Demographic and socio-economic predictors of physical activity among people living with HIV of low socio-economic status

Background: Physical activity (PA) is beneficial for the health of people living with HIV and AIDS (PLWHA). Aim: The aim of this study was to determine if age, body weight, height, gender, waist-to-hip ratio (WHR), educational attainment, employment status, CD4+ cell count and body mass index (BMI) can predict overall PA among PLWHA of low socio-economic status (SES). Setting: Participants in this study were HIV-infected patients on first-line antiretroviral therapy (ART) regimen offered by the South African National Department of Health, and those not on ART. Participants were conveniently sampled from a list at a community health care centre in Cape Town. Methods: This study sample consisted of 978 HIV-infected South Africans. Physical activity data were collected using the Global Physical Activity Questionnaire. Backward multiple linear regression modelling was used to determine the relative influence of variables (age, body weight, height, gender, WHR, educational attainment, employment status, CD4+ count and BMI) on total moderate-to-vigorous PA. Alpha level was set at 0.05. Results: The mean age of the participants was 38.2 (standard deviation [SD] = 8.76) years for men and 33.9 (SD = 8.53) years for women. Physical activity was significantly higher in men (480.2 [SD = 582.9] min/week) than among women (369.35 [SD = 222.53] min/week). The results of the multiple linear regression showed that educational attainment (β = 0.127; p = 0.00), employment (β = −0.087; p = 0.01) and gender (β = 0.235; p = 0.00) significantly predicted total moderate-to-vigorous PA. Gender had the greatest effect, followed by educational attainment and employment status. Conclusion: There is a need for PA programmes that are designed to (1) target women, (2) strengthen programmes for education and promotion of PA and (3) engage the unemployed into PA for PLWHA. Physical activity interventions for this particular group should be tailored for persons of low SES

A phenome-wide association study (PheWAS) in the Population Architecture using Genomics and Epidemiology (PAGE) study reveals potential pleiotropy in African Americans

We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio- metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes

Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study

C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ~200 000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage disequilibrium patterns between race/ ethnicity groups were used to fine-map regions associated with CRP levels. Conditional analyses evaluated for multiple independent signals within genetic regions. One hundred and sixty-three unique variants in 12 loci in overall or race/ ethnicity-stratified Metabochip-wide scans reached a Bonferroni-corrected P-value<2.5E-7. Three loci have no (HACL1, OLFML2B) or only limited (PLA2G6) previous associations with CRP levels. Six loci had different top hits in race/ethnicityspecific versus overall analyses. Fine-mapping refined the signal in six loci, particularly in HNF1A. Conditional analyses provided evidence for secondary signals in LEPR, IL1RN and HNF1A, and for multiple independent signals in CRP and APOE. We identified novel variants and loci associated with CRP levels, generalized known CRP associations to a multiethnic study population, refined association signals at several loci and found evidence for multiple independent signals at several well-known loci. This study demonstrates the benefit of conducting inclusive genetic association studies in large multiethnic populations

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Core banking

Article adapted from authors book 'Banking: Restoring the Health &amp; Profitability of the Banking System' published by Harper Collins 1991SIGLEAvailable from British Library Document Supply Centre- DSC:7755.0344(92/12) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Agroindústria familiar rural, qualidade da produção artesanal e o enfoque da teoria das convenções Rural familiar agroindustry, quality of colonial production and the view of theory of the convention

A agroindústria familiar rural surge como uma alternativa na busca de novos nichos de mercados, utilizando-se da maior diversidade de produtos e da diferenciação dos produtos através da transformação dentro da propriedade. Sua implantação é considerada uma alternativa eficaz como política de Desenvolvimento Rural, mas, com todos os esforços, existem muitas limitações neste setor, principalmente da legislação sanitária. A construção dos mercados e das regras que os regem, mesmo com o cumprimento das normas legais, vem de dentro do processo e com a colaboração de todos os atores: produtores, consumidores. A Teoria das Convenções baseia-se no reconhecimento mútuo e coletivo da qualidade ampla do produto e foi utilizada para explicar como funcionam as interações entre produtores da Região Metropolitana de Porto Alegre com relação às regras de produção ou "modos de fazer" no processo produtivo.<br>The rural familiar agroindustry is an alternative in the search for new niche markets, using the greater diversity of existing products and product differentiation by transforming them inside the property. Its implementation is considered an effective alternative as policy of Rural Development, but despite all efforts there are many limitations in this sector especially in sanitary legislation. Quality is built on the agroindustries by looking not only at a physical process, but also relying on social and cultural aspects, considering personal efforts in making the products, dedication, tradition and artisanal "ways to make", which bring the colonial touch. The Theory of the Convention is based on mutual recognition and collective of wide quality of the product, and was used to explain how interactions are worked among producers at Metropolitan Porto Alegre Area regarding production rules or "ways to make" the production process