Effort-reward imbalance at work and risk of type 2 diabetes in a national sample of 50,552 workers in Denmark : A prospective study linking survey and register data

Objective: To examine the prospective relation between effort-reward imbalance at work and risk of type 2 diabetes. Methods: We included 50,552 individuals from a national survey of the working population in Denmark, aged 30-64 years and diabetes-free at baseline. Effort-reward imbalance was defined, in accordance with the literature, as a mismatch between high efforts at work (e.g. high work pace, time pressure), and low rewards received in return (e.g. low recognition, job insecurity) and assessed as a continuous and a categorical variable. Incident type 2 diabetes was identified in national health registers. Using Cox regression we calculated hazard ratios (HR) and 95% confidence intervals (95% CI) for estimating the association between effort-reward imbalance at baseline and risk of onset of type 2 diabetes during follow-up, adjusted for sex, age, socioeconomic status, cohabitation, children at home, migration background, survey year and sample method. Results: During 136,239 person-years of follow-up (mean = 2.7 years) we identified 347 type 2 diabetes cases (25.5 cases per 10,000 person-years). For each one standard deviation increase of the effort-reward imbalance score at baseline, the fully adjusted risk of type 2 diabetes during follow-up increased by 9% (HR: 1.09, 95% CI: 0.98-1.21). When we used effort-reward imbalance as a dichotomous variable, exposure to effort-reward imbalance was associated with an increased risk of type 2 diabetes with a HR of 1.27 (95% CI: 1.02-1.58). Conclusion The results of this nationwide study of the Danish workforce suggest that effort-reward imbalance at work may be a risk factor for type 2 diabetes.Peer reviewe

Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue

Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias is inherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mm biopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB but low clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure

What do cyclists need to see to avoid single-bicycle crashes?

The number of single-bicycle crash victims is substantial in countries with high levels of cycling. To study the role of visual characteristics of the infrastructure, such as pavement markings, in single-bicycle crashes, a study in two steps was conducted. In Study 1, a questionnaire study was conducted among bicycle crash victims (n = 734). Logistic regression was used to study the relationship between the crashes and age, light condition, alcohol use, gaze direction and familiarity with the crash scene. In Study 2, the image degrading and edge detection method (IDED-method) was used to investigate the visual characteristics of 21 of the crash scenes. The results of the studies indicate that crashes, in which the cyclist collided with a bollard or road narrowing or rode off the road, were related to the visual characteristics of bicycle facilities. Edge markings, especially in curves of bicycle tracks, and improved conspicuity of bollards are recommended. Statement of Relevance: Elevated single-bicycle crash numbers are common in countries with high levels of cycling. No research has been conducted on what cyclists need to see to avoid this type of crash. The IDED-method to investigate crash scenes is new and proves to be a powerful tool to quantify 'visual accessibility'. © 2011 Taylor & Francis

GPR50 Interacts with TIP60 to Modulate Glucocorticoid Receptor Signalling

GPR50 is an orphan G-protein coupled receptor most closely related to the melatonin receptors. The physiological function of GPR50 remains unclear, although our previous studies implicate the receptor in energy homeostasis. Here, we reveal a role for GPR50 as a signalling partner and modulator of the transcriptional co-activator TIP60. This interaction was identified in a yeast-two-hybrid screen, and confirmed by co-immunoprecipitation and co-localisation of TIP60 and GPR50 in HEK293 cells. Co-expression with TIP60 increased perinuclear localisation of full length GPR50, and resulted in nuclear translocation of the cytoplasmic tail of the receptor, suggesting a functional interaction of the two proteins. We further demonstrate that GPR50 can enhance TIP60-coactiavtion of glucocorticoid receptor (GR) signalling. In line with in vitro results, repression of pituitary Pomc expression, and induction of gluconeogenic genes in liver in response to the GR agonist, dexamethasone was attenuated in Gpr50−/− mice. These results identify a novel role for GPR50 in glucocorticoid receptor signalling through interaction with TIP60

A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98–1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11–1.18], p = 1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence