Crowding has consequences: Prevention and management of COVID-19 in informal urban settlements.
COVID-19 spreads via aerosols, droplets, fomites and faeces. The built environment that facilitates crowding increases exposure and hence transmission of COVID-19 as evidenced by outbreaks in both cool-dry and hot-humid climates, such as in the US prison system and dormitories in Singapore, respectively. This paper explores how the built environment influences crowding and COVID-19 transmission, focusing on informal urban settlements (slums). We propose policy and practice changes that could reduce COVID-19 transmission. There are several issues on how COVID-19 affects informal urban settlements. Slum populations tend to be younger than the overall population. Lower numbers of older people lessen the morbidity and mortality of the pandemic in slum areas. Second, many slum populations are highly mobile. By returning to their ancestral villages residents can avoid the risks of overcrowding and reduce the population density in a given area but may spread COVID-19 to other areas. Third, detection and registration of COVID-19 cases depends on patients presenting to health care providers. If the risk of visiting a health care centre outweighs the potential benefits patients may prefer not to seek treatment. The control and prevention of COVID-19 in informal urban settlements starts with organizing community infrastructure for diagnosis and treatment and assuring that basic needs (food, water, sanitation, health care and public transport) are met during quarantine. Next, community members at highest risk need to be identified and protected. Low-income, informal settlements need to be recognized as a reservoir and source for persistent transmission. Solutions to overcrowding must be developed for this and future pandemics. In view of the constant risk that slums present to the entire population decisive steps need to be taken to rehabilitate and improve informal settlements, while avoiding stigmatization.


Structure of the central nervous system of a juvenile acoel, Symsagittifera roscoffensis.
The neuroarchitecture of Acoela has been at the center of morphological debates. Some authors, using immunochemical tools, suggest that the nervous system in Acoela is organized as a commissural brain that bears little resemblance to the central, ganglionic type brain of other flatworms, and bilaterians in general. Others, who used histological staining on paraffin sections, conclude that it is a compact structure (an endonal brain; e.g., Raikova 2004; von Graff 1891; Delage Arch Zool Exp Gén 4:109-144, 1886). To address this question with modern tools, we have obtained images from serial transmission electron microscopic sections of the entire hatchling of Symsagittifera roscoffensis. In addition, we obtained data from wholemounts of hatchlings labeled with markers for serotonin and tyrosinated tubulin. Our data show that the central nervous system of a juvenile S. roscoffensis consists of an anterior compact brain, formed by a dense, bilobed mass of neuronal cell bodies surrounding a central neuropile. The neuropile flanks the median statocyst and contains several types of neurites, classified according to their types of synaptic vesicles. The neuropile issues three pairs of nerve cords that run at different dorso-ventral positions along the whole length of the body. Neuronal cell bodies flank the cords, and neuromuscular synapses are abundant. The TEM analysis also reveals different classes of peripheral sensory neurons and provides valuable information about the spatial relationships between neurites and other cell types within the brain and nerve cords. We conclude that the acoel S. roscoffensis has a central brain that is comparable in size and architecture to the brain of other (rhabditophoran) flatworms.


Nonlinear interaction between single photons.
Harnessing nonlinearities strong enough to allow single photons to interact with one another is not only a fascinating challenge but also central to numerous advanced applications in quantum information science. Here we report the nonlinear interaction between two single photons. Each photon is generated in independent parametric down-conversion sources. They are subsequently combined in a nonlinear waveguide where they are converted into a single photon of higher energy by the process of sum-frequency generation. Our approach results in the direct generation of photon triplets. More generally, it highlights the potential for quantum nonlinear optics with integrated devices and, as the photons are at telecom wavelengths, it opens the way towards novel applications in quantum communication such as device-independent quantum key distribution.


