Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.

Background: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. Results: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. Conclusions: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studie

Diagnostic Accuracy of Diffusion Tensor Imaging in Amyotrophic Lateral Sclerosis

RATIONALE AND OBJECTIVES: There have been a large number of case-control studies using diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS). The objective of this study was to perform an individual patient data (IPD) meta-analysis for the estimation of the diagnostic accuracy measures of DTI in the diagnosis of ALS using corticospinal tract data. MATERIALS AND METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane databases (1966–April 2011) were searched. Studies were included if they used DTI region of interest or tractography techniques to compare mean cerebral corticospinal tract fractional anisotropy values between ALS subjects and healthy controls. Corresponding authors from the identified articles were contacted to collect individual patient data. IPD meta-analysis and meta-regression were performed using Stata. Meta-regression covariate analysis included age, gender, disease duration, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. RESULTS: Of 30 identified studies, 11 corresponding authors provided IPD and 221 ALS patients and 187 healthy control subjects were available for study. Pooled area under the receiver operating characteristic curve (AUC) was 0.75 (95% CI: 0.66–0.83), pooled sensitivity was 0.68 (95% CI: 0.62–0.75), and pooled specificity was 0.73 (95% CI: 0.66–0.80). Meta-regression showed no significant differences in pooled AUC for each of the covariates. There was moderate to high heterogeneity of pooled AUC estimates. Study quality was generally high. Data from 19 of the 30 eligible studies were not ascertained, raising possibility of selection bias. CONCLUSION: Using corticospinal tract individual patient data, the diagnostic accuracy of DTI appears to lack sufficient discrimination in isolation. Additional research efforts and a multimodal approach that also includes ALS mimics will be required to make neuroimaging a critical component in the workup of ALS

The role and utilisation of public health evaluations in Europe: a case study of national hand hygiene campaigns

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Evaluations are essential to judge the success of public health programmes. In Europe, the proportion of public health programmes that undergo evaluation remains unclear. The European Centre for Disease Prevention and Control sought to determine the frequency of evaluations amongst European national public health programmes by using national hand hygiene campaigns as an example of intervention.A cohort of all national hand hygiene campaigns initiated between 2000 and 2012 was utilised for the analysis. The aim was to collect information about evaluations of hand hygiene campaigns and their frequency. The survey was sent to nominated contact points for healthcare-associated infection surveillance in European Union and European Economic Area Member States.Thirty-six hand hygiene campaigns in 20 countries were performed between 2000 and 2012. Of these, 50% had undergone an evaluation and 55% of those utilised the WHO hand hygiene intervention self-assessment tool. Evaluations utilised a variety of methodologies and indicators in assessing changes in hand hygiene behaviours pre and post intervention. Of the 50% of campaigns that were not evaluated, two thirds reported that both human and financial resource constraints posed significant barriers for the evaluation.The study identified an upward trend in the number of hand hygiene campaigns implemented in Europe. It is likely that the availability of the internationally-accepted evaluation methodology developed by the WHO contributed to the evaluation of more hand hygiene campaigns in Europe. Despite this rise, hand hygiene campaigns appear to be under-evaluated. The development of simple, programme-specific, standardised guidelines, evaluation indicators and other evidence-based public health materials could help promote evaluations across all areas of public health