Self-reported adverse reactions in 4337 healthcare workers immunizations against novel H1N1 influenza

Purpose: The use of the 2009 H1N1 vaccine has generated much debate concerning safety issues among the general population and physicians. Therefore, we investigated the safety of an inactivated monovalent H1N1 pandemic influenza vaccine Methods: We focused on the H1N1 pandemic influenza vaccine Pandemrix(R) and applied a self reporting questionnaire in a population of healthcare workers (HCWs) and medical students at a major university hospital. Results: In total, 4337 individuals were vaccinated, consisting of 3808 HCWs and 529 medical students. The vaccination rate of the employees was higher than 40%.The majority of individuals were vaccinated in November 2009. In total, 291 of the 4337 vaccinations were reported to lead to one or more adverse reactions (6.7%). Local reactions were reported in 3.8%, myalgia and arthralgia in 3.7%, fatigue in 3.7%, headache in 3.1%. Conclusions: Our data together with available data from several national and international institutions points to a safe pandemic influenza vaccine

Stochastic search and joint fine-mapping increases accuracy and identifies previously unreported associations in immune-mediated diseases

Abstract: Thousands of genetic variants are associated with human disease risk, but linkage disequilibrium (LD) hinders fine-mapping the causal variants. Both lack of power, and joint tagging of two or more distinct causal variants by a single non-causal SNP, lead to inaccuracies in fine-mapping, with stochastic search more robust than stepwise. We develop a computationally efficient multinomial fine-mapping (MFM) approach that borrows information between diseases in a Bayesian framework. We show that MFM has greater accuracy than single disease analysis when shared causal variants exist, and negligible loss of precision otherwise. MFM analysis of six immune-mediated diseases reveals causal variants undetected in individual disease analysis, including in IL2RA where we confirm functional effects of multiple causal variants using allele-specific expression in sorted CD4+ T cells from genotype-selected individuals. MFM has the potential to increase fine-mapping resolution in related diseases enabling the identification of associated cellular and molecular phenotypes

Effect of Build Parameters and Build Geometries on Residual Microstructures and Mechanical Properties of Ti-6Al-4V Components Built by Electron Beam Melting (EBM)

In this study, involving additive manufacturing (AM) using electron beam melting (EBM), we have examined build defects which result from beam tripping, porosities (including unmelted or unsintered zones) due to excursions from optimal build parameters (especially variations in melt scan beam current and scan speed), and gas bubbles trapped in atomized Ti-6Al-4V starting powder as well as recycled powder, and retained in the build. At optimized build conditions we have also examined microstructure-mechanical property (hardness, tensile strength, and elongation) variations for multiple rake building and multiple melt scans using optical metallography and scanning and transmission electron microscopy (SEM and TEM). These build variances cause cooling rate variances which promote α-phase growth and variations in dislocation density, as well as α-to-α' (martensite) phase changes, all of which produce some degree of mechanical property variations. These features (especially α-to-α' phase changes) are notable on comparing solid builds in comparison with a variety of mesh arrays where strut dimension and build-element complexities alter the cooling rates in a significant way. We illustrate these microstructure variations with corresponding variations in microindentation hardness measurements made directly on fine mesh (strut) structures. Finally, we have examined Ti-6Al-4V powder chemistries and solid build chemistries which for single-pass melt scans at optimized build conditions are shown to be relatively constant up to 40 cycles of powder reuse with the exception of Al content which was reduced by 10 to 15% in solid builds at optimized conditions. However, Al loss in solid builds approached 25% for multiple (2 and 3) melt scans, while no changes in Ar gas-bubble density were observed with changes in α-phase (grain) width which increased from 3 µm for a single melt scan to 4.5 and 6 µm for 2 and 3 melt scans, respectively. Corresponding Rockwell C-scale (HRC) hardness varied from 37, 36, and 35, respectively; with ultimate tensile strengths exceeding 1.2 GPa at elongations of 12% or higher for this melt scan sequence.Mechanical Engineerin

eSport: Construct specifications and implications for sport management

The purpose of this article is to add to the conceptual discussion on eSport, analyze the role of eSport within sport management, and suggest avenues for future eSport research. The authors suggest that debates surround the degree to which eSport represents formal sport, and disagreements likely stem from conceptualizations of sport and context. Irrespective of one’s notion of eSport as formal sport, the authors suggest the topic has a place in sport management scholarship and discourse. Such a position is consistent with the broad view of sport adopted by Sport Management Review, the perspective that eSport represents a form of sportification, and the association among eSport and various outcomes, including physical and psychological health, social well-being, sport consumption outcomes, and diversity and inclusion. Finally, the authors conclude that eSport scholarship can advance through the study of its governance, marketing, and management as well as by theorizing about eSpor

Idd Loci Synergize to Prolong Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice

OBJECTIVE—NOD mice model human type 1 diabetes and are used to investigate tolerance induction protocols for islet transplantation in a setting of autoimmunity. However, costimulation blockade–based tolerance protocols have failed in prolonging islet allograft survival in NOD mice

The Repetitive Landscape of the Barley Genome

While transposable elements (TEs) comprise the bulk of plant genomic DNA, how they contribute to genome structure and organization is still poorly understood. Especially, in large genomes where TEs make the majority of genomic DNA, it is still unclear whether TEs target specific chromosomal regions or whether they simply accumulate where they are best tolerated. The barley genome with its vast repetitive fraction is an ideal system to study chromosomal organization and evolution of TEs. Genes make only about 2% of the genome, while over 80% is derived from TEs. The TE fraction is composed of at least 350 different families. However, 50% of the genome is comprised of only 15 high-copy TE families, while all other TE families are present in moderate or low-copy numbers. The barley genome is highly compartmentalized with different types of TEs occupying different chromosomal “niches”, such as distal, interstitial or proximal regions of chromosome arms. Furthermore, gene space represents its own distinct genomic compartment that is enriched in small non-autonomous DNA transposons, suggesting that these TEs specifically target promoters and downstream regions. Some TE families also show a strong preference to insert in specific sequence motifs which may, in part, explain their distribution. The family-specific distribution patterns result in distinct TE compositions of different chromosomal compartments.Peer reviewe

Blockade of the Programmed Death-1 (PD1) Pathway Undermines Potent Genetic Protection from Type 1 Diabetes

Aims/Hypothesis Inhibition of PD1-PDL1 signaling in NOD mice accelerates onset of type 1 diabetes implicating this pathway in suppressing the emergence of pancreatic beta cell reactive T-cells. However, the molecular mechanism by which PD1 signaling protects from type 1 diabetes is not clear. We hypothesized that differential susceptibility of Idd mouse strains to type 1 diabetes when challenged with anti PDL1 will identify genomic loci that collaborate with PD1 signaling in suppressing type 1 diabetes. Methods: Anti PDL1 was administered to NOD and various Idd mouse strains at 10 weeks of age and onset of disease was monitored by measuring blood glucose levels. Additionally, histological evaluation of the pancreas was performed to determine degree of insulitis. Statistical analysis of the data was performed using Log-Rank and Student's t-test. Results: Blockade of PDL1 rapidly precipitated type 1 diabetes in nearly all NOD Idd congenic strains tested, despite the fact that all are moderately (Idd5, Idd3 and Idd10/18) or highly (Idd3/10/18 and Idd9) protected from spontaneous type 1 diabetes by virtue of their protective Idd genes. Only the Idd3/5 strain, which is nearly 100% protected from spontaneous disease, remained normoglycemic following PDL1 blockade. Conclusions: These results indicate that multiple Idd loci collaborate with PD1 signaling. Anti PDL1 treatment undermines a large portion of the genetic protection mediated by Idd genes in the NOD model of type 1 diabetes. Basal insulitis correlated with higher susceptibility to type 1 diabetes. These findings have important implications since the PD1 pathway is a target for immunotherapy

The vertebrate genome annotation (Vega) database

The Vertebrate Genome Annotation (Vega) database (http://vega.sanger.ac.uk) was first made public in 2004 and has been designed to view manual annotation of human, mouse and zebrafish genomic sequences produced at the Wellcome Trust Sanger Institute. Since its initial release, the number of human annotated loci has more than doubled to close to 33 000 and now contains comprehensive annotation on 20 of the 24 human chromosomes, four whole mouse chromosomes and around 40% of the zebrafish Danio rerio genome. In addition, we offer manual annotation of a number of haplotype regions in mouse and human and regions of comparative interest in pig and dog that are unique to Vega