Perinatal photoperiod associations with bipolar disorder and depression: A systematic literature review and cross-sectional analysis of the UK Biobank database.

Season-of-birth associations with psychiatric disorders point to environmental (co-)aetiological factors such as natural photoperiod that, if clarified, may allow interventions toward prevention. We systematically reviewed the literature concerning season-of-birth and bipolar disorder and depression and explored associations between the perinatal natural photoperiod and these outcomes in a cross-sectional analysis of the UK Biobank database. We used mean daily photoperiod and relative photoperiod range (relative to the mean) in the 3rd trimester and, separately, in the first 3 months post birth as metrics. From review, increased risk of depression with late spring birth is compatible with increased odds of probable single episode-, probable recurrent-, and diagnosed depression (OR 2.85 95 %CI 1.6-5.08, OR 2.20 95 %CI 1.57-3.1, and OR 1.48 95 %CI 1.11-1.97, respectively) with increasing 3rd trimester relative photoperiod range for participants who experienced relatively non-extreme daily photoperiods. Risk of bipolar disorder with winter-spring birth contrasted with no consistent patterns of perinatal photoperiod metric associations with bipolar disorder in the UK Biobank. As natural photoperiod varies by both time-of-year and latitude, perinatal natural photoperiods (and a hypothesized mechanism of action via the circadian timing system and/or serotonergic circuitry associated with the dorsal raphe nucleus) may reconcile inconsistencies in season-of-birth associations. Further studies are warranted.

Circadian epidemiology: Structuring circadian causes of disease and practical implications.

That disruptions of the body's internal clockwork can lead to negative health consequences, including cancer, is a plausible hypothesis. Yet, despite strong mechanistic and animal support, the International Agency for Research on Cancer (IARC) experts considered epidemiological evidence as limited regarding the carcinogenicity of "shift-work involving circadian disruption" (2007) and "night shift work" (2019). We use directed acyclic graphs (DAGs) to outline a concept of circadian causes that discloses challenges when choosing appropriate exposure variables. On this basis, we propose to move beyond shift-work alone as a direct cause of disease. Instead, quantifying chronodisruption as individual doses can lead to interpretable circadian epidemiology. The hypothesis is that doses of chronodisruption cause disrupted circadian organisation by leading to desynchronization of circadian rhythms. Chronodisruption can be conceptualized as the split physiological nexus of internal and external times. Biological (or internal) night - an individual's intrinsically favoured sleep time window - could be the backbone of circadian epidemiology. In practice, individual doses that cause disrupted circadian organisation are derived from the intersection of time intervals of being awake and an individual's biological night. After numerous studies counted work shifts, chronobiology may now advance circadian epidemiology with more specific dose estimation - albeit with greater challenges in measurement (time-dependent individual data) and analysis (time-dependent confounding).

The (mis)use of ChatGPT in science and education: Turing, Djerassi, "athletics" & ethics.

ChatGPT is an amazing advance in technology, but it poses problems for teachers in universities and schools. How should use of ChatGPT by students be dealt with?

Occupational Exposure to Poorly Soluble Low Toxicity Particles and Cardiac Disease: A Look at Carbon Black and Titanium Dioxide.

Environmental particulate exposure and the potential risk to people with various types of cardiac diseases, most notably cardiovascular disease, have aroused scientific and regulatory interest worldwide. Epidemiological studies have shown associations between exposure to airborne environmental particulate matter (PM) and mortality from cardiovascular disease (CVD). The associations reported, however, are complex and may not involve a direct role for PM, since air pollutants are diverse and highly correlated. This study examines the potential role of occupational exposure to two types of particles, namely, manufactured carbon black (CB) and titanium dioxide (TiO2), on the risk of cardiovascular disease. To address the risk of cardiovascular disease from exposure to carbon black and titanium dioxide, as reflective of poorly soluble low toxicity particles, we reviewed the published cohort mortality studies of occupational exposure to carbon black and titanium dioxide. Mortality studies of carbon black have been conducted in the United States, Germany, and the United Kingdom. Five mortality studies related to workers involved in the manufacture of titanium dioxide in the United States and Europe have also been conducted. In addition, a meta-analysis of the three-carbon black mortality studies was performed. In the random-effects meta-analysis, full cohort meta-SMRs were 1.01 (95% confidence interval (CI): 0.79-1.29) for heart disease; 1.02 (95% CI: 0.80-1.30) for ischemic heart disease; and 1.08 (95% CI: 0.74-1.59) for acute myocardial infarction (AMI) mortality. A small but imprecise increased AMI mortality risk was suggested for cumulative exposure by a meta-HR = 1.10 per 100 mg/m3-years (95% CI: 0.92-1.31) but not for lugged exposures, that is, for recent exposures. Results of five cohort mortality studies of titanium dioxide workers in the United States and Europe showed no excess in all heart disease or cardiovascular disease. In the most recent study in the United States, an internal analysis, that is, within the cohort itself, with no lag time, showed that the exposure group 15-35 mg/m3-years yielded a significantly increased risk for heart disease; however, there was no evidence of increasing risk with increasing exposure for any of the exposure categories. In contrast to environmental studies, the results of cohort mortality studies do not demonstrate that airborne occupational exposure to carbon black and titanium dioxide particulates increases cardiovascular disease mortality. The lack of a relationship between carbon black and titanium dioxide and CVD mortality suggests that the associations reported in air pollution studies may not be driven by the particulate component.

