Institution
Medical Research Council
Government•London, United Kingdom•
About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.
Papers published on a yearly basis
Papers
More filters
••
TL;DR: In this article, the HESX1/Hesx1 homozygous mutations were detected in individuals with relatively mild pituitary hypoplasia or SOD, which display incomplete penetrance and variable phenotype amongst heterozygous family members.
Abstract: We have previously shown that familial septo-optic dysplasia (SOD), a syndromic form of congenital hypopituitarism involving optic nerve hypoplasia and agenesis of midline brain structures, is associated with homozygosity for an inactivating mutation in the homeobox gene HESX1/Hesx1 in man and mouse. However, as most SOD/congenital hypopituitarism occurs sporadically, the possible contribution of HESX1 mutations to the aetiology of these cases is presently unclear. Interestingly, a small proportion of mice heterozygous for the Hesx1 null allele show a milder SOD phenocopy, implying that heterozygous mutations in human HESX1 could underlie some cases of congenital pituitary hypoplasia with or without midline defects. Accordingly, we have now scanned for HESX1 mutations in 228 patients with a broad spectrum of congenital pituitary defects, ranging in severity from isolated growth hormone deficiency to SOD with panhypopituitarism. Three different heterozygous missense mutations were detected in individuals with relatively mild pituitary hypoplasia or SOD, which display incomplete penetrance and variable phenotype amongst heterozygous family members. Gel shift analysis of the HESX1-S170L mutant protein, which is encoded by the C509T mutated allele, indicated that a significant reduction in relative DNA binding activity results from this mutation. Segregation analysis of a haplotype spanning 6.1 cM, which contains the HESX1 locus, indicated that only one HESX1 mutation was present in the families containing the C509T and A541G mutations. These results demonstrate that some sporadic cases of the more common mild forms of pituitary hypoplasia have a genetic basis, resulting from heterozygous mutation of the HESX1 gene.
294 citations
••
TL;DR: Methode d'ajustement de courbes centiles lissees a des donnees de reference, basee sur la famille de transformation de Box et Cox as discussed by the authors.
Abstract: Methode d'ajustement de courbes centiles lissees a des donnees de reference, basee sur la famille de transformation de Box et Cox
294 citations
••
TL;DR: The harvest plot is a novel and useful method for synthesising evidence about the differential effects of population-level interventions and contributes to the challenge of making best use of all available evidence by incorporating all relevant data.
Abstract: One attraction of meta-analysis is the forest plot, a compact overview of the essential data included in a systematic review and the overall 'result'. However, meta-analysis is not always suitable for synthesising evidence about the effects of interventions which may influence the wider determinants of health. As part of a systematic review of the effects of population-level tobacco control interventions on social inequalities in smoking, we designed a novel approach to synthesis intended to bring aspects of the graphical directness of a forest plot to bear on the problem of synthesising evidence from a complex and diverse group of studies. We coded the included studies (n = 85) on two methodological dimensions (suitability of study design and quality of execution) and extracted data on effects stratified by up to six different dimensions of inequality (income, occupation, education, gender, race or ethnicity, and age), distinguishing between 'hard' (behavioural) and 'intermediate' (process or attitudinal) outcomes. Adopting a hypothesis-testing approach, we then assessed which of three competing hypotheses (positive social gradient, negative social gradient, or no gradient) was best supported by each study for each dimension of inequality. We plotted the results on a matrix ('harvest plot') for each category of intervention, weighting studies by the methodological criteria and distributing them between the competing hypotheses. These matrices formed part of the analytical process and helped to encapsulate the output, for example by drawing attention to the finding that increasing the price of tobacco products may be more effective in discouraging smoking among people with lower incomes and in lower occupational groups. The harvest plot is a novel and useful method for synthesising evidence about the differential effects of population-level interventions. It contributes to the challenge of making best use of all available evidence by incorporating all relevant data. The visual display assists both the process of synthesis and the assimilation of the findings. The method is suitable for adaptation to a variety of questions in evidence synthesis and may be particularly useful for systematic reviews addressing the broader type of research question which may be most relevant to policymakers.
294 citations
••
TL;DR: It is concluded that telephoning has a minimal effect on the more automatized driving skills, but that perception and decision-making may be critically impaired by switching between visual and auditory inputs.
Abstract: 224 men were given the task of judging whether to drive through gaps which might be larger or smaller than the car, and a telephoning task of checking the accuracy of short sentences. Interference between the concurrently performed tasks was investigated. Telephoning mainly impaired judgments of "impossible" gaps. The control skills employed in steering through "possible" gaps were not reliably degraded, although speed of driving was reduced. Driving increased errors and prolonged RTs on the sentence-checking task. It is concluded that telephoning has a minimal effect on the more automatized driving skills, but that perception and decision-making may be critically impaired by switching between visual and auditory inputs. (PsycINFO Database Record (c) 2012 APA, all rights reserved) Keywords: Driver distraction; Language: en
294 citations
••
University of Bristol1, Hannover Medical School2, University of Copenhagen3, Erasmus University Rotterdam4, QIMR Berghofer Medical Research Institute5, Imperial College London6, University of Kiel7, Technische Universität München8, University of Pennsylvania9, University of Western Australia10, University of Basel11, University of Manchester12, VU University Amsterdam13, Karolinska Institutet14, University of Geneva15, Wellcome Trust Sanger Institute16, University of Oulu17, University of the East18, University of Washington19, University of Melbourne20, Ludwig Maximilian University of Munich21, University of Bonn22, Aarhus University23, Tartu University Hospital24, Statens Serum Institut25, University of Iowa26, Children's Hospital of Philadelphia27, King's College London28, Telethon Institute for Child Health Research29, Children's Medical Research Institute30, Swiss Tropical and Public Health Institute31, Norwegian Institute of Public Health32, Manchester Academic Health Science Centre33, Utrecht University34, Copenhagen University Hospital35, Karolinska University Hospital36, Sahlgrenska University Hospital37, Ontario Institute for Cancer Research38, St George's, University of London39, Medical Research Council40
TL;DR: A genome-wide association meta-analysis of affected individuals and controls and the ten most strongly associated new susceptibility loci examined underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.
Abstract: Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.
294 citations
Authors
Showing all 16441 results
Name | H-index | Papers | Citations |
---|---|---|---|
Shizuo Akira | 261 | 1308 | 320561 |
Trevor W. Robbins | 231 | 1137 | 164437 |
Richard A. Flavell | 231 | 1328 | 205119 |
George Davey Smith | 224 | 2540 | 248373 |
Nicholas J. Wareham | 212 | 1657 | 204896 |
Cyrus Cooper | 204 | 1869 | 206782 |
Martin White | 196 | 2038 | 232387 |
Frank E. Speizer | 193 | 636 | 135891 |
Michael Rutter | 188 | 676 | 151592 |
Richard Peto | 183 | 683 | 231434 |
Terrie E. Moffitt | 182 | 594 | 150609 |
Kay-Tee Khaw | 174 | 1389 | 138782 |
Chris D. Frith | 173 | 524 | 130472 |
Phillip A. Sharp | 172 | 614 | 117126 |
Avshalom Caspi | 170 | 524 | 113583 |