Plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases*

Introduction: Although systemic autoimmune diseases (SAID) share many clinical and laboratory features, whether they also share some common features of pathogenesis remains unclear. We assessed plasma proteomic profiles among different SAID for evidence of common molecular pathways that could provide insights into pathogenic mechanisms shared by these diseases. Methods: Differential quantitative proteomic analyses (one-dimensional reverse-phase liquid chromatography-mass spectrometry) were performed to assess patterns of plasma protein expression. Monozygotic twins (four pairs discordant for systemic lupus erythematosus, four pairs discordant for juvenile idiopathic arthritis and two pairs discordant for juvenile dermatomyositis) were studied to minimize polymorphic gene effects. Comparisons were also made to 10 unrelated, matched controls. Results: Multiple plasma proteins, including acute phase reactants, structural proteins, immune response proteins, coagulation and transcriptional factors, were differentially expressed similarly among the different SAID studied. Multivariate Random Forest modeling identified seven proteins whose combined altered expression levels effectively segregated affected vs. unaffected twins. Among these seven proteins, four were also identified in univariate analyses of proteomic data (syntaxin 17, a-glucosidase, paraoxonase 1, and the sixth component of complement). Molecular pathway modeling indicated that these factors may be integrated through interactions with a candidate plasma biomarker, PON1 and the pro-inflammatory cytokine IL-6. Conclusions: Together, these data suggest that different SAID may share common alterations of plasma protein expression and molecular pathways. An understanding of the mechanisms leading to the altered plasma proteomes common among these SAID may provide useful insights into their pathogeneses

Measurement Methods of Burnup and Heavy Element Isotopic Composition in Irradiated Power Reactor Fuels

Methods for determining the heavy element isotopic compositions and atom percent fission for reactor fuels are briefly described, and their accuracies are discussed. (D.C.W.

Capillary filling with wall corrugations] Capillary filling in microchannels with wall corrugations: A comparative study of the Concus-Finn criterion by continuum, kinetic and atomistic approaches

We study the impact of wall corrugations in microchannels on the process of capillary filling by means of three broadly used methods - Computational Fluid Dynamics (CFD), Lattice-Boltzmann Equations (LBE) and Molecular Dynamics (MD). The numerical results of these approaches are compared and tested against the Concus-Finn (CF) criterion, which predicts pinning of the contact line at rectangular ridges perpendicular to flow for contact angles theta > 45. While for theta = 30, theta = 40 (no flow) and theta = 60 (flow) all methods are found to produce data consistent with the CF criterion, at theta = 50 the numerical experiments provide different results. Whilst pinning of the liquid front is observed both in the LB and CFD simulations, MD simulations show that molecular fluctuations allow front propagation even above the critical value predicted by the deterministic CF criterion, thereby introducing a sensitivity to the obstacle heigth.Comment: 25 pages, 8 figures, Langmuir in pres

Análise de endemismo de táxons neotropicais de Pentatomidae (Hemiptera: Heteroptera)

The definition of areas of endemism is central to studies of historical biogeography, and their interrelationships are fundamental questions. Consistent hypotheses for the evolution of Pentatomidae in the Neotropical region depend on the accuracy of the units employed in the analyses, which in the case of studies of historical biogeography, may be areas of endemism. In this study, the distribution patterns of 222 species, belonging to 14 Pentatomidae (Hemiptera) genera, predominantly neotropical, were studied with the Analysis of Endemicity (NDM) to identify possible areas of endemism and to correlate them to previously delimited areas. The search by areas of endemism was carried out using grid-cell units of 2.5° and 5° latitude-longitude. The analysis based on groupings of grid-cells of 2.5° of latitude-longitude allowed the identification of 51 areas of endemism, the consensus of these areas resulted in four clusters of grid-cells. The second analysis, with grid-cells units of 5° latitude-longitude, resulted in 109 areas of endemism. The flexible consensus employed resulted in 17 areas of endemism. The analyses were sensitive to the identification of areas of endemism in different scales in the Atlantic Forest. The Amazonian region was identified as a single area in the area of consensus, and its southeastern portion shares elements with the Chacoan and Paraná subregions. The distribution data of the taxa studied, with different units of analysis, did not allow the identification of individual areas of endemism for the Cerrado and Caatinga. The areas of endemism identified here should be seen as primary biogeographic hypotheses.A definição de áreas de endemismo é central aos estudos de Biogeografia Histórica e suas inter-relações são questões fundamentais. Hipóteses consistentes sobre a evolução de Pentatomidae (Hemiptera) na Região Neotropical dependem da acuidade das unidades empregadas nas análises, que no caso de estudos de biogeografia histórica, podem ser áreas endêmicas. Neste trabalho foram estudados os padrões de distribuição de 222 espécies, pertencentes a 14 gêneros de Pentatomidae, com ocorrência predominantemente neotropical, com base em uma Análise de Endemicidade (NDM) a fim de inferir possíveis áreas endêmicas e relacioná-las a áreas previamente delimitadas. A busca por áreas endêmicas foi realizada com quadrículas de 2,5° e 5° latitude-longitude. A análise com base em agrupamentos de 2,5° latitude-longitude permitiu identificar 51 áreas de endemismo, sendo que o consenso destas áreas resultou em quatro agrupamentos de quadrículas. A segunda análise, com quadrículas de 5° latitude-longitude, resultou em 109 áreas de endemismo. O consenso flexível empregado resultou em 17 áreas de endemismo. As análises foram sensíveis à identificação de áreas de endemismo na Mata Atlântica em diferentes escalas. A região Amazônica foi identificada como uma área única no consenso, sendo que a porção sudeste compartilha elementos com as sub-regiões do Chaco e Paraná. Os dados de distribuição dos táxons estudados, com diferentes unidades de análises, não permitiram a identificação de áreas endêmicas para o Cerrado e a Caatinga. As áreas de endemismo aqui identificadas devem ser tratadas como hipóteses biogeográficas primárias.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal do Rio Grande do Sul Laboratório de Entomologia Sistemática Departamento de ZoologiaUniversidade Federal do Paraná Departamento de Zoologia Programa de Pós-Graduação em EntomologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de Ciências BiológicasUNIFESP, Depto. de Ciências BiológicasSciEL

Focused HLA analysis in Caucasians with myositis identifies significant associations with autoantibody subgroups.

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. RESULTS: We report associations with eight autoantibodies reaching our study-wide significance level of p\u3c2.9×10 CONCLUSIONS: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research

A new conceptual framework for revenge firesetting

Revenge has frequently been acknowledged to account for a relatively large proportion of motives in deliberate firesetting. However, very little is actually known about the aetiology of revenge firesetting. Theoretical approaches to revenge-seeking behaviour are discussed. A brief review of how revenge is accounted for in existing theoretical explanations of deliberate firesetting and the known characteristics of revenge firesetters are provided. On this basis, the authors suggest, as a motive, revenge firesetting has to date been misconceptualised. A new conceptual framework is thus proposed, paying particular attention to the contextual, affective, cognitive, volitional and behavioural factors which may influence and generate a single episode of revenge firesetting. Treatment implications and suggestions for future research are also provided

Effects of numerical methods on comparisons between experiments and simulations of shock-accelerated mixing.

We consider the detailed structures of mixing flows for Richtmyer-Meshkov experiments of Prestridge et al. [PRE 00] and Tomkins et al. [TOM 01] and examine the most recent measurements from the experimental apparatus. Numerical simulations of these experiments are performed with three different versions of high resolution finite volume Godunov methods. We compare experimental data with simulations for configurations of one and two diffuse cylinders of SF{sub 6} in air using integral measures as well as fractal analysis and continuous wavelet transforms. The details of the initial conditions have a significant effect on the computed results, especially in the case of the double cylinder. Additionally, these comparisons reveal sensitive dependence of the computed solution on the numerical method

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Acute Kawasaki Disease: Not Just for Kids

Kawasaki Disease is a small-to-medium-vessel vasculitis that preferentially affects children. Kawasaki Disease can occur in adults, but the presentation may differ from that observed in children. Typical findings in both adults and children include fever, conjunctivitis, pharyngitis, and skin erythema progressing to a desquamating rash on the palms and soles. Adults more frequently present with cervical adenopathy (93% of adults vs. 15% of children), hepatitis (65% vs. 10%), and arthralgia (61% vs. 24–38%). In contrast, adults are less frequently affected by meningitis (10% vs. 34%), thrombocytosis (55% vs. 100%), and coronary artery aneurysms (5% vs. 18–25%). We report a case of acute Kawasaki Disease in a 24-year-old man who presented with rash, fever, and arthritis. He was successfully treated with high-dose aspirin and intravenous immunoglobulin (IVIG). Our case highlights the importance of considering Kawasaki Disease in adults presenting with symptoms commonly encountered in a general medical practice