Exposure to workplace sexual harassment and risk of cardiometabolic disease: a prospective cohort study of 88 904 Swedish men and women.

AIMS: Exposure to work-related sexual harassment may increase the risk for certain adverse behavioural and emotional outcomes but less is known about its association with somatic diseases such as cardiovascular disease (CVD) and type 2 diabetes. This study investigated the prospective association of work-related sexual harassment and risk of cardiometabolic diseases. METHODS AND RESULTS: This cohort study included 88 904 Swedish men and women in paid work who responded to questions on workplace sexual harassment in the Swedish Work Environment Survey (1995-2015) and were free from cardiometabolic diseases at baseline. Cardiometabolic diseases (CVD and type 2 diabetes) were identified from the National Patient Register and Causes of Death Register through linkage. Cox proportional hazard regression was used, adjusting for socio-demographic, work-related psychosocial, and physical exposure at baseline. Overall, 4.8% of the participants (n = 4300) reported exposure to workplace sexual harassment during the previous 12 months. After adjustment for sex, birth country, family situation, education, income, and work-related factors, workplace sexual harassment was associated with increased incidence of CVD [hazard ratio (HR) 1.25, 95% confidence interval 1.03-1.51] and type 2 diabetes (1.45, 1.21-1.73). The HR for CVD (1.57, 1.15-2.15) and type 2 diabetes (1.85, 1.39-2.46) was increased for sexual harassment from superior or fellow workers, and sexual harassment from others was associated with type 2 diabetes (1.39, 1.13-1.70). The HR for both CVD (1.31, 0.95-1.81) and type 2 diabetes (1.72, 1.30-2.28) was increased for frequent exposure. CONCLUSION: The results of this study support the hypothesis that workplace sexual harassment is prospectively associated with cardiometabolic diseases. Future research is warranted to understand causality and mechanisms behind these associations.

We investigated if workers in Sweden who had experienced sexual harassment at work had a higher risk of developing cardiovascular disease and diabetes than workers who had not experienced sexual harassment at work. The experience of workplace sexual harassment was associated with an increased risk of both cardiovascular disease and diabetes. The risk was highest among those workers who had frequently experienced sexual harassment. Our results suggest that preventive measures directed towards elimination of sexual harassment may contribute to a reduction in cardiovascular disease and diabetes in the population.

Work-related suicide: Evolving understandings of etiology & intervention.

Previously published analyses of suicide case investigations suggest that work or working conditions contribute to 10%-13% of suicide deaths. Yet, the way in which work may increase suicide risk is an underdeveloped area of epidemiologic research. In this Commentary, we propose a definition of work-related suicide from an occupational health and safety perspective, and review the case investigation-based and epidemiologic evidence on work-related causes of suicide. We identified six broad categories of potential work-related causes of suicide, which are: (1) workplace chemical, physical, and psychosocial exposures; (2) exposure to trauma on the job; (3) access to means of suicide through work; (4) exposure to high-stigma work environments; (5) exposure to normative environments promoting extreme orientation to work; and (6) adverse experiences arising from work-related injury or illness. We summarise current evidence in a schema of potential work-related causes that can also be applied in workplace risk assessment and suicide case investigations. There are numerous implications of these findings for policy and practice. Various principle- and evidence-based workplace intervention strategies for suicide prevention exist, some of which have been shown to improve suicide-prevention literacy, reduce stigma, enhance helping behaviours, and in some instances maybe even reduce suicide rates. Prevailing practice in workplace suicide prevention, however, overly emphasises individual- and illness-directed interventions, with little attention directed to addressing the working conditions that may increase suicide risk. We conclude that a stronger emphasis on improving working conditions will be required for workplace suicide prevention to reach its full preventive potential.

Emotional demands at work and risk of disability pension: a nationwide cohort study in Denmark.

INTRODUCTION: Working in emotionally demanding jobs is associated with an increased risk of temporarily leaving the labour market due to long-term sickness absence. We tested whether employees working in emotionally demanding jobs are also at higher risk of permanently leaving the labour market due to disability pension compared with employees working in jobs that are not emotionally demanding. METHODS: We conducted a 10-year cohort study in the workforce in Denmark (n=1 670 825), aged 30-59 years at baseline, by linking job exposure matrices with nationwide registries on social transfer payments and covariates. Using Cox regression, we analysed the risk of disability pension in relation to emotional demands in the full population and sex stratified. Multivariable adjusted models included sex, age, cohabitation, migration background, household disposable income and other work environmental factors (physical workload, influence, possibilities for development and role conflicts). RESULTS: We identified 67 923 new cases of disability pension during 15 649 743 person-years of follow-up (mean follow-up: 9.4 years). We found an increasing risk of disability pension with higher levels of emotional demands, with HRs of 1.20, 1.23 and 1.73 for medium-low, medium-high and high emotional demands, respectively, compared with low emotional demands in the most adjusted model. There was an exposure-response association in women and a tendency towards an exposure-response association in men. DISCUSSION: In this nationwide cohort study, we found an increased risk of permanent exit from the labour market due to disability pension in women and men working in emotionally demanding jobs.

Youth Psychotic Experiences: Diagnostic Associations and Evaluation of the CAPE-16.

Background: Adolescent self-reported psychotic experiences are associated with mental illness and could help guide prevention strategies. The Community Assessment of Psychic Experiences (CAPE) was developed over 20 years ago. In a rapidly changing society, where new generations of adolescents are growing up in an increasingly digital world, it is crucial to ensure high reliability and validity of the questionnaire. Methods: In this observational validation study, we used unique transgenerational questionnaire and health registry data from the Norwegian Mother, Father, and Child Cohort, a population-based pregnancy cohort. Adolescents, aged ~14 years, responded to the CAPE-16 (n = 18,835) and fathers to the CAPE-9 questionnaire (n = 28,793). We investigated the psychometric properties of CAPE-16 through factor analyses, measurement invariance testing across biological sex, response before/ during the COVID-19 pandemic, and generations (comparison with fathers), and examined associations with later psychiatric diagnoses. Outcomes: One third (33·4%) of adolescents reported lifetime psychotic experiences. We confirmed a three-factor structure (paranoia, bizarre thoughts, and hallucinations) of CAPE-16, and observed good scale reliability of the distress and frequency subscales (ω = ·86 and ·90). CAPE-16 measured psychotic experiences were invariant to biological sex and pandemic status. CAPE-9 was non-invariant across generations, with items related to understanding of the digital world (electrical influences) prone to bias. CAPE-16 sum scores were associated with a subsequent psychiatric diagnosis, particularly psychotic disorders (frequency: OR = 2·06; 97·5% CI = 1·70-2·46; distress: OR = 1·93; 97·5% CI = 1·63-2·26). Interpretation: CAPE-16 showed robust psychometric properties across sex and pandemic status, and sum scores were associated with subsequent psychiatric diagnoses, particularly psychotic disorders. These findings suggest that with certain adjustments, CAPE-16 could have value as a screening tool for adolescents in the modern, digital world. Funding: European Union's Horizon 2020 Programme, Research Council of Norway, South-Eastern Norway Regional Health Authority, NIMH, and the KG Jebsen Stiftelsen.

Workplace sexual harassment: a qualitative study of the self-labelling process among employees in Denmark.

PURPOSE: To explore how employees understand work-related sexual harassment and label their experience. METHODS: This study is based on 13 semi-structured in-depth interviews with employees exposed to workplace sexual harassment. We analysed the data using a thematic approach drawing on frameworks of sensemaking in organizations. RESULTS: We identified four major themes. The first two themes, distinguishing between sexual harassment and unwanted sexual attention and labelling real life sexual harassment, outline the interviewees' definitions of the two terms "sexual harassment" and "unwanted sexual harassment" and reveal the challenges of labelling sexually harassing behaviours at work. The last two themes; making the connection and negotiating boundaries and labels, explain the sensemaking process, i.e., how the interviewees come to understand and label their experience. CONCLUSION: The analysis showed that the interviewees related sexual harassment with physical, coercive, and intentional behaviours, whereas unwanted sexual attention was seen as less severe and less intentional. The interviewees often doubted how to label their experience, and making sense of one´s experience could take years. Self-labelling is inherently a social process, and the validation and rejection of others play an important role. Finally, the #MeToo movement constituted a turning point for several interviewees' understandings of events.

Cardiovascular Risk in Young Patients Diagnosed With Obstructive Sleep Apnea.

BACKGROUND: In older adults, obstructive sleep apnea (OSA) has been associated with several cardiovascular complications. Whether young patients diagnosed with OSA also are at higher risk of developing subsequent cardiovascular disease is uncertain. We aimed to estimate the risk of developing an incident cardiovascular event among young patients diagnosed with OSA. METHODS AND RESULTS: We linked nationwide Danish health registries to identify a cohort of patients aged ≤50 years with OSA using data from 2010 through 2018. Cases without OSA from the general population were matched as controls (1:5). The main outcome was any cardiovascular event (including hypertension, diabetes, atrial fibrillation, ischemic heart disease, ischemic stroke, heart failure, and venous thromboembolism). All-cause mortality was a secondary outcome. The study included 20 240 patients aged ≤50 years with OSA (19.6% female; mean±SD age 39.9±7.7 years) and 80 314 controls. After 5-year follow-up, 31.8% of the patients with OSA developed any cardiovascular event compared with 16.5% of the controls, with a corresponding relative risk (RR) of 1.96 (95% CI, 1.90-2.02). At 5-year follow-up, 27.3% of patients with OSA developed incident hypertension compared with 15.0% of the controls (RR, 1.84 [95% CI, 1.78-1.90]). Incident diabetes occurred in 6.8% of the patients with OSA and 1.4% of controls (RR, 5.05 [95% CI, 4.60-5.54]). CONCLUSIONS: Similar to older adults, young adults with OSA demonstrate increased risk of developing cardiovascular events. To prevent cardiovascular disease progression, accumulation of cardiovascular risk factors, and mortality, risk stratification and prevention strategies should be considered for these patients.

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e-29). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e-31). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e-05, 1.7e-12)]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.

Using rare genetic mutations to revisit structural brain asymmetry.

Asymmetry between the left and right hemisphere is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variants, which typically exert small effects on brain-related phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We designed a pattern-learning approach to dissect the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior data fusion highlights the consequences of genetically controlled brain lateralization on uniquely human cognitive capacities.

Sediment discharge from Greenland's marine-terminating glaciers is linked with surface melt.

Sediment discharged from the Greenland Ice Sheet delivers nutrients to marine ecosystems around Greenland and shapes seafloor habitats. Current estimates of the total sediment flux are constrained by observations from land-terminating glaciers only. Addressing this gap, our study presents a budget derived from observations at 30 marine-margin locations. Analyzing sediment cores from nine glaciated fjords, we assess spatial deposition since 1950. A significant correlation is established between mass accumulation rates, normalized by surface runoff, and distance down-fjord. This enables calculating annual sediment flux at any fjord point based on nearby marine-terminating outlet glacier melt data. Findings reveal a total annual sediment flux of 1.324 + /- 0.79 Gt yr-1 over the period 2010-2020 from all marine-terminating glaciers to the fjords. These estimates are valuable for studies aiming to understand the basal ice sheet conditions and for studies predicting ecosystem changes in Greenland's fjords and offshore areas as the ice sheet melts and sediment discharge increase.

Workplace sexual and gender-based harassment in Denmark: a comparison of the self-labelling and behavioural list method.

