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Occupational gender stereotypes develop from early age and contribute to occupational gender imbalance. Previous research used questionnaires or interviews to investigate children's explicit stereotypes and where drawings have been used, mostly men-dominated occupations have been considered. This study used drawings and interviews to assess implicit stereotypes of both men and women-dominated occupations and whether children's sex, age and cultural background predicted these stereotypes. Two hundred and forty-three 6-to-7-year-olds and 10-to-11-year-olds in Britain and Argentina-encompassing both Global South and Global North perspectives- drew five human figures: (i) person of their choice, (ii) dancer, (iii) nanny (iv) firefighter and (v) pilot. In interviews, children confirmed and justified their gender choices for each drawing. Results indicate gender stereotypes in children from both countries, especially towards women-dominated occupations. Girls exhibited more rigid gender views than boys. These findings suggest widespread and culturally consistent occupational gender stereotypes, potentially limiting children's future job choices., (© 2024 The Author(s). British Journal of Developmental Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Background: Major Depressive Disorder (MDD) poses a significant global health challenge, with symptom presentation potentially varying between adolescents and adults. Adolescence is a critical period marked by heightened vulnerability to interpersonal stresses, yet the impact of these stresses on the structure of depressive symptoms is not well understood. Recognizing the cultural nuances in how depression manifests among adolescents is crucial. To this end, this paper employs a network analysis approach, utilizing a comprehensive symptom checklist from the Multidimensional Depression Assessment Scale (MDAS). Our study investigates the role of interpersonal symptoms within the broader cluster of emotional, cognitive, and somatic symptoms and explores variations in adolescent groups in four Asian and European regions., Methods: We recruited a diverse sample of 6,348 adolescents aged 12 to 18 from Hong Kong, Taiwan, the UK, China, and the Netherlands using the Qualtrics platform. Employing the Gaussian Graphical Model, we established a network model of depressive symptoms as measured by the MDAS, segregating the sample into Asian and European regions to examine the interconnections between them. The study focused on identifying central symptom nodes and comparing the network structures between the two groups., Results: The analysis identified feeling worthless, low energy, being a burden to others, and low mood as central symptoms of depression. Notably, there were significant differences in the connections between depressive symptoms among Asian (Hong Kong, China and Taiwan) and European (UK and the Netherlands) adolescents, highlighting cultural variations in how interpersonal symptoms interact with emotional, cognitive, and somatic symptoms., Conclusion: This study is pioneering in applying network analysis to include interpersonal symptoms in examining depression among a diverse adolescent population. It demonstrates that interpersonal symptoms are integral to the central features of depressive symptoms. Furthermore, our findings suggest that, compared to their UK and Dutch peers, interpersonal symptoms in Asian adolescents are uniquely connected to other symptom clusters, reflecting distinct cultural patterns., Limitations: The study engaged a broad community sample; however, future research could benefit from including a larger sample size to allow for a more detailed analysis of a greater number of symptom nodes., (© 2024. The Author(s).)

Drawing on three years of ethnographic engagement with the rare disease community in the United Kingdom and Europe, this article explores the experiences of families who seek and (sometimes) receive a genomic diagnosis. I trace how families learn to enact unexplained symptoms and common disabilities as rare, genetic disorders, and how they coordinate genomic and non-genomic ways of "doing" disease within and beyond the clinic. These experiences shed light on the socio-material processes through which genomic variants become "diseases" (or fail to do so), and on the implications for those whose lives have become entangled with the genomic agenda.

Background: Previous studies have suggested differences in multiple sclerosis (MS) severity according to ethnicity., Methods: Data were obtained from the UK MS Register, a prospective longitudinal cohort study of persons with MS. We examined the association between self-reported ethnic background and age at onset, symptom of onset and a variety of participant-reported severity measures. We used adjusted multivariable linear regression models to explore the association between ethnicity and impact of MS, and Cox proportional hazards models to assess disability progression., Results: We analysed data from 17,314 people with MS, including participants from self-reported Black ( n = 157) or South Asian ( n = 230) ethnic backgrounds. Age at MS onset and diagnosis was lower in those of South Asian (median 30.0) and Black (median 33.0) ethnicity compared with White ethnicity (median 35.0). In participants with online MS severity measures available, we found no statistically significant evidence for an association between ethnic background and physical disability in MS in both cross-sectional and longitudinal analyses., Conclusion: We found no association between ethnic background and MS severity in a large, diverse UK cohort. These findings suggest that other factors, such as socioeconomic status and structural inequalities, may explain previous findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study examined the link between classroom ethnic diversity, cross-ethnic friendships, and children's theory of mind. In total, 730 children in the United Kingdom (54.7% girls, 51.5% White) aged 8 to 13 years completed measures of theory of mind in 2019/2020. Controlling for verbal ability, executive function, peer social preference, and teacher-reported demographic characteristics, greater classroom ethnic diversity provided opportunities for cross-ethnic friendships, and children with cross-ethnic friendships performed better than peers without cross-ethnic friendships on theory of mind. These results extend accounts of intergroup contact by using direct assessments of children's theory of mind and advance social accounts of theory of mind by demonstrating how experiences outside the family are linked with theory of mind., (© 2024 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Background: The COVID-19 pandemic negatively impacted mental health in the general population in Britain. Ethnic minority people suffered disproportionately, in terms of health and economic outcomes, which may contribute to poorer mental health. We compare the prevalence of depression and anxiety across 18 ethnic groups in Britain during the COVID-19 pandemic., Methods: Secondary analysis of cross-sectional data (February-November 2021) from 12,161 participants aged 18-60 years old (N with data on outcomes = 11,540 for depression & 11,825 for anxiety), obtained from the Evidence for Equality National Survey (EVENS). Data were weighted to account for selection bias and coverage bias. Weighted regression models examined ethnic differences in depression (Centre for Epidemiologic Studies Depression Scale) and anxiety (Generalised Anxiety Disorder-7). Effect modification analyses explored whether ethnic differences in outcomes were consistent within age and sex sub-groups., Results: Compared to White British people, greater odds of anxiety caseness (and greater anxiety symptoms) were observed for Arab (OR = 2.57; 95 % CI = 1.35-4.91), Mixed White and Black Caribbean (1.57; 1.07-2.30), any other Black (2.22, 1.28-3.87) and any other Mixed (1.58; 1.08-2.31) ethnic groups. Lower odds of depression caseness (and lower depressive symptoms) were identified for Chinese (0.63; 0.46-0.85), Black African (0.60; 0.46-0.79), and any other Asian (0.55; 0.42-0.72) ethnic groups., Limitations: Cross-sectional data limits the opportunity to identify changes in ethnic inequalities in mental health over time., Conclusions: We have identified certain ethnic groups who may require more targeted mental health support to ensure equitable recovery post-pandemic. Despite finding lower levels of depression for some ethnic groups, approximately one third of people within each ethnic group met criteria for depression., Competing Interests: Declaration of competing interest SVK was co-chair of the Scottish Government's Expert Reference Group on Ethnicity and COVID-19 and a member of the UK Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups., Aims: To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire., Method: Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas., Results: A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased., Conclusions: Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

