the rapid action needed to accelerate vaccination. '' | general |
Home prices rose 19.2% in January from last year | Prices rose 19.2% in January from the year before, up from an 18.9% annual increase in December, according to the S & P CoreLogic Case-Shiller US National Home Price Index.
Phoenix, Tampa and Miami reported the highest annual gains among the 20 cities in the index in January. Phoenix led the way for the 32nd consecutive month with prices 32.6% higher than the year before. It was followed by Tampa with a 30.8% increase, and Miami with a 28.1% gain.
Sixteen of the 20 cities saw higher year-over-year price increases in January than in December. Price growth was strongest in the South, but every region continued to see gains.
`` Home price changes in January 2022 continued the strength we had observed for much of the prior year, '' said Craig J. Lazzara, managing director at S & P Dow Jones Indices.
Last fall, price increases began to slow. But that trend reversed in January, with the year-over-year jump in prices being the fourth largest in the 35 years of data.
`` The macroeconomic environment is evolving rapidly. Declining Covid cases and a resumption of general economic activity has stoked inflation, and the Federal Reserve has begun to increase interest rates in response, '' said Lazzara. `` We may soon begin to see the impact of increasing mortgage rates on home prices. ''
Choppier waters ahead
The numbers showed a strong start to the 2022 housing market, as buyers rushed to snag a home before mortgage rates climbed too high, but many factors have changed since January, said George Ratiu, senior economist and manager of economic research at Realtor.com.
`` The world has changed considerably since the start of the year, with a host of events shuffling the economic and real estate landscape, '' Ratiu said. `` Globally, Russia's invasion in Ukraine destroyed human lives, along with a long stretch of relative stability in Europe. The continuing war is impacting global trade and leading to renewed disruptions in supply chains. ''
In the US, inflation surged to levels not seen since the 1980s, prompting the Federal Reserve to increase the federal funds rate and signal much more aggressive monetary tightening in the coming months, he said.
These factors seem to indicate a significant shift for the real estate market, Ratiu added.
`` While buyers remain interested and willing to purchase homes, mortgage rates are already moving toward 5% and starting to cap their ability to qualify for a loan, '' he said.
The monthly payment for a median-priced home has jumped 30% in the past year, far outpacing even fast-rising consumer prices, which are up almost 8% from a year ago, he said.
Other indicators show that both sales of new and existing homes in February were slower as inventory remains near record lows and costs to own a home continue to rise.
Even as the small number of homes for sale will continue to push prices higher throughout the spring buying season, Ratiu said, he expects real estate conditions to adjust in the months ahead.
`` For sellers, April offers the ideal combination of higher prices and still-limited competition from other homeowners that typically ensure a successful close, '' he said. `` For buyers, local market conditions and personal circumstances will determine if there's more value in securing a fixed mortgage rate now versus holding out for more inventory and better prices later in the year. '' | business |
Health Systems Strengthening Accelerator | Sign up for our monthly newsletter R4D Insights to get the latest tools, resources, and news in global development.
COVID-19 update: Due to its flexible nature, pre-existing infrastructure and remote facilitation approaches, the Accelerator can provide COVID19 support in a range of areas. In Ghana, the Accelerator is providing critical support to the Office of the Presidential Coordinator on COVID-19. This includes advising on staffing structure and facilitating an advisory group tasked with monitoring the socioeconomic impact of the outbreak. It also involves identifying helpful evidence, ideas and experts from around the world — including leaders from Singapore and South Korea — which we help to contextualize get into practice in Ghana. Health officials who are interested in learning more should reach out to their local USAID missions.
Over the past few decades, countries and development partners have greatly improved the health and well-being of people in many places across the globe. This progress has been possible in part because of successful investments that have enhanced countries’ health systems performance. | general |
Asian markets rise as oil prices sink further | BANGKOK — Asian shares were higher Tuesday after an advance on Wall Street ahead of another round of peace talks between Russia and Ukraine.
Crude oil prices fell further after sinking 7% on Monday.
Trading has remained choppy as investors try to gauge what’ s next for inflation and the global economy as the repercussions of Russia’ s invasion of Ukraine continue to play out.
Ukrainian forces claimed to have retaken a Kyiv suburb and an eastern town from the Russians in what is becoming a back-and-forth stalemate on the ground, while negotiators began assembling in Turkey for
another round of talks Tuesday
aimed at stopping the fighting.
Ukrainian President Volodymyr Zelenskyy said his country could declare neutrality to secure peace, but would prioritize protecting its sovereignty and territory.
Tokyo’ s Nikkei 225
NIK,
-1.69%
rose 0.6% and the Kospi
180721,
-1.43%
in Seoul added 0.2%. The Hang Seng
HSI,
-0.96%
in Hong Kong picked up 0.5%, while the Shanghai Composite index
SHCOMP,
-1.17%
lost 0.4% as the city entered a second day of a lockdown to combat a COVID-19 outbreak. Stocks fell in Singapore
STI,
-0.38%
,
Taiwan
Y9999,
-1.96%
and Indonesia
JAKIDX,
+0.29%
.
Australia’ s S & P/ASX 200
XJO,
-0.63%
surged 0.9%. Its government plans to increase spending on national security while reducing costs for households, in part by reducing a tax on gasoline, Treasurer Josh Frydenberg said before presenting a
budget proposal
Tuesday.
Weaker oil prices helped push shares higher, said Yeap Jun Rong of IG.
“ China, Japan, South Korea and Taiwan are major oil importers, hence lower oil prices may be deemed as positive for their economies, ” Yeap said in a commentary.
U.S. crude oil
CLK22,
+1.30%
lost 71 cents to $ 105.21 a barrel in electronic trading on the New York Mercantile Exchange. On Monday, it slumped 7% and Brent crude, the international standard, fell 6.8%.
Brent crude
BRNK22
shed 84 cents to 108.65 per barrel in London.
The latest retreat in oil prices followed the news of China’ s most extensive coronavirus lockdown in two years to control a
growing outbreak in Shanghai
. That could put a dent in global demand for energy.
Oil prices remain volatile amid the backdrop of
Russia’ s invasion of Ukraine
. The United Arab Emirates’ energy minister doubled down Monday on an
oil alliance with Russia
, saying that nation, with its 10 million barrels of oil a day, is an important member of the global OPEC+ energy alliance.
Oil prices are up about 40% globally over concerns about tighter supplies as demand remains strong. Higher oil prices are also raising concerns that already persistently high inflation could be worsened, further threatening global economic growth.
On Wall Street, the S & P 500
SPX,
-0.97%
rose 0.7% to 4,575.52. The Dow Jones Industrial Average
DJIA,
-0.42%
eked out a 0.3% gain, closing at 34,995.89. The tech-heavy Nasdaq composite
COMP,
-2.22%
closed 1.3% higher, at 14,354.90.
Bond yields eased back after shooting higher this month. The yield on the 10-year Treasury fell to 2.46% from 2.49% late Friday. Bond yields have been rising as Wall Street prepares for higher interest rates. The Federal Reserve has already announced a 0.25% hike of its key benchmark interest rate and is prepared to continue raising rates to help temper the impacts of rising inflation.
Investors will get more updates this week on just how much inflation is hurting consumers and businesses. The Conference Board will release its consumer confidence index for March on Tuesday. The Commerce Department will release its February report for personal income and spending on Thursday and the Labor Department will release its employment report for March on Friday.
In currency trading, the dollar
USDJPY,
-0.04%
slipped to 123.48 Japanese yen from 123.77 yen. | business |
Opinion: Why gold and platinum are a window into the stock market's future and what investors can expect | The stock market’ s prospects for the next 12 months are only modestly positive.
That’ s the conclusion of a market-timing model based on the ratio of gold’ s price
GC00,
+0.65%
to platinum’ s
PL00,
+1.83%
.
You might think it’ s good news that equities’ 12-month potential is as promising now as it was in early 2021. But, in fact, most stocks have struggled since then. A relatively small number of large-cap stocks have propelled the S & P 500
SPX,
-0.27%
higher, and the Russell 2000 index
RUT,
-0.76%
is 9.2% lower than where it stood when
my early-2021 column on this gold-platinum ratio was published.
The Nasdaq Composite Index
COMP,
-1.34%
is just 1.8% higher while the Russell Micro-Cap Index is 14.7% lower. ( Data, courtesy of FactSet, are through Mar. 28.)
The discovery of the gold-platinum ratio’ s market-timing potential traces to a
2019 study in the Journal of Financial Economics
. It showed that a rising gold-platinum ratio forecasts higher stock market returns over the subsequent 12 months, and vice versa. Entitled “ Gold, Platinum and Expected Stock Returns, ” its authors are Darien Huang, a former finance professor at Cornell University, and Mete Kilic, a finance professor at the University of Southern California.
The chart below plots this gold-platinum ratio over the last 20 years. Notice that the ratio declined for many years prior to and including the 2008 financial crisis, correctly predicting less upside potential for the stock market. Since 2008, in contrast, the ratio has for the most part steadily risen — as has the stock market.
During the COVID pandemic of the past two years the ratio has been highly volatile: It spiked in the wake of the market’ s waterfall decline in March 2020, anticipating the market’ s huge potential over the subsequent 12 months. Since then it fell, rose again, and over the past couple of months has fallen back.
The ratio works, according to the professors, because platinum and gold respond to different factors. While platinum primarily reflects changes in industrial demand, gold responds both to that demand as well as investors’ desire to hedge against economic and geopolitical uncertainty. By focusing on the ratio of gold’ s price to platinum’ s, you zero in on that portion of gold’ s price that is a hedge against uncertainty. Since the stock market’ s expected return is compensation for uncertainty and risk, this ratio should be particularly valuable to market timers.
That’ s exactly what the professors found. Since 1975, the gold-platinum ratio has had a significantly better track record predicting the market’ s subsequent 12-month return than nine other well-known indicators that other researchers previously found to have predictive ability — including, prominently, the Cyclically-Adjusted PE Ratio, or CAPE, made famous by Yale University ( and Nobel laureate) Robert Shiller.
The ‘ war puzzle
‘
You might find it surprising that the gold-platinum ratio has fallen in recent months, which suggests that risk has declined. Yet in February Russia invaded Ukraine and, according to some, the conflict could lead to World War III. That certainly seems like the very definition of heightened risk.
In fact, however, the gold-platinum ratio’ s decline in the wake of Russia’ s invasion of Ukraine is not that unexpected. In academic circles it’ s been known for some time that the stock market tends to experience below-average volatility during wars and military conflicts — a pattern known as the “ war puzzle. ” According to a study that the National Bureau of Economic Research began circulating a couple of weeks ago, stock market volatility has been “ 33 percent lower during major wars and periods of conflict since 1921. ”
The study, “
Stock Volatility and the War Puzzle
, ” was conducted by Gustavo Cortes, a finance professor at the University of Florida; Angela Vossmeyer, an economics professor at Claremont McKenna College, and Marc Weidenmier, a research associate at Chapman College. They at least partially solved the puzzle, finding that increased defense spending during wars and military conflicts leads corporate profits to become more predictable. That in turn translates to lower stock market volatility and risk.
Regardless of whether this solves the “ war puzzle, ” the message of the gold-platinum based indicator with a good market-timing record is that the stock market’ s potential over the next 12 months is only moderately positive.
Mark Hulbert is a regular contributor to MarketWatch. His Hulbert Ratings tracks investment newsletters that pay a flat fee to be audited. He can be reached at
mark @ hulbertratings.com
Also read:
A key part of the Treasury yield curve has finally inverted, setting off recession warning — here’ s what investors need to know
More:
These 10 dividend stocks with yields of at least 5% can help you take on stagflation or a recession | business |
Student loan debt is testing borrowers. Here are some expert tips to make the grade. | For decades, financial advisers took a straightforward approach to helping clients manage their student loan debt. Sticking to a repayment schedule with a mix of careful planning and disciplined saving set young professionals on the right track.
Today, all bets are off. Since March 2020, borrowers have benefited from a pause for federal student loan payments. The CARES Act didn’ t just suspend repayments; it also ended collections efforts on many defaulted federal student loans and temporarily set interest rates on most of these loans to zero.
Initially set for six months, the relief keeps getting extended as the pandemic drags on. It’ s supposed to expire on May 1, 2022, but it’ s quite possible that President Joe Biden will extend it.
“ There’ s so much uncertainty, ” said Jay Karamourtopoulos, a Boston-based certified financial planner. “ Some people don’ t want to pay if they don’ t have to. They’ re convinced there will be some kind of reduction in their student loan or their debt will be cancelled. Others want to pay it down in any case, ” regardless of the government’ s continued actions.
For advisers, the challenge is strategizing with borrowers when facing an unpredictable future. The government might cancel some types of student loan debt entirely. Some politicians favor modifying the student loan system and introducing a new, income-driven repayment plan while lifting certain people out of default.
Whatever happens next, advisers are focusing on what clients are able to control. They urge borrowers, especially young professionals who have recently moved, to confirm that their loan servicer has their correct contact information.
Depending on the client’ s preferred response to managing their student loan, Karamourtopoulos might model a few repayment-plan options. He will review the pros and cons of each option and let the client pick how to proceed.
All the swirling unknowns put advisers in a position of predicting outcomes that can vary widely. “ I’ ve seen student loan forgiveness proposals at $ 10,000 or maybe $ 50,000, ” said L.J. Jones, an adviser in Pacifica, Calif. “ Even with the higher number, borrowers will still owe a lot of money. They can have $ 150,000 in total student loan debt. ”
Young attorneys, physicians and other professionals are sometimes saddled with debt from both their undergrad and graduate school tuition. As much as they hope for a new loan system that provides permanent relief, they can not count on it.
“ They’ re left with a feeling of restriction and inflexibility, ” Jones said. “ They feel they can’ t leave their firm because of the loans they face. It can be a really substantial financial burden. ”
He cites the example of attorneys earning $ 200,000 a year at a law firm. With rising housing costs ( whether renting or buying) along with owning a car and covering other inflation-driven expenses, keeping up with loan payments can sting.
“ There’ s a tension to make those payments and have the lifestyle you want to have, ” he said. “ Once the Covid freeze ends and any grace period ends, ” it’ s hard to know the long-term repercussions for borrowers.
For clients with a high income and high credit scores, Jones might explore privately
refinancing their student loans
. The downside: withdrawing from the federal student loan program can mean losing future opportunities for relief and loan forgiveness.
To play both sides, Jones might suggest maintaining $ 10,000 in the federal loan system while refinancing the remaining debt privately. But this depends on many variables and a client’ s attitude about managing debt.
“ It’ s a lot of complexity, ” he said. “ There are so many types of repayment programs, including income-driven plans. A big factor is how much other debt they have, ” such as a home mortgage or car loan.
Another consideration is the volume of loans that an individual can amass — and keeping them organized. Some people can have more than a dozen separate loans, representing every semester of schooling. Each one might have its own provisions and quirks, with some subsidized by the government while others are not. “ The sheer number of loans can be overwhelming, ” Jones said.
Administrative hassles alone can pose problems. For example, borrowers who were making automatic payments on their federal student loans from a checking account may need to set up auto-debit again with their bank whenever the suspension period ends.
Of course, there’ s only so much advisers can do if clients lack the ability to repay loans. Even if the government announces a more affordable, income-driven program, it’ s unlikely to address many borrowers’ worries about resuming at least some repayment.
That’ s why advisers tend to focus on clients’ cash flow and their saving and spending habits. Struggling under too much debt that’ s hard to repay or renegotiate can lead to personal bankruptcy. And even bankruptcy may not free borrowers from their obligations.
More:
Did you benefit from student-loan debt relief? Know the tax consequences.
Also read:
If you’ re anxious about markets and investing, make sure your financial adviser gets it | business |
U.S. average daily deaths from COVID fall below 800 to lowest level since mid-August, and FDA allows second booster shot for people 50 and older | The average number of daily deaths from COVID-19 in the U.S. has fallen below 800 for the first time since the highly transmissible omicron variant was first detected in the autumn, and is now trending at the lowest rate since mid-August,
according to a New York Times tracker
.
The seven-day average of new cases now stands at 29,157, down 11% from two weeks ago and at the lowest level since last July. Hospitalizations are down 35% at an average of 17,856 a day, while the number of patients in ICUs has fallen 42% to 2,857.
Tempering that good news, however, is the fact that new cases are climbing in 15 states, as well as in Puerto Rico and American Samoa, driven by the BA.2 omicron subvariant, which is even more contagious than the original omicron variant but seems no more lethal.
Northeastern states are being hardest hit, with cases up 78% in New York, up 77% in Connecticut, up 40% in Massachusetts and up 12% in New Jersey. Other hot spots include Colorado, where cases are up 35% from two weeks ago, and Texas, where they are up 14%.
Experts have said the U.S. is likely facing another wave of cases, following the recent one in Europe, which the U.S. has lagged by a few weeks all through the pandemic.
The White House is planning a virtual event later Tuesday that will focus on improving indoor air quality, as a means to reduce COVID transmission,
according to a statement.
Air quality was a key part of the administration of President Joe Biden’ s
American Pandemic Preparedness Plan
released last September.
The Environmental Protection Agency launched a Clear Air in Buildings Challenge in March and has released a guide aimed at helping a wide range of parties, from homeowners to landlords and business owners, enact measures to improve air quality.
The guide recommends such simple moves as propping open doors and windows, to upgrading ventilation systems with improved filters and portable cleaners. It comes at a time when states and localities have dropped face-mask mandates and encouraged Americans to treat the virus as in an endemic phase, meaning it is still present but no longer likely to create waves that will overwhelm healthcare systems.
But not everyone agrees that the country has reached that phase yet, even though the government is running out of funds for testing, vaccines and boosters, and treatments.
Other COVID-19 news you should know about:
• The U.S. Food and Drug Administration has expanded the emergency-use authorization for companies including Pfizer
PFE,
+0.02%
,
BioNTech
BNTX,
+0.68%
and Moderna
MRNA,
+1.16%
for an additional vaccine booster dose in individuals age 50 and over. The agency has also greenlighted a second booster for people above the age of 12 who are immunocompromised but have had a first booster of any of the authorized vaccines. The second dose is to be given at least four months after the first one.
• British police are fining 20 people over parties held by Prime Minister Boris Johnson and his staff during coronavirus lockdowns, and said that more people could face penalties,
the Associated Press reported.
The Metropolitan Police force said it wouldn’ t identify recipients of the fixed-penalty notices, though Johnson’ s office has said it would reveal it if he gets one. Opponents, and some members of the governing Conservative Party, have said Johnson should resign if he is issued a fine for breaking rules he imposed on the rest of the country during the pandemic.
• A two-phase lockdown of Shanghai’ s 26 million people is testing the limits of China’ s hardline “ zero-COVID ” strategy and is shaking markets far beyond the country’ s borders,
the AP reported separately.
China’ s largest city on Tuesday entered the second day of the lockdown’ s first phase, which includes the Pudong financial district and adjacent areas. The measures confining Pudong residents to their homes, closing nonessential businesses and requiring mass testing are to be lifted Friday. At that time, the vast Puxi area on the opposite side of the river will go under lockdown.
Hong Kong, which has faced a record surge in Covid-19 cases and the world’ s highest death rate, has been under strict restrictions. WSJ’ s Diana Chan reports on how everyday life has changed in the city, from panic buying to an exodus of residents. Photo: Emmanuel Serna/Zuma Press
• The European Medicines Agency, the drug regulator for the European Union, has started a rolling review of the vaccine booster developed by Spanish drug maker Hipra,
AFP reported.
“ Preliminary results suggest that the immune response with Covid-19 vaccine Hipra may be effective against SARS-CoV-2, including variants of concern such as omicron, ” the EMA said in a statement.
Don’ t miss:
The U.S. is talking about a second round of COVID-19 booster shots, and it’ s going to be even more complicated than last year
Here’ s what the numbers say
The global tally of confirmed cases of COVID-19 topped 482.8 million on Tuesday, while the death toll rose above 6.12 million,
according to data aggregated by Johns Hopkins University
.
The U.S. leads the world with 80 million cases and 978,177 fatalities.
The
Centers for Disease Control and Prevention’ s tracker
shows that 217.4 million people living in the U.S. are fully vaccinated, equal to 65.5% of the population. But just 97.3 million are boosted, equal to 44.8% of the vaccinated population. | business |
FDA Briefing Documents in CNS Space Have Investors Jittery | Typically, a few days before a U.S. Food and Drug Administration advisory committee meets to discuss a drug application, the agency publishes submission details and analysis of the data. This is designed to give the advisory committee — and potentially the public — access to a review of the data.
For the most part, the public doesn’ t pay much attention unless it’ s a particularly newsworthy event. For example, some public attention was paid ahead of the FDA’ s decision on Biogen’ s Aduhelm ( aducanumab) for Alzheimer’ s disease. And there was plenty of attention paid to early data on the various COVID-19 vaccinations.
Otherwise, it’ s a bit of “ inside baseball ” for the industry and for investors. And in some cases, for investors, it gives analysts a shot at predicting how the advisory committee will land on their recommendation, which is typically - but not always - an indicator of how the agency will decide on the drug application. In the central nervous system ( CNS) space, such as with Biogen’ s Aduhelm, a notoriously tricky area to get drugs approved in, there has lately been heightened attention to briefing documents, with resultant effects on company stock prices.
As reported yesterday, the FDA released briefing documents ahead of today’ s Peripheral and Central Nervous System Drugs Advisory Committee meeting to discuss Amylyx Pharmaceuticals’ New Drug Application ( NDA) for sodium phenylbutyrate/taurursodiol powder for oral suspension for the treatment of amyotrophic lateral sclerosis ( ALS). The drug has been granted Priority Review.
Company shares took a serious hit after the news and after analysts wrote about their concerns about the data and the FDA’ s position on it. Shares cratered 41.3%, although they 've bounced back a bit today.
In its documents, the FDA argued that there was insufficient data for approval, that Amylyx reported a “ positive result on a prespecified but non-preferred analysis of a functional endpoint in ALS, which did not appropriately account for deaths that occurred during the study. The prespecified statistical result was not exceptionally persuasive and there were analytical and interpretative issues associated with its consideration. ”
Umer Raffat, an analyst with Evercore ISI, wrote to investors, “ Does the briefing document read materially worse than expectation? Absolutely. Does it mean FDA won’ t approve it? That’ s a loaded question … and we will go on a limb to say it still has a very realistic shot. ”
Potentially it might be approved under an Accelerated Review pathway, with further clinical efficacy to be determined with future clinical trials. ALS is a CNS disorder with no cure. Death typically occurs within three to five years from the onset of symptoms. The advisory committee and the agency might decide that even modest benefits in a limited trial are worth the potential of giving these patients a few extra months.
The company recently initiated a Phase III trial in 600 patients worldwide, but the data isn’ t expected to read out until 2024. It is also evaluating data from an open-label extension study, whose findings have already been reported and published but are not necessarily part of the data package the FDA received.
Reata Pharmaceuticals’ stock plunged 31.4%, and some analysts think it’ s because of the FDA’ s briefing documents on Amylyx. Reata started a rolling New Drug Application submission for omaveloxolone for Friedreich’ s ataxia in late February. It hopes to complete the NDA by the end of the first quarter of this year — in other words, this week.
Friedreich’ s ataxia is a rare, genetic degenerative neuromuscular disease. It is caused by a trinucleotide repeat expansion in the first intron of the frataxin gene. This is a sort of genetic stutter, where three nucleotides get repeated over and over again.
The gene encodes the mitochondrial protein frataxin, and the repeats lead to impaired transcription and decreased frataxin expression. This in turn can cause mitochondrial iron overload and poor cellular iron regulation, increased sensitivity to oxidative stress, and impaired ATP production by the mitochondria, the energy-producing organs of the cells. The disease leads to progressive loss of coordination, muscle weakness, and fatigue.
So why would Amylyx’ s neurodegenerative drug affect Reata’ s neuromuscular drug application? This is most likely because investors are suddenly jittery about drug approvals in the CNS space. Another reason is that Reata has submitted limited data for omaveloxolone, but some investors are applying the FDA’ s criticism of Amylyx’ s lack of morbidity analysis to Reata’ s data.
Citi, on its part, thinks the Reata selloff was overblown. “ ALS is a fast-progressing disease where deaths would be expected to occur ( and did occur) over the course of the 24-week Centaur trail, ” wrote Citi analyst Yigal Nochomovitz. FA, on the other hand, is a “ more-slowly progressing neuromuscular disorder. ”
Bloomberg quoted Nochomovitz, saying, “ We confirmed with Reata management today that FDA has not recommended any type of mortality analysis in the key efficacy analyses. ”
It’ s also likely that investors in the life sciences are jittery from news on Monday that Biogen and Ionis Pharmaceuticals were killing off an ALS drug program after the failure of their Phase I trial of BIIB078. The study failed to meet clinical endpoints. And in October 2021, Ionis and Biogen reported another antisense drug failure in ALS. In that case, it was the Phase III VALOR trial of tofersen.
Biogen may be pivotal as well for all the investor nerves. Although its Aduhelm was the first Alzheimer’ s drug to be approved in about twenty years, it’ s controversial and Medicare and insurers are reluctant to pay for it. And in mid-March, Biogen’ s development partner Eisai modified their deal on the drug, with Eisai shifting to royalties-only and taking control of another Alzheimer’ s program with Biogen for lecanemab. | general |
SPACs are no longer the 'it ' investment | Remember all those special purpose acquisition companies that went public and then bought private firms? These so-called blank check deals were all the rage in 2020 and early 2021.
Virgin Galactic ( SPCE) and DraftKings are two well-known companies that went public via SPACs. Mattress seller Purple Innovation ( PRPL) and Twinkies maker Hostess Brands ( TWNK) are also SPAC alumni.
But in the past year, SPAC has become a bit of a dirty word — or acronym — on Wall Street. High profile SPAC blowups such as Nikola, WeWork and BuzzFeed have raised alarm bells.
The Defiance Next Gen SPAC ETF, which owns shares of electric vehicle maker Lucid, Southeast Asian delivery company Grab and the Donald Trump-backed SPAC Digital World Acquisition Corp, has dropped 18% this year, much more than the broader market, and has plunged nearly 35% in the past 12 months.
`` We have definitely seen a slowdown since 2020, '' said Kerry Ann Sullivan, a director in the transaction advisory practice at consulting firm Berkeley Research Group. Sullivan said that demand for due diligence tied to SPAC deals in early 2020 was `` hot and heavy. '' Not anymore
Clock ticking on SPACs to buy
Several blank check firms that went public in recent years haven't yet made a purchase and they're now facing deadlines to make a deal or return cash to their investors. SPACs typically have about 18 to 24 months to complete a merger.
It may be tough for many of them to find willing acquisition partners. The stock market has had a tumultuous year so far. Investors are worried about inflation, rate hikes from the Federal Reserve, the Russian invasion of Ukraine and the ongoing Covid-19 pandemic.
Geopolitical jitters in particular have hurt demand for SPACs, as well as for companies going public through more traditional initial public offerings.
`` The war has tightened the pipeline of new issuances coming to the market in early 2022, '' Ken Leon, director of research at CFRA, said in a report on big banks earlier this month. `` SPACs... already realized steep declines in public market prices prior to the Ukraine crisis. ''
Leon noted that `` underwriting remains a pivotal area for investment banking '' after a record year for IPOs in 2021.
Cautious optimism for a comeback
Big banks like Goldman Sachs ( GS), JPMorgan Chase ( JPM) and Morgan Stanley ( MS) typically generate lucrative fees from advising on SPAC deals as well as IPOs.
Investment banks often help engineer private investment in public equity ( or PIPE) deals in conjunction with SPACs to raise more money for a company going public through a blank check merger.
SPACs aren't completely dead. If nothing else, the massive shakeout has forced investors to look for more quality deals instead of throwing cash at the latest SPAC from an EV or media startup with no revenue, let alone profits.
Sullivan said there has been a greater emphasis on businesses in the health care sector for SPAC deals during the pandemic.
She also welcomes more scrutiny on SPACs from the Securities and Exchange Commission. That will help ensure that the deals getting done now have a better chance of success once they go public.
`` Regulatory involvement should give investors more of a comfort level with SPACs, '' Sullivan said. `` They are honing in on protections for investors, and we hope the mindset on SPACs changes. It's good that the SEC is looking more cautiously. '' | business |
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Natural gas futures floundered on Tuesday as the domestic weather outlook shifted increasingly bearish, production ticked up and energy commodities broadly dipped lower amid pandemic flare-ups and the potential for a cease-fire in Ukraine.
On its final day as the prompt month, the April Nymex gas futures contract lost 17.2 cents day/day and settled at $ 5.336/MMBtu before rolling off the board. May fell 20.8 cents to $ 5.330. Futures faltered for a second straight day – after rallying throughout the prior week.
NGI’ s Spot Gas National Avg. shed 55.0 cents to $ 4.970, led lower by drops across Appalachia and the East.
U.S. production reached 95.5 Bcf on Tuesday, up more than a 1 Bcf from the prior week. This put output near 2022 highs of around 96 Bcf, Bloomberg data showed.
At the same time, the latest weather data Tuesday extended warmer trends as both the American and European models advertised mostly mild temperatures for the northern United States this weekend and through next week, according to NatGasWeather.
“ A relatively cool weather system is still expected to track across the northern U.S. this weekend …However, the amount of subfreezing air with this system decreased yesterday and overnight, resulting in only a minor bump in demand, ” the firm said.
For the April 5-12 time frame, the latest data showed a pattern that could lead to widespread comfortable conditions for the Lower 48, according to the forecaster.
NatGasWeather also noted reports from Ukrainian and Russian officials touting progress in cease-fire talks that eased war-induced concerns about oil and gas shortages. This, the firm said, put downward pressure on prices across most commodity markets. That noted, the Associated Press reported that Russia continued lethal attacks across Ukraine Tuesday.
At the same time, increasingly widespread mobility restrictions to slow coronavirus outbreaks in China, the world’ s second-largest economy, threatened to curb demand for travel fuels and natural gas. Brent crude, the international oil benchmark, dropped nearly 10% over the course of Monday and Tuesday, though prices remained elevated and well above $ 100/bbl.
China and parts of Europe are grappling with a subvariant of the coronavirus Omicron strain that is spreading rapidly. China in recent days locked down much of Shanghai, the country’ s biggest city with more than 20 million residents.
China is the largest importer of liquefied natural gas ( LNG). The Shanghai lockdowns have curbed power and industrial gas demand and, as a result, China has resold LNG cargoes this month, according to Rystad Energy analyst Vinicius Romano.
Additionally, in Western Europe, German officials this week estimated they are tallying nearly 300,000 virus cases daily — more than six times the rate that the United States has reported in recent days. This could slow LNG demand in Europe as well.
Tapered European LNG needs could further ease global supply worries that have been amplified by Russia’ s invasion of Ukraine over the past five weeks. Europe is trying to wind down its use of Russian gas in objection to the war. This has ramped up demand for U.S. LNG exports and fueled price rallies, including the five-day surge in Nymex gas futures last week. American exporters have operated near capacity throughout March.
Fresh coronavirus challenges, however, could at least provide a reprieve, led by the impacts of China’ s actions in Shanghai, Romano said.
Last week, the Biden administration and European Union ( EU) announced a plan to ensure Western supplies of natural gas to the continent through 2022 and beyond. The two set a joint goal to send nearly 1.5 Bcf/d of additional LNG to EU countries this year.
However, as analysts at Goldman Sachs Group Inc. noted, even if demand from Europe holds strong, markets may already have baked in the impact of Russia’ s war in Ukraine on U.S. LNG demand this year, given that U.S. exporters are now effectively maxed out.
[ Actionable Insight: Did you know that NGI is one of only two Price Reporting Agencies that include trade data from the Intercontinental Exchange. Find out more. ]
That noted, the Goldman team said that, in coming years, U.S. companies are expected to expand capacity, and both European and Asia demand will likely be waiting to soak up the added supplies.
“ Further out the curve, we expect the balance between production and LNG exports to drive U.S. gas price cycles, ” the Goldman analysts said. “ Specifically, we expect the next wave of U.S. LNG export capacity additions from 2025 to bring a renewed tightening to U.. S gas markets after softer balances in 2023/24. ”
Cash prices clunked on Tuesday. Despite frosty air lingering across the Great Lakes and Northeast, buyers stepped back amid the forecasts for mild weather later this week and into April.
Northeast prices plummeted and dragged down the national average. Algonquin Citygate, where prices are often volatile, dropped $ 7.200 day/day to average $ 5.525.
Still, there were notable double-digit drops across Appalachia and the Southeast as well.
Columbia Gas shed 37.0 cents to $ 4.765, while Eastern Gas South lost 43.0 cents to $ 4.680.
Meanwhile, Cove Point fell 29.0 cents to $ 5.205 and Florida Gas Zone 3 lost 13.0 cents to $ 5.355.
