White European Origin Research Articles

The Shelf Life of Skulls: Anthropology and 'race' in the Vrolik Craniological Collection.

The Vrolik ethnographical collection consisted of roughly 300 skulls, mummified heads, skeletons, pelvises, wet-preserved preparations, and plaster models, collected by Gerard Vrolik (1775-1859) and his son Willem (1801-1863). Most prominent in this collection were the skulls, of which 177 remain in the collection of present-day Museum Vrolik. These skulls-a troubling heritage of colonialism and scientific racism-are the central subjects of this paper, which considers the changing meanings and values of these skulls for racial science over approximately 160years, between ± 1800 and 1960. These shifting meanings are analysed using the skulls themselves as primary sources, including the labels, numbers and handwriting present on them or their stands. Central topics addressed will be matters of classification, hierarchy, scientific bias, and disciplinary development of racial anthropology from the study and collection of idealized national types to a quantitative craniometry of populations. This paper demonstrates that during 160years of study of this same set of crania, the skulls of white European origin gradually lost racial relevance and were increasingly normalized, whereas the skulls of dark-skinnedpeople of African descent continued to be categorized in a typological racial scheme and as such were increasingly othered.

Is Anisakis simplex a Trigger for Anaphylactic Reactions in Hereditary Alpha-Tryptasemia?

The prevalence of fish, seafood and Anisakis allergy varies greatly depending on country-specific eating habits, assuming that the highest consumption corresponds to the highest prevalence. Mediterranean countries are particularly affected. Hereditary Alpha-Tryptasemia (HaT) is a common autosomal dominant genetic trait recently identified. Although it is estimated to affect approximately 1 in 20 individuals of white European origin, a diagnostic method is not routinely available. Here by we present the cases of two families with different allergic reaction phenotypes to fish and seafood, IgE and no IgE mediated reactions. The current review focused on the impact of the diagnosis of HaT in families, particularly when the mutation is symptomatic and the affectation from an early age and in both sexes and finally this review tried to warn about the possible involvement of Anisakis in allergic reactions in patients with HaT.

Breast cancer polygenic risk scores derived in White European populations are not calibrated for women of Ashkenazi Jewish descent

PurposePolygenic risk scores (PRSs) are a major component of accurate breast cancer (BC) risk prediction but require ethnicity-specific calibration. Ashkenazi Jewish (AJ) population is assumed to be of White European (WE) origin in some commercially available PRSs despite differing effect allele frequencies (EAFs). We conducted a case-control study of WE and AJ women from the Predicting Risk of Cancer at Screening Study. The Breast Cancer in Northern Israel Study provided a separate AJ population–based case-control validation series. MethodsAll women underwent Illumina OncoArray single-nucleotide variation (SNV; formerly single-nucleotide polymorphism [SNP]) analysis. Two PRSs were assessed, SNV142 and SNV78. A total of 221 of 2243 WE women (discovery: cases = 111; controls = 110; validation: cases = 651; controls = 1772) and 221 AJ women (cases = 121; controls = 110) were included from the UK study; the Israeli series consisted of 2045 AJ women (cases = 1331; controls = 714). EAFs were obtained from the Genome Aggregation Database. ResultsIn the UK study, the mean SNV142 PRS demonstrated good calibration and discrimination in WE population, with mean PRS of 1.33 (95% CI 1.18-1.48) in cases and 1.01 (95% CI 0.89-1.13) in controls. In AJ women from Manchester, the mean PRS of 1.54 (1.38-1.70) in cases and 1.20 (1.08-1.32) in controls demonstrated good discrimination but overestimation of BC relative risk. After adjusting for EAFs for the AJ population, mean risk was corrected (mean SNV142 PRS cases = 1.30 [95% CI 1.16-1.44] and controls = 1.02 [95% CI 0.92-1.12]). This was recapitulated in the larger Israeli data set with good discrimination (area under the curve = 0.632 [95% CI 0.607-0.657] for SNV142). ConclusionAJ women should not be given BC relative risk predictions based on PRSs calibrated to EAFs from the WE population. PRSs need to be recalibrated using AJ-derived EAFs. A simple recalibration using the mean PRS adjustment ratio likely performs well.

Risk factors, ethnicity and dementia: A UK Biobank prospective cohort study of White, South Asian and Black participants.

