A model to predict cardiovascular events in patients with newly diagnosed Wegener's granulomatosis and microscopic polyangiitis

Objective To create a prognostic tool to quantify the 5-year cardiovascular (CV) risk in patients with newly diagnosed Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) without premorbid CV disease. Methods We reviewed CV outcomes during the long-term followup of patients in the first 4 European Vasculitis Study Group (EUVAS) trials of WG and MPA. CV events were defined as CV death, stroke, myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention. Logistic regression was performed to create a model to predict the absolute risk of a CV event. The model was tested using the Wegener's Granulomatosis Etanercept Trial (WGET) cohort. Results Seventy-four (13.8%) of 535 patients with 5 years of followup from the EUVAS trials had at least 1 CV event: 33 (11.7%) of 281 WG versus 41 (16.1%) of 254 MPA. The independent determinants of CV outcomes were older age (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.11–1.90), diastolic hypertension (OR 1.97, 95% CI 0.98–3.95), and positive proteinase 3 (PR3) antineutrophil cytoplasmic antibody (ANCA) status (OR 0.39, 95% CI 0.20–0.74). The model was validated using the WGET cohort (area under the receiver operating characteristic curve of 0.80). Conclusion Within 5 years of diagnosis of WG or MPA, 14% of patients will have a CV event. We have constructed and validated a tool to quantify the risk of a CV event based on age, diastolic hypertension, and PR3 ANCA status in patients without prior CV disease. In patients with vasculitis, PR3 ANCA is associated with a reduced CV risk compared to myeloperoxidase ANCA or negative ANCA status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83751/1/20433_ftp.pd

Structurally driven one-dimensional electron confinement in sub-5-nm graphene nanowrinkles

Graphene-based carbon materials such as fullerenes, carbon nanotubes, and graphenes have distinct and unique electronic properties that depend on their dimensionality and geometric structures. Graphene wrinkles with pseudo one-dimensional structures have been observed in a graphene sheet. However, their one-dimensional electronic properties have never been observed because of their large widths. Here we report the unique electronic structure of graphene nanowrinkles in a graphene sheet grown on Ni(111), the width of which was small enough to cause one-dimensional electron confinement. Use of spatially resolved, scanning tunnelling spectroscopy revealed bandgap opening and a one-dimensional van Hove singularity in the graphene nanowrinkles, as well as the chemical potential distribution across the graphene nanowrinkles. This observation allows us to realize a metallic-semiconducting-metallic junction in a single graphene sheet. Our demonstration of one-dimensional electron confinement in graphene provides the novel possibility of controlling its electronic properties not by chemical modification but by 'mechanical structuring'.open

The association of serum calprotectin (S100A8/S100A9) levels with disease relapses in PR3-ANCA-associated vasculitis

OBJECTIVES: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in AAV. This study investigated serum S100A8/A9 levels as a biomarker predicting future relapse in a large cohort of patients with severe ANCA-associated vasculitis (AAV). METHODS: Serum levels of S100A8/A9 were measured at baseline, months 2, and 6 following treatment initiation in 144 patients in the RAVE trial (cyclophosphamide/azathioprine vs. rituximab for induction of remission) who attained complete remission. RESULTS: Patients were divided into 4 groups: PR3-ANCA with (n=37), and without (n=56) relapse, and MPO-ANCA with (n=6) and without (n=45) relapse. Serum S100A8/A9 levels decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between relapsers and non-relapsers in the PR3-AAV group (p=0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 between baseline and month 2 (p=0.006) and baseline and month 6 (p=0.0099) for all patients. Subgroup analysis demonstrated it was patients treated with rituximab and who increased levels of S100A8/A9 who were at greatest risk of future relapse (p=0.028). CONCLUSION: An increase in serum S100A8/A9 by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with rituximab at higher risk of relapse by 18 months. As rituximab is increasingly used for remission induction in relapsing PR3-ANCA patients, S100A8/A9 may assist in identifying those patients requiring more intensive or prolonged treatment

Development of low blood glucose readings in nine non-diabetic patients treated with tumor necrosis factor-alpha inhibitors: a case series

<p>Abstract</p> <p>Introduction</p> <p>Treatment with various biological agents in disease states such as rheumatoid arthritis has been associated with multiple side effects. Whereas many of these are frequently reported in the literature, hypoglycemia, a possible side effect of tumor necrosis factor-alpha inhibitors, may be underpublicized.</p> <p>Case presentation</p> <p>We report nine cases of non-diabetic Caucasian women who were between 29 and 68 years of age and who developed low glucose readings after treatment with tumor necrosis factor-alpha inhibitors. We provide a more detailed discussion of existing evidence of the role of tumor necrosis factor-alpha in the pathogenesis of inflammation and its impact on glycemic equilibrium.</p> <p>Conclusions</p> <p>Physicians using tumor necrosis factor-alpha inhibitors in the treatment of various rheumatic and other autoimmune diseases should be aware of the potential for the development of glycemic disturbance in these patients. A further role of tumor necrosis factor-alpha inhibitors in the glycemic equilibrium warrants larger controlled trials in patients with and those without a history of diabetes.</p

How Do Humans Control Physiological Strain during Strenuous Endurance Exercise?

Background: Methodology/principal Findings: Conclusions/significance: Distance running performance is a viable model of human locomotion.To evaluate the physiologic strain during competitions ranging from 5-100 km, we evaluated heart rate (HR) records of competitive runners (n = 211). We found evidence that: 1) physiologic strain (% of maximum HR (%HRmax)) increased in proportional manner relative to distance completed, and was regulated by variations in running pace; 2) the %HRmax achieved decreased with relative distance; 3) slower runners had similar %HRmax response within a racing distance compared to faster runners, and despite differences in pace, the profile of %HRmax during a race was very similar in runners of differing ability; and 4) in cases where there was a discontinuity in the running performance, there was evidence that physiologic effort was maintained for some time even after the pace had decreased.The overall results suggest that athletes are actively regulating their relative physiologic strain during competition, although there is evidence of poor regulation in the case of competitive failures.2.308 SJR (2008) Q1, 60/1774 Medicine (miscellaneous), 19/144 Biochemistry, genetics and molecular biology (miscellaneous), 15/175 Agricultural and biological sciences (miscellaneous)UE

A Genome-Wide Investigation of SNPs and CNVs in Schizophrenia

We report a genome-wide assessment of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) in schizophrenia. We investigated SNPs using 871 patients and 863 controls, following up the top hits in four independent cohorts comprising 1,460 patients and 12,995 controls, all of European origin. We found no genome-wide significant associations, nor could we provide support for any previously reported candidate gene or genome-wide associations. We went on to examine CNVs using a subset of 1,013 cases and 1,084 controls of European ancestry, and a further set of 60 cases and 64 controls of African ancestry. We found that eight cases and zero controls carried deletions greater than 2 Mb, of which two, at 8p22 and 16p13.11-p12.4, are newly reported here. A further evaluation of 1,378 controls identified no deletions greater than 2 Mb, suggesting a high prior probability of disease involvement when such deletions are observed in cases. We also provide further evidence for some smaller, previously reported, schizophrenia-associated CNVs, such as those in NRXN1 and APBA2. We could not provide strong support for the hypothesis that schizophrenia patients have a significantly greater “load” of large (>100 kb), rare CNVs, nor could we find common CNVs that associate with schizophrenia. Finally, we did not provide support for the suggestion that schizophrenia-associated CNVs may preferentially disrupt genes in neurodevelopmental pathways. Collectively, these analyses provide the first integrated study of SNPs and CNVs in schizophrenia and support the emerging view that rare deleterious variants may be more important in schizophrenia predisposition than common polymorphisms. While our analyses do not suggest that implicated CNVs impinge on particular key pathways, we do support the contribution of specific genomic regions in schizophrenia, presumably due to recurrent mutation. On balance, these data suggest that very few schizophrenia patients share identical genomic causation, potentially complicating efforts to personalize treatment regimens

Will the Conscious–Subconscious Pacing Quagmire Help Elucidate the Mechanisms of Self-Paced Exercise? New Opportunities in Dual Process Theory and Process Tracing Methods

The extent to which athletic pacing decisions are made consciously or subconsciously is a prevailing issue. In this article we discuss why the one-dimensional conscious–subconscious debate that has reigned in the pacing literature has suppressed our understanding of the multidimensional processes that occur in pacing decisions. How do we make our decisions in real-life competitive situations? What information do we use and how do we respond to opponents? These are questions that need to be explored and better understood, using smartly designed experiments. The paper provides clarity about key conscious, preconscious, subconscious and unconscious concepts, terms that have previously been used in conflicting and confusing ways. The potential of dual process theory in articulating multidimensional aspects of intuitive and deliberative decision-making processes is discussed in the context of athletic pacing along with associated process-tracing research methods. In attempting to refine pacing models and improve training strategies and psychological skills for athletes, the dual-process framework could be used to gain a clearer understanding of (1) the situational conditions for which either intuitive or deliberative decisions are optimal; (2) how intuitive and deliberative decisions are biased by things such as perception, emotion and experience; and (3) the underlying cognitive mechanisms such as memory, attention allocation, problem solving and hypothetical thought

Living on the edge: precariousness and why it matters for health

The post-war period in Europe, between the late 1940s and the 1970s, was characterised by an expansion of the role of by the state, protecting its citizens from risks of unemployment, poverty, homelessness, and food insecurity. This security began to erode in the 1980s as a result of privatisation and deregulation. The withdrawal of the state further accelerated after the 2008 financial crisis, as countries began pursuing deep austerity. The result has been a rise in what has been termed ‘precariousness’. Here we review the development of the concept of precariousness and related phenomena of vulnerability and resilience, before reviewing evidence of growing precariousness in European countries. It describes a series of studies of the impact on precariousness on health in domains of employment, housing, and food, as well as natural experiments of policies that either alleviate or worsen these impacts. It concludes with a warning, drawn from the history of the 1930s, of the political consequences of increasing precariousness in Europe and North America

Meta-analysis indicates that common variants at the DISC1 locus are not associated with schizophrenia

Several polymorphisms in the Disrupted-in-Schizophrenia-1 (DISC1) gene are reported to be associated with schizophrenia. However, to date, there has been little effort to evaluate the evidence for association systematically. We carried out an imputation-driven meta-analysis, the most comprehensive to date, using data collected from 10 candidate gene studies and three genome-wide association studies containing a total of 11 626 cases and 15 237 controls. We tested 1241 single-nucleotide polymorphisms in total, and estimated that our power to detect an effect from a variant with minor allele frequency >5% was 99% for an odds ratio of 1.5 and 51% for an odds ratio of 1.1. We find no evidence that common variants at the DISC1 locus are associated with schizophrenia

Supramolecular heterostructures formed by sequential epitaxial deposition of two-dimensional hydrogen-bonded arrays

Two-dimensional (2D) supramolecular arrays provide a route to the spatial control of the chemical functionality of a surface, but their deposition is in almost all cases limited to a monolayer termination. Here we investigated the sequential deposition of one 2D array on another to form a supramolecular heterostructure and realize the growth—normal to the underlying substrate—of distinct ordered layers, each of which is stabilized by in-plane hydrogen bonding. For heterostructures formed by depositing terephthalic acid or trimesic acid on cyanuric acid/melamine, we have determined, using atomic force microscopy under ambient conditions, a clear epitaxial arrangement despite the intrinsically distinct symmetries and/or lattice constants of each layer. Structures calculated using classical molecular dynamics are in excellent agreement with the orientation, registry and dimensions of the epitaxial layers. Calculations confirm that van der Waals interactions provide the dominant contribution to the adsorption energy and registry of the layers