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

Development and testing of the Cholesterol-Lowering Diet Self-Efficacy Scale

A cornerstone of treatment for hypercholesterolemia is dietary therapy. However, maintaining adherence to the therapeutic diet has been difficult for patients. There is evidence that self-efficacy is a predictor of positive behavior change like that involved in or necessary for initiating or maintaining recommended diet therapy for cholesterol reduction. This paper reports on two studies guided by Bandura's self-efficacy theory. The first study focuses on development and initial psychometric evaluation of an instrument measuring self-efficacy for adhering to a cholesterol-lowering diet in a sample of 44 cardiac rehabilitation patients; the second establishes psychometric properties of the instrument in a sample of 228 subjects treated for hypercholesterolemia. In both studies, subgroups completed the instrument a second time to provide data on the instrument's temporal stability. The Cholesterol-Lowering Diet Self-Efficacy Scale consists of 33 statements, some with branches for a total of 56 items. The scale measures several components of the eating habits domain related to adhering to a cholesterol-lowering eating plan, and shows good reliability and validity. Reported self-efficacy is related to prior persistence and past success in modifying and maintaining dietary changes, and also to concurrent measures of dietary adherence behaviors. The scale is psychometrically sound thus far and seems adequate in identifying success in achieving and maintaining a cholesterol-lowering eating plan. © 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved

The Witan, 1975-1976 Academic Year V. 3 No. 8, April 1976

Advertising in Philadelphia Whither Thou Goest ABA?, Federal Penal Code Proposed, Nursing School, Save Yourself the Trouble, Rehabilitation Examined, New Faculty Appointments, Ascent of Man, One for the Road, Buen Provencho, Academy Lauds Show Zanuck to

The Witan, 1975-1976 Academic Year V. 3 No. 8, April 1976

Advertising in Philadelphia Whither Thou Goest ABA?, Federal Penal Code Proposed, Nursing School, Save Yourself the Trouble, Rehabilitation Examined, New Faculty Appointments, Ascent of Man, One for the Road, Buen Provencho, Academy Lauds Show Zanuck to

Evaluating the performance of shading devices and glazing types to promote energy efficiency of residential buildings

10.1007/s12273-010-0007-2Building Simulation33181-19