AIM: Knowledge about the prevalence of sexual and gender-based harassment is hampered by disagreements about definitions and measurement methods. The two most common measurement methods are the self-labelling (a single question about exposure to sexual harassment) and the behavioural list method (an inventory of sexually harassing behaviours). The aim of this paper was to compare the self-labelling and the behavioural list methods for measuring sexual harassment and assess the association with depressive symptoms. METHODS: The study is based on a convenience sample of 1686 individuals employed in 29 workplaces in Denmark. Survey data were collected from November 2020 until June 2021 and there were 1000 participants with full data on key variables. We used a linear mixed-effects model to examine the relationship between sexual harassment and depressive symptoms. RESULTS: In total, 2.5% self-labelled as being sexually harassed, while 19.0% reported exposure to at least one type of sexual and gender-based harassment using the behavioural list method. Both groups reported higher levels of depressive symptoms compared with non-exposed employees. The most common types of behaviours were: that someone spoke derogatorily about women/men (11.6%); being belittled because of one's gender or sexuality (4.7%); and unwanted comments about one's body, clothes or lifestyle (4.5%). CONCLUSIONS: The behavioural list method yielded a higher prevalence of sexual and gender-based harassment compared with the self-labelling method. Self-labelling and reporting at least one type of sexual and gender-based harassment was associated with depressive symptoms.

Work-related causes of mental health conditions and interventions for their improvement in workplaces.

Mental health problems and disorders are common among working people and are costly for the affected individuals, employers, and whole of society. This discussion paper provides an overview of the current state of knowledge on the relationship between work and mental health to inform research, policy, and practice. We synthesise available evidence, examining both the role of working conditions in the development of mental disorders, and what can be done to protect and promote mental health in the workplace. We show that exposure to some working conditions is associated with an increased risk of the onset of depressive disorders, the most studied mental disorders. The causality of the association, however, is still debated. Causal inference should be supported by more research with stronger linkage to theory, better exposure assessment, better understanding of biopsychosocial mechanisms, use of innovative analytical methods, a life-course perspective, and better understanding of the role of context, including the role of societal structures in the development of mental disorders. There is growing evidence for the effectiveness of interventions to protect and promote mental health and wellbeing in the workplace; however, there is a disproportionate focus on interventions directed towards individual workers and illnesses, compared with interventions for improving working conditions and enhancing mental health. Moreover, research on work and mental health is mainly done in high-income countries, and often does not address workers in lower socioeconomic positions. Flexible and innovative approaches tailored to local conditions are needed in implementation research on workplace mental health to complement experimental studies. Improvements in translating workplace mental health research to policy and practice, such as through workplace-oriented concrete guidance for interventions, and by national policies and programmes focusing on the people most in need, could capitalise on the growing interest in workplace mental health, possibly yielding important mental health gains in working populations.

Subcortical Brain Alterations in Carriers of Genomic Copy Number Variants.

OBJECTIVE: Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs), including autism (ASD) and schizophrenia. Little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, the authors investigated gross volume, vertex-level thickness, and surface maps of subcortical structures in 11 CNVs and six NPDs. METHODS: Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (CNVs at 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2; age range, 6-80 years; 340 males) and 782 control subjects (age range, 6-80 years; 387 males) as well as ENIGMA summary statistics for ASD, schizophrenia, attention deficit hyperactivity disorder, obsessive-compulsive disorder, bipolar disorder, and major depression. RESULTS: All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five. Shape analyses detected subregional alterations that were averaged out in volume analyses. A common latent dimension was identified, characterized by opposing effects on the hippocampus/amygdala and putamen/pallidum, across CNVs and across NPDs. Effect sizes of CNVs on subcortical volume, thickness, and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and schizophrenia. CONCLUSIONS: The findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions, as well distinct effects, with some CNVs clustering with adult-onset conditions and others with ASD. These findings provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD and why a single CNV increases the risk for a diverse set of NPDs.

Incidence of venous thromboembolism following head and neck surgery.

PURPOSE: Venous thromboembolism (VTE) is associated with significant morbidity and mortality in patients undergoing surgery, but conflicting data exist on VTE risk in patients undergoing head and neck surgery for malignant and non-malignant conditions. Our aim was to examine the risk of VTE among patients with and without cancer undergoing head and neck surgery. METHODS: We conducted a nationwide cohort study to examine the risk of VTE among patients with an otolaryngological diagnosis using data from the Danish National Patient Register between 2010 and 2018. Analyses were stratified by cancer and anatomical areas of the surgical procedure. RESULTS: In total, 116,953 patients were included of whom 10% (n = 12,083) had active cancer. After 3 months, 1.2% of the patients with cancer and 0.3% of the patients without cancer experienced VTE, respectively. For patients undergoing mouth/throat surgery, 0.8% with cancer and 0.2% without cancer had VTE, respectively. After nose/sinuses surgery 0.7% and 0.2%, respectively. No patients experienced VTE after ear surgery; and after endoscopies the numbers were 1.3% and 0.6% respectively. CONCLUSIONS: While the minority of patients undergoing head and neck surgery develop VTE postoperatively, the risk increases among those with cancer. To support clinical decision making on anticoagulation, risk stratification tools could be further developed to recognize this hazard in patients with cancer undergoing head and neck surgery.

Association of workplace violence and bullying with later suicide risk: a multicohort study and meta-analysis of published data.

BACKGROUND: Workplace offensive behaviours, such as violence and bullying, have been linked to psychological symptoms, but their potential impact on suicide risk remains unclear. We aimed to assess the association of workplace violence and bullying with the risk of death by suicide and suicide attempt in multiple cohort studies. METHODS: In this multicohort study, we used individual-participant data from three prospective studies: the Finnish Public Sector study, the Swedish Work Environment Survey, and the Work Environment and Health in Denmark study. Workplace violence and bullying were self-reported at baseline. Participants were followed up for suicide attempt and death using linkage to national health records. We additionally searched the literature for published prospective studies and pooled our effect estimates with those from published studies. FINDINGS: During 1 803 496 person-years at risk, we recorded 1103 suicide attempts or deaths in participants with data on workplace violence (n=205 048); the corresponding numbers for participants with data on workplace bullying (n=191 783) were 1144 suicide attempts or deaths in 1 960 796 person-years, which included data from one identified published study. Workplace violence was associated with an increased risk of suicide after basic adjustment for age, sex, educational level, and family situation (hazard ratio 1·34 [95% CI 1·15-1·56]) and full adjustment (additional adjustment for job demands, job control, and baseline health problems, 1·25 [1·08-1·47]). Where data on frequency were available, a stronger association was observed among people with frequent exposure to violence (1·75 [1·27-2·42]) than occasional violence (1·27 [1·04-1·56]). Workplace bullying was also associated with an increased suicide risk (1·32 [1·09-1·59]), but the association was attenuated after adjustment for baseline mental health problems (1·16 [0·96-1·41]). INTERPRETATION: Observational data from three Nordic countries suggest that workplace violence is associated with an increased suicide risk, highlighting the importance of effective prevention of violent behaviours at workplaces. FUNDING: Swedish Research Council for Health, Working Life and Welfare, Academy of Finland, Finnish Work Environment Fund, and Danish Working Environment Research Fund.

Opposing impacts of HLA-G haplotypes PROMO-G010104-UTR-3 and PROMO-G010101b/c-UTR-4 on risk of recurrent implantation failure.

RESEARCH QUESTION: The human leukocyte antigen (HLA) class Ib molecules HLA-F and HLA-G are implicated in pregnancy success, but how do HLA-G and HLA-F genetic polymorphisms impact recurrent implantation failure (RIF)? DESIGN: Prospective cohort study at a fertility clinic including a cohort of 84 women experiencing RIF and 35 IVF controls to assess the influence of HLA-G haplotypes and diplotypes and HLA-F single nucleotide polymorphisms (SNP) on RIF. RESULTS: Over-representation trends for HLA-F SNP genotypes rs1362126, rs2523405 and rs2523393, previously linked with a short time-to-pregnancy, were detected in female control groups compared with RIF patients with no identified pathology linked to infertility. The HLA-G promoter haplotype PROMO-G010101b/c linked with the HLA-G 3'-untranslated region (3'UTR) haplotype UTR-4, which previously has been associated with positive IVF outcome and pregnancy success, was less frequent in the RIF group. For RIF patients carrying the UTR-4 haplotype, the odds ratio (OR) was 0.27 (95% CI 0.12-0.66; P = 0.0044, Pc = 0.026). The HLA-G PROMO-G010104-UTR-3 haplotype was associated with an increased risk of RIF. For RIF patients carrying the UTR-3 haplotype, the OR was 5.86 (95% CI 1.52-26.23; P = 0.0115, Pc = 0.069). CONCLUSIONS: These results show that specific HLA-G haplotypes based on the promoter region and the 3'UTR are either associated with an increased risk of reduced fertility, including the manifestation of RIF, and lower chance of achieving pregnancy, or with a reduced risk of experiencing RIF.

