Adverse childhood experiences in the lives of female sex offenders.
This study explored the prevalence of early trauma in a sample of U.S. female sexual offenders (N = 47) using the Adverse Childhood Experiences (ACE) scale. Compared with females in the general population, sex offenders had more than three times the odds of child sexual abuse, four times the odds of verbal abuse, and more than three times the odds of emotional neglect and having an incarcerated family member. Half of the female sex offenders had been sexually abused as a child. Only 20% endorsed zero adverse childhood experiences (compared with 35% of the general female population) and 41% endorsed four or more (compared with 15% of the general female population). Higher ACE scores were associated with having younger victims. Multiple maltreatments often co-occurred in households with other types of dysfunction, suggesting that many female sex offenders were raised within a disordered social environment by adults with problems of their own who were ill-equipped to protect their daughters from harm. By enhancing our understanding of the frequency and correlates of early adverse experiences, we can better devise trauma-informed interventions that respond to the clinical needs of female sex offender clients.


A contemporary perspective on pharmacy's traditional strengths.
To present a framework for recognizing, appreciating, and applying the specific skills used during the processes of medication order screening and therapy monitoring in daily practice. The health care system in which the profession of pharmacy serves is undergoing significant change. The profession is continually reacting to this change. Recently these reactions have included a shift in focus from the medication order processing skills all pharmacists possess to such things as medication prescribing, clinical pathway development, and formulary management. Although some of these activities have merit, we believe that the disregard of pharmacy's traditional strengths applied to medication order processing may damage both patient care and the system in which we practice. Renewed focus must be applied to the development of practice models that include the application of unique pharmacist skills (e.g., optimizing drug doses, safety, routes of administration, and compliance) as integral components. Variances in knowledge and training among pharmacists may result in differences in the level of service provided to a given patient. However, all pharmacists are equipped to provide unique professional services at a level that has demonstrable impact on patient care. Pharmacists are uniquely skilled in ensuring the safe and effective use of medications. The authors believe that the specific skills applied during the processes of medication order screening and therapy monitoring can and should be incorporated into daily practice. Failure to do so will deprive patients of optimal care and pharmacists of professional satisfaction. We encourage pharmacists to recognize and develop their unique, traditional strengths, and subsequently allow these strengths to provide the health benefits for which they were intended.


Onset and recovery from panic disorder in the Baltimore Epidemiologic Catchment Area follow-up.
The objective is to estimate parameters of the natural history of panic disorder, including its prodrome, incidence, recovery and recurrence. In 1981 the Baltimore Epidemiologic Catchment Area Study interviewed 3481 individuals probabilistically selected from the household population. During 1993-1996, 1920 of these individuals (73% of survivors) were interviewed again. Baseline and follow-up interviews included the National Institute of Mental Health Diagnostic Interview Schedule. During the follow-up, a subsample was assessed by psychiatrists using the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry (SCAN). There were 35 new cases of panic disorder in 24,475 person years of exposure, yielding an annual incidence of 1.43 per 1000 per year. Data from the SCAN assessments suggest the incidence estimate is conservative. Incidence is greater in females and declines with age. About one-third of the new cases arise without agoraphobia, but about half have anxiety of some sort present for many years prior to meeting criteria for diagnosis. People with agoraphobia have less intense onsets but slower recoveries than those without agoraphobia. Panic is heterogeneous in its pattern of onset and recovery. Some of the heterogeneity is associated with the presence of other anxiety over a long period of the life.


Defining HIV-1 transmission clusters based on sequence data.
: Understanding HIV-1 transmission dynamics is relevant to both screening and intervention strategies of HIV-1 infection. Commonly, HIV-1 transmission chains are determined based on sequence similarity assessed either directly from a sequence alignment or by inferring a phylogenetic tree. This review is aimed at both nonexperts interested in understanding and interpreting studies of HIV-1 transmission, and experts interested in finding the most appropriate cluster definition for a specific dataset and research question. We start by introducing the concepts and methodologies of how HIV-1 transmission clusters usually have been defined. We then present the results of a systematic review of 105 HIV-1 molecular epidemiology studies summarizing the most common methods and definitions in the literature. Finally, we offer our perspectives on how HIV-1 transmission clusters can be defined and provide some guidance based on examples from real life datasets.


'A smile is most important.' Why chains are not currently the answer to quality concerns in the Indian retail pharmacy sector.
Chain pharmacies are expanding in many low and middle-income countries (LMICs). Historically practices of independent pharmacies in these settings have been poor, and there is a need to understand how these new organisational arrangements are affecting the functioning of pharmacies, and the implications for public health. Drawing on economics literature, we develop a set of hypotheses as to how chains could address the quality failures that typify LMIC retail pharmacy markets, and explore these hypotheses using a set of 38 in-depth interviews, conducted in Bengaluru, India between 2014 and 2015. We look specifically at how being organised in a chain affects several key behaviours: employment of qualified staff; the ability of government authorities to focus regulation on central management structures; the propensity for firms to self-regulate; and the impact of the potentially lower-powered incentives faced by chain employees compared to independent owners. In practice, few differences were identified between chain and independent organisations in these areas. Not all chains were operating with a qualified pharmacist (akin to independent shops). Drug control authorities did not take advantage of the existing chain architecture to enforce regulation. Chains did heavily self-regulate but their focus was on customer service, rather than aspects of quality relevant to health outcomes. Additionally, widespread bribery in the sector was a barrier to effective drug control. Finally, the incentives faced by chain employees were not low-powered due to rewarding sales targets and pressure to increase sales. We observed that chains exerted strong influence over their staff but the potential to exploit this to improve quality of care is not currently being realised. A shift in focus from customer satisfaction to outcomes of public health concern is unlikely without either financial incentives or strengthened external regulation.


Large and transient positive temperature anomalies in Washington's coastal nearshore waters during the 2013-2015 northeast Pacific marine heatwave.
The northern portion of Washington's outer coast-known locally as the Olympic coast-is a dynamic region characterized by seasonal upwelling that predominates during summer interrupted by occasional periods of downwelling. We examined spring-to-fall water temperature records collected along this coast from 2001-2015 from April to October at four nearshore locations (Cape Elizabeth to Makah Bay) that span one degree of latitude and are located within 15 km of the shore. When compared against a long-term climatology created for 2001-2013, seven-day smoothed temperature anomalies of up to 4.5°C at 40 m depth during 2014 and 2015 show short-term warm events lasting 10-20 days. These periods of warming occurred within the well documented marine heatwave in the Northeast Pacific and were about twice the seasonal temperature range in the climatology at that depth. These warm events were strongly correlated with periods of northward long-shore winds and upper ocean currents, consistent with what is expected for the response to downwelling-favorable winds. While our focus a priori was on 2014 and 2015, we also found large positive temperature events in 2013, which were potentially related to the early stage of the marine heatwave, and in 2011, which did not have a documented marine heatwave. This indicates that near-shore short-term warm events occur during periods of large-scale offshore marine heatwave events, but also can occur in the absence of a large-scale marine heatwave event when downwelling-favorable winds occur during the summer/early fall.


Satellite remote sensing of particulate matter air quality: the cloud-cover problem.
Satellite assessments of particulate matter (PM) air quality that use solar reflectance methods are dependent on availability of clear sky; in other words, mass concentrations of PM less than 2.5 microm in aerodynamic diameter (PM2.5) cannot be estimated from satellite observations under cloudy conditions or bright surfaces such as snow/ice. Whereas most ground monitors measure PM2.5 concentrations on an hourly basis regardless of cloud conditions, space-borne sensors can only estimate daytime PM2.5 in cloud-free conditions, therefore introducing a bias. In this study, an estimate of this clear-sky bias is provided from monthly to yearly time scales over the continental United States. One year of the Moderate Resolution Imaging Spectroradiometer (MODIS) 550-nm aerosol optical depth (AOD) retrievals from Terra and Aqua satellites, collocated with 371 U.S. Environmental Protection Agency (EPA) ground monitors, have been analyzed. The results indicate that the mean differences between PM2.5 reported by ground monitors and PM2.5 calculated from ground monitors during the satellite overpass times during cloud-free conditions are less than +/- 2.5 microg m(-3), although this value varies by season and location. The mean differences are not significant as calculated by t tests (alpha = 0.05). On the basis of this analysis, it is concluded that for the continental United States, cloud cover is not a major problem for inferring monthly to yearly PM2.5 from space-borne sensors.


Measuring DNA Replication in Hypoxic Conditions.
It is imperative that dividing cells maintain replication fork integrity in order to prevent DNA damage and cell death. The investigation of DNA replication is of high importance as alterations in this process can lead to genomic instability, a known causative factor of tumor development. A simple, sensitive, and informative technique which enables the study of DNA replication, is the DNA fiber assay, an adaptation of which is described in this chapter. The DNA fiber method is a powerful tool, which allows the quantitative and qualitative analysis of DNA replication at the single molecule level. The sequential pulse labeling of live cells with two thymidine analogues and the subsequent detection with specific antibodies and fluorescence imaging allows direct examination of sites of DNA synthesis. In this chapter, we describe how this assay can be performed in conditions of low oxygen levels (hypoxia)-a physiologically relevant stress that occurs in most solid tumors. Moreover, we suggest ways on how to overcome the technical problems that arise while using the hypoxic chambers.


