Noncoding mutations drive persistence of a founder preleukemic clone which initiates late relapse in T-ALL.

ABSTRACT: T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.

Scientific clickbait: Examining media coverage and readability in genome-wide association research.

In the present study, we analyzed a large corpus of English-language online media articles covering genome-wide association studies (GWAS), exemplifying the use of computational methods to study science communication in biological sciences. We analyzed trends in media coverage, readability, themes, and mentions of ethical and social issues, in over 5,000 websites published from 2005 to 2018 from 3,555 GWAS publications on 1,943 different traits, identified via GWAS Catalog using a text-mining approach to inform the discussion about genetic literacy and media coverage. We found that 22.9% of GWAS papers received media attention but most were described in language too complex to be understood by the public. Ethical issues are rarely mentioned and mentions of translation are increasing over time. We predicted media attention based on year of publication, number of genetic associations identified, study sample size, and journal impact factor, using a regression model (r2 = 38.7%). We found that chronotype, educational attainment, alcohol and coffee consumption, sexual orientation, tanning, and hair color received substantially more attention than predicted by the regression model. We also evaluated the prevalence of the clickbait "one gene, one disease" headlines (e.g., "Scientists Say They've Found Gene That Causes Breast Cancer") and found that it is declining. In sum, online media coverage of GWAS should be more accessible, introduce more modern genetics terms, and when appropriate, ELSI should be mentioned. Science communication research can benefit from big data and text-mining techniques which allow us to study trends and changes in coverage trends across thousands of media outlets. Results can be explored interactively in a website we have built for this manuscript: https://jjmorosoli.shinyapps.io/newas/.

Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.

The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder, and phobias) are highly prevalent, often onset early, persist throughout life, and cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant ANX risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 of the 58 associated variants were replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism, and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism underlying ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.

Genetics of environmental sensitivity to psychiatric and neurodevelopmental phenotypes: evidence from GWAS of monozygotic twins.

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity.

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Five-factor model of personality disorders: Spanish normative data and validation / Modelo de los cinco factores de los trastornos de personalidad: Baremo español y validación

The categorical approach of personality disorders (PD) has given way to a dimensional paradigm. Within this, the Five-factor model (FFM) proposes theoretical hypotheses describing personality pathologies and PD empirical prototypes based on the DSM (DSM-PD). Moreover, a methodology to score DSM-PD using the NEO PI-R facets was developed. In this ex post-facto study FFM-PD count norms were developed using data from the NEO PI-R Spanish adaptation. Furthermore, the diagnostic agreement with the IPDE and validity of FFM-PD counts was analyzed in a clinical (n = 222) and non-clinical sample (n = 742). Based on NEO PI-R scores, we presented Spanish FFM-PD normative data. FFMPD benchmarks were highly likely to be exceeded if subjects were classified as a subclinical case in the DSM-PD. Convergent correlations of FFM-PD counts with their equivalent subclinical cases of DSM-PD were statistically significant and outperformed any divergent correlation as well as the average divergent correlations in all FFM-PD. The use of a count technique based on NEO PI-R facets and Spanish FFM-PD normative data facilitate PD understanding and interpretation in various applied psychology fields

La concepción categórica de los trastornos de personalidad (TP) ha dado paso al paradigma dimensional, donde el modelo de los Cinco Factores (MCF) propone hipótesis teóricas para describir la patología de la personalidad y prototipos empíricos de los TP del DSM, además de técnicas para valorarlos en base a facetas del NEO PI-R. En este estudio ex post-facto se han elaborado baremos para el recuento de TP-MCF a partir de la adaptación española del NEO PI-R. Además, se ha comprobado la coherencia diagnóstica con IPDE y la validez de los recuentos de TP-MCF en una muestra clínica (n = 222) y otra no clínica (n = 742). A partir de las puntuaciones en NEO PI-R se elaboró el baremo español de los TP-MCF, cuyas cotas significativas son superadas con elevada probabilidad por casos subclínicos detectados con IPDE. Las correlaciones convergentes entre los recuentos de TP-MCF y los equivalentes casos de TP-DSM fueron estadísticamente significativas y superaron a cualquier correlación divergente y a la correlación divergente media en todos los TP-MCF. El recuento de facetas relevantes en TP-MCF y el baremo español resultante facilitan la comprensión e interpretación de los TP en distintos ámbitos de la psicología aplicada

El Registro de Gemelos de Murcia. Un recurso para la investigación sobre conductas relacionadas con la salud / The Murcia Twin Registry. A resource for research on health-related behaviour

Los diseños genéticamente informativos, y en particular los estudios de gemelos, constituyen la metodología más utilizada para analizar la contribución relativa de los factores genéticos y ambientales a la variabilidad interindividual. Básicamente, consisten en comparar el grado de similitud, con respecto a una característica o rasgo determinado, entre gemelos monocigóticos y dicigóticos. Además de la clásica estimación de heredabilidad, este tipo de registros permite una amplia variedad de análisis únicos por las características de la muestra. El Registro de Gemelos de Murcia es un registro de base poblacional centrado en el análisis de conductas relacionadas con la salud. Las prevalencias de problemas de salud observadas son comparables a las de otras muestras de referencia de ámbito regional y estatal, lo que avala su representatividad. En conjunto, sus características facilitan el desarrollo de diversas modalidades de investigación, además de diseños genéticamente informativos y la colaboración con distintas iniciativas y consorcios (AU)

Genetically informative designs and, in particular, twin studies, are the most widely used methodology to analyse the relative contribution of genetic and environmental factors to inter-individual variability. These studies basically compare the degree of phenotypical similarity between monozygotic and dizygotic twin pairs. In addition to the traditional estimate of heritability, this kind of registry enables a wide variety of analyses which are unique due to the characteristics of the sample. The Murcia Twin Registry is population-based and focused on the analysis of health-related behaviour. The observed prevalence of health problems is comparable to that of other regional and national reference samples, which guarantees its representativeness. Overall, the characteristics of the Registry facilitate developing various types of research as well as genetically informative designs, and collaboration with different initiatives and consortia (AU)

An explanatory model of underwater adaptation / Un modelo explicativo de la adaptación subacuática

The underwater environment is an extreme environment that requires a process of human adaptation with specific psychophysiological demands to ensure survival and productive activity. From the standpoint of existing models of intelligence, personality and performance, in this explanatory study we have analyzed the contribution of individual differences in explaining the adaptation of military personnel in a stressful environment. Structural equation analysis was employed to verify a model representing the direct effects of psychological variables on individual adaptation to an adverse environment, and we have been able to confirm, during basic military diving courses, the structural relationships among these variables and their ability to predict a third of the variance of a criterion that has been studied very little to date. In this way, we have confirmed in a sample of professionals (N = 575) the direct relationship of emotional adjustment, conscientiousness and general mental ability with underwater adaptation, as well as the inverse relationship of emotional reactivity. These constructs are the psychological basis for working under water, contributing to an improved adaptation to this environment and promoting risk prevention and safety in diving activities

El medio subacuático constituye un entorno extremo que exige un proceso de adaptación humana con demandas psicofisiológicas específicas para garantizar la supervivencia y la actividad productiva. En este trabajo explicativo se analiza, bajo la óptica de los actuales modelos de inteligencia, personalidad y rendimiento, la contribución de las diferencias individuales para explicar la adaptación de personal militar en un entorno estresante. Se verifica, mediante análisis de ecuaciones estructurales, un modelo donde se contemplan los efectos directos de las variables psicológicas sobre la adaptación personal a un medio adverso, comprobando sus relaciones estructurales durante la realización de cursos básicos de buceo militar y su capacidad para predecir un tercio de la varianza de un criterio poco estudiado. De esta manera, se confirma en una muestra de profesionales (N = 575) la relación directa de ajuste emocional, responsabilidad y habilidad mental general con la adaptación subacuática, atribuyendo una relación inversa a reactividad emocional. Estos constructos constituyen el fundamento psicológico para desenvolverse con seguridad y trabajar bajo el agua, contribuyen a la mejora de la adaptación al medio subacuático y favorecen la prevención de riesgos y la seguridad en las actividades de buceo

A Escolarização da leitura literária / Literature and reading

O objetivo do artigo é priorizar o gênero literário como prática de leitura na escolarização. Por meio desse gênero é possível a materialização do diálogo interno que se estabelece entre autor e leitor, captado pelo diário de leitura, novo instrumento de ensino-aprendizagem de leitura. O diário como instrumento escolar possibilita ao aluno construir, com o auxílio da escrita, os significados apreendidos, como também estimula o desenvolvimento do espírito crítico do leitor. Permite ainda, o compartilhamento dos diversos significados tecidos pelos diferentes leitores(AU)

The objective of this article is to prioritize the literary genre as a reading practice in school. Through this literary genre is possible the realization of the internal dialogue established between author and reader, captured by the reading diary, a new tool for teaching and learning process of reading. The reading diary, as a school instrument, enables the student to construct, with the aid of writing skills, not only the meanings grasped, but also stimulates the development of reader´s critical thinking. It also allows sharing the various meanings found by different readers(AU)

Perfil clínico-epidemiológico del paciente con insuficiencia cardiaca en un hospital universitario / Clinical-epidemiological profile of the patient with heart failure at a University Hospital

Objetivo: conocer el perfil sociodemográfico y clínico del paciente con insuficiencia cardiaca atendido en un hospital universitario. Método: estudio observacional prospectivo de una cohorte de pacientes atendidos por insuficiencia cardiaca entre el 1 de enero de 2003 y el 31 de diciembre de 2006 en el Complexo Hospitalario Universitario de Ourense. Se recogieron datos clínico-epidemiológicos a través de la revisión de historias clínicas. Análisis descriptivo y analítico. Programa estadístico SPSS versión 22.0. Resultados: la muestra fue de 665 sujetos, con edad media (desviación estándar) de 76,51 (10,37) años. El 54,4% era varón, el 69,3% residía en el ámbito rural. El 56,7% ingresó en el servicio de cardiología. El 55,6% (n= 370) de los pacientes presentaba la fracción de eyección ventricular izquierda (FEVI) preservada. Un 52,8% presentaba hipertensión arterial (HTA) como antecedente clínico. El 68,0% tenía disnea en el ingreso. Los tratamientos más prescritos al alta fueron los diuréticos no ahorradores de K+ (85,4%), los IECAS-ARA II (66%) y los antiagregantes (42,10%). Conclusiones: el perfil más habitual de pacientes atendidos por insuficiencia cardiaca en el centro es el de varón mayor de 65 años, que vive en el entorno rural, con FEVI preservada, en el que el antecedente clínico más prevalente es la HTA y cuyo síntoma más habitual es la disnea, que requiere tratamiento farmacológico con diuréticos no ahorradores de K+, IECAS-ARA II y antiagregantes para el control de la enfermedad

Objective: to understand the sociodemographical and clinical profile of the patient with heart failure managed at a University Hospital. Method: a prospective observational study in a cohort of patients managed for heart failure between January 1st, 2003 and December 31st, 2006 at the Complexo Hospitalario Universitario of Orense. Clinical-epidemiological data were collected through the review of clinical records. Descriptive and analytical analysis; statistical program SPSS version 22.0. Results: the sample included 665 patients, with a mean age (standard deviation) of 76.51 (10.37) years; 54.4% of them were male, and 69.3% lived in the rural area. Of these patients, 56.7% were admitted at the Cardiology Unit; 55.6% (n= 370) of them had their left ventricular ejection fraction (LVEF) preserved. Also, 52.8% of the patients presented hypertension (HTN) as clinical background, and 68.0% presented dyspnea at admission. The most widely prescribed treatments at discharge where non-K+-saving diuretics (85.4%), ACE inhibitors-ARBs (66%) and antiaggregants (42.10%). Conclusions: the most typical profile of patients managed for heart failure at the centre is a male >65-year-old patient, living in the rural setting, with preserved LVEF, where the most prevalent clinical background is HTN, and with dyspnea as the most usual symptom; this patient requires pharmacological treatment with non-K+-saving diuretics, ACE inhibitors-ARBs and antiaggregants for disease control

