Validación de la versión en español de la escala de evaluación del trastorno por déficit de atención e hiperactividad (ADHD-RS-IV.es) en una muestra española

Objetivos El objetivo de este estudio es validar la versión en castellano del ADHD-RS-IV (ADHD-RS-IV.es) en una muestra española. Métodos A partir de una muestra total de 652 niños y adolescentes (rango edad: 6-17 años; media [DE] = 11,14 [3,27] años), se incluyó a 518 pacientes con TDAH (criterios DSM-IV-TR) y a 134 controles sanos. Para la evaluación de la estructura factorial, la validez y la fiabilidad de la escala se realizó un análisis factorial confirmatorio (CFA) mediante structural equation modeling en una matriz de correlaciones policóricas, y usando el método de máxima verosimilitud para la estimación. Se calcularon la validez discriminante y su valor predictivo mediante curvas receiver operating characteristics. Resultados La escala en castellano mostró una consistencia interna elevada, tanto para la escala total como para sus subescalas. El coeficiente alfa de Cronbach era 0,94 para la escala total y ≥ 0,90 para las subescalas. Los valores alfa ordinales eran 0,95 para la escala total y ≥ 0,90 para las subescalas. El análisis CFA mostró un modelo de 2 factores (inatención e hiperactividad/impulsividad) intercorrelacionados. La escala ofrece buen poder discriminante (AUC = 0,97). Conclusiones La versión española del ADHD-RS-IV (ADHD-RS-IV.es) mostró una estructura bifactorial consistente con los modelos del DSM-IV-TR y DSM-5, y con el modelo propuesto por el autor de la escala original. Además, posee un alto poder discriminante, lo que lo convierte en un instrumento válido y fiable para medir la presencia y severidad de síntomas de TDAH en la población española.Objectives The purpose of this study is to validate a Spanish-language version of the 18-item ADHD Rating Scale-IV (ADHD-RS-IV.es) in a Spanish sample. Methods From a total sample of 652 children and adolescents aged 6 to 17 years (mean age was 11.14 ± 3.27), we included 518 who met the DSM-IV-TR criteria for ADHD and 134 healthy controls. To evaluate the factorial structure, validity, and reliability of the scale, we performed a confirmatory factor analysis (CFA) using structural equation modelling on a polychoric correlation matrix and maximum likelihood estimation. The scale's discriminant validity and predictive value were estimated using ROC (receiver operating characteristics) curve analysis. Results Both the full scale and the subscales of the Spanish-language version of the ADHD-RS-IV showed good internal consistency. Cronbach's alpha was 0.94 for the full scale and ≥ 0.90 for the subscales, and ordinal alpha was 0.95 and ≥ 0.90, respectively. CFA showed that a two-factor model (inattention and hyperactivity/impulsivity) provided the best fit for the data. ADHD-RS-IV.es offered good discriminant ability to distinguish between patients with ADHD and controls (AUC = 0.97). Conclusions The two-factor structure of the Spanish-language version of the ADHD-RS-IV (ADHD-RS-IV.es) is consistent with those of the DSM-IV-TR and DSM-5 as well as with the model proposed by the author of the original scale. Furthermore, it has good discriminant ability. ADHD-RS-IV.es is therefore a valid and reliable tool for determining presence and severity of ADHD symptoms in the Spanish population

The Planetary Nebula Luminosity Function at the Dawn of Gaia

The [O III] 5007 Planetary Nebula Luminosity Function (PNLF) is an excellent extragalactic standard candle. In theory, the PNLF method should not work at all, since the luminosities of the brightest planetary nebulae (PNe) should be highly sensitive to the age of their host stellar population. Yet the method appears robust, as it consistently produces < 10% distances to galaxies of all Hubble types, from the earliest ellipticals to the latest-type spirals and irregulars. It is therefore uniquely suited for cross-checking the results of other techniques and finding small offsets between the Population I and Population II distance ladders. We review the calibration of the method and show that the zero points provided by Cepheids and the Tip of the Red Giant Branch are in excellent agreement. We then compare the results of the PNLF with those from Surface Brightness Fluctuation measurements, and show that, although both techniques agree in a relative sense, the latter method yields distances that are ~15% larger than those from the PNLF. We trace this discrepancy back to the calibration galaxies and argue that, due to a small systematic error associated with internal reddening, the true distance scale likely falls between the extremes of the two methods. We also demonstrate how PNLF measurements in the early-type galaxies that have hosted Type Ia supernovae can help calibrate the SN Ia maximum magnitude-rate of decline relation. Finally, we discuss how the results from space missions such as Kepler and Gaia can help our understanding of the PNLF phenomenon and improve our knowledge of the physics of local planetary nebulae.Comment: 12 pages, invited review at the conference "The Fundamental Cosmic Distance Scale: State of the Art and Gaia Perspective", to appear in Astrophysics and Space Scienc

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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

Clinical and neuropsychological predictors of methylphenidate response in children and adolescents with ADHD: A naturalistic follow-up study in a spanish sample

Background: Methylphenidate (MPH) is the most commonly used medication for Attention-Deficit/Hyperactivity Disorder (ADHD), but to date, there are neither consistent nor sufficient findings on conditions differentiating responsiveness to MPH response in ADHD. Objective: To develop a predictive model of MPH response, using a longitudinal and naturalistic follow-up study, in a Spanish sample of children and adolescents with ADHD. Methods: We included all children and adolescents with ADHD treated with MPH in our outpatient Clinic (2005 to 2015), evaluated with the K-SADS interview. We collected ADHD-RS-IV.es and CGI-S scores at baseline and at follow up, and neuropsychological testing (WISC-IV, Continuous Performance Test (CPT-II) & Stroop). Clinical response was defined as >30% reduction from baseline of total ADHD-RS-IV.es score and CGI-S final score of 1 or 2 maintained for the previous 3 months. Results: We included 518 children and adolescents with ADHD, mean (SD) age of patients was 11.4 (3.3) years old; 79% male; 51.7% had no comorbidities; and 75.31% had clinical response to a mean MPH dose of 1.2 mg/kg/day. Lower ADHD-RS-IV.es scores, absence of comorbidities (oppositional-defiant symptoms, depressive symptoms and alcohol/cannabis use), fewer altered neuropsychological tests, higher total IQ and low commission errors in CPT-II, were significantly associated with a complete clinical response to methylphenidate treatment. Conclusion: Oppositional-defiant symptoms, depressive symptoms, and a higher number of impaired neuropsychological tests are associated with worse clinical response to methylphenidate. Other stimulants or non-stimulants treatment may be considered when these clinical and neuropsychological variables converged in the first clinical intervie

Clinical and neuropsychological predictors of methylphenidate response in children and adolescents with ADHD: A naturalistic follow-up study in a spanish sample

Background: Methylphenidate (MPH) is the most commonly used medication for Attention-Deficit/Hyperactivity Disorder (ADHD), but to date, there are neither consistent nor sufficient findings on conditions differentiating responsiveness to MPH response in ADHD. Objective: To develop a predictive model of MPH response, using a longitudinal and naturalistic follow-up study, in a Spanish sample of children and adolescents with ADHD. Methods: We included all children and adolescents with ADHD treated with MPH in our outpatient Clinic (2005 to 2015), evaluated with the K-SADS interview. We collected ADHD-RS-IV.es and CGI-S scores at baseline and at follow up, and neuropsychological testing (WISC-IV, Continuous Performance Test (CPT-II) & Stroop). Clinical response was defined as >30% reduction from baseline of total ADHD-RS-IV.es score and CGI-S final score of 1 or 2 maintained for the previous 3 months. Results: We included 518 children and adolescents with ADHD, mean (SD) age of patients was 11.4 (3.3) years old; 79% male; 51.7% had no comorbidities; and 75.31% had clinical response to a mean MPH dose of 1.2 mg/kg/day. Lower ADHD-RS-IV.es scores, absence of comorbidities (oppositional-defiant symptoms, depressive symptoms and alcohol/cannabis use), fewer altered neuropsychological tests, higher total IQ and low commission errors in CPT-II, were significantly associated with a complete clinical response to methylphenidate treatment. Conclusion: Oppositional-defiant symptoms, depressive symptoms, and a higher number of impaired neuropsychological tests are associated with worse clinical response to methylphenidate. Other stimulants or non-stimulants treatment may be considered when these clinical and neuropsychological variables converged in the first clinical intervie