While temperatures are expected to shift from chilly early this week in the Midwest and East to mild as April approaches, dampening demand, weather could still prove a wildcard.
AccuWeather noted Tuesday that a “ potent storm is taking aim at the southern United States. ” The storm is packing the potential to deliver “ all facets of severe weather, ” from hail to damaging wind gusts. This could temporarily threaten gas production and cause power outages.
If the expected storm materializes, it would follow a rash of severe thunderstorms and tornadoes that fueled a bump in cash prices last week, from Texas to the Southeast.
“ Residents in portions of the South still reeling from last week’ s bout of destructive weather may find themselves in the path of Mother Nature’ s wrath once again this week, ” said AccuWeather meteorologist Mary Gilbert.
The storm was expected to travel out of East Texas late Tuesday and onward toward the East. AccuWeather forecasters said it could potentially impact Alabama, Arkansas, Kentucky, Louisiana, Mississippi, Tennessee and parts of neighboring states on Wednesday.
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After a bit of hesitation, natural gas futures notched another day in the green as production declined and weather models aligned in showing a cooler-than-normal pattern that would keep hefty storage deficits intact throughout the month. The May Nymex contract settled at $ 6.680/MMBtu, up 3.7 cents day/day. June futures climbed 4.0 cents to $ 6.763. Spot…
Natural Gas Prices
Natural Gas Prices | general |
Who's eligible for second Covid-19 booster shots -- and when to get them |
The US Food and Drug Administration has authorized additional booster doses of the Pfizer/BioNTech and Moderna coronavirus vaccines for adults 50 and older -- and now, many people in that group are wondering whether to get that dose now or later.
FDA authorizes second booster shots for adults age 50 and older
On Tuesday, the FDA announced that it has
expanded the emergency use authorization
for the two vaccines to allow adults 50 and older to get a second booster as early as fourth months after their first booster dose. The amended EUA also authorizes second booster doses for certain people 12 and older who are immunocompromised.
Following the FDA's action, the US Centers for Disease Control and Prevention updated its recommendations to allow a second booster dose for those groups -- and noted that adults who got a primary shot and booster dose of the Johnson & Johnson vaccine at least four months ago may now get a second booster dose of the Pfizer or Moderna vaccine.
The FDA and the CDC emphasized that they `` will continue to evaluate data and information '' around the potential use of second booster doses for other age groups.
But for those who are eligible for a second booster dose, there are plenty of questions about when might be the best time to get vaccinated, where and how.
Read More
I 'm eligible for a second booster. When should I get the shot?
Older adults and certain immunocompromised people who are eligible for a second booster dose of the Pfizer/BioNTech or Moderna vaccine can get it at least four months after their first booster.
`` Evidence that we have now from Israel suggests that by getting this, one can reduce the risk of hospitalization and death in this population of older individuals, and so we think that this is something that is worthwhile for people to consider, '' Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, said Tuesday.
`` If it were my relatives, I 'd be sending them out to do this again because of the higher level of protection, '' Marks said.
Could the Covid-19 vaccine become a yearly shot? Some experts think so
At age 64, Dr. William Moss, executive director of the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public Health, is eligible for a second booster dose -- but he said he plans to wait to get it.
He completed his initial two doses of vaccine, had a booster shot and was infected with the Omicron coronavirus variant.
Studies published in February
suggest that being vaccinated and having been infected with the coronavirus can offer a type of `` durable '' protection called hybrid immunity.
`` And I don't have any underlying medical condition, so I feel pretty comfortable waiting, '' Moss said. `` That could change if we see a huge increase in cases in the United States. But if we don't, I may be more inclined to wait until the fall and perhaps get my second booster then.
`` Now, my parents are 89 and 93 -- and I would recommend that they get a booster dose now, because they're at so much higher risk of severe Covid. ''
Moss added that access to Covid-19 antiviral medications that infected people can take at home with a prescription also can play a role in how comfortable someone might feel with waiting to get their second booster dose.
`` I think that's a very important part of the conversation, '' Moss said.
Several studies have shown that the immunity against Covid-19 elicited by the Pfizer/BioNTech, Moderna and Johnson & Johnson vaccines can
wane over several months
,
especially among older adults
who might have weaker immune systems.
So the timing of a second booster can make a difference, because the benefit of that vaccination can be `` short-lived, '' said Dr. Jorge Salinas, an infectious disease specialist at Stanford University.
`` It's the same as flu vaccination, '' Salinas said. `` We get vaccinated once a year, and we open it pretty early. But some people have shown that if you do it too early, you can lose a bit of the protection towards the tail end of the flu season. ''
Where can I get my second booster shot?
The rollout of additional booster doses is expected to mirror the rollout of initial booster doses, with pharmacies and doctor's offices among the main sites where people could get their vaccinations.
I 'm not eligible for a second booster. How do I know when I can get one?
A second booster shot might be recommended for more Americans as we move into fall.
`` It's possible that people will need to get another vaccine, '' Marks said Tuesday, adding that for adults 50 and older, getting a fourth dose now `` will not preclude '' them from getting an additional dose in the fall `` if there's evidence that another booster could be of benefit. ''
A fourth Covid-19 shot might be recommended this fall, as officials 'continually ' look at emerging data
In other words, a second booster dose now does not necessarily mean you wouldn't be eligible for another boost later this year.
`` It may be that some people who get a second booster dose in April or May, they may need and be eligible for another booster dose in the fall, should we suspect a late fall or winter surge as with other respiratory viruses, '' Moss said.
It is `` almost inevitable '' that most people will need another booster shot at some point, because the coronavirus will continue to change, said Dr. Megan Ranney, a practicing emergency physician and academic dean of the School of Public Health at Brown University.
`` The question is, is that moment today? Or is it sometime down the road, either when we are seeing signs that another surge is hitting us or just in the fall, the same way that we do for flu shot? ''
What vaccines will be used for second booster shots?
The vaccines currently available for second booster shots are the same ones that have been given for initial doses and boosters throughout the pandemic.
But boosters that people receive this fall or winter could be completely different, Moss said. For instance, it could be a protein-based vaccine -- like the one from Novavax, which
has applied for FDA authorization
-- it could be a vaccine administered as a nasal spray, or it could be a vaccine specifically developed to target a certain variant, such as Omicron.
`` There's been a discussion for several months now about Omicron-specific vaccines, and my understanding is that the data on those will be available in May. But many people may be better off -- if not most people -- getting an Omicron-specific booster should that become available. The timing on that is not clear, '' Moss said. `` The point is that in the coming months to year, there may be more options for booster doses that actually may be better than another dose of the original mRNA vaccine. ''
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The Results Are In with Dr. Sanjay Gupta
every Tuesday from the CNN Health team.
The FDA's
Vaccines and Related Biological Products Advisory Committee
is scheduled to meet next week to discuss the need for Covid-19 vaccine booster doses in the future, including the process for selecting variant-specific boosters.
Some companies, including Pfizer and Moderna, are developing variant-specific vaccines that could target whatever strain is circulating when the booster might be needed. Pfizer and Moderna also have said they are working on a vaccine that would specifically protect against the Omicron variant.
`` There may be a need for people to get an additional booster in the fall along with a more general booster campaign, if that takes place, '' Marks said Tuesday. `` Because we may need to shift over to a different variant coverage, '' like a formula developed to target a specific variant or a mix of variants.
CNN's Brenda Goodman contributed to this report. | general |
Opinion: We should fight inflation by adopting supply-side labor reforms that would encourage work | SAN DIEGO, Calif. (
Project Syndicate
) —In the past few years, a million retired Americans have picked up a pickleball racket. We would have less inflation if they had picked up a hammer, wrench, or pencil instead.
“ Help Wanted ” signs are everywhere, from coffee shops to pharmaceutical plants. Advanced economies could ease one major source of inflation by inducing more people to join the workforce, especially those at the two ends of the labor barbell: older people and young people.
Owing to the whirling printing press of central banks, excessive government spending, shipping disruptions, and now Vladimir Putin, inflation has spiked to levels not seen since
Rocky II
( 1979). But with a supply-side labor policy, we can help fill the
11.3 million job vacancies
in the United States, while the Federal Reserve and its counterparts elsewhere figure out how to drain their bloated balance sheet.
“
At the same time, more than 20 million prime-working-age ( 25-54) Americans effectively wake up each morning, smell the coffee, and then scroll through cat videos on TikTok until lunch.
”
In the popular press, the U.S. economy appears to be blessed with Energizer bunnies. Tom Brady breaks touchdown records at age 44, Clint Eastwood directs movies at 89, and William Shatner boldly goes into space at 90. The proportion of seniors in the country has jumped by
one-third
over the past 15 years.
At the same time, more than
20 million
prime-working-age ( 25-54) Americans effectively wake up each morning, smell the coffee, and then scroll through cat videos on TikTok until lunch. They tell Bureau of Labor Statistics surveyors that they “ do not want a job now. ” Sofa-dwelling gamers and crypto bros might help Xbox
MSFT,
-3.66%
and Coinbase
COIN,
-5.83%
prosper, but a low labor-force participation rate is bad for the broader economy—and the country.
Three smart strategies
A smart supply-side labor strategy has three prongs. It should draw some of the “ unworked ” back into jobs by correcting public pension distortions, attacking the epidemic of occupational licensing and credentialism, and defending gig workers and the platform economy from heavy-handed regulation.
Seniors respond to tax incentives, just as they respond to early-bird dinner specials. Unfortunately, Social Security penalizes retirees who return to work by cutting their monthly benefits. A 62-year-old recipient loses $ 1 of benefits for every $ 2 she earns over $ 19,560. The Urban Institute
calculates
that while a median-income 60-year-old faces an implicit tax on work of about 15%, the rate jumps to over 30% at age 66. So why bother working?
With America’ s declining birthrate, each retiree now leans on a mere
2.7 active workers
, a dependency ratio that is expected to worsen to 2.3 active workers per retiree by 2035. Countries like France, Italy, and Japan face an even more dire calculus.
To manage this imbalance, pension taxes for seniors should be eliminated when they reach a certain number of years in the workforce. After 45 years, for example, an individual would be “ paid in full ” and could continue to work without facing penalties or payroll taxes. Too many energetic seniors are moving to “ active ” communities too soon, indulging in rum punch when they might prefer punching a time card.
Incentives for young people
The government should also create better incentives for young people. In Italy, before COVID struck, nearly 30% of young people aged 20 to 34 were classified as NEET ( “ neither in education, employment, nor training ”). The U.S. labor-force participation rate has dropped 17% for 16-24-year-olds since 2000. In 2000,
over half
of teens worked during the summer; now, only about one-third do.
Cooking hot dogs on the boardwalk may not do much for an academic resume, but it does build lifelong skills like self-discipline and time management. Moreover, according to a Northeastern University study, low-income high-schoolers who work are
more likely to graduate
.
With a smarter supply-side labor strategy, 16-24-year-olds who pay into government retirement plans would be credited at double the current payout rate when they retire. A 20-year-old who earns $ 15,000 in 2022 and pays about $ 1,200 in Social Security taxes would be credited at retirement as if she had earned $ 30,000.
Another major problem is that workers of all ages who want to enter new fields must navigate around government barricades, including pricey licensing requirements. Nearly
one-quarter
of EU and U.S. jobs require a license, compared with under 5% in the 1950s. While licensing makes sense for surgeons and pilots, one can only wonder why the state of Arizona forces hair stylists to take 1,600 hours of classes. A Phoenix policeman spends
1,040 hours in training
. Apparently, handling a blow-dryer is far more dangerous than handling a.40 caliber Glock.
This licensing epidemic has driven up costs for workers and consumers. In a world of gig work and online learning, even college-degree requirements seem oldfangled. According to the employment platform Indeed,
72% of employers
think coding boot camp grads “ are just as prepared and likely to be high performers as candidates with computer science degrees. ” A senior executive at Google
GOOG,
-2.76%
declared
that college grades are “ worthless as a criterion for hiring. ”
No surprise then that IBM
IBM,
+0.39%
announced
that half of its U.S. jobs are now open to anyone with the right skills, and Ernst & Young ( U.K.) flung open its doors to non-university grads. To excel at a tech job requires staying on top of the latest industry innovations—hardly a specialty of tenured professors lecturing from last year’ s notes. Governments can take the lead by hiring the best candidates, not necessarily those with gilded diplomas.
Gig workers
Finally, governments should stop undermining the gig economy. Gig workers perform an inflation-fighting service when they bring into use a spare apartment, a garaged car, or an idle dump truck sitting on the side of a construction site. Reclassifying these workers as employees robs them of flexibility and pushes up prices. New York City capped the profits on food-delivery companies, which only hurts city-dwellers. Parliamentary committees in the European Union, Australia, and Canada also are taking aim at firms like Airbnb
ABNB,
-3.83%
and DoorDash
DASH,
-3.89%
.
A smarter labor policy would create opportunities for those who want to work, while combating inflation and helping reopen some of the nearly
one-third
of small businesses that were shuttered by lockdowns. For healthy people, retirement and other noble endeavors like Xbox and pickleball can wait for another day.
Todd G. Buchholz, a former White House director of economic policy under President George H.W. Bush and managing director of the Tiger Management hedge fund, is the author of “
New Ideas from Dead Economists
” ( Plume, 2021) and “
The Price of Prosperity
” ( Harper, 2016).
Michael Mindlin is an investment banker in Los Angeles.
This commentary was published with permission of
Project Syndicate
—
Fight Inflation with Supply-Side Labor Reform
More viewpoints on inflation
Supply shortages—including labor—creating most of the inflation
Why interest rates aren’ t really the right tool to control inflation
Ukraine war is a wake-up call to ditch oil and gas forever | business |
Maersk warns Shanghai city lockdown to boost transport costs further | The Chinese coastal city, home to some of the world's busiest sea and airports, began locking down half of the city on Monday and intends to do the same to the other half for four days starting Friday in a two-stage testing exercise.
While it has kept its airports and deepwater port open, it has imposed stringent movement curbs, barring unapproved vehicles from streets and telling millions of people not to leave their homes.
`` Trucking service in and out ( of) Shanghai will be severely impacted by 30% due to a full lockdown on Shanghai's Pudong and Puxi areas in turn until 5th April, '' Maersk, the world's second-largest container shipping company, said in an advisory to clients on Monday.
It adding that warehouses in Shanghai would be closed until Friday.
`` Consequently, there will be longer delivery time and a possible rise in transport costs such as detour fee and highway fee. ''
SEKO Logistics, a U.S.-based freight transport and warehousing company, said factories in the neighbouring province of Zhejiang were opting to move cargo out of Ningbo's port, rather than Shanghai.
`` We are anticipating: a sharp increase in air freight rates from today. We have already received some sky-high offers for enquires to Europe so far today, '' it said on its website.
China is battling its largest number of COVID-19 infections since the onset of since the country's initial outbreak receded in early 2020. This month it placed lockdowns on other manufacturing exports hubs such as Changchun and Shenzhen, which gave rise to lengthening queues outside major Chinese ports.
Although curbs in Changchun have remained in place, they have been relaxed in Shenzhen, where businesses and factories were allowed to resume operations on March 21.
However, a survey conducted by a state newspaper found Shenzhen's `` war '' on COVID-19 has hurt up to 93% of local small and medium-sized companies, with many suffering production disruptions because of shutdowns, interruptions in supply chains, and delays in order executions.
( Reporting by Brenda Goh. Editing by Gerry Doyle) | business |
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Aerium, based in Boston and Lausanne, Switzerland, said it is developing a two-antibody combination treatment. In pre-clinical studies, the antibodies have been potent neutralisers of SARS-CoV-2 and its variants. That group includes Omicron and its sub-variants, among them the BA.2 strain that has been detected in at least 40 countries.
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Nurses of color confront a ‘ dual pandemic’ of workplace racism and COVID fears | A potent “ dual pandemic ” of COVID-19 worries and workplace racism heightened the emotional distress felt by nurses of color, according to a newly published study of nurses at New Jersey hospitals conducted in fall of 2020.
While all nurses reported some experience of racism in the workplace, nurses of color reported experiencing higher levels of workplace racism compared to white nurses, the study found. They also reported higher levels of overall worry about the coronavirus and emotional distress.
“ It was the combined experience, the intersection of COVID worry and workplace racism experiences … that amplified or increased their emotional distress to severe levels, ” lead study author Charlotte Thomas-Hawkins, the associate dean for the division of nursing science and a tenured associate professor in the Rutgers School of Nursing, told MarketWatch.
Nurses of color reported experiencing racial microaggressions in the workplace ( for example, “ an employer or coworker was unwelcoming or unfriendly because of my race, ” or “ I was treated differently by an employer or coworker than persons of other racial groups ”) at a higher level than white nurses, with Black nurses experiencing the highest level.
The same pattern bore out when participants were asked about their perception of a negative racial climate in their organization — that is, the extent to which there were opportunities for promotion, organizational policies that seemed to advantage or disadvantage them, and organization-wide racism.
As for nurses of color showing higher levels of worry about contracting COVID-19 compared to white nurses, Thomas-Hawkins said she wasn’ t surprised, given the coronavirus’ s
devastating and disproportionate toll
on people of color and, more specifically,
healthcare workers of color
. Eight in 10 nurses overall said they had cared for COVID-19 patients, and nearly half said they’ d cared for coronavirus patients who died.
“
‘ Not only should racism be acknowledged and discussed, but the strategies to address it and mitigate it should be well thought out, long-term, and multi-level.’
”
— Charlotte Thomas-Hawkins, associate dean for the division of nursing science at the Rutgers School of Nursing
The study was conducted during a period when COVID-19 hospitalizations and deaths in New Jersey were trending downward. While the snapshot of nearly 800 nurses may be difficult to generalize beyond the experiences of hospital-based nurses in New Jersey, the findings are consistent with other qualitative and descriptive work reported in national samples, Thomas-Hawkins said.
This study was also unique in that it quantified the experiences and effects of workplace racism on nurses’ wellbeing, she and her co-authors wrote — an approach that “ underscores the need to address the problem, ” Thomas-Hawkins said.
“ The first step is acknowledging that it exists, and no longer ignoring or avoiding the discussions about racism and the work that needs to be done across all workplaces, not just hospitals, to address it, ” she said.
In the midst of concerns about
nursing workforce shortages
that predated
the pandemic
, the study said, these findings point to “ the urgent need for a sustained investment in a racially diverse nursing workforce. ” Having a racially diverse nursing workforce can boost
culturally competent care
, improve care delivery and
help reduce health disparities
, Thomas-Hawkins said.
“ There’ s urgent need to not only recruit but to retain talented nurses of color, ” she said. “ One of the strategies to do that is to make sure that nurses — all nurses, especially nurses of color — are working in healthy work environments. ”
As the U.S. Centers for Disease Control and Prevention
points out
, racism at both the interpersonal and structural levels negatively impacts mental and physical health.
Thomas-Hawkins said she hopes the findings can lead to hospitals rooting out and addressing workplace racism at all levels. Some strategies should be targeted to the individual, like helping people become aware of their own biases; others should be implemented at the interpersonal level, such as training for managers on how to understand and respond to workplace microaggressions reported by an employee.
But strategies at the individual and even interpersonal levels will likely be short-lived if changes aren’ t also implemented at the institutional level, Thomas-Hawkins added. That means hospitals should conduct reviews to ensure policies, practices and procedures don’ t favor one group of employees over another, and address diversity concerns in both mid-level and executive leadership.
“ Not only should racism be acknowledged and discussed, but the strategies to address it and mitigate it should be well thought out, long-term, and multi-level, ” she said. | business |
Cathie Wood says her contrarian views set her apart, not her gender | In this article
It's hard to talk about the topic of women in investing without mentioning Cathie Wood. The founder, CEO and chief investment officer of Ark Investment Management was the first woman to claim the title of manager of the largest actively managed fund.
Yet, when Wood reflects on her career, she said she attributes any professional marginalization to her contrarian views rather than her gender. On any given day, she is rarely reminded that she is a woman, Wood told CNBC in a recent interview.
Her exchange-traded funds, which focus on `` disruptive innovation, '' have suffered year to date. Still, Wood remains among the largest active managers, with more than $ 21 billion invested in her funds.
By being unwavering and publicly vocal about her conviction in investing in the future, Wood gives her critics ample opportunity to take aim at her unique strategies.
`` Other people say that I am attacked in the media because I 'm a woman. I don't think that is [ the case ]... I really think it's because we're disrupting the financial world and we're unsettling people, '' said Wood. `` It's the ideas and the research. They're pretty provocative. ''
Wood, 66, founded Ark Invest in 2014 after a long tenure running AllianceBernstein's Global Thematic Growth Fund, which she navigated through the tech and telecom bust. Wood was 57 years old when she started the research-centric investment group because she found herself frustrated by how little investors were focused on innovation and technology.
`` There was nowhere I was going to fit in and I didn't want to fit in anywhere, '' said Wood. `` I wanted to blaze a trail. ''
Through her mystical conviction in provocative growth strategies in the U.S. equity market, Ark's ETFs were created. Her strategies focus on five disruptive technologies: DNA sequencing, robotics, artificial intelligence, energy storage and blockchain technology. However, Wood is often criticized for the expensive, high-multiple and sometimes illiquid stocks in her funds.
Ark's flagship fund, Ark Innovation, made popular high-growth names like Tesla, Zoom Video, Roku and Teladoc Health.
`` I 've seen people put her down and I 've seen people praise her but neither of those descriptions of Cathie have focused on her gender, '' said economist Arthur Laffer, one of Wood's former teachers and longstanding mentors.
Ark Innovation — which trades under ticker ARKK — was largely put on the map after Ark Innovation's banner year in 2020. The fund was full of equities that thrived during the coronavirus pandemic — a group that became known as stay-at-home stocks — and it rallied nearly 150%. Last year, during a rotation to value as the economy recovered, the fund lost 25%.
2022 has been a dismal year so far for Wood's funds as growth pockets of the market are punished by surging interest rates. Ark Innovation is down more than 30% and sits more than 50% from its 52-week high in June 2021.
The depreciation in Wood's stocks from mid-February of 2021 has not changed Ark's forecast. Wood said she is just getting her highest-conviction stocks at lower prices. This should result in a 30% to 40% compound annual rate of return for Ark's strategies over the next five years, she has said.
Wood, who focuses on a five-year investing time horizon, said attaching yourself to numbers is a great way to set yourself apart in the financial industry.
`` Politics can't take the numbers from you, they are what they are, '' she said. `` Those are going to be good numbers and bad numbers and you hope over time that the average is pretty good. ''
To be sure, Wood's loyal following has not abandoned her or her vision. Ark Innovation is net positive in inflows for the year at more than $ 1 billion of incoming cash.
Wood is the first child of Gerald and Mary Duddy, first-generation immigrants from Ireland. She said she was raised as her parents ' `` first-born son. '' Her parents encouraged her to pursue avenues regardless of gender.
Raising his children in Los Angeles, Gerald Duddy placed an emphasis on education and research, something Wood still values today. In 2018, she launched the Duddy Innovation Center for Excellence at her alma mater, Notre Dame Academy, in Los Angeles.
In 1977, Wood found herself in Laffer's class at the University of Southern California. Wood recalls not even knowing what business was at the time, but she quickly became enamored by economics and research.
Laffer, a former member of President Ronald Reagan's Economic Policy Advisory Board, accepted Wood into his graduate-level class when she was an undergraduate student. Laffer recommended Wood for her first job and has stayed a close friend and confidant.
`` There isn't anyone who has done what she has done, '' said Laffer. `` That's why her returns are unbelievably abnormal. It also works the other direction of course, but her returns over her career have been amazing because of her hard work. ''
Wood started in the industry as an assistant economist on the West Coast at The Capital Group. She said she often was the only woman in the room.
`` Many guests thought I was the secretary and would ask for coffee and I was happy to give it to them.... I was happy to be in that room, '' she said.
As Wood's career progressed, she was accompanied and mentored by many supportive women like Lulu Wang, with whom she started hedge fund Tupelo Capital Management.
Still, other female colleagues suffered from so-called queen bee syndrome, she said, using a term that is used to describe a situation when women fail to support other women.
`` There have been women who didn't make it easy for me, '' Wood recalled.
Wood said she sees a future with diminishing sexism, and the future-proof companies she invests in are helping to pave the way. Companies like Zoom Video are providing tools for more flexible workplaces, which allow families to balance careers and child care more easily. Stocks in Wood's genomics fund are working to address illnesses that disproportionally affect women.
`` Innovation levels the playing field, '' said Wood. `` These technologies are going to transform how we live and work and play and enhance the quality of life. ''
Plus, stocks that focus on cryptocurrencies and blockchain technology, like Coinbase Global, are attempting to level the playing field in personal finance.
`` The more we see these technologies converge, the more we have to strip away the silos that the traditional financial world has been built on, '' said Wood. `` It's a DNA change for the industry. ''
Wood attributed much of her success to her loyal band of followers — who are often Gen Z and millennials.
`` It's the younger population that stuck with us, '' she said.
Wood has garnered much attention from the millennials who were a part of the massive wave of retail investors that hopped into the market during the Covid-19 pandemic. Day traders in online chatrooms will follow Wood's trades and post slogans like `` In Cathie We Trust '' or call her `` Cathie BAE '' ( before anyone else).
While many investors chided these investors as `` dumb money '' trading in speculative stocks, Wood always defended the group.
Ark has an unconventional social strategy where it shares its research, puts its analysts on social media, and sells `` Ark Invest '' swag, like sweatshirts and baseball caps.
She said her younger fanbase appreciates that Ark is willing to be the closest vehicle to a venture capital firm in the public equity market. That is, an ETF that invests in companies ' long-term growth prospects.
`` The younger people have a more innate understanding of these nascent technologies, how volatile they are but also how promising they are, '' she said.
And her amateur following has proved to be anything but fickle, as investors double down on her funds despite this year's troubling performance.
`` They always believed it would come back and we are rebounding a bit now. Truth wins out, '' Wood said. | business |
FDA clears second COVID booster for older adults, immunocompromised | The Food and Drug Administration on Tuesday authorized a second booster dose of either Pfizer's or Moderna's COVID-19 vaccines for older adults and people whose immune systems are compromised in certain ways.
In making the decision, the FDA cited accumulating evidence that indicates `` some waning of protection over time '' against the disease's worst outcomes in individuals who are at higher risk. The agency cleared an initial booster shot of Pfizer's vaccine for older and immunocompromised adults last September and steadily expanded eligibility criteria over the fall to include all adults as well as recipients of Moderna's and Johnson & Johnson's vaccines.
`` Based on an analysis of emerging data, a second booster dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine could help increase protection levels for these higher-risk individuals, '' said Peter Marks, head of the FDA office that reviews vaccines, in a statement.
The agency made its decision on authorization ahead of an advisory meeting currently scheduled for April 6. The expert panel is slated to discuss COVID-19 booster doses as well as the `` process for COVID-19 vaccine strain selection to address current and emerging variants. ''
Under the new authorization, adults aged 50 or older who received their first booster shot at least four months prior can get a second booster dose. The FDA also cleared another booster of Pfizer's vaccine for people who are at least 12 years of age and have received an organ transplant or are similarly immunocompromised. For Moderna's vaccine, the clearance pertaining to immunocompromised individuals only applies to those 18 years or older.
The criteria for older adults are broader than what Pfizer had requested earlier this month, and narrower than what Moderna had sought.
In a Tuesday call with reporters, Marks said the FDA chose 50 years as a cut off for the authorization because one-third of people between 50 and 65 years old have health conditions that put them at higher risk, and because notable side effects like heart inflammation are less common in that age range.
The data were persuasive enough that agency reviewers didn't see the need to convene an advisory committee on these specific authorizations, he said. `` This was a relatively straightforward decision. ''
Soon after the FDA announced its authorizations, the Centers for Disease Control and Prevention updated its recommendations to reflect the new clearances.
Both Pfizer and Moderna cited emerging data from Israel and elsewhere that suggested diminishing protection from vaccination, particularly as the omicron variant became the dominant circulating strain. The FDA also cited evidence from Israel in reaching its decision, including safety surveillance from 700,000 adults, mostly older than 60 years, who had received a fourth dose of Pfizer's vaccine.
No new safety concerns were identified in that analysis, the FDA said. For assessing Moderna's vaccine, the agency noted data from a small study of 120 participants older than 18 who received a second booster dose.
The FDA is relying heavily on antibody data, rather than evidence on clinical outcomes, to assess the added benefit of an additional shot. On that score, a study of healthcare workers at a single site in Israel found a second booster dose could increase neutralizing antibody levels against the coronavirus, according to the FDA.
Experts are still not certain exactly what level of antibodies is needed to confer protection against COVID-19 or how much of a role other immune defenders play in maintaining immunity over time. However, higher antibody levels are associated with greater protection from disease, hospitalization and death.
In the U.S., COVID-19 cases and deaths have decreased significantly in recent weeks, leading to the relaxation of public health measures across the country. But there are concerns that cases could rise again, as has happened in some European nations alongside the spread of an infectious omicron subvariant. That strain, known as BA.2, has become the most prevalent in the U.S. in recent weeks.
The FDA said it would continue to evaluate study data on vaccine protection to assess whether a second booster dose is necessary for other age groups.
Pfizer and Moderna are both testing new formulations of their vaccine tailored to the omicron variant.
Note: This story has been updated to include commentary from an FDA official and mention of the updated CDC guidance.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
For the first time in years, biotechs no longer have an easy path onto Wall Street, a market reversal that could change what the next generation of young drugmakers looks like.
Biotech CEOs Paul Hastings and Jeremy Levin explained the goals behind a letter supported by more than 400 executives and investors that calls for drugmakers to stop working with Russian companies.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
For the first time in years, biotechs no longer have an easy path onto Wall Street, a market reversal that could change what the next generation of young drugmakers looks like.
Biotech CEOs Paul Hastings and Jeremy Levin explained the goals behind a letter supported by more than 400 executives and investors that calls for drugmakers to stop working with Russian companies.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more. | tech |
A half-a-trillion-dollar bet on revolutionising white-collar work | TWO DECADES ago India’ s information-technology ( IT) firms were the stars of the rising country’ s corporate firmament. The industry’ s three giants, Tata Consultancy Services ( TCS), Infosys and Wipro, became household names at home and familiar to chief executives of big businesses abroad, who had outsourced their companies’ countermeasures against the feared “ millennium bug ”, expected to wreak havoc on computers as the date changed from 1999 to 2000, to Indian software engineers. By the mid-2000s the Indian IT trio’ s revenues were growing by around 40% a year, as Western CEOs realised that Indian programmers could do as good a job as domestic ones or better, at a fraction of the price. Then, following the global financial crisis of 2007-09, revenue growth slowed to single digits. For years afterwards the stars seemed to be losing some of their shine.
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Now they are back in the ascendant. Having declined as a share of GDP between 2017 and 2019, exports of Indian software services ticked up again as the world’ s companies turned to them for help amid the disruption to operations and IT systems wrought by the pandemic. In the last financial year they reached an all-time high of $ 150bn, or 5.6% of Indian GDP ( see chart). NASSCOM, a trade body, expects the industry’ s overall revenues to grow from $ 227bn last year to $ 350bn by 2026.
In the 12 months to March sales at TCS, Infosys and Wipro are once again forecast to grow by double digits—this time from a much higher base than 20 years ago. All told, they could rake in nearly $ 60bn next year, up from just over $ 40bn in 2019 ( see chart 3). In the past two years they have added an astonishing 200,000 or so people to their combined workforce, which now numbers nearly 1.1m. Add the Indian businesses of big Western IT-services firms such as Cognizant ( which is based in New Jersey but India-focused), IBM and Capgemini, as well as smaller Indian rivals and around 1,600 “ captives ”, as in-house Indian operations of foreign firms are known, and the headcount rises to 5m.
Both revenues and ranks of Indian IT look poised to keep growing briskly. Lalit Ahuja, who runs a firm that helps set up captives, says a new one opens every other week. TCS, the industry’ s brightest star, reckons that its sales will rise from nearly $ 30bn today to $ 50bn before 2030. The company is eyeing 1m employees. Infosys and Wipro have comparable ambitions. And investors are buying it. The stockmarket value of the big three has doubled to $ 330bn since covid-19 first emerged. With the addition of Cognizant and Tech Mahindra, another Indian firm, the figure is around $ 400bn ( see chart 4). This represents a huge bet on the future of white-collar jobs.
Three global forces lie behind Indian IT’ s sparkling outlook. All manner of businesses are digitising ever more of their operations. They are moving more activities to the computing cloud. And work is becoming more remote. India’ s low-cost, competent coders can help with all three.
