Search

Background: Ocular diseases may exhibit common clinical symptoms and epidemiological comorbidity. However, the extent of pleiotropic mechanisms across ocular diseases remains unclear. We aim to examine shared genetic etiology in age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, retinal detachment (RD), and myopia., Methods: We analyzed genome-wide association analyses for the five ocular diseases in 43,877 cases and 44,373 controls of European ancestry from UK Biobank, estimated their genetic relationships (LDSC, GNOVA, and Genomic SEM), and identified pleiotropic loci (ASSET and METASOFT)., Findings: The genetic correlation of common SNPs revealed a meaningful genetic structure within these diseases, identifying genetic correlations between AMD, DR, and glaucoma. Cross-trait meta-analysis identified 23 pleiotropic loci associated with at least two ocular diseases and 14 loci unique to individual disorders (non-pleiotropic). We found that the genes associated with these shared genetic loci are involved in neuron differentiation (P = 8.80 × 10 -6 ) and eye development systems (P = 3.86 × 10 -5 ), and single cell RNA sequencing data reveals their heightened gene expression from multipotent progenitors to other differentiated retinal cells during retina developmental process., Interpretation: These results highlighted the potential common genetic architectures among these ocular diseases and can deepen the understanding of the molecular mechanisms underlying the related diseases., Funding: The National Natural Science Foundation of China (61871294), Zhejiang Provincial Natural Science Foundation of China (LR19C060001), and the Scientific Research Foundation for Talents of Wenzhou Medical University (QTJ18023)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The Psychiatry Early Experience Programme (PEEP) is a novel enrichment activity at Kings College London medical school. Throughout their five-year degree, students shadow trainee psychiatry doctors. The study aimed to evaluate whether more regular early exposure affects attitudes towards psychiatry., Methods: Forty first-year medical students joined PEEP and completed a baseline survey, including questions on demographics, current top three choices of medical specialty and the 30-item Attitudes Towards Psychiatry questionnaire (ATP-30). Participants completed annual follow up surveys, incorporating free-text questions about what students had learned and whether their views about psychiatry had changed., Results: Over three years there was a sustained improvement in mean ATP-30 scores (8.27 points higher at three years than at baseline [95% CI 2.86-13.7, T=3.2, p=0.005]). There was no significant difference between baseline specialty choice and specialty choice at three-year follow-up. At three years there was a 55% response rate. There was no significant association between non-responders at three years and baseline ATP-30, specialty choice or demographic factors. Thematic analysis of qualitative data suggested that PEEP challenged preconceptions towards psychiatry and highlighted its relevance in medicine., Conclusions: The results offer some support that exposure to clinical psychiatry through longitudinal shadowing experiences can sustain positive attitudes. Areas for development include using a control group and following-up participants to the point when they specialize. It remains unclear whether it is most effective to select participants based on established commitment to psychiatry or to try to influence students who are still undecided.

Background: Temperature variability (TV) is closely associated with climate change, but there is no unified TV definition worldwide. Two novel composite TV indexes were developed recently by calculating the standard deviations of several days' daily maximum and minimum temperatures (TV daily ), or hourly mean temperatures (TV hourly )., Objectives: This study aimed to compare the mortality risks and burden associated with TV daily and TV hourly using large time-series datasets collected from multiple locations in China, United Kingdom and United States., Methods: We collected daily mortality and hourly temperature data through 1987 to 2012 from 63 locations in China (8 communities, 2006-2012), United Kingdom (10 regions, 1990-2012), and USA (45 cities, 1987-2000). TV-mortality associations were investigated using a three-stage analytic approach separately for China, UK, and USA. First, we applied a time-series regression for each location to derive location-specific TV-mortality curves. A second-stage meta-analysis was then performed to pool these estimated associations for each country. Finally, we calculated mortality fraction attributable to TV based on above-described location-specific and pooled estimates., Results: Our dataset totally consisted of 23, 089, 328 all-cause death cases, including 93, 750 from China, 7,573,716 from UK and 15, 421, 862 from USA, respectively. In despite of a relatively wide uncertainty in China, approximately linear relationships were consistently identified for TV daily and TV hourly . In the three countries, generally similar lag patterns of TV effects were consistently observed for TV daily and TV hourly . A 1 °C rise in TV daily and TV hourly at lag 0-7 days was associated with mortality increases of 0.93% (95% confidence interval [CI]: 0.12, 1.74) and 0.97% (0.18, 1.77) in China, 0.33% (0.15, 0.51) and 0.41% (0.21, 0.60) in UK, and 0.55% (0.41, 0.70) and 0.51% (0.35, 0.66) in USA, respectively. Larger attributable fractions were estimated using TV daily than those using TV hourly , with estimates at 0-10 days of 3.69% (0.51, 6.75) vs. 2.59% (0.10, 5.01) in China, 1.14% (0.54, 1.74) vs. 0.98% (0.55, 1.42) in UK, and 2.57% (1.97, 3.16) vs. 1.67% (1.15, 2.18) in USA, respectively. Our meta-regression analyses indicated higher vulnerability to TV-induced mortality risks in warmer locations., Conclusions: Our study added multi-country evidence for increased mortality risk associated with short-term exposure to large temperature variability. Daily and hourly TV exposure metrics produced generally comparable risk effects, but the attributable mortality burden tended to be higher using TV daily instead of TV hourly ., (Copyright © 2019 Elsevier Inc. All rights reserved.)