This study investigated the experience of self-harming behaviour that inflicts external injuries to the body in UK based Indian, Pakistani, and Bangladeshi (UKBIP) women. A total of eight participants were recruited via purposive sampling and semi-structured interviews were carried out. The interviews were analysed using Interpretative Phenomenological Analysis (IPA). Analyses were carried out on an individual and group level and three super-ordinate themes, and nine sub-ordinate themes emerged. The superordinate themes were: 'Powerlessness' ('Entrapment', 'Internalised Negativity' and 'Abused by my Environment'), 'Mitigation' ('Releasing my Overwhelming Emotions', 'Connecting to my Pain' and 'Addicted to Self-harm') and 'Self-harm is Wrong' ('It must be Hidden', 'What have I done to myself?' & 'My Self-harm is Sinful'). The analyses revealed novel insights on the impact and importance of some South-Asian cultural values and beliefs on the experience of self-harm in South-Asian women. This paper will focus on the third superordinate theme and related sub themes, that of 'Self-harm is Wrong'.

Studies carried out on self-harm in the UK have consistently reported a higher level of self-harm among women with South Asian heritage resident in the UK when age-compared with other British women. The reasons for this variation are many including but not limited exclusively to family environment and gender role expectations. These studies have also shown that these women are also least likely to seek psychological support from mental health professionals again with a number of explanations including stigma against help-seeking, notions of shame and other culture-specific factors. However, previous studies have clustered this large group together based on geographical heritage, regardless of the differences between religious and heritage groups and have reported on all types of self-harming behaviours as similar and predominantly carried out quantitative studies which while providing important statistical data have not always looked at the meaning of this experience for the participants. This paper presents a review of the relevant literature within the area of self-harm among Bangladeshi, Indian, and Pakistani women living in the UK. It is noteworthy that many studies discussed are dated, this appears to reflect an apparent lack of recent interest in the topic.

This study investigated self-harming behaviours among UK-based women of Bangladeshi, Indian and Pakistani origin (UKBIP). Through purposive sampling, eight participants who had engaged in self-harm, specifically through cutting, were selected for semi-structured interviews. The qualitative data gathered from these interviews underwent analysis using interpretative phenomenological analysis (IPA), which involved analysis at individual and group levels. Consequently, three super-ordinate themes and nine sub-ordinate themes emerged. The themes were 'Powerlessness' ('Entrapment', 'Internalised Negativity' and 'Abused by my Environment'), 'Mitigation' ('Releasing my Overwhelming Emotions', 'Connecting to my Pain' and 'Addicted to Self-harm') and 'Self-harm is Wrong' ('It must be Hidden', 'What have I done to Myself?', and 'My Self-harm is Sinful'). This paper focuses specifically on the 'Powerless' theme, exploring its relevance to self-harming behaviours in UKBIP women. The analyses provided novel insights into the impact and significance of the South-Asian cultural values and beliefs on the relevance to self-harming experiences in UKBIP women.

The self-face advantage (SFA) is reflected through a faster recognition of a self-face compared with familiar and unfamiliar faces. Nevertheless, as Westerners and East Asians tend to present differences in self-concept styles, it is possible that the SFA is modulated by culture. The present study explored this possibility using a visual search task. British Caucasians and Malaysian Chinese participants were asked to search for frontal view images of self, friend, and unfamiliar faces among an array of unfamiliar faces. Regardless of race, participants were more accurate and faster in searching for the own face and friend's face compared with an unfamiliar face, with no differences in the search between the own and friend's face, and these findings could not be accounted by the cultural differences in self-concept (i.e., operationalised by scores from the Independent and Interdependent Self-Concept Scale and the Horizontal and Vertical Individualism and Collectivism Scale). Altogether our results suggest that culture does not modulate the SFA and that this effect is better explained by a familiar face advantage.

Infectious disease outbreaks have historically been associated with stigmatisation towards minority groups, specifically those associated with the geographical region that the disease was first identified. We aimed to investigate how the emerging COVID-19 pandemic was experienced by UK-resident individuals of Chinese ethnicity: how their perceived cultural and ethnic identity influenced their experiences, and how early insights into the pandemic in China influenced attitudes and behaviours. We undertook in-depth semi-structured interviews with individuals who self-identified as UK-Chinese. Participants were recruited from three cities in the UK. Interviews were undertaken over the telephone between 9th April 2020 and 16th July 2020. Interviews were digitally recorded and transcribed verbatim. Transcripts were coded using NVivo software and analysed using inductive thematic analysis. Sixteen individuals were interviewed. Three main themes were identified: (1) Attribution of stigma, (2) Pandemic legacies, and (3) Individual versus societal responses. These reflected six sub-themes: (1) Stigmatisation through (mis)identity, (2) Markers of pandemic awareness, (3) Legacies of previous pandemics, (4) Ascription of blame, (5) Extent of freedom, and (6) Implicit faith in government. Experiences of xenophobia included accounts of physical violence. UK-Chinese individuals experienced and perceived widespread xenophobia, in the context of media representations that ascribed blame and exacerbated stigmatisation. Prior experience of respiratory epidemics, and insight into the governmental and societal response in China, contributed to the early adoption of face masks. This in turn marked UK-Chinese individuals as targets for abuse. Awareness is needed to safeguard stigmatized groups from social and economic harm in future infectious disease pandemics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Al-Talib et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access., (© 2022. The Author(s).)

Background: Individuals of South Asian ancestry represent 23% of the global population, corresponding to 1.8 billion people, and have substantially higher risk of atherosclerotic cardiovascular disease compared with most other ethnicities. US practice guidelines now recognize South Asian ancestry as an important risk-enhancing factor. The magnitude of enhanced risk within the context of contemporary clinical care, the extent to which it is captured by existing risk estimators, and its potential mechanisms warrant additional study., Methods: Within the UK Biobank prospective cohort study, 8124 middle-aged participants of South Asian ancestry and 449 349 participants of European ancestry who were free of atherosclerotic cardiovascular disease at the time of enrollment were examined. The relationship of ancestry to risk of incident atherosclerotic cardiovascular disease-defined as myocardial infarction, coronary revascularization, or ischemic stroke-was assessed with Cox proportional hazards regression, along with examination of a broad range of clinical, anthropometric, and lifestyle mediators., Results: The mean age at study enrollment was 57 years, and 202 405 (44%) were male. Over a median follow-up of 11 years, 554 of 8124 (6.8%) individuals of South Asian ancestry experienced an atherosclerotic cardiovascular disease event compared with 19 756 of 449 349 (4.4%) individuals of European ancestry, corresponding to an adjusted hazard ratio of 2.03 (95% CI, 1.86-2.22; P <0.001). This higher relative risk was largely consistent across a range of age, sex, and clinical subgroups. Despite the >2-fold higher observed risk, the predicted 10-year risk of cardiovascular disease according to the American Heart Association/American College of Cardiology Pooled Cohort equations and QRISK3 equations was nearly identical for individuals of South Asian and European ancestry. Adjustment for a broad range of clinical, anthropometric, and lifestyle risk factors led to only modest attenuation of the observed hazard ratio to 1.45 (95% CI, 1.28-1.65, P <0.001). Assessment of variance explained by 18 candidate risk factors suggested greater importance of hypertension, diabetes, and central adiposity in South Asian individuals., Conclusions: Within a large prospective study, South Asian individuals had substantially higher risk of atherosclerotic cardiovascular disease compared with individuals of European ancestry, and this risk was not captured by the Pooled Cohort Equations.

The ability to identify segments of genomes identical-by-descent (IBD) is a part of standard workflows in both statistical and population genetics. However, traditional methods for finding local IBD across all pairs of individuals scale poorly leading to a lack of adoption in very large-scale datasets. Here, we present iLASH, an algorithm based on similarity detection techniques that shows equal or improved accuracy in simulations compared to current leading methods and speeds up analysis by several orders of magnitude on genomic datasets, making IBD estimation tractable for millions of individuals. We apply iLASH to the PAGE dataset of ~52,000 multi-ethnic participants, including several founder populations with elevated IBD sharing, identifying IBD segments in ~3 minutes per chromosome compared to over 6 days for a state-of-the-art algorithm. iLASH enables efficient analysis of very large-scale datasets, as we demonstrate by computing IBD across the UK Biobank (~500,000 individuals), detecting 12.9 billion pairwise connections.

Introduction: The majority of combat deaths occur before arrival at a medical treatment facility but no previous studies have comprehensively examined this phase of care., Methods: The UK Joint Theatre Trauma Registry was used to identify all UK military personnel who died in Afghanistan (2004-2014). These data were linked to non-medical tactical and operational records to provide an accurate timeline of events. Cause of death was determined from records taken at postmortem review. The primary objective was to report time between injury and death in those killed in action (KIA); secondary objectives included: reporting mortality at key North Atlantic Treaty Organisation timelines (0, 10, 60, 120 min), comparison of temporal lethality for different anatomical injuries and analysing trends in the case fatality rate (CFR)., Results: 2413 UK personnel were injured in Afghanistan from 2004 to 2014; 448 died, with a CFR of 18.6%. 390 (87.1%) of these died prehospital (n=348 KIA, n=42 killed non-enemy action). Complete data were available for n=303 (87.1%) KIA: median Injury Severity Score 75.0 (IQR 55.5-75.0). The predominant mechanisms were improvised explosive device (n=166, 54.8%) and gunshot wound (n=96, 31.7%).In the KIA cohort, the median time to death was 0.0 (IQR 0.0-21.8) min; 173 (57.1%) died immediately (0 min). At 10, 60 and 120 min post injury, 205 (67.7%), 277 (91.4%) and 300 (99.0%) casualties were dead, respectively. Whole body primary injury had the fastest mortality. Overall prehospital CFR improved throughout the period while in-hospital CFR remained constant., Conclusion: Over two-thirds of KIA deaths occurred within 10 min of injury. Improvement in the CFR in Afghanistan was predominantly in the prehospital phase., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenile-onset SLE (jSLE), when compared to individuals with adult-onset SLE, develop more severe organ involvement, increased disease activity and greater tissue and organ damage. In adult-onset SLE, clinical characteristics, pathomechanisms, disease progression and outcomes do not only vary between individuals and age groups, but also ethnicities. However, in children and young people, the influence of ethnicity on disease onset, phenotype and outcome has not been investigated in detail. In this study, we investigated clinical and laboratory characteristics in pediatric SLE patients from different ethnic backgrounds (White Caucasian, Asian, Black African/Caribbean) accessing data from a national cohort of jSLE patients (the UK JSLE Cohort Study). Among jSLE patients in the UK, ethnicity affects both the disease's clinical course and outcomes. At diagnosis, Black African/Caribbean jSLE patients show more "classical" laboratory and clinical features when compared to White Caucasian or Asian patients. Black African/Caribbean jSLE patients exhibit more renal involvement and more frequently receive cyclophosphamide and rituximab. Studies targeting ethnicity-specific contributors to disease expression and phenotypes are necessary to improve our pathophysiological understanding, diagnosis and treatment of jSLE.

Background: Many patients at the end of life require analgesia to relieve pain. Additionally, up to 1/5 of patients in the UK receive sedation for refractory symptoms at the end of life. The use of sedation in end-of-life care (EOLC) remains controversial. While gradual sedation to alleviate intractable suffering is generally accepted, there is more opposition towards deliberate and rapid sedation to unconsciousness (so-called "terminal anaesthesia", TA). However, the general public's views about sedation in EOLC are not known. We sought to investigate the general public's views to inform policy and practice in the UK., Methods: We performed two anonymous online surveys of members of the UK public, sampled to be representative for key demographic characteristics (n = 509). Participants were given a scenario of a hypothetical terminally ill patient with one week of life left. We sought views on the acceptability of providing titrated analgesia, gradual sedation, terminal anaesthesia, and euthanasia. We asked participants about the intentions of doctors, what risks of sedation would be acceptable, and the equivalence of terminal anaesthesia and euthanasia., Findings: Of the 509 total participants, 84% and 72% indicated that it is permissible to offer titrated analgesia and gradual sedation (respectively); 75% believed it is ethical to offer TA. Eighty-eight percent of participants indicated that they would like to have the option of TA available in their EOLC (compared with 79% for euthanasia); 64% indicated that they would potentially wish for TA at the end of life (52% for euthanasia). Two-thirds indicated that doctors should be allowed to make a dying patient completely unconscious. More than 50% of participants believed that TA and euthanasia were non-equivalent; a third believed they were., Interpretation: These novel findings demonstrate substantial support from the UK general public for the use of sedation and TA in EOLC. More discussion is needed about the range of options that should be offered for dying patients., Competing Interests: No competing interests to declare.

Background: Ethnic phenotypic differences in Parkinson's disease (PD) are important to understand the heterogeneity of PD and develop biomarkers and clinical trials., Objective: To investigate (i) whether there are non-motor symptoms (NMS)- and comorbidity-based phenotypic differences between Black, Asian and Minority Ethnic (BAME) and White PD patients and (ii) whether clinically available biomarkers may help differentiate and explain the differences between the groups., Methods: This is a multicentre (four sites, London), real-life, cross-sectional study including PD patients of BAME or White ethnicity. The primary outcome was a detailed NMS assessment; additional measurements included disease and motor stage, comorbidity, sociodemographic parameters and brain MRI imaging., Results: 271 PD patients (54 Asian, 71 Black, and 146 White) were included balanced for age, gender, and disease severity (HY). Black patients had a shorter disease duration compared to White and Asian populations. The SCOPA-Motor activities of daily living scores as well as the NMSS scores were significantly higher in both Black (total score and domain "miscellaneous") and Asian (total score and domains "sleep/fatigue", "mood/apathy" and "perception/hallucinations") than White individuals. Both BAME populations had higher prevalence of arterial hypertension, and the Black population had a higher prevalence of diabetes mellitus. Brain MRI revealed a greater severity of white matter changes in Black compared to the White and Asian cohorts., Conclusion: These findings suggest differences in phenotype of PD in BAME populations with greater burden of NMS and motor disability and a higher rate of cardiovascular comorbidities.

Background and Objectives: GSK2982772 is an oral small-molecule RIPK1 inhibitor with potential therapeutic efficacy in immune-mediated inflammatory diseases (IMIDs). An inter-ethnic comparison of GSK2982772 pharmacokinetics was conducted based on data from Western (Study 1) and Japanese subjects (Study 2)., Methods: Both studies were single-centre, randomised, double-blind, placebo-controlled studies with objectives to assess the safety and characterise the pharmacokinetics of GSK2982772. Western subjects in Study 1 (NCT03305419), Part A (N = 15), were randomly assigned to receive 120 mg three times daily (TID), 240 mg TID, or 360 mg twice daily (BID) doses of GSK2982772, or placebo (TID or BID) for 1 day. Part B subjects (N = 47) received GSK2982772 120 mg TID, 240 mg TID, or placebo TID for 14 days. Japanese subjects in Study 2 (N = 13) (NCT03590613) were randomly assigned to receive TID doses of GSK2982772 60, 120, 240 mg TID or placebo TID for 1 day., Results: GSK2982772 was well tolerated and adverse events were generally mild. Maximum observed plasma drug concentration (C max ), time to reach C max (T max ), area under the plasma drug concentration versus time curve after the first GSK2982772 dose (AUC (0-7) ) of 120 and 240 mg, and (AUC (0-24) ) values for the 120 and 240 mg TID doses over a single day were similar in Japanese and Western subjects., Conclusions: The pharmacokinetics and tolerability of GSK2982772 were similar between Western and Japanese subjects, justifying inclusion of Japanese subjects in future global clinical studies to assess the therapeutic potential of RIPK1 inhibition for the treatment of IMIDs. Clinical Trials: NCT03305419 and NCT03590613 available from http://www.clinicaltrials.gov .

Many Western industrialized nations have high levels of ethnic diversity but to date there are very few studies which investigate prelinguistic and early language development in infants from ethnic minority backgrounds. This study tracked the development of infant communicative gestures from 10 to 12 months (n = 59) in three culturally distinct groups in the United Kingdom and measured their relationship, along with maternal utterance frequency and responsiveness, to vocabulary development at 12 and 18 months. No significant differences were found in infant gesture development and maternal responsiveness across the groups, but relationships were identified between gesture, maternal responsiveness, and vocabulary development., (© 2020 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Genome-wide association studies (GWAS) have identified many genetic risk variants for cancers. The utility of these variants in assessing risk of esophageal, gastric and endometrial cancers, as well as melanoma, glioma, diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphoid leukemia and multiple myeloma, has not been adequately investigated. We constructed a site-specific polygenic risk score (PRS) for each of these nine cancers using their GWAS-identified risk variants. Using data from 400 807 participants of European descent in the UK Biobank, a population-based cohort study, we estimated the hazard ratios of each cancer associated with its PRS using Cox proportional hazard models. During a median follow-up of 5.8 years, 3905 incident cases of these nine cancers were identified in the cohort. The area under the receiver operating characteristic curve ranged from 0.53 to 0.69 for these cancers. Except for esophageal cancer, significant dose-response associations were observed between PRS and cancer risk. Compared to individuals in the middle quintile (40%-60%) at an average risk, those among the highest 5% of the PRS had a twofold elevated risk of melanoma, glioma, follicular lymphoma or multiple myeloma, and a fourfold elevated risk of chronic lymphoid leukemia. Using PRS, 63.0% of the participants could be classified as having an over twofold elevated risk for at least one cancer. The PRS derived using risk variants identified to date by GWAS showed the potential in identifying individuals at a significantly elevated risk of cancer for prevention., (© 2020 UICC.)

Autosomal recessive retinitis pigmentosa is caused by mutations in over 40 genes, one of which is the ceramide kinase-like gene ( CERKL ). We present a case series of six patients from six unrelated families diagnosed with inherited retinal dystrophies (IRD) and with two variants in CERKL recruited from a multi-ethnic British population. A retrospective review of clinical data in these patients was performed and included colour fundus photography, fundus autofluorescence (AF) imaging, spectral domain-optical coherence tomography (SD-OCT), visual fields and electroretinogram (ERG) assessment where available. Three female and three male patients were included. Age at onset ranged from 7 years old to 45 years, with three presenting in their 20s and two presenting in their 40s. All but one had central visual loss as one of their main presenting symptoms. Four patients had features of retinitis pigmentosa with significant variation in severity and extent of disease, and two patients had no pigment deposition with only macular involvement clinically. Seven variants in CERKL were identified, of which three are novel. The inherited retinopathies associated with the CERKL gene vary in age at presentation and in degree of severity, but generally are characterised by a central visual impairment early on.

UK Exercise SAIF SAREEA 3 saw components of first Armoured Infantry Brigade conduct kinetic armoured infantry manoeuvres in Oman in temperatures that at times exceeded 50°C. This paper presents the methods of acclimatisation, recreational physical training in the heat, and reacclimatisation training conducted in theatre during this exercise. In order to reduce the risk of heat illness, individuals underwent either validated heat acclimatisation training in accordance with current policy, or adapted training as dictated by musculoskeletal restrictions or job specification. Direction was issued regarding recreational training. There was a theatre medical consensus agreed for the practice of returning soldiers to the exercise after admission to a medical treatment facility due to the effects of heat and data were collated on all LAND (Army) acclimatisation and heat illness presentations. The rates of climatic effect were much lower than expected in the medical estimate based on Exercise SAIF SAREEA 2 and similar exercises. Only five LAND patients fulfilled the in-theatre case definition of exertional heat illness of a deployed LAND forces population at risk of 2550. Zero patients who were returned to the exercise after symptoms associated with climatic exposure were subsequently readmitted with heat illness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

As the Queen Alexandra's Royal Army Nursing Corps celebrates its 70th Anniversary, army nursing continues to advance patient care delivery to new levels. Advanced level nursing practice has moved from the relatively 'calm' confines of the NHS to the austere desert of Oman. This article will provide a personal account of the first deployment of a military nurse practitioner since it was formally introduced in 2012 to frontline medicine, leading an armoured prehospital treatment team., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The prehospital treatment team (PHTT) involves a small team working under the clinical supervision of a clinical lead. The clinical lead can be a general duties medical officer (Post Foundation Years Doctor), military nurse practitioner or more senior clinician. The team is mounted in vehicles appropriate to the environment they expect to operate in. A PHTT is closely located to the front line reducing transportation timelines from the point of wounding to more definitive care. The PHTT can provide medical support on the move or when time is available; a more permanent fully erected treatment facility can be established. Either configuration can provide both trauma and primary care. The size of the team allows for multiple trauma subteams enabling care to casualties that arrive simultaneously. The PHTT can move independently which could leave the team vulnerable as there is no integral force protection within the current structure. In such a small team, the right balance of medical and soldiering skills among team members is essential to success. Exercise SAIF SAREEA 3 represented a large-scale battlegroup exercise to the Middle East in the austere desert of Oman. This provided an ideal environment for employing the PHTT concept is a large deployed force undertaking dynamic activity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Ex SAIF SAREEA 3 was a joint British-Omani military exercise involving approximately 5500 British personnel deployed to Oman over a 6-month period. Role 1 medical care was provided by medical treatment facilities (MTFs) deployed with medical equipment as per the UK 300 medical module., Method: Retrospective analysis was undertaken of prospectively collected equipment usage data from two Role 1 MTFs in Duqm (MTF 1) and Muaskar Al Murtafa (MTF 2) camps over a period of 6-8 weeks. Data were analysed alongside routinely collected epidemiological data (EPINATO) during the deployment. Equipment used in addition to the module was also recorded., Results: MTF 1 used 50 out of the 179 different items from the module over the 8-week period. MTF 2 used 45 out of the 179 different items from their module over the 6-week period. The most commonly used items across the sites were non-sterile examination gloves, plastic aprons, tympanic thermometer probe covers, disinfectant wipes and self-adhesive plasters. Extramodular items (blunt fill needle, water pump sprayer, Jelonet gauze and stool specimen pot) accounted for 5% of all equipment used in MTF 1., Conclusion: The study showed that the 300 module accommodates 95% of Role 1 patients' needs but highlights the requirement for dedicated equipment for the treatment of heat casualties if deemed likely and blunt fill/filter needles for the administration of parenteral medication. Commanders must perform a thorough medical estimate and risk assessment prior to deployment to ensure that the 300 medical module is likely to provide the necessary equipment and supplement the module if required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This paper presents the burden of mental health cases throughout UK military exercise SAIF SAREEA 3 (SS3), a low-tempo armoured brigade exercise in Oman from June to November 2018, and aims to discuss ways that mental health may be better managed on future large exercises., Methods: A retrospective review of all attendances at army medical facilities and relevant computerised medical records was undertaken., Results: 14 mental health cases were identified, which required 51 follow-up presentations throughout the duration of SS3. This represented 1.2% of all first patient presentations, and 6.3% of all follow-up work. 64% had diagnoses which predated deployment and could all be classified within 10th revision of International Statistical Classification of Diseases and Related Health Problems as either F30-F39 mood (affective) disorders, or F40-F48 neurotic, stress-related and somatoform disorders; all new diagnoses made while deployed were adjustment disorders. The medical officer spent an average of 147 min total clinical care time per patient. Six patients were aeromedically evacuated (AE), which represented 26% of all AE cases from SS3., Conclusions: Presentations were low, but time consuming and with poor disposal outcomes. Most conditions predated the exercise, and could have been predicted to worsen through the deployment. Given the disproportionate burden that mental health cases afforded during SS3, future brigade-sized deployments should include deployed mental health professionals in order to offer evidence-based therapy which should lead to improved disposal outcomes and a reduced AE burden., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Coronavirus disease caused by the novel coronavirus Covid-19 is a current worldwide outbreak. The use of quarantine and isolation proved effective in containing the spread of infection., Objectives: The purpose of this cross-sectional study was to assess the mental health of Albanian people residing in the country and abroad during the quarantine period for the Covid-19 pandemic., Design: This study was carried out from 25th March - 20th April 2020 through a web survey shared on social networks. The goal was to reach at least the minimum sample size for cross-sectional studies. The Patient Health Questionnaire (PHQ-9) was used to assess mental health. Chi-square (χ 2 ) and Fisher -Exact test were used to assess the statistical significance among variables. P values ≤0.05 were considered statistically significant., Results: 715 participants were included in the final analyses (78.41% females and 21.53% males). Most were residents in Albania (80.41%) and the others resided mainly in Italy (6.89%), Greece (3.51%), Germany (2.43%), Kosovo (1.62%) and the UK (1.69%). Statistical association was found between gender, country of residency and measures taken. Summary score of PHQ-9 items was 6.4662. The total score of depression classification shows that 31.82% and 12.90% of participants have respectively mild and moderate depression. Female participants showed the highest score for some items of PHQ-9, p≤0.05., Conclusions: Findings suggest that health care professionals should recognize and address mental health problems associated with Covid-19 especially in vulnerable groups. Acting in a timely and proper manner is essential in preventing these problems from becoming chronic., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Disease non-battle injury has plagued British expeditionary forces through the ages. While in recent years significant mortality has reduced, it has had a large impact on operational effectiveness, at times leading to closure of major medical treatment facilities (MTFs).Infection Prevention and Control (IPC) benefits from a subject matter expert and champion to ensure it remains at the front of people's minds and to be on hand to manage acute and dynamic situations. To mitigate the lack of an IPC Nursing Officer, we piloted a deployed military IPC Lead Link Practitioner (IPC-LL) for the first time on a large-scale overseas exercise (SAIF SAREEA 3). An experienced generalist nurse deploying as the IPC-LL (after specific training) provided pre-deployment IPC education and preparation, deployed IPC advice, undertook mandatory audits and monitored IPC compliance throughout the MTFs on the exercise. Data from 22 IPC audits conducted on the exercise showed that the presence of the IPC-LL improved IPC compliance and standards overall in the MTF where based, compared with others. In addition, a gastroenteritis outbreak occurred and was successfully managed with significant input from the IPC-LL. The IPC-LL was also able to add value by pre-empting potential IPC problems from occurring.There is a small pool of deployable Infection Prevention and Control Nursing Officers, so this new IPC-LL role could help to fill the capability gap. The IPC-LL could be the dedicated person focusing on IPC elements, reducing the IPC risk within the deployed field hospital setting where deployed experts are not available., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Epidemiological data captured from military exercises and operations can highlight treatment requirements specific to operating in certain environmental conditions. Such data is invaluable to enable accurate planning for future exercises. Epidemiological data were collected during Exercise SAIF SAREEA 3 (SS3) to provide an insight into medical provision requirements for low-tempo military operations in hot, desert climates., Method: Epidemiological data was collected from all consultations conducted during the exercise within the LAND Medical Reception Station, 24 August-14 November 2018, using Epi-NATO surveillance systems., Results: Of the 1414 total consultations recorded, 759 were first presentations and 665 were follow-up consultations, with 35 referrals made to hospitals. 1348 days of limited duties were given and 258 working days were lost. The most common coding reported for consultations were ' non-battle non-sport related injuries' , ' sport related injuries' and ' dermatological'. DISCUSSION: The data highlight the most common cause of injuries and the role of assets such as dental, sexual and mental health services for future deployments. A number of explanations are considered in relation to the patterns identified and the effect on future planning for working in hot climates. Furthermore, Exercise SS3 had reduced numbers of personnel requiring deployed Role 2 or host nation hospital services, which again raises further considerations for future deployments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Previous long-term memory (LTM) research found that angry faces were more poorly recognised when encoded with averted vs. direct gaze, while memory for happy faces was unaffected by gaze. Contrastingly, working memory (WM) accuracy for angry faces was unaffected by gaze, but WM was enhanced for happy faces with averted vs. direct gaze. Because the LTM study was conducted in an Eastern culture (Japan) with Japanese faces, while the WM study was conducted in a Western culture (UK) with Caucasian faces, here we investigated WM further to examine whether gaze effects diverge due to cultural variation between the faces and participants. When Western participants viewed Japanese faces (Experiment 1), the happy-averted gaze advantage in WM was replicated. In contrast, Japanese participants viewing Caucasian faces (Experiment 2a) showed poorer WM for angry faces with averted vs. direct gaze, and no influence of gaze on WM for happy faces. When Japanese participants viewed Japanese faces (Experiment 2b), gaze did not modulate WM. Therefore, the way in which expression and gaze interact to influence face WM does not appear to rely on the specific memory system engaged, but instead may be attributed to cultural differences in display rules between Eastern and Western cultures.