Propranolol Reduces Cardiac Index But does not Adversely Affect Peripheral Perfusion in Severely Burned Children.
The aim of this study was to quantify the effect of propranolol on hemodynamic parameters assessed using the PiCCO system in burned children. We analyzed hemodynamic data from patients who were randomized to receive either propranolol (4 mg/kg/day) or placebo (control), which was initiated as a prospective randomized controlled trial. Endpoints were cardiac index (CI), percent predicted heart rate (%HR), mean arterial pressure (MAP), percent predicted stroke volume (%SV), rate pressure product (RPP), cardiac work (CW), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), arterial blood gases, events of lactic acidosis, and mortality. Mixed multiple linear regressions were applied, and a 95% level of confidence was assumed. One hundred twenty-one burned children (control: n = 62, propranolol: n = 59) were analyzed. Groups were comparable in demographics, EVLWI, SVRI, %SV, arterial blood gases, Denver 2 postinjury organ failure score, incidence of lactic acidosis, or mortality. Percent predicted HR, MAP, CI, CW, and RPP were significantly reduced in the propranolol-treated group (P <0.01). Propranolol significantly reduces cardiogenic stress by reducing CI and MAP in children with severe burn injury. However, peripheral oxygen delivery was not reduced and events of lactic acidosis as well as organ dysfunction was not higher in propranolol treated patients.


Healthcare IT Utilization and Penetration among Physicians: Novel IT Solutions in Healthcare - Use and Acceptance in Hospitals.
Healthcare IT (HIT) increasingly gains public attention and clinical daily relevance. A growing number of patients and physicians increasingly relies on IT services to monitor and support well-being and recovery both in their private and professional environment. This is assumed to develop rapidly in the upcoming years. This study examines the current status of HIT, its use and penetration among physicians in hospitals and researches utilization as well as future expectations regarding HIT. Physicians in Germany, Austria and Switzerland were addressed via e-mail to answer a standardized Internet-based questionnaire consisting of 17 multiple-choice and 3 open text questions. Parameters were evaluated in 5 categories: general use, frequency, acceptance, IT needs and future expectations. An overall 234 physicians (response rate 83.6%) with a median age of 45 (range 25-60) responded and filled out the entire online questionnaire. A significant correlation between parameters gender, age and level of training (resident, specialist, consultant etc.) was proven. The professional, medical employment of technology shows a strong correlation with age as well as level of training. Whereas increasing age among physicians is associated with a decreasing level of application of HIT, a higher training level is accompanied by an increasing level of professional application of IT services and tools within the healthcare context. Routine employment of HIT is regarded as a necessary and positive standard. Most users assume the importance of HIT to strongly grow in the future in comparison to current use. A clear lack of trust towards data security and storage is recognized on both patient and physician sides. Needs are currently satisfied by employing privately acquired IT in the professional setup rather than the hospitals'. Future expectations from HIT show a clear demand for interoperability and exchangeability of data. The results display a clear gap between demand and expectations of IT for medical purposes. The rate of use of HIT applications generally correlates with age, gender as well as role within the hospital and type of employment within the healthcare sector. The current offering does not satisfy the needs of healthcare professionals.


Prevalence and descriptors of aspirin use as an antiplatelet agent in two New England communities.
To determine the overall prevalence of aspirin use as an antiplatelet agent in a population-based sample of respondents between the ages of 18 and 64 years, and to describe their sociodemographic characteristics. Data were derived from five biennial cross-sectional household surveys conducted between 1981 and 1990 in two southeastern New England communities by the Pawtucket Heart Health Program. Individuals reporting aspirin use as an antiplatelet agent were identified using data from a structured medication interview. The prevalence of aspirin use per 1000 population was 2.5 (95 percent confidence interval [CI] 0.5, 4.4), 5.0 (95 percent CI 2.4, 7.6), 7.8 (95 percent CI 4.6, 11.0), 7.5 (95 percent CI 4.3, 10.6), and 11.8 (95 percent CI 7.1, 16.5) in the first through the fifth survey periods, respectively (p = 0.0002). The prevalence of aspirin use per 1000 men increased from 4.9 (95 percent CI 0.6, 9.1), 8.7 (95 percent CI 3.3, 14.1), 12.3 (95 percent CI 6.1, 18.5), 8.5 (95 percent CI 3.5, 13.5) to 23.2 (95 percent CI 13.4, 32.9) for the first through the fifth survey periods, respectively. The corresponding prevalence rates of aspirin use per 1000 women were 0.7 (95 percent CI 0, 2.1), 2.43 (95 percent CI 0.05, 4.80), 4.6 (95 percent CI 1.4, 7.8), 6.6 (95 percent CI 2.7, 10.6), and 2.7 (95 percent CI 0, 5.7). Both a gender trend (p = 0.0002) and a survey trend (p = 0.0001) were detected. A gender-survey interaction was not found. In this population, aspirin use was reported primarily by middle-aged men who had coexisting cardiovascular disease as indicated by concurrent medications. Aspirin use as antiplatelet therapy increased in the population-based samples of two New England communities over the past nine years, with slightly more than one percent of the respondents reporting its use in the fifth cross-sectional survey conducted in 1989-1990. This finding may reflect the publication of important clinical trials near the time the survey was performed and subsequent dissemination of the findings both in the professional and lay press.


Effect of Multi-Ingredient Supplement Containing Satiereal, Naringin, and Vitamin D on Body Composition, Mood, and Satiety in Overweight Adults.
The purpose of this investigation was to examine the effects of 28 days of a dietary supplement on body composition, mood, and satiety in overweight adults. Twenty healthy adults (25.5 ± 3.8 years; 87.3 ± 20.7 kg; 169.9 ± 10.6 cm; 29.9 ± 5.1 body mass index) participated in this randomized, double-blind, placebo-controlled investigation. Ten participants were provided with a dietary supplement containing 178 mg satiereal, 100 mg naringin, and 2,000 IU vitamin D3 daily (SUPP), and ten participants were provided a placebo (PL) for 28 days. Baseline (PRE) and post (POST) assessments included body mass, BMI, and waist circumference measures. In addition, participants provided self-reported food records and completed study questionnaires twice weekly. Questionnaires consisted of profile of mood states, visual analog scales, modified trait food-cravings questionnaire, and a modified state food-cravings questionnaire. No significant differences were noted between groups for total calorie or macronutrient intake (p = 0.65-0.92), body mass (p = 0.34), BMI (p = 0.24), or waist circumference measures (p = 0.56-0.94). In addition, no significant differences between groups were observed for mood states, subjective measures of food cravings, or feelings of anxiety, fullness, bloating, hunger, craving, and stress (p >.05). In conclusion, 28 days of a dietary supplement containing satiereal, naringin, and vitamin D3 did not have any detectable beneficial effects on body-weight management.


Formation of morphogen gradients: local accumulation time.
Spatial regulation of cell differentiation in embryos can be provided by morphogen gradients, which are defined as the concentration fields of molecules that control gene expression. For example, a cell can use its surface receptors to measure the local concentration of an extracellular ligand and convert this information into a corresponding change in its transcriptional state. We characterize the time needed to establish a steady-state gradient in problems with diffusion and degradation of locally produced chemical signals. A relaxation function is introduced to describe how the morphogen concentration profile approaches its steady state. This function is used to obtain a local accumulation time that provides a time scale that characterizes relaxation to steady state at an arbitrary position within the patterned field. To illustrate the approach we derive local accumulation times for a number of commonly used models of morphogen gradient formation.


Current primary care management of children aged 1-36 months with urinary tract infections in Europe: large scale survey of paediatric practice.
To describe current practice among European paediatricians regarding diagnosis and management of urinary tract infections in children aged 1-36 months and to compare these practices with recently published guidelines. Web-based large scale survey evaluating knowledge of, attitudes towards and the methods for diagnosing, treating and managing urinary tract infections in children. Primary and secondary care practices in Europe. 1129 paediatricians. A diagnosis of urinary tract infection is considered by 62% of the respondents in children aged 1-36 months with unexplained fever. The preferred method of urine collection is use of a bag (53% for infants <3 months and 59% for children 4-36 months of age). 60% of paediatricians agree that oral and parenteral antibiotics have equal efficacy. Co-amoxiclav is the antibiotic of choice for 41% of participants, while 9% prescribe amoxicillin. 80% of respondents prescribe ultrasound in all children with a confirmed urinary tract infection. 63% of respondents prescribe a cystography when abnormalities are revealed during ultrasound evaluation. A quarter of respondents recommend antibiotic prophylaxis for all children with any vesicoureteral reflux. The data among European countries are very heterogeneous. The three most recent urinary tract infection guidelines (the National Institute for Health and Care Excellence (NICE), the American Academy of Paediatrics and the Italian Society of Paediatric Nephrology) are not followed properly. Management of febrile urinary tract infections remains controversial and heterogeneous in Europe. Simple, short, practical and easy-to-remember guidelines and educational strategies to ensure their implementation should be developed.


Longterm treatment of irritable bowel syndrome with cimetropium bromide: a double blind placebo controlled clinical trial.
The aim of this study was to evaluate the efficacy of cimetropium bromide, a new antimuscarinic compound, in relieving symptoms of patients with irritable bowel syndrome over a three month period. Seventy consecutive outpatients were given cimetropium (50 mg tid) or placebo according to a double blind, randomised, parallel groups design. Symptoms were evaluated initially and at monthly intervals up to the end of the study period. One patient receiving placebo withdrew because of treatment failure. Pain score decreased by 40, 66, 85% in the cimetropium group, at the end of the first, second and third months respectively, compared with 26, 32 and 52% reductions among controls (p = 0.0005). At the end of treatment there was a 86% reduction in the number of abdominal pain episodes per day in the cimetropium group compared with 50% in the placebo group (p = 0.001). Constipation and diarrhoea scores decreased by 59 and 49% in the cimetropium treated patients, compared with 37 and 39% in controls, the differences between being not significant. At the end of the study 89% of the patients treated with cimetropium considered themselves as globally improved as opposed to 69% in the placebo group (p = 0.039). The corresponding 95% confidence intervals for the differences between the proportion of improved patients in the two groups were from 11% to 29%. Six patients taking cimetropium complained of slight dry mouth. The results of this study showed that cimetropium bromide is effective in relieving pain in patients with irritable bowel syndrome.


Herniation of the gravid uterus through a mesoduodenal defect and concurrent omental hernia in a cow.
To describe surgical treatment of herniation of the gravid uterus through the mesoduodenum, displacement of the descending duodenum around the gravid uterus, and concurrent herniation of the small and large intestines into the omental bursa in a cow. Clinical report. Three-year-old, five-month-pregnant Swiss Braunvieh cow. Repositioning of the displaced uterus and descending duodenum without transection and anastomosis of the duodenum was performed through a right flank laparotomy. Concurrent displacement of a large portion of the small and large intestines into the omental bursa was not associated with intestinal strangulation and was corrected manually. The defects in the omentum and mesoduodenum were sutured. There were no postoperative complications, and the cow was healthy at discharge from the clinic 1 week after surgery. Telephone follow-up revealed that the cow had delivered a live calf and was producing a normal amount of milk. The cow was slaughtered 14 months after the surgery because of an udder problem. Herniation of the gravid uterus through a tear in the mesoduodenum with subsequent displacement of the descending duodenum around the uterus combined with internal omental herniation caused nonspecific clinical signs and no ileus. Exploratory laparotomy in an early stage of pregnancy facilitated reduction of the displaced uterus without transection of the descending duodenum.


Closed-loop and decision-assist resuscitation of burn patients.
Effective resuscitation is critical in reducing mortality and morbidity rates of patients with acute burns. To this end, guidelines and formulas have been developed to define infusion rates and volume requirements during the first 48 hours postburn. Even with these standardized resuscitation guidelines, however, over- and under-resuscitation are not uncommon. Two approaches to adjust infusion rate are decision-assist and closed-loop algorithms based on levels of urinary output. Specific decision assist guidelines or a closed-loop system using computer-controlled feedback technology that supplies automatic control of infusion rates can potentially achieve better control of urinary output. In a properly designed system, closed-loop control has the potential to provide more accurate titration rates, while lowering the incidence of over- and under-resuscitation. Because the system can self-adjust based on monitoring inputs, the technology can be pushed to environments such as combat zones where burn resuscitation expertise is limited. A closed-loop system can also assist in the management of mass casualties, another scenario in which medical expertise is often in short supply. This article reviews the record of fluid balance of contemporary burn resuscitation and approaches, as well as the engineering efforts, animal studies, and algorithm development of our most recent autonomous systems for burn resuscitation.


Differences in alcohol expectancy between aggressive and nonaggressive social drinkers.
Previous reports have shown that drinkers with aggressive personalities not only hold the strongest beliefs that alcohol facilitates aggressive behavior, but they also display the greatest increases in laboratory aggression after receiving alcohol. Given that several studies have demonstrated that a portion of the behavioral and subjective effects of alcohol are due to psychological expectancy, this study explored whether aggressive drinkers have elevated intoxication expectancies from laboratory beverages with unknown alcohol content. The rates of aggressive responses emitted in a money subtraction aggression model under baseline conditions were used to select an aggressive group and a nonaggressive group, each with five male and five female participants. Subjects then ingested and rated each of three placebo (1 ml alcohol) beverages administered hourly during a subsequent laboratory visit, and rated a series of three 0.35 g/kg of alcohol beverages the following day. Whereas nonaggressive subjects clearly discriminated the relative alcohol content of alcohol and placebo drinks, aggressive subjects gave progressively elevated shot equivalent ratings to placebo drinks, similar to their ratings of alcohol doses. However, despite similar self-reported drinking histories, aggressive subjects reported anticipating only half the intoxication from the alcohol doses (and in fact achieved a lower peak breath alcohol concentration) than was expected by nonaggressive subjects.


The transcription factor GATA3 is a downstream effector of Hoxb1 specification in rhombomere 4.
In this paper, we show that the transcription factor GATA3 is dynamically expressed during hindbrain development. Function of GATA3 in ventral rhombomere (r) 4 is dependent on functional GATA2, which in turn is under the control of Hoxb1. In particular, the absence of Hoxb1 results in the loss of GATA2 expression in r4 and the absence of GATA2 results in the loss of GATA3 expression. The lack of GATA3 expression in r4 inhibits the projection of contralateral vestibuloacoustic efferent neurons and the migration of facial branchiomotor neurons similar to Hoxb1-deficient mice. Ubiquitous expression of Hoxb1 in the hindbrain induces ectopic expression of GATA2 and GATA3 in ventral r2 and r3. These findings demonstrate that GATA2 and GATA3 lie downstream of Hoxb1 and provide the first example of Hox pathway transcription factors within a defined population of vertebrate motor neurons.


Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are believed to partially share genetic factors and biological influences. As the number of children with these diagnoses rises, so does the number of younger siblings at presumed risk for ADHD and ASD; reliable recurrence risk estimates within and across diagnoses may aid screening and early detection efforts and enhance understanding of potential shared causes. To examine within-diagnosis sibling recurrence risk and sibling cross-aggregation of ADHD and ASD among later-born siblings of children with either disorder. Using data extracted from medical records of 2 large health care systems in the United States, estimates of recurrence risk and cross-aggregation in later-born siblings of children with ADHD or ASD were compared with later-born siblings of children without these diagnoses. One data set included children seen between January 1, 1995, and December 31, 2013; the other included children born between January 1, 1998, and May 17, 2010. Participants included 15 175 later-born siblings of children with ADHD, ASD, and no known diagnosis. The study was conducted from October 2, 2017, to August 14, 2018. Diagnoses of ASD or ADHD in the later-born sibling, ascertained from medical records, were the primary outcomes of interest; moderators included sex, gestational age, and maternal age. A total of 15 175 later-born siblings were classified by familial risk status based on the older child's diagnostic status: ADHD risk (n = 730; male [51.92%]), ASD risk (n = 158; male [48.10%]), and no known risk (n = 14 287; male [50.73%]). Compared with later-born siblings of children without ADHD or ASD, later-born siblings of children with ASD were more likely to be diagnosed with ASD (odds ratio [OR], 30.38; 95% CI, 17.73-52.06) or ADHD in the absence of ASD (OR, 3.70; 95% CI, 1.67-8.21). Compared with later-born siblings of children without a diagnosis, later-born siblings of children with ADHD were more likely to be diagnosed with ADHD (OR, 13.05; 95% CI, 9.86-17.27) or ASD in the absence of ADHD (OR, 4.35; 95% CI, 2.43-7.79). Later-born siblings of children with ASD or ADHD appear to be at elevated risk for the same disorder, but also of being diagnosed with the other disorder. These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies. Later-born siblings of children with ADHD or ASD should be monitored for both conditions.


Substrate specificity and excision kinetics of Escherichia coli endonuclease VIII (Nei) for modified bases in DNA damaged by free radicals.
Endonuclease VIII (Nei) is one of three enzymes in Escherichia coli that are involved in base-excision repair of oxidative damage to DNA. We investigated the substrate specificity and excision kinetics of this DNA glycosylase for bases in DNA that have been damaged by free radicals. Two different DNA substrates were prepared by gamma-irradiation of DNA solutions under N(2)O or air, such that they contained a multiplicity of modified bases. Although previous studies on the substrate specificity of Nei had demonstrated activity on several pyrimidine derivatives, this present study demonstrates excision of additional pyrimidine derivatives and a purine-derived lesion, 4,6-diamino-5-formamidopyrimidine, from DNA containing multiple modified bases. Excision was dependent on enzyme concentration, incubation time, and substrate concentration, and followed Michaelis-Menten kinetics. The kinetic parameters also depended on the identity of the individual modified base being removed. Substrates and excision kinetics of Nei and a naturally arising mutant form involving Leu-90-->Ser (L90S-Nei) were compared to those of Escherichia coli endonuclease III (Nth), which had previously been determined under experimental conditions similar to those in this study. This comparison showed that Nei and Nth significantly differ from each other in terms of excision rates, although they have common substrates. The present work extends the substrate specificity of Nei and shows the effect of a single mutation in the nei gene on the specificity of Nei.


Microsatellite analysis and telomerase activity in archived tissue and urine samples of bladder cancer patients.
We performed microsatellite analysis and tested telomerase activity in paired tissue and urine of bladder cancer patients from frozen archived samples. DNA obtained from microdissected tumor and urine sediment was analyzed and compared to peripheral lymphocytes for microsatellite alterations (loss of heterozygosity [LOH] or instability) using a panel of 20 microsatellite markers in 15 patients with transitional or squamous cell carcinoma of the urinary tract. Additionally, telomerase activity was determined in 12 microdissected tumor specimens and corresponding frozen urine pellets. Tumor cell DNA was detected by microsatellite analysis (LOH or shift) in at least one marker in 14/15 microdissected tumor specimens and in 13/15 DNA samples obtained from urine sediments. Telomerase activity was present in 11/12 tumor samples but could not be detected in any of the corresponding urine sediments. Frozen archived urine samples are useful for retrospective studies utilizing microsatellite analysis or other PCR-based approaches after DNA extraction. However, the evaluation of telomerase protein activity in stored urine samples appears to be unsuitable.


Interface deformations affect the orientation transition of magnetic ellipsoidal particles adsorbed at fluid-fluid interfaces.
Manufacturing new soft materials with specific optical, mechanical and magnetic properties is a significant challenge. Assembling and manipulating colloidal particles at fluid interfaces is a promising way to make such materials. We use lattice-Boltzmann simulations to investigate the response of magnetic ellipsoidal particles adsorbed at liquid-liquid interfaces to external magnetic fields. We provide further evidence for the first-order orientation phase transition predicted by Bresme and Faraudo [Journal of Physics: Condensed Matter, 2007, 19, 375110]. We show that capillary interface deformations around the ellipsoidal particle significantly affect the tilt-angle of the particle for a given dipole-field strength, altering the properties of the orientation transition. We propose scaling laws governing this transition, and suggest how to use these deformations to facilitate particle assembly at fluid-fluid interfaces.


Robust Bayesian General Linear Models.
We describe a Bayesian learning algorithm for Robust General Linear Models (RGLMs). The noise is modeled as a Mixture of Gaussians rather than the usual single Gaussian. This allows different data points to be associated with different noise levels and effectively provides a robust estimation of regression coefficients. A variational inference framework is used to prevent overfitting and provides a model order selection criterion for noise model order. This allows the RGLM to default to the usual GLM when robustness is not required. The method is compared to other robust regression methods and applied to synthetic data and fMRI.


The striated musculature of blood vessels. II. Cell interconnections and cell surface.
The interconnections and the surfaces of the striated muscle cells which occur in thoracic and in lung veins of the mouse were studied with the electron microscope. The osmium-fixed tissues were embedded in methacrylate or in araldite and sectioned with a Porter-Blum microtome. Many preparations were stained before embedding with phosphotungstic acid or after sectioning with uranyl acetate. Typical intercalated discs are observed in this muscle. They are similar to the discs found in heart muscle. These intercalated discs represent boundaries between separate muscle cells. Along the discs, cells are joined in planes normal to their myofilaments. The same cells are also joined in planes parallel to the myofilaments by means of lateral interconnections. These lateral cell boundaries are in continuity with the intercalated discs. Three morphologically distinct parts occur within the lateral cell interconnections: One is characterized by small vesicles along the plasma membrane, the second part has the structure of desmosomes, and a third part represents an external compound membrane (formed by the two plasma membranes of the adjoining cells) and is termed "quintuple-layered cell interconnection." Small vesicles and plasma membrane enfoldings along the free surface of muscle cells are interpreted as products of a pinocytosis (phagocytosis) process. Some of them are seen to contain small membrane-bounded bodies or granules. The free cell surface shows a characteristic outer dense layer ("basement membrane") which accompanies the plasma membrane. The topographic relation of this dense layer with the plasma membrane seems to vary in different preparations. The significance of this variation is not well understood. On two occasions a typical arrangement o vesicles and tubules was observed at Z band levels, just beneath the plasma membrane. These structures are believed to represent endoplasmic reticulum. Their possible significance for the conduction of excitation is discussed.


Long non-coding RNA DANCR upregulates IGF2 expression and promotes ovarian cancer progression.
Recent studies have revealed the important role of long non-coding RNA (lncRNAs) in the development of malignant tumors. In this work, we explored the exact role of lncRNA DANCR in ovarian cancer progression and the underlying mechanism. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect DANCR expression in both ovarian cancer cells and tissue samples. Subsequently, cell proliferation assay and transwell assay were conducted. Furthermore, the underlying mechanism was explored via qRT-PCR and Western blot assay. The expression of DANCR in ovarian cancer samples was significantly higher than that of the corresponding normal tissues. After DANCR overexpression in vitro, the proliferation, invasion and migration of ovarian cancer cells were markedly promoted. In addition, both the mRNA and protein expression levels of insulin-like growth factor 2 (IGF2) were remarkably upregulated after DANCR overexpression. Furthermore, the results found that the expression level of IGF2 was positively correlated with DANCR expression in ovarian cancer tissues. In this study, we revealed that DANCR could enhance the proliferation, migration and invasion capacities of ovarian cancer cells by upregulating IGF2. Our findings might offer a potential therapeutic choice for patients with ovarian cancer.


The cerebral cortex of Albert Einstein: a description and preliminary analysis of unpublished photographs.
Upon his death in 1955, Albert Einstein's brain was removed, fixed and photographed from multiple angles. It was then sectioned into 240 blocks, and histological slides were prepared. At the time, a roadmap was drawn that illustrates the location within the brain of each block and its associated slides. Here we describe the external gross neuroanatomy of Einstein's entire cerebral cortex from 14 recently discovered photographs, most of which were taken from unconventional angles. Two of the photographs reveal sulcal patterns of the medial surfaces of the hemispheres, and another shows the neuroanatomy of the right (exposed) insula. Most of Einstein's sulci are identified, and sulcal patterns in various parts of the brain are compared with those of 85 human brains that have been described in the literature. To the extent currently possible, unusual features of Einstein's brain are tentatively interpreted in light of what is known about the evolution of higher cognitive processes in humans. As an aid to future investigators, these (and other) features are correlated with blocks on the roadmap (and therefore histological slides). Einstein's brain has an extraordinary prefrontal cortex, which may have contributed to the neurological substrates for some of his remarkable cognitive abilities. The primary somatosensory and motor cortices near the regions that typically represent face and tongue are greatly expanded in the left hemisphere. Einstein's parietal lobes are also unusual and may have provided some of the neurological underpinnings for his visuospatial and mathematical skills, as others have hypothesized. Einstein's brain has typical frontal and occipital shape asymmetries (petalias) and grossly asymmetrical inferior and superior parietal lobules. Contrary to the literature, Einstein's brain is not spherical, does not lack parietal opercula and has non-confluent Sylvian and inferior postcentral sulci.


Use of DAMPs and SAMPs as Therapeutic Targets or Therapeutics: A Note of Caution.
This opinion article discusses the increasing attention paid to the role of activating damage-associated molecular patterns (DAMPs) in initiation of inflammatory diseases and suppressing/inhibiting DAMPs (SAMPs) in resolution of inflammatory diseases and, consequently, to the future roles of these novel biomarkers as therapeutic targets and therapeutics. Since controlled production of DAMPs and SAMPs is needed to achieve full homeostatic restoration and repair from tissue injury, only their pathological, not their homeostatic, concentrations should be therapeutically tackled. Therefore, distinct caveats are proposed regarding choosing DAMPs and SAMPs for therapeutic purposes. For example, we discuss the need to a priori identify and define a context-dependent "homeostatic DAMP:SAMP ratio" in each case and a "homeostatic window" of DAMP and SAMP concentrations to guarantee a safe treatment modality to patients. Finally, a few clinical examples of how DAMPs and SAMPs might be used as therapeutic targets or therapeutics in the future are discussed, including inhibition of DAMPs in hyperinflammatory processes (e.g., systemic inflammatory response syndrome, as currently observed in Covid-19), administration of SAMPs in chronic inflammatory diseases, inhibition of SAMPs in hyperresolving processes (e.g., compensatory anti-inflammatory response syndrome), and administration/induction of DAMPs in vaccination procedures and anti-cancer therapy.


POT1 as a terminal transducer of TRF1 telomere length control.
Human telomere maintenance is essential for the protection of chromosome ends, and changes in telomere length have been implicated in ageing and cancer. Human telomere length is regulated by the TTAGGG-repeat-binding protein TRF1 and its interacting partners tankyrase 1, TIN2 and PINX1 (refs 5-9). As the TRF1 complex binds to the duplex DNA of the telomere, it is unclear how it can affect telomerase, which acts on the single-stranded 3' telomeric overhang. Here we show that the TRF1 complex interacts with a single-stranded telomeric DNA-binding protein--protection of telomeres 1 (POT1)--and that human POT1 controls telomerase-mediated telomere elongation. The presence of POT1 on telomeres was diminished when the amount of single-stranded DNA was reduced. Furthermore, POT1 binding was regulated by the TRF1 complex in response to telomere length. A mutant form of POT1 lacking the DNA-binding domain abrogated TRF1-mediated control of telomere length, and induced rapid and extensive telomere elongation. We propose that the interaction between the TRF1 complex and POT1 affects the loading of POT1 on the single-stranded telomeric DNA, thus transmitting information about telomere length to the telomere terminus, where telomerase is regulated.


Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.
Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Treatment with 0.5 μg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. UMIN-CTR Identifier: UMIN000001194.


