Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Objectives: No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods: In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results: Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL. Conclusions: We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL. HIV Medicin

Effects of Training and Competition Load on Neuromuscular Recovery, Testosterone, Cortisol, and Match Performance During a Season of Professional Football

Introduction: Training load and other measures potentially related to match performance are routinely monitored in team-sport athletes. The aim of this research was to examine the effect of training load on such measures and on match performance during a season of professional football.Materials and Methods: Training load was measured daily as session duration times perceived exertion in 23 A-League football players. Measures of exponentially weighted cumulative training load were calculated using decay factors representing time constants of 3–28 days. Players performed a countermovement jump for estimation of a measure of neuromuscular recovery (ratio of flight time to contraction time, FT:CT), and provided a saliva sample for measurement of testosterone and cortisol concentrations 1-day prior to each of 34 matches. Match performance was assessed via ratings provided by five coaching and fitness staff on a 5-point Likert scale. Effects of training load on FT:CT, hormone concentrations and match performance were modeled as quadratic predictors and expressed as changes in the outcome measure for a change in the predictor of one within-player standard deviation (1 SD) below and above the mean. Changes in each of five playing positions were assessed using standardization and magnitude-based inference.Results: The largest effects of training were generally observed in the 3- to 14-day windows. Center defenders showed a small reduction in coach rating when 14-day a smoothed load increased from −1 SD to the mean (-0.31, ±0.15; mean, ±90% confidence limits), whereas strikers and wide midfielders displayed a small increase in coach rating when load increased 1 SD above the mean. The effects of training load on FT:CT were mostly unclear or trivial, but effects of training load on hormones included a large increase in cortisol (102, ±58%) and moderate increase in testosterone (24, ±18%) in center defenders when 3-day smoothed training load increased 1 SD above the mean. A 1 SD increase in training load above the mean generally resulted in substantial reductions in testosterone:cortisol ratio.Conclusion: The effects of recent training on match performance and hormones in A-League football players highlight the importance of position-specific monitoring and training

Normal Variability of Weekly Musculoskeletal Screening Scores and the Influence of Training Load across an Australian Football League Season

Aim: The sit and reach test (S&amp;R), dorsiflexion lunge test (DLT), and adductor squeeze test (AST) are commonly used in weekly musculoskeletal screening for athlete monitoring and injury prevention purposes. The aim of this study was to determine the normal week to week variability of the test scores, individual differences in variability, and the effects of training load on the scores.Methods: Forty-four elite Australian rules footballers from one club completed the weekly screening tests on day 2 or 3 post-main training (pre-season) or post-match (in-season) over a 10 month season. Ratings of perceived exertion and session duration for all training sessions were used to derive various measures of training load via both simple summations and exponentially weighted moving averages. Data were analyzed via linear and quadratic mixed modeling and interpreted using magnitude-based inference.Results: Substantial small to moderate variability was found for the tests at both season phases; for example over the in-season, the normal variability ±90% confidence limits were as follows: S&amp;R ±1.01 cm, ±0.12; DLT ±0.48 cm, ±0.06; AST ±7.4%, ±0.6%. Small individual differences in variability existed for the S&amp;R and AST (factor standard deviations between 1.31 and 1.66). All measures of training load had trivial effects on the screening scores.Conclusion: A change in a test score larger than the normal variability is required to be considered a true change. Athlete monitoring and flagging systems need to account for the individual differences in variability. The tests are not sensitive to internal training load when conducted 2 or 3 days post-training or post-match, and the scores should be interpreted cautiously when used as measures of recovery

Global COVID-19 lockdown highlights humans as both threats and custodians of the environment

The global lockdown to mitigate COVID-19 pandemic health risks has altered human interactions with nature. Here, we report immediate impacts of changes in human activities on wildlife and environmental threats during the early lockdown months of 2020, based on 877 qualitative reports and 332 quantitative assessments from 89 different studies. Hundreds of reports of unusual species observations from around the world suggest that animals quickly responded to the reductions in human presence. However, negative effects of lockdown on conservation also emerged, as confinement resulted in some park officials being unable to perform conservation, restoration and enforcement tasks, resulting in local increases in illegal activities such as hunting. Overall, there is a complex mixture of positive and negative effects of the pandemic lockdown on nature, all of which have the potential to lead to cascading responses which in turn impact wildlife and nature conservation. While the net effect of the lockdown will need to be assessed over years as data becomes available and persistent effects emerge, immediate responses were detected across the world. Thus initial qualitative and quantitative data arising from this serendipitous global quasi-experimental perturbation highlights the dual role that humans play in threatening and protecting species and ecosystems. Pathways to favorably tilt this delicate balance include reducing impacts and increasing conservation effectiveness