Reproducibility in the absence of selective reporting: An illustration from large-scale brain asymmetry research.

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions

Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Background: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. Methods: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. Results: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. Conclusions: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD

Cystic fibrosis with liver involvement in adults has a benign course. Results from a tertiary referral center cohort

Cystic fibrosis liver disease is a poorly understood entity, especially in adults, in terms of its real prevalence, natural history and diagnostic criteria, despite being the most important extrapulmonary cause of mortality. The aim was to evaluate the prevalence, characteristics and potential risk factors of liver disease in adults with cystic fibrosis, according to two diagnostic criteria accepted in the scientific literature. Patients were recruited in a tertiary referral hospital, and laboratory, ultrasound, non-invasive liver fibrosis tests (AST to Platelet Ratio Index [APRI]; Fibrosis-4 Index [FIB4]) and transient elastography (Fibroscan®) were performed. The proportion of patients with liver disease according to the Debray and Koh criteria were evaluated. ninety-five patients were included, 48 (50.5 %) females, with a mean age of 30.4 (28.6-32.2) years. According to the Debray criteria, six (6.3 %) patients presented liver disease. According to the Koh criteria, prevalence increased up to 8.4 %, being statistically different from the 25 % value described in other published series (p = 0.005). Seven (7.5 %) presented ultrasonographic chronic liver disease. Eleven (13 %) presented liver fibrosis according to the APRI score; 95 (100 %) had a normal FIB-4 value. Mean liver stiffness value was 4.4 (4.1-4.7) kPa. FEV1 (OR = 0.16, p 0.05), meconium ileus (OR = 14.16, p 0.002), platelets (Pearson coefficient -0.25, p 0.05) and younger age (Pearson coefficient -0.19, p 0.05) were risk factors. prevalence and severity of liver disease in adult cystic fibrosis patients were lower than expected. Meconium ileus, platelets, age and respiratory function were confirmed as risk factors associated to cystic fibrosis liver diseas

Adenomatous tumor of epididymis. Case presentation

Introduction: the adenomatous tumor is the most common of the solid tumors of the epididymis. It is of benign nature and is not well known its origin yet. Objective: to show a new case of adenomatous tumor of the epididymis, the diagnostic sequence, used therapeutic procedure and the differential diagnostic. Case presentation: patient of 39 years old with antecedents of health that assisted to the outpatient clinic of Urology in the Multi proposal Clinic of Luanda, because increased painless and volume of the right hemi scrotal sac of 4 years of evolution. It did not refer traumatisms or previous inflammatory genital processes. To the physical examination confirmed the presence of a spherical tumor in the head of the right epididymis, around 4 cm of diameter with firm consistency. The homolateral testicle, as well as the contralateral epididymis and the testicle, were normal. The echography revealed a heterogeneous mass, well delimited and little vascularized. The nuclear magnetic resonance denoted an tumor low intense in weighted images in T1, and high intense in weighted images in T2 after the administration of the contrast. The fine needle aspirate biopsy was negative of neoplastic cells. The total excision of the tumor was performed, road Trans scrotal, without complications. Histopathological report of the surgical piece corroborated adenomatous tumor, the patient going on satisfactorily. Conclusions: the adenomatous tumor of epididymis is infrequent. The echography and the Magnetic Resonance Image are useful for the image study. The fine needle aspirate biopsy allows to obtain the pre-surgical histological diagnostic. The treatment of election is the total excision.Key words: epididymis, benign tumor of the epididymis, adenomatoide tumor of epididymis, fine needle aspiration biopsy.</p

Integrating genetic, neuropsychological and neuroimaging data to model early-onset obsessive compulsive disorder severity

We propose an integrative approach that combines structural magnetic resonance imaging data (MRI), diffusion tensor imaging data (DTI), neuropsychological data, and genetic data to predict early-onset obsessive compulsive disorder (OCD) severity. From a cohort of 87 patients, 56 with complete information were used in the present analysis. First, we performed a multivariate genetic association analysis of OCD severity with 266 genetic polymorphisms. This association analysis was used to select and prioritize the SNPs that would be included in the model. Second, we split the sample into a training set (N = 38) and a validation set (N = 18). Third, entropy-based measures of information gain were used for feature selection with the training subset. Fourth, the selected features were fed into two supervised methods of class prediction based on machine learning, using the leave-one-out procedure with the train- ing set. Finally, the resulting model was validated with the validation set. Nine variables were used for the creation of the OCD severity predictor, including six genetic polymorphisms and three variables from the neuropsychological data. The developed model classified child and adolescent patients with OCD by disease severity with an accuracy of 0.90 in the testing set and 0.70 in the validation sample. Above its clinical applicability, the combination of particular neuropsychological, neuroimaging, and genetic characteristics could enhance our under- standing of the neurobiological basis of the disorder