Our knowledge of the effect of potentially modifiable risks factors on people developing dementia is mostly from European origin populations. We aimed to explore if these risk factors had similar effects in United Kingdom (UK) White, South Asian and Black UK Biobank participants recruited from 2006-2010 and followed up until 2020. We reviewed the literature to 25.09.2020 for meta-analyses identifying potentially modifiable risk factors preceding dementia diagnosis by ≥10 years. We calculated prevalence of each identified risk factor and association with dementia for participants aged ≥55 at registration in UK Biobank. We calculated hazard ratios using Cox regression for each risk factor, stratified by ethnic group, and tested for differences using interaction effects between each risk factor and ethnicity. We included education, hearing loss, hypertension, obesity, excess alcohol consumption, physical inactivity, smoking, high total cholesterol, depression, diabetes, social isolation, and air pollution as risks. Out of 294,162 participants, there were 287,806 White, 3590 South Asian and 2766 Black people, followed up for up to 14.8 years, with a total follow-up time of 3,392,095 years. During follow-up, 5,972 people (2.03%) developed dementia. Risk of dementia was higher in Black participants than White participants (HR for dementia compared to White participants as reference 1.43, 95% CI 1.16-1.77, p = 0.001) but South Asians had a similar risk. Association between each risk factor and dementia was similar in each ethnic group with no evidence to support any differences. We find that Black participants were more likely to develop dementia than White participants, but South Asians were not. Identified risk factors in White European origin participants had a similar effect in Black and South Asian origin participants. Volunteers in UK Biobank are not representative of the population and interaction effects were underpowered so further work is needed.

The importance of ethnicity: Are breast cancer polygenic risk scores ready for women who are not of White European origin?

Polygenic risk scores (PRS) for disease risk stratification show great promise for application in general populations, but most are based on data from individuals of White European origin. We assessed two well validated PRS (SNP18, SNP143) in the Predicting‐Risk‐of‐Cancer‐At‐Screening (PROCAS) study in North‐West England for breast cancer prediction based on ethnicity. Overall, 9475 women without breast cancer at study entry, including 645 who subsequently developed invasive breast cancer or ductal carcinoma in situ provided DNA. All were genotyped for SNP18 and a subset of 1868 controls were genotyped for SNP143. For White Europeans both PRS discriminated well between individuals with and without cancer. For n = 395 Black (n = 112), Asian (n = 119), mixed (n = 44) or Jewish (n = 120) women without cancer both PRS overestimated breast cancer risk, being most marked for women of Black and Jewish origin (P < .001). SNP143 resulted in a potential mean 40% breast cancer risk overestimation in the combined group of non‐White/non‐European origin. SNP‐PRS that has been normalized based on White European ethnicity for breast cancer should not be used to predict risk in women of other ethnicities. There is an urgent need to develop PRS specific for other ethnicities, in order to widen access of this technology.

Potentially Modifiable Risk Factors, Ethnicity and Dementia: A UK Biobank Prospective Cohort Study of White, South Asian and Black Participants

Background: Our knowledge of potentially modifiable risks factors for dementia are from European origin populations. We aimed to explore if these risk factors had similar effects in United Kingdom (UK) White, South Asian and Black UK Biobank participants recruited from 2006-2010 and followed up until 2020. Methods: We reviewed the literature to 25.09.2020 for meta-analyses identifying potentially modifiable risk factors preceding dementia diagnosis by ≥ 10 years. We calculated prevalence of each identified risk factor and association with dementia for participants aged ≥ 55 at registration in UK biobank. We calculated hazard ratios using Cox regression for each risk factor, stratified by ethnic group and tested for differences using interaction effects between each risk factor and ethnicity. Findings: We included education, hearing loss, hypertension, obesity, excess alcohol consumption, physical inactivity, smoking, high total cholesterol, depression, diabetes, social isolation, and air pollution as risks. Out of 294,725 participants, there were 287,806 White, 3590 South Asian and 2766 Black people, followed up for up to 14.8 years, with a total follow-up time of 3,392,095 years. During follow-up, 5,972 people developed dementia. Risk of dementia was higher in Black participants than White participants (HR 1.43, 95% CI 1.16-1.77, p=0.001) but South Asians had a similar risk. Association between each risk factor and dementia was similar in each ethnic group with no evidence of interaction effects. Interpretation: We find that Black participants were more likely to develop dementia than White participants, but South Asians were not. Identified risk factors in White European origin participants had a similar effect in Black and south Asian origin participants. Volunteers in biobank are not representative of the population and interaction effects were likely underpowered so further work is needed. Registration Details: We registered the protocol for this project online prior to data analysis (https://osf.io/d2j4z/). Funding Information: NM is funded by an Alzheimer’s Society Senior Fellowship (AS-SF-18b-001). We received no other funding for this research. Declaration of Interests: None to declare. Ethics Approval Statement: The UK Biobank received approval from the National Information Governance Board for Health and Social Care and the National Health Service North West Multicentre Research Ethics Committee. All participants provided informed consent through electronic signature at baseline assessment.

Ethnicity and Arterial Stiffness.

Early vascular aging reflects increased arterial stiffness of central blood vessels at young chronological ages and powerfully predicts cardiovascular events and mortality, independent of routine brachial blood pressure and other risk factors. Since ethnic disparities exist in routine blood pressure, in hypertension and cardiovascular outcomes, this review evaluates major studies comparing arterial stiffness through the life course between different ethnic groups or races (which have no biological definition)-in children, adolescents, young, and middle-aged adults and the very elderly. Most report that compared with white European-origin samples, populations of black African descent have increased central arterial stiffness throughout different life stages, as well as a more rapid increase in arterial stiffness at young ages. Exceptions may include African Caribbean origin people in Europe. Differences in vascular structure and function are clearest, where obesity, socioeconomic, and psychosocial factors are most marked. Few studies evaluate a wider spectrum of ethnic groups or factors contributing to these ethnic disparities. Genetic effects are not obvious; maternal risk and intergenerational studies are scarce. Nevertheless, across all ethnic groups, for given levels of blood pressure and age, some people have stiffer central arteries than others. These individuals are most at risk of vascular events and mortality and, therefore, may benefit from early, as yet untested, preventive action and treatment.

Characterising variability and regional correlations of microstructure and mechanical competence of human tibial trabecular bone: An in-vivo HR-pQCT study.

Quantifying spatial distribution of trabecular bone mechanical competence and microstructure is important for early diagnosis of skeletal disorders and potential risk of fracture. The objective of this study was to determine a spatial distribution of trabecular mechanical and morphological properties in human distal tibia and examine the contribution of regional variability of trabecular microarchitecture to mechanical competence. A total of 340 representative volume elements at five anatomic regions of trabecular bone - anterior, posterior, lateral, medial and centre - from ten white European-origin postmenopausal women were studied. Region-specific trabecular parameters such as trabecular volume fraction, trabecular thickness, trabecular number, trabecular surface area, trabecular separation, plate-like structure fraction and finite element analysis of trabecular stiffness were determined based on in-vivo high resolution peripheral quantitative computed tomographic (HR-pQCT) images of distal tibiae from ten postmenopausal women. Mean values were compared using analysis of variance. The correlations between morphological parameters and stiffness were calculated. Significant regional variation in trabecular microarchitecture of the human distal tibia was observed (p < 0.05), with up to 106% differences between lowest (central and anterior) and highest (medial and posterior) regions. Higher proportion of plate-like trabecular morphology (63% and 53%) was found in medial and posterior regions in the distal tibia. Stiffness estimated from finite element models also differed significantly (p < 0.05), with stiffness being 4.5 times higher in the highest (medial) than lowest (central) regions. The bone volume fraction was the strongest correlate of stiffness in all regions. A novel finding of this study is the fact that significant regional variation of stiffness derived from two-phased FEA model with individual trabecula representation correlated highly to regional morphology obtained from in-vivo HR-pQCT images at the distal tibia. The correlations between regional morphological parameters and mechanical competence of trabecular bone were consistent at all regions studied, with regional BV/TV showing the highest correlation. The method developed for regional analysis of trabecular mechanical competence may offer a better insight into the relationship between mechanical behaviour and microstructure of bone. The findings provide evidence needed to further justify a larger-cohort feasibility study for early detection of bone degenerative diseases: examining regional variations in mechanical competence and trabecular specifications may allow better understanding of fracture risks in addition to others contributing factors.

Gestational diabetes and ultrasound-assessed fetal growth in South Asian and White European women: findings from a prospective pregnancy cohort

BackgroundMaternal gestational diabetes (GDM) is an established risk factor for large size at birth, but its influence on intrauterine fetal growth in different ethnic populations is less well understood. Here, we examine the joint associations of GDM and ethnicity with longitudinal fetal growth in South Asian and White European origin women.MethodsThis study included 10,705 singletons (4747 White European and 5958 South Asian) from a prospective cohort of women attending an antenatal clinic in Bradford, in the North of England. All women completed a 75-g oral glucose tolerance test at 26–28 weeks’ gestation. Ultrasound measurements of fetal head circumference (HC), femur length (FL) abdominal circumference (AC), and estimated fetal weight (EFW), and corresponding anthropometric measurements at birth were used to derive fetal growth trajectories. Associations of GDM and ethnicity with these trajectories were assessed using multilevel fractional polynomial models.ResultsEight hundred thirty-two pregnancies (7.8%) were affected by GDM: 10.4% of South Asians and 4.4% of White Europeans. GDM was associated with a smaller fetal size in early pregnancy [differences (95% CI) in mean HC at 12 weeks and mean AC and EFW at 16 weeks comparing fetuses exposed to GDM to fetuses unexposed (reference) = − 1.8 mm (− 2.6; − 1.0), − 1.7 mm (− 2.5; − 0.9), and − 6 g (− 10; − 2)] and a greater fetal size from 24 weeks’ gestation through to term [differences (95% CI) in mean HC, AC, and EFW comparing fetuses exposed to GDM to those unexposed = 0.9 mm (0.3; 1.4), 0.9 mm (0.2; 1.7), and 7 g (0; 13) at 24 weeks]. Associations of GDM with fetal growth were of similar magnitude in both ethnic groups. Growth trajectories, however, differed by ethnicity with South Asians being smaller than White Europeans irrespective of GDM status. Consequently, South Asian fetuses exposed to GDM were smaller across gestation than fetuses of White Europeans without GDM.ConclusionsIn both ethnic groups, GDM is associated with early fetal size deviations prior to GDM diagnosis, highlighting the need for novel strategies to diagnose pregnancy hyperglycemia earlier than current methods. Our findings also suggest that ethnic-specific fetal growth criteria are important in identifying hyperglycemia-associated pathological effects.

Effect of l-arginine on energy metabolism, skeletal muscle and brown adipose tissue in South Asian and Europid prediabetic men: a randomised double-blinded crossover study

Aims/hypothesisIndividuals of South Asian origin are at increased risk of developing type 2 diabetes mellitus and associated comorbidities compared with Europids. Disturbances in energy metabolism may contribute to this increased risk. Skeletal muscle and possibly also brown adipose tissue (BAT) are involved in human energy metabolism and nitric oxide (NO) is suggested to play a pivotal role in regulating mitochondrial biogenesis in both tissues. We aimed to investigate the effects of 6 weeks of supplementation with l-arginine, a precursor of NO, on energy metabolism by BAT and skeletal muscle, as well as glucose metabolism in South Asian men compared with men of European descent.MethodsWe included ten Dutch South Asian men (age 46.5 ± 2.8 years, BMI 30.1 ± 1.1 kg/m2) and ten Dutch men of European descent, that were similar with respect to age and BMI, with prediabetes (fasting plasma glucose level 5.6–6.9 mmol/l or plasma glucose levels 2 h after an OGTT 7.8–11.1 mmol/l). Participants took either l-arginine (9 g/day) or placebo orally for 6 weeks in a randomised double-blind crossover study. Participants were eligible to participate in the study when they were aged between 40 and 55 years, had a BMI between 25 and 35 kg/m2 and did not have type 2 diabetes. Furthermore, ethnicity was defined as having four grandparents of South Asian or white European origin, respectively. Blinding of treatment was done by the pharmacy (Hankintatukku) and an independent researcher from Leiden University Medical Center randomly assigned treatments by providing a coded list. All people involved in the study as well as participants were blinded to group assignment. After each intervention, glucose tolerance was determined by OGTT and basal metabolic rate (BMR) was determined by indirect calorimetry; BAT activity was assessed by cold-induced [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography–computed tomography scanning. In addition, a fasting skeletal muscle biopsy was taken and analysed ex vivo for respiratory capacity using a multisubstrate protocol. The primary study endpoint was the effect of l-arginine on BAT volume and activity.Resultsl-Arginine did not affect BMR, [18F]FDG uptake by BAT or skeletal muscle respiration in either ethnicity. During OGTT, l-arginine lowered plasma glucose concentrations (AUC0–2 h − 9%, p < 0.01), insulin excursion (AUC0–2 h − 26%, p < 0.05) and peak insulin concentrations (−26%, p < 0.05) in Europid but not South Asian men. This coincided with enhanced cold-induced glucose oxidation (+44%, p < 0.05) in Europids only. Of note, in skeletal muscle biopsies several respiration states were consistently lower in South Asian men compared with Europid men.Conclusions/interpretationl-Arginine supplementation does not affect BMR, [18F]FDG uptake by BAT, or skeletal muscle mitochondrial respiration in Europid and South Asian overweight and prediabetic men. However, l-arginine improves glucose tolerance in Europids but not in South Asians. Furthermore, South Asian men have lower skeletal muscle oxidative capacity than men of European descent.FundingThis study was funded by the EU FP7 project DIABAT, the Netherlands Organization for Scientific Research, the Dutch Diabetes Research Foundation and the Dutch Heart Foundation.Trial registration:ClinicalTrials.gov NCT02291458.

Sex and area differences in the association between adiposity and lipid profile in Sub-Saharan Africa: A comparison with a European population

Introduction Sub-Saharan African (SSA) countries are facing a rising epidemic of non-communicable diseases (NCDs) alongside a persistent burden from undernutrition and infectious diseases. Mendelian randomization (using genetic variants as instrumental variables) and randomised controlled trial (RCT) evidence show that high levels of total (TC) and low-density lipoprotein-cholesterol (LDL-C) and of triglycerides (TG) are key causal risk factors for coronary heart diseases (CHD), that can be effectively modified to prevent CHD. Studies in high-income countries show that higher adiposity results in an adverse lipid profile, but whether this association is similar in SSA populations is unclear. One previous small study from Cameroon suggested higher adiposity increased dyslipidaemia in urban dwelling SSA populations but not in those in rural areas, but to our knowledge previous studies have not sought to replicate this. This study aimed to (i) assess the association between total and central adiposity measures and lipid profile in Malawi, exploring differences by sex and area of residence and (ii) compare the associations with observations from a predominantly white European-origin population cohort from the United Kingdom (UK). Methods Baseline data from the Malawi Epidemiology and Intervention Research Unit Non-Communicable Disease study (MEIRU NCD) were used. The study assessed adults in a rural (Karonga, Northern Malawi; n = 12,153) and an urban (area 25 of Lilongwe, the capital city; n= 12,869) of Malawi. The association of body mass index (BMI) and waist-hip ratio (WHR) with fasting lipids [TC, LDL-C, high density lipoprotein-cholesterol (HDL-C) and TG] was assessed by area and sex. Data from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) were used for the comparison with a population from a high-income European setting, and included 3286 adolescents (mean age 17.8), 4107 mothers (mean age 47.9), and 1933 fathers (mean age 53.3). Multiple linear regression was used to examine the association of both BMI and WHR with each lipid measure, adjusted initially for age and then for potential confounding by household assets, education, marital status, number of children, smoking, alcohol, physical activity, lipid-lowering medication, and HIV status. As the UK data were taken from largely urban/sub-urban dwelling adolescents and middle-aged females and males, we selected two age groups of participants from the urban group of the Malawi cohort that had similar age distributions to the UK cohorts to compare associations between Malawians and UK residents. Results We observed positive linear associations of BMI and WHR with TC, LDL-C and TG and inverse association with HDL-C. Associations between BMI/WHR and serum lipids were in general similar in females and males, however, differed by area, with the associations between BMI and all serum lipids being stronger in rural than urban females, except for HDL-C, which was stronger in urban females. Associations did not differ consistently between rural and urban male residents. Associations of BMI and WHR with lipids were mostly similar or weaker in Malawi than the UK urban residents in both sexes and age groups. However, in middle-aged males, there was some evidence that associations of BMI and WHR with TC and LDL-C were stronger in Malawians. Conclusions The consistent associations observed of higher adiposity with adverse lipid profiles in females and males living in rural and urban areas of Malawi highlight the emerging adverse cardio-metabolic epidemic in this poor population. The similarity (or even stronger) associations between the Malawian and UK population highlight the importance of early interventions to control the emerging obesity epidemic in SSA populations.

The contribution of physical fitness to individual and ethnic differences in risk markers for type 2 diabetes in children: The Child Heart and Health Study in England (CHASE).

BackgroundThe relationship between physical fitness and risk markers for type 2 diabetes (T2D) in children and the contribution to ethnic differences in these risk markers have been little studied. We examined associations between physical fitness and early risk markers for T2D and cardiovascular disease in 9‐ to 10‐year‐old UK children.MethodsCross‐sectional study of 1445 9‐ to 10‐year‐old UK children of South Asian, black African‐Caribbean and white European origin. A fasting blood sample was used for measurement of insulin, glucose (from which homeostasis model assessment [HOMA]‐insulin resistance [IR] was derived), glycated hemoglobin (HbA1c), urate, C‐reactive protein (CRP), and lipids. Measurements of blood pressure (BP) and fat mass index (FMI) were made; physical activity was measured by accelerometry. Estimated VO2 max was derived from a submaximal fitness step test. Associations were estimated using multilevel linear regression.ResultsHigher VO2 max was associated with lower FMI, insulin, HOMA‐IR, HbA1c, glucose, urate, CRP, triglycerides, LDL‐cholesterol, BP and higher HDL‐cholesterol. Associations were reduced by adjustment for FMI, but those for insulin, HOMA‐IR, glucose, urate, CRP, triglycerides and BP remained statistically significant. Higher levels of insulin and HOMA‐IR in South Asian children were partially explained by lower levels of VO2max compared to white Europeans, accounting for 11% of the difference.ConclusionsPhysical fitness is associated with risk markers for T2D and CVD in children, which persist after adjustment for adiposity. Higher levels of IR in South Asians are partially explained by lower physical fitness levels compared to white Europeans. Improving physical fitness may provide scope for reducing risks of T2D.

