The evolution and distribution of phage ST160 within Salmonella enterica serotype Typhimurium

Salmonellosis is an internationally important disease of mammals and birds. Unique epidemics in New Zealand in the recent past include two Salmonella serovars: Salmonella enterica subsp. enterica serovar Typhimurium definitive type (DT) 160 (S. Typhimurium DT160) and S. Brandenburg. Although not a major threat internationally, in New Zealand S. Typhimurium DT160 has been the most common serovar isolated from humans, and continues to cause significant losses in wildlife. We have identified DNA differences between the first New Zealand isolate of S. Typhimurium DT160 and the genome-sequenced strain, S. Typhimurium LT2. All the differences could be accounted for in one cryptic phage ST64B, and one novel P22-like phage, ST160. The majority of the ST160 genome is almost identical to phage SE1 but has two regions not found in SE1 which are identical to the P22-like phage ST64T, suggesting that ST160 evolved from SE1 via two recombination events with ST64T. All of the New Zealand isolates of DT160 were identical indicating the clonal spread of this particular Salmonella. Some overseas isolates of S. Typhimurium DT160 differed from the New Zealand strain and contained SE1 phage rather than ST160. ST160 was also identified in New Zealand isolates of S. Typhimurium DT74 and S. Typhimurium RDNC-April06 and in S. Typhimurium DT160 isolates from the USA. The emergence of S. Typhimurium DT160 as a significant pathogen in New Zealand is postulated to have occurred due to the sensitivity of the Salmonella strains to the ST160 phage when S. Typhimurium DT160 first arrived. © 2010 Cambridge University Press

Vancomycin-resistant Enterococcus faecium sequence type 796 - rapid international dissemination of a new epidemic clone

Background: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. Methods: Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. Results: A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. Conclusions: Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed

Radiation effects in glasses used for immobilization of high-level waste and plutonium disposition

This paper is a comprehensive review of the state-of-knowledge in the field of radiation effects in glasses that are to be used for the immobilization of high-level nuclear waste and plutonium disposition. The current status and issues in the area of radiation damage processes, defect generation, microstructure development, theoretical methods and experimental methods ase reviewed. Questions of fundamental and technological interest that offer opportunities for research are identified

The hidden burden of adult allergic rhinitis : UK healthcare resource utilisation survey

Funding Funding for this survey was provided by Meda Pharma.Peer reviewedPublisher PD

Transmission of highly virulent community-associated MRSA ST93 and livestock-associated MRSA ST398 between humans and pigs in Australia

Pigs have been recognised as a reservoir of livestock associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in Europe, Asia and North America. However, little is known about the presence and distribution of MRSA in the Australian pig population and pig industry. This study describes the presence, distribution and molecular characteristics of the human adapted Australian CA-MRSA ST93 isolated from pigs, people, and the environment within a piggery. Isolates were subjected to antibiotic susceptibility testing, DNA microarray, whole genome sequencing, multi locus sequence typing, virulence and resistance gene characterization and phylogenetic analysis. MRSA were isolated from 60% (n = 52) of farm workers where 84% of isolates returned ST93 and the rest ST398. Of the thirty-one pig isolates tested further, an equal number of ST398 and ST93 (15 each) and one as ST30-V were identified. Four of six environmental isolates were identified as ST93 and two as ST398. This study has identified for the first time in Australia the occurrence of CA-MRSA ST93 and LA-MRSA ST398 amongst farm workers, pigs, and the farm environment. Comparative genome analysis indicates that ST398 is likely to have been introduced into Australia from Europe or North America. This study also reports the first linezolid resistant MRSA isolated in Australia

Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis

Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth. Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic. Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65). Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users

Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes

BACKGROUND: GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans. METHODS: Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM. RESULTS: Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P ≥ 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls. CONCLUSION: From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans

High platelet reactivity in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Randomised controlled trial comparing prasugrel and clopidogrel

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit

Incompressible Fluids of the de Sitter Horizon and Beyond

There are (at least) two surfaces of particular interest in eternal de Sitter space. One is the timelike hypersurface constituting the lab wall of a static patch observer and the other is the future boundary of global de Sitter space. We study both linear and non-linear deformations of four-dimensional de Sitter space which obey the Einstein equation. Our deformations leave the induced conformal metric and trace of the extrinsic curvature unchanged for a fixed hypersurface. This hypersurface is either timelike within the static patch or spacelike in the future diamond. We require the deformations to be regular at the future horizon of the static patch observer. For linearized perturbations in the future diamond, this corresponds to imposing incoming flux solely from the future horizon of a single static patch observer. When the slices are arbitrarily close to the cosmological horizon, the finite deformations are characterized by solutions to the incompressible Navier-Stokes equation for both spacelike and timelike hypersurfaces. We then study, at the level of linearized gravity, the change in the discrete dispersion relation as we push the timelike hypersurface toward the worldline of the static patch. Finally, we study the spectrum of linearized solutions as the spacelike slices are pushed to future infinity and relate our calculations to analogous ones in the context of massless topological black holes in AdS$_4$.Comment: 27 pages, 8 figure