Meningococcal core and accessory phasomes vary by clonal complex

Neisseria meningitidis is a Gram-negative human commensal pathogen, with extensive phenotypic plasticity afforded by phase-variable (PV) gene expression. Phase variation is a stochastic switch in gene expression from an ON to an OFF state, mediated by localized hypermutation of simple sequence repeats (SSRs). Circulating N. meningitidis clones vary in propensity to cause disease, with some clonal complexes (ccs) classified as hypervirulent and others as carriage-associated. We examined the PV gene repertoires, or phasome, of these lineages in order to determine whether phase variation contributes to disease propensity. We analysed 3328 genomes representative of nine circulating meningococcal ccs with PhasomeIt, a tool that identifies PV genes by the presence of SSRs and homologous gene clusters. The presence, absence and functions of all identified PV gene clusters were confirmed by annotation or blast searches within the Neisseria PubMLST database. While no significant differences were detected in the number of PV genes or the core, conserved phasome content between hypervirulent and carriage lineages, individual ccs exhibited major variations in PV gene numbers. Phylogenetic clusters produced by phasome or core genome analyses were similar, indicating co-evolution of PV genes with the core genome. While conservation of PV clusters is high, with 76 % present in all meningococcal isolates, maintenance of an SSR is variable, ranging from conserved in all isolates to present only in a single cc, indicating differing evolutionary trajectories for each lineage. Diverse functional groups of PV genes were present across the meningococcal lineages; however, the majority directly or indirectly influence bacterial surface antigens and could impact on future vaccine development. Finally, we observe that meningococci have open pan phasomes, indicating ongoing evolution of PV gene content and a significant potential for adaptive changes in this clinically relevant genus

University vaccine campaign increases meningococcal ACWY vaccine coverage

In this study, we report MenACWY vaccine coverage in first year students arriving at the University of Nottingham (UoN) in September 2015. We also report the uptake of MenACWY vaccine offered to unvaccinated students via a campus-based mass vaccination campaign as part of a local initiative by the University of Nottingham Health Service (UNHS), in liaison with UoN, during the registration period. [Taken from introduction

The Cost of Implementing and Sustaining the COMprehensive Post-Acute Stroke Services Model

Background:The COMprehensive Post-Acute Stroke Services (COMPASS) model, a transitional care intervention for stroke patients discharged home, was tested against status quo postacute stroke care in a cluster-randomized trial in 40 hospitals in North Carolina. This study examined the hospital-level costs associated with implementing and sustaining COMPASS.Methods:Using an activity-based costing survey, we estimated hospital-level resource costs spent on COMPASS-related activities during approximately 1 year. We identified hospitals that were actively engaged in COMPASS during the year before the survey and collected resource cost estimates from 22 hospitals. We used median wage data from the Bureau of Labor Statistics and COMPASS enrollment data to estimate the hospital-level costs per COMPASS enrollee.Results:Between November 2017 and March 2019, 1582 patients received the COMPASS intervention across the 22 hospitals included in this analysis. Average annual hospital-level COMPASS costs were $2861 per patient (25th percentile:$735; 75th percentile: $3,475). Having 10% higher stroke patient volume was associated with 5.1% lower COMPASS costs per patient (P=0.016). About half (N=10) of hospitals reported postacute clinic visits as their highest-cost activity, while a third (N=7) reported case ascertainment (ie, identifying eligible patients) as their highest-cost activity.Conclusions:We found that the costs of implementing COMPASS varied across hospitals. On average, hospitals with higher stroke volume and higher enrollment reported lower costs per patient. Based on average costs of COMPASS and readmissions for stroke patients, COMPASS could lower net costs if the model is able to prevent about 6 readmissions per year

Pion contamination in the MICE muon beam

The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240\,MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than $\sim$1\% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is $f_\pi < 1.4\%$ at 90\% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.Department of Energy and National Science Foundation (U.S.A.), the Instituto Nazionale di Fisica Nucleare (Italy), the Science and Technology Facilities Council (U.K.), the European Community under the European Commission Framework Programme 7 (AIDA project, grant agreement no. 262025, TIARA project, grant agreement no. 261905, and EuCARD), the Japan Society for the Promotion of Science and the Swiss National Science Foundation, in the framework of the SCOPES programme