A field study of team working in a new human supervisory control system

This paper presents a case study of an investigation into team behaviour in an energy distribution company. The main aim was to investigate the impact of major changes in the company on system performance, comprising human and technical elements. A socio-technical systems approach was adopted. There were main differences between the teams investigated in the study: the time of year each control room was studied (i.e. summer or winter),the stage of development each team was in (i.e. 10 months), and the team structure (i.e. hierarchical or heterarchical). In all other respects the control rooms were the same: employing the same technology and within the same organization. The main findings were: the teams studied in the winter months were engaged in more `planning’ and `awareness’ type of activities than those studies in the summer months. Newer teams seem to be engaged in more sharing of information than older teams, which maybe indicative of the development process. One of the hierarchical teams was engaged in more `system-driven’ activities than the heterarchical team studied at the same time of year. Finally, in general, the heterarchical team perceived a greater degree of team working culture than its hierarchical counterparts. This applied research project confirms findings from laboratory research and emphasizes the importance of involving ergonomics in the design of team working in human supervisory control

Delivery of chlamydia screening to young women requesting emergency hormonal contraception at pharmacies in Manchester, UK: a prospective study

<p>Abstract</p> <p>Background</p> <p>More women are requesting Emergency Hormonal Contraception (EHC) at pharmacies where screening for <it>Chlamydia trachomatis </it>is not routinely offered. The objective of this study was to assess the uptake of free postal chlamydia screening by women under 25 years who requested EHC at pharmacies in Manchester, UK.</p> <p>Methods</p> <p>Six Primary Care Trusts (PCTs) that had contracted with pharmacies to provide free EHC, requested the largest EHC providers (≥ 40 doses annually) to also offer these clients a coded chlamydia home testing kit. Pharmacies kept records of the ages and numbers of women who accepted or refused chlamydia kits. Women sent urine samples directly to the laboratory for testing and positive cases were notified. Audit data on EHC coverage was obtained from PCTs to assess the proportion of clients eligible for screening and to verify the uptake rate.</p> <p>Results</p> <p>33 pharmacies participated. Audit data for 131 pharmacy months indicated that only 24.8% (675/2718) of women provided EHC were also offered chlamydia screening. Based on tracking forms provided by pharmacies for the whole of the study, 1348/2904 EHC clients (46.4%) who had been offered screening accepted a screening kit. 264 (17.6%) of those who accepted a kit returned a sample, of whom 24 (9.1%) were chlamydia-positive. There was an increase in chlamydia positivity with age (OR: 1.2 per year; 1.04 to 1.44; p = 0.015).</p> <p>Conclusion</p> <p>Chlamydia screening for EHC pharmacy clients is warranted but failure of pharmacists to target all EHC clients represented a missed opportunity for treating a well defined high-risk group.</p

Uncovering the Importance of Selenium in Muscle Disease

A connection between selenium bioavailability and development of muscular disorders both in humans and livestock has been established for a long time. With the development of genomics, the function of several selenoproteins was shown to be involved in muscle activity, including SELENON, which was linked to an inherited form of myopathy. Development of animal models has helped to dissect the physiological dysfunction due to mutation in the SELENON gene; however the molecular activity remains elusive and only recent analysis using both in vivo and in vitro experiment provided hints toward its function in oxidative stress defence and calcium transport control. This review sets out to summarise most recent findings for the importance of selenium in muscle function and the contribution of this information to the design of strategies to cure the diseases

Characterization of an Nmr Homolog That Modulates GATA Factor-Mediated Nitrogen Metabolite Repression in Cryptococcus neoformans

Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis

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 hospitalization2–4 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

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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