The accessory cell function of human alveolar macrophages in specific T cell proliferation.
The capacity of alveolar macrophages to support mitogen- and antigen-induced proliferation of autologous, monocyte-depleted T cells in normal, nonsmoking volunteers was studied. Purified T cells failed to proliferate in response to mitogen or antigen, whereas co-culture with peripheral blood monocytes restored responsiveness. Alveolar macrophages (AM) reconstituted the response of T cells to mitogen, indicating that AM can deliver a second proliferative signal. AM, however, were markedly inferior to monocytes in supporting antigen-induced proliferation. Thus, in 19 normal volunteers, the mean response of immune T cells to diphtheria toxoid in cultures reconstituted with normal AM was only 25% of the proliferative response to diphtheria in cultures with monocytes. Although four volunteers demonstrated antigen-presenting function equivalent to monocytes, in the remaining 15 antigen-presenting ability of AM was less than 15% that of monocytes. The difference in antigen-presenting function between AM and monocytes was not due to a difference in their display of HLA-D/DR determinants because 80% of AM were HLA-DR positive. The role of suppression in the diminished antigen-presenting function of AM was assessed in 12 volunteers utilizing mixing experiments. Eight volunteers demonstrated suppressor AM but four did not, suggesting that AM from at least some normal individuals have a faulty antigen-processing mechanism. Taken together, these studies demonstrate that AM may play three different roles in modulating T lymphocyte responses, i.e., they may present antigen, they may suppress normal responses, or they may remain immunologically inert. The factors that determine which function is expressed in vivo may determine the pulmonary response to inhaled antigen.


Polypharmacy and suicide attempts in bipolar disorder.
The aim of this study was to assess the association between suicide attempts and the use of multiple drugs in patients with bipolar disorder. One hundred sixty-nine bipolar disorder outpatients diagnosed using the DSM-IV Structured Clinical Interview were included. Demographic and socioeconomic data, number of medications currently in use, history of suicide attempts, number of years undiagnosed, age of onset and current psychiatric co-morbidities were assessed using a structured questionnaire and DSM-IV criteria. The main outcome measure was the number of psychotropic drugs currently in use. Approximately half of all patients (48.5%) presented a history of suicide attempt; 84% were using more than one medication, and 19% were using more than three drugs. The most frequent combinations of drugs used by these patients were: lithium + valproate (17%); lithium + antipsychotics (10%); lithium + valproate + antipsychotics (9%); and antidepressants + any drug (6%). The number of suicide attempts was associated with the use of multiple drugs. Our findings support the notion that the use of combination therapy in bipolar disorder may be related to severity of the BD, such as number of suicide attempts.


Clinicopathological and treatment analysis of 13 extragastrointestinal stromal tumors of mesentery and retroperitoneum.
Extragastrointestinal stromal tumors (EGISTs) are extremely rare mesenchymal tumors histologically and immunophenotypically similar to GI stromal tumors (GISTs). The aim of this study was to analyze the clinicopathological factors and treatment outcome in 13 patients with EGISTs treated at a tertiary care center. Of 109 patients with GISTs treated at our center between April 2002 and December 2012, 13 patients with EGISTs were analyzed for clinicopathological factors and treatment outcome. Mean age was 45.8 (range 30-61) years, and females constituted 62% with a male:female ratio of 0.6:1. The most common tumor sites were mesentery in 10 patients and retroperitoneum in 3 patients. Mean tumor size was 11.7 (range 5-18) cm. Four (31%) patients were metastatic at presentation, the most common site of metastases being the liver in 3 (75%) patients. Lymph node enlargement was seen in 2 patients. Surgery was performed in 8 (62%) patients, 7 with localized disease, and 1 with metastatic disease. R0 resection was achieved in 3 (38%) patients. Five (71%) patients were considered as high-risk. Recurrences were seen in 3 patients (patient 3, 5 and 13) with localized disease after surgical resection, at 18, 7 and 137 months, respectively. At the last follow up, 7 patients were alive and 6 died of disease progression. The median overall survival was 34 (7-148) months. EGISTs present at a younger age in the developing than in the developed countries. Females are more commonly affected than males. Lymph node metastases may be commonly present.


A probiotic Bacillus strain containing amorphous poly-beta-hydroxybutyrate (PHB) stimulates the innate immune response of Penaeus monodon postlarvae.
In this study, the PHB-accumulating Bacillus sp. JL47 strain (capable of accumulating 55% PHB on cell dry weight) was investigated for its effects on the immune response of giant tiger shrimp (Penaeus monodon) postlarvae (PL) before and after the Vibrio campbellii challenge. Briefly, shrimp PL were cultured and fed with Artemia nauplii enriched with Bacillus sp. JL47. Shrimp receiving the Artemia nauplii without JL47 enrichment were used as control. After 15 days of feeding, the shrimp were challenged with pathogenic V. campbellii LMG 21363 at 106 cells mL-1 by immersion. Relative expression of the immune related genes encoding for prophenoloxidase (proPO), transglutaminase (TGase) and heat shock protein 70 (Hsp70) in the shrimp were measured before (0 h) and after (3, 6, 9, 12, 24 h) the Vibrio challenge by quantitative real-time PCR using β-actin as the reference gene. The expressions of TGase and proPO were significantly up-regulated (p < 0.05) within 9 h and 12 h, respectively after challenge in shrimp receiving the Bacillus sp. JL47 as compared to the challenged and non-challenged controls. Hsp70 expression was significantly increased (p < 0.05) at 3 h post-challenge in all challenged shrimp. Interestingly, proPO and TGase genes were significantly up-regulated (p < 0.05) in Bacillus sp. JL47 treated shrimp even before the Vibrio challenge was applied. No up-regulation in the Hsp70 gene, however, was observed under these conditions. The data suggest that the protective effect of the PHB-accumulating Bacillus sp. JL47 in shrimp was due to its capacity to stimulate the innate immune related genes of the shrimp, specifically the proPO and TGase genes. The application of probiotic Bacillus species, capable of accumulating a significant amount of PHB, is suggested as potential immunostimulatory strategy for aquaculture.


Compact source of coherent blue light.
Generation of 22 mW of narrow-band radiation near 430 nm was achieved by frequency doubling the 100-mW output of a single-mode GaAIAs diode laser near 860 nm. A monolithic potassium niobate ring resonator serves as the nonlinear medium and at the same time as a reference cavity for the diode-laser frequency, which optically self-locks to a cavity resonance frequency. Continuous scans of the second-harmonic frequency over 330 MHz are achieved with the electro-optic effect. The results demonstrate a portable, economical, and efficient source of coherent blue light.


Impact of kidney donor hemostasis on risk of complications after transplantation--preliminary outcomes.
This study analyzes the influence the of kidney donor hemostasis on the risk of complications in the kidney recipient after transplantation. We enrolled 38 deceased kidney donors, of whom 14 donors died from a physical injury and the others died from ischemic or bleeding central nervous system stroke. The donors were categorized into 2 subgroups. If the recipient's postoperative period proceeded smoothly, the kidney donor was assigned to the uncomplicated donors (UD) group. If the recipient's postoperative period was complicated, the donor was assigned to the complicated (CD) Group. The CD group of consisted of 9 donors who died from strokes or bleedings and 2 who died from physical injury. We examined the antithrombin (AT) protein C (PC), complexes of thrombin/antithrombin (TAT), fragments F1+2 of prothrombin (F1+2), plasminogen (Pl), complexes of plasmin/antiplasmin (PAP), and D-dimers (D-d). In the CD group had decreased activity of AT, PC, and Pl and increased activity of F1+2, TAT, and D-d. The UD group had a higher level of PAP. The CD group had evidence of intensive blood coagulation, but the UD group had evidence of fibrinolysis. Fisher's exact test revealed an increased risk in recipients who received a kidney from the CD group. The hemostasis of the kidney donors had a correlation with the occurrence of some complications in the kidney recipients, especially complications connected with activation of blood coagulation. It seems that the activation of fibrinolysis could be positive prognostic factor, but this requires further investigations.


Common carotid intima-media thickness relates to cardiovascular events in adults aged <45 years.
Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixed-effects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden.


Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.
This study sought to establish the long-term effects of Covid-19 following hospitalisation. 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females. National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation.


Bundle sheath chloroplast volume can house sufficient Rubisco to avoid limiting C4 photosynthesis during chilling.
C4 leaves confine Rubisco to bundle sheath cells. Thus, the size of bundle sheath compartments and the total volume of chloroplasts within them limit the space available for Rubisco. Rubisco activity limits photosynthesis at low temperatures. C3 plants counter this limitation by increasing leaf Rubisco content, yet few C4 species do the same. Because C3 plants usually outperform C4 plants in chilling environments, it has been suggested that there is insufficient chloroplast volume available in the bundle sheath of C4 leaves to allow such an increase in Rubisco at low temperatures. We investigated this potential limitation by measuring bundle sheath and mesophyll compartment volumes and chloroplast contents, as well as leaf thickness and inter-veinal distance, in three C4 Andropogoneae grasses: two crops (Zea mays and Saccharum officinarum) and a wild, chilling-tolerant grass (Miscanthus × giganteus). A wild C4 Paniceae grass (Alloteropsis semialata) was also included. Despite significant structural differences between species, there was no evidence of increased bundle sheath chloroplast volume per leaf area available to the chilling-tolerant species, relative to the chilling-sensitive ones. Maximal theoretical photosynthetic capacity of the leaf far exceeded the photosynthetic rates achieved even at low temperatures. C4 bundle sheath cells therefore have the chloroplast volume to house sufficient Rubisco to avoid limiting C4 photosynthesis during chilling.