Exercise-induced circulating microRNA changes in athletes in various training scenarios.

BackgroundThe aim of the study was to compare selected extracellular miRNA levels (miR-16, miR-21, miR-93 and miR-222 with the response to 8-week-long explosive strength training (EXPL), hypertrophic strength training (HYP) and high-intensity interval training (HIIT).Methods30 young male athletes of white European origin (mean age: 22.5 ± 4.06 years) recruited at the Faculty of Sports Studies of Masaryk University were enrolled in this study. The study participants were randomly assigned to three possible training scenarios: EXPL, HYP or HITT and participated in 8-week-long program in given arm. Blood plasma samples were collected at the baseline and at week 5 and 8 and anthropometric and physical activity parameters were measured. Pre- and post-intervention characteristics were compared and participants were further evaluated as responders (RES) or non-responders (NRES). RES/NRES status was established for the following characteristics: 300°/s right leg extension (t300), 60°/s right leg extension (t60), isometric extension (IE), vertical jump, isometric extension of the right leg and body fat percentage (BFP).ResultsNo differences in miRNA levels were apparent between the intervention groups at baseline. No statistically significant prediction role was observed using crude univariate stepwise regression model analysis where RES/NRES status for t300, t60, IE, vertical jump and pFM was used as a dependent variable and miR-21, miR-222, miR-16 and miR-93 levels at baseline were used as independent variables. The baseline levels of miR-93 expressed an independent prediction role for responder status based on isometric extension of the right leg (beta estimate 0.76, 95% CI: -0.01; 1.53, p = 0.052).DiscussionThe results of the study indicate that 8-week-long explosive strength training, hypertrophic strength training and high-intensity interval training regimens are associated with significant changes in miR-16, mir-21, miR-222 and miR-93 levels compared to a baseline in athletic young men.

Psychosocial stressors contributing to emergency psychiatric service utilization in a sample of ethno-culturally diverse clients with psychosis in Toronto

BackgroundUnderstanding the psychosocial stressors of people with psychoses from minority ethnic groups may help in the development of culturally appropriate services. This study aimed to compare psychosocial factors associated with attendance at an emergency department (ED) for six ethnic groups. Preventing crises or supporting people better in the community may decrease hospitalization and improve outcomes.MethodA cohort was created by retrospective case note analysis of people of East-Asian, South-Asian, Black-African, Black-Caribbean, White-North American and White-European origin groups attending a specialized psychiatric ED in Toronto with a diagnosis of psychosis between 2009 and 2011. The psychological or social stressors which were linked to the presentation at the ED that were documented by the attending physicians were collected for this study. Logistic regression models were constructed to analyze the odds of presenting with specific stressors.ResultsSeven hundred sixty-five clients were included in this study. Forty-four percent of the sample did not have a psychiatrist, and 53% did not have a primary care provider. Social environmental stressors were the most frequent psychosocial stressor across all six groups, followed by issues in the primary support group, occupational and housing stressors. When compared to White-North American clients, East-Asian and White-European origin clients were less likely to present with a housing stressor, while Black-African clients had decreased odds of presenting with primary support group stressor. Having a primary care provider or psychiatrist were predominantly protective factors.ConclusionIn Toronto, moving people with chronic mental health conditions out of poverty, increasing the social safety net and improving access to primary care and community based mental health services may decrease many of the stressors which contribute to ED attendance.

Paranasal sinus size is decreased in CFTR heterozygotes with chronic rhinosinusitis.

Cystic fibrosis (CF) heterozygotes with a single mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are at significantly higher risk to develop chronic rhinosinusitis (CRS). However the reasons why remain unknown. We tested the hypothesis that CFTR heterozygotes would have smaller sinus volumes than healthy controls. To exclude sinus disease as a confounding factor we also assessed paranasal sinus volume in those with CRS, but without known CFTR mutations. A total of 131 adults of white Northern European and Latino origin were recruited: 81 diagnosed with CRS and 50 healthy controls. Subjects were genotyped for 9 common CFTR mutations covering >80% of mutation prevalence. Those with CRS were separated by CFTR mutational status and matched demographically to healthy controls. Three-dimensional sinus volume, mucosal opacification, and skull volume were quantified to obtain the percentage of pneumatization and extent of mucosal disease in each sinus. Twenty-item Sino-Nasal Outcome Test (SNOT-20) and endoscopy scores were also analyzed. In individuals diagnosed with CRS we identified 7 CFTR heterozygotes (8.64%); no CFTR mutations were identified in our healthy controls. There were no significant differences between the 3 matched groups other than sinus pneumatization. The frontal and maxillary sinuses were significantly smaller in CFTR heterozygotes with CRS compared to CFTR wild-type subjects with or without disease. CFTR heterozygotes with CRS have significantly smaller frontal and maxillary sinus size compared to those without mutations, irrespective of disease state. This sinus hypoplasia may contribute to impaired mucus clearance and chronic sinus disease development.

