WRAPPING SURFACES TO CONTROL MOMENT ARM LENGTHS DURING A SQUAT TASK

Simulation of high flexion tasks such as squatting is hindered through invalid moment length estimation when using generic musculoskeletal (MSK) models. The purpose of this study was to examine the effect of wrapping surface (WS) at the knee and hip joints on the muscle moment arms calculated using a MSK model during squatting tasks. A generic full body model was modified by (1) increasing knee and hip flexion range of motion (ROM), (2) adjusting translation and size parameters of two WS, and (3) implementing three additional WS. Muscle moment-arm lengths were calculated in OpenSim using motion capture data. The WS prevent muscles to cross into the bones, and the moment arm length of several hip extensors reach a plateau after 85º of hip flexion. The use of the modified MSK that includes additional WS is suited for the analysis of high flexion tasks

Association of same-sex criminalisation laws and national HIV policies with HIV testing in African MSM: an ecological single-level and multilevel cross-sectional study of sub-Saharan African countries

Background: HIV incidence among men who have sex with men (MSM) in sub-Saharan Africa (SSA) remains high compared with the general population. Many countries in the region still criminalise consensual homosexual relationships, and some are yet to adopt WHO-recommended interventions for MSM into national HIV policies. This study examines how HIV testing of adult MSM in SSA varies according to the legal climate and presence of targeted HIV policy using data from the cross-sectional 2019 Global LGBTI Internet Survey study. Methods: Using data from 3191 MSM in 44 SSA countries, we assessed associations of legal climate and HIV policy with ever and recent HIV testing using linear ecological and logistic multilevel analyses. From the single-level analysis, we can compare our findings to previously reported data, then, extending to a two-level multilevel analysis, we account for the hierarchical structure of the population and simultaneously adjust for differences in context and composition in each country. We then test the sensitivity of our analyses to excluding countries from the model. Results: We find evidence that legalised same-sex relationships were associated with increased odds of ever testing (OR=2.00, 95% CI 1.04, 3.82) in multilevel analyses. We also find evidence of an association of targeted HIV policies with increased odds of ever testing (OR=2.49, 95% CI 1.12, 5.52). We did not find evidence of an association of the legal climate (OR=1.01, 95% CI 0.69, 1.46) and targeted HIV policies (OR=1.26, 95% CI 0.78, 2.04) with recent testing. Conclusions: This study suggests elimination of discriminatory laws and policies might be important for increasing HIV status awareness of MSM, an important first step in epidemic control. Additionally, we highlight heterogeneity between South Africa and other SSA countries, which has implications for studying SSA countries as a homogeneous group

Identification of the signals for glucose-induced insulin secretion in INS1 (832/13) -cells using metformin-induced metabolic deceleration as a model

Metabolic deceleration in pancreatic -cells is associated with inhibition of glucose-induced insulin secretion (GIIS), but only in the presence of intermediate/submaximal glucose concentrations. Here, we used acute metformin treatment as a tool to induce metabolic deceleration in INS1 (832/13) -cells, with the goal of identifying key pathways and metabolites involved in GIIS. Metabolites and pathways previously implicated as signals for GIIS were measured in the cells at 2-25 mm glucose, with or without 5 mm metformin. We defined three criteria to identify candidate signals: 1) glucose-responsiveness, 2) sensitivity to metformin-induced inhibition of the glucose effect at intermediate glucose concentrations, and 3) alleviation of metformin inhibition by elevated glucose concentrations. Despite the lack of recovery from metformin-induced impairment of mitochondrial energy metabolism (glucose oxidation, O-2 consumption, and ATP production), insulin secretion was almost completely restored at elevated glucose concentrations. Meeting the criteria for candidates involved in promoting GIIS were the following metabolic indicators and metabolites: cytosolic NAD(+)/NADH ratio (inferred from the dihydroxyacetone phosphate:glycerol-3-phosphate ratio), mitochondrial membrane potential, ADP, Ca2+, 1-monoacylglycerol, diacylglycerol, malonyl-CoA, and HMG-CoA. On the contrary, most of the purine and nicotinamide nucleotides, acetoacetyl-CoA, H2O2, reduced glutathione, and 2-monoacylglycerol were not glucose-responsive. Overall these results underscore the significance of mitochondrial energy metabolism-independent signals in GIIS regulation; in particular, the candidate lipid signaling molecules 1-monoacylglycerol, diacylglycerol, and malonyl-CoA; the predominance of K-ATP/Ca2+ signaling control by low ADPMg(2+) rather than by high ATP levels; and a role for a more oxidized state (NAD(+)/NADH) in the cytosol during GIIS that favors high glycolysis rates.This study was supported by grants from Canadian Institutes of Health Research (to MP and SRMM) and a scholarship from Kuwait University to AA. MP holds the Canada Research Chair in Diabetes and Metabolis

Is Internalised Homonegativity associated with HIV testing and HIV risk behaviours of men who have sex with men: a multilevel cross-sectional study of sub-Saharan African countries