Extended Investigation of Exposure to Respirable Synthetic Amorphous Silica Dust and Its Potential Impact on Non-malignant Respiratory Morbidity.

Objectives: The present analysis aims to study the health impact of an occupational exposure to respirable synthetic amorphous silica (SAS) dusts, based on the available data from the German study. Methods: The effect of cumulative exposure to respirable SAS dust on respiratory morbidity were investigated in 462 exposed male workers. Multiple exposure assessments was performed anchored by a most recent measurement series. Internal regression models in addition to Monte Carlo-Multi Model were fitted. Results: An averaged cumulative respirable SAS dust concentration of 6.44 mg/m3-years was estimated. Internal regression models suggested a reduction of 8.11 ml (95% confidence interval: 0.49-15.73) in forced vital capacity (FVC) per 1 mg/m3-year increase of exposure. But no effect on forced expiratory volume in 1 s (FEV1) and the ratio of the parameters FEV1/FVC was observed in association with exposure to a respirable fraction of SAS. No adverse effects on the occurrence of respiratory diseases were indicated. Conclusion: This study provides no clear evidence of adverse health effects from occupational exposure to respirable SAS. Sponsor: Evonik Operations GmbH/Smart Materials, Cabot Corporation, Wacker Chemie AG.

Before, During, and After the First Wave of COVID-19: Mortality Analyses Reveal Relevant Trends in Germany and its States until June 2020.

OBJECTIVE: Well-established mortality ratio methodology can contribute to a fuller picture of the SARS-CoV-2/COVID-19 burden of disease by revealing trends and informing mitigation strategies. This work examines respective data from Germany by way of example. METHODS: Using monthly and weekly all-cause mortality data from January 2016 to June 2020 (published by the German Federal Statistical Institute) for all ages,<65 years and≥65 years, and specified for Germany's federal states, we explored mortality as sequela of COVID-19. We analysed standardized mortality ratios (SMRs) comparing 2020 with 2016-2019 as reference years with a focus on trend detection. RESULTS: In Germany as a whole, elevated mortality in April (most pronounced for Bavaria) declined in May. The states of Hamburg and Bremen had increased SMRs in all months under study. In Mecklenburg-Western Pomerania, decreased SMRs in January turned monotonically to increased SMRs by June. Irrespective of age group, this trend was pronounced and significant. CONCLUSIONS: Increased SMRs in Hamburg and Bremen must be interpreted with caution because of potential upward distortions due to a "catchment bias". A pronounced excess mortality in April across Germany was confirmed and a hitherto undetected trend of increasing SMRs for Mecklenburg-Western Pomerania was revealed. To meet the pandemic challenge and to benefit from research based on data collected in standardized ways, national authorities should regularly conduct SMR analyses. For independent analyses, national authorities should also expedite publishing raw mortality and population data, including detailed information on age, sex, and cause of death, in the public domain.

COVID-19: Heterogeneous Excess Mortality and "Burden of Disease" in Germany and Italy and Their States and Regions, January-June 2020.

Total mortality and "burden of disease" in Germany and Italy and their states and regions were explored during the first COVID-19 wave by using publicly available data for 16 German states and 20 Italian regions from January 2016 to June 2020. Based on expectations from 2016 to 2019, simplified Standardized Mortality Ratios (SMRs) for deaths occurring in the first half of 2020 and the effect of changed excess mortality in terms of "burden of disease" were assessed. Moreover, whether two German states and 19 Italian cities appropriately represent the countries within the European monitoring of excess mortality for public health action (EuroMOMO) network was explored. Significantly elevated SMRs were observed (Germany: week 14-18, Italy: week 11-18) with SMR peaks in week 15 in Germany (1.15, 95%-CI: 1.09-1.21) and in week 13 in Italy (1.79, 95%-CI: 1.75-1.83). Overall, SMRs were 1.00 (95%-CI: 0.97-1.04) in Germany and 1.06 (95%-CI: 1.03-1.10) in Italy. Significant SMR heterogeneity was found within both countries. Age and sex were strong modifiers. Loss of life expectancy was 0.34 days (1.66 days in men) for Germany and 5.3 days (6.3 days in men) for Italy [with upper limits of 3 and 6 weeks among elderly populations (≥65 years) after maximum potential bias adjustments]. Restricted data used within EuroMOMO neither represents mortality in the countries as a whole nor in their states and regions adequately. Mortality analyses with high spatial and temporal resolution are needed to monitor the COVID-19 pandemic's course.

Perinatal photoperiod associations with diabetes and chronotype prevalence in a cross-sectional study of the UK Biobank.

Experimental studies indicate that perinatal light may imprint the circadian timing system, subsequently affect later life physiology, and possibly disease risk. We combined individual time-of-year of birth and corresponding latitude to determine perinatal photoperiod characteristics for UK Biobank participants (n = 460,761) and tested for associations with diabetes mellitus (DM, the pathophysiology of which is often linked with circadian disruption) and chronotype (a trait co-governed by the circadian timing system) prevalence in a cross-sectional investigation. The UK Biobank is a population-based cohort with a 5.5% participation rate (~9.2 million individuals were invited into the study between 2006 and 2010). We defined three groups based on photoperiods experienced in the 3rd trimester of pregnancy and first 3 months post-birth time windows: (1) those who exclusively experienced non-extreme photoperiods (NEP, 8-16 hours), (2) those who experienced at least one extreme short photoperiod (ESP, <8 hours), and those who experienced at least one extreme long photoperiod (ELP, >16 hours). For individuals in each group and time window, mean daily photoperiod and relative photoperiod range (relative = relative to the mean) were calculated. Inclusion of relative photoperiod range adds dispersion information (relative change of photoperiods) to statistical models. Multivariable and multinomial logistic regression analyses were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Increased 3rd trimester relative range was associated with decreased odds of DM (OR 0.63 95%CI 0.49-0.81) in the NEP group, but increased odds of DM were detected for the ESP (OR 1.34, 95%CI 0.96-1.86) and ELP groups (OR 1.32, 95%CI 0.78-2.22). Increased 3rd trimester relative range was associated with increased odds of being a "Morning" (OR 1.20, 95%CI 1.02-1.41) or "Evening" (OR 1.43, 95%CI 1.21-1.69) chronotype in the NEP group, but this was not observed in other groups. Additionally, different effect sizes and directions of association with DM were observed in different strata of ethnicity and chronotype and statistically significant odds ratio modifications were detected. In conclusion, perinatal photoperiod associations with DM and chronotype prevalence are detected in the UK Biobank. NEP, ESP, and ELP differences are speculated to be caused by a non-linear dose-response to photoperiods from 0-24 hours or by confounding due to artificial light playing a dominant role in ESP individuals and seeking darkness in ELP individuals. Ethnicity and chronotype may be important effect modifiers of perinatal photoperiod associations with DM. Potential for selection biases due to low UK Biobank participation rate disallows stating conclusions too strongly. Overall, further studies are needed to confirm different perinatal photoperiod associations with DM and chronotype. Further investigations into the hypothesized imprinting mechanism are also warranted.

The riddle of shiftwork and disturbed chronobiology: a case study of landmark smoking data demonstrates fallacies of not considering the ubiquity of an exposure.

BACKGROUND: Failing to integrate all sources of a ubiquitous hazard candidate may explain inconsistent and/or null, and overall misleading, results in epidemiological studies such as those related to shift-work. METHODS: We explore this rationale on the assumption that Doll and Hill had confined their 1950 landmark study to smoking at workplaces alone. We assess how non-differential, or how differential, underestimation of exposure could have biased computed risks. RESULTS: Systematically unappreciated exposures at play could have led to substantial information bias. Beyond affecting the magnitude of risks, not even the direction of risk distortion would have been predictable. CONCLUSIONS: Disturbed chronobiology research should consider cumulative doses from all walks of life. This is a conditio sine qua non to avoid potentially biased and uninterpretable risk estimates when assessing effects of a ubiquitous hazard candidate.