39 research outputs found
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
Making the best of a bad job Homeworking in secretarial and clerical occupations
SIGLEAvailable from British Library Document Supply Centre- DSC:DX79466 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Recommended from our members
Making the best of a bad job: Homeworking in secretarial and clerical occupations
The last two decades have produced much research about women's employment, yet one area which has received relatively little attention is that of homeworking. This thesis begins by considering theories of women's employment and different definitions of homeworking. It continues by using data from the OPCS Longitudinal Study (LS) to examine homeworking and some of the misconceptions surrounding it. A minimal estimate of homeworking in England and Wales is presented together with an examination of homeworking in the two largest occupation groups - clerical and clothing. There is also an analysis of socio-economic and demographic information.
This analysis provides the basis for two surveys of secretarial and clerical homeworkers (the single largest group of homeworkers in the LS) . Firstly, employers of homeworkers were interviewed to investigate their policies towards homeworkers, their patterns of recruitment and the conditions of work they provided for them. The advantages to employers of using homeworkers to cope with a flexible workload are described as well as the disadvantages to homeworkers. Although the homeworkers' conditions of work and pay appear to be better than those of homeworkers in other occupations, the homeworkers themselves still have little control over their employment situation.
Secondly, interviews with homeworkers were carried out to examine how homeworking fits into women's work histories, in addition to focussing on their work conditions. The question of whether women see homeworking as desirable or as the only solution available to them is also considered. The evidence suggests that these homeworkers' conditions of employment are as unsatisfactory as those of many other homeworkers, and that they have had to prioritise their domestic responsibilities over any career plans they might have had. Having become mothers the majority of women found working in their homes was the best option available to them
Recommended from our members
SEARCH FOR FREE QUARKS PRODUCED AT 800 GEV/C USING A NEW CONCENTRATION TECHNIQUES
Recommended from our members
Search for stable quarks produced by the Tevatron
An experiment has been run at the Tevatron to search for stable fractionally charged particles (i.e., quarks) produced by the 800 GeV/c proton beam. The experiment was performed in two phases. In the first run, 1.0 x 10/sup 15/ protons passed through a series of four mercury targets which were distributed among several lead degraders. The lead degraders were arranged so that fractionally charged particles over a wide range of production angles, masses, and energies would stop in the mercury targets. A small amount of this mercury has been analyzed for fractional charge in an automated Millikan apparatus. A second run, which had an integrated proton intensity of 4.1 x 10/sup 13/, used liquid nitrogen tanks to stop any fractionally charged particles produced when the proton beam interacted in an upstream lead target. In the four tanks, electrically charged gold-plated glass fibers attracted and then trapped any fractional charges which were stopped in the liquid nitrogen. After the exposure, the wires were moved through small beads of mercury in which the gold was dissolved. One of these small beads of mercury also has been analyzed in the same Millikan apparatus. The results from the first run show that the upper limit for quark production is less than 1 x 10/sup -6/ quarks per proton interaction at 90% confidence limit, the results from the second run show that the upper limit is 9.3 x 10/sup -10/. The analysis of the mercury is continuing