Objectives This study assessed the associations of Internalised Homonegativity (IH) with HIV testing and risk behaviours of adult men who have sex with men (MSM) in sub-Saharan Africa (SSA) and effect modification by the legal climate.DesignWe used data from the cross-sectional 2019 Global Lesbian, Gay, Bisexual, Transgender and Intersex (LGBTI+) Internet survey study. Setting and participants Overall, the 2019 Global LGBTI Internet Survey collected data from 46 SSA countries. In this secondary analysis, we included data from 3191 MSM in 44 SSA countries as there were no eligible MSM responses in the 2 countries excluded. Outcome measures Our response variables were self-reported binary indicators of ever tested for HIV, recently tested in the past 6 months (from those who reported ever testing), transactional sex (paying for and being paid for sex in the past 12 months), and unprotected anal sex (that is without a condom or pre-exposure prohylaxis (PrEP)) with a non-steady partner (in the past 3 months). Results Our findings showed high levels of IH (range 1-7) in MSM across SSA (mean (SD)=5.3 (1.36)). We found that MSM with higher IH levels were more likely to have ever (adjusted OR (aOR) 1.18, 95% CI 1.03 to 1.35) and recently tested (aOR 1.19, 95% CI 1.07 to 1.32) but no evidence of an association with paying for sex (aOR 1.00, 95% CI 0.89 to 1.12), selling sex (aOR 1.06, 95% CI 0.95 to 1.20) and unprotected sex (aOR 0.99, 95% CI 0.89 to 1.09). However, we observed that a favourable legal climate modifies the associations of IH and paying for sex (aOR 0.75, 95% CI 0.60 to 0.94). Increasing levels of IH had a negative association with paying for sex in countries where same-sex relationships are legal. We found no associations of IH with unprotected anal sex in the population surveyed. Conclusions We confirm that IH is widespread across SSA but in countries that legalise same-sex relationships, MSM were less likely to engage in transactional sex compared with those in countries where homosexuality is criminalised

Prediction of RECRUITment In randomized clinical Trials (RECRUIT-IT)— : —rationale and design for an international collaborative study

Funding: BK has received a project specific grant from the University of Basel to realize this project. In addition, this study is supported by the Swiss National Science Foundation (grant 320030_149496/1) and the Gottfried and Julia Bangerter-Rhyner Foundation. The provided work by BG, JHL, CW, and JY has been supported by the National Cancer Institute Cancer Centre Support Grant P30 CA168524 and used BISR core. The Health Services Research Unit, University of Aberdeen, receives core funding from the Chief Scientist Office of the Scottish Government Health Directorates. DC is supported by a Research Chair from the Canadian Institute for Health Research. The mentioned funding sources have no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.Peer reviewedPublisher PD

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic

Premature Discontinuation of Pediatric Randomized Controlled Trials : A Retrospective Cohort Study

Objectives To determine the proportion of pediatric randomized controlled trials (RCTs) that are prematurely discontinued, examine the reasons for discontinuation, and compare the risk for recruitment failure in pediatric and adult RCTs. Study design A retrospective cohort study of RCTs approved by 1 of 6 Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics, trial discontinuation, and reasons for discontinuation from protocols, corresponding publications, REC files, and a survey of trialists. Results We included 894 RCTs, of which 86 enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56% of pediatric RCT discontinuations and 43% of adult RCT discontinuations. Multivariable logistic regression analyses suggested that pediatric RCT was not an independent risk factor for recruitment failure after adjustment for other potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship (aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95% CI 1.01-1.09, in decrements of 100 participants). Conclusion Forty percent of pediatric RCTs were discontinued prematurely, owing predominately to slow recruitment. Enrollment of children was not an independent risk factor for recruitment failure.Peer reviewe

The Macroeconomic Consequences of Renouncing to Universal Access to Antiretroviral Treatment for HIV in Africa: A Micro-Simulation Model

AIM: Previous economic literature on the cost-effectiveness of antiretroviral treatment (ART) programs has been mainly focused on the microeconomic consequences of alternative use of resources devoted to the fight against the HIV pandemic. We rather aim at forecasting the consequences of alternative scenarios for the macroeconomic performance of countries. METHODS: We used a micro-simulation model based on individuals aged 15-49 selected from nationally representative surveys (DHS for Cameroon, Tanzania and Swaziland) to compare alternative scenarios : 1-freezing of ART programs to current levels of access, 2- universal access (scaling up to 100% coverage by 2015, with two variants defining ART eligibility according to previous or current WHO guidelines). We introduced an "artificial" ageing process by programming methods. Individuals could evolve through different health states: HIV negative, HIV positive (with different stages of the syndrome). Scenarios of ART procurement determine this dynamics. The macroeconomic impact is obtained using sample weights that take into account the resulting age-structure of the population in each scenario and modeling of the consequences on total growth of the economy. RESULTS: Increased levels of ART coverage result in decreasing HIV incidence and related mortality. Universal access to ART has a positive impact on workers' productivity; the evaluations performed for Swaziland and Cameroon show that universal access would imply net cost-savings at the scale of the society, when the full macroeconomic consequences are introduced in the calculations. In Tanzania, ART access programs imply a net cost for the economy, but 70% of costs are covered by GDP gains at the 2034 horizon, even in the extended coverage option promoted by WHO guidelines initiating ART at levels of 350 cc/mm(3) CD4 cell counts. CONCLUSION: Universal Access ART scaling-up strategies, which are more costly in the short term, remain the best economic choice in the long term. Renouncing or significantly delaying the achievement of this goal, due to "legitimate" short term budgetary constraints would be a misguided choice