Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

GEN Z'S PERCEPTION OF ORGANIZATIONAL ALIGNMENT AND ITS IMPACT ON EMPLOYEE ENGAGEMENT

<p>As members of Generation Z (Gen Z) become integral parts of the contemporary workforce, characterized by their tech-savvy nature, they bring distinct perspectives and expectations to the workplace. This paper aims to comprehensively explore the factors influencing Gen Z's engagement in the workplace and elucidate the correlation of these factors with overall employee engagement. The foundation of this research lies in a thorough literature review, which informs the development of hypotheses. Leveraging insights from existing research papers, this study employs MS Excel for data analysis, utilizing statistical tools such as correlation coefficient and regression. The findings reveal a positive correlation between identified factors and both organizational performance and employee engagement among Gen Z. Notably, career development and rewards and recognitions emerge as pivotal factors. The paper underscores the necessity for policy adaptations to accommodate the unique expectations of this emerging workforce. Failure to address these evolving dynamics may impede companies' ability to effectively attract, retain, and engage Gen Z in the evolving workplace landscape</p&gt

High-pressure studies of GaAs-AlxGa1-xAs quantum wells at 300 and 80 K using photoreflectance spectroscopy

URL:http://link.aps.org/doi/10.1103/PhysRevB.38.9790 DOI:10.1103/PhysRevB.38.9790A detailed photoreflectance study of a GaAs-Al0.3Ga0.7As multiple quantum well of well width 260 Å is carried out at 300 and 80 K. The pressure dependence of a large number of quantized states is observed. The sublinearity of pressure dependence increases with increasing quantum number. A model calculation that includes the pressure dependence of electron effective mass accurately describes the data. Transitions associated with L and X band extrema are observed and their pressure coefficients deduced.This work was supported by the U.S. Department of Energy under Contract No. DE-AC02-84ER45048 and by the U.S. Army under Contract No. DAAL03-86-K0083

Temperature dependence of the quantized states in a GaAs-Ga1-xAlxAs superlattice

URL:http://link.aps.org/doi/10.1103/PhysRevB.37.1035 DOI:10.1103/PhysRevB.37.1035A detailed study of the photoreflectance spectra of a GaAs-Al0.3Ga0.7As superlattice as a function of temperature has revealed the temperature coefficients of the quantum- well transitions associated with the direct Γ conduction band (CB) of GaAs and the staggered transitions from the X-CB of AlxGa1-xAs to the valence band of GaAs. The data have been fitted to Varshni's equation. We have also observed the evolution of the excitonic transitions, especially for lower quantized states, as the temperature is decreased yielding the binding energies.This work ws supported by the u.S. Department of Energy under Contract No. DE-AC0284ER45048. The work by one of us (M.C.) was supported in part by the Alfred P. Sloan Foundation