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

Impact of the source-correlation model in jet-noise prediction by acoustic analogy

For both Lilley and moving-frame Lighthill analogies the applied-stress equivalent source is given by the Reynolds stress. Previous jet-noise predictions based on the acoustic analogy adopted a frequency/wave-number source spectrum obtained by applying Fourier transform in space and time on an analytically suitable expression for the Reynolds-stress 2-point cross-correlation coefficient. Very few experimental data for the Reynolds-stress correlation are available in literature. Harper-Bourne has published a limited set of hot-wire measurements taken on a low-speed jet and corresponding to a single location on the nozzle lip line. In this paper a model for the 2-point correlation of the fluctuating Reynolds stress is introduced and compared to two previous correlation models and to the Harper-Bourne data. This shows to which extent the two-point correlation models can be adopted to t the turbulence measurements. The acoustic-source strength per unit volume is modelled in the frequency domain and broken down as product of different factors. The determination of these factors is performed by starting from some suitable 2-point correlation models including the model proposed here and one of the previous models. The output volumetric-strength spectra are used in turn as source master spectrum for a RANS-based jet-noise prediction. This shows the incidence of different correlation models on the estimation of isothermal 90-degree 1/3-octave jet-noise spectra

The Swiss Federation of Clinical Neuro-Societies and Young Clinical Neuroscientists Network.

The Swiss Federation of Clinical Neuro-Societies (SFCNS) was founded in 2009 and currently unites 14 clinical neuroscience associations. Its primary goals are the promotion of clinical, scientific, and educational interdisciplinary collaboration, as well as to establish a united voice towards other organisations, policy makers, and society.1 The SFCNS has received a mandate from the Swiss public health authorities to coordinate the implementation of highly specialised medicine in clinical neuroscience. Similar to the German Neurowoche,2 the SFCNS organises an interdisciplinary congress every 3 years (the next taking place in Lausanne, Switzerland, on Oct 23–25, 2019). This congress and our annual SFCNS Summer School promote education and discussion in clinical neuroscience. Last year, the SFCNS launched the journal Clinical and Translational Neuroscience, as successor of the Swiss Archives of Neurology and Psychiatry, founded by Constantin von Monakow about a century ago..

Swiss Narcolepsy Scale: a valid tool for the identification of hypocretin-1 deficient patients with narcolepsy

Paroxysmal Cerebral Disorder