Modeling offenses among motorcyclists involved in crashes in Spain

In relative terms, Spanish motorcyclists are more likely to be involved in crashes than other drivers and this tendency is constantly increasing. The objective of this study is to identify the factors that are related to being an offender in motorcycle accidents. A binary logit model is used to differentiate between offender and non-offender motorcyclists. A motorcyclist was considered to be offender when she had committed at least one traffic offense at the moment previous to the crash. The analysis is based on the official accident database of the Spanish general directorate of traffic (DGT) for the 2003-2008 time period. A number of explanatory variables including motorcyclist characteristics and environmental factors have been evaluated. The results suggest that inexperienced, older females, not using helmets, absent-minded and non-fatigued riders are more likely to be offenders. Moreover, riding during the night, on weekends, for leisure purposes and along roads in perfect condition, mainly on curves, predict offenses among motorcyclists. The findings of this study are expected to be useful in developing traffic policy decisions in order to improve motorcyclist safety

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Identification of candidate Parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets

Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objective To investigate what genes and genomic processes underlie the risk of sporadic PD. Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance. Conclusions and Relevance Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies

Revista de la Facultad de Ciencias Médicas de la Universidad de Cuenca

Objetivo: Determinar las características de la investigación en el posgrado con la finalidad de generar políticas de investigación. Métodos: Se realizó una investigación analítica de corte transversal para determinar las características de la investigación en los diferentes niveles de posgrado. Se utilizó una muestra aleatoria estratificada de la base de datos de las investigaciones de posgrado que constan en la página web de la Universidad de Cuenca. La muestra fue de 98 trabajos de investigación. Se utilizó el estadístico chi2, y se aceptó un nivel de significancia de p:<0,05 en la prueba de hipótesis. Resultados: El modelo de investigación predominante es el biomédico (79,6%), en las maestrías es el social (65,5%), (p: 0.000). La mayor parte son investigaciones clínicas (78,6%). Las investigaciones con componentes sociales se desarrollan en las maestrías (72,4%), (p: 0,000). El número de investigadores varones (50%) es similar al de mujeres (50%). Las investigaciones son elaboradas por un autor. Las investigaciones son aplicadas (100%) y cuantitativas (94,9%). Solo en las maestrías existen investigaciones cualitativas (6,9%), mixtas (6,9%) y otras (3,4%), (p: 0,051). Predominan las investigaciones observacionales (78,6%); las de intervención constituyen el 21,4% (p: 0,889). Las investigaciones descriptivas (36,7%), analíticas (39,8%), tienen mayor peso que las de intervención (23,5%), (p: 0,321). En las analíticas predominan las investigaciones transversales (89,7%), y en las de intervención las experimentales (78,3%). No existe colaboración internacional y la interinstitucional es mínima (7,1%) que se refiere a las maestrías. Existe buena correspondencia con las líneas de investigación institucionales (57,1%) en la mayor parte de investigaciones y, el uso de normas bibliográficas internacionales es alto (99,6%). Conclusiones: Las características fundamentales de la investigación en el posgrado no han variado esencialmente. La investigación predominante sigue siendo biomédica, cuantitativa, clínica, observacional; se ha dado avances en la disminución de las investigaciones descriptivas y se han incrementado las analíticas (transversales) y experimentales. En las maestrías se ha desarrollado más la investigación social de la salud. La investigación no ha logrado superar el ámbito académico y de interés individual, no hay colaboración internacional y la interinstitucional es escasa. Ha mejorado el componente técnico, es mayoritario el uso de normas bibliográficas internacionalesObjective: To determine the characteristics of the postgraduate research in order to generate research policies. Methods: A cross-sectional analytical research was conducted to determine the characteristics of research in the various postgraduate levels. A stratified random sample of the database of postgraduate research contained in the website of the University of Cuenca was used. Chi2 statistic was used, and a level of significance was accepted p <0.05 in hypothesis testing. The sample consisted of 98 research papers. Results: The model for biomedical research is predominant (79.6%) in the Masters is the social (65.5%). (p: 0.000). Most are clinics (78.6%) investigations. Research with social components developed in the masters (72.4%). (p: 0.000). The number of researchers males (50.0%) is similar to that of women (50.0%). The investigations are made by an author. Investigations are applied (100.0%) and quantitative (94.9%). Only the Masters there are qualitative (6.9%), mixed (6.9%) and other (3.4%) investigations. (p = 0.051). Dominated by observational studies (78.6%); the intervention constitute 21.4% (p = 0.889). The descriptive research (36.7%), analytical (39.8%) have greater weight than those of intervention (23.5%), p: 0.321). In the analytical cross-sectional research predominate (89.7%), and the experimental intervention (78.3%). There is no international cooperation and inter is minimal (7.1%) referred to the Masters. There is good correspondence with the lines of institutional research (57.1%) in most research and the use of international bibliographic standards is high (99.6%). Conclusions: The fundamental characteristics of research at the graduate has not changed substantially. The predominant biomedical research remains, quantitative, clinical, observational, there has been progress in reducing the descriptive investigations and have increased (transverse) and experimental analytics. The master has developed more social health research. Research has failed to overcome the academic and personal interest level, no international collaboration and inter is scarce. It has improved the technical component, is majority use international bibliographic standardsCuencavolumen 32 número

Modeling item banking: analysis and design of a computerized system

Computerized adaptive tests rely on item banks from which to select the more suited items to be applied along the test administration; however, the availability of item banks is rather limited and, on the other hand, the development of an item bank can involve a great deal of effort for test users. The aim of this work concerned the analysis and design of a computerized system aimed to support the whole process of developing and maintaining item banks. Resulting from it, an item banking model is proposed which provides the basis to implement such a computerized system and, also, to encourage the discussion about the more suitable model for this goal. It is to be expected that the availability of sound item banking software could help to extend the application of item-bank based tests, like computerized adaptive tests, beyond the boundaries of large-scale testing programs.Los tests adaptativos informatizados dependen de la existencia de bancos de ítems de los que seleccionar los ítems más adecuados a aplicar a lo largo de la administración del test. Ahora bien, la disponibilidad de bancos de ítems es bastante limitada y, por otra parte, el desarrollo de bancos de ítems suele representar un esfuerzo considerable en la práctica. Ello motivó el desarrollo de este trabajo, centrado en el análisis y diseño de un sistema orientado a dar soporte informatizado a todo el proceso de construcción y mantenimiento de bancos de ítems. Así, el modelo de desarrollo de bancos de ítems propuesto provee las bases para implementar un programa orientado a tal fin y, también, promover la discusión acerca del modelo más conveniente en el desarrollo de tal programa. Es de esperar que la disponibilidad de software para desarrollar y trabajar con bancos de ítems ayude a extender la aplicación de los tests basados en bancos de ítems, como es el caso de los tests adaptativos informatizados

Effectiveness of an online multicomponent program (FATIGUEWALK) for Chronic Fatigue Syndrome : a randomized controlled trial

OBJECTIVE: This study aimed to evaluate the effectiveness of an online multicomponent intervention called FATIGUEWALK (FaW) compared to treatment as usual (TAU) in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). METHOD: FaW included pain neuroscience education, therapeutic exercise, cognitive restructuring, and mindfulness training. A total of 428 patients with CFS/ME were randomized into two study arms: online FaW plus TAU versus TAU alone. A single-blinded randomized controlled trial was conducted. Validated patient-reported outcome measures of fatigue, pain, anxiety, depression, and physical function were collected at baseline and posttreatment, following the FaW intervention, which lasted 12 weeks. RESULTS: Statistically significant improvements (with small-to-moderate effect sizes) were observed in online FaW versus TAU alone with respect to multidimensional aspects of fatigue (Cohen's d ranging from 0.25 to 0.73) and most secondary outcomes (pain and fatigue intensity, depressive and anxious symptomatology, functional impairment, kinesiophobia, physical functioning). The absolute risk reduction in FaW versus TAU was 19%, 95% confidence interval (CI) [12.19, 25.80] with number needed to treat = 6, 95% CI [3.9, 8.2]. Overall, similar clinical improvements were observed in sensitivity analyses including a subgroup of patients without comorbidity with fibromyalgia ( n = 70). CONCLUSIONS: This is the first study to assess the short-term effectiveness of an online multicomponent intervention added to TAU, compared to TAU alone, for the management of CFS/ME. Further trials, including active control groups with an equivalent treatment dose, and assessing the long-term effectiveness of the online FaW, are warranted. (PsycInfo Database Record (c) 2023 APA, all rights reserved).Objetivo: Este estudio tuvo como objetivo evaluar la efectividad de una intervención multicomponente en línea llamada FATIGUEWALK (FaW) en comparación con el tratamiento habitual (TAU, por sus siglas en inglés) en pacientes con síndrome de fatiga crónica/encefalomielitis miálgica (CFS/ME, por sus siglas en inglés). Método: FaW incluyó educación en neurociencia del dolor, ejercicio terapéutico, reestructuración cognitiva y entrenamiento de atención plena. Un total de 428 pacientes con CFS/ME fueron asignados aleatoriamente a dos grupos de estudio: FaW en línea más TAU versus TAU solo. Se llevó a cabo un estudio controlado aleatorio (ECA) simple ciego. Se recopilaron medidas de resultado validadas informadas por los pacientes de fatiga, dolor, ansiedad, depresión y función física al inicio y después del tratamiento, después de la intervención FaW, que duró 12 semanas. Resultados: Se observaron mejoras estadísticamente significativas (con tamaños de efecto pequeños a moderados) en FaW en línea versus TAU solo con respecto a los aspectos multidimensionales de la fatiga (la d de Cohen oscila entre 0.25 y 0.73) y la mayoría de los resultados secundarios (intensidad de dolor y la fatiga, depresión y ansiedad sintomatológica, deterioro funcional, kinesiofobia, funcionamiento físico). La reducción del riesgo absoluto en FaW versus TAU fue del 19% (IC del 95% = [12.19, 25.80]) con número necesario a tratar (NNT) = 6 (IC del 95% = 3.9-8.2). En general, se observaron mejoras clínicas similares en los análisis de sensibilidad que incluyeron un subgrupo de pacientes sin comorbilidad con fibromialgia (n = 70). Conclusiones: Este es el primer estudio que evalúa la efectividad a corto plazo de una intervención multicomponente en línea agregada a TAU, en comparación con TAU sola, para el tratamiento del CFS/ME. Se justifican ensayos adicionales, que incluyan grupos de control activo con una dosis de tratamiento equivalente y que evalúen la eficacia a largo plazo del FaW en línea

Non-embolic outcomes in patients with cardiovascular disease and atrial fibrillation treated with rivaroxaban

Aim: It is not well known how comorbidities may change the prognosis of atrial fibrillation (AF) patients. This study was aimed to analyze the impact of cardiovascular disease on this population. Materials & methods: EMIR was a multicenter, prospective study, including 1433 AF patients taking rivaroxaban for ≥6 months. Data were analyzed according to the presence of vascular disease. Results: Coronary artery disease was detected in 16.4%, peripheral artery disease/aortic plaque in 6.7%, vascular disease in 28.3%. Patients with coronary artery disease had higher rates (per 100 patient-years) of major adverse cardiovascular events (2.98 vs 0.71; p < 0.001) and cardiovascular death (1.79 vs 0.41; p = 0.004). Those with vascular disease had higher rates of thromboembolic events (1.47 vs 0.44; p = 0.007), major adverse cardiovascular events (2.03 vs 0.70; p = 0.004), and cardiovascular death (1.24 vs 0.39; p = 0.025). Patients with peripheral artery disease/aortic plaque had similar rates. Conclusion: AF patients with vascular disease have a higher risk of non-embolic outcomes