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Objective: To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). Methods: We performed a genome‐wide association study (GWAS) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima‐media thickness (CIMT) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals. Results: A genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome‐wide level of significance (minor allele [G] β coefficient 0.142, P = 1.86 × 10−8). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biologic pathway enrichment and predictive protein–protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (Gene Ontology no. 0032964; false discovery rate–adjusted P = 4.01 × 10−3). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB1,MSRA, and ZC3HC1 (P = 8.12 × 10−4, P = 5.94 × 10−4, and P = 2.46 × 10−4, respectively). Conclusion: The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10 -54 , per-allele OR = 1.79; and rs9275592, p = 1.14 × 10 -40 , OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10 -10 , OR = 1.28; and rs128738, p = 4.60 × 10 -9 , OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have reported that the quality of cardiopulmonary resuscitation (CPR) is important for patient survival. Real time objective feedback during manikin training has been shown to improve CPR performance. Objective measurement could facilitate competition and help motivate participants to improve their CPR performance. The aims of this study were to investigate whether real time objective feedback on manikins helps improve CPR performance and whether competition between separate European Emergency Medical Services (EMS) and between participants at each EMS helps motivation to train., Methods: Ten European EMS took part in the study and was carried out in two stages. At Stage 1, each EMS provided 20 pre-hospital professionals. A questionnaire was completed and standardised assessment scenarios were performed for adult and infant out of hospital cardiac arrest (OHCA). CPR performance was objectively measured and recorded but no feedback given. Between Stage 1 and 2, each EMS was given access to manikins for 6 months and instructed on how to use with objective real-time CPR feedback available. Stage 2 was undertaken and was a repeat of Stage 1 with a questionnaire with additional questions relating to usefulness of feedback and the competition nature of the study (using a 10 point Likert score). The EMS that improved the most from Stage 1 to Stage 2 was declared the winner. An independent samples Student t-test was used to analyse the objective CPR metrics with the significance level taken as p < 0.05., Results: Overall mean Improvement of CPR performance from Stage 1 to Stage 2 was significant. The improvement was greater for the infant assessment. The participants thought the real-time feedback very useful (mean score of 8.5) and very easy to use (mean score of 8.2). Competition between EMS organisations recorded a mean score of 5.8 and competition between participants recorded a mean score of 6.0., Conclusions: The results suggest that the use of real time objective feedback can significantly help improve CPR performance. Competition, especially between participants, appeared to encourage staff to practice and this study suggests that competition might have a useful role to help motivate staff to perform CPR training.

Systemic sclerosis (SSc) is complex autoimmune disease affecting the connective tissue; influenced by genetic and environmental components. Recently, we performed the first successful genome-wide association study (GWAS) of SSc. Here, we perform a large replication study to better dissect the genetic component of SSc. We selected 768 polymorphisms from the previous GWAS and genotyped them in seven replication cohorts from Europe. Overall significance was calculated for replicated significant SNPs by meta-analysis of the replication cohorts and replication-GWAS cohorts (3237 cases and 6097 controls). Six SNPs in regions not previously associated with SSc were selected for validation in another five independent cohorts, up to a total of 5270 SSc patients and 8326 controls. We found evidence for replication and overall genome-wide significance for one novel SSc genetic risk locus: CSK [P-value = 5.04 × 10(-12), odds ratio (OR) = 1.20]. Additionally, we found suggestive association in the loci PSD3 (P-value = 3.18 × 10(-7), OR = 1.36) and NFKB1 (P-value = 1.03 × 10(-6), OR = 1.14). Additionally, we strengthened the evidence for previously confirmed associations. This study significantly increases the number of known putative genetic risk factors for SSc, including the genes CSK, PSD3 and NFKB1, and further confirms six previously described ones.