62 research outputs found

    Choosing between print and electronic… Or keeping both? Academic Reading Format International Study (ARFIS) UK Report

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    The Academic Reading Format International Study (ARFIS) is an initiative led by Diane Mizrachi of the University of California Los Angeles (UCLA) and other partners from universities across the world. The aim of the study is to identify students’ format preferences and behaviours when engaging with academic reading (Mizrachi et al, 2015). The collection of data at an international level, offers the opportunity to identify if there are any variations across cultures and institutions, in the attitudes and behaviours of the students regarding the formats (digital and/or print) in which they do their academic reading. The first study of this kind took place at UCLA and involved undergraduate students. To date, the study has been conducted in more than 20 countries in Asia, Europe, Latin America and Oceania (see Mizrachi et al, 2015 for a full list of countries)

    Eficacia de la excepción de inconstitucionalidad como mecanismo de control constitucional

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    This article assesses the effectiveness of the unconstitutionality exception as a constitutional control mechanism in the contentious-administrative jurisdiction of the Quindío province, based on a socio-juridical study, with a mixed approach (quantitative and qualitative), which includes the analysis of 363 sentences pronounced by the Administrative Court of Quindío related with control of nullity and the restoration of labor and pension rights between 2011 and 2016, and of the perception that the magistrates of the High Court have on the unconstitutionality exception. The concept of effectiveness is explained from the thesis of the range of significance proposed by Navarro and Moreso, an approach that allows to conclude that the exception of unconstitutionality, in the studied cases, is effective.En el presente escrito se evalúa la eficacia de laexcepción de inconstitucionalidad como mecanismode control constitucional en la jurisdicción contenciosoadministrativa del departamento del Quindío a partir deun estudio sociojurídico, con enfoque mixto (cuantitativoy cualitativo), que incluye el análisis de 363 sentenciasproferidas por el Tribunal Administrativo del Quindío en elmedio de control de nulidad y restablecimiento de derechoen materia laboral y pensional entre los años 2011 y 2016y de la percepción que los magistrados del Alto Tribunaltienen sobre la excepción de inconstitucionalidad. Elconcepto de eficacia se explica desde la tesis del rango designificación propuesta por Navarro y Moreso, enfoque quepermite concluir que la excepción de inconstitucionalidad,en los casos estudiados, sí es eficaz

    A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

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    Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

    Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

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    Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

    Methodologies used to estimate tobacco-attributable mortality: a review

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    <p>Abstract</p> <p>Background</p> <p>One of the most important measures for ascertaining the impact of tobacco on a population is the estimation of the mortality attributable to its use. To measure this, a number of indirect methods of quantification are available, yet there is no consensus as to which furnishes the best information. This study sought to provide a critical overview of the different methods of attribution of mortality due to tobacco consumption.</p> <p>Method</p> <p>A search was made in the Medline database until March 2005 in order to obtain papers that addressed the methodology employed for attributing mortality to tobacco use.</p> <p>Results</p> <p>Of the total of 7 methods obtained, the most widely used were the prevalence methods, followed by the approach proposed by Peto et al, with the remainder being used in a minority of studies.</p> <p>Conclusion</p> <p>Different methodologies are used to estimate tobacco attributable mortality, but their methodological foundations are quite similar in all. Mainly, they are based on the calculation of proportional attributable fractions. All methods show limitations of one type or another, sometimes common to all methods and sometimes specific.</p

    A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

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    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 analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, 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

    Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

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    OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

    A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

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    We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function

    Eficacia de la excepción de inconstitucionalidad como mecanismo de control constitucional

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    This article assesses the effectiveness of the unconstitutionality exception as a constitutional control mechanism in the contentious-administrative jurisdiction of the Quindío province, based on a socio-juridical study, with a mixed approach (quantitative and qualitative), which includes the analysis of 363 sentences pronounced by the Administrative Court of Quindío related with control of nullity and the restoration of labor and pension rights between 2011 and 2016, and of the perception that the magistrates of the High Court have on the unconstitutionality exception. The concept of effectiveness is explained from the thesis of the range of significance proposed by Navarro and Moreso, an approach that allows to conclude that the exception of unconstitutionality, in the studied cases, is effective.En el presente escrito se evalúa la eficacia de laexcepción de inconstitucionalidad como mecanismode control constitucional en la jurisdicción contenciosoadministrativa del departamento del Quindío a partir deun estudio sociojurídico, con enfoque mixto (cuantitativoy cualitativo), que incluye el análisis de 363 sentenciasproferidas por el Tribunal Administrativo del Quindío en elmedio de control de nulidad y restablecimiento de derechoen materia laboral y pensional entre los años 2011 y 2016y de la percepción que los magistrados del Alto Tribunaltienen sobre la excepción de inconstitucionalidad. Elconcepto de eficacia se explica desde la tesis del rango designificación propuesta por Navarro y Moreso, enfoque quepermite concluir que la excepción de inconstitucionalidad,en los casos estudiados, sí es eficaz

    Características clínico-epidemiológicas de un brote de influenza A en personal militar de Trujillo, Perú 2008

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    We describe an acute febrile respiratory infection outbreak in a military unit in Trujillo, Peru. Cases were identified using the influenza like illness (ILI) definition of the Ministry of Health. Nasal swab samples used for a rapid influenza test (RIT) and pharyngeal swab samples for viral isolation were taken. For influenza A, genotyping of a partial sequence of the hemagglutinin region was performed. The rate attack was 82.9%. Fifty-nine cases appeared between April 1 and 8, 2008; 58 came from the military unit (MU) #1 and one from the MU #2. The RIT identified 40 cases of influenza A and 43 cases were confirmed through cell culture. Isolations were genetically similar to the A H1N1 Brisbane strain. Early detection of outbreaks in confined locations such as military bases permits immediate action in preventing disease propagation.Se describe un brote de infección respiratoria febril aguda en una unidad militar de Trujillo, Perú. Se usó la definición de caso de síndrome gripal del Ministerio de Salud, se tomó hisopado nasal para prueba rápida de influenza (PRI) e hisopado faríngeo para aislamiento viral en cultivo celular. La genotipificación de influenza A fue por secuenciamiento genético de una región del gen de hemaglutinina teniendo como base la cepa vacunal de 2008. Se presentaron 59 casos entre el 01 y 08 de abril de 2008, la tasa de ataque fue de 82,9%. La PRI identificó a 40 casos positivos de influenza A y 43 casos fueron confirmados mediante cultivo celular. Los aislamientos fueron genéticamente similares con la cepa A H1N1 Brisbane . La detección precoz de un brote en lugares cerrados como las bases militares permite actuar de manera inmediata para prevenir su diseminación
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