68 research outputs found
Pedagogy in a pandemic – COVID‐19 and virtual continuing medical education (vCME) in obstetrics and gynecology
No full text10.1111/aogs.13885ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA996692-69
Ethnic differences in bone mineral density among midlife women in a multi-ethnic Southeast Asian cohort
No full text10.1007/s11657-019-0631-0ARCHIVES OF OSTEOPOROSIS14
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Association between urinary biomarkers of total sugars intake and measures of obesity in a cross-sectional study
No full textabstract: Obesity is an important modifiable risk factor for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative sample of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24 h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between biomarker-based estimated intake and measures of obesity (body mass intake (BMI), waist circumference and waist-to-hip ratio) and obesity risk, respectively. Estimated sugar intake was significantly associated with BMI, waist circumference and waist-to-hip ratio; these associations remained significant after adjustment for estimated protein intake as a marker of non-sugar energy intake. Estimated sugar intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95%CI 1.00–1.04 per 10g), waist-circumference (1.03; 1.01–1.05) and waist-to-hip ratio (1.04; 1.02–1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results strongly support positive associations between total sugar intake, measures of obesity and likelihood of being obese. It is the first time that such an association has been shown in a nationally-representative sample of the general population using a validated biomarker. This biomarker could be used to monitor the efficacy of public health interventions to reduce sugar intake.The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.017950
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
No full textThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
A framework for artificial intelligence in cancer research and precision oncology
No full textArtificial intelligence; Precision oncologyIntel·ligència artificial; Oncologia de precisióInteligencia artificial; Oncología de precisiónR.P.L. is supported by LaCaixa Foundation, a CRIS Foundation Talent Award (TALENT19-05), the FERO Foundation, the Instituto de Salud Carlos III-Investigacion en Salud (PI18/01395 and PI21/01019), the Prostate Cancer Foundation (18YOUN19) and the Asociación Española Contra el Cancer (AECC) (PRYCO211023SERR, funding C.M.). J.N.K. is supported by the German Federal Ministry of Health (DEEP LIVER, ZMVI1-2520DAT111) and the Max-Eder-Program of the German Cancer Aid (grant #70113864), the German Federal Ministry of Education and Research (PEARL, 01KD2104C; CAMINO, 01EO2101; SWAG, 01KD2215A; TRANSFORM LIVER, 031L0312A; TANGERINE, 01KT2302 through ERA-NET Transcan), the German Academic Exchange Service (SECAI, 57616814), the German Federal Joint Committee (Transplant.KI, 01VSF21048) the European Union’s Horizon Europe and innovation program (ODELIA, 101057091; GENIAL, 101096312) and the National Institute for Health and Care Research (NIHR, NIHR213331) Leeds Biomedical Research Centre. JSR-F is funded in part by the Breast Cancer Research Foundation, a Susan G Komen Leadership grant, an NIH/NCI P50 CA247749 01 grant, and an NIH/NCI grant No. P30CA008748. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
No full textElevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets
DNA methylation patterns in cord blood DNA and body size in childhood.
No full textThis 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.BACKGROUND: Epigenetic markings acquired in early life may have phenotypic consequences later in development through their role in transcriptional regulation with relevance to the developmental origins of diseases including obesity. The goal of this study was to investigate whether DNA methylation levels at birth are associated with body size later in childhood. PRINCIPAL FINDINGS: A study design involving two birth cohorts was used to conduct transcription profiling followed by DNA methylation analysis in peripheral blood. Gene expression analysis was undertaken in 24 individuals whose biological samples and clinical data were collected at a mean ± standard deviation (SD) age of 12.35 (0.95) years, the upper and lower tertiles of body mass index (BMI) were compared with a mean (SD) BMI difference of 9.86 (2.37) kg/m(2). This generated a panel of differentially expressed genes for DNA methylation analysis which was then undertaken in cord blood DNA in 178 individuals with body composition data prospectively collected at a mean (SD) age of 9.83 (0.23) years. Twenty-nine differentially expressed genes (>1.2-fold and p<10(-4)) were analysed to determine DNA methylation levels at 1-3 sites per gene. Five genes were unmethylated and DNA methylation in the remaining 24 genes was analysed using linear regression with bootstrapping. Methylation in 9 of the 24 (37.5%) genes studied was associated with at least one index of body composition (BMI, fat mass, lean mass, height) at age 9 years, although only one of these associations remained after correction for multiple testing (ALPL with height, p(Corrected) = 0.017). CONCLUSIONS: DNA methylation patterns in cord blood show some association with altered gene expression, body size and composition in childhood. The observed relationship is correlative and despite suggestion of a mechanistic epigenetic link between in utero life and later phenotype, further investigation is required to establish causality
The campaign for democratic socialism 1960-1964.
No full textPhDIn early 1960 it seemed likely that the official Labour
Party defence policy would be defeated by a unilateralist
resolution at the Scarborough Conference. In response to
this possibility the Campaign for Democratic Socialism,
or CDS, was established.
The CDS projected the image of a grass-roots movement
inspired by Gaitskell's "fight and fight again" speech.
But it was run by a Campaign Committee which included
leading members of the Party like Tony Crosland, Roy
Jenkins and Patrick Gordon Walker, as well as less well
known members like Bill Rodgers, Dick Taverne, Philip
Williams, Brian Walden, Denis Howell and David Marquand.
This highly talented group launched an elaborate and
successful lobbying, publicity and briefing operation
which was influential in overturning the unilateralist
vote at the Blackpool Conference of 1961. After Blackpool
the Campaign helped many of its leading members find
seats in the House of Commons while continuing to put the
"revisionist" case through its newspaper Campaign.
The importance of the CDS in the history of the Labour
Party is, primarily, as the first internal pressure group
organised by the right of the Party. It was also the
first internal Party group to use such sophisticated
lobbying techniques. Moreover, the subsequent careers of
the leading members of the Campaign influenced the
development of the Labour Party. The CDS was an important
formative political action for many of them. Finally many
of the CDS supporters set-up or joined the SDP when it
was launched
Impact of Asthma on Educational Attainment in a Socioeconomically Deprived Population: A Study Linking Health, Education and Social Care Datasets
No full textPMCID: PMC3498297This 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
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
No full textMultiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis
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