scispace - formally typeset
Search or ask a question
Institution

University of Cambridge

EducationCambridge, United Kingdom
About: University of Cambridge is a education organization based out in Cambridge, United Kingdom. It is known for research contribution in the topics: Population & Galaxy. The organization has 118293 authors who have published 282289 publications receiving 14497093 citations. The organization is also known as: Cambridge University & Cambridge.
Topics: Population, Galaxy, Transplantation, Redshift, Gene


Papers
More filters
Journal ArticleDOI
TL;DR: This paper considers the advantages and disadvantages associated with the use of vignettes as data collection tools, concluding with a check-list to help critique vignette studies.
Abstract: Vignettes are simulations of real events which can be used in research studies to elicit subject's knowledge, attitudes or opinions according to how they state they would behave in the hypothetical situation depicted Advantages associated with the use of vignettes as research tools include: the ability to collect information simultaneously from large numbers of subjects, to manipulate a number of variables at once in a manner that would not be possible in observation studies, absence of observer effect and avoidance of the ethical dilemmas commonly encountered during observation Difficulties include problems establishing reliability and validity, especially external validity This paper considers the advantages and disadvantages associated with the use of vignettes as data collection tools, concluding with a check-list to help critique vignettes studies

267 citations

Journal ArticleDOI
TL;DR: An epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake identified a robust alcohol-related DNA methylation signature and shown the potential utility ofDNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.
Abstract: The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

267 citations

Journal ArticleDOI
02 Jul 2020-Nature
TL;DR: This study used whole-genome sequencing in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome, finding that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells.
Abstract: Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.

267 citations

Journal ArticleDOI
TL;DR: In this paper, the distribution of stress and velocity in an ideal glacier and an ideal ice-sheet is calculated for the two-dimensional flow of a long slab of ice down a gently undulating rough slope.
Abstract: A calculation is made of the distribution of stress and velocity in an ideal glacier and in an ideal ice-sheet. The ice is assumed to have a constant yield stress and to obey, like other polycrystalline plastic aggregates, the Levy-Mises equations of flow and either the Mises or the Tresca criterion of yielding. The solution obtained for an ideal glacier represents the two-dimensional flow of a long slab of ice down a gently undulating rough slope. The addition of ice to the upper surface by snowfall and the removal of ice by ablation are allowed for, but the frictional resistance of the sides of the glacier valley is neglected. Two states of flow are possible, 'active' and 'passive', corresponding to the active and passive Rankine states in soil mechanics. Which of these states occurs at a given place depends upon the relative magnitudes of the curvature of the bed and the rate of snowfall or ablation; a simple algebraic expression of this dependence is obtained. In both states of flow the velocity is greatest at the surface and decreases with depth according to an elliptical law. It is shown that, in accordance with observation, crevasses of limited depth can open in active flow but not in passive flow. The slip-line field for the problem has a close connexion with the directions and positions of shear faults (although the laminated structure of a glacier is doubtless also an important factor here). In passive flow the faults to be expected are similar to the 'thrust planes' often seen on glaciers. The theory suggests that in active flow a complementary sort of shear fault with the opposite direction of movement may occur-and there is some observational evidence for this. The tendency of glaciers to accentuate hollows in their beds is connected with the suggestion that erosion should proceed faster under passive flow than under active flow. The second solution obtained is formally similar but represents the two-dimensional flow of a large ice-sheet, such as the Greenland ice-cap. If a horizontal bed is assumed the profile is calculated to be formed from parts of two parabolas, the maximum height being given by the yield stress of ice. In the accumulation area flow is active. The maximum velocity is everywhere at the surface while the maximum shear rate is on the bed. The solution thus gives no support to the belief that the weight of ice above squeezes out the underlying ice at a faster rate.

267 citations

Journal ArticleDOI
TL;DR: In this paper, a simple model was proposed which qualitatively accounts for all observed notch phenomena including non-propagating cracks and size effects, and quantitatively predicts the experimental fatigue failure limit of sharply notched specimens.

267 citations


Authors

Showing all 119522 results

NameH-indexPapersCitations
Albert Hofman2672530321405
Zhong Lin Wang2452529259003
Solomon H. Snyder2321222200444
Trevor W. Robbins2311137164437
George Davey Smith2242540248373
Nicholas J. Wareham2121657204896
Cyrus Cooper2041869206782
Eric B. Rimm196988147119
Martin White1962038232387
Simon D. M. White189795231645
Michael Rutter188676151592
George Efstathiou187637156228
Mark Hallett1861170123741
David H. Weinberg183700171424
Paul G. Richardson1831533155912
Network Information
Related Institutions (5)
University of Oxford
258.1K papers, 12.9M citations

98% related

University College London
210.6K papers, 9.8M citations

97% related

Imperial College London
209.1K papers, 9.3M citations

97% related

McGill University
162.5K papers, 6.9M citations

94% related

University of Toronto
294.9K papers, 13.5M citations

93% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023466
20222,048
202115,690
202015,352
201913,664
201812,549