96,908 research outputs found

    Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome

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    Background: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture, characterized by multiple motor tics and at least one vocal tic persisting for more than one year. Methods: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6,133 TS individuals and 13,565 ancestry-matched controls. Results: We identified a genome-wide significant locus on chromosome 5q15. Integration of eQTL, Hi-C and GWAS data implicated the NR2F1 gene and associated lncRNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring on brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. Conclusions: Our work presents novel insights in the neurobiology of TS opening up new directions for future studies

    Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders

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    MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants. Utilizing exome sequencing and extensive international genetic data sharing, 39 unpublished affected individuals from 18 independent families with biallelic missense variants in MED27 have been identified (29 females, mean age at last follow-up 17±12.4 years, range 0.1-45). Follow-up and hitherto unreported clinical features were obtained from the published 12 families. Brain MRI scans from 34 cases were reviewed. MED27-related disease manifests as a broad phenotypic continuum ranging from developmental and epileptic-dyskinestic encephalopathy to variable neurodevelopmental disorder with movement abnormalities. It is characterised by mild to profound global developmental delay/intellectual disability (100%), bilateral cataracts (89%), infantile hypotonia (74%), microcephaly (62%), gait ataxia (63%), dystonia (61%), variably combined with epilepsy (50%), limb spasticity (51%), facial dysmorphism (38%), and death before reaching adulthood (16%). Brain MRI revealed cerebellar atrophy (100%), white matter volume loss (76.4%), pontine hypoplasia (47.2%), and basal ganglia atrophy with signal alterations (44.4%). Previously unreported 39 affected individuals had seven homozygous pathogenic missense MED27 variants, five of which were recurrent. An emerging genotype-phenotype correlation was observed. This study provides a comprehensive clinical-radiological description of MED27-related disease, establishes genotype-phenotype and clinical-radiological correlations, and suggests a differential diagnosis with syndromes of cerebello-lental neurodegeneration and other subtypes of “neuro-MEDopathies”

    Supplemental Material: Geoelectric evidence for a wide spatial footprint of active extension in central Colorado

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    Additional information pertaining to methodology and results.  </p

    Diccionario Griego-Español, DGE, Volumen VIII

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    El volumen VIII del Diccionario Griego Español (DGE) continúa la redacción lexicográfica de la letra griega épsilon, con una profunda investigación de autores y obras, papiros y ostraca, e Inscripciones. Se realiza en el Instituto de Lenguas y Culturas del Mediterráneo y Oriente Próximo (ILC) del Centro de Ciencias Humanas y Sociales (CCHS) del CSIC (Madrid). Aspira a convertirse en el diccionario de griego antiguo más completo y actualizado, empleando métodos lexicográficos modernos para la estructuración interna de sus artículos

    Where should hydrology go? An early-career perspective on the next IAHS Scientific Decade: 2023-2032

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    This paper shares an early-career perspective on potential themes for the upcoming International Association of Hydrological Sciences (IAHS) scientific decade (SD). This opinion paper synthesizes six discussion sessions in western Europe identifying three themes that all offer a different perspective on the hydrological threats the world faces and could serve to direct the broader hydrological community: “Tipping points and thresholds in hydrology”, “Intensification of the water cycle”, and “Water services under pressure”. Additionally, four trends were distinguished concerning the way in which hydrological research is conducted: big data, bridging science and practice, open science, and inter- and multidisciplinarity. These themes and trends will provide valuable input for future discussions on the theme for the next IAHS SD. We encourage other Early-Career Scientists to voice their opinion by organizing their own discussion sessions and commenting on this paper to make this initiative grow from a regional initiative to a global movement

    Addressing climate change with behavioral science: A global intervention tournament in 63 countries

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    Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.</p

    Synoptic conditions conducive for compound wind-flood events in Great Britain in present and future climates

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    Extreme wind is the main driver of loss in North-West Europe, with flooding being the second-highest driver. These hazards are currently modelled independently, and it is unclear what the contribution of their co-occurrence is to loss. They are often associated with extra-tropical cyclones, with studies focusing on co-occurrence of extreme meteorological variables. However, there has not been a systematic assessment of the meteorological drivers of the co-occurring \textit{impacts} of compound wind-flood events. This study quantifies this using an established storm severity index (SSI) and recently developed flood severity index (FSI), applied to the UKCP18 12km regional climate simulations, and a Great Britain (GB) focused hydrological model. The meteorological drivers are assessed using 30 weather types, which are designed to capture a broad spectrum of GB weather. &amp;#xD;&amp;#xD;Daily extreme compound events (exceeding 99th percentile of both SSI and FSI) are generally associated with cyclonic weather patterns, often from the positive phase of the North Atlantic Oscillation (NAO+) and Northwesterly classifications. Extreme compound events happen in a larger variety of weather patterns in a future climate. The location of extreme precipitation events shifts southward towards regions of increased exposure. The risk of extreme compound events increases almost four-fold in the UKCP18 simulations (from 14 events in the historical period, to 55 events in the future period). It is also more likely for there to be multi-day compound events. At seasonal timescales years tend to be either flood-prone or wind-damage-prone. In a future climate there is a larger proportion of years experiencing extreme seasonal SSI and FSI totals. This could lead to increases in reinsurance losses if not factored into current modelling

    The contribution of external factors to the marketing management of appealing hospitality experiences

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    This research tests a framework of external factors presented in the literature that contribute to the marketing management of hospitality experiences, in a rural tourism context. Data analysis begins with an exploratory factor analysis (EFA) on the items used to measure the concept of appealing hospitality experience. Once established this second order construct, structural equation modelling (SEM) was used to estimate and test the complete proposed model that links: (1) the second-order construct appealing hospitality experience with its first order indicators; (2) the constructs appealing hospitality experience and tourist loyalty. The analysis of data collected from a questionnaire administered in rural lodgings in the region of Southwest Portugal suggests that five factors contribute to appealing hospitality experiences which lead to tourist loyalty: staff performance, physical features, product-related aspects, social interactions, and the existence of a theme. Practical implications for managing responsible hospitality experiences in rural destinations are presented.</p
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