67 research outputs found
Age, growth and reproduction of Coryphaena hippurus (Linnaeus, 1758) in Maltese waters, Central Mediterranean
Age, growth and reproduction of the dolphinfish Coryphaena hippurus Linnaeus, 1758 collected from the Central Mediterranean in the period 2004-2010 by the traditional Maltese fish aggregating devices (FAD) and surface longline fisheries were studied. The a and b parameters of the length-weight relationship for fish 11-142 cm fork length (FL) (n = 4042) were determined as a = 0.018 and 0.022 with b = 2.85 and 2.79, for males and females respectively. The counting of annual increments from dorsal spines of >65 cm FL dolphinfish at X25 magnification (n = 47) permitting an age reading resolution in years, and the counting of daily increments from sagittal otoliths of <65 cm FL dolphinfish at X400 magnification (n = 583) permitting an age reading resolution in days, were estimated; the von Bertalanffy growth model applied to these fish gave the following parameters: L∞ = 107.8 cm FL and 120.2 cm FL, and K = 1.9 yr-1 and 1.56 yr-1, for males and females respectively. The maximum age observed was 2 years. Size at 50% maturity for fish 10-131 cm FL (n = 1376) was 58.9 cm FL and 62.5 cm FL for males and females, respectively. The sex ratio for the fish sampled from the FAD fishery (10.5-131 cm FL) was 1:1.54 (M:F) and for dolphinfish sampled from the surface longline fishery (91-130 cm FL) was 1:0.76 (M:F). Back-calculated hatch dates from age-0 dolphinfish (n = 518) suggested that spawning occurs from June to September with the highest levels in June. This study is the first to use dorsal spines to determine the age of adult dolphinfishpeer-reviewe
Drug repurposing for Alzheimer's disease based on transcriptional profiling of human iPSC-derived cortical neurons
Alzheimer's disease is a complex disorder encompassing multiple pathological features with associated genetic and molecular culprits. However, target-based therapeutic strategies have so far proved ineffective. The aim of this study is to develop a methodology harnessing the transcriptional changes associated with Alzheimer's disease to develop a high content quantitative disease phenotype that can be used to repurpose existing drugs. Firstly, the Alzheimer's disease gene expression landscape covering severe disease stage, early pathology progression, cognitive decline and animal models of the disease has been defined and used to select a set of 153 drugs tending to oppose disease-associated changes in the context of immortalised human cancer cell lines. The selected compounds have then been assayed in the more biologically relevant setting of iPSC-derived cortical neuron cultures. It is shown that 51 of the drugs drive expression changes consistently opposite to those seen in Alzheimer's disease. It is hoped that the iPSC profiles will serve as a useful resource for drug repositioning within the context of neurodegenerative disease and potentially aid in generating novel multi-targeted therapeutic strategies.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was funded by the Wellcome foundation: A systematic programme to develop and evaluate the best candidate treatments for repositioning as therapies for Alzheimer’s disease (SMART-AD) reference 102001/Z/13/Z.
C.B. reports grants and personal fees from Lundbeck and Acadia and personal fees from Roche, Orion, GSK, Otusaka, Heptares and Lilly outside the submitted work.published version, accepted version, submitted versio
Corrigendum: Centeredness Theory: Understanding and Measuring Well-Being Across Core Life Domains
Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.
The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.NIHR HT
Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)
BACKGROUND: Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. METHODS/DESIGN: The LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. DISCUSSION: The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease
GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors
Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.</p
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe
Installation de production énergétique comprenant un dispositif de prédiction météorologique, notamment une installation de chauffe-eau solaire comprenant un tel dispositif
L'invention concerne une installation de production énergétique destinée à satisfaire un besoin d'utilisateurs (BU) comprenant des moyen de production d'énergie utilisant des énergies renouvelables (1) et non renouvelables (5) ainsi qu'un calculateur (CA) qui reçoit des données de prédictions météorologiques (DM) pour réduire le coût énergétique de fonctionnement de l'installation, les données météorologiques (DM) étant reçues sous la forme d'au moins 4 différents types de niveau de nébulosité de sorte à déterminer un profil d'irradiance globale journalier permettant d'estimer la production du moyen de production d'énergie utilisant des énergies renouvelables (1), le moyen de production énergétique à énergie non renouvelable (5) étant mis en marche ou arrêté de sorte à minimiser son utilisation tout en maintenant dans le dispositif de stockage d'énergie (2) le niveau d'énergie minimal qui permette de satisfaire le besoin des utilisateurs (BU). L'invention concerne notamment une installation de chauffe-eau solaire qui utilise de telles prédictions météorologiques
Contrôleurs Régulateurs Embarqués pour des Systèmes Utilisant l'énergie Solaire
Ce livrable décrit l'ensemble des travaux d'aménagement et de développement une plate-forme expérimentale de PERSEE pour « Contrôleurs Régulateurs Embarqués pour des Systèmes Utilisant l'énergie Solaire » au travers de la réalisation d’une maquette expérimentale d’un contrôleur prédictif pour chauffe-eau solaire individuel CESI
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