Bending insensitive sensors for strain and temperature measurements with Bragg gratings in Bragg fibers.
A novel fiber Bragg grating (FBG) has been inscribed in all solid Bragg fiber by an infrared femtosecond laser. Temperature, strain and bending characteristics of the induced FBG are investigated experimentally. Four resonant dips in the transmission spectrum show positive sensitivity for temperature/strain and zero-sensitivity for bending in wavelength. Cross-sensitivity between strain/temperature and bending can thus be avoided since the resonant wavelengths are insensitive to curvature variation when the fiber is bent toward two opposite directions. Evident wavelength hysteresis is observed during the isochronal annealing test and it can be eliminated by a pre-annealing treatment. These proposed FBGs are very attractive candidates for multi-parameter sensors in harsh environment.


Magnetic resonance imaging predictors of treatment response in late-life depression.
In older adults, depression not only results in more years lived with disability than any other disease but it also carries additional risks of suicide, medical comorbidities, and family caregiving burden. Because it can take many months to identify an effective treatment regimen, it is of utmost importance to shorten the window of time and identify early on what medications and dosages will work effectively for individuals having depression. Late-life depression (LLD) has been associated with greater burden of age-related changes (eg, atrophy, white matter ischemic changes, and functional connectivity). Depression in midlife has been shown to alter affective reactivity and regulation, and functional magnetic resonance imaging (fMRI) studies in LLD have replicated the same abnormalities. Effective treatment can normalize these alterations. This article provides a review of the current literature using structural and functional neuroimaging to identify MRI predictors of treatment response in LLD. The majority of the literature on structural MRI has focused on the vascular depression hypothesis, and studies support the view that loss of brain volume and white matter integrity was associated with poorer treatment outcomes. Studies using fMRI have reported that lower task-based activity in the prefrontal cortex and limbic regions was associated with poorer outcome. These imaging markers may be integrated into clinical decision making to attain better treatment outcomes in the future.


Quantitative Real-Time Polymerase Chain Reaction for the Diagnosis of Mycoplasma genitalium Infection in South African Men With and Without Symptoms of Urethritis.
This study was done to diagnose Mycoplasma genitalium infection based on bacterial load in urine specimens from symptomatic and asymptomatic men. Urine specimens from 94 men with visible urethral discharge, 206 with burning on micturition and 75 without symptoms presenting to a family practitioner were tested for M. genitalium as well as Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis by transcription-mediated amplification assays. A quantitative polymerase chain reaction assay was used to determine the bacterial load for all specimens in which M. genitalium was the only organism detected. Among the 375 specimens collected, M. genitalium was detected in 59 (15.7%) men (both symptomatic and asymptomatic) using the transcription-mediated amplification assay, and in 45 (12.0%) of the total population, it was the only pathogen detected. One or more pathogens were detected in 129 (43%) of the symptomatic men, with N. gonorrhoeae in 50 (16.7%); C. trachomatis in 37 (12.3%) and T. vaginalis present in 24 (8.0%) patients. Among the 17 patients where mixed infections were detected, M. genitalium with N. gonorrhoeae was the most common (11/17; 64.7%). Patients with visible urethral discharge had significantly higher M. genitalium concentrations than those with burning on micturition. The median M. genitalium load in symptomatic men was significantly higher than that in asymptomatic men. This study confirms the high prevalence of M. genitalium among men with urethritis in South Africa and demonstrates that there is a strong association with M. genitalium bacterial load and clinical urethritis. As the number of organisms increased, the severity of the symptoms increased, an indication of the role that the organism plays in disease progression.


Functional characterization of the sigmaB-dependent yabJ-spoVG operon in Staphylococcus aureus: role in methicillin and glycopeptide resistance.
The alternative sigma factor sigma(B) of Staphylococcus aureus controls the expression of multiple genes, including virulence determinants and global regulators; promotes capsule production; and increases the resistance levels of methicillin-resistant S. aureus (MRSA) and glycopeptide-intermediate-resistant S. aureus (GISA) strains. We show here that deletion of the sigma(B)-controlled yabJ-spoVG operon, which codes for potential downstream regulators of sigma(B), abolished capsule synthesis and reduced resistance in MRSA and GISA to the same extent that sigma(B) inactivation did. Introduction of the yabJ-spoVG operon in trans restored the original phenotype. By genetic manipulations, we show that SpoVG but not YabJ is required for complementation. We therefore postulate that SpoVG is the major factor of the yabJ-spoVG operon required in S. aureus for capsule formation and antibiotic resistance.