Start with digitisation. The pandemic has turbocharged efforts by companies of all stripes to make their businesses more agile, efficient and clever. Retailers have introduced kerbside pickup. Clinics have launched digital doctor’ s appointments. Schools have run online classes. Factories have been kitted out with sensors to allow remote monitoring in the absence of workers, locked down at home. Data from covid-19 vaccine trials have been crunched. All these innovations required sophisticated software. A lot if it has been developed in India since early 2020. And there is more to come. Among Infosys’ s projects are several connected to electric cars ( including software for the vehicles themselves and for petrol stations to offer charging).
The corporate great migration to the cloud offers further opportunities. According to Anuj Kadyan of McKinsey, a consultancy, big ones include supervising the migration itself for clients, ensuring that the new cloud operations are cyber-secure and adding advanced cloud-based data analytics and artificial intelligence ( AI) on top. Earlier this year JPMorgan Chase, an American bank, announced it would add 6,000 people to its substantial Indian business to work on the cloud, cyber-security and AI. IBM has opened a cyber-security centre in India to cater to its Asian clients.
Combined, digitisation and the cloud make it possible for companies to untether from their physical headquarters not just peripheral functions but parts of their ever more digital core business. Many have done just that during the pandemic, thanks to remote work. This opens up the third opportunity for India’ s IT consultants. They could assume some of the core corporate roles from white-collar workers in the rich world. Wages for new hires in India can be as little as $ 5,000 annually, less than a tenth of the going rate in rich countries. Even factoring in other costs, Indian projects are at least 20% cheaper than the same endeavours in the West, estimates Peter Bendor-Samuel, boss of the Everest Group, a consultancy.
A ballooning Indian “ talent cloud ”, as TCS calls it, is the biggest opportunity of all. It is also the most uncertain. Some Western companies are having second thoughts about hybrid work ( which requires at least partial presence in the office), let alone the fully remote sort. Indian wages are also beginning to rise. India’ s IT giants and captives are competing for the best and brightest among themselves, as well as with a vibrant startup scene. McKinsey estimates that compensation costs have risen by 20-30% over the past year. Company executives say it is not uncommon for employees to ask for their wages to be doubled. Attrition at the big firms has spiked.
As the nature of outsourced work changes, the Indian advantage may erode further. It is easier for clients to outsource standardised assignments on the periphery of corporate functions to faraway India. It is harder to do so for high-value projects at the heart of their business, which require constant communication, continuity and confidentiality. For these reasons, proximity matters. At the very least, it means being in the same time zone as your client. Infosys and TCS now operate in more than 40 countries. Infosys has more than 30 outposts across America and is building a new $ 245m campus in Indiana polis. The firm plans to add 10,000 American workers in the next few years, bringing the total to 35,000. “ We needed capacity closer to the customers, ” explains Ravi Kumar, who oversees Infosys’ s global services business. Mr Kumar’ s own job has relocated from Bengaluru to New York.
Still, India accounts for the bulk of its IT firms’ workforce. Although the companies are cagey about where their employees are based, securities filings by Infosys and Cognizant show that, give or take, three-quarters of staff are based in India. If India’ s entire IT industry grew at the same rate as TCS, more or less doubling its workforce this decade, that could mean nearly 5m new Indian white-collar jobs—and potentially 5m fewer in the West.
This points to a final hurdle. Amid supply-chain disruptions from the pandemic, now compounded by Russia’ s war in Ukraine, and a geostrategic contest with China, the West is in a protectionist mood. Few politicians would relish millions of well-paid positions moving to India on their watch. Critical visas that once allowed the Indian firms to send star employees abroad to work directly with clients have already grown harder to come by, forcing these positions to be filled locally. Although data can in theory be stored and analysed anywhere, governments are increasingly keen to limit cross-border information flows, often invoking national security. By building a few more campuses in Western countries India’ s IT titans may alleviate some of those concerns. They are unlikely to make them disappear. ■
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This article appeared in the Business section of the print edition under the headline `` Outsourcing 2.0 ''
Published since September 1843 to take part in “ a severe contest between intelligence, which presses forward, and an unworthy, timid ignorance obstructing our progress. ”
Copyright © The Economist Newspaper Limited 2022. All rights reserved. | business |
Stephen Takacsy's Top Picks: March 29, 2022 | The information you requested is not available at this time, please check back again soon.
Volatility has increased significantly in capital markets due to a confluence of factors, not least is the recent invasion of Ukraine by Russia. The investment environment remains very foggy due to the ongoing effects of the pandemic, central banks increasing interest rates due to high inflation fueled by supply-demand imbalances, labour shortages and supply chain disruptions that have worsened as a result of the war in Ukraine.
We expect markets to remain volatile as central banks are caught between raising rates quickly to tame high inflation ( and fearing a wage price spiral) while liquidity levels are still high and trying to engineer a “ soft landing ” to avoid a recession.
We believe that the rate of inflation will gradually ease while the economy simultaneously slows down. As a result, we are staying diversified by industry and company in recession-resistant businesses, such as CareRx, Pet Value, Jamieson Wellness and Park Lawn. At the same time, we are finding good long-term investment opportunities at attractive valuations in the non-resource small-mid cap sector, such as Pollard Banknote, Stella-Jones, and AG Growth.
Stephen Takacsy, president, CEO, and chief investment officer at Lester Asset Management, discusses his top picks: Pollard Banknote, Ag Growth International, and Stella-Jones.
Pollard is the second largest supplier of instant lottery tickets in the world and a leader in electronic lotteries in the U.S. ( iLottery). There are only three players licensed in North America, so barriers to entry are huge. After a big run to over $ 60, Pollard’ s stock has pulled back to a very attractive level of $ 25 due to some margin compression on higher input costs for paper, ink and foil, as well as some production inefficiencies due to overly strong demand and sales delays on higher margin products. The North American instant lottery market continues to grow as governments use it as an important source of funding, while state iLotteries are still in their early days. We expect 2022 could be another record year for Pollard. It’ s such a great business that Brookfield Business Partners is paying US $ 6 billion, or nearly 14 X EBITDA, for Scientific Games’ instant lottery business, which would value Pollard at over $ 40 per share.
Here’ s a great way to play growth in global agriculture. AG Growth is a leading manufacturer of grain handling equipment and storage for the agriculture industry. The company recently announced record results of $ 1.2 billion in sales and record EBITDA of $ 176 million. They also have a record backlog and have provided guidance for EBITDA of over $ 200 million up 14 per cent. North American farm equipment demand is very strong as is their international business in Brazil, India and Eastern Europe as these regions are investing heavily to upgrade their farming infrastructure. This is a great way to play the global agriculture sector without taking commodity risk. While the stock is up 35 per cent this year, it still trades at a very cheap 8X 2022 EBITDA. We also think that AG Growth would make a great take out candidate for AGCO, a large U.S. competitor.
Looking for high-quality earnings at a dirt-cheap price? Stella Jones is the leading North American producer of railway ties and utility poles. Most of their sales are re-occurring from the replacement of wooden ties and poles, although there is strong growth in utility poles from expanding the power grid and new fire-resistant poles. They also have a residential lumber business ( roughly 30 per cent of revenue) through Home Depot, which boomed during the pandemic as people stayed home and spent on home renovations. The balance sheet is very strong, allowing more acquisitions in infrastructure-related products and returns ranging from $ 500 million to $ 600 million for shareholders over the next few years through aggressive share buy-backs and annual dividend hikes. The stock is down nearly 30 per cent, and is being treated as an “ unwinding of the COVID trade, ” even though the lumber business continues to grow above pre-pandemic levels. The stock is a high quality name trading at a dirt cheap valuation of around 11X earnings.
Stephen Takacsy, president, CEO, and chief investment officer at Lester Asset Management, discusses his past picks: Savaria Corp., Goodfood Market, and Andrew Peller.
Hours after delivering the biggest interest-rate hike in 22 years in Canada, Tiff Macklem had a message for investors: There’ s no reason to worry about inflation getting out of hand.
Canada's big banks didn’ t waste much time following the Bank of Canada’ s lead, announcing Wednesday afternoon they will raise their prime rates half a percentage point to 3.2%, effective Thursday.
The Bank of Canada raised its interest rate by half a percentage point in its biggest hike in 22 years and said rates are poised to move significantly higher as it moves aggressively to wrestle inflation down from a three-decade high.
It’ s decision time for the people who control the fate of one of Canada’ s biggest-ever mergers.
The Bank of Canada delivered its biggest interest rate increase in 22 years on Wednesday, lifting its benchmark policy rate by half a percentage point to 1.0%. Here’ s what Bay Street is saying about the decision:
Veronica Clark, economist at Citi, joins BNN Bloomberg for her outlook on the Bank of Canada raising rates by 50 basis points and how that will impact the economy and inflation rate moving forward.
Paul Sandhu, president and CEO of Marret Asset Management, joins BNN Bloomberg for his outlook on the Bank of Canada's latest rate decision, and why he sees risk of a recession on the horizon.
Doug Hoyes, co-founder of Hoyes, Michalos & Associates, joins BNN Bloomberg to share reaction to Bank of Canada hiking rates and what this means for Canadian consumers. He says Canadians will need to earn significantly more to keep up with rising everyday costs. | general |
Facebook owner Meta to hire 2,500 in Canadian roles, create Toronto engineering hub | The information you requested is not available at this time, please check back again soon.
Meta founder Mark Zuckerberg’ s ambitious vision to create an immersive digital realm will be aided by thousands of Canadian hires and a new engineering hub in the country.
Facebook owner Meta announced Tuesday that it will add more than 2,500 office and remote workers to its Canadian contingent over the next five years and situate many of them in a Toronto engineering hub.
The hiring spree is meant to advance Meta’ s plans to build a metaverse, an emerging and interactive world making use of virtual and augmented reality to help people connect, enjoy entertainment and conduct business.
The company chose Canada because of its `` deep talent pool '' and `` vibrant tech ecosystem, '' said Rachel Curran, Meta's public policy manager.
`` Ontario, Toronto in particular, is becoming a real centre of the innovation economy and the tech economy and … so we're jumping on board, '' she said.
The new hires will join Meta’ s first Canadian engineering teams working on WhatsApp, Messenger and Remote Presence, which build synchronous communications products allowing users to complete tasks like watching videos together on multiple devices.
Other hires will join the company’ s artificial intelligence research departments and Reality Labs, which have worked on the Oculus and Portal devices.
Many will be housed in a new downtown Toronto space larger than Meta's current home in the MaRS Discovery District, Curran said. She declined to share further details.
She did, however, note that many new hires will work remotely, helping the company attract even more talent.
`` Canadians have in the past had to move to the U.S. to work for big tech companies frequently, so now we're saying 'no, you can stay in Canada, ' '' said Curran.
`` You can stay in your community, you can stay close to your family, and still do one of these highly paid, highly skilled jobs of the future, which is a really neat evolution. ''
But that evolution worries startups and homegrown businesses.
During the COVID-19 pandemic, they watched foreign giants Microsoft, DoorDash, Amazon, Google, Wayfair, Twitter, Pinterest, Reddit and Netflix reveal Canadian hiring plans. Many intended to place workers in technical or engineering roles and some even said they would bolster hiring with new offices.
Many smaller, local companies feared they wouldn’ t be able to keep up with the higher salaries and bigger names these companies offer. To draw in staff, they turned to flashy benefits such as unlimited vacation, Fridays off and wellness stipends.
`` When they're literally in your own country, your backyard, that increases the pressure even more, '' said Leah Nord, senior director of workforce strategies for the Canadian Chamber of Commerce.
The timing couldn't be worse, she added, because many businesses are grappling with supply chain troubles and recovering from closures and high debt levels seen during the pandemic. Many can't even find workers to fill open positions and immigration levels are still taking time to bounce back.
`` We have labour shortages in this country that are unprecedented and quite frankly, really unfathomable, '' said Nord.
Waterloo, Ont. innovation hub Communitech said as of February, the number of Canadian tech job postings doubled from pre-pandemic levels. It attributed much of the increase to tech companies thriving during the pandemic.
`` The reality is the talent market is tight, '' said Kyra Jones, Communitech's head of talent. `` There is no question that this does put pressure on the Canadian founder, domestic organizations where you're scaling and you're trying to compete in this talent market, but I think there's other ways that you can compete. ''
For example, the tech sector's acceptance of remote work means borders don't inhibit global hiring the way they used to, so Canadian companies are often looking farther afield for themselves, she said.
Curran believes Meta's expansion will help Canadian businesses.
`` These investments make the pie bigger. They make Toronto, they make Ontario more of an attraction for workers, for companies of different sizes, '' she said.
`` As the system becomes stronger and as it grows, that's going to be good for everyone. ''
She also announced Meta will offer $ 510,000 in unrestricted grants to 17 Canadian research labs working on projects poised to advance metaverse-related innovations.
The recipients of the $ 30,000 grants include researchers from the University of Toronto, University of British Columbia and University of Waterloo.
Meta will not place conditions on the funding or ask that it be applied to particular initiatives, Curran said. | general |
Design Week Awards 2022 | Explore the new Design Climate Action, and Sonic Identities categories alongside all the others and find out how to enter.
You now have until 6 April to enter the Design Week Awards 2022, which we aim to bring to our largest ever audience.
Having already undertaken a major overhaul of categories to make them as relevant to your work as possible, this year we’ re adding the Design, Climate, Action award, which recognises work that is making a tangible difference to the health of the planet.
It could be a physical or digital product, a service, a piece of visual communication or another type of deign entirely.
Entrants must be able to demonstrate that their design is improving the health of the planet as part of a sustainable endeavour.
, which is exploring how designers and their clients can use design to help tackle the climate crisis.
section alongside Social Design, Service Design and Best In-house Design Team. We’ re running the Designing Out COVID 19 award again as we saw some highly innovative entries in that category last year and are aware of more great work which has been happening in the fight against COVID over the last 12 months. As ever, Rising Star is free to enter.
section reflects the broad nature of modern branding work with specific awards for Identity Launches and Identity Rebrands, 2D Packaging – Graphics and 3D Structural Packaging, as well Brand Strategy, Writing for Design and more.
It also contains our new Sonic Identities category, which we define as signature sounds used by a brand or product to communicate its brand values, purpose or function.
Submissions might be sonic identities representing a brand or sonic identities designed to be familiar cues which form part of a product’ s user experience.
section in 2020 following consultation with leading designers, it allowed us to think less in terms of outputs ( like website design) and more in terms of beauty, craft and user experiences across digital platforms. To this end our Interaction Design category celebrates design work that engages with end users in a meaningful way and provides a valuable user experience.
section is where you will find Consumer and Industrial Product Design as separate categories alongside Furniture Design.
section: Exhibition; Retail; Wayfinding and Environmental Graphics; Hospitality; and Workplace, noting that some work had been disrupted by the pandemic.
In recognition of this we adapted the entry criteria for these categories. This means entries will be judged against their brief and long term goals, despite any COVID interruption they may have faced.
Given that the UK didn’ t come out of a phased lockdown until July 2021 and that other lockdowns have carried on around the world intermittently since, we are leaving this caveat in place.
Also if your entry has been specifically designed with COVID compliancy or restricted operation in mind, it will be judged on this basis. This might apply to any of the categories coming under Spaces.
Our eligibility period is for projects that have taken or will take place between March 2021 and March 2022, a period in which exhibitions roared back, so we are looking forward to seeing what is entered here.
In short we are taking an even-handed approach to anything which is entered into Spaces.
Our largest ever panel of independent judges will be looking for design excellence across the entire spectrum of the design industry and we are looking forward to announcing them in the coming weeks.
In total there are 32 categories to explore across five broad sections.
and we’ ll be updating the Awards page and the Design Week site with more information soon, so stay tuned. | business |
Millennial Money: Please don’ t go broke attending weddings | The information you requested is not available at this time, please check back again soon.
Sure, you want to feel joy and love upon receiving a wedding invitation. But one little postcard or email can also pack loads of pricey pressure.
Perhaps you must secure travel and lodging, buy gifts and attire, or call off work. Or maybe you have the honor — and extra expense — of being in the wedding party.
This may be your reality soon, as wedding season looms and events that were postponed or rescheduled because of COVID-19 reappear on the calendar.
Before stressing about these upcoming weddings, take comfort from Crystal L. Bailey, director of The Etiquette Institute of Washington, in D.C.: “ Your loved one would not want you to spend in a way that would make you financially struggle. ”
For less struggling and more celebrating, here’ s how to handle the financial load of attending weddings.
As you learn about upcoming weddings, “ map out your year, ” Bailey says.
This planning is useful if you’ re invited to multiple weddings, or bridal showers, bachelor or bachelorette parties and rehearsal dinners. If you’ re inclined to say yes to everything, this mapping could show how much time ( and money) “ everything ” will cost.
Also check your bank account balance or budget to understand what’ s available to spend after accounting for needs. Ideally, this financial reality check helps you prioritize expenses, says Landis Bejar, a New York City-based licensed mental health counselor and founder of AisleTalk, which provides therapy to individuals getting married.
For example, maybe you realize you can’ t swing the out-of-state bachelorette party but can attend the wedding.
If you still feel compelled to overspend, “ take inventory of where that expectation is coming from, ” Bejar says. “ That can usually help you navigate what’ s important in your decision making. ”
For example, perhaps this reflection shows that you simply yearn to get out of the house and celebrate after so much quarantining. So you prioritize attending the wedding and feel less pressure to buy a new outfit for it.
Prioritizing your values may help you save money. So, if being present at the wedding is most important, you may be able to trim expenses in these categories:
The most effective way to cut wedding costs? Decline the invitation. That’ s fine, particularly if you’ re more of an acquaintance than a close friend or family member, or if you don’ t want to go.
If you must pass up the wedding of someone you’ re close with, Bailey recommends calling or writing a note. Thank them for the invitation and consider sending a gift.
Bejar suggests seeing if you can participate in other ways. For example, if you can’ t make the destination wedding or shower, maybe you can have champagne delivered to the couple.
Remember: If you can’ t afford the event, “ it doesn’ t mean you’ re a bad friend or a bad person, ” Goren says.
If you wanted to go but couldn’ t come up with a relatively small amount of money — say, for a local event — aim to see the situation as a “ wake-up call, ” he says. After all, how would you handle an urgent expense, like an emergency room visit?
Use this experience as motivation to build financial security, Goren says, so you can afford emergencies and weddings alike. Track your money so you know where it goes, and explore ways to spend less and make more.
Say you’ re close with the betrothed and can’ t afford the wedding or a related obligation, like being in the bridal party. “ The worst thing you can do is have the money fears override the friendship, ” Goren says.
So discuss your money concern with the bride or groom — soon, ideally months before the event.
“ Good friends will understand if you’ re honest and transparent, ” Bejar says. Avoid complaining or making the conversation about you. Instead, ask what’ s most important to your loved one, then brainstorm and possibly compromise.
For example, maybe your friend most values your presence at the wedding and is OK with you passing on bridesmaid duty ( and the hair, makeup and outfit expenses that may come with it).
Whether you find solutions or not, Bejar suggests acknowledging the importance of this milestone. “ Brides and grooms want to feel special, ” she says. | general |
Dyadic Reports 2021 Year End Results and Recent Company | March 29, 2022 16:00 ET | Source: Dyadic International, Inc. Dyadic International, Inc.
JUPITER, Fla., March 29, 2022 ( GLOBE NEWSWIRE) -- Dyadic International, Inc. ( “ Dyadic ”, “ we ”, “ us ”, “ our ”, or the “ Company ”) ( NASDAQ: DYAI), a global biotechnology company focused on further improving, applying and deploying its proprietary C1-cell protein production platform to accelerate development, lower production costs and improve the performance of biologic vaccines and therapeutics today announced its financial results for year end 2021 and highlighted recent Company progress.
Mark Emalfarb, Dyadic's President and Chief Executive Officer, said, `` The C1-cell protein production platform has the potential to address the ongoing need to affordably and rapidly produce vast amounts of vaccines in response to emerging infectious disease threats. We are very encouraged by the growing industry interest and broad commercial possibilities of leveraging our C1-cell protein production platform and our other technologies for use in manufacturing a growing number of vaccines, antibodies, therapeutic proteins and other biologic products. Dyadic continues to develop both strategically and operationally, enhancing our business development and scientific capabilities enabling us to focus our 2022 operating plan on human and animal health, while leveraging other biomolecule market opportunities. As such, we believe that Dyadic has the potential to reshape the current landscape of biomanufacturing. In the meantime, we are pivoting from successfully demonstrating the safety of C1-cells in the production of antigens that are safe, effective, and protective in animals to demonstrating positive human safety data for C1-cell produced proteins with the anticipated initiation of the DYAI-100 Phase 1 clinical trial. ”
Dyadic appointed Joseph Hazelton as the Chief Business Officer in November of 2021. Mr. Hazelton was brought on to lead Dyadic’ s transition from research and development activities into commercialization endeavors. With over 20 years in the pharmaceutical industry, Mr. Hazelton brings extensive commercial, operational, and leadership experience to expand Dyadic’ s business development opportunities for the C1-cell protein production platform across the company’ s core verticals of Human Health, Animal Health, and Industrial Enzymes.
Cash Position: As of December 31, 2021, cash, cash equivalents, and the carrying value of investment grade securities, including accrued interest were approximately $ 20.4 million compared to $ 29.2 million at December 31, 2020.
Revenue: Research and development revenue for the year ended December 31, 2021, increased to approximately $ 2,404,000 compared to $ 1,602,000 for the year ended December 31, 2020. At December 31, 2021, the Company recorded the $ 500,000 upfront payment received from the collaboration and license agreement with Janssen as deferred license revenue.
Cost of Revenue: Cost of research and development revenue for the year ended December 31, 2021, increased to approximately $ 1,944,000 compared to $ 1,425,000 for the year ended December 31, 2020. The increase in revenue and cost of research and development revenue for the year ended December 31, 2021, was due to a number of larger research collaborations conducted in 2021. There was no provision for contract losses for the year ended December 31, 2021.
R & D Expenses: Research and development expenses for the year ended December 31, 2021, increased to approximately $ 8,392,000 compared to $ 3,868,000 for the year ended December 31, 2020. The increase primarily reflected the engagement of a contract research organization and pharmaceutical quality and regulatory consultants to manage and support pre-clinical and clinical development as well as an increase in cGMP manufacturing costs as the Company moves towards its anticipated Phase 1 clinical trial of DYAI-100 COVID-19 vaccine candidate in the amount of approximately $ 5,145,000 offset by a decrease of $ 621,000 in other internal research and development costs.
G & A Expenses: General and administrative expenses for the year ended December 31, 2021, increased 10.1% to approximately $ 6,698,000 compared to $ 6,085,000 for the year ended December 31, 2020. The increase principally reflected increases in legal expenses of $ 447,000, insurance premiums and other outside services of $ 220,000, payroll and share based compensation related costs of $ 40,000, offset by reductions in business development and investor relations costs of $ 94,000.
Foreign Currency Exchange: Foreign currency exchange loss for the year ended December 31, 2021, was approximately $ 97,000 compared to $ 62,000 for the year ended December 31, 2020. The increase reflected the currency fluctuation of the Euro in comparison to the U.S. dollar.
Interest Income: Interest income for the year ended December 31, 2021, decreased to approximately $ 52,000 compared to $ 447,000 for the year ended December 31, 2020. The decrease was primarily due to a decrease in interest rate and yield on the Company’ s investment grade securities, which are classified as held-to-maturity.
Other Non-Operating Items: For the year ended December 31, 2021, the Company recorded a gain from the sale of its investment in BDI in the amount of approximately $ 1,606,000.
Net Loss: Net loss for the year ended December 31, 2021, was approximately $ 13.1 million, or $ ( 0.47) per share, compared to a net loss of $ 9.3 million, or $ ( 0.34) per share, for the year ended December 31, 2020.
Date: Tuesday, March 29, 2022Time: 5:00 p.m. Eastern TimeDial-in numbers: Toll Free: 877-407-0784 International: 201-689-8560Conference ID: 13727862
Webcast Link: https: //themediaframe.com/mediaframe/webcast.html? webcastid=NtIEiElb
An archive of the webcast will be available within 24 hours after completion of the live event and will be accessible on the Investor Relations section of the Company's website at http: //www.dyadic.com. To access the replay of the webcast, please follow the webcast link above.
Dyadic International, Inc. is a global biotechnology company which is developing what it believes will be a potentially significant biopharmaceutical gene expression platform based on the fungus Thermothelomyces heterothallica ( formerly Myceliophthora thermophila), named C1. The C1 microorganism, which enables the development and large-scale manufacture of low-cost proteins, has the potential to be further developed into a safe and efficient expression system that may help speed up the development, lower production costs and improve the performance of biologic vaccines and drugs at flexible commercial scales. Dyadic is using the C1-cell protein production platform and other technologies to conduct research, development and commercial activities for the development and manufacturing of human and animal vaccines and drugs, such as virus like particles ( VLPs) and antigens, monoclonal antibodies, Fab antibody fragments, Fc-Fusion proteins, biosimilars and/or biobetters, and other therapeutic proteins. Certain other research activities are ongoing which include the exploration of using C1 to develop and produce certain metabolites and other biologic products. Dyadic pursues research and development collaborations, licensing arrangements and other commercial opportunities with its partners and collaborators to leverage the value and benefits of these technologies in development and manufacture of biopharmaceuticals. As the aging population grows in developed and undeveloped countries, Dyadic believes the C1-cell protein production platform may help bring biologic vaccines, drugs, and other biologic products to market faster, in greater volumes, at lower cost, and with new properties to drug developers and manufacturers, and improve access and cost to patients and the healthcare system, but most importantly save lives.
Please visit Dyadic’ s website at http: //www.dyadic.com for additional information, including details regarding Dyadic’ s plans for its biopharmaceutical business.
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, including those regarding Dyadic International's expectations, intentions, strategies, and beliefs pertaining to future events or future financial performance. Actual events or results may differ materially from those in the forward-looking statements because of various important factors, including those described in the Company's most recent filings with the SEC. Dyadic assumes no obligation to update publicly any such forward-looking statements, whether because of new information, future events or otherwise. For a more complete description of the risks that could cause our actual results to differ from our current expectations, please see the section entitled `` Risk Factors '' in Dyadic's annual reports on Form 10-K and quarterly reports on Form 10-Q filed with the SEC, as such factors may be updated from time to time in Dyadic's periodic filings with the SEC, which are accessible on the SEC's website and at www.dyadic.com.
Dyadic International, Inc.Ping W. RawsonChief Financial OfficerPhone: ( 561) 743-8333Email: ir @ dyadic.com
DYADIC INTERNATIONAL, INC. AND SUBSIDIARIESCONSOLIDATED STATEMENTS OF OPERATIONS
See Notes to Consolidated Financial Statements in Part I of Dyadic's Annual Report on Form 10-K filed with Securities and Exchange Commission on March 29, 2022.
DYADIC INTERNATIONAL, INC. AND SUBSIDIARIESCONSOLIDATED BALANCE SHEETS
See Notes to Consolidated Financial Statements in Part I of Dyadic's Annual Report on Form 10-K filed with Securities and Exchange Commission on March 29, 2022. | general |
The future of work is flexible: Hybrid is here to stay | A Cisco-commissioned study with MIT Sloan Management Review highlights progress toward the future of work. Now comes an equal challenge: building on its promise.
Hybrid work is the most transformative workforce trend in a generation. It promises a more inclusive, flexible, and collaborative future. Yet I fear that we could regress if work cultures fail to evolve at the pace of technology change, and leaders don’ t adapt to the evolving “ mixed mode ” with some people in the office and others at home ( or anywhere else they choose).
Despite all of its challenges and tragedies, the COVID-19 pandemic unveiled what’ s possible with work. Much of the global workforce moved to remote work all but overnight. And despite fears to the contrary, we proved that we can be more productive than ever before. But now comes an equally difficult part — building on the knowledge gained these past two years to build a future of work that’ s great for everyone, regardless of where they happen to be.
To shed some light on current attitudes about work and how leaders can prepare for what’ s coming, MIT Sloan Management Review and Webex by Cisco conducted a comprehensive survey. Its 1,561 respondents ranged from corporate directors and C-level executives to supervisors, managers, and individual contributors — all from a variety of industries and spread across 12 countries.
The results reveal much about what’ s going right — and what isn’ t.
For starters, 59 percent still consider the ability to work from a place of their own choice to be a benefit, while only 36 percent believe it’ s a given. Seventy-five percent said that working remotely gives them a sense of not being “ in the know. ” And another 72 percent feared a pay gap between hybrid workers and their in-office counterparts.
For us to fully reap the rewards of hybrid work, there should be no difference in where you choose to work. That means seamless, secure technology — in the office and remotely — that dissolves the distance between people. And it means a culture that supports this new paradigm.
The emerging mixed mode will be harder to manage than when everyone was in the office — and harder than when everyone was working remotely. So, organizations will need to be more aware of how their physical spaces are laid out as well as the quality of experience for those working from afar. And meetings will need to be better organized and facilitated — to avoid burnout and to ensure that everyone has a voice ( not just the loudest person in the physical meeting room).
That means that organizations will need to ensure that no one feels left out because of their geography, language, personality, disposition, or any other differences. Because if anyone feels unable to fully contribute due to any of those differences, that will be a great loss — and a setback for the progress that we’ ve made over the past couple of years to this dimension of inclusivity.
The good news is that many companies have done a good job of preserving their cultures despite moving to a dispersed workforce. In Cisco’ s survey with MIT, a majority said that camaraderie, closeness to the organization, and feelings of inclusion and diversity have improved, or at least stayed the same, since the pandemic began. They also applauded their leaders’ ability to model empathy, work-life balance, and candid discussions.
But I think we need to do more. Moving forward, there may be team members who will never even meet face to face. But close human connections will still need to be cultivated, so that interactions and engagements aren’ t simply transactional. Leaders need to build relationships and establish trust. And that emotional intelligence needs to be fundamental to company cultures.
At the same time, the office still matters. In the study, respondents cited in-office benefits like face-to-face creativity, collaboration, and learning. But the office experience needs to be great to get people to go there. That comes down to more welcoming physical layouts, better technology, and more inclusive, empathetic in-office cultures. The days of rigid hierarchical structures and 9 am-5 pm, Monday through Friday working weeks are gone. People demand the freedom to meet one, two, three, or zero days in the office, if that’ s what suits their lifestyle. ( And the Great Resignation shows that they mean business.)
These changes culminate in a profound evolution in work. But I believe that the full dimension of hybrid work has not yet been completely grasped. If we get it right, the ultimate benefit will be in ensuring that anyone anywhere can participate in the global economy. Because it’ s about leveling the playing field — whether someone is in Silicon Valley or three thousand miles away.
We are beginning to see more and more companies evolve in these directions. And the ones that don’ t evolve their technology and cultures won’ t be able to attract the best talent — or customers. And leaders that can’ t manage highly diverse and distributed teams with empathy and open communication will not advance.
As culture change evolves, so does technology. I’ m excited at how new innovations can help support equal collaboration in a meeting — regardless of who is or isn’ t in the office. For example, innovations like background noise reduction and real-time language translations go a long way to foster inclusivity. In the office, intelligent video cameras can zero in on individuals and ensure they are being seen and given a chance to speak. And technology can ensure meetings are more interactive. Looking forward, we can expect a hyper-real 3D experience that will blur the lines between face-to-face and virtual experiences, to the point where the technology itself will be rendered all but invisible.
In a few years, we’ ll look back at how we once communicated with dozens of two-inch-by-two-inch video images on a square screen and laugh. The progress in augmented reality and holograms will move fast. And no doubt there’ s plenty of exciting stuff we haven’ t even imagined yet.
In short, hybrid work is here to stay, and there’ s no going back. So, be sure your technology and culture are ready.
Jeetu Patel is EVP and General Manager of Security & Collaboration at Cisco
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Snowflake readies Amazon retail data for demand forecasting | To further strengthen our commitment to providing industry-leading coverage of data technology, VentureBeat is excited to welcome Andrew Brust and Tony Baer as regular contributors. Watch for their articles in the Data Pipeline.
Cloud data warehouse darling Snowflake has been investing a lot in its data ecosystem. Yesterday, the company made a broad announcement around the launch of its Retail Data Cloud, which integrates the core Snowflake platform with partner-delivered solutions and industry-specific datasets. Today, the company is announcing an important initiative within that rollout, which it shared exclusively with VentureBeat: it’ s partnering with Amazon Web Services ( AWS) to bring Amazon.com sales channel data directly into customers’ Snowflake data warehouse instances.
This is a data-driven age for retail, a phenomenon accelerated by the pandemic and the twists and turns COVID has created in buyer preferences and purchasing patterns. The provision of the Amazon.com data is intended to help retail and CPG ( consumer packaged goods) customers not only monitor Amazon.com Vendor Central PO data, but also leverage Amazon Forecast functionality within their Snowflake environments.
The offering enables sophisticated demand forecasting and helps manage upstream logistics, including lead times for manufacturing and delivery. The companies also explain the data enables customers to track product weight or dimension changes; reduce on-time in-full ( OTIF) penalties/improve OTIF metrics; and ensure high-sales SKUs ( items) stay in-stock. Such analyses can help companies mitigate the impact of supply chain irregularities and improve the all-important customer experience.
As the folks from Snowflake and AWS tell the story, this initiative is about way more than raw data feeds. Rather, it provides a collection of high-value data sets that have already gone through significant data integration processes to help customers avoid pulling and blending data from multiple accounts.
The data also goes through significant data engineering processes that make it analysis-ready right out of the gate. The result: retail brands and CPG businesses get purchase order history and updates, down to the line item level, as well as granular product catalog metadata, providing the ability to perform probabilistic PO forecasting at the ASIN ( Amazon Standard Identification Number) or fulfillment center level.
This all goes beyond abstract concepts expressed in a press release. In fact, in an exclusive briefing with VentureBeat, Rosemary Hua, global head of Retail & CPG at Snowflake, and Justin Honaman, head of Worldwide Consumer Packaged Goods at AWS, showed how BI tools could be used directly against the Amazon retail data. Creating visualizations of demand against current stock levels, or top-selling product forecast shortage by geographical region ( partially shown in the figure at the top of this post), become fairly straightforward, right from a major BI tool ( Tableau, in the case of screenshots shown to us).
If you’ re interested in the mechanics of all this, they’ re remarkably straightforward. Data is inserted directly into customer Amazon S3 buckets. From there, Snowflake can detect the presence of the data, determine its schema and automatically refresh the latter as necessary. Customers then have the ability to use and analyze the data in a standalone fashion or join it to data from other, third-party sources in the Snowflake Data Marketplace.
When it comes to looking at the cloud data warehouse market, it’ s fairly easy to focus on which competitor has the most born-in-the-cloud solution, the best enterprise-class performance and pedigree, or the smoothest combination of the two. But maybe the contest between those sets of criteria misses the point.
The technology, including its performance and features, is critical, of course. But so too is the partner ecosystem and, yes, the data. Enterprise application companies like SAP and Oracle appreciate that, offering analytics in the context of transactional data. Snowflake seems to see that value too. Perhaps, as an independent cloud data warehouse provider, emphasizing its partner and data ecosystem is Snowflake’ s biggest innovation. If we look past the core platforms themselves, and take seriously the notion of what a “ data cloud ” really means, then maybe the metrics and dimensions of the cloud data warehouse market start to change.
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Salesforce offers the Glue for virtual collaboration | GamesBeat Summit 2022 returns with its largest event for leaders in gaming on April 26-28th. Reserve your spot here!
Roasting marshmallows around a fire pit: Not necessarily the most conducive scenario for serious business discussions.
Or so you might think.
But that’ s exactly what Salesforce has experienced with its customers when using the Glue Collaboration virtual collaboration platform. Attendees of the software giant’ s virtual expos and meetings have gathered in woodsy, wildflower-blooming environs to discuss customer relationship management ( CRM) software, use cases, and strategy — sometimes when calmly toasting the central ingredient for s’ mores over a campfire.
“ This is one of the most popular places, ” Nick Botter, chief innovation officer and retail lead for Northern Europe for Salesforce, said during a recent demo of the virtual environment for VentureBeat. “ People love this, they can sit here in this beautiful natural environment, put their feet up, roast marshmallows and have quite a relaxed discussion. ”
Not long before the onset of COVID-19, many companies, including Salesforce, were focused on cultivating engaging, in-person experiences at their various global locations and events.
Now, just the fact that we use the term “ in-person experiences ” indicates how much the world has changed in such a short time. To adapt, Salesforce — which has commanded a global physical presence with its giant office towers and expos drawing attendees in the tens of thousands — is leading the charge in its adoption of VR and AR tools.
Over the last year, the CRM leader has implemented virtual collaborative tools developed by Finland company Glue Collaboration. These create “ true presence ” with spatial audio and customizable, 3D avatars that mimic the gestures and movements of their users while sharing media, notes and presentations both live and asynchronously.
When COVID-19 hit and remote work became the norm, “ it was very difficult to have a really good group discussion — our brain is just not wired to look into a camera the whole time, ” said Botter. “ We had a vision to build these immersive environments. ”
The use of AR and VR has been growing exponentially in recent years, and that trend is only expected to continue: According to Technavio, the AR/VR market size will be $ 162.71 billion by 2025, representing a 46% compound annual growth rate ( CAGR) since 2020. Furthermore, Superdata says that the enterprise sector will generate more than 70% of the overall AR/VR revenue by the end of 2022.
Glue, which was founded in 2016 and is supported by $ 8 million in investments from Maki.vc, Reaktor Innovations, Tesi, Braigel Brothers, Foobar.vc and angels, is helping fuel this trend with its remote presence technology. Competing with the likes of The Wild, Party.Space, Yullo, Breakroom, and Facebook Horizons, the company’ s platform combines immersive 3D graphics, VR and cloud computing technology to allow companies to “ maximize their collaboration potential, ” said Jussi Havu, CEO of Glue.
Whereas organizations used to spend more than $ 1.3 trillion a year on business travel, “ Now they are faced with the remote engagement pain points of ‘ Can you hear me now?’ and ‘ Oh sorry, you go first…ok, I can go first,’ ” said Havu. “ Dispersed teams are burdened by ‘ Zoom fatigue.’ ”
“ The way we work has fundamentally changed, ” said Havu. “ Remote is the new norm. Our social interactions are becoming predominantly virtual. This is also impacting the way we work and do business. ”
Leveraging its team’ s broad background in advertising and movie production environments, CGI, graphics, video games and enterprise-level security platforms, Glue tested its first commercial pilots in 2019.
The company today counts among its customers Deutsche Telekom, Axel Springer, and Salesforce — the latter choosing its platform, Botter said, because of its capabilities with spatial audio, which mimics real multidimensional sound.
As Havu explained, Glue offers about a dozen different templates, but users can create custom platforms as well. Salesforce, for its part, has digitally replicated its San Francisco tower and Dreamforce expo. It is also in the process of building an environment that provides a more dynamic, customer-tailored demo space. For example, it could mimic a manufacturing plant with assembly lines, or an oil platform with working rigs.
These platforms provide venues for larger creative workshops and smaller roundtables, and are used in a mix of in-person meetings and collaborations via Zoom, Google Hangouts and Slack for groups of roughly five to 40 people.
“ We’ ve been able to gather all these people, create moments for smaller groups, bigger groups, one-on-one interactions, ” Botter said. “ They really have the feeling that they are connected with each other, but without the travel. ”
In the Dreamforce expo platform, for instance, customers start out in “ Dreamforce Park, ” then traverse along a stone walkway through groves of pine trees and patches of wildflowers surrounded with fluttering butterflies.
Botter explained of the backdrop: “ The idea is that we came out of the pandemic into new beginnings, sprouting new flowers. ”
Along the way, user pass billboards with automatically uploaded, industry-relevant customer stories, watch videos, converse in “ mindfulness corners, ” and request more information by tapping big red buttons. They can virtually high-five each other, and avatars gesture along with their movements ( either as they gesticulate or shift their gaze to a group’ s dominant speaker).
Meanwhile, the Salesforce tower platform features a seating area in a pavilion with floor-to-ceiling windows offering sweeping views of San Francisco Bay. Users can even pour themselves virtual cups of coffee before gathering in a presentation area, settling into casual clusters of tables and chairs, or gazing out the windows at iconic city landmarks including Alcatraz and the Golden Gate Bridge. Botter himself, who was once based in the Golden City but now works out of Amsterdam, noted that he sometimes uses the platform for scenic purposes: “ I miss San Fran, sometimes I go and look at the city that I miss. ”
Salesforce relied heavily on its real estate and marketing departments in designing the spaces, and the physical limitations ( or lack thereof) took some getting used to. For instance, the ceiling could be raised in the Salesforce tower without concerns for heightened earthquake impact.
“ You can really play with the environments, ” Botter said.
However, he stressed: “ When we started doing this, we didn’ t want to build a gimmick. We thought it should be fun, but that it should also be useful and bring value to us and our customers. ”
To that end, users can draw on whiteboards and take advantage of tools including screen shares, giant sticky notes and freehand 3D drawings. These materials can all remain in the platform for as long as users need them, or be exported via the web user interface to various supported file formats. The platform will also eventually include automatic note-taking capabilities, Havu said.
“ The future will be about these systems being smarter and understanding what is happening in meetings and trainings, making participants more productive, ” he said.
How many people can be involved and what can be done with the technology will be dependent upon how fast hardware becomes more affordable and scalable, he added. Enterprise is also still learning what can be done with VR and AR and the implications when it comes to spatial anchors and retention — which has shown to be higher compared to reading a book, watching a video or attending a lecture.
But overall, Havu emphasized, “ We’ re not expecting this to remove the need for other existing communication tools. They all have certain use cases and purposes. This will just be one tool in an information user’ s toolbox. ”
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PwC says work needs to be reinvented to make it fairer — Quartz at Work | When PwC released its 2022 Women in Work Index, the big reveal—that women had been set back by the pandemic by at least two years—was depressing, yes, but surprising? No.
By now, we all know that the imperatives of caregiving dragged more women than men out of the workforce, and kept them there. We’ ve all read the stats which show that industries which employ more women, like hospitality, were hardest hit, and even in other sectors companies fired more women than men.
We know that people of color were hit worse than white people in rich societies. And we’ ve heard so many calls for retraining, up-skilling, and general system-tweaking that would help get more women into growth areas of the workforce, that it’ s hard to focus on the substance of them any more.
But Larice Stielow, a senior PwC economist and the lead author of the report, is calling for something more radical than tweaks. The pandemic, she said, was the biggest thing to happen to work since the global financial crisis back in 2008. What’ s coming down the road—automation, and a wholesale change to a “ net zero economy ” as PwC phrases it—means that work has to change. This is an opportunity to make a plan.
Companies need to recognize that this post-pandemic moment is “ a real opportunity to design a future world of work that actually works better for women, ” Stielow said.
That means urgently re-thinking leave and flexibility policies. Crucially, flexibility to arrange work around caregiving and emergencies needs to be available to everyone, not just women. Mothers with children under 12 were three percentage points more likely to leave the workforce during Covid than similar fathers, the PwC report found, while there was only a negligible difference in every other group: Proof that a big reason for women leaving was “ the burden of unpaid care work. ”
Paid parental leave, meanwhile, should follow the Icelandic model where both parents get equal paid leave on a “ use it or lose it ” basis, meaning more fathers take longer leaves and women’ s careers take a smaller hit, Stielow said. Affordable child care is the third part of the puzzle.
Governmental change takes a very long time, Stielow said, so companies can prove themselves progressive by leading the way on this change, and enhancing their reputation and attracting talent in the process.
Business already knows it needs to do more to make the workplace—from hiring policies to company culture—fairer for minorities.
But as companies plan their next big transitions—the post-covid return ( or not) to offices, increased automation, and a much greater focus on sustainability—they have the opportunity to make plans that actually lead to equality, instead of maintaining the current unequal system. In the UK, for example, PwC discovered that unemployment had fallen over the past decade for every group except ethnic minority women, for whom it had risen. Those women were also paid almost 15% less than white men even when controlling for education, job title, and just about everything else the economists could think of.
Take the transition to net zero—whereby economies stop adding to the emission problem wrecking the climate—as an example: All the key areas of job growth like utilities, construction and manufacturing, are male-dominated, and without a concerted effort the transition to net zero will widen existing gaps in unemployment and pay. PwC suggests looking to women and ethnic minority women especially, in adjacent sectors that have transferrable skills.
“ If we don’ t now plan for the gender impacts of the net zero transition we’ re only going to further increase the disparity and the job inequality between men and women, ” Stielow said. | tech |
Is this the most outrageous tipping request you’ ve ever heard? ' I looked at the sales person with a confused expression ' | Dear Quentin,
I read
your response
to the person who was asked to tip using a touchscreen in a coffee house and an ice cream parlor, among other places. I also have a story.
I recently paid $ 3,000 for new windows. When the salesman came by to collect the payment and see that the job was completed, he handed me his payment device. There were “ 15%, 20% or other ” tipping options across the top.
I looked at the sales person with a confused expression, and I tilted the device to show my husband. I could not believe they were asking for a tip on a $ 3,000 purchase! Is this the most outrageous tipping request?
I love the new windows, but I probably won’ t use that company again. Was I wrong to refuse to tip?
Still in Disbelief
Dear Disbelief,
It’ s not customary to tip people who work on your home, whether they’ re installing windows or putting in a new kitchen, but if you are pleased with the results and liked the contractors in question and bonded with them over a cup of tea, it’ s not out of the question to tip them a nominal amount ( approximately $ 50 each). The reason is that they are often paid an hourly rate by the company, and their labor is baked into the price.
It may be that the window-pane company was using software that included a tipping option and it was there “ accidentally on purpose, ” or they genuinely overlooked it as a potential problem, given that such digital tipping has become so ubiquitous. If a person installs your air conditioner, you might happily tip. But if the A/C installer asked for one? Yes, I would also regard that as overstepping. If you liked their work, don’ t let it stop you from employing them again.
In a survey of 5,000 home professionals released last month by the online marketplace Angie’ s List, home remodelers said they only expect a tip 6% of the time, while only 7% of painters and handymen said they expected a tip. Plumbers, electricians and the cable guy don’ t expect tips, the survey said. Ditto interior decorators. You could choose to give a gardener or house cleaner a little extra every visit or — as many people likely do — wait until the holidays to give them a bonus.
If you had a good experience and want to tip, no contractor will refuse it. “ It’ s still OK to tip contractors if they go above and beyond to provide outstanding service, or even if you just feel like it, ”
according to Angie’ s List
. “ How much you should tip is very much up to you. Was it a big job? Did they have to deal with terrible weather? Was it back-breaking work? What extra services did they perform? Do you simply feel like showing some extra gratitude today? ”
The upside of having a tipping option is that you are free to silently choose “ No tip. ” Your experience is not so dissimilar from someone handing you a credit-card receipt with a tipping option to sign in a department store or a bodega. In those circumstances, most people would draw a line through the space for a tip. Your window-company representative did not
ask
for a tip.
If you do not wish to tip, tap each option as gingerly as you can, and employ your best poker face.
Yo
u
can email The Moneyist with any financial and ethical questions related to coronavirus at qfottrell @ marketwatch.com, and follow Quentin Fottrell on
Twitter.
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‘ We’ ve been left out in the cold’: My mother named my sister beneficiary of her estate, but wrote a letter wishing to divide it among her 3 children. What now?
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‘ She had a will, but it was null and void’: My friend and her sister are fighting over their mother’ s life-insurance policy and bank account. Who should win out? | business |
Cruise Ship in Santa Barbara Harbor Gets F Grade - The Santa Barbara Independent | Failing Grade Due to Residual Air and Water Quality
The cruise ship bobbing offshore of Santa Barbara Harbor on Tuesday got a grade of F from Friends of the Earth for the air and water quality it leaves in its wake, failing grades called out by the watchdog nonprofit Santa Barbara Channelkeeper in a press release.
Many of the ships slated to arrive through May have been given D or F grades in the annual survey conducted by Friends of the Earth.
Cruise ships are also tracked by the Centers for Disease Control, which rated today’ s vessel — the Koningsdam, operated by Holland America — with a middling “ orange ” status. The ship was considered “ highly vaccinated ” but reported enough cases of COVID-19 to come under investigation and observation.
The City of Santa Barbara asks each ship’ s captain to sign an agreement to respect the “ no discharge ” guidelines regarding pollution within 12 nautical miles of shore, and that the Harbor Patrol would be notified if any discharge or incineration took place.
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Erik Engebretson, manager of the city’ s Harbor operations, said that if violations are brought to his office, they would be “ investigated to the full extent of the law. ”
Santa Barbara Channelkeeper’ s research vessel goes out to meet some of the visiting ships, a program it has relaunched this year. “ The cruise-ship captains are generally polite, though surprised, to encounter our team, ” said Ben Pitterle, science and policy director for S.B. Channelkeeper. “ It’ s clear that they aren’ t used to being monitored. ”
Ships get rid of hundreds of thousands of gallons of laundry, shower, and bilge water and treated sewage, according to Channelkeeper. On-board incinerators are used to burn trash, which causes air pollution, though some are equipped with scrubbers to reduce the pollutants, said Ted Morton, executive director of S.B. Channelkeeper.
The voluntary program has a new request that asks that ships slow to no more than 10 knots to avoid striking whales within the 12-mile limit, Pitterle said.
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Catherine the Great was a pioneer of inoculation | The Empress and the English Doctor. By Lucy Ward. Oneworld Publications; 352 pages; $ 30 and £20
THE MOST dramatic showdown between humans and smallpox probably took place in Europe in the 18th century. The disease had by then been gathering momentum for a couple of hundred years, and despite the advent of the first effective tool for stopping it in its tracks—inoculation—it embarked on a spree of regicide, diverting more than one royal house’ s line of succession.
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So recounted Donald Hopkins in his encyclopedic history of the disease, “ Princes and Peasants ”, published in 1983. Now Lucy Ward has zoomed in on one of the more dramatic episodes in that dramatic century, blowing it up to book length. Whether it merits retelling in such detail is debatable, but Catherine the Great of Russia’ s decision to get both herself and her son inoculated certainly resonates in these contagious times. It marked a watershed in popular acceptance of the prophylactic technique and showed the power of leadership by example. Irresponsible rulers of the covid-19 era could take a leaf out of the empress’ s book.
Born in Prussia, Catherine was on a drive to modernise her adopted country, and as the first reigning European monarch to volunteer herself—as well as her offspring—for inoculation, she was taking a brave step and a calculated risk. The procedure involved smearing pus from an infected person’ s blisters into small incisions in a healthy person’ s skin. It was far safer than catching the disease naturally, but not as safe as vaccination, which would develop out of the inoculation method and used the related but milder cowpox virus to confer protection.
Smallpox at that time was often lethal. When it did not kill, it could blind or disfigure. So when, in 1768, the English doctor Thomas Dimsdale was summoned to St Petersburg to do the honours, he had understandable qualms about the assignment. Catherine assured him that a yacht would be standing by in the Gulf of Finland, ready to whisk him out of Russia should anything go wrong.
Nothing did go wrong, and once the clandestine procedure was deemed a success, news of it was broadcast from the onion-domed rooftops. There were fireworks and religious blessings, poems and plays were penned, a national holiday was declared. Voltaire wrote to Catherine, his longtime correspondent, lamenting the French ban on the technique: “ You have been inoculated with less fuss than a nun taking an enema. ”
Ms Ward’ s vivid and well-told story raises the interesting question of who deserves credit for inoculation. The aristocratic Mary Wortley Montagu had brought it back to England earlier in the century, having seen elderly Turkish women perform it on her travels. English medics then modified it—making it more rather than less dangerous.
But an enterprising layman, Daniel Sutton, stripped away the modifications to produce the method that Dimsdale publicised and carried to Russia. ( Dimsdale’ s genteel manners and scientific standing made him a better emissary than the less polished, more commercially minded Sutton.) In the absence of sufficient numbers of doctors to roll it out in Russia, after inoculation caught on, peasant women were deputised to help once again—only now to perform a technique that had the stamp of scientific approval.
As so often, many people contributed to the success of the invention. But successful it indubitably was. In the last hundred years of its existence, smallpox is estimated to have killed half a billion people; but in Russia, Catherine’ s gesture made inoculation fashionable and later led to the rapid adoption of vaccination. In this way she helped set the world on the path to the eradication of the scourge. That milestone was announced in 1980, just over two centuries after she, her son and their doctor risked their lives to demonstrate that disease need not be destiny. ■
All our stories relating to the pandemic can be found on our coronavirus hub.
Published since September 1843 to take part in “ a severe contest between intelligence, which presses forward, and an unworthy, timid ignorance obstructing our progress. ”
Copyright © The Economist Newspaper Limited 2022. All rights reserved. | business |
Envoy: Russian MP's anti-Azerbaijan remarks detrimental to bilateral ties [ PHOTO ] | Russian ambassador to Azerbaijan Mikhail Bocharnikov has said that Russian State Duma MP Mikhail Delyagin's earlier anti-Azerbaijan statement is detrimental to relations between the two countries.
He made the remarks at a press conference in Baku on March 30.
`` I consider such statements detrimental to relations between Russia and Azerbaijan, '' he said.
The ambassador called the MP's remarks unacceptable, adding that they do not reflect Moscow's official position and have already been condemned by the Kremlin and the Russian Foreign Ministry.
Delyagin earlier described Azerbaijan as a “ proxy state ” and suggested launching a tactical nuclear strike on Baku and destroying Azerbaijan’ s oil industry on Russia’ s “ 60 minutes ” political talk show broadcast on Russia 1 TV channel on March 28.
He stressed that Azerbaijan “ needs to be punished for its attempt to open a second front ”. Delyagin accused the country of violating the truce in Karabakh and not observing the trilateral statement signed by Baku, Yerevan and Moscow in 2020. Moreover, the MP called Azerbaijan a “ real danger to Russia ”.
The frenzy was quickly followed by a rebuttal from Russia's Presidential Press Secretary Dmitry Peskov, who urged Delyagin to control his personal emotions and refrain from making hostile statements toward Azerbaijan.
`` This statement is the result of a personal emotional outburst. We would urge you to control your emotions and refrain from making such statements, especially against our partners. Azerbaijan is one of our partner countries, '' Peskov said.
Later, Delyagin apologized for his remarks.
During the same conference, Bocharnikov stated that the Azerbaijan-Russia Declaration on Allied Cooperation, dated February 22, 2022, is bringing the parties ' relations to a new level of development.
According to him, this document has become a key aspect of the meeting of the two countries ' presidents.
`` The provisions of this declaration lay the foundation for our cooperation in accordance with international law, '' he noted.
In response to payment difficulties caused by a change in the ruble exchange rate, Bocharnikov stated Russia's intention to expand banking cooperation with Azerbaijan in national currencies.
He stated that the shift to payments in national currencies will aid in resolving this issue.
According to him, expanding banking cooperation in national currencies in accordance with the declaration will also help to solve the aforementioned problem. He went on to say that positive steps had already been taken in this direction.
The diplomat also spoke about the Russian customs service's March visit to Azerbaijan, during which a pilot project to simplify the customs corridor for participants in foreign economic activity was presented.
Furthermore, Bocharnikov stated that the majority of Russian regions are interested in long-term cooperation with Azerbaijan.
There is great potential for the two countries ' scientific cooperation to grow. Furthermore, relations in the humanitarian sphere are developing, he added.
“ Over the past 30 years, Azerbaijan-Russia relations have developed regularly and successfully in the political, trade, economic, and interregional sectors, '' the ambassador said.
Talking about the 30th anniversary of the establishment of Azerbaijani-Russian diplomatic relations, he suggested holding joint events on this occasion.
Every year, a large number of students leave for Russia under the state quota, and there are joint ties through the Moscow State Institute of International Relations, according to Bocharnikov.
“ We know that our partners are interested in the education of many Azerbaijani young people in Russia, ” he added.
Despite Russia's current unstable foreign trade and economic relations with other countries, Bocharnikov stated that all contracts with Azerbaijan will be fully implemented.
Furthermore, the diplomat stated that Russia supports Azerbaijan's admission as an observer to the Shanghai Cooperation Organization ( SCO).
The ambassador stated that Azerbaijan's closer interaction with the SCO must come from within the country and that joint participation in the organization by Azerbaijan and Russia will help strengthen cooperation in trade, economy, and culture.
“ Azerbaijan has great prestige in the international arena, its authority is growing and joining SCO would correspond to this trend, ” Bocharnikov added.
The ambassador stated in a separate speech that the Azerbaijan Export and Investment Promotion Foundation ( AZPROMO) has developed a concept for information technology cooperation that Russian companies will be able to use.
According to the ambassador, the parties signed a document in 2020 envisioning cooperation in innovations and technologies, with which technology companies are actively cooperating.
Russian innovations, he claims, are in high demand in the Azerbaijani market.
“ All Azerbaijani chain stores operate upon the Russian technologies. Moreover, both countries also cooperate in the field of space, which is of national importance for our countries, ” he added.
Concerning agricultural exports, Bocharnikov stated that Russia's restrictions on wheat exports are only temporary and that all restrictions on the Azerbaijani tomato supply have been lifted.
According to the ambassador, Azerbaijan exported $ 1 billion in tomatoes to Russia in 2021.
`` Azerbaijan's export to Russia increased by 38 percent during the first two months of 2022 compared to the same period in 2021, reaching $ 123 million, '' said Bocharnikov.
He said that Russia is willing to offer Azerbaijan projects for product supply to other markets.
`` It is planned to increase the volume of deliveries of goods by rail and road from Azerbaijan to Russia and in the opposite direction, we are working on this issue. It is also planned to expand trade through the use of maritime transport, '' Bocharnikov said.
He mentioned that the Russian Export Center has tools to support the import of Azerbaijani goods.
`` A solid foundation for trade and economic cooperation will allow us to expand our existing potential, '' Bocharnikov said.
In 2021, the trade turnover between Azerbaijan and Russia amounted to $ 3.3 billion, which is more than before the COVID-19 pandemic, said the diplomat.
Bocharnikov also discussed the opportunities for tourism in the current situation.
He stated that the opening of the Azerbaijani-Russian land border will bring a large number of tourists to both countries.
The ambassador stated that Azerbaijan has always been a popular tourist destination for Russians and that the ability to pay with MIR cards would help with the tourism flow.
`` The flow of tourists from Russia to Azerbaijan has been actively growing lately and the possibility of paying with MIR payment system cards would greatly help to increase the number of Russian tourists in Azerbaijan, '' Bocharnikov said. | general |
Can Germany cope without Russian gas? | OLAF SCHOLZ reacted on March 27th with unusually harsh words to a question by Anne Will, a popular Sunday talk-show host, about studies by economists that suggest an immediate stop of imports of Russian energy would reduce German economic growth by only a modest amount. “ Their view is wrong, ” said Mr Scholz, adding that it was “ irresponsible ” to feed numbers into mathematical models to arrive at this conclusion.
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For several weeks prominent economists have argued passionately among themselves and with Mr Scholz’ s ministers about the possible consequences of banning Russian energy. The government, as well as industrial lobby groups and think-tanks close either to it or to trade unions, argue that a ban would lead to high unemployment, mass poverty and a recession. But some independent economists, as well as a number of opposition politicians, insist that the consequences would be manageable, if substantial.
The debate may yet become moot. On March 30th Robert Habeck, Germany’ s minister for economy and climate, activated the first stage of an emergency plan to manage gas supplies in case Russia turns off the tap. Russia is threatening to do so because Germany and the rest of the G7 are refusing to accept its demand that “ unfriendly ” countries pay for gas in roubles rather than euros or dollars, which sanctions have made it hard for Russia to use.
But if the gas keeps flowing, so will the debate about the morality of buying it. Germany has been importing around €1.8bn ( $ 2bn) -worth of Russian gas, oil and coal a month, thereby helping to finance Vladimir Putin’ s war in Ukraine. Mr Scholz says stopping that would hurt Germany more than Russia, even though other European governments have called for an embargo. This week the IMK, a think-tank close to Germany’ s trade unions, published a study that backs the government’ s gloomy assessment. It says halting energy imports from Russia would cause a deep recession, with GDP shrinking by more than 6% even if alternative suppliers could make up for half of the gas supplied by Russia. These are rough estimates. “ It is impossible to model a stop of gas imports seriously, ” cautions Sebastian Dullien of the IMK.
The IMK finds itself in rare agreement with industrial lobbies such as the BDI, the association of German industry. In early March, Siegfried Russwurm, the BDI’ s boss, warned that talk about an EU embargo on Russian energy is “ playing with fire ” and would harm the EU more than the aggressor. BASF, a German chemicals giant, said that if its gas supply is halved it will need to halt production at the world’ s biggest chemicals plant in Ludwigshafen, which employs around 40,000 people. Hundreds of thousands of related jobs would be in danger. Martin Brudermüller, the boss of BASF, told investors on March 26th, “ There is no way Russian gas can be replaced in the short term. ”
These pessimistic assessments are contradicted by the German Institute for Economic Research ( DIW); a working paper co-written by a group of German and international economists and published by IFO, another research outfit; and ECONtribute, an economics research group involving the universities of Bonn and Cologne. These suggest that German GDP would take a hit of up to 3% if imports of Russian energy were to cease immediately. That is substantially less than the 4.5% decline of German GDP in 2020, the first year of the covid-19 pandemic, which Germany stoically managed to weather.
“ The big problem is gas, ” says Moritz Schularick, one of the authors of the paper. The loss of Russian oil and coal could be managed relatively easily, since they can be replaced by imports from other countries. But Germany gets roughly half its gas from Russia. An increase in gas imports from other countries, the substitution of electricity from coal or nuclear power for the gas-fired sort and a steady refilling of storage facilities over the summer could only make up for 70% of that, he reckons.
The central question is how German industry would cope. Everyone agrees that finding quick substitutes for gas in industrial processes is a daunting task. Yet Benjamin Moll, one of the other authors of the paper, notes that during the second world war the American economy showed an astonishing ability to adapt to similar shortages. When in 1940 America’ s president, Franklin Roosevelt, demanded that American firms produce 50,000 fighter planes a year, economists deemed his request insane, because yearly aircraft production for the military in 1939 was fewer than 3,000. By the end of the war America had produced 300,000 fighters.
In an interview with Welt am Sonntag, a weekly newspaper, Wolfgang Schäuble, a former finance minister, argues that people sometimes have to make substantial sacrifices for their way of life and their freedoms. Moreover, prolonging the war in Ukraine is also costly for European economies. “ There are lots of hidden costs because of the uncertainty, ” says Luis Garicano, a Spanish member of the European Parliament, who backs an immediate EU energy embargo. Mr Garicano fears that such an embargo will only happen after Russia further escalates its brutal war. “ We should not wait for that, ” he says. ■
Correction ( April 4th 2022): A previous version of this article stated that America produced 300,000 fighter planes annually.
Published since September 1843 to take part in “ a severe contest between intelligence, which presses forward, and an unworthy, timid ignorance obstructing our progress. ”
Copyright © The Economist Newspaper Limited 2022. All rights reserved. | business |
Fourth COVID-19 mRNA vaccine dose approved for all older Americans | The U.S. Food and Drug Administration ( FDA) has authorized a fourth mRNA vaccine dose for all individuals aged 50 and over. The authorization includes both Pfizer and Moderna vaccines and is recommended to be administered at least four months after a third dose.
As the United States continues to experience a downturn in COVID-19 cases and hospitalizations following the sharp Omicron spike at the beginning of the year, epidemiologists are warning of a looming new wave. The Omicron variant BA.2 is rapidly becoming dominant in the US and, as demonstrated in several countries around the world, it has the potential to cause significant new surges in hospitalizations and deaths.
A third mRNA vaccine dose has been shown to be crucial in generating robust protection against the Omicron variant, but that protection has been seen to wane after three to four months. At the end of 2021 Israel began rolling out a fourth vaccine dose to some older or at-risk populations and early data has indicated the extra dose could be helpful for more vulnerable individuals.
“ Current evidence suggests some waning of protection over time against serious outcomes from COVID-19 in older and immunocompromised individuals, ” said Peter Marks, head of the FDA’ s Center for Biologics Evaluation and Research. “ Based on an analysis of emerging data, a second booster dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine could help increase protection levels for these higher-risk individuals. ”
The FDA authorization is calling the fourth dose a “ second booster, ” and is targeting all “ individuals 50 years of age and older ” who are at least 4 months past their previous vaccine shot. For those under the age of 50 the authorization is much more limited, focusing only on those aged 12 and older with particular medical conditions that leave them in highly immunocompromised states.
“ These are people who have undergone solid organ transplantation, or who are living with conditions that are considered to have an equivalent level of immunocompromise, ” the FDA authorization stated.
The fourth dose authorization notably cites a lower age cut-off than was expected following a recent application by Pfizer looking only at boosters for those aged over 65 years. In a recent press conference Marks addressed the lower age range by pointing out one in three people between the age of 50 and 65 suffer from pre-existing health conditions that are known to increase their risk of severe COVID-19. So, by authorizing a fourth dose for those 50 and over he hopes to protect a large population of vulnerable individuals in that age bracket.
Rochelle Walensky, director of the Centers for Disease Control and Prevention ( CDC) echoed Marks’ comments in a statement announcing updated CDC recommendations regarding COVID-19 vaccines.
“ Boosters are safe, and people over the age of 50 can now get an additional booster 4 months after their prior dose to increase their protection further, ” Walensky said. “ This is especially important for those 65 and older and those 50 and older with underlying medical conditions that increase their risk for severe disease from COVID-19 as they are the most likely to benefit from receiving an additional booster dose at this time. ”
Sources: FDA, CDC | science |
How This Founder Is Bringing Automation to Sales Teams | Welcome to Inc.'s Founders Project podcast with Alexa Von Tobel, where we bring you tales of guts, inspiration, and drive that define the entrepreneurs building the future. Each week, we dig into a founder's professional playbook and uncover what makes them tick. On this week's episode:
In 2015, Amit Bendov was not looking to start a company. But he was looking for a way for his sales team to more automatically capture CRM data. So he and his co-founder ended up launching Gong to help sales teams have better conversations with customers and win more deals. Gong quickly found product-market fit, which only accelerated when Covid pushed most sales calls to a digital format. Gong has since grown to over 2,000 customers with a valuation north of $ 7 billion. Bendov shares why he charged early customers a high price to stay in beta, why he believes autonomous applications are the way of the future, and why you learn more from successes than failures. | business |
Processa Pharmaceuticals Announces Year-End 2021 Results | March 30, 2022 16:00 ET | Source: Processa Pharmaceuticals, Inc. Processa Pharmaceuticals, Inc.
HANOVER, Md., March 30, 2022 ( GLOBE NEWSWIRE) -- Processa Pharmaceuticals, Inc. ( Nasdaq: PCSA) ( `` Processa '' or the `` Company ''), a clinical stage company developing drugs for patients who have unmet medical conditions that require better treatment options to improve a patient’ s survival and/or quality of life, today announced financial results for the year ended December 31, 2021, and provided a corporate update.
Dr. David Young, CEO and chairman of Processa, commented, “ Although COVID presented challenges for us and our industry in 2021, we commenced and enrolled patients in PCS499 for the treatment of uNL, PCS6422 ( Next Generation Capecitabine) for the treatment of GI cancer, and received clearance for an IND for PCS12852 for gastroparesis. We were excited to learn that Next Generation Capecitabine is fifty times more potent than presently approved capecitabine and modified the protocol to further enhance the efficacy and safety of Next Generation Capecitabine. In addition, our modifications to the protocol now allow us to evaluate the possibility of treating patients using an individualized-personalized medicine approach for Next Generation Capecitabine. We completed the administrative efforts to commence our study in gastroparesis with the first patient to be dosed imminently. These efforts will produce three catalytic data events in the coming 9-10 months each in indications that could potentially exceed markets of $ 1 billion. ”
We continue to manage our cash efficiently and as of December 31, 2021 we had a cash balance of $ 16.5 million. During the year ending on December 31, 2021 we increased our cash balance by $ 1.1 million compared to December 31, 2020 by raising net proceeds of $ 9.8 million in a private placement in early 2021 and in our ATM offering offset by $ 8.7 million in costs we incurred related to our three clinical trials and our spending for operating and other related costs.
We define overhead as our general and administrative expenses plus the salaries for our development and administrative teams. Our cash outlay for overhead expenses for the year ended December 31, 2021 was only $ 3.0 million. We accomplished this in part by having the cash portion of our six executive team members totaling only $ 525,000 for 2021. We are focused on directing our cash toward activities that move our drug products forward.
For the year ending on December 31, 2021 we reported a net loss of $ 11.4 million, or $ 0.75 per share compared to a net loss of $ 14.4 million, or $ 2.54 per share for the same period of 2020. The primary reduction in our net loss was due a decline in licensing activity in 2021 versus 2020. During 2021 we licensed PCS3117 from Ocuphire Pharma. Inc. for cash and stock totaling $ 567 thousand while in 2020, we incurred. $ 8.7 million related to licensing PCS12852 from Yuhan Pharmaceuticals, PCS6422 from Elion Oncology and PCS11T from Aposense. Adjusting for in-process research and development acquisition costs, our net loss increased by $ 5.1 million for the year ended December 31, 2021 compared to the comparable period in 2020. This increase primarily relates to increased clinical trial costs we incurred as we progress with our clinical trials.
During the year ended December 31, 2021, we incurred research and development expenses totaling $ 6.9 million compared to $ 3.2 million for the same period in 2020. The increase in our R & D costs of $ 3.7 million in 2021 was primarily due to costs we incurred related to our active clinical trials. Our general and administrative expenses totaled $ 4.7 million for the year ended December 31, 2021 compared to $ 3.3 million for the same period in 2020. The increase related primarily to increases in professional and other consulting fees, as well as non-cash stock-based compensation. Allocated between our R & D and G & A costs is $ 3.4 million of non-cash compensation costs.
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Date: March 30, 2022Time: 4:30 p.m. ETToll Free: 888-506-0062International: 973-528-0011Entry Code: 837465Live Webcast: https: //www.webcaster4.com/Webcast/Page/2572/44826
Toll-free: 877-481-4010International: 919-882-2331Replay Passcode: 44826Replay Webcast: https: //www.webcaster4.com/Webcast/Page/2572/44826
The mission of Processa is to develop products with existing clinical evidence of efficacy for patients with unmet or underserved medical conditions who need treatment options that improve survival and/or quality of life. The Company uses these criteria for selection to further develop its pipeline programs to achieve high-value milestones effectively and efficiently. Active clinical pipeline programs include: PCS6422 ( metastatic colorectal cancer and breast cancer), PCS499 ( ulcerative necrobiosis lipoidica) and PCS12852 ( GI motility/gastroparesis). The members of the Processa development team have been involved with more than 30 drug approvals by the FDA ( including drug products targeted to orphan disease conditions) and more than 100 FDA meetings throughout their careers. For more information, visit the company’ s website at www.processapharma.com.
This release contains forward-looking statements. The statements in this press release that are not purely historical are forward-looking statements which involve risks and uncertainties. Actual future performance outcomes and results may differ materially from those expressed in forward-looking statements. Please refer to the registration statement relating to the securities being sold in this offering, which identifies important risk factors which could cause actual results to differ from those contained in the forward-looking statements.
For More Information: Michael Floyd mfloyd @ processapharma.com301-651-4256
Patrick Linplin @ processapharma.com925-683-3218 | general |
Supply fears ease as Shanghai Port stays open in lockdown | The Port of Shanghai - one of the world’ s largest - is continuing operation, despite a staggered citywide lockdown imposed in China, easing fears that a port shutdown would see widespread and prolonged supply chain disruption.
The lockdown, which was imposed on 28 March in Pudong on the east side of the Huangpu River, has seen businesses close and people told to stay at home. But Chinese state media confirmed that the Port of Shanghai is to continue operating.
Meanwhile, the shipping line Maersk - in an advisory note on its website - revealed that some depots in Shanghai remain closed “ until further notice ”.
The Shanghai lockdown is China’ s biggest city-wide lockdown since the Covid outbreak began more than two years ago. The city is to be locked down in two stages over nine days while authorities carry out Covid-19 testing.
The key financial and trading metropolis - home to 25 million people - has been battling a new wave of infections for nearly a month, even though case numbers are extremely low by most international standards.
The Shanghai lockdown follows hot on the heels of a lockdown in the manufacturing centre of Shenzhen.
Following that lockdown, which was triggered by a mere 60 Covid cases, supply chain visibility specialist project44 released a report decrying the damaging effect on supply chains of China's zero-tolerance Covid approach.
“ China’ s manufacturing sector is paying a high price for this zero-tolerance policy, which leading medical experts think is fundamentally flawed, ” a project44 spokesperson said. “ Maybe this will lead the Chinese authorities at some point to rethink the reasoning of shutting down a 17.5-million metropolis for just 60 Covid cases. ”
Supply Chain Digital is the digital community for the global supply chain & logistics industry that connects the world's largest supply chain & logistics brands. Supply Chain Digital focuses on procurement and supply chain news, key interviews, supply chain videos, along with an ever-expanding range of focused procurement and supply chain white papers and webinars. | general |
Microsoft Build 2022 developer conference: Coming May 24 to a screen near you | Microsoft's annual Build developer conference is happening from May 24 to 26 and again will be a virtual event.
Mary Jo Foley has covered the tech industry for 30 years for a variety of publications, including ZDNet, eWeek, and Baseline. She is the author of Microsoft 2.
Microsoft has announced the dates for its annual Build developer conference: May 24 to 26. And like the past two Build events, the 2022 Build will be virtual due to continued worries about the COVID-19 coronavirus pandemic. Build is a showcase for what Microsoft is doing for and with developers in the cloud, in its own apps and across Windows and other platforms. Registration for this year's event -- which will be free -- will be open in late April, according to the company's Build site. In 2020, Microsoft made a conscious effort to refocus Build on developers rather than on higher-level, cross-company strategies. Last year at Build, which was from May 25 to 27, Microsoft announced the 0.8 preview release of Project Reunion; tools for building collaborative apps in Teams; support for Linux GUI apps in the Windows Subsystem for Linux; Azure Confidential Ledger; Power Fx's ability to build apps with GPT-3 and more. Microsoft Inspire, its annual event for partners, will be held July 12 to 13 and be virtual, not in-person, officials have said. Microsoft isn't holding a Spring Ignite event this year, but its fall Ignite event for IT pros is expected around November. Officials have not said yet publicly whether Ignite will be virtual, hybrid, or in-person.
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Automotive Semiconductor Market Expected to Accumulate a | New York, USA, March 30, 2022 ( GLOBE NEWSWIRE) -- According to the latest report published by Research Dive, the global automotive semiconductor market is predicted to rise at a tremendous CAGR of 12.2%, thereby garnering a revenue of $ 93,696.2 million in the 2021-2028 timeframe. This integrated report presents a brief outlook of the current framework of the automotive semiconductor market including its cardinal features like growth drivers, growth opportunities, restraints, and hindrances during the forecast timeframe of 2021-2028. All the necessary market figures are also provided in this report to help new entrants analyze the market easily.
Drivers: Growing popularity of electric cars and the consequent use of automotive semiconductors is estimated to drive the growth of the global automotive semiconductor market by 2028. Moreover, increasing safety concerns over vehicular transport is compelling vehicle manufacturers and buyers to prefer cars with automotive semiconductors. This has further augmented the growth of this market by 2028.
Opportunities: Mergers, acquisitions and business expansions by key players in the automotive semiconductor market are expected to offer huge growth opportunities to the market. Additionally, since there is an increasing demand for electric vehicles, many new automobile manufacturers are entering this arena of electric vehicle manufacturing. This will also increase the growth opportunities that are available to the automotive semiconductor industry by 2028.
Restraints: Exorbitant prices of vehicles across the world is the major factor expected to impede the market growth.
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The novel coronavirus has wreaked havoc in the world. Millions of lives are affected, either directly due to the disease, or indirectly due to government-imposed lockdowns to curb the spread of the virus. This affected numerous manufacturing and service industries by hampering both the supply-side and demand-side supply chains. Similarly, the automobile manufacturing industry and consequently, the automotive semiconductor market faced dual problems of irregular supply of raw materials and reduced demand for manufactured products that resulted in the fall of the market growth.
However, given the rate at which developing economies have turned around the sorry state of their economic conditions as soon as lockdowns were lifted, presents a hopeful picture for many industries. Moreover, various governments have started giving subsidies on electric vehicles to counter the fall in demand for automobiles. All these factors together have made market analysts predict that the automotive semiconductor market is bound to grow in the forecast period.
Get in touch with our Expert Analyst @ https: //www.researchdive.com/connect-to-analyst/8547
The report has divided the global automotive semiconductor market into certain segments based on component, vehicle type, propulsion type, application, and region.
Among all types of automotive semiconductors, processors are the most widely used components. They help in controlling various parts of the vehicle and at the same time act as the coordinator between various actions taken by the user. Moreover, many different types of automotive semiconductors like sensors, or different components of vehicles like control lights, navigation systems, run with the help of processors. Thus, the crucial role played by processors in the working of any vehicle has helped in making the processor sub-segment of the global automotive semiconductor market the fastest growing among others. This sub-segment is predicted to garner a revenue of $ 21,367.6 million by 2028.
By vehicle type, light commercial sub-segment is expected to be the fastest growing of the automotive semiconductor market and is predicted to reach $ 33,651.0 million by 2028. The main reason behind this anticipated growth is the growing popularity for adoption of electric vehicles among people. Moreover, various governments have formulated policies to cut down the carbon emissions that are created due to vehicles running on conventional fossil fuels. Both these factors have helped in the growing of this sub-segment.
By propulsion type, electric engine sub-segment is expected to be the fastest growing of the automotive semiconductor industry. It is expected to gather a huge revenue of $ 36,720.1 million by 2018. The growing awareness about climate change and global warming have convinced many governments to legislate and formulate laws that curb the vehicular emissions that arise due to combustion of conventional fossil fuels. Moreover, the ever-increasing prices of crude oil and petrol across the globe have made people consider electric vehicles as a serious option to traditional vehicles. As a result, there is a growing demand for electric vehicles ( EVs) - both for public transport purposes and individual use. This growing demand for EVs is, in turn, expected to boost the automotive semiconductor market.
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By application, telematics and infotainment sub-segment is expected to grow the highest by garnering a substantial revenue of $ 30,947.6 million by 2028. Wireless technology which helps the user to locate his/her own car during emergencies has helped this sub-segment to flourish. Also, easy exchange of information across wirelessly connected cars has made telematics and infotainment sub-segment the highest gaining of the automotive semiconductor market.
By regional analysis, the market in Asia-Pacific region is predicted to be the fastest growing one. It is expected to amass a revenue of $ 21,615.7 million by 2028. Direct partnerships between automotive semiconductor manufacturers and the vehicle OEMs have been the prime reason behind this high growth rate of market in Asia-Pacific region. Moreover, this region has been witnessing a rise in demand for luxury and semi-luxury vehicles that has further helped in boosting the automotive semiconductor market.
These players are adopting various business strategies like mergers, acquisitions, and collaborations to gain a prominent position in the market.
For instance, in January 2022, Infineon Technologies AG, a German semiconductor manufacturing giant, and Deeyook, an Israeli firm, announced that they will be collaborating to provide precise location solutions. The main area of focus of this collaboration would be to provide new Internet-of-Things ( IoT) solutions that will help in several location tracking technologies and thus can be integrated with vehicular GPS or RFID technologies.
Finally, the report also summarizes many crucial aspects of the automotive semiconductor market including SWOT analysis, latest strategic developments, financial performance of the key players, and product portfolio.
Full Report Overview & TOC: https: //www.researchdive.com/8547/automotive-semiconductor-market
Blog: https: //www.researchdive.com/blog/what-are-the-reasons-for-the-exponential-increase-in-demand-for-automotive-semiconductors
Analyst Review: https: //www.researchdive.com/blog/what-are-the-reasons-for-the-exponential-increase-in-demand-for-automotive-semiconductors | general |
Australia: Chemical Restraint Persists in Aged Care | Help us continue to fight human rights abuses. Please give now to support our work
One Year After Royal Commission Report, Older People Still Not Protected
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( Sydney) – The Australian government should end nursing homes’ use of chemical restraints to control the behavior of older people with dementia, Human Rights Watch said today. One year ago, in March 2021, the Royal Commission into Aged Care Quality and Safety issued its final report, calling for urgent reforms to protect older people from unnecessary chemical restraint.
A Human Rights Watch review of non-compliance reports for aged care facilities across Australia from July 1, 2020, to June 30, 2021, found use of chemical restraints in more than 150 aged care facilities, despite regulations first introduced in 2019 that aim to minimize the use of restrictive practices. Chemical restraint is the use of medications to control the behavior of aged care residents without a therapeutic purpose.
“ The Australian government should ensure that policies for older people respect their dignity and human rights, ” said Elaine Pearson, Australia director at Human Rights Watch. “ Policies minimizing the use of restraints to modify behavior are failing to protect older people, showing the need for an outright ban on chemical restraints. ”
Human Rights Watch in 2019 documented the use of chemical restraint in aged care homes in Australia. In its final report in 2021, the Royal Commission found the overuse of restrictive practices to be a major issue that affects the liberty and dignity of people receiving aged care.
Many Australian aged care facilities have used chemical restraints on older people, without informed consent or documentation that it was obtained, Human Rights Watch found. Some aged care facilities which did not meet compliance standards failed to regularly monitor the use of drugs that are administered for chemical restraint, failed to provide individual care plans with ways to manage behavior without the use of chemical restraints, and did not provide alternative strategies to ensure that chemical restraint is a last resort.
The Aged Care Quality and Safety Commission is responsible for monitoring and investigating aged care provider compliance with the restrictive practices regulations, and can take enforceable regulatory action including withdrawing accreditation when providers fail to comply with responsibilities.
In July 2021, ABC News reported that a nursing home in Newcastle had allegedly failed compliance standards after auditors discovered that 90 percent of residents had received psychotropic drugs without written consent. In response to a letter from Human Rights Watch inquiring about the practice, the company said that “ after careful consideration, we have decided not to participate due to the highly sensitive nature of the subject matter and out of respect for the privacy of the aged care residents we serve and support. ”
According to an Aged Care Quality and Safety Commission audit report, at an aged care facility in Sydney in November 2020, a resident called out and informed compliance auditors of being in pain and requiring assistance. Care staff allegedly responded by automatically giving the resident a psychotropic medication to address the calling out behavior, rather than providing support and managing the pain itself. The aged care facility responded to a Human Rights Watch request for comment, saying that the company has a strategy for achieving zero chemical restraint by June 30, 2022. It also said that among other measures taken since the February 2021 audit report, it had updated its restrictive practice policy in line with the latest legislation.
The Aged Care Quality and Safety Commission, in response to a February 2022 inquiry from Human Rights Watch, said that for the year July 1, 2020, to June 30, 2021, 347 aged care services were found to be non-compliant with the three requirements of the Quality Standards that may indicate issues with chemical restraint. However, as these requirements are broader than the use of restraints, the commission could not specify at how many of these facilities chemical restraint was identified as an issue.
The commission should publish annual data on the number and names of aged care facilities where they document chemical restraint, Human Rights Watch said.
The Quality of Care Amendment ( Restraints Principles) were introduced in mid-2019, with updated regulations introduced to replace them on June 30, 2021. While the principles clarify that using chemical restraint is a last resort, it falls short of an outright ban on the practice.
An independent review released in March 2021 said that while there were some indications that the use of restraint in aged care facilities was declining, it was not possible to draw definitive conclusions about the effectiveness of the Restraints Principles due to limited data and the short timeframe the regulations had been in place.
The use of chemical restraints in aged care homes is closely related to inadequate staffing and training. A key recommendation of the Royal Commission was to set out minimum staffing times for qualified staff in aged care facilities. The Covid-19 pandemic has exacerbated the existing strain on aged care staffing.
The Australian government should act to end the use of chemical restraints as a means of managing or disciplining older people in aged care. Aged care facilities should instead develop individualized support for older people experiencing emotional distress or pain that do not involve restraints. Meaningful penalties should be imposed on aged care facilities for failure to obtain informed consent for the use of chemical restraints, Human Rights Watch said.
“ Ending the abusive practice of chemical restraint will not be achieved by policies that merely minimize its use, ” Pearson said. “ The Australian government should ensure aged care providers that wrongly administer medication to restrain older people are held accountable for their actions. ”
How Aged Care Facilities in Australia Chemically Restrain Older People with Dementia | general |
Shanghai locks down as COVID surges in China's financial hub | China's financial hub of Shanghai launched a two-stage lockdown of its 26 million residents on Monday, closing bridges and tunnels and restricting highway traffic in a scramble to contain surging COVID-19 cases, Trend reports citing Reuters.
The snap lockdown, announced by the local government late on Sunday, will split China's most populous city roughly along the Huangpu River for nine days to allow for `` staggered '' testing by healthcare workers in white hazmat suits.
It is the biggest COVID-related disruption to hit Shanghai, and sent prices of commodities including oil and copper lower on fears that any further curbs could hurt demand in China, the world's second-largest economy. | general |
Is a'recharge break ' the key to your employees ' happiness? | Last year, as summer was approaching, Austrian cryptobroker Bitpanda shut down for a whole week.
Apart from those working in customer support, the entire company logged off. No emails were responded to, no meetings were held. After a year of superfast growth, Slack was finally silent.
Bitpanda is not the only tech business to experiment with giving entire weeks off to the whole company, sometimes referred to as “ recharge weeks ”. Managers say they give employees a chance to unplug and destress, hopefully without finding a mountain of emails when they return.
Bitpanda decided to give the week off after massive growth. From the beginning of 2020 to mid-2021, it grew its team from 150 to 500 and tripled its valuation to $ 4.1bn after Valar Ventures, the VC firm of billionaire Peter Thiel, plugged yet more cash into the company.
“ The industry was going through what we call a massive bull run; it was just crazy busy, ” says Bitpanda’ s chief human resources officer, Lindsay Ross. “ At that moment in time we looked around and thought, ‘ oh my gosh, everyone is working so hard. Let people take a break and fully shut everything down’. ”
The scheduled break paid off, says Ross. Employees — who were still largely working from home due to Covid restrictions — came back to their desks recharged and ready to work. So Bitpanda decided to make recharge weeks a permanent thing. As of this month, the company is offering its staff of 800 employees two separate “ recharge ” weeks in addition to unlimited paid time off per year.
Bitpanda isn’ t the first company to implement a week-long unplug.
Last year, Berlin-based fashion retailer Zalando introduced a “ zacation ” where employees could take an extra five days of paid holiday at the start of August. Dating app Bumble gave its then 750 staffers a week off to help “ combat pandemic-induced burnout ” and now offers two company-wide weeks off per year.
Over in the US, Coinbase announced it will shut down for four long breaks this year. Meanwhile, LinkedIn has been offering its US employees — who are typically entitled to less paid time off than Europeans — a week off in each of July and December for years.
Bitpanda’ s Ross explains that the company schedules a one-week break twice a year which works well for all departments and that doesn’ t leave anything “ crazy pressing ” in the lurch. The breaks may, for instance, be scheduled near a public holiday season — at a time when people are slowing down and wrapping things up anyway — so that employees can enjoy extended time off.
That doesn’ t mean that the entire business has to grind to a halt, however. Bitpanda has a cover team in place to keep the platform and customer support services going while the majority of employees are away. They can then take time off in lieu at a later date.
While some leaders are overwhelmingly positive about the benefits of a recharge week for employees, others are sceptical.
Rhys Black, head of workplace design at Oyster, which helps companies build distributed teams, says that companies need to be careful that recharge weeks don’ t become “ a plaster to patch more fundamental problems with the ways companies operate, ” leading them to implement “ damage control measures ” instead of resolving the problems beneath the surface.
“ What is going on in the companies that they think recharge weeks are needed in the first place? ” says Black. “ Is it month-after-month of Zoom calls causing people to burn out? Is it lack of manager support and feedback leading to employees having a crisis of confidence? ”
He adds: “ It is likely a mixture of many things. In these cases there are a lot of operational and cultural changes that need to be made to manage these problems. A recharge week is nice, but it isn’ t going to do that. ”
Bitpanda has tried to avoid some of the potential pitfalls of recharge weeks, like employees feeling pressured to work even harder when they return or not taking regular holidays also. Their answer: combining recharge weeks with unlimited holidays.
“ Some companies might say ‘ hey we’ re going to take 20 days a year off altogether,’ which means they can better control the holiday flex ( the coming and going) of employees. But actually, we’ re saying, you are an adult, tell us what you need and when you need it, ” says Ross.
On the other hand, Oyster has experimented with different methods over the last two years to give employees enough downtime. Instead of implementing recharge weeks, the company offers employees a 40-day minimum holiday allowance. It also has “ Focus Fridays ”, where workers don’ t have any meetings.
Ultimately, implementing a “ recharge week ” is based on how busy things are ( whether you, as a company, have the capacity to allow people to take time off) and how your employees are feeling.
“ The most important thing is to check with your employee base. Ask them, How are you doing? Do you need a break? What does that look like? Do we all need a break? Are we all noticing that we’ re really struggling to disconnect? ” says Ross.
People can only run so fast for so long, adds Ross, so if you see employees flagging, recharge weeks can be extremely useful. “ Because then they come back and they’ re excited to run and energised to continue to deliver. ”
Miriam Partington is Sifted’ s Germany correspondent. She also covers future of work, coauthors Sifted’ s Startup Life newsletter and tweets from @ mparts | tech |
Running order for Eurovision 2022 revealed [ VIDEO ] | Eurovision Song Contest 2020 has announced the running orders of the contestants.
Azerbaijan's entry for Eurovision 2022 Nadir Rustamli will perform in the first part of the second semi-final of the contest under the number four.
The order of performance of the contestants is determined by the results of the draw.
Nadir Rustamli will represent Azerbaijan in Turin with the song `` Fade To Black '' released on March 21 2022.
The song is written and composed by Thomas Stengaard and Andreas Stone Johansson. Thomas Stengaard songs are well known to Eurovision viewers, Eurovoix reported.
The songwriter was a part of the teams that produced the Eurovision entries `` El Diablo '' and `` Adrenalina '' for Cyprus and San Marino respectively last year.
Swedish songwriter Andreas Stone Johansson is best known for working on 2019 Eurovision entire `` Too Late for Love '' which was performed and co-written by John Lundvik.
Nadir has been into music since a young age. He took piano lessons for seven years, studied in music school and, while at university and joined a music band `` Sunrise '' as the front man. In the music band, he also served as the art director for the music band. Moreover, Nadir Rustamli is the winner of the Voice of Azerbaijan singing competition's winner.
Meanwhhile, Eurovision 2022 will take place in Turin, Italy on May 10-14.
Nadir Rustamli will perform in the first part of the second semi-final of the Eurovision Song Contest 2022.
As a result of the draw, Azerbaijan's entry will perform on May 12. The first semi-final will take place on May 10.
The Azerbaijani delegation at Eurovision 2022 will be headed by composer and producer Isa Melikov.
Azerbaijan marked its debut in 2008 with the duo of Elnur and Samir, who managed to become the eighth in the final with their song `` Day after day ''.
The brilliant duet of Aysel and Arash, which represented Azerbaijan next year, took third place at the song contest, while Safura Alizada, who represented the country at the Eurovision 2010 in Oslo, became fifth.
On its fourth attempt with Ell and Nikki's `` Running Scared '' song, the Land of Fire won the event, bringing the contest to Baku's Crystal Hall in 2012. Ell and Nikki were the first mixed-gender duo to win the contest since 1963 and the first winners from Azerbaijan.
It is noteworthy that Azerbaijan reached the Top 5 in five consecutive contests - 3rd in 2009, 5th in 2010, 1st in 2011, 4th in 2012, and 2nd in 2013.
In 2018, Aysel Mammadova performed brilliantly at the Eurovision 2018 semi-final, but she couldn't make it to the final. The singer represented Azerbaijan with the song `` X My Heart ''.
Azerbaijan's Chingiz Mustafayev impressed all Eurovision fans with his stunning performance in 2019. The singer finished in eighth place at the song contest.
In 2020, the song contest was cancelled amid the coronavirus pandemic. However, fans of the music contest had a great chance to enjoy a spectacular show `` Eurovision: Europe Shine A Light '', featuring 41 songs of this year's entries.
During the show, Samira Efendi pleased Eurovision fans with the song `` Cleopatra '' about trusting your gut instinct, standing up for yourself and being a `` Queen '' - even when things get tough and especially if someone betrays or hurts you.
Last year, Samira Efendi performed in the second half of the Eurovision 2021 final with the song `` Mata Hari '' and took place the 20th place. Speaking about the meaning of the song, Efendi noted that it is about female power.
She thrilled Eurovision fans with stunning performance that featured a giant orb in the background.
At the end of the stage show, the orb was lifted into the air where it exploded in a rain of golden sparkles, leaving the image of Nazar, a symbol of fortune in Azerbaijan.
Efendi's costume was adorned with precious and semi-precious stones; it combined Azerbaijan's traditional elements but with a modern twist. The costume was designed by world-famous fashion designer Rufat Ismayil was behind her outfit. | general |
How `` Shadow IT '' Puts a Business at Risk: 5 Hazards for GRC Professionals to Watch | Unauthorized use of unsecured business applications presents growing danger. So-called shadow IT presents GRC teams with the need to prevent end users from taking actions that while seemingly expedient, completely undermine otherwise robust cybersecurity and data protection measures.
Let’ s say your sales team spends a lot of time on conference calls. Their assigned enterprise application is clunky, disconnects frequently and the video keeps buffering. Out of frustration, they decide to use another tool they find more stable. The problem: The IT team is out of the loop, does not know of the software’ s existence and therefore can not manage its risks.
Shadow IT, the unauthorized use of software, applications or hardware, is an ongoing IT blind spot for many organizations. Moreover, the proliferation of software-as-a-service applications, the sudden rise of remote work and the ubiquity of smartphones significantly amplify the scale of the problem. In fact, for the second of half of 2021, industry analysts from CybelAngel report a 40 percent rise in shadow IT incidents. The result is an increase in cybersecurity loopholes that can lead to dire consequences for the business.
The use of shadow IT significantly increases the threat surface because it is unregulated and unsanctioned by the business. Applications may have unpatched errors and vulnerabilities that can leave gaping holes in the security posture. Cyber criminals can use these weak spots to carry out surveillance, launch damaging attacks or steal sensitive information. Use of shadow IT by malicious insiders is also a major concern. For example, in the Coca-Cola trade secret theft case, an engineer leveraged Google Drive to facilitate the IP theft.
It is impossible for IT teams to have visibility or control over company software and data that is outside their purview. This can create a major governance issue for IT teams, especially in an environment where there is an expanding list of rapidly evolving compliance mandates ( e.g. GDPR, CCPA, etc.) forcing businesses to maintain tighter security standards.
Employees who use shadow IT put their organization at risk of not meeting compliance obligations. This can be particularly concerning in a situation where organizations are subject to stringent compliance laws that govern collection, storage, transmission and use of sensitive data. Organizations can face expensive lawsuits and run the risk of losing brand reputation, customer trust and competitive edge.
There is always the potential for businesses to lose sensitive data if it is stored in unregulated or unprotected locations. A simple example can be Google Drive or Dropbox, where an employee may choose to store contracts or customer lists or sales presentations. If that worker leaves the organization or terminates their personal cloud storage accounts, this data is lost permanently. Moreover, in the case of a cyber incident, the data is neither accessible nor backed up and may be impossible to recover.
Instances of shadow IT in an organization signify a problem. It could mean that end users are not being given the IT resources they need to do their jobs, so they instead look to alternative tools. It might indicate a general lack of support from leadership or issues with line managers allowing their teams to work around mandated IT guidelines and policies. It could also mean the IT team has not clearly communicated the risks of shadow IT.
Overall, GRC professionals need to recognize the risks and causes then take steps to enact more effective IT controls. While shadow IT is nearly impossible to eliminate, risk and compliance teams can use a “ defense-in-depth ” approach to mitigate risks. Such an approach consists of three main elements:
Ultimately, organizations must recognize that, at the core, shadow IT is a cultural problem. For employees to embrace a security culture, leaders and end-users must engage in ongoing two-way dialogues. That is, end-users should communicate needs and expectations from the business in the same way that IT expresses potential risks.
Both groups need to come together to proactively understand what employees need plus identify opportunities for new technologies. If a company is experiencing chronic incidence of shadow IT, that’ s a sure sign that certain tools and services may not be keeping up with existing and evolving end-user requirements.
Stu Sjouwerman is founder and CEO of KnowBe4 [ NASDAQ: KNBE ], developer of security awareness training and simulated phishing platforms, with 41,000 customers and more than 25 million users. He was co-founder of Sunbelt Software, the anti-malware software company acquired in 2010. He is the author of four books, including “ Cyberheist: The Biggest Financial Threat Facing American Businesses. ” He can be reached at ssjouwerman @ knowbe4.com.
SAN FRANCISCO ( June 7, 2021) – ForgeRock®, a global digital identity leader, today announced findings from its 2021 Identity Breach...
On Data Privacy Day, Kroll’ s Alan Brill and Brian Lapidus share recommendations for companies who have fallen victim to ransomware...
LMG Security’ s Madison Iler discusses how to structure a vendor risk management program ( and where to spend your time) and...
The COVID-19 crisis has necessitated technological advancements across the board as many industries have gone remote. FairWarning CEO Ed Holmes...
Founded in 2010, CCI is the web’ s premier global independent news source for compliance, ethics, risk and information security.
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Balenciaga Is One of TIME's Most Influential Brands | Every year, TIME Magazine publishes a list of the world's top 100 influential companies, ranging from innovators to companies, and more.
This year, the industry disruptors include Kim Kardashian's $ 3.2 billion dollar company SKIMS, which has become much more than just a shapewear brand, as well as social media platform TikTok, which has basically become the go-to for Gen Z, Supergoop! which has managed to make sunscreen and SPF+ cool, and even Shein, which ( in the worst way possible) has redefined what `` fast fashion '' means.
Big players including Amazon, Netflix, IBM, Apple, Disney, Microsoft, and Meta are of course also on the list, featured as `` Titans. '' It comes as no surprise as these companies continue to grow bigger, and we're also seeing companies such as Pfizer on the list as a result of the COVID-19 pandemic, and the vaccine rollout.
One brand on the list stands out, however.
Amongst the technology giants and new initiatives stands one luxury player – Balenciaga.
`` Thanks to creative director Demna, luxury powerhouse Balenciaga is not only reflecting the cultural zeitgeist, it’ s also driving it, '' TIME writes.
Currently, Balenciaga is the most relevant brand in luxury, continuously working with top-tier talent including Kim Kardashian and most recently Kendall Jenner at the Oscars, as well as shooting Justin Bieber, Cardi B, and more for its various campaigns. Demna understands what it means to be culturally relevant, and also understands how to create conversation.
Since his appointment at Balenciaga, the creative director has been all about creating controversial pieces and tongue-in-cheek capsules, featuring collaborations with The Simpsons and Fortnite, as well as creating heeled Crocs. Polarizing, and optimized for conversation, it is clear that everything Demna does is carefully planned, and intentional.
This year, he's also worked with Kanye West as the creative director of the DONDA listening parties, as well as collaborated with the rapper on the YEEZY x GAP Engineered by Balenciaga capsule collection which brought in a humble $ 2 billion dollars post-release.
With Balenciaga also making moves to enter the digital world by dedicating an entire team to expanding its presence in the Metaverse and within web3, the label will continue to be fashion's most relevant label for years to come.
If you're interested in exploring the full list of influential companies, you can do so over at the TIME website.
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Drop U.S. Airline Mask Mandate, Say 21 State Attorneys General | Get exclusive stories and unlimited access to Skift.com news
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David Shepardson, Reuters
March 30th, 2022 at 5:35 AM EDT
The CDC and the airlines are focused on caution while the attorneys general are focused on politics. Only one of these will help speed along the recovery of tourism.
Jason Clampet
A group of 21 states led by Florida on Tuesday asked a U.S. judge to block a federal COVID-19 mandate requiring masks on airplanes and other forms of transportation.
The lawsuit is the latest in a series of recent legal challenges to a Centers for Disease Control and Prevention ( CDC) public health order and Transportation Security Administration ( TSA) directive that have been in place since February 2021 covering airports, trains, buses, ride-share vehicles and transit hubs.
The administration of President Joe Biden said earlier this month it would extend the transportation mask requirements through at least April 18 and is reviewing if they should be extended again.
The White House and CDC did not immediately comment.
State attorneys general joining the lawsuit include Arizona, Georgia, Kentucky, Missouri, Ohio, Utah and Virginia.
On Wednesday, the chief executives of American Airlines, United Airlines, Delta Air Lines and other carriers urged Biden to end the airplane mask mandate, which has resulted in significant friction on airplanes. The Federal Aviation Administration says since January 2021, there have been a record 6,900 unruly passenger incidents reported – and 70% involved masking rules.
Advocates of ending the ban point out that the vast majority of Americans live in places where the CDC has said it is safe to ditch indoor masks.
The CDC order said the mask mandate could help prevent the spread of COVID-19 in crowded transport settings.
Last month, Texas Attorney General Ken Paxton and U.S. Representative Beth Van Duyne jointly filed a lawsuit challenging the mandate. More than a dozen Republican lawmakers have filed a separate challenge in a federal court in Kentucky.
Copyright ( 2022) Thomson Reuters. Click for restrictions
This article was written by David Shepardson from Reuters and was legally licensed through the Industry Dive Content Marketplace. Please direct all licensing questions to [ email protected ]. | general |
Emirates President Forecasts Return to Profit in 2023 | Get exclusive stories and unlimited access to Skift.com news
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Yousef Saba, Reuters
March 30th, 2022 at 4:08 AM EDT
The airline has been cash-positive since October and Tim Clark thinks he's `` swung it. '' It's a precarious statement to make in the face of rising fuel costs and the ongoing war in Ukraine.
Matthew Parsons
Dubai’ s Emirates expects to significantly reduce losses in the current financial year and return to profit next year, the airline’ s president indicated on Tuesday.
“ We are in for a good set of results, we haven’ t reversed it completely but we have swung it, ” Tim Clark told reporters, adding the carrier had been cash-positive since October.
“ We’ ve swung the business back to profitability, we are cash-positive again big time, we have a very strong balance sheet again which we have been rebuilding, ” Clark said.
“ We are forecasting profits next year and hopefully to pay a dividend and repay some of the equity that the government has put into the business, ” he added.
The carrier’ s financial year runs through March.
In June last year, Emirates got an additional $ 1.1 billion in state support from Dubai after the coronavirus pandemic hurt long-haul travel and triggered the airline’ s first annual loss in more than three decades.
Speaking on the sidelines of the World Government Summit in Dubai, Clark said Emirates would not take delivery of A350 passenger jets if they have surface problems similar to those reported by Qatar Airways.
“ We’ re not going to take airplanes with degradation. I made clear … that this has to be resolved prior to delivery to Emirates. ”
Airbus is locked in a UK court dispute with Qatar Airways over the contractual and safety implications of paint and lightning protection damage on existing A350 passenger jets.
Several airlines have reported A350 paint problems, while Qatar Airways has complained of deeper underlying issues with a layer of lightning protection attached to the paint and said these raised questions over the safety of the affected jets.
Airbus, which has acknowledged quality problems but denied any safety threat, had no immediate comment on Clark’ s remarks.
( Reporting by Yousef Saba; Editing by Tim Hepher and Bernadette Baum)
Copyright ( 2022) Thomson Reuters. Click for restrictions
This article was written by Yousef Saba from Reuters and was legally licensed through the Industry Dive Content Marketplace. Please direct all licensing questions to [ email protected ]. | general |
Eurostar and Thalys European High-Speed Rail Merger Approved | Get exclusive stories and unlimited access to Skift.com news
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Edward Russell, Skift
March 30th, 2022 at 5:42 AM EDT
Rail travel in Western Europe is about to get a little bit easier. European authorities have signed off on the merger of high-speed rail operators Eurostar and Thalys that will create a single company connecting some of Europe's largest cities.
Edward Russell
European rail travel is about to get a little easier with official approval of the long-planned merger of rail operators Eurostar and Thalys. The resulting company will connect some of Europe’ s largest cities, including London, Paris, and Amsterdam, with a single offering.
European Commission authorities approved the merger without conditions on Tuesday saying the combination would do little to change the structure of the market. The merged company will use the Eurostar name and be based in Belgium, the current home of Thalys. French rail company SNCF already controls Eurostar, and splits control of Thalys with Belgian rail operator SNCB.
The combined operator would carry as many as 19 million travelers based on 2019 numbers. While significant, that is still less than some of Europe’ s best known high-speed rail systems. For example, the TGV high-speed network in France carried more than 100 million passengers in 2019.
A single high-speed rail offering connecting Belgium, France, Germany, the Netherlands, and the UK is the latest step towards the EU’ s goal of increasing cross-border rail trips across Europe. Only about 7 percent of cross-border trips are currently made by rail, which is a percentage the EU wants to increase under an action plan released in December.
“ People will only take the train if it’ s easy for them to find the information, ” said Kathrin Obst, the deputy head of unit in the European Commission’ s directorate general of mobility and transport, during a United Europe panel on improving European rail connections earlier in March. She cited booking and itinerary changes as problem areas for many rail operators.
Eurostar and Thalys have promised easier bookings, streamlined schedules, and a new unified loyalty program across their combined network as part of their merger.
Spokespeople for neither rail company were immediately available to comment on the merger, or when it could close now that the they have European Commission approval.
The merger is also seen as a way to support the companies as they emerge from the Covid-19 crisis. Demand for train travel, like for flying, was hit hard early in the pandemic. And while it has recovered significantly since the darkest days of the crisis, it has yet to return to pre-Covid levels. While neither Eurostar or Thalys has released 2021 data, both said at various time last year that they were hit hard by the pandemic. Thalys’ passenger numbers were down 70 percent to 2.5 million in 2020 compared to the year before.
Eurostar and its lenders closed a $ 328 million ( £250 million) debt refinancing deal in May 2021 that CEO Jacques Damas described at the time as “ crucial to the restoring of demand and the financial recovery of our business. ”
And Thalys CEO Bertrand Gosselin said in May 2021 that the operator would likely need to raise external funds for its recovery.
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Edward Russell, Skift
March 30th, 2022 at 5:42 AM EDT
Tags: european commission, eurostar, high-speed rail, Thalys, United Europe | general |
Chinese Airlines Still in Covid's Grip Report Wider 2021 Losses | Get exclusive stories and unlimited access to Skift.com news
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Stella Qiu and Jamie Freed, Reuters
March 30th, 2022 at 3:00 PM EDT
Chinese airlines are walking a tricky tightrope with their efforts to knock out the Omicron variant. The consequences are brutal, and amid a plane crashe, inflated fuel prices due to the Russian-Ukrainian conflict, and Covid-positive Chinese citizens flying internationally, they fear there will be more to come.
Mary Ann Ha
China’ s three biggest airlines on Wednesday reported wider losses in the final quarter of 2021, marking the second year in the red due to COVID-19 as hopes for a recovery remain distant while the country tries to halt the virus’ fast spread.
Shanghai-based China Eastern Airlines said its net loss rose to 4.05 billion yuan ( $ 637.64 million) from 2.95 billion yuan in the third quarter, taking its full-year loss to 12.2 billion yuan. That is deeper than an 11.8 billion yuan loss in 2020.
The airline also faces closer regulatory scrutiny following the crash of a Boeing 737-800 jet last week that killed 132 people on board, which has led it to ground 223 planes of that type as a precaution while the investigation proceeds.
The company will closely monitor the ongoing investigation into the cause of the crash and evaluate the impact on its financial performance and operational results, said the carrier in its annual report.
Beijing-based Air China, the country’ s flag carrier, said its net loss widened to 6.32 billion yuan in the fourth quarter from 3.54 billion yuan and it posted a full-year loss of 16.6 billion yuan.
China Southern Airlines fell to a fourth-quarter net loss of 5.98 billion yuan, after posting 1.43 billion yuan in the red the previous quarter. It reported a full-year loss of 12.1 billion yuan.
The Guangzhou-based airline also forecasted a pickup in deliveries of the Boeing 737 series aircraft from 2022, as Chinese carriers are set to resume commercial services of the 737 MAX, which was grounded in China for over two and a half years.
China’ s domestic travel market, which had rebounded quickly due to its successful containment of the COVID-19 virus in the early days of the pandemic, is nursing heavy losses as authorities struggle to stop the spread of the highly transmissible Omicron variant under its strategy of eliminating cases.
More than two-thirds of planned flights are being canceled every day across China, according to third-party aviation data providers, while financial capital Shanghai is in the middle of a two-stage lockdown of 26 million people.
Data firm OAG said on Tuesday that China’ s available seat capacity this week was down 10.2% from a week earlier and 24.4% from the same week last year.
A strong yuan currency was again a favorable factor this year, offering some relief to Chinese airlines that have financed a large portion of their foreign debt obligations in U.S. dollars.
However, high fuel costs, which already inflated costs last year, are set to weigh on bottom lines this year, as Russia’ s war in Ukraine heightens geopolitical risks and reinforces broader inflationary pressures across the supply chain.
Brent crude futures stood at $ 113 a barrel, up 45% from the end of last year.
China remains virtually shut off from international markets as already reduced flights get suspended under its “ circuit breaker ” system when there are COVID-19 positive arrivals, leaving many passengers stranded abroad.
Domestic flights over the northern summer season that began this week and lasts through October are set to reach 117,000 flights per day, up 6.8% from a year ago, according to aviation data provider Flight Master, although a large number of them could be canceled. ( $ 1 = 6.3515 Chinese yuan renminbi)
( Reporting by Stella Qiu in Beijing and Jamie Freed in Sydney; Editing by Andrea Ricci)
Copyright ( 2022) Thomson Reuters. Click for restrictions | general |
Living with… or forgetting about COVID? | Ian Bolland provides his thoughts on the end of free COVID-19 testing in England.
The 1st of April marks the end of the free provision of lateral flow testing in the UK. Some would suggest that the date is quite apt, as it’ s part of the government’ s living with COVID plan, which removes one of the key tools that allows us to recognise whether we have a strain of a condition that has taken the lives of more than 162,000 people across the country, with deaths still averaging 140 per day at the time of writing this column.
Tests are still readily available but if you want a test, that must be paid for out of your own pocket, not by the money that you have already paid to the taxman. Though you can argue that the cost of purchasing a test – with some companies offering them for £1.99 – isn’ t that much, it’ s still an unwelcome choice falling upon the population when other world and economic events are fuelling a rise in the cost of living.
Taking a step back, it would appear that those who can afford to test regularly may continue to do so – though this is not a guarantee, but an obvious knock-on effect of this policy is likely to be a widening health inequality in the UK dependent on income.
It’ s hard to argue against it being a more ideological choice when it comes to reducing public spending after there has been such a necessary outlay to prevent even more suffering across the country.
Then there’ s the aspect of people getting COVID that don’ t know about it. Chains of transmission are not broken and though the threat of the disease has now reduced due to most of the population having received three vaccinations, the daily death count shows that a diminishing threat is not one that’ s eliminated.
This reduces oversight on the disease which caused many operations to be cancelled, patients needing essential treatment, meaning there is a huge backlog that needs to be tackled. Though plans have been announced to try and tackle said backlog, allowing the disease to go through the population unmonitored appears counterproductive to those efforts.
And what about new variants? There is a good chance that Omicron may not be the last of the variants. How do we know if we need to step up testing again to the same degree as previously if case numbers are slipping through the net?
Recent months has seen a return to normality. With masks and testing to protect each other, these are not restrictions and never have been. To portray any public health measure that allows you to go about doing everyday things is barmy.
The elephant in the room here is that this is entirely political after the prime minister presided over several seemingly lockdown breaching events that have belatedly required a police investigation, and a time when his own position has come under threat. With many lockdown sceptics in his party, should we really be surprised that getting rid of every aspect of ensuring that COVID is controlled and managed, is abolished and we pretend like nothing else ever happened?
Maybe this will be one of many aspects investigated in the public inquiry which is due to begin soon. | tech |
Defining the New Chinese Tourist | Get exclusive stories and unlimited access to Skift.com news
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Peden Doma Bhutia, Skift
March 30th, 2022 at 8:00 AM EDT
Even as a McKinsey report deciphers key trends in China’ s tourism market this year, the million-dollar question of when the world will get to welcome back Chinese tourists remains largely unanswered. That means a new type of Chinese tourist is opting for deeper local culture experiences.
Peden Doma Bhutia
As more and more countries open up, we might still be watching the curious case of the missing Chinese tourist play out in destinations across the world. That’ s helping to define a new Chinese tourist, whose domestic travel is boosting the country’ s economy.
Its borders sealed, China continues to maintain a strict zero-Covid policy even as the rest of the world moves to adopt an endemic approach towards the virus. So, while in 2019, 150 million Chinese tourists traveled abroad and spent about $ 255 billion in international destinations, the scenario in 2022 is very different.
A report from consulting firm McKinsey predicting key trends in China’ s tourism market in 2022 shows that desire for overseas travel has rebounded to pre-pandemic levels with APAC being the top choice ( 24 percent). Southeast Asia, Europe, Russia, and Japan are named as the most desired overseas destinations.
However, outbound travel seems to be still a long way off as China’ s policy announcements continue to delay any international opening. China now has a 14-day central quarantine and an additional seven-day home quarantine in most places — enough to deter any outbound leisure travel. “ Nobody will choose leisure travel if you end up spending three weeks in quarantine, ” reasoned Steve Saxon, partner at McKinsey & Company.
Saxon noted that even if travel returns, albeit gradually, outbound leisure tourism would be the last priority of the Chinese government. This is in sharp contrast to the rest of the world where the easing of travel restrictions results in the leisure traveler being the first to travel.
At the moment, the government is not issuing passports. Also, many Chinese tourists travel internationally on tour groups, which needs government approval, said Saxon. “ Once borders open, international business travel will be the first to take off, followed by visiting friends and relatives. Leisure travel will be the last to make a comeback. ”
And even when travel returns it will probably not be on the same scale as before, he noted.
But if you thought that China’ s current Covid policy has put a spanner in the works of its tourism industry, think again. Saxon pointed out that it instead boosted the country’ s domestic tourism up until the last few months.
The report states that new domestic tourism products have already been developed to substitute for overseas travel as travelers plan trips around their hometowns as a first choice.
This reinforces what previous McKinsey reports indicated — that the resurgence of domestic travel would support China’ s travel industry recovery. “ Before the current outbreak, when domestic travel was open and encouraged, many of the 150 million Chinese outbound tourists were instead travelling domestically, ” Saxon says.
Recent sporadic outbreaks though, have affected confidence in domestic travel. But McKinsey in its report notes that confidence in domestic travel safety quickly rebounds, showing a predictable pattern of recovery.
To take an example, a few months ago, the city of Xi’ an, home to the popular tourist attraction The Terracotta Warriors, had an alarming Covid outbreak. The city went into lockdown, rolled out largescale testing, got back to zero cases and opened up again. “ So, if the current set of lockdowns is successful, I would expect domestic tourism to recover within three months, ” Saxon said, drawing upon the Xi’ an example.
On Monday, Shanghai became the latest city to impose a phased lockdown as daily Covid infections surged over 3000, with Sunday’ s tally going up to 3500.
However, McKinsey doesn’ t foresee tourism business being adversely affected even as the current outbreak may lead up to the next two months being challenging for the country.
Splitting it up across stakeholders in the value chain, Saxon said most of the big airlines in China are state linked and would receive government support for survival. “ Hotel occupancies hold up because of the sheer number of quarantine facilities required. Many owners have switched their hotels to quarantine facilities. China sends close contacts of people with Covid to centralized quarantine in hotels. All international inbound passengers are also quarantined in hotels for a couple of weeks. ”
The worst hit would continue to be the private sector — travel agencies and tourism destinations heavily reliant on tourist arrivals, he added.
“ There will be caution for a long time about going to crowded places. The winners would be destinations with more outdoors and more experiences, as Chinese tourists opt for experienced-based tourism, ” said Saxon.
The McKinsey report holds out this observation, showing that tourists are opting for deeper local culture experiences and exploring activities like snow tourism and wellness.
Highlighting how snow-themed trips are expected to become a regular routine for Chinese travelers, the report notes that there are 800+ ski facilities in China, featuring 12 national outdoor ski resorts and 36 indoor ski fields. Ski simulators, a popular feature of many Chinese malls, also feature on the list. | general |
Azerbaijan confirms 62 more COVID-19 cases, 46 recoveries | Azerbaijan has detected 62 new COVID-19 cases, 46 patients have recovered, and four patients have died, Trend reports citing the Operational Headquarters under Azerbaijani Cabinet of Ministers.
Up until now, 791,876 people have been infected with coronavirus in the country, 781,865 of them have recovered, and 9,691 people have died. Currently, 320 people are under treatment in special hospitals.
To reveal the COVID-19 cases, 5,122 tests have been carried out in Azerbaijan over the past day, and a total of 6,697,184 tests have been conducted so far.
Some 16,678 people were vaccinated against COVID-19 in Azerbaijan on March 30.
The first dose of the vaccine was injected into 965 citizens, the second one to 1,874 citizens, the third dose and the next doses to 13,104 citizens. Some 735 citizens were vaccinated with a booster dose after a positive test result for COVID-19.
Totally, up until now, 13,441,710 vaccine doses were administered, 5,323,392 citizens received the first dose of the vaccine, 4,823,150 people - the second dose, 3,067,193 people - the third dose and the next doses.
Some 227,975 citizens were vaccinated with a booster dose after a positive test result for COVID-19. | general |
Mlađi od 18 godina više se neće slati u ustanove za mlade prijestupnike | Škotska vlada napravila je novi plan prema kojem 16-godišnjaci i 17-godišnjaci u Škotskoj neće biti smješteni u ustanove za mlade prijestupnike. Ideja iza ovog plana je da se finansiraju `` alternative zasnovane na njezi '' i da se pristup pomjeri sa `` kažnjavanja na ljubav i podršku '', oni žele okončati smještaj mlađih od 18 godina u pritvor `` bez odlaganja ''.
To je jedan od 80 koraka sadržanih u
planu za poboljšanje života djece u sistemu brige i njihovih porodica
. Dokument, također, navodi planove da se godišnje daje 200 funti u vidu donacije mladim ljudima od 16 do 25 godina sa iskustvom u sistemu brige. Uvest će se preporučeni nacionalni dodatak za hraniteljske i srodničke staratelje.
Ovaj korak je uslijedilo nakon objavljivanja
The Promise by Independent Care Review
2020. godine, u kojem se navodi da su mnogi mladi ljudi iskusili `` frakturiran, birokratski i bezosjećajan '' sistem.
Clare Haughey, ministrica za djecu i mlade, rekla je da je vlada opredijeljena da ispuni obećanje do 2030. godine.
Ove ambiciozne akcije pomoći će porodicama da napreduju kako bi mogle bezbjedno da ostanu zajedno... podržati staratelje i porodice koje su angažovane u sistemu brige, kao i one koji napuštaju brigu i iskusne ljude u obrazovanju i zapošljavanju
Nacrtu zakona o brizi o djeci i pravosuđu
- za zaustavljanje ove prakse pokrenute su u krajem marta 2022. godine.
Škotska vlada kaže da ako dijete treba da bude lišeno slobode, to bi trebalo biti u okruženju ``
prijateljskom prema djeci uz poštivanje prava
``. Trebalo bi da imaju pristup osoblju sa stručnim znanjem o traumi.
Buduća ponuda će biti osmišljena u najboljem interesu svakog djeteta i uključivat će specijalističke usluge i pakete po mjeri kako bi se zadovoljile često složene potrebe djece i mladih
Razmatrat će širi sistem zaštite i pravosuđa, a ne osiguravati njegu u izolaciji.
Meghan Gallacher iz reda konzervativaca rekla je da je njena stranka podržala plan implementacije, ali je istakla da neki u sektoru zdravstvene zaštite smatraju da nije bilo napretka tokom pandemije.
Fiona McFarlane, šefica nadzora u The Promise Scotland, ranije je opisala nedostatak napretka kao `` srceparajuće i sramotno ''. Gospođa Gallacher je rekla: ``
Dok MSP u ovoj komori razumiju da je Covid uticao na rad u nekim područjima, zabrinjavajuće je primijetiti da su sveukupni napredak kritizirale organizacije, dobrotvorne organizacije i oni koji su iskusili sistem njege.
Martin Whitfield iz Škotskih laburista rekao je da su potrebni značajni ciljevi za mjerenje ishoda za mlade ljude u sistemu brige. On je naveo: ``
Ishodi su trenutno, sasvim iskreno, strašni i stvari se moraju promijeniti... a škotski laburisti vjeruju da će nam ovi ciljevi u cijelosti pomoći da utvrdimo gdje područja zaostaju, ishode koje treba kritički sagledati.
https: //www.bbc.com/news/uk-scotland-60934546
https: //www.bbc.com/news/uk-scotland-60934546
Ovaj sadržaj je relevantan za državu ( e)
Protective factors & resilience | general |
Under 18s will no longer be sent to young offenders institutions | The Scottish government made a new plan according to which Sixteen and 17-year-olds in Scotland will not be placed in young offenders ' institutions. The idea behind this plan is idea to fund `` care-based alternatives '' and shift the approach from `` one of punishment to one of love and support '' they want to end the placement of under 18s in custody `` without delay ''.
It is one of 80 steps contained in a
plan to improve the lives of children in care and their families
. The document also outlines plans to give a £200 annual grant to young people aged 16-25 with experience of the care system. And it says a recommended national allowance for foster and kinship carers will be introduced.
The Promise by the Independent Care Review
in 2020, which said many young people experienced a `` fractured, bureaucratic and unfeeling '' system.
Clare Haughey, the minister for children and young people, said the government was committed to fulfilling The Promise by 2030.
These ambitious actions will help families to thrive so they can safely stay together... support carers and families engaged with the care system, as well as care leavers and care experienced people in education and employment.
A consultation on legislation -
the Children's Care and Justice Bill
- to stop this practice was launched on the end of march.
The Scottish government says that if a child needs to be deprived of their liberty, it should be in a
`` child friendly and rights respecting '' environment.
They should have access to staff with expertise in dealing with trauma.
The future offer will be designed in the best interests of each child and will include specialist services and bespoke packages in order to meet the often complex needs of children and young people
It will consider the wider care and justice systems rather than secure care in isolation
Conservative MSP Meghan Gallacher said her party supported the implementation plan but noted that some in the care sector felt there had been a lack of progress during the pandemic.
Fiona McFarlane, head of oversight at The Promise Scotland, has previously described the lack of progress as `` heartbreaking and shameful ''. Ms. Gallacher said: ``
While MSPs across this chamber understand that Covid has impacted delivery across some areas, it is concerning to note that the overall progress has been criticized by organizations, charities, and those who have experienced the care system.
Scottish Labour's Martin Whitfield said meaningful targets were needed to measure the outcomes for young people in care.
The outcomes are currently, quite frankly, dreadful and things must change... and Scottish Labour believes that these targets across the board will help us identify where areas are falling behind, outcomes that need to be critically looked at.
https: //www.bbc.com/news/uk-scotland-60934546
https: //www.bbc.com/news/uk-scotland-60934546
Protective factors & resilience | general |
Dow, S & P 500 snap four-session win streak as stocks close lower on fading Ukraine optimism | U.S. stock benchmarks finish lower in choppy trade Wednesday, as investors reassessed potential progress between Russia and Ukraine negotiators and heard more hawkish tones from the Federal Reserve.
On Tuesday, the Dow Jones Industrial Average rose 338.30 points, or 1%, to close at 35,294.19, rising for a fourth straight day. The S & P 500 gained 1.2% to finish at 4,631.60, exiting correction territory and marking its fourth straight gain, according to Dow Jones Market Data. The Nasdaq Composite climbed 1.8% to end at 14,619.64, its second consecutive day of gains.
Read: S & P 500 exits correction: Here's what history says happens next to U.S. stock-market benchmark
Stocks slipped and oil prices pushed higher Wednesday after Russian forces shelled areas around Kyiv and another Ukrainian city overnight, just hours after it pledged to `` fundamentally '' cut back operations in the areas, Associated Press reported.
`` We do expect a little profit-taking after four days of gains but big picture-wise, we continue to expect volatility, '' Greg Bassuk, chief executive at AXS Investments, said in a phone interview.
In addition to developments in the Russia-Ukraine war, investors also heard from Kansas City Federal Reserve President Esther George, who said the central bank must move expeditiously away from an easy policy stance. That should include a significant reduction of the Fed's near $ 9 trillion balance sheet, she said.
`` We essentially have an economy that is operating still under very significant stimulus and very low rates compared with historical averages, '' said Matt Peden, senior portfolio manager of the Invesco Global Select Equity Strategies, in a phone call.
`` That leads to a lot of uncertainty as to the true underlying state of the economy. ''
To that end, Peden's focus is long-term and on stocks that can manage revenue growth despite higher interest rates, elevated inflation and the threat of an economic slowdown, such as the technology and payment sectors, rather than shorter term plays in commodity and financial companies that have seen gains in recent months.
Crude oil prices rose 3.4% to settle at $ 107.82 a barrel, recouping losses from Tuesday when the commodity briefly dipped below $ 100 for the first time since midmonth.
In U.S. economic data, U.S. fourth-quarter gross domestic product growth was revised to an annualized 6.9% from 7%. Meanwhile, ADP said the private sector added 455,000 jobs in March. Economists surveyed by Dow Jones Newswires and The Wall Street Journal forecast a private-sector payrolls gain of 450,000.
On the COVID-front, the omicron subvariant known as BA.2, which is even more contagious than the original omicron but seems no more lethal, accounted for more than half of new COVID cases in the U.S., according to estimates from the Centers for Disease Control and Prevention on Tuesday.
President Joe Biden on Wednesday said improvements on the vaccination front, treatments and more means the COVID-19 pandemic `` no longer controls our lives, '' in a speech, while unveiling a new website that aims to help Americans deal with the pandemic.
Investors also kept watch on the bond market after the yield on the 2-year Treasury note traded briefly above the yield on the 10-year note Tuesday afternoon, temporarily inverting the yield curve.
The phenomenon is widely viewed as an early warning signal of a potential economic downturn, though some analysts caution that it serves as a poor market timing tool. Yields were easing across the board on Wednesday.
`` We think investors aren't so sure that these inverted yield curves really will lead to a recession, '' due to `` the other, more positive indicators, '' according to AXS's Bassuk.
-- Barbara Kollmeyer contributed reporting to this article.
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Corporate Liability Reform in the UK is Accelerating: Your GRC Teams Need to Future-Proof Compliance | The UK’ s just-enacted corporate crime legislation is a step in the right direction but failed to address a wide range of risks and challenges. Nonetheless, in the current climate, more legislation will soon follow. In light of such developments, global risk and compliance teams need to take a fresh look at their UK operations.
Does the UK face a corruption challenge? In January, Lord Theodore Agnew, the minister in the treasury and cabinet office with responsibility for counter-fraud and cross-government efficiency, unexpectedly resigned. His cited reason: the government’ s “ lamentable ” oversight of the COVID-19 loans schemes and ministers “ foolishly ” shelving plans to introduce a new economic crime bill in the coming parliamentary session.
The stir following Agnew’ s statements and resignation prompted members of Parliament to debate the urgent need to reform the allegedly weak and outdated legislation that, according to them, has turned the city of London into a haven for illicit financial flows from across the world. Enter the surprise crisis in Ukraine, and a UK government economic crime bill suddenly found swift passage to become law.
The Economic Crime ( Transparency and Enforcement) Act focuses on foreign ownership of UK property, unexplained wealth orders and proposals to assist the Office of Financial Sanctions Implementation ( OFSI) in sanctions enforcement actions. The government has also published proposed reforms to Companies House, the entity responsible for maintaining a register of companies in the UK.
A handful of issues deserving attention are disappointingly overlooked by the legislation. In particular, the director of the Serious Fraud Office ( SFO) previously advocated changing the law relating to corporate criminal liability. In particular, the House of Commons Treasury Committee re-emphasised in its Jan. 26 2022 report that failure to reform these rules would mean “ corporate criminals will continue to [ … ] escape prosecution. ”
The first mooted aspect is the need to reform or expand the “ controlling mind ” test. Under current legislation, corporates can only be liable for most criminal offences if those who represent the “ directing mind and will ” committed the wrongdoing.
As the SFO commented in June 2021, this test makes it difficult to prosecute companies where mid-level employees commit misconduct. For example, the SFO prosecution of Barclays bank in 2018 failed when the high court interpreted the requirement as meaning members of the bank’ s board had to have committed the alleged misconduct to warrant charges.
The second key issue absent resolution within the crime bill is the need to create a new criminal offense for “ failing to prevent economic crime. ” Such a rule would be similar to the existing offenses of failure to prevent bribery and failure to prevent the facilitation of tax evasion. This would allow, for example, banks to be held to account for granting fraudulent coronavirus bounce-back loans.
The hastily enacted crime bill is not the only piece of economic crime legislation with which corporate compliance executives need to grapple. But in general, the recent flurry of activity which aims to improve the UK’ s response to economic crime is to be welcomed.
Moreover, experts in economic crime have long argued that these and other changes are essential given the UK’ s major role in the global economy. Given current attitudes and momentum, GRC managers should expect to see more changes arriving in the short term.
Note that a robust and effective compliance structure may accomplish more than prevention or mitigation. In the event of an offense, evidence of a robust and effective compliance structure can be a mitigating factor in reducing a penalty or sentence imposed by the courts.
Each organization and sector are different. Nonetheless, all should consider taking actions such as:
Sanctions have entered the public consciousness to a degree and manner previously unseen. This will undoubtedly spotlight economic crime and sanctions violations in the coming months. However, in the absence of concrete reforms to corporate liability legislation, it can be difficult for companies to respond. Taking steps now to strengthen existing compliance structures will help future-proof organizations and lessen the potential burden to compliance teams.
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SBA Will Expand a Key Obama-Era Lending Program for Low-Income Business Owners | The Small Business Administration's Community Advantage pilot program is getting an upgrade.
In a joint announcement today, Vice President Kamala Harris and SBA administrator Isabel Guzman signaled key changes to the loan program, initialized in during the Obama administration to help improve access to SBA programs, among community lending partners including Community Development Financial Institutions ( CDFIs), Community Development Companies ( CDCs), and micro-lenders.
Designed to meet the credit, management, and technical assistance needs of small businesses in underserved markets, the SBA's Community Advantage pilot loan program was originally set to expire in September 2022. After today's announcement, the program's new sunset date is September 30, 2024.
Business owners applying for 7 ( a) working capital loans through the community institutions will receive up to $ 350,000, up from $ 250,000. They will be able to access up to $ 50,000 in unsecured loans, up from $ 25,000. The reforms will also let lenders and other institutions make available revolving lines of credit, interest-only periods, and other loan modifications to provide more capital options for those who need it. Former restrictions that kept individuals with criminal backgrounds from accessing these programs will also be lifted.
`` America's mission-driven lenders have been a critical partner to the SBA in getting much-needed financial relief to underserved businesses throughout the Covid pandemic. Scaling the SBA's Community Advantage pilot program will help us build on that momentum, '' said Guzman in a press release.
The changes will be effective 30 days after publication of this notice in the Federal Register, which is expected early next month, according to the SBA. Borrowers can already apply for regular 7 ( a) and 504 loans for up to $ 5 million through existing program lenders, some of which are Minority Depository Institutions ( MDIs) and credit unions, institutions that tend to cater to founders in underrepresented communities.
There's a full list of all the community lenders on the SBA's website. | business |
A most crucial time to debate commodity flows | Many of you will be familiar with the famous saying that: ‘ The first casualty of war is truth’. Following the Russian invasion of Ukraine, this saying is highly poignant as truth continues to not only be twisted but also turned around, and in some cases dumped completely upside down or shut out altogether. Some governments and their official news media seem to be pretending the war is not even happening! However, one thing is sure, one month in and the suffering for the Ukrainian people is continuing relentlessly and large parts of the country have been and continue to be devastated by Russian military attacks – from land, sea and air.
This war is not the Russian people’ s war – it is a war wrongly designed and thrust forward by Putin. Consequently, Russia is now being squeezed by a range of sanctions on financial institutions, companies and individuals as well as through asset freezes and other financial measures. Many foreign companies have exited business in Russia or temporarily halted activities. But as we all know, despite the conflict, the sanctions and other restrictions, trade obviously goes on. At the same time, huge questions are raised. How does this conflict impact us all on a commercial and financial level? What should we be doing to protect our interests? What commercial problems have arisen and are looming regionally/globally? How will commodity supply chains be impacted? Are there immediate trading opportunities elsewhere? What might we expect in the short- to medium-term?
As TXF brings together the commodity finance community on 10-11 May in Amsterdam for the TXF Global Commodity Finance Conference, we will be able to discuss many of the issues surrounding the impact of the war in Ukraine on the commodity markets, supply chains, financing and logistics – as well as how it affects global flows and costs. We have revised the programme and have introduced some new sessions so that a better understanding of the commercial picture can be discussed.
On day 1 of the conference we will have a key supply chain disruption panel entitled: ‘ Which other regions can cushion the fall?’ With heavy sanctions in place against Russia, and serious reputational risk associated with doing business even with unsanctioned Russian entities, a huge part of the commodity trade finance world has been cut off. It will also be extremely difficult to do business in Ukraine and Russia for the next few years at least. Where will banks be looking to open new credit lines in the wake of this? Do some of the emerging regions, such as Africa, LatAm, and South-East Asia, have the capacity to bridge the production gap left by Russia and Ukraine at such short notice? And what impact will this have on already skyrocketing energy and agri commodity prices?
On day 2, we have a dedicated session on the Ukraine/Russia situation entitled: ‘ Can existing solutions help the fall-out?’ Supply chain disruption was an issue before the Covid pandemic, but as this, and the Russian war on Ukraine has shown, the commodity finance industry is never far from the next big threat to supply. What solutions are already available to corporates to help secure access to supply? Are these solutions enough to hedge the mammoth fall-out of the Russia/Ukraine conflict? What will happen to sectors such as grain/fertilisers, gas, and metals if severe supply shortages are ongoing?
As I wrote in the Weekly blog on 2 March entitled: Russia/Ukraine: economic fallout will be extreme!, some four weeks on and the serious reality of the commodity supply situation is now much more obvious. Much has been said already on the issue of Russian gas and oil in particular, but beyond the energy sector there are real and very serious concerns around global food security.
The supply of grains and oilseeds from Ukraine and Russia – as well as fertiliser, where Russia is the world’ s biggest exporter - is of immediate global concern, particularly as much of the exports go to Africa and the Middle East. Supplies are becoming increasingly tight, storage capacity in many countries is minimal and prices across the board have increased dramatically. For example, wheat prices climbed to an all-time record in Chicago earlier this month.
Russia is the largest exporter of wheat in the world and Ukraine is the fourth. Both countries are leading producers of maize ( corn), barley and oilseeds such as sunflower. According to the USDA in 2020/2021 Russia and Ukraine combined accounted for approximately 26% of global wheat exports, 46% of global barley exports, and 16% of global maize ( corn) exports. In addition, on the oilseeds front, Ukraine and Russia combined accounted for a staggering 80% of global exports in sunflower seed meal and sunflower seed oil in 2020/2021. As a comparison to this, International Grains Council data shows that Ukraine was the world’ s fourth largest grain exporter in the 2020/21 season while Russia ranked third. The two countries combined accounted for 22% of global grain exports.
On 23 March the director-general of Unctad, Ngozi Okonjo-Iweala, stated: “ It is becoming clear that the Ukraine war’ s economic and humanitarian repercussions – especially rising food prices – will be felt far beyond Europe. The international community must act now to prevent some of the world’ s poorest and most vulnerable people from becoming collateral damage. ”
And with this in mind, just two days ago, Okonjo-Iweala, called for coordinated action to address the recent sharp rise in commodity prices that threatens food security in many countries. `` Trade has been and will remain a critical means of adaptation to the mounting global shocks that the world is currently experiencing, '' the director-general declared. `` This is not the time to retreat inward … This is the time to stress the importance of multilateralism, global solidarity and cooperation. ''
The war in Ukraine has caused immense human suffering and loss of life and unleashed an ongoing humanitarian crisis, the director-general noted. It has also dealt a severe blow to the global economy still recovering from the impacts of the pandemic and has raised the spectre of food shortages in countries dependent on Ukraine and Russia for imports of key staples like wheat. Already in Africa, prices of key commodities have risen by 20% -50% between January and March.
`` For dozens of poor countries and tens of millions of people, basic food security is in danger, '' she warned. `` These countries already have been some of the slowest economic recoveries from the pandemic, and international cooperation on trade is necessary to help mitigate risks of poverty, hunger, even famine and social unrest. ''
In the near-term, international cooperation on trade will be needed to minimise the impact of supply crunches for key commodities where prices are already high by historical standards and to keep markets functioning smoothly, the director-general said.
Okonjo-Iweala also pointed out that countries with buffer stocks that can afford to share could coordinate the release of wheat, barley, other cereals and grains and oils into international markets, thereby alleviating the supply squeeze. Countries such as the United States, Canada, Australia, Argentina, and France could increase wheat cultivation while others such as China, Germany, Morocco, Saudi Arabia, Egypt, and Nigeria could increase the global supply of fertiliser.
With the Russian navy controlling access to the Ukrainian ports in the Black Sea and Sea of Azov, most eastern Ukrainian ports are completely blocked. Beyond this, Russia would appear to have specifically targeted some key port commodity exporting infrastructure. In Mykolayiv on the Black Sea, for example, which handles around one fifth of Ukraine’ s grain exports, it has been reported that a grain exporting site owned by soft commodity trader Bunge had been destroyed. Many other international soft commodity trading companies also have facilities and silos at Ukrainian ports. While in Mariupol, heavy shelling has also severely damaged the major Azovstal steel plant.
These examples and others, led the Ukrainian agriculture minister, Roman Leshchenko, to inform the European Parliament last week: “ This is a war not only in the military sense, it’ s an economic war, because Ukrainian exports are metals, chemicals, machine building and grain. Having destroyed our sea access, they are destroying us economically. We wouldn’ t have any income to our budget. We wouldn’ t have any means to survive as a state. ”
Ukraine exported around $ 27 billion in agricultural products in 2021, making up about half of its total export income. And, according to a Reuters report, with ports closed off, Mykola Gorbachev, chairman of the Ukrainian Grain Association, stated: “ We are sitting on a potential loss of $ 6 billion. ” This is related to wheat and maize exports which had been earmarked for export by June. He is also reported to have said Ukraine had around 20 million tonnes of wheat and corn still to export from the 2021/22 season, which ends in June, at an average price of around $ 300 per tonne. In addition, Ukrainian maritime officials said fighting had left around 100 foreign-flagged vessels stranded in the country’ s ports.
It is also a crucial time of the year for Ukrainian agriculture as Spring planting of key crops needs to take place over the next month or so. The war makes this immensely difficult. Last year, Ukrainian farmers produced a record crop, but some farmers this year lack fuel for machinery and fertiliser for land preparation. The Ukrainian Agriculture Ministry estimates sowing areas may shrink by 30% to 50% from last year.
In the meantime, some Ukrainian grain exports are getting out. According to Bloomberg, Ukraine’ s deputy economy minister, Taras Kachka, said that shippers managed to export more than 1 million tons of corn and 300,000 tons of wheat since the beginning of March, mostly from seaports that are under Ukraine’ s control near the border with Romania. More exports would be possible apparently if the country’ s rail network was functioning properly.
On the other hand, Russian grain exports are understood to be at near normal levels through March, with around 2 million tons of grain exported. However, going forward reports indicate that new orders are minimal compared to previous seasons. Operational risks related to delivery and payment are likely to see business plummet in coming months. Bunge has said that it has suspended new export business with Russia, although some other grain traders are continuing with Russian exports but operating in line compliant with the current imposed sanctions.
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TXF and the TXF: Trade and Export Finance logo are registered and owned by TXF Limited, a company registered in England and Wales with company number 08421624. | general |
Biden administration to lift COVID limitations on asylum claims at southern border | WASHINGTON ( AP) — The Biden administration is expected to end the asylum limits at the U.S.-Mexico border by May 23 that were put in place to prevent the spread of COVID-19, according to people familiar with the matter.
The decision, not yet final, would halt use of public health powers to absolve the United States of obligations under American law and international treaty to provide haven to people fleeing persecution, and would apply to all asylum seekers.
Ending the limitations in May would allow for time to prepare at the border, the people said. But the delay runs against the wishes of top Democrats and others who say COVID-19 has long been used as an excuse for the U.S. to get out of asylum obligations.
It also raises the possibility that more asylum-seeking migrants will come to the border at a time when flows are already high. The Department of Homeland Security said Tuesday that about 7,100 migrants were coming daily, compared with an average of about 5,900 a day in February and on pace to match or exceed highs from last year, 2019 and other peak periods.
The Centers for Disease Control and Prevention had extended its asylum-blocking powers for two months in late January, near the height of the omicron variant. The authority is up for renewal this week, but officials have not formally decided to terminate it yet and an announcement was expected over the next few days.
The people familiar with the plans saw a draft report that has not been finalized and they spoke to the Associated Press on condition of anonymity to discuss the plans.
Biden on Wednesday declined to discuss his administration’ s plans, telling reporters at the White House, “ We’ ll have a decision on that soon. ”
The limits went into place in March 2020 under the Trump administration as coronavirus cases soared. While officials said at the time that it was a way to keep COVID-19 out of the United States, there always has been criticism that the restrictions were used as an excuse to seal the border to migrants unwanted by then-President Donald Trump.
It was perhaps the broadest of Trump’ s actions at the border to restrict crossings and crack down on migrants. The health order has caused migrants to be expelled from the United States more than 1.7 million times since March 2020 without a chance for them to request asylum.
The limits took effect over the objections of CDC officials, and Dr. Martin Cetron of the Division of Migration and Quarantine refused the order to begin its use. He said there was no public health basis for such a drastic move, the AP reported. But then-Vice President Mike Pence ordered the CDC’ s director to use the agency’ s emergency powers and it went into effect.
The limitations on seeking asylum became more difficult to defend on scientific grounds as mask mandates were lifted, vaccination rates climbed and COVID-19 rates dropped among migrants crossing from Mexico.
President Joe Biden, who has rolled back some of Trump’ s other more restrictive policies and reinstated higher asylum figures, has taken increasing criticism for maintaining the so-called Title 42 policy.
From WSJ.com:
Court upholds federal government’ s Title 42 border policy
Homeland Security officials, Senate Majority Leader Chuck Schumer of New York and other top Democrats were increasingly vocal about wanting to end Title 42 authority, named for a 1944 public health law to prevent communicable disease.
Schumer called it “ perplexing that the [ CDC ] continues to recommend the extended use of this draconian policy at the border, contradicting the overwhelming signs of America’ s pandemic recovery under President Biden’ s leadership. ” His comments were in a joint statement this month with Democratic Sens. Cory Booker and Bob Menendez of New Jersey, and Alex Padilla of California.
Not all Democratic elected officials agreed, including some from border and swing states. Sens. Mark Kelly and Kyrsten Sinema, both Arizona Democrats, sided with Republican leaders to say Title 42 should remain until U.S. border authorities were prepared for sharp increases in new arrivals.
And they’ re not. Homeland Security officials said Tuesday they were planning for as many as 18,000 arrivals daily, an astounding number that they cautioned was simply to prepare for all possible outcomes, not projections.
But there has been no major changes to how migrants are processed at the U.S.-Mexico border and no increase in holding facilities for them. The immigration court backlog continues to soar to more than 1.7 million cases.
While there is no aggregate rate for migrants, COVID-19 test results from several major corridors for illegal border crossings suggest it is well below levels that have triggered concerns among U.S. officials.
In California, 54 of 2,877 migrants tested positive in the first two weeks of March, according to the state Department of Social Services. That’ s a rate of just 1.9%, down from a peak of 28.2% on Jan. 8.
In Pima County in Arizona, which includes Tucson, the seven-day positivity rate among migrants didn’ t exceed 1.3% in early March. The positivity rate among 5,300 migrants tested last month at the Regional Center for Border Health near Yuma, Ariz., was 0.1%.
McAllen, Texas, the largest city in the busiest corridor for illegal crossings, has a higher rate among migrants — 11.3% for the week ending March 16 — but it has been consistently lower than the general population.
Critics say Title 42 has been an excuse to avoid asylum obligations under U.S. law and international treaty, buying Biden time to create the “ humane ” asylum system that he promised during his 2020 campaign.
Justin Walker, a federal appeals court judge in Washington, wrote this month in an order restricting the policy that it was “ far from clear that the CDC order serves any purpose ” for public health. Walker, who was appointed by Trump, noted that the Biden administration has not provided detailed evidence to support the restrictions.
“ The CDC’ s order looks in certain respects like a relic from an era with no vaccines, scarce testing, few therapeutics, and little certainty, ” Walker wrote for a three-judge panel.
CDC Director Dr. Rochelle Walensky noted falling rates when she ended asylum limits on unaccompanied child migrants on March 11, while keeping them for adults and families with kids. In August, U.S. border authorities began testing children traveling alone in their busiest areas: Positives fell to 6% in the first week of March from a high of nearly 20% in early February. | business |
Opec-Plus Eyes Modest Bump Up in Supply | Opec-plus is expected to implement a previously agreed plan to change oil production baselines for five countries on Thursday, which could lead to a modest increase in volumes reaching the market, delegates told Energy Intelligence.
If approved by member states ' ministers on Thursday, monthly increases in the alliance's combined output would rise to around 432,000 barrels per day in May-September, from 400,000 b/d since August of last year — at least on paper.
While the alliance has been targeting steady monthly increases, it has recently been falling short of its 400,000 b/d goal because many members are unable to raise their output any further.
On top of this, Kazakhstan has said it expects its crude production to fall by around 320,000 b/d in April because of repairs at the Caspian Pipeline Consortium ( CPC) loading terminal on Russia's Black Sea coast.
It has also become difficult to quantify Russia's production and exports since it invaded neighboring Ukraine on Feb. 24.
The higher monthly increases from May are the result of a compromise reached last summer, when the United Arab Emirates ( UAE) requested a higher baseline production figure. The baseline numbers are used to determine countries ' quotas.
It was also agreed at the time that the group would gradually return 5.76 million b/d of production to the market over a 14-month period, which ends when the current pact expires in September.
Opec-plus had started out in May 2020 with production cuts of 9.7 million b/d to balance the market after the Covid-19 pandemic caused demand for oil to collapse.
The agreement reached with the UAE also provided for increases in the baselines of Saudi Arabia, Russia, Kuwait and Iraq from May of this year.
The baselines of Saudi Arabia and Russia will each rise by 500,000 b/d, while the UAE's will go up by 332,000 b/d and Iraq's and Kuwait's each by 150,000 b/d.
Energy Intelligence understands that delegates agreed in July that the 432,000 b/d increment would be redistributed among the group’ s members bearing in mind the new baselines.
This means that from May, Saudi Arabia would have a production quota of 10.549 million b/d and the UAE of 3.04 million b/d.
The targeted increases in Opec-plus output should reach the market as both Saudi Arabia and the UAE — which hold most of the group's spare capacity — will be allowed to pump more oil.
During a meeting on Wednesday of the alliance's Joint Technical Committee ( JTC), technocrats agreed that, for now at least, the market remains balanced — despite supply risks associated in particular with the war in Ukraine.
`` There is no reason to change the agreement now because there is no shortage in the market, '' said one delegate.
Delegates also said Opec-plus is dropping the International Energy Agency ( IEA) as one of the secondary sources used to assess members ' crude oil production and compliance with production cuts. Wood Mackenzie and Rystad Energy will replace it.
Tension has been building between the IEA and Opec-plus for some time.
IEA Executive Director Fatih Birol recently said that he was `` really disappointed '' by Opec-plus producers ' lack of a sense of urgency during the current tight market.
The agency's position on the transition to low-carbon energy, particularly last year’ s net-zero report, has also annoyed some in Opec-plus.
Earlier this week, Saudi Energy Minister Prince Abdulaziz bin Salman and his Emirati counterpart Suhail al-Mazrouei stressed the importance of maintaining unity within Opec-plus and underlined the importance of Russia's membership.
As Russia continues to attack cities in Ukraine, Western efforts to isolate Moscow will continue, inevitably raising pressure on other countries to choose sides.
Energy Intelligence understands that US officials have quietly lobbied Opec-plus to eject Moscow but have met strong pushback from Mideast Gulf producers, who insist the alliance must divorce politics from its supply management work.
However, at a time of geopolitical upheaval and intense back channel diplomacy, surprises remain a possibility.
The alliance will also have to take into account the production outage in Kazakhstan, the possibility of Iranian oil returning to the market if a new nuclear deal is struck, and rising Covid-19 infections in China. | general |
SARUS-CPR hood adopted by NHS Tayside | A piece of equipment named the SARUS-CPR hood has been adopted into clinical practice by NHS Tayside following its development in response to the COVID-19 pandemic.
SARUS-CPR hood to be formally adopted into clinical practice after positive report.Hood inventor Professor Peter Stonebridge with Sam Fernando, sales director at Keela at Ninewells Hospital in Dundee.Photograph by Martin Shields Tel 07572 457000www.martinshields.com© Martin Shields
The hood was invented by Professor Peter Stonebridge, NHS Tayside’ s medical director, and further developed by ENT surgeon and NHS Tayside clinical lead for the project, Rod Mountain.
The SARUS hood is made from transparent fabric and creates a barrier between the patient and the individual performing resuscitation. It reduces the risk of contamination and infection from bacteria and viruses such as COVID-19.
NHS Tayside, Scottish Health Innovations Ltd ( SHIL), and performance manufacturer Keela Outdoors collaborated to design and develop the game-changing device that is set to revolutionise the resuscitation process for first responders.
Robert Rea, head of innovation at Scottish Health Innovations Ltd ( SHIL), said: “ The SARUS-CPR hood is a real testament to home grown collaborative expertise, taking clinician-led insight from the NHS and turning it into a tangible device that has now been launched onto the market. ”
The SARUS-CPR hood – an acronym of Safer Airway Resuscitation – has been designed to allow trained CPR responders to easily fit it onto a collapsed patient as soon as they arrive on the scene. This helps to also reduce the time taken to initiate airway ventilation and makes resuscitation much safer for both patients and personnel.
It can be used by trained personnel in a wide range of settings, including hospitals, GP surgeries and ambulances.
Reflecting on device’ s development, NHS Tayside’ s medical director, Professor Peter Stonebridge said: “ The entire spectrum of healthcare workers and caregivers has been absolutely vital to fighting the pandemic and in analysing potential solutions to the challenges of COVID-19 – there has been a lot of innovative problem-solving.
“ In this instance, thanks to the input of other experts, the kernel of an idea has been developed into the fully realised SARUS-CPR hood. I am very grateful to all the collaborators on this project whose ideas and ingenuity helped us get to this landmark moment as we adopt the SARUS-CPR hood into clinical practice here at NHS Tayside. ”
Rod Mountain, NHS Tayside clinical lead for the project added: “ As an NHS worker, I am immensely proud to have been part of its development. This has been a genuine collaborative effort between NHS Tayside, SHIL, and Keela, drawing upon fantastic local engineering and garment manufacturing expertise. COVID-19 drove the innovation, prompting us to look at different approaches to PPE, but we now know its applications go well beyond the current pandemic. ”
Robert Rea, Head of Innovation at SHIL, said: “ The teams at NHS Tayside and Keela have played a vital role in realising thisambition. Their clinical and manufacturing expertise combined with SHIL’ s intellectual property and commercialisation expertise has accelerated the hood’ s adoption. ”
The SARUS-CPR hood is an example of Scottish Health Innovations Ltd ( SHIL) working collaboratively to create an innovative, commercial product which provides a simple solution to globally relevant disease transmission risks faced by CPR personnel.
Keela managing director, Ruwan Fernando, said: “ After creating surgical gowns for the NHS, we were delighted to be approached by NHS Tayside to be part of the SARUS-CPR hood project. Our team of designers worked in collaboration with the NHS to design, prototype, and engineer the Safer Airway Resuscitation Hood.
“ The device itself is made up of existing CPR airway components encapsulated within a protective barrier hood allowing for efficient adoption in a clinical setting. With the support, guidance, and funding of SHIL, we are delighted to be able to reveal and launch the SARUS-CPR hood. ”
As part of the development process, the SARUS-CPR hood has undergone extensive trials. The Scottish Health Technologies Group ( SHTG), a national health technology assessment ( HTA) agency, reported positively on the SARUS-CPR hood.
SHTG provides advice to NHS Scotland on the use of new and existing health technologies that are likely to have significant implications for people’ s care. SHTG’ s SARUS findings – in the form of an Innovative Medical Technology Overview ( IMTO) – have allowed NHS Tayside to formally adopt the hood into clinical practice.
Among key findings, it was found that the technical tasks of performing CPR using a mannequin were conducted “ equally well with the hood employed when compared with the use of standard CPR equipment. ”
After its initial launch by NHS Tayside, it is expected the SARUS-CPR hood will be available for wider use later this year. | tech |
Vietnam to invest $ 2 billion in a US-based EV factory | With a goal of becoming an all EV manufacturer.
Vietnamese automaker VinFast announced on Tuesday that it signed a preliminary deal to make an initial investment of $ 2 billion to construct its first U.S. factory in North Carolina.
VinFast’ s factory investment will be to manufacture electric buses, SUVs, and electric vehicle batteries.
The company is owned by Vietnam’ s biggest conglomerate, Vingroup, and it plans to make a total investment of $ 4 billion in its factory complex. VinFast became Vietnam's first completely domestic car manufacturer in 2019 and it plans to be an all-electric vehicle manufacturer by late 2022.
This will be North Carolina’ s first car plant and it is the largest economic development announcement in the state’ s history, the governor's office announced in a statement.
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VinFast’ s factory will create a major manufacturing center on a 1,977-acre plot for phase 1 with 3 main areas: electric cars and buses production and assembly, EVs batteries production, and ancillary industries for suppliers.
U.S. President Joe Biden said the VinFast investment, which will create more than 7,000 jobs, is `` the latest example of my economic strategy at work. ''
`` It builds on recent announcements from companies like GM, Ford, and Siemens to invest in America again and create jobs '' added Biden, as he set an ambitious goal of making half of the new car sales to be electric vehicles by 2030.
The first phase of the investment is expected to be completed by July 2024 and the company will have the annual capacity of producing 150,000 vehicles, according to VinFast.
The company has begun accepting pre-orders globally for two electric SUVs and aims to begin delivering said vehicles in the fourth quarter of the year. VinFast aims to sell 42,000 electric vehicles globally this year.
The company also announced that prices for its VF8 sports SUV start from $ 41,000 in the U.S. Compared to Tesla’ s SUV price at around $ 63,000, that's quite affordable.
`` With a manufacturing facility right in the U.S. market, VinFast can stabilize prices and shorten product delivery time, making our EVs more accessible to customers, '' said Nguyen Thi Thu Thuy, Vingroup vice-chair and VinFast Global CEO.
Let’ s see if VinFast can achieve its goal of manufacturing 150,000 vehicles per year. Raw material costs have surged as the supply chain disruptions caused by COVID-19 pandemic still haven’ t recovered, which increases the costs of production.
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By subscribing, you agree to our Terms of Use and Privacy Policy. You may unsubscribe at any time. | tech |
Chris Froome STILL has disc brake problems | Like this site? Help us to make it better.
Four-time Tour de France winner Chris Froome has revealed that he still regularly experiences disc brake issues but he has a solution of sorts: he puts earphones in so he can’ t hear them rubbing.
Froome has had well-documented issues with disc brakes in the past. Way back in 2016, before the widespread adoption of disc brakes in professional road racing, Froome said that having different braking systems in the peloton would be more dangerous.
“ I’ d say either everyone uses them, or no-one does, ” he commented.
Then Froome spoke about disc brakes in a YouTube video early last year. He said, “ I don't think the technology is quite where it needs to be. ”
He said that he wasn't “ 100 per cent sold ” on the technology and mentioned that he had concerns over rubbing, overheating and the potential for rotors to warp.
Froome tried a number of different parts with the aim of alleviating the problems. Rather than the Shimano equipment normally used by Israel Start-Up Nation, Froome’ s bike was fitted with Magura MT8 SL FM disc brakes during the 2021 Tour de France. The team also used SwissStop pads and rotors.
Froome returns to the subject of disc brakes in his latest YouTube video.
“ I don’ t know if you can hear that, ” he says.
We can hear that – ‘ that’ being the sound of his disc brakes rubbing.
“ My entertainment with disc brakes continues. I think they're sort of work in progress. I think the technology is improving but the margins are so slim. You do a big descent and the alignment moves completely so I need to stop and readjust everything again.
“ We’ re riding Shimano at the moment. I hear the new 12-speed Shimano has sorted out some of these issues but… with the 11-speed [ we’ re ] still getting a lot of rubbing, getting one piston firing more than the other one, which always puts things out of alignment.
Read our review of the Shimano Dura-Ace R9200 groupset
“ No matter how many mechanics I’ ve spoken to or taken the bike to, you just can't get 100% on top of that. [ You ] always… start getting a few issues as soon as you start doing some some really big descents.
“ But c’ est la vie, for the time being. Just put the earphones in and pretend I can't hear it. ”
Okay, it’ s not tackling the issue at source but this is one way of dealing with it.
Froome is still using 11-speed Shimano Dura-Ace R9100 components because, although launched last year, there have been supply issues with Shimano Dura-Ace R9200 mostly due to fallout from the Covid-19 pandemic.
Here’ s why the bike shortage isn’ t going away any time soon
Shimano says that its R9270 Dura-Ace hydraulic disc brake calliper has a 10% wider pad clearance than previously to reduce the chance of rotor rub.
Shimano also says that there’ s less heat deformation with its RT-MT900 rotors, meaning a reduced chance of interference.
In our review of the Shimano Dura-Ace R9200 groupset, Liam said, “ Yes, the pad clearance has been increased by 10 per cent but that is 10 per cent of a tiny gap. It isn't enough to clear a rotor warped by heat, and while the MT900 rotors are better than the old Dura-Ace design, I still prefer SwissStop or Campagnolo rotors with their solid design. They might be a touch heavier, but they don't seem to warp quite as easily.
“ This rotor warping results in that annoying ting-ting-ting sound when you come off the brakes after scrubbing off a lot of speed. You can also get a tiny bit of noise if you lean the bike over excessively when sprinting or out of the saddle on a climb. For me, it's an issue that can be solved by using a better rotor, though that will be a change you make based on personal preference. ”
It’ ll be interesting to hear Chris Froome’ s reaction when he gets to use Shimano Dura-Ace R9200
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Mat has been in cycling media since 1996, on titles including BikeRadar, Total Bike, Total Mountain Bike, What Mountain Bike and Mountain Biking UK, and he has been editor of 220 Triathlon and Cycling Plus. Mat has been road.cc technical editor for over a decade, testing bikes, fettling the latest kit, and trying out the most up-to-the-minute clothing. We send him off around the world to get all the news from launches and shows too. He has won his category in Ironman UK 70.3 and finished on the podium in both marathons he has run. Mat is a Cambridge graduate who did a post-grad in magazine journalism, and he is a winner of the Cycling Media Award for Specialist Online Writer. Now pushing 50, he's riding road and gravel bikes most days for fun and fitness rather than training for competitions.
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Hirokazu Matsuno, Japan's top spokesman, to also serve as vaccine minister | Chief Cabinet Secretary Hirokazu Matsuno said Tuesday he will take over the post of vaccination minister from Noriko Horiuchi, who is set to leave the job at the end of March.
Horiuchi’ s departure coincides with the end of a period designated by law for creation of the ministerial post in charge of work related to last summer’ s Tokyo Olympics and Paralympics, a title under which she has doubled up in the Cabinet of Prime Minister Fumio Kishida.
The total number of Cabinet ministers will decrease to 19 from the current 20 on Friday. When Kishida launched his Cabinet last October after becoming prime minister, he gave Horiuchi, who belongs to the faction he leads within the ruling Liberal Democratic Party, her first ministerial post.
Education minister Shinsuke Suematsu will be responsible for affairs associated with the Tokyo Games after Horiuchi leaves.
“ Third vaccine shots are critical in preventing COVID-19 infections or the risk of developing severe symptoms ( once infected), ” Matsuno said at a news briefing. He described accelerating the booster shot program as “ one of the most pressing issues for the Cabinet. ”
Kishida’ s pick of Matsuno, the public face of the Cabinet, is apparently intended to underscore that the government is fully committed to the vaccination drive. But Matsuno already has multiple titles in the Cabinet and faces the challenge of speeding up the booster shot program.
Japan has been accelerating provision of third COVID-19 vaccine shots but the inoculation rate was still below 40% as of Tuesday.
The infection situation in Japan has shown some signs of stabilizing after a surge in cases driven by the highly transmissible omicron variant, allowing the nation’ s 47 prefectures to be free of quasi-emergency measures against the pandemic.
But medical experts have cautioned against a lowered guard amid growing concern about the more contagious BA.2 subvariant of omicron.
Aside from the post of chief Cabinet secretary, Matsuno serves as minister in charge of mitigating the impact on Okinawa Prefecture from hosting the bulk of U.S. military installations as well as minister tasked with addressing North Korea’ s abductions of Japanese nationals in the 1970s and 1980s. | tech |
Five Critical Challenges Facing Pharma Supply Chains | There’ s little room for error in most global supply chains, but none for the pharmaceutical cold chain. Real-time visibility and tracking are critical to order accuracy, schedule reliability, inventory management and compliance in a high-value, highly regulated industry. Failure is measured in lost revenue, reputation and potentially patient lives.
Inability to easily identify potential disruptive events. The COVID-19 pandemic highlighted many of the core problems that pharma producers and distributors encounter daily, with vaccines produced at mass scale and requiring refrigeration within precise temperature ranges in transit and in storage. Q1 2021 Centers for Disease Control data suggested a 20% Covid vaccine loss due to cold chain issues, according to SDCExecutive.
For many pharmaceuticals, temperature deviations, or “ excursions ” of even a single degree or two beyond acceptable ranges during transit, or exposure to moisture, can render a shipment unusable, potentially triggering millions of dollars in losses.
A lot can go wrong in transit, from a truck breakdown to a refrigerated container genset malfunction, to human error in handling, to production or congestion delays. Exception events can quickly result in damaged or destroyed product, write-offs and subsequent lost sales. The IQVIA Institute for Human Data Science estimates that the biopharma industry loses $ 34 billion annually due to supply chain temperature-control failures.
Common practice among pharma shippers and logistics providers has been to use passive data logging devices that record data for downloading upon retrieval. Active devices that monitor and transmit back data in real time from the field have been available, but until recently active trackers were expensive and limited in their monitoring, with short battery life during frequent reporting. Software modules to collect, process and interpret that raw sensor data were costly and complicated to install and use before cloud computing.
