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

Elevated gastrin levels after pancreatic duct ligation.

[No abstract available

Derived limits for routine discharges of gaseous effluents from buildings 220, 393.6, 459, 336.17 and 462 at Harwell Laboratory

SIGLEAvailable from British Library Lending Division - LD:9091.9F(AERE-R--11346) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The importance of behavioral and situational characteristics for entrepeneurial success: an international rating study

A judgemental analysis has been executed of the job of entrepreneur in terms of the required behavioural, or 'human', attributes and in terms of the relevance of 'situational' attributes for entrepreneurial success. Ratings were given by 235 consultants and starting entrepreneurs from five European countries. By means of generalizability analysis it was investigated whether ratings generalized across countries: Nationality barely had an influence on the ratings. Next, it was questioned whether the type of judge, i.e. consultants or starting entrepreneurs, made a difference. No difference was found for the situational attributes. However, the behavioural attributes as a whole were judged to be more important by starters than by consultants. In general, it was not so much the type or nationality of the judge, as individual differences between judges that had an effect on the ratings. Overall, consensus was higher among consultants than among starting entrepreneurs, and higher on the importance of the situational than of the behavioural attributes. The three situational agttributes judged as most important were: Number of Clients, Type of Product, and Competition. The three most important behavioural attributes were judged to be Market Orientedness, Perseverance, and Independence (consultants), and Perseverence, Independence, and Financial Control (starters)