Five-year diagnostic stability among adolescents in an inpatient psychiatric unit

Introduction: In childhood, diagnoses made at the first admission to a psychiatric unit are frequently unstable and temporary. In this study, we examined the stability of DSM-IV-TR disorders and groups of disorders among adolescents followed-up for 5 years after hospitalization. Method: All inpatients admitted for the first time between 2007 and 2008 were included and contacted after 5 years for re-evaluation. The final sample comprised 72 patients. At admission, diagnoses were based on the DSM-IV-TR criteria, Fourth Edition. At five years, diagnoses were made using structured clinical interviews for DSM-IV axis I Disorders and for axis II (SCID-I and SCID-II) as well as the Personality Diagnostic Questionnaire, Fourth Edition (PDQ-4). We also evaluated and collected information on the global assessment of functioning using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) instrument. Depending on the distribution of variables, we used the chi-squared and Fisher exact tests or the Student t and McNemar tests for statistical analyses. Results: The most stable diagnoses were schizophrenia spectrum disorders, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, Tourette syndrome, and pervasive developmental disorder. The most unstable diagnoses were disruptive disorders. Participants were satisfied with their quality of life and the global outcomes of the sample were positive. Conclusion: Major psychiatric disorders, including mood and schizophrenia spectrum disorders, were significantly more stable than other diagnoses and tended to continue into adulthood. In the case of study participants, suffering a mental disorder during adolescence did not appear to affect global functioning outcomes

Fundamentos Necesarios para Alcanzar el Desarrollo Socioeconômico Local a Través de la Gestón Turística Patrimonial

El proceso de gestión turística patrimonial con los enfoques del Desarrollo Socioeconómico Local se revierte cada vez más en el aumento de la calidad de vida de los pobladores. Hoy los notables estudios de este fenómeno se realizan a partir de diagnósticos socioculturales y económicos que conducen a elaborar estrategias para la revalorización de los recursos patrimoniales y una nueva forma de economía en aras del desarrollo. Recurrir a los fundamentos del Patrimonio y la cultura y su vinculación con el sector turístico, y a las consideraciones de esta actividad como una nueva forma de economía hacen que la inserción del desarrollo local como tendencia ha permitido interpretar este fenómeno desde la identidad propia de cada una de las localidades, buscando solucionar las problemáticas asociadas a la conversión de expresiones patrimoniales en recursos, y a la revalorización de los mismos, facilitando su preservación y uso; con posibles beneficios para la comunidad, así como los procesos de capacitación de las diversas expresiones culturales en la transmisión a las futura

Inflammatory dysregulation of monocytes in pediatric patients with obsessive-compulsive disorder

BACKGROUND: Although the exact etiology of obsessive-compulsive disorder (OCD) is unknown, there is growing evidence of a role for immune dysregulation in the pathophysiology of the disease, especially in the innate immune system including the microglia. To test this hypothesis, we studied inflammatory markers in monocytes from pediatric patients with OCD and from healthy controls. METHODS: We determined the percentages of total monocytes, CD16+ monocytes, and classical (CD14highCD16-), intermediate (CD14highCD16low), and non-classical (CD14lowCD16high) monocyte subsets in 102 patients with early-onset OCD and in 47 healthy controls. Moreover, proinflammatory cytokine production (GM-CSF, IL-1β, IL-6, IL-8, and TNF-α) was measured by multiplex Luminex analysis in isolated monocyte cultures, in basal conditions, after exposure to lipopolysaccharide (LPS) to stimulate immune response or after exposure to LPS and the immunosuppressant dexamethasone. RESULTS: OCD patients had significantly higher percentages of total monocytes and CD16+ monocytes than healthy controls, mainly due to an increase in the intermediate subset but also in the non-classical monocytes. Monocytes from OCD patients released higher amounts of GM-CSF, IL-1β, IL-6, IL-8, and TNF-α than healthy controls after exposure to LPS. However, there were no significant differences in basal cytokine production or the sensitivity of monocytes to dexamethasone treatment between both groups. Based on monocyte subset distribution and cytokine production after LPS stimulation, patients receiving psychoactive medications seem to have an intermediate inflammatory profile, that is, lower than non-medicated OCD individuals and higher than healthy controls. CONCLUSIONS: These results strongly support the involvement of an enhanced proinflammatory innate immune response in the etiopathogenesis of early-onset OCD

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker