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

India's National Action Plan on Antimicrobial Resistance: a critical perspective

Antimicrobial resistance (AMR) is widely recognised as a global health threat, which is projected to account for more deaths than cancer by 2050. The Government of India has formulated a National Action Plan to tackle AMR (NAP-AMR), largely modelled on the World Health Organization's Global Action Plan on AMR. While the NAP-AMR successfully mirrors the Global Action Plan and lays out ambitious goals, we find that the lack of financial allocation across states, poor enforcement and inadequate multisectoral co-ordination have hampered progress. A broader focus on improving infrastructure for water and sanitation, linking the issue of AMR to existing vertical health programmes for human immunodeficiency virus (HIV) and tuberculosis (TB), prioritising infection prevention and control, strengthening the frontline healthcare workforce in rural and peri-urban settings to reduce reliance on antibiotics, leveraging pointof-care testing and mobile app-based health interventions for diagnosis and surveillance, and adopting a socioecological approach to health and development would help to create an enabling environment for concrete action on AMR in India. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/

When the native is also a non-native: “retrodicting” the complexity of language teacher cognition

Abstract: The impact of native (NS) and non-native speaker (NNS) identities on second or foreign language teachers’ cognition and practices in the classroom has mainly been investigated in ESL/EFL contexts. Using complexity theory as a framework, this case study attempts to fill the gap in the literature by presenting a foreign language teacher in the United States who teaches French as a NS and German as a NNS teacher at the college level. Specifically, the study explores the interface between NS/NNS identities, teacher cognition, practice, and professional identity. The retrodictive qualitative analysis of semi-structured interviews and classroom observations reveals that the participant teacher’s NS French and NNS German identities influenced her teacher cognition, specifically in beliefs about teaching grammar. In addition, previous language learning experiences affect current decision-making processes in teaching. In terms of teaching practice, the dual NS French and NNS German identity affects teaching practice in the formal areas of language, target culture knowledge and awareness, teaching style, and perceptions about language varieties. Professional identity is construed here as being the mediator of target second language (L2) cultures in the classroom. The implications of teacher cognition as a complex system for L2 teaching and teacher education are discussed

From numbers to ecosystems and biodiversity: A mechanistic approach to monitoring

Diverse political, cultural and biological needs epitomise the contrasting demands impacting on the mandate of the South African National Parks (SANParks) to maintain biological diversity. Systems-based approaches and strategic adaptive management (learn by doing) enable SANParks to accommodate these demands. However, such a management strategy creates new information needs, which require an appropriate analytical approach. We use conceptual links between objectives, indicators, mechanisms and modulators to identify key concerns in the context of and related to management objectives. Although our suggested monitoring designs are based mostly on defined or predicted underlying mechanisms of a concern, SANParks requires inventory monitoring to evaluate its key mandate. We therefore propose a predictive inventory approach based on species assemblages related to habitat preferences. Inventories alone may not always adequately serve unpacking of mechanisms: in some cases population size needs to be estimated to meet the information needs of management strategies, but actual population sizes may indirectly affect how the species impact on other values. In addition, ecosystem objectives require multivariate assessments of key communities, which can be used in trend analysis. SANParks therefore needs to know how to detect and define trends efficiently, which, in turn, requires precision of measures of variables. Conservation implications: Current research needs with regard to monitoring should focus on defining designs to yield optimal precision whilst taking methodology, survey trade-offs and analytical approaches into account. Use of these directives and research will guide monitoring during evaluation of SANParks objectives at various scales

Analysis of test beam data taken with a prototype of TPC with resistive Micromegas for the T2K Near Detector upgrade

In this paper we describe the performance of a prototype of the High Angle Time Projection Chambers (HA-TPCs) that are being produced for the Near Detector (ND280) upgrade of the T2K experiment. The two HA-TPCs of ND280 will be instrumented with eight Encapsulated Resistive Anode Micromegas (ERAM) on each endplate, thus constituting in total 32 ERAMs. This innovative technique allows the detection of the charge emitted by ionization electrons over several pads, improving the determination of the track position. The TPC prototype has been equipped with the first ERAM module produced for T2K and with the HA-TPC readout electronics chain and it has been exposed to the DESY Test Beam in order to measure spatial and dE/dx resolution. In this paper we characterize the performances of the ERAM and, for the first time, we compare them with a newly developed simulation of the detector response. Spatial resolution better than 800 ${\mu \rm m}$ and dE/dx resolution better than 10% are observed for all the incident angles and for all the drift distances of interest. All the main features of the data are correctly reproduced by the simulation and these performances fully fulfill the requirements for the HA-TPCs of T2K