Inflammatory bowel disease (IBD) is an established risk factor for colorectal cancer. Recent reports suggesting IBD is also a risk factor for prostate cancer (PC) require further investigation. We studied 218 084 men in the population-based UK Biobank cohort, aged 40 to 69 at study entry between 2006 and 2010, with follow-up through mid-2015. We assessed the association between IBD and subsequent PC using multivariable Cox regression analyses, adjusting for age at assessment, ethnic group, UK region, smoking status, alcohol drinking frequency, body mass index, Townsend Deprivation Index, family history of PC and previous prostate-specific antigen testing. Mean age at study entry was 56 years, 94% of the men were white, and 1.1% (n = 2311) had a diagnosis of IBD. After a median follow-up of 78 months, men with IBD had an increased risk of PC (adjusted hazard ratio [aHR] = 1.31, 95% confidence interval [CI] = 1.03-1.67, P = .029). The association with PC was only among men with the ulcerative colitis (UC; aHR = 1.47, 95% CI = 1.11-1.95, P = .0070), and not Crohn's disease (aHR 1.06, 95% CI = 0.63-1.80, P = .82). Results are limited by lack of data on frequency of health care interactions. In a large-scale, prospective cohort study, we detected an association between IBD, and UC specifically, with incident PC diagnosis., (© 2020 UICC.)

To determine if metabolic characteristics differed in women with and without polycystic ovary syndrome (PCOS) between a Caucasian and Middle East population. Comparative cross-sectional analysis. Demographic and metabolic data from Middle Eastern women from Qatar Biobank (97 with PCOS, 622 controls) were compared to a Caucasian PCOS biobank in Hull UK (108 with PCOS, 69 controls). In both populations, PCOS women showed a worse cardiovascular risk profile of increased systolic and diastolic blood pressure, increased C-reactive protein (CRP), reduced HDL, insulin resistance as well as increased androgens compared to their respective controls without PCOS. UK women without PCOS had higher systolic and diastolic blood pressures, and increased testosterone results (p < 0.01) compared to Middle Eastern women without PCOS who had higher inflammatory markers (WBC and CRP), HDL and insulin resistance (p < 0.001). UK PCOS women had a higher body mass index, systolic and diastolic blood pressures, triglycerides (p < 0.01), whilst Middle Eastern PCOS women showed increased testosterone, free androgen index, HDL and CRP (P < 0.01). There was no difference in insulin or insulin resistance between the two PCOS cohorts. This study highlights ethnic population differences because, whilst cardiovascular risk indices were increased for both PCOS cohorts, this may be for different reasons: BMI, waist and hip measurements, systolic and diastolic blood pressure, and triglycerides were higher in the UK cohort whilst testosterone, HDL and CRP were higher in the Middle East population. Insulin resistance did not differ between the two PCOS populations despite differences in BMI.

The "positivity effect" (PE) reflects an age-related increase in the preference for positive over negative information in attention and memory. The present experiment investigated whether Chinese and UK participants produce a similar PE. In one experiment, we presented pleasant, unpleasant, and neutral pictures simultaneously and participants decided which picture they liked or disliked on a third of trials, respectively. We recorded participants' eye movements during this task and compared time looking at, and memory for, pictures. The results suggest that older but not younger adults from both China and UK participant groups showed a preference to focus on and remember pleasant pictures, providing evidence of a PE in both cultures. Bayes Factor analysis supported these observations. These findings are consistent with the view that older people preferentially focus on positive emotional information, and that this effect is observed cross-culturally.

Background: In the UK, Gypsy, Roma and Traveller (GRT) communities are generally considered to be at risk of low or variable immunisation uptake. Many strategies to increase uptake for the general population are relevant for GRT communities, however additional approaches may also be required, and importantly one cannot assume that "one size fits all". Robust methods are needed to identify content and methods of delivery that are likely to be acceptable, feasible, effective and cost effective. In this paper, we describe the approach taken to identify potential interventions to increase uptake of immunisations in six GRT communities in four UK cities; and present the list of prioritised interventions that emerged., Methods: This work was conducted in three stages: (1) a modified intervention mapping process to identify ideas for potential interventions; (2) a two-step prioritisation activity at workshops with 51 GRTs and 25 Service Providers to agree a prioritised list of potentially feasible and acceptable interventions for each community; (3) cross-community synthesis to produce a final list of interventions. The theoretical framework underpinning the study was the Social Ecological Model., Results: Five priority interventions were agreed across communities and Service Providers to improve the uptake of immunisation amongst GRTs who are housed or settled on an authorised site. These interventions are all at the Institutional (e.g. cultural competence training) and Policy (e.g. protected funding) levels of the Social Ecological Model., Conclusions: The "upstream" nature of the five interventions reinforces the key role of GP practices, frontline workers and wider NHS systems on improving immunisation uptake. All five interventions have potentially broader applicability than GRTs. We believe that their impact would be enhanced if delivered as a combined package. The robust intervention development and co-production methods described could usefully be applied to other communities where poor uptake of immunisation is a concern., Study Registration: Current Controlled Trials ISRCTN20019630, Date of registration 01-08-2013, Prospectively registered.

We aimed to assess if the same cognitive batteries can be used cross-nationally to monitor the effect of Phenylketonuria (PKU). We assessed whether a battery, previously used with English adults with PKU (AwPKU), was also sensitive to impairments in Italian AwPKU. From our original battery, we selected a number of tasks that comprehensively assessed visual attention, visuo-motor coordination, executive functions (particularly, reasoning, planning, and monitoring), sustained attention, and verbal and visual memory and learning. When verbal stimuli/or responses were involved, stimuli were closely matched between the two languages for psycholinguistic variables. We administered the tasks to 19 Italian AwPKU and 19 Italian matched controls and compared results from with 19 English AwPKU and 19 English matched controls selected from a previously tested cohort. Participant election was blind to cognitive performance and metabolic control, but participants were closely matched for age and education. The Italian AwPKU group had slightly worse metabolic control but showed levels of performance and patterns of impairment similar to the English AwPKU group. The Italian results also showed extensive correlations between adult cognitive measures and metabolic measures across the life span, both in terms of Phenylalanine (Phe) levels and Phe fluctuations, replicating previous results in English. These results suggest that batteries with the same and/or matched tasks can be used to assess cognitive outcomes across countries allowing results to be compared and accrued. Future studies should explore potential differences in metabolic control across countries to understand what variables make metabolic control easier to achieve.

Objectives: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016., Methods: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time-updated CD4 cell count and HIV RNA measurements., Results: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m 2 , and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was -2.08 [95% confidence interval (CI) -2.24, -1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m 2 /year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m 2 /year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001)., Conclusions: Significant improvement in eGFR slope was observed in patients who switched from TDF- to TAF-containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF., (© 2020 British HIV Association.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Objectives: The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL)., Methods: A cross-sectional analysis was carried out of baseline data from the three groups ["older" people with HIV infection (PWH) aged ≥ 50 years, "younger" PWH aged < 50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) > 30 kg/m 2 ., Results: A total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status., Conclusions: Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined., (© 2020 British HIV Association.)

This article outlines the mental health burden of COVID-19 in the United Kingdom population, and presents preliminary evidence of less common psychiatric issues, such as paranoia and hallucinations, to which vulnerable groups in the U.K. population may be more vulnerable. It is argued that cognitive-behavioral therapy, with components of mindfulness, should be part of the therapeutic response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD., Methods: We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans., Results: We identified 3 new loci on chromosome 1q21 ( CTSS ), 10q26 ( WDR11-FGFR2 ), and 11q22 ( RDX - FDX1 ). Quantitative trait locus analyses suggested the association of CTSS and RDX - FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans., Conclusions: We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.

Principal component analysis (PCA) is a key tool for understanding population structure and controlling for population stratification in genome-wide association studies (GWAS). With the advent of large-scale datasets of genetic variation, there is a need for methods that can compute principal components (PCs) with scalable computational and memory requirements. We present ProPCA, a highly scalable method based on a probabilistic generative model, which computes the top PCs on genetic variation data efficiently. We applied ProPCA to compute the top five PCs on genotype data from the UK Biobank, consisting of 488,363 individuals and 146,671 SNPs, in about thirty minutes. To illustrate the utility of computing PCs in large samples, we leveraged the population structure inferred by ProPCA within White British individuals in the UK Biobank to identify several novel genome-wide signals of recent putative selection including missense mutations in RPGRIP1L and TLR4., Competing Interests: The authors have declared that no competing interests exist.