Emotional demands and all-cause and diagnosis-specific long-term sickness absence: a prospective cohort study in Sweden.

BACKGROUND: High emotional demands at work require sustained emotional effort and are associated with adverse health outcomes. We tested whether individuals in occupations with high emotional demands, compared with low demands, had a higher future risk of all-cause long-term sickness absence (LTSA). We further explored whether the risk of LTSA associated with high emotional demands differed by LTSA diagnoses. METHODS: We conducted a prospective, nationwide cohort study on the association between emotional demands and LTSA (>30 days) in the workforce in Sweden (n = 3 905 685) during a 7-year follow-up. Using Cox regression, we analyzed sex-stratified risks of all-cause and diagnosis-specific LTSA due to common mental disorders (CMD), musculoskeletal disorders (MSD) and all other diagnoses. Multivariable adjusted models included age, birth country, education, living area, family situation and physical work demands. RESULTS: Working in emotionally demanding occupations was associated with a higher risk of all-cause LTSA in women [hazard ratio (HR) = 1.92, 95% confidence interval (CI): 1.88-1.96] and men (HR = 1.23, 95% CI: 1.21-1.25). In women, the higher risk was similar for LTSA due to CMD, MSD and all other diagnoses (HR of 1.82, 1.92 and 1.93, respectively). In men, risk of LTSA due to CMD was pronounced (HR = 2.01, 95% CI: 1.92-2.11), whereas risk of LTSA due to MSD and all other diagnoses was only slightly elevated (HR of 1.13, both outcomes). CONCLUSIONS: Workers in occupations with high emotional demands had a higher risk of all-cause LTSA. In women, risk of all-cause and diagnosis-specific LTSA were similar. In men, the risk was more pronounced for LTSA due to CMD.

Using rare genetic mutations to revisit structural brain asymmetry.

Asymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We quantitatively dissected the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior mapping highlights the consequences of genetically controlled brain lateralization on human-defining cognitive traits.

Small-Area Analysis of Treatment and Clinical Outcomes in Patients with Venous Thromboembolism in Denmark: A Nationwide Cohort Study.

OBJECTIVES: To investigate geographical variation in initiation and extended treatment with anticoagulants and clinical outcomes among patients hospitalized with first-time venous thromboembolism (VTE) in Denmark between 2007 and 2018. METHODS: Using nationwide health care registries, we identified all patients with a first-time VTE hospital diagnosis supported by imaging data from 2007 to 2018. Patients were grouped according to residential region (5) and municipality (98) at the time of VTE diagnosis. Cumulative incidence of initiation of and extended (beyond 365 days) anticoagulation treatment as well as clinical outcomes, including recurrent VTE, major bleeding, and all-cause death, were assessed. Sex- and age-adjusted relative risks (RRs) of the outcomes were computed when comparing across individual regions and municipalities. Overall geographic variation was quantified by computing the median RR. RESULTS: We identified 66,840 patients with a first-time VTE hospitalization. A difference in initiation of anticoagulation treatment of more than 20 percentage points between regions was observed (range: 51.9-72.4%, median RR: 1.09, 95% confidence interval [CI]: 1.04-1.13). Variation was also observed for extended treatment (range: 34.2-46.9%, median RR: 1.08, 95% CI: 1.02-1.14). The cumulative incidence of recurrent VTE ranged from 3.6 to 5.3% at 1 year (median RR: 1.08, 95% CI: 1.01-1.15). The difference remained after 5 years, and variation was also observed for major bleeding (median RR: 1.09, 95% CI: 1.03-1.15), whereas it appeared smaller for all-cause mortality (median RR: 1.03, 95% CI: 1.01-1.05). CONCLUSION: Substantial geographical variation in anticoagulation treatment and clinical outcomes occurs in Denmark. These findings indicate a need for initiatives to ensure uniform high-quality care for all VTE patients.