Does metabolic health in overweight and obesity persist? - Individual variation and cardiovascular mortality over two decades.

Overweight and obese individuals may be metabolically healthy, but attention needs to be given to long-term persistence of this trait and any associated variation in cardiovascular risk. Cross-sectional and longitudinal variation in metabolic health and associated cardiovascular mortality were analysed in 1099 white European-origin normal-weight and overweight or obese males followed for 20years. Definitions of metabolic health were based on LDL and HDL cholesterol, triglycerides, blood pressure, fasting glucose and cardiovascular risk. Insulin resistance (e.g. HOMA-IR) and sub-clinical inflammation (ESR and white blood cell count) were explored. Cardiovascular mortality risks and persistence of metabolic health status were evaluated. There were 87 cardiovascular deaths. Insulin resistance was increased in metabolically healthy overweight or obese participants (median HOMA-IR 2.63, 95% CI: 1.79-3.65, P<0.001) relative to normal-weight participants (median HOMA-IR 1.67, 95% CI: 1.08-2.67, P<0.001) as was sub-clinical inflammation but metabolically healthy overweight or obese individuals were not at increased risk of cardiovascular mortality compared with the metabolically healthy normal-weight individuals (hazard ratio 1.13, 95% CI: 0.34-3.72, P=0.8). The proportions of initially metabolically healthy overweight or obese who remained metabolically healthy for visits 2, 3 and 4 were 54, 48 and 39% respectively, and for initially normal-weight individuals, 68, 51 and 41%. A lower proportion of metabolically healthy overweight or obese individuals remained metabolically healthy at visit 2 compared with normal-weight individuals (P=0.007), but proportions converged thereafter. Despite being insulin resistant and having greater sub-clinical inflammation, and despite instability in metabolic health status, metabolically healthy overweight or obese individuals were at no greater risk of cardiovascular mortality than their normal-weight equivalents.

Cross-sectional study of ethnic differences in physical fitness among children of South Asian, black African–Caribbean and white European origin: the Child Heart and Health Study in England (CHASE)

ObjectiveLittle is known about levels of physical fitness in children from different ethnic groups in the UK. We therefore studied physical fitness in UK children (aged 9–10 years) of South...

Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment

The Gly-to-Arg substitution at the 16 position (rs1042713) in the β2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of β2-receptors. We sought to undertake a meta-analysis to test the hypothesis that there is an interaction between the Aallele of rs1042713 (Arg16 amino acid) and long-acting β-agonist (LABA) exposure for asthma exacerbations in children. Children with diagnosed asthma were recruited in 5 populations (BREATHE, Genes-Environments and Admixture in Latino Americans II, PACMAN, the Paediatric Asthma Gene Environment Study, and the Pharmacogenetics of Adrenal Suppression with Inhaled Steroid Study). Ahistory of recent exacerbation and asthma treatment was determined from questionnaire data. DNA was extracted, and the Gly16Arg genotype was determined. Data from 4226 children of white Northern European and Latino origin were analyzed, and the odds ratio for exacerbation increased by 1.52 (95% CI, 1.17-1.99; P=.0021) for each copy of the Aallele among the 637 children treated with inhaled corticosteroids (ICSs) plus LABAs but not for treatment with ICSs alone (n=1758) or ICSs plus leukotriene receptor antagonist (LTRAs; n=354) or ICSs plus LABAs plus LTRAs (n=569). The use of a LABA but not an LTRA as an "add-on controller" is associated with increased risk of asthma exacerbation in children carrying 1 or 2 Aalleles at rs1042713. Prospective genotype-stratified clinical trials are now required to explore the potential role of rs1042713 genotyping for personalized asthma therapy in children.