Prediction of human adaptation and performance in underwater environments / Predicción de la adaptación y rendimiento humanos en el medio subacuático

BACKGROUND: Environmental stressors require the professional diver to undergo a complex process of psychophysiological adaptation in order to overcome the demands of an extreme environment and carry out effective and efficient work under water. The influence of cognitive and personality traits in predicting underwater performance and adaptation has been a common concern for diving psychology, and definitive conclusions have not been reached. METHOD: In this ex post facto study, psychological and academic data were analyzed from a large sample of personnel participating in scuba diving courses carried out in the Spanish Navy Diving Center. In order to verify the relevance of individual differences in adaptation to a hostile environment, we evaluated the predictive validity of general mental ability and personality traits with regression techniques. RESULTS: The data indicated the existence of psychological variables that can predict the performance (R2 = .30, p<.001) and adaptation (R2N= .51, p<.001) of divers in underwater environment. CONCLUSIONS: These findings support the hypothesis that individual differences are related to the probability of successful adaptation and effective performance in professional diving. These results also verify that dispositional traits play a decisive role in diving training and are significant factors in divers' psychological fitness

ANTECEDENTES: los estresores ambientales exigen al buceador profesional un complejo proceso de adaptación psicofisiológica para superar las demandas de un medio extremo y desarrollar trabajos subacuáticos efectivos. La influencia de los rasgos cognitivos y de personalidad para predecir la adaptación y el rendimiento ha constituido una preocupación constante en Psicología del buceo, aunque no se han alcanzado conclusiones definitivas. MÉTODO: en este estudio ex post facto se analizaron datos psicológicos y académicos de personal que realiza cursos de buceo en el Centro de Buceo de la Armada Española. Con el fin de verificar la relevancia de las diferencias individuales en la adaptación a un ambiente hostil, hemos evaluado la validez predictiva de la inteligencia y personalidad mediante técnicas de regresión. RESULTADOS: los datos obtenidos indicaron la existencia de variables psicológicas útiles para predecir el rendimiento (R2 = .30, p<.001) y la adaptación (R2N = .51, p<.001) en el medio subacuático. CONCLUSIONES: estos hallazgos confirman la hipótesis de que las diferencias individuales guardan relación con la probabilidad de obtener una satisfactoria adaptación y rendimiento efectivo en buceo profesional, tienen un papel decisivo en la formación de buceadores y son factores significativos en su aptitud psicológica

Incremental validity of personality measures in predicting underwater performance and adaptation

Intelligence and personality traits are currently considered effective predictors of human behavior and job performance. However, there are few studies about their relevance in the underwater environment. Data from a sample of military personnel performing scuba diving courses were analyzed with regression techniques, testing the contribution of individual differences and ascertaining the incremental validity of the personality in an environment with extreme psychophysical demands. The results confirmed the incremental validity of personality traits (ΔR2 = .20, f 2 = .25) over the predictive contribution of general mental ability (ΔR2 = .07, f 2 = .08) in divers’ performance. Moreover, personality ( 2 L R = .34) also showed a higher validity to predict underwater adaptation than general mental ability ( 2 L R = .09). The ROC curve indicated 86% of the maximum possible discrimination power for the prediction of underwater adaptation, AUC = .86, p < .001, 95% CI (.82–.90). These findings confirm the shift and reversal of incremental validity of dispositional traits in the underwater environment and the relevance of personality traits as predictors of an effective response to the changing circumstances of military scuba diving. They also may improve the understanding of the behavioral effects and psychophysiological complications of diving and can also provide guidance for psychological intervention and prevention of risk in this extreme environment (AU)

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