Attitudes to ageing, biomarkers of ageing and mortality:The Lothian Birth Cohort 1936

Objective: To investigate whether people with more positive attitudes to ageing are biologically younger as defined by leucocyte telomere length, accelerated DNA methylation GrimAge (AgeAccelGrim) and brain-predicted age difference, and whether these biomarkers explain relationships between attitudes to ageing and mortality.Methods: We used linear regression to examine cross-sectionally attitudes to ageing (measured using the Attitudes to Ageing Questionnaire) and the three biomarkers in 758 adults, mean age 72.5 years, from the Lothian Birth Cohort 1936. We used Cox proportional hazards models to examine longitudinally attitudes to ageing and mortality and the role of the biomarkers.Results: More positive attitude to physical change was associated with younger biological age, as measured by AgeAccelGrim and brain-predicted age difference in age-adjusted and sex-adjusted models: for an SD higher score, AgeAccelGrim was lower by -0.73 (95% CI -1.03 to -0.42) of a year, and brain-predicted age difference was lower by -0.87 (1.51 to 0.23) of a year. Both associations were attenuated by adjustment for covariates and not significant after simultaneous adjustment for all covariates and correction for multiple testing. More positive attitudes to physical change were associated with lower mortality: for an SD higher score the age-adjusted and sex-adjusted HR (95% CI) was 0.66 (0.56 to 0.78). Adjustment for AgeAccelGrim or brain-predicted age difference attenuated this association slightly. It remained significant after adjustment for all covariates.Conclusion: We found partial evidence that attitudes to ageing are linked with ageing biomarkers but they accounted for only a little of the association between attitudes and mortality

Carnivore Translocations and Conservation: Insights from Population Models and Field Data for Fishers (Martes pennanti)

Translocations are frequently used to restore extirpated carnivore populations. Understanding the factors that influence translocation success is important because carnivore translocations can be time consuming, expensive, and controversial. Using population viability software, we modeled reintroductions of the fisher, a candidate for endangered or threatened status in the Pacific states of the US. Our model predicts that the most important factor influencing successful re-establishment of a fisher population is the number of adult females reintroduced (provided some males are also released). Data from 38 translocations of fishers in North America, including 30 reintroductions, 5 augmentations and 3 introductions, show that the number of females released was, indeed, a good predictor of success but that the number of males released, geographic region and proximity of the source population to the release site were also important predictors. The contradiction between model and data regarding males may relate to the assumption in the model that all males are equally good breeders. We hypothesize that many males may need to be released to insure a sufficient number of good breeders are included, probably large males. Seventy-seven percent of reintroductions with known outcomes (success or failure) succeeded; all 5 augmentations succeeded; but none of the 3 introductions succeeded. Reintroductions were instrumental in reestablishing fisher populations within their historical range and expanding the range from its most-contracted state (43% of the historical range) to its current state (68% of the historical range). To increase the likelihood of translocation success, we recommend that managers: 1) release as many fishers as possible, 2) release more females than males (55–60% females) when possible, 3) release as many adults as possible, especially large males, 4) release fishers from a nearby source population, 5) conduct a formal feasibility assessment, and 6) develop a comprehensive implementation plan that includes an active monitoring program

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The effects of psychological distress and its interaction with socioeconomic position on risks of developing four chronic diseases.

Objective: To examine the relationship between psychological distress and risk of developing arthritis, cardiovascular disease, chronic obstructive pulmonary disease and diabetes across the range of distress severity, investigate the mediating roles of health behaviours and explore whether the associations vary with socioeconomic position.Methods: Participants were 16,485 adults from the UK Household Longitudinal Study We examined prospective relationships between psychological distress at baseline (measured using the 12-item General Health Questionnaire) and incidence of arthritis, cardiovascular disease, chronic obstructive pulmonary disease and diabetes (measured using self-report) over 3 years using logistic regression. We then examined the mediating effects of health behaviours and investigated whether the associations varied with socioeconomic position.Results: Distress significantly increased risk of incident arthritis, cardiovascular disease and chronic obstructive pulmonary disease in a dose-response pattern after controlling for age, sex, socioeconomic position, neighbourhood cohesion, marital status, BMI and baseline disease. High levels of distress (GHQ≥7) increased risk of arthritis (OR 2.22; 1.58-2.13), cardiovascular disease (OR 3.06; 1.89-4.98) and chronic obstructive pulmonary disease (OR 3.25; 1.47-7.18). These associations were partially mediated by smoking status but remained significant after controlling for smoking status, diet and exercise. Distress significantly predicted incident diabetes in manual socioeconomic groups only. Effect sizes did not vary with socioeconomic position for arthritis, cardiovascular disease and chronic obstructive pulmonary disease.Conclusion: Psychological distress increases risk of incident arthritis, cardiovascular disease and chronic obstructive pulmonary disease in a dose-response pattern, even at low and moderate distress levels. Future research should investigate the mediating role of inflammatory biomarkers.Keywords: psychological distress; depression; arthritis; cardiovascular disease; chronic obstructive pulmonary disease; diabetes.Abbreviations: BMI=Body Mass Index, COPD=Chronic Obstructive Pulmonary Disease, CVD=Cardiovascular disease, GHQ=General Health Questionnaire, OR=Odds Ratio, SEP=Socioeconomic Positio