Medium-term environmental changes influence age-specific survival estimates in a salmonid population

Human-induced environmental change is a major stressor on freshwater habitats that has resulted in the population declines of many freshwater species. Ontogenetic shifts in habitat use and associated (st)age-specific requirements mean that impacts of environmental stressors can influence (st)ages in a population differently, and yet relatively few studies of freshwater fish populations account for their detail. We aimed to identify environmental and biotic factors affecting survival estimated for six age-classes of a European grayling population in the River Wylye, UK over a 17-year period. We used a Bayesian age-structured state space model to estimate survival of grayling cohorts between subsequent life stages (eggs to age 5 adults) for 16 annual transitions (2003–2004 to 2018–2019), whilst accounting for imperfect sampling of the population. We quantified the effects of seasonal water flow and temperature, in-stream habitat and prey resource, and potential competitors and predators on survival between subsequent life stages. We used Bayesian variable selection to gauge their relative importance on survival. Grayling abundances declined during the study period (>75% in all age-classes), predominately driven by a loss of mature adults. Changes to seasonal flows negatively influenced their survival: increased days of summer low flow related to decreased survival of subadults and mature adults, and lower winter flows related to reduced recruitment of juveniles from eggs. Higher summer macrophyte cover negatively influenced juvenile and subadult survival and increasing days of high temperature in summer appeared detrimental to juvenile survival. Abundance of brown trout (a potential competitor and predator) did not negatively influence grayling survival. Our results reveal the implications of environmental change on a salmonid population, where recent low summer flows and high temperatures, and below average winter flows, have negatively influenced grayling survival. These conditions appear to be becoming more frequent and persistent in our study river, which is towards the species’ southern range limit, which could render the population vulnerable to climate change. Our study demonstrates how careful analysis of long-term population monitoring and environmental datasets can identify factors affecting (st)age-specific fish population dynamics, and when combined with local expertise, results in realistic mitigation proposals to promote wildlife population persistence

Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. CONCLUSIONS AND RELEVANCE: Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months