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Introduction The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally and as of February 4, 2021, there are more than 26 million confirmed cases and more than 440,000 deaths in the United States (US). A top priority of the Centers for Disease Control and Prevention (CDC) is to identify risk factors for severe COVID-19 illness. The objective of this study was to analyze the characteristics and outcomes of COVID-19 adults who were managed in an outpatient setting compared to patients who required hospitalization at US academic centers. Methods Using the Vizient clinical database, Discharge records of adults with a diagnosis of COVID-19 between March 1, 2020 and January 31, 2021 were reviewed. Outcome measures included demographics, characteristics, rate of hospitalization, and mortality, and data were analyzed based on inpatient versus outpatient management. Results Among COVID-19 adults, 1,360,078 patients were managed in an outpatient setting while 545,635 patients required hospitalization. Compared to hospitalized COVID-19 adults, COVID-19 adults who were managed in an outpatient setting were more likely to be female (56.1% vs 47.5%, p 75 years. The rate of hospitalization was lowest for age group 18–30 years at 10.6% (35,607 of 330,719) and highest for age group >75 years at 56.1% (150,381 of 268,247). Conclusion This analysis of US academic centers showed that 28.6% of COVID-19 adults who sought care at one of the hospitals reporting data to the Vizient clinical database required in-patient treatment. The rate of hospitalization in our study was lowest for the youngest age group of 18–30 years and highest for age group >75 years. Beside older age, other factors associated with outpatient management included female gender, white race, and having commercial insurance.

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions.

Coronavirus disease 2019 (COVID-19) was first identified in respiratory samples and was found to commonly cause cough and pneumonia. However, non-respiratory symptoms including gastrointestinal disorders are also present and a big proportion of patients test positive for the virus in stools for a prolonged period. In this cross-sectional study, we investigated viral load trends in stools and nasopharyngeal swabs and their correlation with multiple demographic and clinical factors. The study included 211 laboratory-confirmed cases suffering from a mild form of the disease and completing their isolation period at a non-hospital center in the United Arab Emirates. Demographic and clinical information was collected by standardized questionnaire and from the medical records of the patient. Of the 211 participants, 25% tested negative in both sample types at the time of this study and 53% of the remaining patients had detectable viral RNA in their stools. A positive fecal viral test was associated with male gender, diarrhea as a symptom, and hospitalization during infection. A positive correlation was also observed between a delayed onset of symptoms and a positive stool test. Viral load in stools positively correlated with, being overweight, exercising, taking antibiotics in the last 3 months and blood type O. The viral load in nasopharyngeal swabs, on the other hand, was higher for blood type A, and rhesus positive (Rh factor). Regression analysis showed no correlation between the viral loads measured in stool and nasopharyngeal samples in any given patient. The results of this work highlight the factors associated with a higher viral count in each sample. It also shows the importance of stool sample analysis for the follow-up and diagnosis of recovering COVID-19 patients.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic continues to be a global threat, with tremendous resources invested into identifying risk factors for severe COVID-19 illness. The objective of this study was to analyze the characteristics and outcomes of male compared to female adults with COVID-19 who required hospitalization within US academic centers.MethodsUsing the Vizient clinical database, discharge records of adults with a diagnosis of COVID-19 between March 1, 2020 and November 30, 2020 were reviewed. Outcome measures included demographics, characteristics, length of hospital stay, rate of respiratory intubation and mechanical ventilation, and rate of in-hospital mortality of male vs female according to age, race/ethnicity, and presence of preexisting comorbidities.ResultsAmong adults with COVID-19, 161,206 were male while 146,804 were female. Adult males with COVID-19 were more likely to have hypertension (62.1% vs 59.6%, p ConclusionThis large analysis of 308,010 COVID-19 adults hospitalized at US academic centers showed that males have a higher rate of respiratory intubation and longer length of hospital stay compared to females and have a higher death rate even when compared across age groups, race/ethnicity, payers, and comorbidity.

Many Service members and Veterans with lower-limb amputations have the potential for high function and the desire to resume physically demanding occupations that require them to carry heavy loads (e.g., military service, firefighters, farmers, ranchers, construction workers). However, it is currently unclear which prosthetic feet best accommodate heavy load carriage while also providing good overall function and mobility during unweighted activities. The main objective of this study was to investigate the ability of currently available prosthetic ankle-foot systems to accommodate weighted walking by examining the mechanical characteristics (i.e., forefoot stiffness) and dynamic function (i.e., rocker radius, effective foot length ratio, and late-stance energy return) of prosthetic feet designed for high activity users. Load versus deflection curves were obtained for nine prosthetic ankle-foot systems using a servohydraulic test frame and load cell. Effective roll-over shape characteristics and late-stance energy return measures were then obtained using quantitative gait analysis for three users with unilateral, transtibial amputation. Results from mechanical and dynamic testing showed that although forefoot stiffness varied across the nine feet investigated in this study, changes measured in roll-over shape radius and effective foot length ratio were relatively small in response to weighted walking. At the same time, prosthetic feet with more compliant forefoot keel structures appeared to provide more late-stance energy return compared to feet with stiffer forefoot keel structures. These results suggest that prosthetic ankle-foot systems with compliant forefoot keel structures may better accommodate weighted walking by reducing the metabolic cost of physically demanding activities. However, to more fully understand the biomechanical and functional implications of these results, other factors, such as the residual-limb strength of the user and the overall stiffness profile of the prosthetic foot, should also be considered.

KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS), characterized by dysmorphic features and intellectual disability; amiable personality, congenital malformations and seizures also commonly occur. The epilepsy phenotypic spectrum in KdVS is broad, but most individuals have focal seizures with some having a phenotype resembling the self-limited focal epilepsies of childhood (SFEC). We hypothesized that variants in KANSL1 contribute to pathogenesis of SFEC.We screened KANSL1 for single nucleotide variants in 90 patients with SFEC. We then screened a cohort of 208 patients with two specific SFEC syndromes, childhood epilepsy with centrotemporal spikes (CECTS) and atypical childhood epilepsy with centrotemporal spikes (ACECTS) for KANSL1 variants. The second cohort was also used to evaluate minor allelic variants that appeared overrepresented in the initial cohort.One variant, p.Lys104Thr, was predicted damaging and appeared overrepresented in our 90-patient cohort compared to Genome Aggregation Database (gnomAD) allele frequency (0.217 to 0.116, with no homozygotes in gnomAD). However, there was no difference in p.Lys104Thr allele frequency in the follow-up CECTS/ACECTS cohort and controls. Four rare KANSL1 variants of uncertain significance were identified in the CECTS/ACECTS cohort.Our data do not support a major role for KANSL1 variants in pathogenesis of SFEC.

The composition of the scientific workforce shapes the direction of scientific research, directly through the selection of questions to investigate, and indirectly through its influence on the training of future scientists. In most fields, however, complete census information is difficult to obtain, complicating efforts to study workforce dynamics and the effects of policy. This is particularly true in computer science, which lacks a single, all-encompassing directory or professional organization. A full census of computer science would serve many purposes, not the least of which is a better understanding of the trends and causes of unequal representation in computing. Previous academic census efforts have relied on narrow or biased samples, or on professional society membership rolls. A full census can be constructed directly from online departmental faculty directories, but doing so by hand is expensive and time-consuming. Here, we introduce a topical web crawler for automating the collection of faculty information from web-based department rosters, and demonstrate the resulting system on the 205 PhD-granting computer science departments in the U.S. and Canada. This method can quickly construct a complete census of the field, and achieve over 99% precision and recall. We conclude by comparing the resulting 2017 census to a hand-curated 2011 census to quantify turnover and retention in computer science, in general and for female faculty in particular, demonstrating the types of analysis made possible by automated census construction.

Persistent atrial fibrillation (AF) can be viewed as disintegrated patterns of information transmission by action potential across the communication network consisting of nodes linked by functional connectivity. To test the hypothesis that ablation of persistent AF is associated with improvement in both local and global connectivity within the communication networks, we analyzed multi-electrode basket catheter electrograms of 22 consecutive patients (63.5 ± 9.7 years, 78% male) during persistent AF before and after the focal impulse and rotor modulation-guided ablation. Eight patients (36%) developed recurrence within 6 months after ablation. We defined communication networks of AF by nodes (cardiac tissue adjacent to each electrode) and edges (mutual information between pairs of nodes). To evaluate patient-specific parameters of communication, thresholds of mutual information were applied to preserve 10% to 30% of the strongest edges. There was no significant difference in network parameters between both atria at baseline. Ablation effectively rewired the communication network of persistent AF to improve the overall connectivity. In addition, successful ablation improved local connectivity by increasing the average clustering coefficient, and also improved global connectivity by decreasing the characteristic path length. As a result, successful ablation improved the efficiency and robustness of the communication network by increasing the small-world index. These changes were not observed in patients with AF recurrence. Furthermore, a significant increase in the small-world index after ablation was associated with synchronization of the rhythm by acute AF termination. In conclusion, successful ablation rewires communication networks during persistent AF, making it more robust, efficient, and easier to synchronize. Quantitative analysis of communication networks provides not only a mechanistic insight that AF may be sustained by spatially localized sources and global connectivity, but also patient-specific metrics that could serve as a valid endpoint for therapeutic interventions.

The United Nations Millennium Development Goals galvanized global efforts to alleviate suffering of the world's poorest people through unprecedented public-private partnerships. Donor aid agencies have demonstrably saved millions of lives that might otherwise have been lost to disease through increased access to quality-assured vaccines and medicines. Yet, the introduction of these health interventions in low- and middle-income countries (LMICs) continues to face a time lag due to factors which remain poorly understood.A recurring theme from our partnership engagements was that an optimized regulatory process would contribute to improved access to quality health products. Therefore, we investigated the current system for medicine and vaccine registration in LMICs as part of our comprehensive regulatory strategy. Here, we report a fact base of the registration timelines for vaccines and drugs used to treat certain communicable diseases in LMICs. We worked with a broad set of stakeholders, including the World Health Organization's prequalification team, national regulatory authorities, manufacturers, procurers, and other experts, and collected data on the timelines between first submission and last approval of applications for product registration sub-Saharan Africa. We focused on countries with the highest burden of communicable disease and the greatest need for the products studied. The data showed a typical lag of 4 to 7 years between the first regulatory submission which was usually to a regulatory agency in a high-income country, and the final approval in Sub-Saharan Africa. Two of the three typical registration steps which products undergo before delivery in the countries involve lengthy timelines. Failure to leverage or rely on the findings from reviews already performed by competent regulatory authorities, disparate requirements for product approval by the countries, and lengthy timelines by manufacturers to respond to regulatory queries were key underlying factors for the delays.We propose a series of measures which we developed in close collaboration with key stakeholders that could be taken to reduce registration time and to make safe, effective medicines more quickly available in countries where they are most needed. Many of these recommendations are being implemented by the responsible stakeholders, including the WHO prequalification team and the national regulatory authorities in Sub-Saharan Africa. Those efforts will be the focus of subsequent publications by the pertinent groups.

Decisions typically comprise several elements. For example, attention must be directed towards specific objects, their identities recognized, and a choice made among alternatives. Pairs of competing accumulators and drift-diffusion processes provide good models of evidence integration in two-alternative perceptual choices, but more complex tasks requiring the coordination of attention and decision making involve multistage processing and multiple brain areas. Here we consider a task in which a target is located among distractors and its identity reported by lever release. The data comprise reaction times, accuracies, and single unit recordings from two monkeys' lateral interparietal area (LIP) neurons. LIP firing rates distinguish between targets and distractors, exhibit stimulus set size effects, and show response-hemifield congruence effects. These data motivate our model, which uses coupled sets of leaky competing accumulators to represent processes hypothesized to occur in feature-selective areas and limb motor and pre-motor areas, together with the visual selection process occurring in LIP. Model simulations capture the electrophysiological and behavioral data, and fitted parameters suggest that different connection weights between LIP and the other cortical areas may account for the observed behavioral differences between the animals.

We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets.

Insects face the challenge of navigating to specific goals in both bright sun-lit and dim-lit environments. Both diurnal and nocturnal insects use quite similar navigation strategies. This is despite the signal-to-noise ratio of the navigational cues being poor at low light conditions. To better understand the evolution of nocturnal life, we investigated the navigational efficiency of a nocturnal ant, Myrmecia pyriformis, at different light levels. Workers of M. pyriformis leave the nest individually in a narrow light-window in the evening twilight to forage on nest-specific Eucalyptus trees. The majority of foragers return to the nest in the morning twilight, while few attempt to return to the nest throughout the night. We found that as light levels dropped, ants paused for longer, walked more slowly, the success in finding the nest reduced and their paths became less straight. We found that in both bright and dark conditions ants relied predominantly on visual landmark information for navigation and that landmark guidance became less reliable at low light conditions. It is perhaps due to the poor navigational efficiency at low light levels that the majority of foragers restrict navigational tasks to the twilight periods, where sufficient navigational information is still available.

