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Although HIV self-testing (HIVST) has expanded in many regions, a few HIVST services have been tailored for and organized by youth. Innovative HIVST models are needed to differentiate testing services and generate local demand for HIVST among youth. The current pilot study aimed at examining the feasibility and efficacy of crowdsourced youth-led strategies to enhance HIVST as well as sexually transmitted infection (STI) testing. Teams of youth iteratively developed HIVST interventions using crowdsourcing approaches and apprenticeship training. Five interventions were selected and then evaluated among youth (ages 14-24) from September 2019 to March 2020. Given the similar outcomes and approaches, we present cumulative data from the completed interventions. We assessed HIVST uptake (self-report), STI uptake (facility reports for gonorrhea, syphilis, hepatitis B, and chlamydia testing), and quality of youth participation. Mixed-effect logistic regression models estimated intervention effects at baseline and 6 months. Of the 388 youths enrolled, 25.3% were aged 14-19, 58.0% were male, and 54.1% had completed secondary education. We observed a significant increase in HIVST from 3 months compared with 6 months (20% vs. 90%; p < 0.001). Among those who received an HIVST at 3 months, 324 out of 388 were re-tested at 6 months. We also observed significant increases in testing for all four STIs: syphilis (5-48%), gonorrhea (5-43%), chlamydia (1-45%), and hepatitis B testing (14-55%) from baseline to the 6-month follow-up. Youth participation in the intervention was robust. Youth-led HIVST intervention approaches were feasible and resulted in increased HIV/STI test uptake. Further research on the effectiveness of these HIVST services is needed.

The Coronavirus 2019 (COVID-19) pandemic has affected the delivery of healthcare around the world. We assessed the impact of the COVID-19 pandemic on hospital presentations, reperfusion treatment and outcomes in a comprehensive stroke centre. In this observational study seven months of retrospective data from February 2020 (at the beginning of the pandemic) were compared to data collected for the same time frame in 2019. There was a transient reduction in stroke presentation only at the beginning of the wave of COVID-19 community transmissions in Sydney. There were significantly more haemorrhagic strokes in the COVID-19 period (n = 66, 15.4 % vs n = 95, 21.5 %, P = 0.02) and baseline stroke severity was higher (NIHSS median 3 vs 4, P = 0.049). Similar proportions of ischaemic stroke patients received reperfusion therapy in the two time periods (IV thrombolysis [n = 51, 17.3% vs n = 52, 17.9%, P = 0.838]; and ECR [n = 38, 12.9% vs n = 46, 15.9%, P = 0.30]). The time from presentation to stroke bed admission was significantly shorter during the COVID-19 period (median 295 vs 260 minutes, P = 0.031). Three-month follow-up Modified Rankin Score was 2 (median) in both periods (P = 0.92). There was no change in stroke presentations overall during the 2020 COVID 19 pandemic time period with the exception of the first phase of the pandemic. Baseline stroke severity scores were higher. There was no a difference in the degree of disability at three-month follow-up.

Adolescence is a developmental period in which disordered eating and negative body image are highly prevalent, yet their risk factors are insufficiently understood and targeted. Despite research implicating both teasing and bullying victimization in the development of eating disorders, these strands of research are yet to be integrated. This systematic review hence aimed to identify whether teasing and bullying victimization are associated with greater risk of eating disorders and body image disturbance for adolescents. Systematic searches of PsycINFO and PubMed databases identified 79 papers that included quantitative analyses of the relationship between weight-related or nonspecific teasing or bullying victimization and disordered eating or body image disturbance. Overall, studies indicated that adolescents who are teased or bullied are more likely to experience disordered eating and negative body image compared to nonvictimized adolescents. This was more consistently observed in cross-sectional studies than in longitudinal findings. We identify several methodological limitations of the literature, including the infrequent consideration of potential mediating and moderating variables. Finally, we outline future directions such as temporal sequencing of the complex interrelationships among teasing and bullying, disordered eating, and body image disturbance in adolescents.

The Dec. 22, 2018 lateral collapse of the Anak Krakatau (AK) volcano in the Sunda Straits of Indonesia discharged volcaniclastic material into the 250 m deep caldera southwest of the volcano and generated a large tsunami, causing runups of up to 85 m in the near-field, and 13.5 m in the far-field, on the nearby coasts of Sumatra and Java. The tsunami caused 437 fatalities, the greatest number from a volcanically-induced tsunami since the catastrophic explosive caldera-forming eruption of Krakatau in 1883 and the sector collapse of Ritter Island in 1888. For the first time in over 100 years, the 2018 AK event provides an opportunity to study a major volcanically-generated tsunami that caused widespread loss of life and significant damage. Here, we present numerical simulations of the collapse and tsunami generation, propagation, and coastal impact, with state-of the-art numerical models, using both a new parametrization of the collapse and a near-field bathymetric dataset based on our 2019 field surveys and satellite images. These subaerial and submarine data sets are used to constrain the geometry and magnitude of the landslide mechanism, which show that the primary landslide scar bisected the AK edifice, cutting behind the central vent and removing 50% of its subaerial volume. The primary landslide volume is estimated to range from 0.175–0.313 km3, based on uncertainties in the shape of the submerged part of the failure plane. This is supported by an independent estimate of the primary landslide deposit volume of 0.214 ± 0.036 km3. Given uncertainties in the failure volume, we define a range of potential failure surfaces that span these values in 4 collapse scenarios of volume ranging from 0.175 to 0.313 km3. These AK collapses are modeled, assuming either a granular or viscous fluid rheology, together with their corresponding tsunami generation and propagation. Observations of a single tsunami, with no subsequent waves, are consistent with our interpretation of la

