Pre-vaccine serotype composition within a lineage signposts its serotype replacement – a carriage study over 7 years following pneumococcal conjugate vaccine use in the UK

Serotype replacement has been reported in carriage and disease after pneumococcal conjugate vaccine (PCV) introductions in the UK and globally. We previously described concurrent expansion and decline of sequence types associated with serotype replacement over 5 years following PCV introductions in the UK. Here we use whole-genome sequencing to fully characterise the population structure of pneumococcal isolates collected over seven winters encompassing PCV7 and PCV13 introductions in the UK, investigating the importance of lineages in serotype replacement. We analysed 672 pneumococcal genomes from colonised children of 4 years old or less. The temporal prevalence of 20 lineages, defined by hierarchical Bayesian analysis of population structure (BAPS), was assessed in the context of serotype replacement. Multiple serotypes were detected in the primary winter of sampling within three vaccine-type (VT) lineages BAPS4, BAPS10 and BAPS11, in which serotype replacement were observed. In contrast, serotype replacement was not seen in the remaining three VT lineages (BAPS1, BAPS13 and BAPS14), that expressed a single serotype (6B, 6A and 3, respectively) in the primary winter. One lineage, BAPS1 serotype 6B was undetectable in the population towards the end of the study period. The dynamics of serotype replacement, in this UK population, was preceded by the presence or absence of multiple serotypes within VT lineages, in the pre-PCV population. This observation could help predict which non-vaccine types (NVTs) may be involved in replacement in future PCV introductions here and elsewhere. It could further indicate whether any antibiotic resistance associated with the lineages is likely to be affected by replacement.</p

Comparative Genomics of Carriage and Disease Isolates of Streptococcus pneumoniae Serotype 22F Reveals Lineage-Specific Divergence and Niche Adaptation

Streptococcus pneumoniae is a major cause of meningitis, sepsis, and pneumonia worldwide. Pneumococcal conjugate vaccines have been part of the United Kingdom’s childhood immunization program since 2006 and have significantly reduced the incidence of disease due to vaccine efficacy in reducing carriage in the population. Here we isolated two clones of 22F (an emerging serotype of clinical concern, multilocus sequence types 433 and 698) and conducted comparative genomic analysis on four isolates, paired by Sequence Type (ST) with one of each pair being derived from carriage and the other disease (sepsis). The most compelling observation was of nonsynonymous mutations in pgdA, encoding peptidoglycan N-acetylglucosamine deacetylase A, which was found in the carriage isolates of both ST433 and 698. Deacetylation of pneumococcal peptidoglycan is known to enable resistance to lysozyme upon invasion. Althought no other clear genotypic signatures related to disease or carriage could be determined, additional intriguing comparisons between the two STs were possible. These include the presence of an intact prophage, in addition to numerous additional phage insertions, within the carriage isolate of ST433. Contrasting gene repertoires related to virulence and colonization, including bacteriocins, lantibiotics, and toxin-–antitoxin systems, were also observed

The Grizzly, April 7, 1992

Mr. Resident Assistant, Chris Foust, Wins Mr. Ursinus Title • First Phi Beta Kappa Members Inducted • Today\u27s Health • New College House • Health Service Changes Set for Next Year • Congratulations to the Newly Elected USGA and Class Officers! • Lindback Award Nominations • Key Senior Donations • Roving Reporter: Should Marijuana be Legalized? • The Academy Awards and High Hollywood Fashion • Berman Exhibits Students\u27 Work • New Carnivore Kingdom to Open at the Zoo • Olin Cellist • A Measurable Success • Celebrity Spotlight • D.C. Art Internship • USGA Minutes • Environmental Notes • Talk Shows: TV\u27s Big Lie • Campus Memo • Special Olympics Hosted • Golf Goes 4-0https://digitalcommons.ursinus.edu/grizzlynews/1990/thumbnail.jp

Physical viscosity in smoothed particle hydrodynamics simulations of galaxy clusters

Most hydrodynamical simulations of galaxy cluster formation carried out to date have tried to model the cosmic gas as an ideal, inviscid fluid, where only a small amount of (unwanted) numerical viscosity is present, arising from practical limitations of the numerical method employed, and with a strength that depends on numerical resolution. However, the physical viscosity of the gas in hot galaxy clusters may in fact not be negligible, suggesting that a self-consistent treatment that accounts for the internal gas friction would be more appropriate. To allow such simulations using the smoothed particle hydrodynamics (SPH) method, we derive a novel SPH formulation of the Navier-Stokes and general heat transfer equations and implement them in the GADGET-2 code. We include both shear and bulk viscosity stress tensors, as well as saturation criteria that limit viscous stress transport where appropriate. Adopting Braginskii's parameterization for the shear viscosity of hot gaseous plasmas, we then study the influence of viscosity on the interplay between AGN-inflated bubbles and the surrounding intracluster medium (ICM). We find that certain bubble properties like morphology, maximum clustercentric radius reached, or survival time depend quite sensitively on the assumed level of viscosity. Interestingly, the sound waves launched into the ICM by the bubble injection are damped by physical viscosity, establishing a non-local heating process. Finally, we carry out cosmological simulations of galaxy cluster formation with a viscous intracluster medium. Viscosity modifies the dynamics of mergers and the motion of substructures through the cluster atmosphere. Substructures are generally more efficiently stripped of their gas, leading to prominent long gaseous tails behind infalling massive halos. (Abridged)Comment: 24 pages, 13 figures, minor revisions, MNRAS accepte

Accounting regulation and management discretion - a case note

Pre-print version. Final version published by Wiley. The definitive version is available at http://onlinelibrary.wiley.com/This article explores the manipulation of published financial reports in order to counter the potentially unfavourable impact of newly introduced regulation. In this case the reported capital ratio of a major British building society was enhanced using a sale and leaseback transaction with a related party and a change in depreciation policy, methods which reflected limited alternatives. Analysis of the case is set in the context of the sector and addresses the questions of whether these manipulations were within then-prevailing generally accepted accounting principles and why, despite disclosure in the society's financial statements, they failed to attract public comment or concern, regulatory action or an audit qualification. In examining a major British mutual financial organization we depart from traditional analyses of managerial discretion in accounting choices in British companies

The Grizzly, April 28, 1992

Earth Day 1992: Fun for All • CoreStates Grants Grant • UC History Majors Present Papers • U.C. a hit at U.N. • Holocaust Survivor Speaks • Scholarly Hat Trick in Biology • Political Cartoonist To Speak • Strunk Runs for Office • Spring Weekend Great Success • Concert Band & Jazz Ensemble Perform • Exam Schedule • Student Art Exhibition Opens, Awards Presented • Wismer\u27s Modern Art Spy • First Friends First • Sophomore Chats Tell All • Letter: Strunk Thanks Democrats • Men\u27s Lacrosse Splits Weekendhttps://digitalcommons.ursinus.edu/grizzlynews/1296/thumbnail.jp

Medial open transversus abdominis plane (MOTAP) catheters for analgesia following open liver resection: study protocol for a randomized controlled trial

Background: The current standard for pain control following liver surgery is intravenous, patient-controlled analgesia (IV PCA) or epidural analgesia. We have developed a modification of a regional technique called medial open transversus abdominis plane (MOTAP) catheter analgesia. The MOTAP technique involves surgically placed catheters through the open surgical site into a plane between the internal oblique muscle and the transverse abdominis muscle superiorly. The objective of this trial is to assess the efficacy of this technique. Methods/design: This protocol describes a multicentre, prospective, blinded, randomized controlled trial. One hundred and twenty patients scheduled for open liver resection through a subcostal incision will be enrolled. All patients will have two MOTAP catheters placed at the conclusion of surgery. Patients will be randomized to one of two parallel groups: experimental (local anaesthetic through MOTAP catheters) or placebo (normal saline through MOTAP catheters). Both groups will also receive IV PCA. The primary endpoint is mean cumulative postoperative opioid consumption over the first 2 postoperative days (48 hours). Secondary outcomes include pain intensity, patient functional outcomes, and the incidence of complications. Discussion: This trial has been approved by the ethics boards at participating centres and is currently enrolling patients. Data collection will be completed by the end of 2014 with analysis mid-2015 and publication by the end of 2015. Trial registration: The study is registered with http://clinicaltrials.gov (NCT01960049; 23 September 2013)This research is supported by the Innovation Fund of the Alternative Funding Plan from the Academic Health Sciences Centres of Ontario

Respiratory carriage of hypervirulent Klebsiella pneumoniae by indigenous populations of Malaysia

Klebsiella pneumoniae is a Gram-negative Enterobacteriaceae that is classified by the World Health Organisation (WHO) as a Priority One ESKAPE pathogen. South and Southeast Asian countries are regions where both healthcare associated infections (HAI) and community acquired infections (CAI) due to extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant K. pneumoniae (CRKp) are of concern. As K. pneumoniae can also exist as a harmless commensal, the spread of resistance genotypes requires epidemiological vigilance. However there has been no significant study of carriage isolates from healthy individuals, particularly in Southeast Asia, and specially Malaysia. Here we describe the genomic analysis of respiratory isolates of K. pneumoniae obtained from Orang Ulu and Orang Asli communities in Malaysian Borneo and Peninsular Malaysia respectively. The majority of isolates were K. pneumoniae species complex (KpSC) 1 K. pneumoniae (n = 53, 89.8%). Four Klebsiella variicola subsp. variicola (KpSC3) and two Klebsiella quasipneumoniae subsp. similipneumoniae (KpSC4) were also found. It was discovered that 30.2% (n = 16) of the KpSC1 isolates were ST23, 11.3% (n = 6) were of ST65, 7.5% (n = 4) were ST13, and 13.2% (n = 7) were ST86. Only eight of the KpSC1 isolates encoded ESBL, but importantly not carbapenemase. Thirteen of the KpSC1 isolates carried yersiniabactin, colibactin and aerobactin, all of which harboured the rmpADC locus and are therefore characterised as hypervirulent. Co-carriage of multiple strains was minimal. In conclusion, most isolates were KpSC1, ST23, one of the most common sequence types and previously found in cases of K. pneumoniae infection. A proportion were hypervirulent (hvKp) however antibiotic resistance was low