Translating bacterial detection by DNAzymes into a litmus test.
Microbial pathogens pose serious threats to public health and safety, and results in millions of illnesses and deaths as well as huge economic losses annually. Laborious and expensive pathogen tests often represent a significant hindrance to implementing effective front-line preventative care, particularly in resource-limited regions. Thus, there is a significant need to develop low-cost and easy-to-use methods for pathogen detection. Herein, we present a simple and inexpensive litmus test for bacterial detection. The method takes advantage of a bacteria-specific RNA-cleaving DNAzyme probe as the molecular recognition element and the ability of urease to hydrolyze urea and elevate the pH value of the test solution. By coupling urease to the DNAzyme on magnetic beads, the detection of bacteria is translated into a pH increase, which can be readily detected using a litmus dye or pH paper. The simplicity, low cost, and broad adaptability make this litmus test attractive for field applications, particularly in the developing world.


Induction of cytochrome P4503A by the antiglucocorticoid mifepristone and a novel hypocholesterolaemic drug.
Rat liver microsomal testosterone (250 microM) hydroxylation and immunoreactive CYP3A protein were compared after administration of the antiglucocorticoid RU 486 (50 mg.kg-1.day-1 for 4 days) and the hypocholesterolaemic drug SR-12813 (150 mg.kg-1.day-1 for 4 days). Markers of CYP3A-mediated enzyme activity (testosterone 15 beta-, 6 beta-, and 2 beta-hydroxylation) were increased after administration of both drugs. Testosterone 6 beta-hydroxylation was increased 5-fold by RU 486 and 9-fold by SR-12813. Administration of dexamethasone alone at 150 mg.kg-1.day-1 or in combination with RU 486 induced testosterone 6 beta-hydroxylation 15- to 20-fold. The lack of antagonistic effect of RU 486 on dexamethasone-mediated CYP3A induction strengthens support for the hypothesis that the "classical glucocorticoid receptor" does not play a part in this process. The induction of CYP3A enzymes by the bisphosphonate SR-12813 suggests the existence of a new class of compounds with CYP3A inducing properties.


Modeling of nitrate leaching during the fall-winter season in artificially drained soils.
The nitrogen processes that occur within the soil play a major role in determining the nitrate leaching to shallow groundwater. In this study, the transport and fate of nitrate within the soil profile were analyzed by comparing field data with the simulation results of a mathematical model. The objective was to study the transport and fate of nitrate within the soil profile and nitrate leaching to shallow groundwater for the fall-winter season, by applying the methodology in Elverdinge experiment, situated in the sandy loam region in Belgium, from October 1, 2000 to March 31, 2001. The analysis by comparing field data with the simulation results of DRAINMOD-N model is given. The research indicated that the DRAINMOD-N model can, after calibration and validation, be used as a useful fertilizer management tool in predicting the nitrate transport and transformation in the soil profile and the nitrate leaching to shallow groundwater and surface waters. The model can also be used as an environmental control when the environmental objective has a greater importance than profits in the agriculture field.


Antibody-mediated binding of a murine ecotropic Moloney retroviral vector to human cells allows internalization but not the establishment of the proviral state.
We have attempted to introduce a neomycin-resistance gene, recombined in a murine (ecotropic) Moloney retrovirus, into HEp2 human cells which are resistant to infection by this retrovirus. To allow the binding of the retroviral vector on HEp2 cells, we have tested several antibody constructions between two monoclonal antibodies, one (mAb 5E9) directed against the human transferrin receptor and the other (mAb 615) directed against the gp70 envelope viral protein. The crosslinking of mAbs 5E9 and 615 by a sheep anti-murine kappa light chain antibody allowed the binding of virus on HEp2 cells. After incubation at 37 degrees, virus was internalized by HEp2 cells. However, no neomycin-resistant colonies of HEp2 cells have been obtained under various conditions. Our results suggest that binding and internalization of a retrovirus are not sufficient for establishment of the proviral state in cells which do not express a specific receptor.


Tropospheric ozonesonde profiles at long-term U.S. monitoring sites: 1. A climatology based on self-organizing maps.
Sonde-based climatologies of tropospheric ozone (O3) are vital for developing satellite retrieval algorithms and evaluating chemical transport model output. Typical O3 climatologies average measurements by latitude or region, and season. Recent analysis using self-organizing maps (SOM) to cluster ozonesondes from two tropical sites found clusters of O3 mixing ratio profiles are an excellent way to capture O3 variability and link meteorological influences to O3 profiles. Clusters correspond to distinct meteorological conditions, e.g. convection, subsidence, cloud cover, and transported pollution. Here, the SOM technique is extended to four long-term U.S. sites (Boulder, CO; Huntsville, AL; Trinidad Head, CA; Wallops Island, VA) with 4530 total profiles. Sensitivity tests on k-means algorithm and SOM justify use of 3×3 SOM (nine clusters). At each site, SOM clusters together O3 profiles with similar tropopause height, 500 hPa height/temperature, and amount of tropospheric and total column O3. Cluster means are compared to monthly O3 climatologies. For all four sites, near-tropopause O3 is double (over +100 parts per billion by volume; ppbv) the monthly climatological O3 mixing ratio in three clusters that contain 13 - 16% of profiles, mostly in winter and spring. Large mid-tropospheric deviations from monthly means (-6 ppbv, +7 - 10 ppbv O3 at 6 km) are found in two of the most populated clusters (combined 36 - 39% of profiles). These two clusters contain distinctly polluted (summer) and clean O3 (fall-winter, high tropopause) profiles, respectively. As for tropical profiles previously analyzed with SOM, O3 averages are often poor representations of U.S. O3 profile statistics.


[A case of diffuse cystic malformation in which submucosal tumor-like advanced gastric cancer was identified during 10-year follow-up].
A 66-year-old man with giant gastric folds had been followed up since February 2000. In March 2010, a submucosal tumor of 35mm was identified with endoscopy and a low echoic mass was identified with endoscopic ultrasonography. After histologic diagnosis by endosonography-guided fine needle aspiration biopsy, he underwent a total gastrectomy. Histologic examination of the resected specimen revealed a tumor 20mm in diameter consisting of well-to-moderately differentiated tubular adenocarcinoma in the thickened wall of the gastric greater curvature, which contained small cystic lesions in the lamina propria. Immunohistochemical staining showed thick gastric wall consisting of not only multiple cysts but also smooth muscle, elastic and collagen fibers. The histologic diagnosis was advanced gastric cancer accompanied by diffuse cystic malformation (DCM). Although it is a rare condition, DCM should be considered in the differential diagnosis of giant gastric folds and as a pre-cancerous lesion.


Entrapment of ketorolac tromethamine in polymeric vehicle for controlled drug delivery.
The most common method for applying a drug in to the eye is to formulate the drug in the form of an eye drop, but this method is not considered ideal for ocular delivery of drug because of poor bioavailability arising from precorneal loss processes, this loss of drug from the precorneal area is a net effect of drainage, tear secretion and noncorneal absorption. Following the above lead we tried to improve the ocular bioavailability by increasing the corneal contact time and the feasible way was to formulate a drug with mucoadhesive/viscosity imparting agents. The adhesive strength of various polymers on corneal surface was studied with the help of self modified Franz diffusion cell and freshly excised goat/bovine cornea. The polymers hydroxypropylmethylcellulose, carboxymethylcellulose sodium, Eudragit type E/RL/RS, Carbopol ETD 2020 and Carbopol 934 National Formulary were formulated with drug, ketorolac tromethamine. The adhesive strength of polymers on corneal surface and permeation characteristics of drug through cornea were investigated by using above said formulations. Eudragit type E/RL/RS did not show any improvement in mucoadhesion, but the formulations containing Carbopol ETD 2020 and Carbopol 934 national formulary showed good mucoadhesion on corneal surface in the concentration as low as 0.75%. The mucoadhesive strength was also evaluated using the combination of Carbopol acrylates/C 10-30 alkylacrylate with allylpentaerithrital and preservative benzalkonium chloride, which also resulted in good mucoadhesion with improved corneal permeation. Observations made in this study indicate the potentiality of the ophthalmic formulations containing mucoadhesive/viscosity imparting agents.


Thermo-optical static and dynamic analysis of a digital optical switch based on amorphous silicon waveguide.
In this paper, static and dynamic thermo-optical numerical analysis of a Digital Optical Switch (DOS), based on amorphous silicon waveguide and operating at the infrared communications wavelength of 1550 nm, are presented. The aim of our design is to achieve good performances in terms of cross talk and switching time, considering relaxed requirements for the realization of device: large cross section single mode waveguides and an angle between the output branches not too small. Using a low temperature difference between the two output branches, an optical switching with a crosstalk of 25 dB and a response time of the order of ten microseconds are obtained. The device, designed for low-cost photonic applications, could be easily integrated in silicon optoelectronic circuits.


The prevalence of celiac disease in children and adolescents in Germany.
Untreated celiac disease is associated with increased morbidity and mortality. Until now, no up-to-date figures have been available on the prevalence of celiac disease among children and adolescents in Germany, or on the percentage of undiagnosed cases. To estimate the prevalence of celiac disease, serum samples obtained from 2003 to 2006 from participants in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were studied for celiac disease-specific autoantibodies and total IgA. Of the 12 741 study participants aged 1 to 17 years (6546 boys, 6195 girls), 9 (0.07%) had a reported history of celiac disease. An elevated concentration of serum autoantibodies to tissue transglutaminase was found in 91 children with a normal IgA concentration and in 7 with IgA deficiency. The prevalence of undiagnosed celiac disease, based on positive autoantibody findings, was 0.8% (95% confidence interval 0.6-1.0%), and the overall prevalence of the disease was 0.9%. Seropositive children and adolescents had lower ferritin and red blood cell folate concentrations than seronegative ones; they also tended to be shorter and to weigh less as reflected by age- and sex-standardized z-scores. The 0.9% prevalence of celiac disease in Germany, as determined from a combination of serological findings and clinical histories, is similar to reported prevalences elsewhere in Europe and North America. Pediatricians, primary care physicians, internists, and other specialists should be aware of the broad spectrum of clinical manifestations of this disease. Children who have symptoms suggestive of celiac disease or belong to a group at risk for it should be tested for antibodies against tissue transglutaminase, as should symptomatic adults after the exclusion of other possible causes. It is not yet clear whether asymptomatic adults from high-risk groups should be tested.


Recent advances in the detection of repeat expansions with short-read next-generation sequencing.
Short tandem repeats (STRs), also known as microsatellites, are commonly defined as consisting of tandemly repeated nucleotide motifs of 2-6 base pairs in length. STRs appear throughout the human genome, and about 239,000 are documented in the Simple Repeats Track available from the UCSC (University of California, Santa Cruz) genome browser. STRs vary in size, producing highly polymorphic markers commonly used as genetic markers. A small fraction of STRs (about 30 loci) have been associated with human disease whereby one or both alleles exceed an STR-specific threshold in size, leading to disease. Detection of repeat expansions is currently performed with polymerase chain reaction-based assays or with Southern blots for large expansions. The tests are expensive and time-consuming and are not always conclusive, leading to lengthy diagnostic journeys for patients, potentially including missed diagnoses. The advent of whole exome and whole genome sequencing has identified the genetic cause of many genetic disorders; however, analysis pipelines are focused primarily on the detection of short nucleotide variations and short insertions and deletions (indels). Until recently, repeat expansions, with the exception of the smallest expansion (SCA6), were not detectable in next-generation short-read sequencing datasets and would have been ignored in most analyses. In the last two years, four analysis methods with accompanying software (ExpansionHunter, exSTRa, STRetch, and TREDPARSE) have been released. Although a comprehensive comparative analysis of the performance of these methods across all known repeat expansions is still lacking, it is clear that these methods are a valuable addition to any existing analysis pipeline. Here, we detail how to assess short-read data for evidence of expansions, reviewing all four methods and outlining their strengths and weaknesses. Implementation of these methods should lead to increased diagnostic yield of repeat expansion disorders for known STR loci and has the potential to detect novel repeat expansions.


Ni-Catalyzed regio- and stereoselective addition of arylboronic acids to terminal alkynes with a directing group tether.
Addition of arylboronic acids to directing group tethered acetylenes in a regio and stereoselective manner using an inexpensive catalytic system is achieved for the first time to access highly sought after allyl/homoallyl alcohol/amine units. The apparent vinylnickel intermediate was successfully trapped by the Michael electrophiles to get defined tri- and tetra-substituted olefins. An interesting selectivity switch was observed with internal alkynes.


Issues concerning relative speed of processing hypotheses, schizophrenic performance deficits, and prefrontal function: comment on Schooler et al. (1997)
The authors have found the data presented in the C. Schooler, E. Neumann, L. J. Caplan, and B. R. Roberts (1997) article to be interesting and of potential value in constraining the further development of detailed theoretical models of Stroop performance. However, the authors have found that the relative speed of processing account of stimulus onset asynchrony (SOA) effects given by Schooler et al. in Experiment 1 fails to address several important and vexing issues faced by such accounts, which have been highlighted by existing formal models. The authors also have expressed concerns about Schooler et al.'s, interpretation of the reduction in Stroop interference observed among individuals with schizophrenia in Experiment 2. Whereas the authors have acknowledged that it is plausible to relate this to a dysfunction of prefrontal cortex, they have pointed to equally plausible alternative explanations, which are not addressed by the experiment or in the discussion in the Schooler et al. article.


Is emergency research without initial consent justified?: the consent substitute model.
Emergency research poses a fundamental ethical dilemma: prohibit valuable research because informed consent is not possible or enroll individuals in clinical trials without informed consent. Although emergency research without initial consent is allowable in the United States, its regulatory status remains uncertain internationally. More important, no ethical justification for emergency research without consent has been widely accepted. Whether emergency research without initial consent can be justified depends on whether the values that are secured by informed consent-respect for autonomy and protection of well-being-can be secured by other means. Analysis suggests that these values can be secured by the satisfaction of 5 conditions: (1) responsiveness (the experimental intervention must be responsive to an urgent medical need of the patients), (2) comparable risk-benefit ratio (the risk-benefit ratio of the experimental intervention is favorable, and at least as favorable as that of available alternatives and the control, if any), (3) no conflicting preferences (there is no compelling reason to think that participation in the research conflicts with enrolled patients' values or interests), (4) minimal net risks (nonbeneficial procedures included in the study cumulatively pose no greater than minimal risk), and (5) prompt consent (consent for ongoing and additional emergency research interventions is obtained as soon as possible). Together, these conditions constitute an ethical substitute for informed consent in emergency research-forming the consent substitute model.


The antioxidant edaravone attenuates ER-stress-mediated cardiac apoptosis and dysfunction in rats with autoimmune myocarditis.
Experimental autoimmune myocarditis (EAM) is mediated by myocardial infiltration by myosin-specific T-cells secreting inflammatory cytokines. In this study, rat models of EAM were prepared by injection with porcine cardiac myosin. One week after immunization, edaravone was administered intraperitoneally at 3 or 10 mg/kg/day to rats for 2 weeks. Cardiac function was measured by haemodynamic and echocardiographic studies and TUNEL assay was performed. Left ventricular (LV) expression of NADPH oxidase sub-units (p47(phox) and p67(phox)), pro-inflammatory cytokines (TNF-alpha), endoplasmic reticulum (ER) stress signalling proteins (GRP78, caspase-12 and GADD153) and mitogen-activated protein kinase (MAPK) family proteins (phospho-p38 MAPK and phospho-JNK) were measured by western blotting. Edaravone improved LV function in a dose-dependent manner. Central venous pressure was significantly low and LV ejection fraction and fractional shortening was significantly high in edaravone groups compared with those in the vehicle group. In addition, edaravone treatment down-regulated LV expressions of p47(phox), TNF-alpha, GADD153, phospho-p38 MAPK and phospho-JNK. Furthermore, the LV expressions of p67(phox), GRP78, caspase-12 and TUNEL-positive cells of rats with EAM treated with edaravone were significantly low compared with those of the vehicle group. These findings suggest that edaravone ameliorated the progression of EAM by inhibiting oxidative and ER stress and, subsequently, cardiac apoptosis.


Does neighbourhood deprivation cause poor health? Within-individual analysis of movers in a prospective cohort study.
Neighbourhood deprivation has been associated with poor health. The evidence for social causation, however, remains scarce because selective residential mobility may also create neighbourhood differences. The present study examined whether individuals had poorer health when they were living in a deprived neighbourhood compared to another time when the same individuals were living in a less deprived neighbourhood. Participants were from the British Household Panel Survey prospective cohort study with 18 annual measurements of residential location and self-reported health outcomes between 1991 and 2009 (n=137 884 person-observations of 17 001 persons in England). Neighbourhood deprivation was assessed concurrently with health outcomes using the Index of Multiple Deprivation at the geographically detailed level of Lower Layer Super Output Areas. The main analyses were replicated in subsamples from Scotland (n=4897) and Wales (n=4442). Multilevel regression was used to separate within-individual and between-individuals associations. Neighbourhood deprivation was associated with poorer self-rated health, and with higher psychological distress, functional health limitations and number of health problems. These associations were almost exclusively due to differences between different individuals rather than within-individual variations related to different neighbourhoods. By contrast, poorer health was associated with lower odds of moving to less deprived neighbourhoods among movers. The analysis was limited by the restricted within-individual variation and measurement imprecision of neighbourhood deprivation. Individuals living in deprived neighbourhoods have poorer health, but it appears that neighbourhood deprivation is not causing poorer health of adults. Instead, neighbourhood health differentials may reflect the more fundamental social inequalities that determine health and ability to move between deprived and non-deprived neighbourhoods.


