Reassortment between Influenza B Lineages and the Emergence of a Coadapted PB1-PB2-HA Gene Complex

Influenza B viruses make a considerable contribution to morbidity attributed to seasonal influenza. Currently circulating influenza B isolates are known to belong to two antigenically distinct lineages referred to as B/Victoria and B/Yamagata. Frequent exchange of genomic segments of these two lineages has been noted in the past, but the observed patterns of reassortment have not been formalized in detail. We investigate interlineage reassortments by comparing phylogenetic trees across genomic segments. Our analyses indicate that of the eight segments of influenza B viruses only segments coding for polymerase basic 1 and 2 (PB1 and PB2) and hemagglutinin (HA) proteins have maintained separate Victoria and Yamagata lineages and that currently circulating strains possess PB1, PB2, and HA segments derived entirely from one or the other lineage; other segments have repeatedly reassorted between lineages thereby reducing genetic diversity. We argue that this difference between segments is due to selection against reassortant viruses with mixed-lineage PB1, PB2, and HA segments. Given sufficient time and continued recruitment to the reassortment-isolated PB1–PB2–HA gene complex, we expect influenza B viruses to eventually undergo sympatric speciation

Delivery of drinking, eating and mobilising (DrEaMing) and its association with length of hospital stay after major noncardiac surgery: observational cohort study

BACKGROUND: Enhanced recovery pathways are associated with improved postoperative outcomes. However, as enhanced recovery pathways have become more complex and varied, compliance has reduced. The ‘DrEaMing’ bundle re-prioritises early postoperative delivery of drinking, eating, and mobilising. We investigated relationships between DrEaMing compliance, postoperative hospital length of stay (LOS), and complications in a prospective multicentre major surgical cohort. METHODS: We interrogated the UK Perioperative Quality Improvement Programme dataset. Analyses were conducted in four stages. In an exploratory cohort, we identified independent predictors of DrEaMing. We quantified the association between delivery of DrEaMing (and its component variables) and prolonged LOS in a homogenous colorectal subgroup and assessed generalisability in multispecialty patients. Finally, LOS and complications were compared across hospitals, stratified by DrEaMing compliance. RESULTS: The exploratory cohort comprised 22 218 records, the colorectal subgroup 7230, and the multispecialty subgroup 5713. DrEaMing compliance was 59% (13 112 patients), 60% (4341 patients), and 60% (3421), respectively, but varied substantially between hospitals. Delivery of DrEaMing predicted reduced odds of prolonged LOS in colorectal (odds ratio 0.51 [0.43–0.59], P<0.001) and multispecialty cohorts (odds ratio 0.47 [0.41–0.53], P<0.001). At the hospital level, complications were not the primary determinant of LOS after colorectal surgery, but consistent delivery of DrEaMing was associated with significantly shorter LOS. CONCLUSIONS: Delivery of bundled and unbundled DrEaMing was associated with substantial reductions in postoperative LOS, independent of the effects of confounder variables. Consistency of process delivery, and not complications, predicted shorter hospital-level LOS. DrEaMing may be adopted by perioperative health systems as a quality metric to support improved patient outcomes and reduced LOS

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.PREDICTS has been supported by U.K. Natural Environment Research Council grants (NE/J011193/2 and NE/L002515/1), the United Nations Environment Program World Conservation Monitoring Centre, Biotechnology and Biological Sciences Research Council grant (BB/F017324/1), a Hans Rausing PhD Scholarship and COLCIENCIAS (Departamento Administrativo de Ciencia, Tecnología e Innovación de Colombia)

The Perioperative Quality Improvement Programme (PQIP patient study): protocol for a UK multicentre, prospective cohort study to measure quality of care and outcomes after major surgery

INTRODUCTION: Major surgery accounts for a substantial proportion of health service activity, due not only to the primary procedure, but the longer-term health implications of poor short-term outcome. Data from small studies or from outside the UK indicate that rates of complications and failure to rescue vary between hospitals, as does compliance with best practice processes. Within the UK, there is currently no system for monitoring postoperative complications (other than short-term mortality) in major non-cardiac surgery. Further, there is variation between national audit programmes, in the emphasis placed on quality assurance versus quality improvement, and therefore the principles of measurement and reporting which are used to design such programmes. METHODS AND ANALYSIS: The PQIP patient study is a multi-centre prospective cohort study which recruits patients undergoing major surgery. Patient provide informed consent and contribute baseline and outcome data from their perspective using a suite of patient-reported outcome tools. Research and clinical staff complete data on patient risk factors and outcomes in-hospital, including two measures of complications. Longer-term outcome data are collected through patient feedback and linkage to national administrative datasets (mortality and readmissions). As well as providing a uniquely granular dataset for research, PQIP provides feedback to participating sites on their compliance with evidence-based processes and their patients' outcomes, with the aim of supporting local quality improvement. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Health Research Authority in the UK. Dissemination of interim findings (non-inferential) will form a part of the improvement methodology and will be provided to participating centres at regular intervals, including near-real time feedback of key process measures. Inferential analyses will be published in the peer-reviewed literature, supported by a comprehensive multi-modal communications strategy including to patients, policy makers and academic audiences as well as clinicians

Design of Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Crystallographic Surrogate Derived from Checkpoint Kinase 1 (CHK1)

Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson’s disease. Surrogates for the LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed, expressed in insect cells infected with baculovirus, purified, and crystallized. X-ray structures of the surrogates complexed with known LRRK2 inhibitors rationalized compound potency and selectivity. The CHK1 10-point mutant was preferred, following assessment of surrogate binding affinity with LRRK2 inhibitors. Fragment hit-derived arylpyrrolo­[2,3-<i>b</i>]­pyridine LRRK2 inhibitors underwent structure-guided optimization using this crystallographic surrogate. LRRK2-pSer935 HEK293 IC₅₀ data for <b>22</b> were consistent with binding to Ala2016 in LRRK2 (equivalent to Ala147 in CHK1 10-point mutant structure). Compound <b>22</b> was shown to be potent, moderately selective, orally available, and brain-penetrant in wild-type mice, and confirmation of target engagement was demonstrated, with LRRK2-pSer935 IC₅₀ values for <b>22</b> in mouse brain and kidney being 1.3 and 5 nM, respectively

Rockport Comprehensive Plan

This document was developed and prepared by Texas Target Communities (TxTC) at Texas A&M University in partnership with the City of Rockport, Texas Sea Grant, Texas A&M University - Corpus Christi, Texas A&M University - School of Law and Texas Tech University.Founded in 1871, the City of Rockport aims to continue growing economically and sustainably. Rockport is a resilient community dedicated to sustainable growth and attracting businesses to the area. Rockport is a charming town that offers a close-knit community feel and is a popular tourist destination for marine recreation, fairs, and exhibitions throughout the year. The Comprehensive Plan 2020-2040 is designed to guide the city of Rockport for its future growth. The guiding principles for this planning process were Rockport's vision statement and its corresponding goals, which were crafted by the task force. The goals focus on factors of growth and development including public participation, development considerations, transportation, community facilities, economic development, parks, and housing and social vulnerability

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment