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

Performance analysis of Pareto optimal bearings subject to surface error variations

A Pareto optimization study was carried out on a flat pad aerostatic bearing design. Some of the Pareto optimal configurations were then subjected to surface profiling errors including tilt, concavity, convexity and waviness and key performance parameters such as load capacity, stiffness and flow rate determined. From these studies it was concluded that multi-orifice aerostatic flat pad bearings are highly sensitive to surface profile variations and these surface profile variations are inherent limitations of the current manufacturing techniques. A technique to account for the sensitivity to manufacturing tolerance within air bearing optimization studies is also proposed

Designing the interface to encourage more cognitive processing

Cognitive engineering aims to provide operators with immediate access to as much relevant information as possible. However, this can encourage display-based strategies that do not involve committing information to memory. To overcome this problem, a somewhat counterintuitive method is discussed, based upon the theory of soft constraints [1], that involves delaying access to some critical information by one or two seconds. This design technique induces a more planful and memory-based strategy that can improve recall, develop more planning behavior, improve problem solving, and protect against the negative effects of interruption. Furthermore, we provide some preliminary results that this more memory-intensive strategy can be trained through past experience with high access cost and then used in situations where access cost is minimal. This was the case when only half of the training trials involved a higher access cost. Further research is needed to ascertain how long training effects last and what are the ideal training regimes for different types of task

Unemployment and psychological distress one year after childbirth in France

STUDY OBJECTIVE—To analyse the relation between unemployment and the psychological distress of mothers one year after childbirth.
DESIGN—Multicentric survey concerning births occurring between September 1993 and July 1994.
SETTING—In France: two maternity units in the Parisian area and one in Champagne-Ardennes, in the east of France, comprising both urban and rural areas.
PARTICIPANTS—Primipara and secondipara women were interviewed three times: at birth by a face to face interview, five months and 12 months after the birth, by postal questionnaires, with a 83% response rate for the two postal questionnaires. The analysis includes 632 women who answered all three stages of the survey.
MEASUREMENTS—Psychological distress was mainly assessed one year after birth by the 12-item General Health Questionnaire.
RESULTS—After adjustment for unwanted pregnancy, marital conflicts, marital status, hospitalisation of the baby during the last year, lack of confiding relationship, depressive or anxious troubles before pregnancy, age, educational level and parity, unemployed women had an excess of psychological distress compared with employed women (OR = 1.87; 95%CI = 1.12, 3.13). The ratios for housewives were very close to those of employed women. Among the unemployed women, 60% had recently been without a job, since a few months before or after the birth. An excess of psychological distress among unemployed compared with employed women was observed in all social groups defined by the current or last occupation, but with various extents. Psychological distress was specially linked to the employment status in the group of women with the more qualified occupations.
CONCLUSION—Even after a birth, when women are very much involved in their maternal role, those seeking a job have worse mental health than those in a stable situation, either employed or housewives. In France, the unemployment rate among young women is high. It is specially important that social regulations protecting employment during and after pregnancy are adequately applied. Employers, legislators, such as medical doctors, have to be aware to this situation.


Keywords: psychological distress; unemployment; childbirth; women's healt