A 2020 survey of 200 pharma manufacturers and distributors by supply chain analysts ParkourSC showed that more than a quarter of firms had experienced damaged, spoiled or lost inventory. Roughly 90% reported said they didn’ t have full visibility into their supply chains and didn’ t trust the in-transit data they were receiving.
The lack of real-time visibility slows response time to spot problems and take corrective measures. Lack of analytical capability after the fact hinders efforts to get at root causes and drive improvements.
Risk of OTIF failures. On-time in-full ( OTIF) delivery, a supply chain compliance measure developed by Walmart in 2017 that’ s now a pharma industry standard, gauges supplier performance in delivering to a customer exactly what was ordered, in the amount requested, at the correct location, on time. In pharma, OTIF is a top priority and an all-or-nothing proposition: delivering on time but not in full, or in full but not on time, is equivalent to not delivering at all.
If a truck breaks down or gets delayed, replacement stock must be sent, often at a much higher cost, to meet service-level agreement terms. Similarly, if any portion of a load is damaged and unusable, the entire load may be rejected. Building a replacement load dramatically increases the transportation spend, along with associated labor, fuel and packaging costs. Compounding the problem, manufacturers and retailers often have different definitions of “ on time ” and “ in full, ” creating confusion in supplier and carrier selection and in assessing penalties when partners fall short.
Real-time, end-to-end data insights and visibility from a trusted source, are key to collaborating and managing around in-transit shipments, to meet OTIF commitments.
Optimizing inventory levels, just in time. It would seem intuitive that pharma cold chain distribution would lend itself to a lean, just-in-time ( JIT) inventory model, because medicines and biologics are expensive to produce and can’ t be stored for extended periods. COVID-19 has demonstrated the risks to that model from supply chain uncertainty. At the same time, the perishable nature of drugs and their loss of efficacy as effective dates undercut resiliency strategies dependent on maintaining safety stocks.
Finding the right balance to optimize inventory based on the product portfolio and on historic demand and shipment patterns will be a continuing challenge.
Overstocking and the potential ripple effect. A related challenge experienced across industries during Covid is overstocking upstream in response to initial shortages — the so-called “ bullwhip effect ” — due in part to inadequate sharing of information. When orders sent to manufacturers and suppliers create larger variances or “ waves ” than sales to end customers, they can negatively impact operations, causing each link of the supply chain to underestimate or overestimate product demand.
Pharma is among the hardest-hit sectors from the bullwhip effect, due to the high shipment values involved, perishability of the product, and often the urgency in getting vaccines and other medicines where they’ re needed quickly. Residual effects from the pandemic haven’ t abated. Some of the causes are chronic, like infrastructure congestion or labor shortages; viruses and extreme climate events will likely be recurring. Resiliency will rely on end-to-end supply chain transparency and sharing of reliable, real-time data from a central, trusted source by supply chain partners.
Compliance-related issues. Pharma is among the most regulated of industries, subject to strict regulations and guidelines at all levels of government, including international bodies dealing with trade, public health, product safety and industry standards. Regulations extend beyond conditions like temperature or humidity in transit, to strict packaging, labeling and handling protocols.
Pharma shippers are required to maintain complete records of procure-to-pay shipment status that are easily accessible for regulatory review. Specifically, the U.S. Food and Drug Administration requires FDA-regulated companies to use digitized systems for electronic recordkeeping, signatures and data storage. Three-point National Institute of Standards and Technology ( NIST) calibration is mandated to certify accuracy of location, temperature, humidity and other tracking sensors. Good Automated Manufacturing Process ( GAMP 5) guidelines must be followed for validating computer systems that manage regulated content and compliance.
Navigating compliance at each step of the supply chain in this complex environment is a minefield, especially when undertaken by companies internally.
Boston-based Tive is a cloud-based, sensor-driven platform-as-a-service provider, delivering real-time, end-to-end supply chain visibility and shipment tracking on a subscription-lease model. In 2020 the company invented the first safety-approved, non-lithium-ion battery-powered tracker.
Tive’ s Solo trackers provide hyper-accurate location and condition reporting across all transport modes, to identify and help shippers mitigate service disruptions and manage logistics costs. Embedded at the container or SKU level, they generate and transmit real-time data, capturing temperature, humidity, shock, motion and light. GPS, Wi-Fi and cellular triangulation provide location accuracy within 10 meters — or better, with 2G-5G platform connectivity.
Temperature accuracy is within 0.5 degrees Celsius at ranges within 60 to minus 20 degrees. Each tracker meets FDA, 3-point NIST and GAMP 5 standards.
The cloud-based application, integrated with customer supply chain management or enterprise resource planning ( ERP) systems, conducts real-time, accurate visualization and monitoring of sensor data to develop predictive ETAs and improve OTIF rates. Real-time alerts enable proactive planning and rapid response to disruptions. Data and analytics, on user-friendly dashboards, simplify production of shipment analysis scorecards.
“ We prevent shipment delays and damage by reporting possible exceptions in real time, ” says Tive vice president-global marketing Jim Waters. “ It’ s about saving the shipment and executing on OTIF. ” Failing that, trackers provide a real-time record of events for purposes of a claim or compliance review.
Tive’ s shipment visibility solution helped pharma and life sciences 3PL Optimize Courier identify the source of a client’ s recurring cargo losses, and retrieve and redirect a $ 500,000 shipment misplaced in an aircraft refrigerated cooler at the wrong temperature. A European drug manufacturer shipping temperature-controlled medicines rescued a $ 1.5 million time-sensitive shipment, in a refrigerated container set to 6 degrees rather than 20 degrees, by reaching the carrier directly to reset the temperature and by ordering replacement products as a precaution.
In addition to pharmaceuticals, Tive serves clients with high-value, fragile or perishable shipments of art, electronics, coffee, automotive components and industrial equipment.
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COVID-19 Update: Adagio Gunning for EUA and mRNA Boosters Recommended | Although it looks — keep your fingers crossed — that we’ re on the downside of the COVID-19 pandemic in the United States, biopharma companies are still working on developing better treatments and preventions. Public health experts are keeping a close eye on the now-dominant Omicron subvariant BA.2 and ways of mitigating the spread of the virus. For those and more COVID-19 stories, continue reading.
Adagio Therapeutics announced that its Phase II/III trials evaluating adintrevimab as pre-and post-exposure prophylaxis ( EVADE) and treatment ( STAMP) for COVID-19 hit the primary endpoints. Adintevimab is a potent, broadly neutralizing antibody against SARS-CoV-2. Administered intramuscularly, it had a similar safety profile to a placebo. The company expects to submit an Emergency Use Authorization to the U.S. Food and Drug Administration soon.
Michael Ison, M.D., professor of Medicine in the Division of Infectious Diseases and of Surgery in the Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, said, “ The compelling data generated on adintrevimab in both of Adagio’ s clinical trials represent an important step toward further addressing the continuation of the COVID-19 pandemic. I am particularly encouraged by the consistent treatment effect observed across all three clinical settings and patient subpopulations, and the favorable safety profile, with just a single dose and convenient IM delivery for all patients. The risk reduction in the post-exposure prophylaxis setting regardless of serostatus translates to real-world use when clinicians might not know the vaccination or prior infection status of their patients. In the STAMP trial, adintrevimab showed prevention of hospitalization and death in the face of the ‘ highest-risk’ variant ( Delta) to date. ”
The U.S. Centers for Disease Control and Prevention recommend that the 17 million Americans given the single-shot Johnson & Johnson COVID-19 vaccine consider getting a booster with one of the mRNA vaccines from Pfizer-BioNTech or Moderna. They should also consider a second mRNA booster for the best protection. The recommendation is based on an analysis of data of so-called “ mix and match ” vaccines and boosters during the four months of the Omicron surge. The data found that even the J & J shot with a booster of J & J or one of the mRNA vaccines wasn’ t as effective as three shots of the mRNA vaccines in preventing ER visits or hospitalizations.
Omicron Sister Variant ( BA.2) Now Dominant Strain in the U.S.
As expected, the Omicron subvariant BA.2 is now the dominant strain in the U.S., according to the CDC. Believed to be anywhere from 30% to 50% more infectious than the original Omicron variant, BA.1, it does not appear to cause more severe disease. And so far, at least, it is not associated with significant increases in hospitalizations or deaths. It was reported to make up more than 70% of COVID-19 cases in New York. Overall, cases in the U.S. appear to be dropping, and per CDC’ s calculations, more than 91% of the U.S. falls into a low-risk category.
In a related story, the CDC conducted a survey of blood donor samples in December and then updated the data in February, finding that about 95% of people in the U.S. 16 years and older have identifiable SARS-CoV-2 antibodies. This indicates that most people have been exposed to COVID-19 or received vaccinations at least in the blood donor population. About 77% of the U.S. population has received at least one COVID-19 vaccine.
The CDC released an online calculator to assist people in deciding if they should isolate or quarantine after being diagnosed with COVID-19 or being exposed. After answering a few questions, the calculator will make recommendations on whether you should isolate, quarantine, get tested and how long you should take precautions such as masking. The program differentiates between isolating and quarantine, with isolation for mild or no symptoms, but testing positive. Quarantine is for close contact with a COVID-19-positive person but without testing positive.
Although current trends generally look positive, public health experts and epidemiologists note how unpredictable COVID-19 has been. As a result, Dr. Anthony Fauci, White House chief medical adviser and director of the National Institute of Allergy and Infectious Diseases, told BBC’ s “ Sunday Morning, ” that people in the U.S. “ need to be prepared for the possibility ” of more restrictions if another surge occurs. He added, “ I don’ t want to use the word ‘ lockdowns.’ That has a charged element to it. But I believe that we must keep our eye on the pattern of what we’ re seeing with infections. ”
Numerous research studies determined that poor indoor ventilation helped spread the virus during the pandemic. The Biden administration is taking that into account now, urging businesses, homeowners and schools to improve air quality. | general |
U.S. Importers Are Paying Anything to Avoid Shipping Woes | U.S. importers, straining under a tapped-out supply chain, are increasingly offering top dollar for long-term shipping contracts that may not even be honored as they try whatever it takes to guarantee the arrival of their products.
The pandemic-driven boom in demand for goods pushed both contract and spot rates for shipping to records — getting merchandise from place to place costs about 11 times more than it did before the COVID-19 outbreak. With demand so high and capacity limited, importers are paying up to avoid a repeat of 2021, when some contracts set at lower prices weren’ t honored, leaving customers without their stuff.
Importers are accepting higher contract rates because they “ fear that the market can get even worse, ” said Lars Jensen, chief executive officer of Copenhagen-based Vespucci Maritime, a shipping market-analysis firm. “ Fear of losing out on capacity to some degree trumps fear of paying too much right now. ”
Contracts are typically negotiated on a yearly basis with importers and carriers agreeing to a minimum capacity level between certain ports, and the spot market used for freight shipped outside of the agreed terms. But this year, importers are prepared to pay more, locking in higher, pandemic-era prices for two or even three years — despite some predictions they won’ t stay as elevated — in order to protect themselves from the volatile spot market.
The shipping chaos has completely changed how David Kunelius, president of Minnesota-based medical device company MedSource Labs, gets merchandise to the U.S. from Asia.
“ Pre-pandemic, we would set up shipping contracts for an entire year, ” paying about $ 4,000 per 40-foot container, which allowed for planned investment in research and development, Kunelius said. But starting last year, MedSource Labs was getting a new quote for cargo every two weeks, increasing by thousands of dollars each time to about $ 23,000 now.
Rates are unlikely to return where they were before the pandemic, when carriers suffered from overcapacity and low profits for years, said Stephanie Loomis, vice president of international procurement at freight forwarder CargoTrans, Inc.
“ It’ s settling into the market now that the days of really very low, ridiculously cheap ocean rates are over, ” she said, adding that prices are unlikely to stay at these levels for more than a couple of years and will likely settle a little lower.
While shippers are interested in securing longer-term freight contracts earlier and for greater durations to best ensure reliability and predictability, carriers only have so much space aboard ships. Orders for new capacity reached a record last year, but that will only relieve markets in 2023 and 2024, according to VesselsValue data.
And with supply chain disruptions stemming from Russia’ s invasion of Ukraine and China’ s Covid Zero policy locking down major manufacturing regions in the Asian nation, things could get harder to predict in the short term. All this while U.S. goods imports continue at records amid decades-high inflation rates.
The major ocean carriers have faced criticism for charging such high rates, leaving many shippers and importers — or beneficial cargo operators known as BCOs — without options.
President Joe Biden asked Congress to look at the biggest ocean carriers and whether the three major shipping alliances they’ ve formed are anticompetitive. Exporters are paying the price too, as carriers often skip picking up goods to rush containers back to Asia for another load of more lucrative imports to the U.S. West Coast.
Larger freight forwarders are also signing multiyear agreements, and paying more for securities through add-ons, said Robert Khachatryan, CEO of Los Angeles-based cargo forwarder Freight Right Global Logistics.
Besides a contract rate with a guaranteed allocation of space, a carrier may take 20% of your contracted containers at a lower price with guaranteed space — provided importers also book others at premium rates, Khachatryan said.
Last year, ocean carriers offered a lot of “ premium services, ” including ensuring cargo was loaded on the first ship out, for example. Those extra charges became a substantial part of container movement from Asia to the U.S. and while they’ re less common right now, they could make a comeback, Loomis said.
Meanwhile, importers like Kunelius continue to battle the volatility.
“ If we can get back to some of those more stable prices on the long-term contracts, we would definitely do that. ” He said. For now the company will pass some of the price increase on to its distributors, who stock hospitals, emergency services and fire departments. “ It can’ t last forever, ” Kunelius said.
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High Efficiency, Increased Demand Send U.S. LNG Exports to 2021 Record | Sign in to get the best natural gas news and data. Follow the topics you want and receive the daily emails.
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U.S. liquefied natural gas ( LNG) producers, riding a wave of heightened demand, pushed the limits of nameplate capacity last year to set an export record.
According to updated data by the Energy Information Administration ( EIA), domestic export terminals sent an average of 9.7 Bcf/d of the super-chilled gas abroad last year. It was a 50% increase over 2020 and the highest recorded volume of annual exports since the first cargo more than six years ago.
EIA said the export spike was driven by a combination of increased demand from Asia and Europe, along with expanded domestic capacity. The six terminals in operation last year averaged 102% of nameplate capacity and 89% of peak capacity, according to the EIA.
As in years past, Asian countries led the rankings in destinations for U.S. cargoes, with South Korea and China nearly tied for first with around 1.2 Bcf/d each, according to the EIA. As China emerged from some Covid-19 restrictions, it increased energy demand and had the largest increase in U.S. volumes.
Japan was the third-largest importer in 2021, at 1.0 Bcf/d. Combined, China, Japa and South Korea accounted for 35% of all domestic gas exports.
European countries also increased U.S. cargoes, especially last spring and early winter. December’ s export volumes set a record for the most U.S. gas exported in a month, rising to 6.7 Bcf/d. Since then, the record has been surpassed in January and February.
As Europe has continued to struggle to replace Russian gas in the aftermath of the invasion of Ukraine, more attention from gas buyers and Western governments has been placed on U.S. LNG to fill the void.Brazil and other South American countries helped add to the export jump as well, with limited hydroelectric power because of an intense drought. U.S. exports to Brazil increased by 0.5 Bcf/d from 2020, averaging 0.8 Bcf/d.
Goldman Sachs Commodities Research analysts in a recent note to clients said the United States may see export volumes remain high as a result of the conflict, but there is a natural ceiling to how high exports could increase With U.S. LNG exports at capacity, “ it will likely take years before Europe’ s efforts to boost LNG imports result in added U.S. export demand, ” analysts said.
There are also expectations that the high utilization rate at U.S. terminals could mean “ slightly more maintenance impact ” than in 2021. Goldman’ s team has raised domestic export demand forecasts by 1.5 Bcf/d to 12.6 Bcf/d, with the assumption that domestic LNG producers could continue “ learning-by-doing. ”
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U.S. Oil Production Ticks Up First Time in Two Months; OPEC’ s Next Move Looms Large | Sign in to get the best natural gas news and data. Follow the topics you want and receive the daily emails.
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Contrary to the dominant theme of 2022, U.S. crude producers nudged output higher last week, while travel fuel consumption declined along with overall petroleum demand, the U.S. Energy Information Administration ( EIA) said Wednesday.
Production for the week ended March 25 ticked up to 11.7 million b/d after holding at 11.6 million b/d through all of February and most of March, EIA’ s latest Weekly Petroleum Status Report showed. American producers have been under pressure to increase crude supplies amid mounting global demand and waning Russian oil exports during the Kremlin’ s war in Ukraine.
Exploration and production companies, however, have cautioned that it takes time to ramp up drilling and output – and that is particularly true in the current inflation-infused environment. High labor and input costs are making it difficult to secure the staff and resources needed to boost output, said director Tom Biracree, Oil and Gas Financial Analytics.
[ Want today’ s Henry Hub, Houston Ship Channel and Chicago Citygate prices? Check out NGI’ s daily natural gas price snapshot now. ]
The “ same post-pandemic inflation that is plaguing the broader U.S. economy ” is hampering energy companies, said Biracree, in a report for RBN Energy LLC. He also noted that major producers are under pressure to invest in renewable energy and return capital to shareholders via dividends and share buybacks.
Still, he and other analysts anticipated that production would rise this year, and the latest EIA data may signal a beginning. That would be significant, if it proves true, because global supplies trailed demand in the second half of 2021 and into this year, resulting in lofty prices. The war in Ukraine has amplified this, with major energy companies pulling out of Russia in protest and Western governments slapping the Kremlin with waves of economic sanctions.
The United States, for one, banned imports of Russian oil earlier this month.
Russian crude exports are falling as a result. Rystad Energy estimated that between 1.2 million and 1.5 million b/d of Russian exports have been lost since the start of the conflict on Feb. 24.
“ The destination of the remaining crude exports from Russia ( approximately 4.5 million b/d) is increasingly unknown, although it will likely be Asia, primarily China and India, ” as European countries are weaning themselves from Russian energy, said Rystad’ s Claudio Galimberti, senior vice president of analysis.
This could leave Europe short on supplies – absent increases from the United States or Saudi Arabia-led OPEC, the world’ s largest producers.
OPEC and its partner countries known as OPEC-plus – which includes Russia – are scheduled to meet Thursday to discuss their collective production goals for the coming months.
Analysts are looking to see if OPEC members may bolster output to offset Russia’ s woes. A Bloomberg survey this week, however, found that a majority of Wall Street analysts expect OPEC and its partners to hold the line at monthly production increases of 400,000 b/d. This has been policy since last August, which sets a measured pace that gradually unwinds production cuts of nearly 10 million b/d made in April 2020 amid the pandemic.
OPEC members in recent weeks have said publicly that, while the war creates a major wildcard on the supply front, the pandemic continues to present unknowns on the demand side. Because of this, they are leery of increasing production too quickly.
Indeed, said Rystad’ s Galimberti, demand has tapered in China this month amid fresh outbreaks of the coronavirus there. A combination of virus flare-ups and war uncertainty, he said, has tapered demand in parts of Europe as well.
In the United States, meanwhile, demand has climbed most of this year alongside a growing U.S. economy. However, petroleum consumption for the March 25 period declined 6% week/week, with demand for gasoline, jet fuels and distillates all down.
“ Gasoline demand decreased week-over-week and is tracking below pre-Covid levels while distillate demand experienced a severe drop and is now underperforming the five-year average, ” said Randy Ollenberger, BMO Capital Markets analyst.
Analysts blame soaring prices. Gasoline costs reached record level earlier this month after Brent crude, the international benchmark, soared to $ 130/bbl. Oil prices in the second half of the month have been choppy, but Brent held well above $ 110 Wednesday, up about 45% this year.
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Watch: How are AI and Robotics Changing Logistics? | Oliver Hedgepeth, professor of logistics with American Public University System online, offers guidance on what warehouse employers and workers must do to adjust to the new age of automation.
The increasing reliance by warehouse and logistics operations on robot arms is just a continuation of a trend toward automation that had been evident for a century or more. But the pace of automation, driven by advances in robotics and artificial intelligence, has quickened with the COVID-19 pandemic, as workers were forced to go home and refused to return to the workplace. “ Where we are now [ with automation ] is where we would be in five years without the pandemic, ” Hedgepeth says.
For the most part, warehouse automation takes over repetitive and even dangerous jobs, even if those jobs paid well when humans were required to do them. “ It’ s not a bad thing, ” says Hedgepeth. “ Product is being made better and safer. I don’ t see a risk involved in [ the coming of ] AI and robots. ”
As with any advance in technology, however, there’ s a price to pay — in this case, fewer jobs for humans in the warehouse. And retraining those individuals to take over more complex tasks isn’ t an automatic answer to the problem. There’ s a dual responsibility involved: facilities must offer retraining opportunities, and workers must accept them. In addition, most of the workers laid off in a particular facility due to automation likely won’ t be rehired by that same company; they’ ll have to seek opportunities elsewhere. Yet they have no choice but to adjust to the impacts of automation, as they have for decades.
For the foreseeable future, Hedgepeth, humans will still be needed in many positions relating to supply chain management. It’ s just a question of making the necessary adjustments, including a willingness to be retrained.
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Online posts may not reflect Chinese opinion when it comes to the Russian invasion of Ukraine | While the Russian invasion of Ukraine has rallied public support for Ukraine in Canada and other western countries, China may position itself differently.
In recent years, the deteriorating relationship between China and the West has resulted in the expulsion of foreign journalists from China. In this information vacuum, China’ s official announcements and social media have become the two primary sources about China for external analysts.
When it comes to the Russian invasion, Chinese authorities claim neutrality, and the New York Times reports that heavy pro-war views seen in Chinese social media have surprised many Chinese people. However, China’ s social media opinions seem more pronounced: many enthusiastically praised Russian President Vladimir Putin as “ the greatest strategist of this century, ” and more users support Russia than Ukraine in online polls.
Many news articles have argued that the Chinese internet is cheering Russia’ s invasion, which serves as the social basis for the Chinese authority’ s attitude.
Despite formal announcements adopting a neutral tone, Chinese officials display a more pro-Russian message by embracing Russia’ s disinformation.
Social media platforms in China are co-operating with this official stance. They amplify the official voice and prioritize posts sent by state outlets in users’ interface.
Social media accounts run by news media are also asked to align their opinions with the official ones. In practice, they need to avoid sending any anti-war, pro-Ukraine content, and are responsible for removing critical comments. A leaked corporate direction from a news agency states:
“ Do not post anything unfavourable to Russia or pro-Western.… Carry out selection and control of comments…. If using hashtags, only use those started by People’ s Daily, Xinhua or CCTV ( major state-affiliated media). ”
The rise of social media in China, as elsewhere, has contributed to the influencer economy, in which social media influencers generate revenues by creating content and monetizing their online popularity.
An investigation by the New Yorker found that a popular influencer account, College Daily, has an internal reward system based on the number of clicks and shares. This account has frequently published articles with headlines that can arouse patriotic and nationalist sentiments, such as “ Of course, only Chinese people can save the Earth. ”
The growth of a social media influencer economy means that Chinese influencers operate according to the political and economic logic at the same time. In other words, influencers did not stop with adopting the official pro-Russian tone. They took it one step further and embraced — and created — dramatic narratives picturing Putin as a national hero.
A popular influencer with more than four million followers on multiple Chinese social media platforms posted an article that claimed Putin’ s strongman leadership was built on “ fire and blood. ” He praises Putin’ s heroic role in conquering Chechnya, Rugghia, Syria and Crimea, and describes Russia’ s invasion as a righteous “ peacekeeping operation. ”
Similarly, another influencer adoringly describes Putin as a real lone hero: “ At the age of 70, he still shoulders the mission of governing the country and bringing peace to the world. He challenges half the world by himself. ”
This is no surprise considering influencers’ position in China’ s social media ecosystem. Expressing anti-official opinions is likely to cause suspension of accounts, if not being permanently blocked by all Chinese platforms. Therefore, influencers are motivated to follow the official tone, submitting themselves to the political logic.
Within the safe zone, the economic logic comes into play. Influencers are racing to generate inflammatory, eye-catching articles so as to attract more followers, clicks, and shares.
In the case of the Russia-Ukraine war, that means more glorification of Putin and more conspiracy theories on the origin of the war.
Figuring it out is no easy task. Indeed, even Chinese authorities sometimes miscalculate public response.
During the pandemic, a social media account linked to the Chinese Communist Party posted an offensive picture mocking India’ s COVID-19 crisis, assuming that it would highlight China’ s success in curbing COVID-19. However, the post received criticism rather than unanimous nationalist praise. It was soon deleted, along with the criticisms received.
During the Russian invasion of Ukraine, many Chinese people have expressed anti-war opinions. On Feb. 26, five Chinese historians published an anti-war open letter.
Two days later, over 130 alumni of China’ s top universities issued a statement condemning the invasion. Several social media celebrities, one of whom has more than 13 million followers, posted messages calling for peace. All of these posts have been deleted by the social media platforms within hours, leaving no traces for observers.
We should be cautious in assuming the levels of support for war among the Chinese population, especially when the evidence comes from social media. | business |
Still coughing after COVID? Here's why it happens and what to do about it | Coughing is a socially awkward symptom, particularly since the COVID pandemic hit.
The problem is, coughing may persist for weeks or months after the infection has gone. Around 2.5% of people are still coughing a year after being infected with COVID.
A recurrent cough can undermine your capacity to work, leave you with medical bills, and prompt a withdrawal from social situations because you don’ t want others to fear you’ re spreading COVID.
As a GP, I have patients ask whether there’ s anything that can fix their post-COVID cough. Here’ s how I answer.
It’ s not surprising COVID causes a cough, because the virus affects our respiratory tract, from our nasal passages right down to our lungs.
Coughing is one of the body’ s ways of getting rid of unwanted irritants such as viruses, dust and mucus. When something “ foreign ” is detected in the respiratory tract, a reflex is triggered to cause a cough, which should clear the irritant away.
While this is an effective protective mechanism, it’ s also the way the COVID virus spreads. This is one reason the virus has so effectively and quickly travelled around the world.
Inflammation is a defensive process our immune system uses to fight off COVID. Inflamed tissues both swell up and produce fluid. This can last a long time, even after the virus has gone.
if the upper airways ( nasal passages and sinuses) stay inflamed, the fluid produced drips down the back of your throat causing a “ post-nasal drip ”. This makes you feel the need to “ clear your throat ”, swallow and/or cough
if the lungs and lower airways are affected, coughing is the body’ s way of trying to clear the fluid and swelling it senses there. Sometimes there isn’ t a lot of fluid ( so the cough is “ dry ”), but the swelling of the lung tissue still triggers a cough
the neural pathways may be where inflammation is lurking. This means the nervous system is involved, either centrally ( the brain) and/or peripherally ( nerves), and the cough isn’ t primarily from the respiratory tissues themselves
a less common but more serious cause may be the lung tissue being scarred from the inflammation, a condition called “ interstitial lung disease ”. This needs to be diagnosed and managed by respiratory specialists.
Interestingly, people may experience a range of post-COVID symptoms, including coughing, regardless of whether they were sick enough to be hospitalised. Some patients tell me they weren’ t particularly unwell during their COVID infection, but the post-infective cough is driving them crazy.
We need to be wary not to label a cough as a post-COVID cough and miss other serious causes of chronic coughs.
One thing to watch out for is a secondary bacterial infection, on top of COVID. Signs you may have a secondary infection include:
Other potentially serious illnesses can cause a chronic cough, including heart failure and lung cancer, so if you’ re in any doubt about the cause of your cough, have a check-up.
Read more: We can expect more colds and flu as COVID restrictions lift. 5 germs to look out for
If the cough is mainly from post-nasal drip, it will respond to measures to reduce this, such as sucking lozenges, saline rinses, nasal sprays, and sleeping in an upright posture.
Some people may develop cough hypersensitivity, where the threshold of the cough reflex has been lowered, so it takes a lot less to set off a cough. It’ s a common response to colds and it can take a while for our bodies to “ reset ” to a less sensitive state.
If a dry or tickly throat sets off your cough reflex, solutions include sipping water slowly, eating or drinking honey, and breathing slowly through your nose.
By slow-breathing through your nose, the air hitting the back of your throat is warmed up and moisturised by first passing through the nasal cavities. Your cough reflex is therefore less likely to be triggered, and over time the hypersensitivity should settle.
If the cause originates from inflammation in the lungs, controlled breathing exercises and inhaled steam ( in a hot shower or via a vaporiser) may help.
Thick mucus can also be made more watery by inhaling saline through a device called a nebuliser, which turns liquid into vapour and delivers it directly to the mucus built up in your lungs. This makes it easier to clear out with a cough.
Budesonide ( a steroid inhaler), when given early after a COVID diagnosis, has been shown to reduce the likelihood of needing urgent medical care, as well as improving recovery time.
Unfortunately, there are no good trials on using budesonide inhalers for a post-COVID cough.
However, anecdotally, it has been of help to some patients who have a post-COVID cough, when nothing else is helping them.
Trials on steroid tablets to treat a post-COVID cough are still underway, and won’ t be recommended unless they’ re shown to result in significant improvement.
Concerningly, some countries have guidelines that suggest using antibiotics to treat COVID, showing just how prevalent this misunderstanding is.
Unless there is a secondary bacterial infection, antibiotics are not appropriate and may contribute to the development of antibiotic resistance.
Post-COVID coughing can last for weeks, be debilitating, and have a variety of causes. Most of the ways to manage it are simple, cheap and can be done without needing medical intervention.
However, if you have any doubts about the cause or the progression of your cough, it is worth a visit to your GP to have it checked out. | business |
The 25 happiest U.S. city park systems, ranked by scientists: Researchers measure the happiness effects of nature with digital technology -- ScienceDaily | That's the upshot of a major new study that measures the happiness effects of city parks in the 25 largest U.S. cities, from New York City to Los Angeles.
The happiness benefit of urban nature on users was so strong -- the team of University of Vermont scientists discovered -- it was roughly equivalent to the mood spike people experience on holidays like Thanksgiving or New Year's Day.
The research is the largest study of its kind -- using massive amounts of data from social media -- to quantify the mood boosting benefits on urban nature. It was published March 30 by PLOS One.
`` These new findings underscore just how essential nature is for our mental and physical health, '' says University of Vermont scientist Taylor Ricketts. `` These results are especially timely given our increased reliance on urban natural areas during the COVID pandemic. ''
New way to measure happiness
The study builds on the team's landmark San Francisco research, which used unlikely tools -- Twitter posts and geolocation data -- to create an effective method to quantify the happiness benefit that people get from nature.
The new study expanded the focus to the 25 largest American cities by population. The team analyzed a whopping 1.5 million Twitter posts to measure differences in online sentiment, comparing tweets posted inside city parks to those posted elsewhere.
The happiest place on Twitter? The great outdoors
Researchers found a powerful happiness benefit from city parks, which was present across all seasons, months, weeks, days, and times of the day -- not just weekends and summer holidays.
`` We understand the irony of using Twitter and technology to measure happiness from nature, '' says lead author and recent UVM PhD student Aaron Schwartz, noting Twitter's reputation for 'doom-scrolling. ' `` But our goal is to use technology for the greater good -- to better understand the effect nature has on humans, which until now has been difficult to quantify in such large numbers. ''
Given the findings, the researchers argue that urban nature should be protected, expanded, and made as accessible as possible. City parks are the primary source of nature for millions of people, they add.
Whose parks make them happiest?
Researchers found that U.S. cities differed a lot in the size of the happiness benefit that their parks provided to users:
Some surprises
Scientists were surprised by several top ranked cities in the study -- including Indianapolis, Austin and Jacksonville -- which have lower per capita funding levels for parks compared to some other cities on the list.
While people wrote far happier tweets in parks -- words like `` beautiful, '' `` fun, '' `` enjoying, '' and `` amazing '' -- these top ranked cities saw people write dramatically fewer negative words on Twitter in parks -- such as `` hate, '' `` don't, '' and `` not. ''
A more powerful predictor of happiness than park funding per capita ( which previous research by others had suggested would be key) was park size. The happiness benefit was highest in parks over 100 acres in area, followed by parks 1 to 10 acres in size.
`` Being in nature offers restorative benefits not available for purchase in a store, or downloadable on a screen, '' says UVM's Chris Danforth, a mathematics professor and Gund Fellow. `` However, not all parks appear to be equal when it comes to happiness. The ability to immerse yourself in a larger, greener natural areas had a greater effect than smaller paved city parks. ''
`` One possible explanation, '' the researchers write, `` is that larger parks provide greater opportunities for mental restoration and separation from the taxing environment of the city. ''
This study brought together multiple UVM research groups, including the Gund Institute for Environment, Vermont Advanced Computing Center, The Spatial Analysis Lab, the MassMutual Center of Excellence in Complex Systems and Data Science, and the Hedonometer, an effort to measure global happiness using Twitter. | science |
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