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

Resonant cavity enhanced photodetectors for the mid-wave infrared

We present III-Sb resonant cavity-enhanced (RCE) photodetectors suitable for gas detection in the mid-wave infrared. AlAsSb/GaSb DBRs and absorbers of bulk InAsSb or a type-II InAsSb-InAs SLS were grown on GaSb, allowing for operation at 3.72 μm or 4.52 μm, with linewidth Δλ 20x reduction in noise compared with a conventional nBn detector with full thickness absorber. At 3.72 μm, performance above the BLIP limit imposed on broadband photodetectors was found by calculating for the specific detectivity

Chronic nonpulsatile blood flow. III. Effects of pump flow rate on oxygen transport and utilization in chronic nonpulsatile biventricular bypass

AbstractThe relationship between blood flow and oxygen transport was studied in five calves with chronic nonpulsatile biventricular bypass. Seven days was allowed for recovery from the effects of anesthesia and operation; the natural heart was then fibrillated. Pump flows were maintained at nominal rates of 90, 100, or 120 ml ·kg-1 · min for 1 week each, with the sequence varied from experiment to experiment. Venous and arterial blood samples were taken at rest for blood gas analysis. Serum lactate analysis was done twice a week, on the third and seventh days after each pump flow change. Serum catecholamine levels were assayed on the seventh day of each flow rate. Progressive exercise tests were also conducted during each test segment. Basal oxygen consumption of a 4-month-old calf was 6.3 ± 0.3 ml · kg-1 · min-1. The mixed venous oxygen tension decreased when pump flow rate was reduced (29.6 ± 1.0, 28.3 ± 1.2, and 23.8 ± 0.9 mm Hg at 120, 100, and 90 ml · kg-1 · min-1 of pump flow, respectively), and oxygen extraction increased linearly when pump flow rate was reduced. Hemoglobin concentration significantly affected oxygen extraction rate. Serum lactate concentration increased significantly at a 90 ml · kg-1 · min-1 perfusion compared with concentrations at other pump flow rates (7.81 ± 2.42 mEq/L at 90 ml · kg-1 · min-1 vs 0.71 ± 0.19 and 0.73 ± 0.81 mEq/L at 100 and 120 ml · kg-1 · min-1, respectively; p < 0.01, analysis of variance, Scheffe F test). Maximum oxygen extraction during exercise was 78%. These results suggest that a critical flow level between 90 and 100 ml · kg-1 · min-1 maintains oxidative metabolism in the calf with chronic nonpulsatile flow. The resulting oxygen delivery was slightly higher than that indicated in the literature. Maximal oxygen extraction was normal. (J THORAC CARDIOVASC SURG 1996;111:863-72

Design and development of a system for the detection of agreement errors in basque

Abstract. This paper presents the design and development of a system for the detection and correction of syntactic errors in free texts. The system is composed of three main modules: a) a robust syntactic analyser, b) a compiler that will translate error processing rules, and c) a module that coordinates the results of the analyser, applying different combinations of the already compiled error rules. The use of the syntactic analyser (a) and the rule processor (b) is independent and not necessarily sequential. The specification language used for the description of the error detection/correction rules is abstract, general, declarative, and based on linguistic information.