Cystic Fibrosis (CF) is primarily a progressive lung disease, characterized by chronic pulmonary infections with opportunistic pathogens. Such infections typically commence early in life, producing an inflammatory response marked by IL-8 chemokine production and neutrophilic infiltration, major contributory factors in CF progression. Studying this inflammation, especially early in life, is critical for developing new strategies for preventing or slowing disruption to the structural integrity of the CF airways. However, evaluating the immune responses of bronchoalveolar lavage (BAL) cells from children with CF faces technical challenges, including contamination carried from the lung due to pre-existing infections and low cell number availability. Here, we describe a technique for preparing BAL cells from young children with CF and using those cells in a bacterial stimulation assay. Initial antibiotic treatment proved essential for preventing resident bacteria from overgrowing BAL cell cultures, or non-specifically activating the cells. ACTB, identified as an optimal reference gene, was validated for accurate analysis of gene expression in these cells. Pseudomonas aeruginosa and Staphylococcus aureus were used as bacterial stimulants to evaluate the immune response of BAL cells from young children with CF. Addition of gentamicin prevented bacterial overgrowth, although if added after 3 hours of culture an extremely variable response resulted, with the bacteria causing a suppressive effect in some cultures. Addition of gentamicin after 1 hour of culture completely prevented this suppressive effect. This technique was then able to reproducibly measure the IL-8 response to stimulation with S. aureus and P. aeruginosa, including co-stimulation with both bacteria.

INTRODUCTION: Youth engagement in HIV research is generally recognized as essential, but often neglected or minimally implemented in practice. Engagement is a process of working collaboratively with diverse groups of people to address common issues. We conducted a scoping review of youth HIV prevention interventions in sub-Saharan Africa to identify and categorize forms and levels of youth engagement across the lifespan of intervention research. METHODS: We followed Arksey and O'Malley's framework for organizing a scoping review. We searched seven databases for related articles on identified intervention studies through May 28th 2020. Included studies focused on youth (10 to 24 years old) HIV prevention interventions in sub-Saharan Africa. Two reviewers independently examined citations and full manuscripts for inclusion. Data were extracted on study characteristics, location, description of youth engagement and extent of engagement. Youth engagement approaches were categorized based on Hart's ladder as substantial engagement (strong youth decision-making power), moderate engagement (shared decision making with adults), minimal engagement (no youth decision-making power) or no engagement. RESULTS: We identified 3149 citations and included 112 studies reporting on 74 unique HIV interventions. Twenty-two interventions were in low-income countries, 49 in middle-income countries, and three were in both. Overall, only nine interventions (12%) had substantial or moderate youth engagement, two-thirds (48, 65%) had minimal youth engagement and 17 interventions (23%) had no youth engagement. We also identified specific engagement strategies (e.g. youth-led research, crowdsourcing) that were feasible in multiple settings and resulted in substantial engagement. CONCLUSIONS: We found limited youth engagement in youth HIV prevention intervention studies in sub-Saharan Africa. However, several activities resulted in substantial youth engagement and could be relevant in many low-an

Purpose: Accurate discrimination of benign and pathogenic rare variation remains a priority for clinical genome interpretation. State-of-the-art machine learning variant prioritization tools are imprecise and ignore important parameters defining gene–disease relationships, e.g., distinct consequences of gain-of-function versus loss-of-function variants. We hypothesized that incorporating disease-specific information would improve tool performance. Methods: We developed a disease-specific variant classifier, CardioBoost, that estimates the probability of pathogenicity for rare missense variants in inherited cardiomyopathies and arrhythmias. We assessed CardioBoost’s ability to discriminate known pathogenic from benign variants, prioritize disease-associated variants, and stratify patient outcomes. Results: CardioBoost has high global discrimination accuracy (precision recall area under the curve [AUC] 0.91 for cardiomyopathies; 0.96 for arrhythmias), outperforming existing tools (4–24% improvement). CardioBoost obtains excellent accuracy (cardiomyopathies 90.2%; arrhythmias 91.9%) for variants classified with >90% confidence, and increases the proportion of variants classified with high confidence more than twofold compared with existing tools. Variants classified as disease-causing are associated with both disease status and clinical severity, including a 21% increased risk (95% confidence interval [CI] 11–29%) of severe adverse outcomes by age 60 in patients with hypertrophic cardiomyopathy. Conclusions: A disease-specific variant classifier outperforms state-of-the-art genome-wide tools for rare missense variants in inherited cardiac conditions (https://www.cardiodb.org/cardioboost/), highlighting broad opportunities for improved pathogenicity prediction through disease specificity.

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