Comparative genomic analysis of a multiple antimicrobial resistant enterotoxigenic E. coli O157 lineage from Australian pigs

© 2015 Wyrsch et al. Background: Enterotoxigenic Escherichia coli (ETEC) are a major economic threat to pig production globally, with serogroups O8, O9, O45, O101, O138, O139, O141, O149 and O157 implicated as the leading diarrhoeal pathogens affecting pigs below four weeks of age. A multiple antimicrobial resistant ETEC O157 (O157 SvETEC) representative of O157 isolates from a pig farm in New South Wales, Australia that experienced repeated bouts of pre- and post-weaning diarrhoea resulting in multiple fatalities was characterized here. Enterohaemorrhagic E. coli (EHEC) O157:H7 cause both sporadic and widespread outbreaks of foodborne disease, predominantly have a ruminant origin and belong to the ST11 clonal complex. Here, for the first time, we conducted comparative genomic analyses of two epidemiologically-unrelated porcine, disease-causing ETEC O157; E. coli O157 SvETEC and E. coli O157:K88 734/3, and examined their phylogenetic relationship with EHEC O157:H7. Results: O157 SvETEC and O157:K88 734/3 belong to a novel sequence type (ST4245) that comprises part of the ST23 complex and are genetically distinct from EHEC O157. Comparative phylogenetic analysis using PhyloSift shows that E. coli O157 SvETEC and E. coli O157:K88 734/3 group into a single clade and are most similar to the extraintestinal avian pathogenic Escherichia coli (APEC) isolate O78 that clusters within the ST23 complex. Genome content was highly similar between E. coli O157 SvETEC, O157:K88 734/3 and APEC O78, with variability predominantly limited to laterally acquired elements, including prophages, plasmids and antimicrobial resistance gene loci. Putative ETEC virulence factors, including the toxins STb and LT and the K88 (F4) adhesin, were conserved between O157 SvETEC and O157:K88 734/3. The O157 SvETEC isolate also encoded the heat stable enterotoxin STa and a second allele of STb, whilst a prophage within O157:K88 734/3 encoded the serum survival gene bor. Both isolates harbor a large repertoire of antibiotic resistance genes but their association with mobile elements remains undetermined. Conclusions: We present an analysis of the first draft genome sequences of two epidemiologically-unrelated, pathogenic ETEC O157. E. coli O157 SvETEC and E. coli O157:K88 734/3 belong to the ST23 complex and are phylogenetically distinct to EHEC O157 lineages that reside within the ST11 complex

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

Attentional differences in a driving hazard perception task in adults with autism spectrum disorders

The current study explored attentional processing of social and non social stimuli in ASD within the context of a driving hazard perception task. Participants watched videos of road scenes and detected hazards while their eye movements were recorded. Although individuals with ASD demonstrated relatively good detection of driving hazards, they were slower to orient to hazards. Greater attentional capture in the time preceding the hazards’ onset was associated with lower verbal IQ. The findings suggest that individuals with ASD may distribute and direct their attention diferently when identifying driving hazards

In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.

BACKGROUND: The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape. METHODOLOGY/PRINCIPAL FINDINGS: Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages. CONCLUSIONS: We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies

Shear capacity of reinforced concrete corbels using mechanism analysis

A mechanism analysis is developed to predict the shear capacity of reinforced concrete corbels. Based on shear failure observed in experimental tests, kinematically admissible failure mechanisms are idealised as an assemblage of two rigid blocks separated by a failure plane of displacement discontinuity. Shear capacity predictions obtained from the developed mechanism analysis are in better agreement with corbel test results of a comprehensive database compiled from the available literature than other existing models for corbels. The developed mechanism model shows that the shear capacity of corbels generally decreases with the increase of shear span-to-depth ratio, increases with the increase of main longitudinal reinforcement up to a certain limit beyond which it remains constant, and decreases with the increase of horizontal applied loads. It also demonstrates that the smaller the shear span-to-overall depth ratio of corbels, the more effective the horizontal shear reinforcement

Revisions to the derivation of the Australian and New Zealand guidelines for toxicants in fresh and marine waters

The Australian and New Zealand Guidelines for Fresh and Marine Water Quality are a key document in the Australian National Water Quality Management Strategy. These guidelines released in 2000 are currently being reviewed and updated. The revision is being co-ordinated by the Australian Department of Sustainability, Environment, Water, Population and Communities, while technical matters are dealt with by a series of Working Groups. The revision will be evolutionary in nature reflecting the latest scientific developments and a range of stakeholder desires. Key changes will be: increasing the types and sources of data that can be used; working collaboratively with industry to permit the use of commercial-in-confidence data; increasing the minimum data requirements; including a measure of the uncertainty of the trigger value; improving the software used to calculate trigger values; increasing the rigour of site-specific trigger values; improving the method for assessing the reliability of the trigger values; and providing guidance of measures of toxicity and toxicological endpoints that may, in the near future, be appropriate for trigger value derivation. These changes will markedly improve the number and quality of the trigger values that can be derived and will increase end-users’ ability to understand and implement the guidelines in a scientifically rigorous manner

The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels nonselective. We interpret the effects of these—and of other mutations—in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter

You are Not Welcome: Social Exchanges between Female Spider Monkeys (Ateles geoffroyi)

Group living leads to competition for food between group members. Two types of intragroup food competition may occur: scramble competition, in which all group members use the same resource, such that feeding opportunities are equal for everyone; and contest competition, in which some group members monopolize resources through aggression and dominance. In species in which females disperse from the natal group and immigrate into other groups, immigrant females increase group size and thus possibly food competition. Under these circumstances, other females may use aggression to discourage new females from joining the group. We assessed the distribution of aggression, embraces, and kisses among female spider monkeys (Ateles geoffroyi) in relation to group tenure. We recorded social interactions during 1688 10-min focal animal samples on 11 females in Santa Rosa, Costa Rica. We found that aggression was rare between long-term resident females and aggression rates were not higher during feeding than in other contexts, suggesting there was little contest competition. Long-term residents and less recently immigrant females showed higher aggression rates toward the most recent immigrants than toward other females, especially during the first months after a female immigrated, which coincided with the dry season. We did not find similar patterns for embrace and kiss. These results suggest that other females target aggression toward the most recent immigrants to reduce scramble competition. This finding suggests that group tenure should be included in socioecological models for species with female dispersal. © 2017 Springer Science+Business Media, LL

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente