445 research outputs found

    Trajectories of deficit accumulation and their predictors in older age

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    Correction to: Barriers and facilitators for the management of vertigo: a qualitative study with primary care providers

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    After publication of the original article 1 it was brought to the authors' attention that a sentence was missing in the acknowledgement section. The full acknowledgement is included in this Correction article

    Development of a complex intervention to improve participation of nursing home residents with joint contractures: a mixed-method study

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    Joint contractures in nursing home residents limit the capacity to perform daily activities and restrict social participation. The purpose of this study was to develop a complex intervention to improve participation in nursing home residents with joint contractures

    The ARCA Registry: A Collaborative Global Platform for Advancing Trial Readiness in Autosomal Recessive Cerebellar Ataxias.

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    Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (>15 countries, >30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of patients with established genetic diagnoses capture all the main ARCA genes, and 35% with unsolved diagnoses are targets for advanced next-generation sequencing. The ARCA Registry serves as the backbone of many major European and transatlantic consortia, such as PREPARE, PROSPAX, and the Ataxia Global Initiative, with additional data input from SPORTAX. It has thus become the largest global trial-readiness registry in the ARCA field

    New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

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    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Study of the BΛc+ΛˉcKB^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

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    The decay BΛc+ΛˉcKB^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} is studied in proton-proton collisions at a center-of-mass energy of s=13\sqrt{s}=13 TeV using data corresponding to an integrated luminosity of 5 fb1\mathrm{fb}^{-1} collected by the LHCb experiment. In the Λc+K\Lambda_{c}^+ K^{-} system, the Ξc(2930)0\Xi_{c}(2930)^{0} state observed at the BaBar and Belle experiments is resolved into two narrower states, Ξc(2923)0\Xi_{c}(2923)^{0} and Ξc(2939)0\Xi_{c}(2939)^{0}, whose masses and widths are measured to be m(Ξc(2923)0)=2924.5±0.4±1.1MeV,m(Ξc(2939)0)=2938.5±0.9±2.3MeV,Γ(Ξc(2923)0)=0004.8±0.9±1.5MeV,Γ(Ξc(2939)0)=0011.0±1.9±7.5MeV, m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV}, where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt Λc+K\Lambda_{c}^{+} K^{-} sample. Evidence of a new Ξc(2880)0\Xi_{c}(2880)^{0} state is found with a local significance of 3.8σ3.8\,\sigma, whose mass and width are measured to be 2881.8±3.1±8.5MeV2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV} and 12.4±5.3±5.8MeV12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}, respectively. In addition, evidence of a new decay mode Ξc(2790)0Λc+K\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-} is found with a significance of 3.7σ3.7\,\sigma. The relative branching fraction of BΛc+ΛˉcKB^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} with respect to the BD+DKB^{-} \to D^{+} D^{-} K^{-} decay is measured to be 2.36±0.11±0.22±0.252.36 \pm 0.11 \pm 0.22 \pm 0.25, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

    Measurement of the ratios of branching fractions R(D)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

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    The ratios of branching fractions R(D)B(BˉDτνˉτ)/B(BˉDμνˉμ)\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu}) and R(D0)B(BD0τνˉτ)/B(BD0μνˉμ)\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu}) are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb1{ }^{-1} of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode τμντνˉμ\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}. The measured values are R(D)=0.281±0.018±0.024\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024 and R(D0)=0.441±0.060±0.066\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is ρ=0.43\rho=-0.43. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

    Traces of trauma – a multivariate pattern analysis of childhood trauma, brain structure and clinical phenotypes

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    Background: Childhood trauma (CT) is a major yet elusive psychiatric risk factor, whose multidimensional conceptualization and heterogeneous effects on brain morphology might demand advanced mathematical modeling. Therefore, we present an unsupervised machine learning approach to characterize the clinical and neuroanatomical complexity of CT in a larger, transdiagnostic context. Methods: We used a multicenter European cohort of 1076 female and male individuals (discovery: n = 649; replication: n = 427) comprising young, minimally medicated patients with clinical high-risk states for psychosis; patients with recent-onset depression or psychosis; and healthy volunteers. We employed multivariate sparse partial least squares analysis to detect parsimonious associations between combinations of items from the Childhood Trauma Questionnaire and gray matter volume and tested their generalizability via nested cross-validation as well as via external validation. We investigated the associations of these CT signatures with state (functioning, depressivity, quality of life), trait (personality), and sociodemographic levels. Results: We discovered signatures of age-dependent sexual abuse and sex-dependent physical and sexual abuse, as well as emotional trauma, which projected onto gray matter volume patterns in prefronto-cerebellar, limbic, and sensory networks. These signatures were associated with predominantly impaired clinical state- and trait-level phenotypes, while pointing toward an interaction between sexual abuse, age, urbanicity, and education. We validated the clinical profiles for all three CT signatures in the replication sample. Conclusions: Our results suggest distinct multilayered associations between partially age- and sex-dependent patterns of CT, distributed neuroanatomical networks, and clinical profiles. Hence, our study highlights how machine learning approaches can shape future, more fine-grained CT research

    New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

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    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P <5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.Peer reviewe
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