Validación de la versión en español de la escala de evaluación del trastorno por déficit de atención e hiperactividad (ADHD-RS-IV.es) en una muestra española

Objetivos El objetivo de este estudio es validar la versión en castellano del ADHD-RS-IV (ADHD-RS-IV.es) en una muestra española. Métodos A partir de una muestra total de 652 niños y adolescentes (rango edad: 6-17 años; media [DE] = 11,14 [3,27] años), se incluyó a 518 pacientes con TDAH (criterios DSM-IV-TR) y a 134 controles sanos. Para la evaluación de la estructura factorial, la validez y la fiabilidad de la escala se realizó un análisis factorial confirmatorio (CFA) mediante structural equation modeling en una matriz de correlaciones policóricas, y usando el método de máxima verosimilitud para la estimación. Se calcularon la validez discriminante y su valor predictivo mediante curvas receiver operating characteristics. Resultados La escala en castellano mostró una consistencia interna elevada, tanto para la escala total como para sus subescalas. El coeficiente alfa de Cronbach era 0,94 para la escala total y ≥ 0,90 para las subescalas. Los valores alfa ordinales eran 0,95 para la escala total y ≥ 0,90 para las subescalas. El análisis CFA mostró un modelo de 2 factores (inatención e hiperactividad/impulsividad) intercorrelacionados. La escala ofrece buen poder discriminante (AUC = 0,97). Conclusiones La versión española del ADHD-RS-IV (ADHD-RS-IV.es) mostró una estructura bifactorial consistente con los modelos del DSM-IV-TR y DSM-5, y con el modelo propuesto por el autor de la escala original. Además, posee un alto poder discriminante, lo que lo convierte en un instrumento válido y fiable para medir la presencia y severidad de síntomas de TDAH en la población española.Objectives The purpose of this study is to validate a Spanish-language version of the 18-item ADHD Rating Scale-IV (ADHD-RS-IV.es) in a Spanish sample. Methods From a total sample of 652 children and adolescents aged 6 to 17 years (mean age was 11.14 ± 3.27), we included 518 who met the DSM-IV-TR criteria for ADHD and 134 healthy controls. To evaluate the factorial structure, validity, and reliability of the scale, we performed a confirmatory factor analysis (CFA) using structural equation modelling on a polychoric correlation matrix and maximum likelihood estimation. The scale's discriminant validity and predictive value were estimated using ROC (receiver operating characteristics) curve analysis. Results Both the full scale and the subscales of the Spanish-language version of the ADHD-RS-IV showed good internal consistency. Cronbach's alpha was 0.94 for the full scale and ≥ 0.90 for the subscales, and ordinal alpha was 0.95 and ≥ 0.90, respectively. CFA showed that a two-factor model (inattention and hyperactivity/impulsivity) provided the best fit for the data. ADHD-RS-IV.es offered good discriminant ability to distinguish between patients with ADHD and controls (AUC = 0.97). Conclusions The two-factor structure of the Spanish-language version of the ADHD-RS-IV (ADHD-RS-IV.es) is consistent with those of the DSM-IV-TR and DSM-5 as well as with the model proposed by the author of the original scale. Furthermore, it has good discriminant ability. ADHD-RS-IV.es is therefore a valid and reliable tool for determining presence and severity of ADHD symptoms in the Spanish population

Finding genetically-supported drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome

Parkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson’s disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson’s disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson’s disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson’s disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson’s disease drug development

Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

Altres ajuts: Leonard Wolfson Foundation; United Kingdom Medical Research Council (MRC, MR/N008324/1); DRI Limited; UK Medical Research Council; Alzheimer's Society and Alzheimer's Research UK; Medical Research Council (MR/N026004/1); Wellcome Trust (202903/Z/16/Z); Dolby Family Fund; National Institute for Health Research; University College London; Fundación Séneca, Agencia de Ciencia y Tecnología de la Región de Murcia (00007/COVI/20).Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer's disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease

Moving beyond neurons : the role of cell type-specific gene regulation in Parkinson's disease heritability

Parkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types