The effects of selection on genome variation were investigated and visualized in tomato using a high-density single nucleotide polymorphism (SNP) array. 7,720 SNPs were genotyped on a collection of 426 tomato accessions (410 inbreds and 16 hybrids) and over 97% of the markers were polymorphic in the entire collection. Principal component analysis (PCA) and pairwise estimates of F(st) supported that the inbred accessions represented seven sub-populations including processing, large-fruited fresh market, large-fruited vintage, cultivated cherry, landrace, wild cherry, and S. pimpinellifolium. Further divisions were found within both the contemporary processing and fresh market sub-populations. These sub-populations showed higher levels of genetic diversity relative to the vintage sub-population. The array provided a large number of polymorphic SNP markers across each sub-population, ranging from 3,159 in the vintage accessions to 6,234 in the cultivated cherry accessions. Visualization of minor allele frequency revealed regions of the genome that distinguished three representative sub-populations of cultivated tomato (processing, fresh market, and vintage), particularly on chromosomes 2, 4, 5, 6, and 11. The PCA loadings and F(st) outlier analysis between these three sub-populations identified a large number of candidate loci under positive selection on chromosomes 4, 5, and 11. The extent of linkage disequilibrium (LD) was examined within each chromosome for these sub-populations. LD decay varied between chromosomes and sub-populations, with large differences reflective of breeding history. For example, on chromosome 11, decay occurred over 0.8 cM for processing accessions and over 19.7 cM for fresh market accessions. The observed SNP variation and LD decay suggest that different patterns of genetic variation in cultivated tomato are due to introgression from wild species and selection for market specialization.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic continues to spread globally and as of February 4, 2021, there are more than 26 million confirmed cases and more than 440,000 deaths in the United States (US). A top priority of the Centers for Disease Control and Prevention (CDC) is to identify risk factors for severe COVID-19 illness. The objective of this study was to analyze the characteristics and outcomes of COVID-19 adults who were managed in an outpatient setting compared to patients who required hospitalization at US academic centers.MethodsUsing the Vizient clinical database, Discharge records of adults with a diagnosis of COVID-19 between March 1, 2020 and January 31, 2021 were reviewed. Outcome measures included demographics, characteristics, rate of hospitalization, and mortality, and data were analyzed based on inpatient versus outpatient management.ResultsAmong COVID-19 adults, 1,360,078 patients were managed in an outpatient setting while 545,635 patients required hospitalization. Compared to hospitalized COVID-19 adults, COVID-19 adults who were managed in an outpatient setting were more likely to be female (56.1% vs 47.5%, p 75 years. The rate of hospitalization was lowest for age group 18-30 years at 10.6% (35,607 of 330,719) and highest for age group >75 years at 56.1% (150,381 of 268,247).ConclusionThis analysis of US academic centers showed that 28.6% of COVID-19 adults who sought care at one of the hospitals reporting data to the Vizient clinical database required in-patient treatment. The rate of hospitalization in our study was lowest for the youngest age group of 18-30 years and highest for age group >75 years. Beside older age, other factors associated with outpatient management included female gender, white race, and having commercial insurance.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic continues to be a global threat, with tremendous resources invested into identifying risk factors for severe COVID-19 illness. The objective of this study was to analyze the characteristics and outcomes of male compared to female adults with COVID-19 who required hospitalization within US academic centers.MethodsUsing the Vizient clinical database, discharge records of adults with a diagnosis of COVID-19 between March 1, 2020 and November 30, 2020 were reviewed. Outcome measures included demographics, characteristics, length of hospital stay, rate of respiratory intubation and mechanical ventilation, and rate of in-hospital mortality of male vs female according to age, race/ethnicity, and presence of preexisting comorbidities.ResultsAmong adults with COVID-19, 161,206 were male while 146,804 were female. Adult males with COVID-19 were more likely to have hypertension (62.1% vs 59.6%, p

Coronavirus disease 2019 (COVID-19) was first identified in respiratory samples and was found to commonly cause cough and pneumonia. However, non-respiratory symptoms including gastrointestinal disorders are also present and a big proportion of patients test positive for the virus in stools for a prolonged period. In this cross-sectional study, we investigated viral load trends in stools and nasopharyngeal swabs and their correlation with multiple demographic and clinical factors. The study included 211 laboratory-confirmed cases suffering from a mild form of the disease and completing their isolation period at a non-hospital center in the United Arab Emirates. Demographic and clinical information was collected by standardized questionnaire and from the medical records of the patient. Of the 211 participants, 25% tested negative in both sample types at the time of this study and 53% of the remaining patients had detectable viral RNA in their stools. A positive fecal viral test was associated with male gender, diarrhea as a symptom, and hospitalization during infection. A positive correlation was also observed between a delayed onset of symptoms and a positive stool test. Viral load in stools positively correlated with, being overweight, exercising, taking antibiotics in the last 3 months and blood type O. The viral load in nasopharyngeal swabs, on the other hand, was higher for blood type A, and rhesus positive (Rh factor). Regression analysis showed no correlation between the viral loads measured in stool and nasopharyngeal samples in any given patient. The results of this work highlight the factors associated with a higher viral count in each sample. It also shows the importance of stool sample analysis for the follow-up and diagnosis of recovering COVID-19 patients. [ABSTRACT FROM AUTHOR]

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions. [ABSTRACT FROM AUTHOR]

Environmental exposure to cold is increasingly being associated with changes in metabolism. We developed and tested the hypothesis that exposure to cold drives systemic effects in lipid metabolism. Specifically, (i) that energy storage and provision adapts to the cold by altering triglyceride distribution and (ii) that membranes adapt to cold conditions by becoming more unsaturated. These hypotheses were designed to identify the underlying mechanisms that govern the response of mammalian systems to cold. To test these hypotheses, we used a metabolic network analysis. An established model of cold exposure was used, from which lipidomics data that represents the system was collected. The network analysis showed that triglyceride metabolism is altered on exposure to cold, with several smaller effects that are not straightforward, such as changes to the abundance and distribution of odd chain fatty acids. The range and profile of phosphatidylcholine and phosphatidylinositol were modified, but there was little change in phosphatidylethanolamine or sphingomyelin. These results support the hypothesis, and show that exposure to cold is a system-wide phenomenon that requires or drives changes across a range of metabolic pathways.

IntroductionVaccination during pregnancy protects both the mother and the foetus from vaccine-preventable diseases. However, uptake of the recommended vaccines (influenza, pertussis, COVID-19) by pregnant women remains low in Europe and the USA. Understanding the reasons for this is crucial to inform strategies to increase vaccination rates in pregnant women. This qualitative systematic review aimed to identify the barriers and facilitators to vaccination against influenza, pertussis/whooping cough and COVID-19 during pregnancy and identify possible strategies to increase vaccination rates.MethodsWe conducted a comprehensive search of electronic databases, including Medline, PsycINFO, CINAHL, Web of Science, WHO database, Embase and grey literature to identify qualitative studies that explored barriers and facilitators to vaccine uptake among pregnant women (PROSPERO CRD42023399488). The search was limited to studies published between 2012 and 2022 conducted in high-income countries with established vaccination programmes during pregnancy. Studies were thematically analysed and underwent quality assessment using the Joanna Briggs Institute validated critical appraisal tool for qualitative research.ResultsOut of 2681 articles screened, 28 studies (n = 1573 participants) were eligible for inclusion. Five overarching themes emerged relating to personal, provider and systemic factors. Barriers to vaccine uptake included concerns about vaccine safety and efficacy, lack of knowledge about vaccines' benefits and necessity, fear of adverse effects on the foetus or mother and low perception of disease severity. Facilitators included recommendations from trusted healthcare providers, easy access to vaccination, clear communication on the benefits and safety of vaccination, and positive social influences from family and friends. Strategies for increasing vaccination uptake included strong and proactive vaccine recommendations by trusted healthcare professionals, provision of vaccines during routine antenatal care, and clear and consistent communication about vaccines addressing pregnant women's concerns.ConclusionThis review highlights the need for interventions that address the identified barriers to vaccine uptake among pregnant women. Recommendation from a healthcare provider can play a significant role in promoting vaccine uptake, as can clear risk/benefit communication and convenient access to vaccination. Addressing concerns about vaccine safety and providing accurate information about vaccines is also important.

Introduction Treatment failure (TF) in HIV infected children is a major concern in resource-constrained settings in Sub-Saharan Africa (SSA). This study investigated the prevalence, incidence, and factors associated with first-line cART failure using the virologic (plasma viral load), immunologic and clinical criteria among HIV-infected children. Methods A retrospective cohort study of children ( 6 months) enrolled in the pediatric HIV/AIDs treatment program at Orotta National Pediatric Referral Hospital from January 2005 to December 2020 was conducted. Data were summarized using percentages, medians (± interquartile range (IQR)), or mean ± standard deviation (SD). Where appropriate, Pearson Chi-Squire (χ2) tests or Fishers exacts test, Kaplan–Meier (KM) estimates, and unadjusted and adjusted Cox-proportional hazard regression models were employed. Results Out of 724 children with at least 24 weeks’ follow-up 279 experienced therapy failure (TF) making prevalence of 38.5% (95% CI 35–42.2) over a median follow-up of 72 months (IQR, 49–112 months), with a crude incidence of failure of 6.5 events per 100- person-years (95% CI 5.8–7.3). In the adjusted Cox proportional hazards model, independent factors of TF were suboptimal adherence (Adjusted Hazard Ratio (aHR) = 2.9, 95% CI 2.2–3.9, p < 0.001), cART backbone other than Zidovudine and Lamivudine (aHR = 1.6, 95% CI 1.1–2.2, p = 0.01), severe immunosuppression (aHR = 1.5, 95% CI 1–2.4, p = 0.04), wasting or weight for height z-score < -2 (aHR = 1.5, 95% CI 1.1–2.1, p = 0.02), late cART initiation calendar years (aHR = 1.15, 95% CI 1.1–1.3, p < 0.001), and older age at cART initiation (aHR = 1.01, 95% CI 1–1.02, p < 0.001). Conclusions Seven in one hundred children on first-line cART are likely to develop TF every year. To address this problem, access to viral load tests, adherence support, integration nutritional care into the clinic, and research on factors associated with suboptimal adherence should be prioritized.

Background This study aimed to identify a Relative Age Effect (RAE) among French young swimmers and apply corrective adjustment procedures to rebalance performances according to categories and events. Methods 5,339,351 performances of French swimmers aged 10 to 18 were collected between 2000 and 2019. Birth quarters distribution was examined according to competitiveness level (‘All’, ‘Top50%’, ‘Top25%’ and ‘Top10%’), event and age category. A linear relationship between the distribution of performances and calendar days provides a calibration coefficient allowing to rebalance performances by considering the effect of RAE for each event. Then, adjusted performances are recalculated using this coefficient, the initial performance and the relative age. Results Proportion of swimmers born in the first quarter was higher than the proportion of those born in the last quarter for all events and strokes (p < 0.01). RAE increases with the competitiveness level for all events. Indeed, among ’All’ 12 years old 50m freestyle swimmers, the proportion born in the first quarter is 30.9% vs 19.2% in the fourth quarter, while among the “Top10%”, 47.5% were born in the first quarter vs 10.3% in the last one. (p-value < 0.01). In average, each day represents a gap of 0.008 second, resulting in a difference of almost 3 seconds over a year. This tool is validated by comparing swimmers who have performed at least twice in a season. It provides a day by day rebalancing method for all swimming events and age categories. Conclusions Relative age effect is present among French young male and female swimmers, and is strengthened by competitiveness level. A new corrective adjustment procedure to rebalance performances considering categories and events is proposed and validated. By applying such a tool, we are able to reveal the full potential of swimmers and make it possible to compare them at the same relative age.

The vast amount of images generated by aerial imagery in the context of regular wildlife surveys nowadays require automatic processing tools. At the top of the mountain of different methods to automatically detect objects in images reigns deep learning’s object detection. The recent focus given to this task has led to an influx of many different architectures of neural networks that are benchmarked against standard datasets like Microsoft’s Common Objects in COntext (COCO). Performance on COCO, a large dataset of computer vision images, is given in terms of mean Average Precision (mAP). In this study, we use six pretrained networks to detect red deer from aerial images, three of which have never been used, to our knowledge, in a context of aerial wildlife surveys. We compare their performance along COCO’s mAP and a common test metric in animal surveys, the F1-score. We also evaluate how dataset imbalance and background uniformity, two common difficulties in wildlife surveys, impact the performance of our models. Our results show that the mAP is not a reliable metric to select the best model to count animals in aerial images and that a counting-focused metric like the F1-score should be favored instead. Our best overall performance was achieved with Generalized Focal Loss (GFL). It scored the highest along both metrics, combining most accurate counting and localization (with average F1-score of 0.96 and 0.97 and average mAP scores of 0.77 and 0.89 on both datasets respectively) and is therefore very promising for future applications. While both imbalance and background uniformity improved the performance of our models, their combined effect had twice as much impact as the choice of architecture. This finding seems to confirm that the recent data-centric shift in the deep learning field could also lead to performance gains in wildlife surveys.

We study the wealth distribution of UK households through a detailed analysis of data from wealth surveys and rich lists, and propose a non-linear Kesten process to model the dynamics of household wealth. The main features of our model are that we focus on wealth growth and disregard exchange, and that the rate of return on wealth is increasing with wealth. The linear case with wealth-independent return rate has been well studied, leading to a log-normal wealth distribution in the long time limit which is essentially independent of initial conditions. We find through theoretical analysis and simulations that the non-linearity in our model leads to more realistic power-law tails, and can explain an apparent two-tailed structure in the empirical wealth distribution of the UK and other countries. Other realistic features of our model include an increase in inequality over time, and a stronger dependence on initial conditions compared to linear models.

ObjectiveEvaluate the accuracy and precision of the copd-6 mini-spirometer for FEV1 in a rural Ugandan population.MethodsIn a cross-sectional study, 171 smallholder farmers performed spirometry with copd-6, and a diagnostic-quality spirometer.Results and discussionThe copd-6 underestimated FEV1 at low flows and overestimated FEV1 at high flows. Across all participants, the device slightly overestimated FEV1 by 0.04 [0.02; 0.06] L. Calibration data showed similar patterns.ConclusionThe copd-6 could be considered as an affordable tool for research on lung function impairment in resource-constrained settings. However, further validation in a study population with obstructive lung disease is needed.

Insects face the challenge of navigating to specific goals in both bright sun-lit and dim-lit environments. Both diurnal and nocturnal insects use quite similar navigation strategies. This is despite the signal-to-noise ratio of the navigational cues being poor at low light conditions. To better understand the evolution of nocturnal life, we investigated the navigational efficiency of a nocturnal ant, Myrmecia pyriformis, at different light levels. Workers of M. pyriformis leave the nest individually in a narrow light-window in the evening twilight to forage on nest-specific Eucalyptus trees. The majority of foragers return to the nest in the morning twilight, while few attempt to return to the nest throughout the night. We found that as light levels dropped, ants paused for longer, walked more slowly, the success in finding the nest reduced and their paths became less straight. We found that in both bright and dark conditions ants relied predominantly on visual landmark information for navigation and that landmark guidance became less reliable at low light conditions. It is perhaps due to the poor navigational efficiency at low light levels that the majority of foragers restrict navigational tasks to the twilight periods, where sufficient navigational information is still available. [ABSTRACT FROM AUTHOR]