Sleep duration and risk markers for type 2 diabetes: a cross-sectional study in children aged 9–10 years

BackgroundShorter sleep duration has been associated with obesity, increased cardiovascular morbidity, and mortality in adults and with obesity in children. However, effects on childhood risk markers for cardiometabolic disease have been little studied. We examined associations between self-reported sleep duration and cardiometabolic risk markers in children and whether sleep duration might explain ethnic differences in insulin resistance. MethodsThis was a cross-sectional study of 4560 children aged 9–10 years, predominantly of white European, South Asian, and black African origin, from 200 UK primary schools. Children were asked to recall usual time of going to sleep and awakening on a school day. Fasting blood samples provided concentrations of serum insulin, plasma glucose, HbA1c, and serum lipids. Physical measures included height, weight, bioimpedance, and blood pressures. Multilevel linear regression models examined the association of sleep duration (in hours) with blood markers and anthropometric measures, adjusted for sex, age quartiles, month, ethnicity, socioeconomic status, observer (physical measures only), and random effect for school; percentange changes are given for log transformed outcomes. Informed consent was obtained from parents or children, and ethics approval was given by the Multicentre Research Ethics Committee (Wales). FindingsMedian sleep duration was 10·5 h (95% central range 8–12). On average, white European children slept longer than South Asian and black African children (10·4 h/night, 10·2, and 10·1, respectively). There were strong inverse graded associations between sleep duration, adiposity, and diabetes risk markers. Per hour increase in sleep duration was associated with 0·8 kg/m3 lower ponderal index (95% CI 1·2–0·3), 0·03 kg/m5 lower fat-mass index (0·05–0·0), 1·73% lower HOMA (homoeostatis model assessment) insulin resistance (0·50–3·91), 2·43% lower fasting glucose (0·86–3·97), and 0·19% lower HbA1c (0·0–0·39) after adjustment. Associations with diabetes risk markers remained after adjustment for adiposity and objective measures of physical activity. Sleep duration did not account for ethnic differences in insulin resistance, and was unrelated to blood pressure and serum lipids. InterpretationThe inverse association between type 2 diabetes risk markers and sleep duration in childhood is novel. Intervention studies are needed to establish causal associations, especially since increased sleep duration might offer a strategy for early prevention of type 2 diabetes. FundingThis research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (South London) and by grants from Diabetes UK and the Wellcome Trust.

Recalibration of overweight–obesity prevalence from body-mass index in UK children of South Asian and black African origin: cross-sectional study based on National Child Measurement Programme data

BackgroundThe accurate assessment of overweight–obesity prevalence in UK children of South Asian and black African origin (in whom its consequences are especially adverse) is an important challenge. However, body-mass index (BMI), the marker of body fatness used in most national surveys, differs in its association to body fatness between ethnic groups, which biases ethnic comparisons of body fatness based on BMI. We recalibrated BMI values for ethnicity to assess overweight–obesity prevalence more accurately in UK South Asian and black African children in recent survey data from the National Child Measurement Programme (NCMP), an inclusive assessment programme in English primary schools. MethodsDeuterium dilution measurements of body fat and BMI were collated from four recent UK population-based studies (three in schools selected to provide balanced ethnic representation) in 873 children of South Asian, black African, and white European origin aged 9−11 years. Data were analysed with linear regression models to determine the age-adjusted and sex-adjusted BMI differences in South Asian and black African children compared with white Europeans at an equivalent level of body fatness (denoted by fat mass index [kg/m5], which is uncorrelated with height). These BMI adjustments were applied to NCMP 2012–13 survey data in 489 146 children aged 10–11 years to determine ethnic-specific overweight–obesity prevalences; standard NCMP overweight–obesity definitions were used. FindingsBMI adjustments for equivalent body fatness were +1·11 kg/m2 and +0·98 kg/m2 for South Asian boys and girls, respectively, and −1·20 kg/m2 and −1·66 kg/m2 for black African boys and girls, respectively; these adjustments were applied to NCMP data for South Asian and black African children. Overweight–obesity was recorded in 14 538 of 38 201 South Asian children (38·1%, 95% CI 37·6–38·5) and 9839 of 22 672 black African children (43·4%, 42·8–44·0) before BMI adjustment and in 18 145 of 38 201 (47·5%, 47·0–48·0) and 7065 of 22 672 (31·2%, 30·6–31·8), respectively, after adjustment; overweight–obesity was recorded in 92 002 of 292 467 white European children (31·5%, 95%CI 31·3–31·6). InterpretationUse of ethnic-specific BMI adjustments to obtain comparable assessments of body fatness substantially changed observed overweight–obesity prevalences in ethnic minority groups. Adjusted BMI particularly emphasised the substantial overweight–obesity burden in South Asian children, an important priority for prevention. FundingThis research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London and by grants from the British Heart Foundation (PG/11/42/28895), the Child Growth Foundation (GR 10/03), and the Wellcome Trust (WT094129MA).