Learning agile and dynamic motor skills for legged robots.
Legged robots pose one of the greatest challenges in robotics. Dynamic and agile maneuvers of animals cannot be imitated by existing methods that are crafted by humans. A compelling alternative is reinforcement learning, which requires minimal craftsmanship and promotes the natural evolution of a control policy. However, so far, reinforcement learning research for legged robots is mainly limited to simulation, and only few and comparably simple examples have been deployed on real systems. The primary reason is that training with real robots, particularly with dynamically balancing systems, is complicated and expensive. In the present work, we introduce a method for training a neural network policy in simulation and transferring it to a state-of-the-art legged system, thereby leveraging fast, automated, and cost-effective data generation schemes. The approach is applied to the ANYmal robot, a sophisticated medium-dog-sized quadrupedal system. Using policies trained in simulation, the quadrupedal machine achieves locomotion skills that go beyond what had been achieved with prior methods: ANYmal is capable of precisely and energy-efficiently following high-level body velocity commands, running faster than before, and recovering from falling even in complex configurations.


When Cigarette Sales Suddenly Become Illegal: Evidence From an Online Survey of South African Smokers During COVID-19 Lockdown.
Despite high levels of illicit trade in the tobacco market, the South African government banned the sale of tobacco products in March 2020 as part of its COVID-19 response. The ban lasted five months. We assess how the ban affected the cigarette market for a sample of smokers by comparing the price, consumption, and competitive landscapes before (March), during (May and June), and after (September) the ban. We conducted three online surveys of cigarette smokers, asking about smoking behavior before, during, and after the ban. We use descriptive statistics and OLS regressions to estimate the impact of the ban on the South African cigarette market, focusing on the price of cigarettes. Most smokers continued smoking despite the sales ban. During the ban, prices increased by over 240%. Purchases shifted away from the normally dominant brands of the multinational tobacco companies to local/regional producers. The covariates of price changed substantially during the sales ban, the most pronounced being inter-provincial effects. After the ban, the market shifted back to its preban state, with an overall increase in price of 3.6%. Cigarette sales continued despite the sales ban, further entrenching an already large illicit market. Had the government substantially increased the excise tax, rather than banned the sale of tobacco products, it would have achieved a similar public health outcome, received more revenue, and presumably not further entrenched the illicit market. South Africa temporarily banned the sale of tobacco as part of its COVID-19 response. Despite the ban, the sale of cigarettes did not cease; rather, it caused major disruption to the cigarette market. The ban inadvertently benefited manufacturers who were previously disproportionately involved in illicit activities; these manufacturers increased their market share even after the ban was lifted. The ban may have further entrenched South Africa's already large illicit market. Our results show that there are unintended consequences associated with a temporary ban on the sale of cigarettes.


General practice palliative care: patient and carer expectations, advance care plans and place of death-a systematic review.
With an increasing ageing population in most countries, the role of general practitioners (GPs) and general practice nurses (GPNs) in providing optimal end of life (EoL) care is increasingly important. To explore: (1) patient and carer expectations of the role of GPs and GPNs at EoL; (2) GPs' and GPNs' contribution to advance care planning (ACP) and (3) if primary care involvement allows people to die in the place of preference. Systematic literature review. Papers from 2000 to 2017 were sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases. From 6209 journal articles, 51 papers were relevant. Patients and carers expect their GPs to be competent in all aspects of palliative care. They valued easy access to their GP, a multidisciplinary approach to care and well-coordinated and informed care. They also wanted their care team to communicate openly, honestly and empathically, particularly as the patient deteriorated. ACP and the involvement of GPs were important factors which contributed to patients being cared for and dying in their preferred place. There was no reference to GPNs in any paper identified. Patients and carers prefer a holistic approach to care. This review shows that GPs have an important role in ACP and that their involvement facilitates dying in the place of preference. Proactive identification of people approaching EoL is likely to improve all aspects of care, including planning and communicating about EoL. More work outlining the role of GPNs in end of life care is required.