BackgroundDespite considerable efforts to prevent HIV and other sexually transmitted infections (STI) among female sex workers (FSW), other sexual and reproductive health (SRH) needs, such preventing unintended pregnancies, among FSW have received far less attention. Programs targeting FSW with comprehensive, accessible services are needed to address their broader SRH needs. This study tested the effectiveness of an intervention to increase dual contraceptive method use to prevent STIs, HIV and unintended pregnancy among FSW attending services in drop-in centers (DIC) in two cities in Kenya. The intervention included enhanced peer education, and routine screening for family planning (FP) needs plus expanded non-condom FP method availability in the DIC.MethodsWe conducted a two-group, pre-/posttest, quasi-experimental study with 719 FSW (360 intervention group, 359 comparison group). Participants were interviewed at baseline and 6 months later to examine changes in condom and non-condom FP method use.ResultsThe intervention had a significant positive effect on non-condom, FP method use (OR = 1.38, 95%CI (1.04, 1.83)), but no effect on dual method use. Consistent condom use was reported to be high; however, many women also reported negotiating condom use with both paying and non-paying partners as difficult or very difficult. The strongest predictor of consistent condom use was partner type (paying versus non-paying/emotional); FSW reported both paying and non-paying partners also influence non-condom contraceptive use. Substantial numbers of FSW also reported experiencing sexual violence by both paying and non-paying partners.ConclusionsSelf-reported difficulties with consistent condom use and the sometimes dangerous conditions under which they work leave FSW vulnerable to unintended pregnancy STIs/HIV. Adding non-barrier FP methods to condoms is crucial to curb unintended pregnancies and their potential adverse health, social and economic consequences. Findings also highlight the need for additional strategies beyond condoms to reduce HIV and STI risk among FSW.Trial registrationClinicaltrials.gov NCT01957813.

Checkpoint inhibitor immunotherapies have had major success in treating patients with late-stage cancers, yet the minority of patients benefit. Mutation load and PD-L1 staining are leading biomarkers associated with response, but each is an imperfect predictor. A key challenge to predicting response is modeling the interaction between the tumor and immune system. We begin to address this challenge with a multifactorial model for response to anti-PD-L1 therapy. We train a model to predict immune response in patients after treatment based on 36 clinical, tumor, and circulating features collected prior to treatment. We analyze data from 21 bladder cancer patients using the elastic net high-dimensional regression procedure and, as training set error is a biased and overly optimistic measure of prediction error, we use leave-one-out cross-validation to obtain unbiased estimates of accuracy on held-out patients. In held-out patients, the model explains 79% of the variance in T cell clonal expansion. This predicted immune response is multifactorial, as the variance explained is at most 23% if clinical, tumor, or circulating features are excluded. Moreover, if patients are triaged according to predicted expansion, only 38% of non-durable clinical benefit (DCB) patients need be treated to ensure that 100% of DCB patients are treated. In contrast, using mutation load or PD-L1 staining alone, one must treat at least 77% of non-DCB patients to ensure that all DCB patients receive treatment. Thus, integrative models of immune response may improve our ability to anticipate clinical benefit of immunotherapy.

INTRODUCTION:Crohn's disease (CD) is a chronic inflammatory bowel disease known to carry a high risk of disabling and many times requiring surgical interventions. This article describes a decision-tree based approach that defines the CD patients' risk or undergoing disabling events, surgical interventions and reoperations, based on clinical and demographic variables. MATERIALS AND METHODS:This multicentric study involved 1547 CD patients retrospectively enrolled and divided into two cohorts: a derivation one (80%) and a validation one (20%). Decision trees were built upon applying the CHAIRT algorithm for the selection of variables. RESULTS:Three-level decision trees were built for the risk of disabling and reoperation, whereas the risk of surgery was described in a two-level one. A receiver operating characteristic (ROC) analysis was performed, and the area under the curves (AUC) Was higher than 70% for all outcomes. The defined risk cut-off values show usefulness for the assessed outcomes: risk levels above 75% for disabling had an odds test positivity of 4.06 [3.50-4.71], whereas risk levels below 34% and 19% excluded surgery and reoperation with an odds test negativity of 0.15 [0.09-0.25] and 0.50 [0.24-1.01], respectively. Overall, patients with B2 or B3 phenotype had a higher proportion of disabling disease and surgery, while patients with later introduction of pharmacological therapeutic (1 months after initial surgery) had a higher proportion of reoperation. CONCLUSIONS:The decision-tree based approach used in this study, with demographic and clinical variables, has shown to be a valid and useful approach to depict such risks of disabling, surgery and reoperation.

A retrospective study was carried out to define the spectrum of spontaneous diseases in ostriches and few other captive ratites, order Struthioniformes, in northwestern Germany. The investigation included 71 ratites necropsied between 1968 and 2014. They consisted of 54 ostriches, 5 emus, and 12 rheas with 37 adults, 23 juveniles and 11 neonates and embryonated eggs. Necropsy reports were reviewed, histologic preparations were re-examined and additional histochemical and immunohistochemical stains were carried out in selected cases. In many animals more than one morphologic diagnosis attributable to different disease processes was found. In adult animals (n = 37), the most commonly altered organ systems were the musculoskeletal system (49%), the digestive system (46%), and the cardiovascular system (46%) affected by traumatic lesions, inflammatory and degenerative changes, respectively. A spongy degeneration was found in the brain (35%); however, immunohistochemistry and western blotting failed to detect pathological prion protein. In juvenile animals (n = 23), the musculoskeletal (44%) and the digestive system (43%) were mainly affected by traumatic and inflammatory lesions, respectively. In embryonated eggs and neonates (n = 11) the major cause of death was circulatory failure associated with generalized subcutaneous edema as described for improper incubation conditions (64%). Summarized, most of the findings observed in adult and juvenile ratites in northwestern Germany are related to trauma, inflammatory and degenerative disorders, whereas death in embryonated eggs and neonates was most likely related to breeding conditions. A spongy encephalopathy awaits further studies to elucidate cause and pathogenesis.

