Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10 -11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.

Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis

Introduction: The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage. Methods: Serum sRAGE, S100A9, S100A8 and S100A12 levels from 138 patients with established RA and 44 healthy controls were measured by ELISA and compared by unpaired t test. In RA patients, associations with disease activity and severity variables were analyzed by simple and multiple linear regressions. Results: Serum S100A9, S100A8 and S100A12 levels were correlated in RA patients. S100A9 levels were associated with body mass index (BMI), and with serum levels of S100A8 and S100A12. S100A8 levels were associated with serum levels of S100A9, presence of anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF). S100A12 levels were associated with presence of ACPA, history of diabetes, and serum S100A9 levels. sRAGE levels were negatively associated with serum levels of C-reactive protein (CRP) and high-density lipoprotein (HDL), history of vasculitis, and the presence of the RAGE 82Ser polymorphism. Conclusions: sRAGE and S100 proteins were associated not just with RA inflammation and autoantibody production, but also with classical vascular risk factors for end-organ damage. Consistent with its role as a RAGE decoy molecule, sRAGE had the opposite effects to S100 proteins in that S100 proteins were associated with autoantibodies and vascular risk, whereas sRAGE was associated with protection against joint and vascular damage. These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients.

Cardiovascular disease is increased prior to onset of rheumatoid arthritis but not osteoarthritis: The population-based Nord-Trøndelag health study (HUNT)

Introduction: Patients with rheumatoid arthritis (RA) have increased risk of cardiovascular (CV) events. We sought to test the hypothesis that due to increased inflammation, CV disease and risk factors are associated with increased risk of future RA development. Methods: The population-based Nord-Trøndelag health surveys (HUNT) were conducted among the entire adult population of Nord-Trøndelag, Norway. All inhabitants 20 years or older were invited, and information was collected through comprehensive questionnaires, a clinical examination, and blood samples. In a cohort design, data from HUNT2 (1995-1997, baseline) and HUNT3 (2006-2008, follow-up) were obtained to study participants with RA (n = 786) or osteoarthritis (n = 3,586) at HUNT3 alone, in comparison with individuals without RA or osteoarthritis at both times (n = 33,567). Results: Female gender, age, smoking, body mass index, and history of previous CV disease were associated with self-reported incident RA (previous CV disease: odds ratio 1.52 (95% confidence interval 1.11-2.07). The findings regarding previous CV disease were confirmed in sensitivity analyses excluding participants with psoriasis (odds ratio (OR) 1.70 (1.23-2.36)) or restricting the analysis to cases with a hospital diagnosis of RA (OR 1.90 (1.10-3.27)) or carriers of the shared epitope (OR 1.76 (1.13-2.74)). History of previous CV disease was not associated with increased risk of osteoarthritis (OR 1.04 (0.86-1.27)). Conclusion: A history of previous CV disease was associated with increased risk of incident RA but not osteoarthritis.

Fiber Bragg grating accelerometer based on a transversely rotating stick

Fiber Bragg Grating (FBG) accelerometers using transverse forces with an inertial object placed at the middle of the FBG have a high sensitivity but low resonant frequency. The resonant frequency 26 Hz and sensitivity at 6 Hz 1.29 nm/g were reported based on a 50mm-long FBG accelerometer. We demonstrate that the first FBG accelerometer based on a transversely rotating stick, which can, at the same or even larger size, keep the high sensitivity and significantly increase the low resonant frequency. In our experiments, a 77.5mm-long FBG accelerometer has achieved a similar sensitivity but 65% higher resonant frequency. This novel structure not only significantly widens the potential applications of FBG accelerometers by increasing their resonant frequencies but also provides a new route to design other accelerometers, e.g. micro accelerometers.

Validation and reliability of a Spanish version of Simple Shoulder Test (SST-Sp)

Background: The Simple Shoulder Test (SST-Sp) is a widely used outcome measure. Objective: The purpose of this study was to develop and validate a Spanish-version SST (SST-Sp). Methods: A two-stage observational study was conducted. The SST was initially cross-culturally adapted to Spanish through double forward and backward translation and then validated for its psychometric characteristics. Participants (n = 66) with several shoulder disorders completed the SST-Sp, DASH, VAS and SF-12. The full sample was employed to determine factor structure, internal consistency and concurrent criterion validity. Reliability was determined in the first 24–48 h in a subsample of 21 patients. Results: The SST-Sp showed three factors that explained the 56.1 % of variance, and the internal consistency for each factor was α = 0.738, 0.723 and 0.667, and reliability was ICC = 0.687–0.944. The factor structure was three-dimensional and supported construct validity. Criterion validity determined from the relationship between the SST-Sp and DASH was strong (r = −0.73; p < 0.001) and fair for VAS (r = −0.537; p < 0.001). Relationships between SST-Sp and SF-12 were weak for both physical (r = −0.47; p < 0.001) and mental (r = −0.43; p < 0.001) dimensions. Conclusions: The SST-Sp supports the findings of the original English version as being a valid shoulder outcome measure with similar psychometric properties to the original English version.

Experimental studies on the performance of rail joints with modified wheel/railhead contact

Rail joints are provided with a gap to account for thermal movement and to maintain electrical insulation for the control of signals and/or broken rail detection circuits. The gap in the rail joint is regarded as a source of significant problems for the rail industry since it leads to a very short rail service life compared with other track components due to the various, and difficult to predict, failure modes – thus increasing the risk for train operations. Many attempts to improve the life of rail joints have led to a large number of patents around the world; notable attempts include strengthening through larger-sized joint bars, an increased number of bolts and the use of high yield materials. Unfortunately, no design to date has shown the ability to prolong the life of the rail joints to values close to those for continuously welded rail (CWR). This paper reports the results of a fundamental study that has revealed that the wheel contact at the free edge of the railhead is a major problem since it generates a singularity in the contact pressure and railhead stresses. A design was therefore developed using an optimisation framework that prevents wheel contact at the railhead edge. Finite element modelling of the design has shown that the contact pressure and railhead stress singularities are eliminated, thus increasing the potential to work as effectively as a CWR that does not have a geometric gap. An experimental validation of the finite element results is presented through an innovative non-contact measurement of strains. Some practical issues related to grinding rails to the optimal design are also discussed.

Au-Pd alloy nanoparticle catalyzed selective oxidation of benzyl alcohol and tandem synthesis of imines at ambient conditions

Alloy nanoparticles (NPs) of gold and palladium on ZrO2 support (Au–Pd@ZrO2) were found to be highly active in oxidation of benzyl alcohols and can be used for the tandem synthesis of imines from benzyl alcohols and amines via a one-pot, two-step process at mild reaction conditions. The first step of the process is oxidation of benzyl alcohol to benzaldehyde, excellent yields were achieved after 7 h reaction at 40 °C without addition of any base. In the second step, aniline was introduced into the reaction system to produced N-benzylideneaniline. The benzaldehyde obtained in the first step was completely consumed within 1 h. A range of benzyl alcohols and amines were investigated for the general applicability of the Au–Pd alloy catalysts. It is found that the performance of the catalysts depends on the Au–Pd metal contents and composition. The optimal catalyst is 3.0 wt% Au–Pd@ZrO2 with a Au:Pd molar ratio 1:1. The alloy NP catalyst exhibited superior catalytic properties to pure AuNP or PdNP because the surface of alloy NPs has higher charge heterogeneity than that of pure metal NPs according to simulation of density function theory (DFT)