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

A Public Choice Analysis of Endangered Species Listings

Sizable economic consequences may resultfrom listing under the Endangered SpeciesAct (ESA). Potentially adversely affectedparties will attempt to use the politicalprocess to protect their interests. Thequestion is, “are listing determinationssubject to political manipulation?” Inthis paper, we explore empirically thepossibility that implementation of the ESAis determined, in part, by politicalconsiderations. Specifically, weinvestigate whether states with strongcongressional representation are able touse their political muscle to reduce thenumber of listings in their states, ascompared to states with weak congressionalrepresentation. Controlling for otherfactors, we find that states with greaterrepresentation on the U.S. Fish andWildlife Service’s budgetary oversightsubcommittee in the U.S. House ofRepresentatives have significantly fewerESA listings than states with weakerrepresentation on that subcommittee. Copyright Kluwer Academic Publishers 2004

ADM1-based mechanistic model for the role of trace elements in anaerobic digestion processes

An original mechanistic model able to describe the fate of trace elements (TE) in anaerobic digestion systems has been synthetized from mass balance equations. The model takes into account the main biochemical and physico-chemical processes affecting TE bioavailability and it is aimed at evaluating the effect that the combination of such processes exerts on the system performance. Five main modules have been introduced: biochemistry, physico-chemistry, sorption, complexation and precipitation. The model is based on mass conservation principles and is formulated as a set of ordinary differential equations for the soluble and particulate components constituting the system. Model applications of two illustrative cases are provided. The first case is based on experimental results and examines the effect of TE depletion in an AD process of food waste (FW). The second case shows the effects of different metal supplements on methane production and biogas composition. The simulation results confirm that the model can fairly be used to predict the effect of TE dynamics and bioavailability, by considering biological, chemical and physicochemical processes in AD environments.This work has been developed in the framework of the COST Action 1302 (“European Network on Ecological Roles of Trace Metals in Anaerobic Biotechnologies”) supported by COST (European Cooperation in Science and Technology). L. Frunzo and M.R. Mattei acknowledge the support from the Progetto Giovani G.N.F.M. 2017 >Analisi di Sistemi Biologici Complessi>. L. Frunzo also acknowledges the support from the project VOLAC - Valorization of OLive oil wastes for sustainable production of biocide-free Antibiofilm Compounds, funded by CARIPLO foundation.Peer Reviewe

Topics, Skills, and Cases for an Undergraduate Musculoskeletal Curriculum in Southern Africa

Background: Most patients with orthopaedic pathology in low to middle-income countries are treated by nonspecialists. A curriculum to prepare undergraduate medical students for this duty should reflect the local pathology and skills that are required to manage patients in a resource-restricted environment. The aim of this study was to establish and prioritize a list of core orthopaedic-related knowledge topics, clinical cases, and skills that are relevant to medical students in southern Africa and areas with a similar clinical context. Methods: A modified Delphi consensus study was conducted with 3 interactive iterative rounds of communication and prioritization of items by experts from Africa, Europe, and North America. Preferred priorities were selected but were limited to 50% of all of the possible items. Percent agreement of ≥75% was defined as consensus on each of these items. Results: Most of the 43 experts who participated were orthopaedic surgeons from 7 different countries in southern Africa, but 28% were general practitioners or doctors working in primary or secondary-level facilities. Experts prioritized cases such as patients with multiple injuries, a limping child, and orthopaedic emergencies. Prioritized skills were manipulation and immobilization of dislocations and fractures. The most important knowledge topics included orthopaedic infections, the treatment of common fractures and dislocations, any red flags alerting to specialist referral, and back pain. Surgical skills for the treatment of urgent care conditions were included by some experts who saw a specific need in their clinical practice, but these were ranked lower. Conclusions: A wide geographic, academic, and expertise-specific footprint of experts informed this international consensus through their various clinical and academic circumstances. Knowledge topics, skills, and cases concerning orthopaedic trauma and infection were prioritized by the highest percent agreement. Acute primary care for fractures and dislocations ranked high. Furthermore, the diagnosis and the treatment of conditions not requiring specialist referral were prioritized. This study can inform national curricula in southern Africa and assist in the allocation of student clinical rotations