22 research outputs found
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)
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
El papel de las cogniciones en el juego de azar: distorsiones o sesgos cognitivos
El abuso de Internet puede interferir negativamente en la vida cotidiana de algunas personas y afectar al rendimiento académico, al laboral, a la calidad de las relaciones sociales y a una ocupación sana del tiempo libre.Depto. de Personalidad, Evaluación y Psicología ClínicaFac. de PsicologíaTRUEpu
Cognitive distortions in gamblers and non-gamblers of a representative Spanish sample
Cognitive biases or distortions related to gambling, present in all people, are considered a relevant factor in the development of gambling-related problems. Objective: to establish whether the presence of these biases or cognitive distortions, in gamblers and nongamblers, is related to the presence of gambling problems. Method: 3000 people aged 18–81 years, representative of the Spanish adult population, underwent a structured survey. Results: the presence of distortions was relevant to distinguish gamblers according to their level of gambling engagement and problems. There is a constant and significant tendency to have more cognitive distortions as gambling problems increase. But not all distortions have the same ability to distinguish between the different groups of gamblers. The results seem to group gamblers into three groups according to the presence of cognitive distortions, from less to more: (1) non-gamblers, (2) low-risk and at-risk gamblers, and (3) problem and pathological gamblers. The relevance of this research and its practical implications for both treatment and prevention work is discussed.Sociedad Española de Apuestas y Loterías del EstadoDepto. de Personalidad, Evaluación y Psicología ClínicaFac. de PsicologíaTRUEpu
Probability and predictors of remission from life-time prescription drug use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions
While prescription drug use disorders (PDUD) has become an important and growing public health problem, little is known about their course. This study aims to estimate cumulative probability of remission from sedatives, tranquilizers, opioids and stimulants, and to identify predictors of remission across substances. Analyses were done for the sub-sample of individuals with lifetime history of abuse or dependence on sedatives (n = 402), tranquilizers (n = 372), opioids (n = 521), and stimulants (n = 765) at Wave 1 of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Cumulative probability estimates and hazard ratios for remission from PDUD were obtained for the general population. Lifetime cumulative probability estimates of remission were above 96% for all substances assessed. Half of the cases of PDUD remitted between 4 and 5 years after onset. Remission from PDUD was greater for younger individuals. Males exhibited lower hazards of remission for stimulants use disorder. A diagnosis of personality disorders decreased probability of remission for sedatives and stimulants. Only abuse or dependence on some prescription drugs decreased the probability of remission from other PDUD, whereas other drug disorders did not predict remission. A significant proportion of individuals with PDUD achieve remission at some point in their life-time. Predictors of remission were found to be mostly substance-specific rather than common across substances. The lower rates of remission among some subgroups of the population highlight the need to strengthen preventive and intervention efforts among vulnerable population subgroups.Depto. de Personalidad, Evaluación y Psicología ClínicaFac. de PsicologíaTRUEpu
Factors associated with prolonging psychological treatment for anxiety disorders
Background: Anxiety disorders are one of the disorders most frequently
requested for psychological attention. The purpose of this study is to
identify the factors that can explain a longer duration of psychological
treatment for anxiety disorders. Method: 202 patients from the University
Psychology Clinic of the Complutense University of Madrid were
analyzed. Results: Multivariate regression analysis showed that the
presence of obsessive-compulsive disorder and the application of arousal
control techniques followed by modeling and other specifi c techniques
were the best predictors of treatment duration. Conclusion: Reducing
as much as possible the number of techniques applied without reducing
intervention effi cacy is suggested. In some disorders that produce a greater
life disorganization, it may be useful to try to organize the patient´s life
either as a fi rst goal or at the same time as the intervention program, so as
to increase its effectiveness and reduce the number of sessions.Depto. de Personalidad, Evaluación y Psicología ClínicaFac. de PsicologíaTRUEpu
Propiedades psicométricas de un instrumento de cribado breve on-line para la detección de jugadores de riesgo.
Background: Gambling facilitates the development of psychopathological
problems in some gamblers. Rapid and easy detection of the presence
of these problems, or the risk of their development, will allow early
action at the beginning of the problem, including preventive action.
For this purpose, we developed the “Sistema de Cribado de Riesgo de
Problemas de Juegos” (SCRI-PJ [Risk of Gambling Problems Screening
System]), an on-line instrument for the detection of people who have,
or may develop, gambling problems. The goal of this work is to present
and validate the SCRI-PJ. Method: 85 people with gambling problems
undergoing treatment and 119 people from the general population were
assessed with the SCRI-PJ and the DSM-RT Diagnostic Criteria for
Pathological Gambling questionnaire. Results: The SCRI-PJ showed
high internal consistency (α = .96), sensitivity (94.2%) specifi city (91.4%),
with a negative predictive value of 98.6%. Conclusion: The SCRI-PJ is a
brief and effective screening instrument to detect people with gambling
problems or who are at risk of developing them.Depto. de Personalidad, Evaluación y Psicología ClínicaFac. de PsicologíaTRUEpu
Factores que interfieren en el curso del tratamiento de los problemas de ansiedad: la prolongación y la terminación prematura del tratamiento
The efficacy and the effectiveness of anxiety disorder treatments have been proven. However, the desired results are not always
achieved. Studying the factors that interfere with the natural course of the treatments could help to correct and to adapt them.
Two of these factors are the unnecessary prolongation of treatments and their premature termination. As expected, the duration
of the treatment depends on the nature of the problem and the existence of comorbid problems, however treatments that are too
ambitious (an excess of techniques) or combined with pharmacological treatments (increasing sessions by up to 21%) also have
a longer duration. Premature termination is around 30-35% and patients “announce” the dropout by displaying poorer task
performance and more irregular attendance from the beginning. More than 50% of the therapeutic dropout occurs before the
eighth session and 80% of successful treatments are completed before the 20th session.Depto. de Personalidad, Evaluación y Psicología ClínicaFac. de PsicologíaTRUEpu
Sistemas de detección y evaluación de los problemas de juego
El abuso de Internet puede interferir negativamente en la vida cotidiana de algunas personas y afectar al rendimiento académico, al laboral, a la calidad de las relaciones sociales y a una ocupación sana del tiempo libre.Depto. de Personalidad, Evaluación y Psicología ClínicaFac. de PsicologíaTRUEpu