Selective accumulation of differentiated CD8+ T cells specific for respiratory viruses in the human lung

The lungs are frequently challenged by viruses, and resident CD8+ T cells likely contribute to the surveillance of these pathogens. To obtain insight into local T cell immunity to respiratory viruses in humans, we determined the specificity, phenotype, and function of lung-residing CD8+ T cells and peripheral blood CD8+ T cells in a paired analysis. The lung contained markedly higher frequencies of influenza (FLU)-specific and respiratory syncytial virus (RSV)-specific CD8+ T cells when compared with the circulation. This contrasted with an equal distribution of cytomegalovirus- and Epstein-Bar virus–specific CD8+ T cells. Noticeably, a substantial fraction of the lung-residing FLU- and RSV-specific CD8+ T cells had progressed to a relatively late differentiation phenotype, reflected by low expression of CD28 and CD27. Lung-derived FLU-specific CD8+ T cells had low activation requirements, as expansion of these cells could be initiated by cognate peptide in the absence of helper cell–derived signals. Thus, the human lung contains high numbers of differentiated FLU- and RSV-specific memory CD8+ T cells that can readily expand upon reexposure to virus. Resident lung T cells may provide immediate immunological protection against pulmonary virus infections

Deep-Sequencing Analysis Reveals that the miR-199a2/214 Cluster within DNM3os Represents the Vast Majority of Aberrantly Expressed MicroRNAs in Sézary Syndrome

Dermatology-oncolog

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Recommendations for a uniform assessment of publication bias related to funding source

Contains fulltext : 125836.pdf (publisher's version ) (Open Access)BACKGROUND: Numerous studies on publication bias in clinical drug research have been undertaken, particularly on the association between sponsorship and favourable outcomes. However, no standardized methodology for the classification of outcomes and sponsorship has been described. Dissimilarities and ambiguities in this assessment impede the ability to compare and summarize results of studies on publication bias. To guide authors undertaking such studies, this paper provides recommendations for a uniform assessment of publication bias related to funding source. METHODS AND RESULTS: As part of ongoing research into publication bias, 472 manuscripts on randomised controlled trials (RCTs) with drugs, submitted to eight medical journals from January 2010 through April 2012, were reviewed. Information on trial results and sponsorship was extracted from manuscripts. During the start of this evaluation, several problems related to the classification of outcomes, inclusion of post-hoc analyses and follow-up studies of RCTs in the study sample, and assessment of the role of the funding source were encountered. A comprehensive list of recommendations addressing these problems was composed. To assess internal validity, reliability and usability of these recommendations were tested through evaluation of manuscripts submitted to journals included in our study. CONCLUSIONS: The proposed recommendations represent a first step towards a uniform method of classifying trial outcomes and sponsorship. This is essential to draw valid conclusions on the role of the funding source in publication bias and will ensure consistency across future studies