Factors influencing the visual acuity of chronic central serous chorioretinopathy.
To investigate correlated factors on final visual acuity in conjunction with fluorescein angiography (FA) and optical coherence tomography (OCT) findings of chronic central serous chorioretinopathy (CSCR). Twenty-four patients (36 eyes) with typical findings of chronic CSCR based on medical records, FA and OCT results were enrolled in this study. We investigated demographic findings, initial and final visual acuity (VA), and some typical findings of FA including the type of leakage pattern, the existence of a gravitational tract and an abnormal hyperfluorescent area centered on the fovea. We also investigated OCT findings to examine serous retinal detachment, outer photoreceptor layer (OPRL) preservation, continuity of the inner segment (IS) and the outer segment (OS) of the photoreceptor layer in case of macular attachment, and other typical findings. The converted logarithm of the minimum angle of resolution VA was used to investigate the statistical correlation with these FA and OCT findings. An abnormal hyperfluorescent area within 1 macular photocoagulation study disc area on FA and cystoid degeneration on OCT were correlated with poor final VA of less than 20 / 40. However, the preserved OPRL and the continuity of IS / OS junction were correlated with a good final VA of 0.5 or more. These specific findings could be associated with recurrent or persistent subretinal fluid and could be important parameters of decision for treatment.


Polar switching in trialkylbenzene-1,3,5-tricarboxamides.
The hydrogen-bonded hexagonal columnar LC (Col(hd)) phases formed by benzene-1,3,5-tricarboxamide (BTA) derivatives can be aligned uniformly by an electric field and display switching behavior with a high remnant polarization. The polar switching in three symmetrically substituted BTAs with alkyl chains varying in length between 6 and 18 carbon atoms (C6, C10, and C18) was investigated by electro-optical switching experiments, dielectric relaxation spectroscopy (DRS), and solid-state NMR. The goal was to characterize ferroelectric properties of BTA-based columnar LCs, which display a macroscopic axial dipole moment due to the head-to-tail stacking of hydrogen-bonded amides. The Col(hd) phase of all three BTAs can be aligned uniformly by a dc field ∼30 V/μm. Moreover, C10 and C18 display extrinsic polar switching characterized by a remnant polarization and coercive field of 1-2 μC/cm(2) and 20-30 V/μm, respectively. In the absence of an external field, the polarization is lost in 1-1000 s, depending on device details and temperature. DRS revealed a columnar glass transition in the low-temperature region of the LC phase related to collective vibrations in the hydrogen-bonded columns that freeze out below 41-54 °C. At higher temperatures, a relaxation process is present originating from the collective reorientation of amide groups along the column axis (inversion of the macrodipole). Matching activation energies suggest that the molecular mechanism underlying the polar switching and the R-processes is identical. These results illustrate that LC phases based on BTAs offer the unique possibility to integrate polarization with other functionalities in a single nanostructured material.


The Effects of Hemianopia on Perception of Mutual Gaze.
Individuals with left hemianopic field loss (HFL), especially with neglect history, may have greater difficulties than individuals with right HFL in judging the direction of another person's gaze. Individuals with HFL often show a spatial bias in laboratory-based perceptual tasks. We investigated whether such biases also manifest in a more real-world task, perception of mutual gaze direction, an important, nonverbal communication cue in social interactions. Participants adjusted the eye position of a life-size virtual head on a monitor at a 1-m distance until (1) the eyes appeared to be looking straight at them, or (2) the eyes were perceived to be no longer looking at them (to the right and left). Participants with right HFL (n = 8) demonstrated a rightward error in line bisection but made gaze judgments within the range of normally sighted controls (n = 17). Participants with left HFL without neglect history (n = 6) made leftward errors in line bisection and had more variable gaze judgments; three had estimates of gaze direction outside the reference range. Four participants with left HFL and neglect history made estimates of gaze direction that were to the right of the reference range. Our results suggest that individuals with left HFL, especially with neglect history, may have greater difficulties than individuals with right HFL in compensating for low-level spatial biases (as manifested in line bisection) when performing the more complex, higher-level task of judging gaze direction.


The evolution of fairness: explaining variation in bargaining behaviour.
Conceptions of fairness vary across the world. Identifying the drivers of this variation is key to understanding the selection pressures and mechanisms that lead to the evolution of fairness in humans. Individuals' varying fairness preferences are widely assumed to represent cultural norms. However, this assumption has not previously been tested. Fairness norms are defined as culturally transmitted equilibria at which bargainers have coordinated expectations from each other. Hence, if fairness norms exist at the level of the ethno-linguistic group, we should observe two patterns. First, cultural conformism should maintain behavioural homogeneity within an ethno-linguistic group. Second, bargainers' expectations should be coordinated such that proposals and responses to proposals should covary. Here we show that neither of these patterns is observed across 21 populations of the same ethno-linguistic group, the Pahari Korwa of central India. Our findings suggest that what constitutes a fair division of resources can vary on smaller scales than that of the ethno-linguistic group. Individuals' local environments may play a central role in determining conceptions of fairness.


Commodity risk assessment of Robinia pseudoacacia plants from Turkey.
The European Commission requested the EFSA Panel on Plant Health to prepare and deliver risk assessments for commodities listed in Commission Implementing Regulation EU/2018/2019 as 'High risk plants, plant products and other objects'. This Scientific Opinion covers plant health risks posed by bare rooted and potted plants of Robinia pseudoacacia that are imported from Turkey, taking into account the available scientific information, including the technical information provided by the Turkish NPPO. The relevance of any pest for this opinion was based on evidence following defined criteria. Three species, the EU-quarantine pests Anoplophora chinensis and Lopholeucapsis japonica, and the EU non-regulated pest Phocazia shantungensis fulfilled all relevant criteria and were selected for further evaluation. For these pests, the risk mitigation measures proposed in the technical dossier from Turkey were evaluated taking into account the possible limiting factors. For these pests, an expert judgement is given on the likelihood of pest freedom taking into consideration the risk mitigation measures acting on the pest, including uncertainties associated with the assessment. The estimated degree of pest freedom varies among the pests evaluated, with L. japonica being the pest most frequently expected on the imported plants. The Expert Knowledge Elicitation indicated, with 95% certainty, that between 9,521 and 10,000 plants per 10,000 would be free of L. japonica.


Loss of p53 in stromal fibroblasts enhances tumor cell proliferation through nitric-oxide-mediated cyclooxygenase 2 activation.
Overexpression of cyclooxygenase 2 (COX-2) by stromal fibroblasts plays a critical role in the early stage of carcinogenesis. COX-2 expression is thought to be positively or negatively regulated by inflammatory chemical mediators or tumor suppressors. In this study, the contributions of inducible nitric oxide synthase (iNOS) and p53 to COX-2 expression were examined using mouse embryonic fibroblasts (MEFs) from wild-type, p53-deficient, iNOS-deficient, and p53/iNOS-deficient mice. These MEFs were treated with 1 μg/mL of lipopolysaccharide and 100 IU/mL of interferon gamma for up to 72 h. iNOS and COX-2 expression were analyzed by Western blotting. iNOS was induced earlier (16 h) in p53-deficient MEFs than in wild-type MEFs (48 h). Elevated expression of COX-2 was sustained for a longer duration in the p53-deficient MEFs. In contrast, COX-2 expression was reduced earlier in the iNOS-deficient MEFs. Addition of an exogenous NO donor (0.8 mM of S-nitroso-l-glutathione) to the iNOS-deficient MEFs augmented COX-2 expression. Co-culture with stimulated p53-deficient MEFs promoted cell proliferation of mouse rectal polyploid carcinoma CMT93 cells, but treatment with a COX-2-specific inhibitor counteracted this effect. These results suggest that loss of function of the p53 gene in stromal fibroblasts enhances COX-2 expression by enhancing iNOS expression and the resultant production of NO, contributing to the promotion of tumor growth.


Structural Studies of Lipopolysaccharide-defective Mutants from Brucella melitensis Identify a Core Oligosaccharide Critical in Virulence.
The structures of the lipooligosaccharides fromBrucella melitensismutants affected in the WbkD and ManBcoreproteins have been fully characterized using NMR spectroscopy. The results revealed that disruption ofwbkDgives rise to a rough lipopolysaccharide (R-LPS) with a complete core structure (β-d-Glcp-(1→4)-α-Kdop-(2→4)[β-d-GlcpN-(1→6)-β-d-GlcpN-(1→4)[β-d-GlcpN-(1→6)]-β-d-GlcpN-(1→3)-α-d-Manp-(1→5)]-α-Kdop-(2→6)-β-d-GlcpN3N4P-(1→6)-α-d-GlcpN3N1P), in addition to components lacking one of the terminal β-d-GlcpN and/or the β-d-Glcpresidues (48 and 17%, respectively). These structures were identical to those of the R-LPS fromB. melitensisEP, a strain simultaneously expressing both smooth and R-LPS, also studied herein. In contrast, disruption ofmanBcoregives rise to a deep-rough pentasaccharide core (β-d-Glcp-(1→4)-α-Kdop-(2→4)-α-Kdop-(2→6)-β-d-GlcpN3N4P-(1→6)-α-d-GlcpN3N1P) as the major component (63%), as well as a minor tetrasaccharide component lacking the terminal β-d-Glcpresidue (37%). These results are in agreement with the predicted functions of the WbkD (glycosyltransferase involved in the biosynthesis of the O-antigen) and ManBcoreproteins (phosphomannomutase involved in the biosynthesis of a mannosyl precursor needed for the biosynthesis of the core and O-antigen). We also report that deletion ofB. melitensis wadCremoves the core oligosaccharide branch not linked to the O-antigen causing an increase in overall negative charge of the remaining LPS inner section. This is in agreement with the mannosyltransferase role predicted for WadC and the lack of GlcpN residues in the defective core oligosaccharide. Despite carrying the O-antigen essential inB. melitensisvirulence, the core deficiency in thewadCmutant structure resulted in a more efficient detection by innate immunity and attenuation, proving the role of the β-d-GlcpN-(1→6)-β-d-GlcpN-(1→4)[β-d-GlcpN-(1→6)]-β-d-GlcpN-(1→3)-α-d-Manp-(1→5) structure in virulence.


Quantitative biomolecular imaging by dynamic nanomechanical mapping.
The ability to 'see' down to nanoscale has always been one of the most challenging obstacles for researchers to address fundamental questions. For many years, researchers have been developing scanning probe microscopy techniques to improve imaging capability at nanoscale. Among them, atomic force microscopy (AFM) has received considerable attention, which allows probing topography of biological species at real space under physiological environment. Importantly, force measurements in AFM enable researchers to reveal not only the topography but also the relevant physical-chemical properties. AFM-based dynamic nanomechanical mapping (DNM) provides insights into the functions of biological systems by the interpretation of 'force', which are inaccessible by most of the other analytic techniques. This review is aiming to shed light on these recently developed AFM-based DNM techniques for biomolecular imaging, and discuss the relative applications in biological research from the nanomechanical point of view.