Coordinated collective behaviors often emerge from simple rules governing the interactions of individuals in groups. We model mechanisms of coordination among ants during cooperative transport, a challenging task that requires a consensus on travel direction. Our goal is to determine whether groups following simple behavioral rules can reach a consensus using minimal information. Using deterministic and stochastic models, we investigate behavioral factors that affect coordination. We define and investigate three types of behavioral rules governing individual behavior that differ in the information available: individuals either 1) have no information, 2) can measure transport success, or 3) measure success while also knowing whether they are aligned with the majority. We find that groups break deadlocks only if individuals more readily give up when they are going against the majority, corresponding to rule type 3 -such groups are "informed." These behavioral rules succeed through positive and negative feedbacks that are implemented in our model via a single mechanism: individuals only need to measure the relative group sizes to make effective decisions. We also find that groups reach consensus more quickly if they have either a shared bias, high sensitivity to group behavior, or finely tuned persistence. Each of these is a potential adaptation for efficient cooperative transport. This flexibility makes the behavioral rules in the informed case relatively robust to deficiencies in the individuals' capabilities. While inspired by ants, our results are generalizable to other collective decisions with deadlocks, and demonstrate that groups of behaviorally simple individuals with no memory and extremely limited information can break symmetry and reach a consensus in a decision between two equal options.

The objective of this study was to identify and describe levels of household economic vulnerability in HIV-affected communities in Côte d'Ivoire, defined as those with a high prevalence of HIV and large numbers of orphans and vulnerable children. We conducted a cross-sectional survey of 3,749 households in five health regions of Côte d'Ivoire. Using principal component analysis, we attempted to identify sets of correlated vulnerabilities and derive a small number of composite scores to create an index for targeting interventions to vulnerable populations. The 65 vulnerability measures examined did not cluster in ways that would allow for the creation of a small number of composite measures. Instead, we found that households face numerous unique pathways to vulnerability.

Large valleys with opposing slopes may act as a model system with which the effects of strong climatic gradients on biodiversity can be evaluated. The advantage of such comparisons is that the impact of a change of climate can be studied on the same species pool without the need to consider regional differences. The aim of this study was to compare the assemblage of saproxylic beetles on such opposing slopes at Lower Nahal Oren, Mt. Carmel, Israel (also known as "Evolution Canyon") with a 200-800% higher solar radiation on the south-facing (SFS) compared to the north-facing slope (NFS). We tested specific hypotheses of species richness patterns, assemblage structure, and body size resulting from interslope differences in microclimate. Fifteen flight-interception traps per slope were distributed over three elevation levels ranging from 50 to 100 m a.s.l. Richness of saproxylic beetles was on average 34% higher on the SFS compared with the NFS, with no detected influence of elevation levels. Both assemblage structure and average body size were determined by slope aspect, with more small-bodied beetles found on the SFS. Both the increase in species richness and the higher prevalence of small species on the SFS reflect ecological rules present on larger spatial grain (species-energy hypothesis and community body size shift hypothesis), and both can be explained by the metabolic theory of ecology. This is encouraging for the complementary use of micro- and macroclimatic gradients to study impacts of climate warming on biodiversity.

INTRODUCTION:Several clinical trials have demonstrated the efficacy of pre-exposure prophylaxis (PrEP) in reducing HIV risk. One concern with introducing PrEP is whether users will engage in riskier sexual behaviors. METHODS:We assessed the effect that PrEP may have on sexual risk behaviors by administering a survey to 799 women in Bondo, Kenya, and Pretoria, South Africa. Participants were asked about their sexual behavior intentions twice--once as if they were taking PrEP and once as if they were not taking PrEP--within four risk situations (vignettes). They responded using a 5-point ordinal scale. We used a series of linear mixed effects models with an unstructured residual covariance matrix to estimate the between- and within-subject differences in the mean likelihood of engaging in risky sexual behavior across the PrEP and non-PrEP contexts. We also calculated the total percentage of participants who reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP, by vignette. RESULTS:We found statistically significant differences in the mean likelihood of engaging in risky sexual behavior with the between-subject comparison (-0.17, p < 0.01) and with the within-subject comparison (-0.31, p < 0.001). Depending on the vignette, 27% to 40% of participants reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP. CONCLUSIONS:Our findings indicate that modest increases in risky sexual behavior could occur with PrEP. Although responses from the majority of participants suggest they would not be more likely to engage in risky sexual behavior if they took PrEP, a substantial proportion might. Programs rolling out PrEP should be prepared to assist similar women in making informed choices about reducing their risk of HIV and about their sexual health beyond HIV prevention.