A Protein Epitope Signature Tag (PrEST) library allows SILAC-based absolute quantification and multiplexed determination of protein copy numbers in cell lines.
Mass spectrometry-based proteomics increasingly relies on relative or absolute quantification. In relative quantification, stable isotope based methods often allow mixing at early stages of sample preparation, whereas for absolute quantification this has generally required recombinant expression of full length, labeled protein standards. Here we make use of a very large library of Protein Epitope Signature Tags (PrESTs) that has been developed in the course of the Human Protein Atlas Project. These PrESTs are expressed recombinantly in E. coli and they consist of a short and unique region of the protein of interest as well as purification and solubility tags. We first quantify a highly purified, stable isotope labeling of amino acids in cell culture (SILAC)-labeled version of the solubility tag and use it determine the precise amount of each PrEST by its SILAC ratios. The PrESTs are then spiked into cell lysates and the SILAC ratios of PrEST peptides to peptides from endogenous target proteins yield their cellular quantities. The procedure can readily be multiplexed, as we demonstrate by simultaneously determining the copy number of 40 proteins in HeLa cells. Among the proteins analyzed, the cytoskeletal protein vimentin was found to be most abundant with 20 million copies per cell, while the transcription factor and oncogene FOS only had 6000 copies. Direct quantification of the absolute amount of single proteins is possible via a SILAC experiment in which labeled cell lysate is mixed both with the heavy labeled solubility tag and with the corresponding PrEST. The SILAC-PrEST combination allows accurate and streamlined quantification of the absolute or relative amount of proteins of interest in a wide variety of applications.


Polyimidazolium Salts: Robust Catalysts for the Cycloaddition of Carbon Dioxide into Carbonates in Solvent-Free Conditions.
There is a growing interest in sustainable heterogeneous catalysts based on organic polymers. Here, we describe a series of polyimidazolium salt catalysts, prepared from the direct reaction of arene-bridged bis- and tris-alkyl halides with trimethylsilylimidazole. The polyimidazolium salts were characterized by spectroscopic and analytical techniques and it was found that their morphology and porosity could be controlled by adjusting the steric parameters of the spacer in the alkyl-halide starting materials. Moreover, the polymers are excellent heterogeneous organocatalysts for the cycloaddition of CO2 to epoxides to afford cyclic carbonates at atmospheric pressure under solvent-free conditions. The polymer catalysts exhibit long-term stability and may be recycled and reused at least 10 times.


Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.
Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function. AMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed. Macrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function. ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.


Real-time characterization and source apportionment of fine particulate matter in the Delhi megacity area during late winter.
National Capital Region (NCR) encompassing New Delhi is one of the most polluted urban metropolitan areas in the world. Real-time chemical characterization of fine particulate matter (PM1 and PM2.5) was carried out using three aerosol mass spectrometers, two aethalometers, and one single particle soot photometer (SP2) at two sites in Delhi (urban) and one site located ~40 km downwind of Delhi, during January-March 2018. The campaign mean PM2.5 (NR-PM2.5 + BC) concentrations at the two urban sites were 153.8 ± 109.4 μg.m-3 and 127.8 ± 83.2 μg.m-3, respectively, whereas PM1 (NR-PM1 + BC) was 72.3 ± 44.0 μg.m-3 at the downwind site. PM2.5 particles were composed mostly of organics (43-44)% followed by chloride (14-17)%, ammonium (9-11)%, nitrate (9%), sulfate (8-10)%, and black carbon (11-16)%, whereas PM1 particles were composed of 47% organics, 13% sulfate as well as ammonium, 11% nitrate as well as chloride, and 5% black carbon. Organic aerosol (OA) source apportionment was done using positive matrix factorization (PMF), solved using an advanced multi-linear engine (ME-2) model. Highly mass-resolved OA mass spectra at one urban and downwind site were factorized into three primary organic aerosol (POA) factors including one traffic-related and two solid-fuel combustion (SFC), and three oxidized OA (OOA) factors. Whereas unit mass resolution OA at the other urban site was factorized into two POA factors related to traffic and SFC, and one OOA factor. OOA constituted a majority of the total OA mass (45-55)% with maximum contribution during afternoon hours ~(70-80)%. Significant differences in the absolute OOA concentration between the two urban sites indicated the influence of local emissions on the oxidized OA formation. Similar PM chemical composition, diurnal and temporal variations at the three sites suggest similar type of sources affecting the particulate pollution in Delhi and adjoining cities, but variability in mass concentration suggest more local influence than regional.


Artificial embolization of the middle cerebral artery in primates. Description of an experimental model with extracranial technique.
Artificial embolization of the middle cerebral artery (MCA) was produced in the primate, with a technique similar to that described by Luessenhop and Spence (1960) for the treatment of an inoperable arteriovenous malformation in the territory of the MCA. Silicone spheres (1 to 1.5 mm in diameter) were introduced into the internal carotid artery (ICA) via the external carotid artery (ECA). Emboli (1 to 1.3 mm) passed into the anterior cerebral artery (ACA) in 12%, and into the MCA in 50%. Emboli (1.2 to 1.5 mm) stopped at the ICA bifurcation in 54%. In all primates (82.35%1 in which the emboli occluded the ICA bifurcation or the MCA, immediate contralateral hemiplegia developed. The correlation of the anatomical characteristics of the intracranial vasculature of the ICA bifurcation, the diameter of the emboli, and the anatomical localization of the silicone spheres suggests that this experimental model can produce a selective acute "point" occlusion of the MCA in at least 75% of the cases without violating the cranium, in which the resultant changes in the distribution of water and electrolytes in the brain during the acute ischemic event in the territory of the MCA of the primate can be studied.


Predicting the conductance of strongly correlated molecules: the Kondo effect in perchlorotriphenylmethyl/Au junctions.
Stable organic radicals integrated into molecular junctions represent a practical realization of the single-orbital Anderson impurity model. Motivated by recent experiments for perchlorotriphenylmethyl (PTM) molecules contacted to gold electrodes, we develop a method that combines density functional theory (DFT), quantum transport theory, numerical renormalization group (NRG) calculations and renormalized super-perturbation theory (rSPT) to compute both equilibrium and non-equilibrium properties of strongly correlated nanoscale systems at low temperatures effectively from first principles. We determine the possible atomic structures of the interfaces between the molecule and the electrodes, which allow us to estimate the Kondo temperature and the characteristic transport properties, which compare well with experiments. By using the non-equilibrium rSPT results we assess the range of validity of equilibrium DFT + NRG-based transmission calculations for the evaluation of the finite voltage conductance. The results demonstrate that our method can provide qualitative insights into the properties of molecular junctions when the molecule-metal contacts are amorphous or generally ill-defined, and that it can further give a fully quantitative description when the experimental contact structures are well characterized.


What does "disability" mean for medical students? An exploration of the words medical students associate with the term "disability".
Disability teaching is a core theme in undergraduate medical education. Medical students bring a range of experiences of disability to their medical training. The principal aim of this study was to explore the words that medical students associate with the term "disability" and to consider how the resulting information could inform teaching. A secondary aim was to see if a short disability course changed the word associations. Students were asked to write down 2 words that came to mind when they heard the word "disability", before and after a 4-day course in disability. Words from 4 cohorts were analysed by frequency and the following word dichotomies: visual icons/personal attributes; loss/enabling, and medical model/social model. A random sample of students took part in focus groups at the beginning and end of the course. A total of 381 students provided 667 before-course words and 189 students provided 336 after-course words. Before the course, words denoting visual icons of disability, and loss were prominent, accounting for 85% of the words, and 74% of the words describing personal attributes were negative. Focus group responses at this stage reflected an eagerness to help but patronising terms were prominent, along with concern about political correctness. Students also expressed nervousness about encountering disabled people. In response, teaching was adapted to make it more learner-focused, to offer a safe environment in which students can test out their language, to build on the positive associations and to develop a range of pre-course creative activities with disabled people. After the course a considerable and significant shift in emphasis was observed, with a reduction in the use of visual icon words, an increase in words denoting enablement, and an increase in words relating to the social model of disability and to positive personal attributes (P < 0.001). Focus group participants at this stage reported greater confidence in approaching disabled people but continued to question political correctness. Medical students associate disability predominantly with depersonalised or negative words. A short disability course appears to change these associations. Reasons for this and implications for teaching are discussed.


Efficacy of psychedelic treatments on depressive symptoms: A meta-analysis.
Psychedelic drugs have shown an efficacy in some psychiatric disorders and have an original mechanism of action with a 5-HT2A agonism. The aim of this meta-analysis was to assess by a quantitative analysis the putative efficacy of psychedelic drugs on depressive symptoms and to investigate the kinetic of this efficacy. We searched the MEDLINE and PsycINFO databases through April 2019, without limits on year of publication. Means and standard deviations were extracted to calculate standardized mean differences (SMD). Scores of depressive symptoms were compared with baseline scores at days 7, 14, and 21; weeks 4-5 and 6-8; and months 3 and 6. Eight studies were included in this meta-analysis. A significant decrease of depressive symptoms was found from day 1 (n = 5 studies; SMD = ‒1.4, 95% confidence interval (CI): ‒2.33 to ‒0.48, p = 0.003) to 6 months (n = 4 studies; SMD = ‒1.07, 95% CI: ‒1.44 to ‒0.7, p < 0.001) after psychedelic sessions. No serious adverse effect was reported in all included studies. A transient increase of the heart rate, blood systolic, and diastolic pressure were found after psychedelics compared with placebo. This meta-analysis shows that psychedelic treatments were safe and could contribute to a rapid improvement of depressive symptoms.