Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5–21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n=664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).
Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5-21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics, and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n = 664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).. CC-BY-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/149369 doi: bioRxiv preprint first posted online Jun. 13, 2017; PURPOSE OF DATA COLLECTIONPsychiatric and learning disorders are among the most common and debilitating illnesses across the lifespan. Epidemiologic studies indicate that 75% of all diagnosable psychiatric disorders begin prior to age 241 . This underscores the need for increased focus on studies of the developing brain 2 . Beyond improving our understanding of the pathophysiology that underlies the emergence of psychiatric illness throughout development, such research has the potential to identify clinically useful markers of illness that can improve the early detection of pathology and guide interventions. Although the use of neuroimaging, neuropsychology, neurophysiology and genetics has made significant strides in revealing biological correlates for a broad array of illnesses, findings have been lacking in specificity 3 . Consequently, progress in finding clinically useful brain-based biomarkers has been disappointing 4,5 .Given the slow pace in biomarker identification, investigators have been prompted to rethink research paradigms and practices. Most notably, the emphasis on mapping diagnostic labels from a clinically defined nosology (e.g., the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases) to varying biological indices has proven to be problematic, as it assumes consistent biological relationships with broad constellations of signs and symptoms 6,7 . Epidemiologists, psychopathologists, geneticists and neuroscientists are reconsidering the relevance of diagnostic boundaries due to the lack of specif...
On the basis of sensitivity and specificity, basal serum or plasma cortisol concentrations had high negative predictive values over a wide range of prevalence rates and can be used to rule out a diagnosis of hypoadrenocorticism. Dogs with basal cortisol concentrations > 2 microg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is
Background: Dogs with protein-losing nephropathy (PLN) are at risk of thromboembolic disease, but the mechanism leading to hypercoagulability and the population of dogs at risk are unknown.Objectives: To characterize thromboelastography (TEG) and its association with serum albumin (SALB), UPC, and antithrombin activity in dogs with PLN.Animals: Twenty-eight client-owned dogs with PLN (urine protein:creatinine ratio [UPC] > 2.0) and 8 control dogs were prospectively enrolled in this observational study.Methods: TEG parameters, antithrombin activity, serum biochemical profiles, and UPC were measured. TEG analyses were run in duplicate with kaolin activation; reaction time (R), clot formation time (K), a-angle (a), maximal amplitude (MA), and global clot strength (G) were analyzed.Results: Dogs with PLN had lower K (P = .004), and higher a (P = .001), MA (P < .001), and G (P < .001) values than controls. No significant correlation between TEG parameters and UPC, SALB, or antithrombin was noted. Twelve PLN dogs (42.8%) were azotemic and 19 (67.8%) were hypoalbuminemic (SALB < 3.0 g/dL); 11 had SALB < 2.5 g/dL.Conclusions and Clinical Importance: These results indicate that dogs with PLN have TEG values that demonstrate hypercoagulability compared with a control population but that antithrombin, SALB, or UPC cannot be used in isolation to predict this result. A comprehensive evaluation of the coagulation system in individual patients may be necessary to predict the point at which anti-thrombotic therapy is indicated.
OBJECTIVES Recent evidence suggests higher prevalence of autism spectrum disorder (ASD) in NICU graduates. This aim of this study was to identify retrospectively early behaviors found more frequently in NICU infants who went on to develop ASD. METHODS Twenty-eight NICU graduates who later received a diagnosis of ASD were compared with 2169 other NICU graduates recruited from 1994 to 2005. They differed in gender, gestational age, and birth cohort. These characteristics were used to draw a matched control sample (n = 112) to determine which, if any, early behaviors discriminated subsequent ASD diagnosis. Behavioral testing at targeted ages (adjusted for gestation) included the Rapid Neonatal Neurobehavioral Assessment (hospital discharge, 1 month), Arousal-Modulated Attention (hospital discharge, 1 and 4 months), and Bayley Scales of Infant Development (multiple times, 4–25 months). RESULTS At 1 month, children with ASD but not control children had persistent neurobehavioral abnormalities and higher incidences of asymmetric visual tracking and arm tone deficits. At 4 months, children with ASD had continued visual preference for higher amounts of stimulation than did control children, behaving more like newborns. Unlike control children, children with ASD had declining mental and motor performance by 7 to 10 months, resembling infants with severe central nervous system involvement. CONCLUSIONS Differences in specific behavior domains between NICU graduates who later receive a diagnosis of ASD and matched NICU control children may be identified in early infancy. Studies with this cohort may provide insights to help understand and detect early disabilities, including ASD.
Objective(s): To define the evolving role of integrative surgical management including transplantation for patients gut failure (GF). Methods: A total of 500 patients with total parenteral nutrition-dependent catastrophic and chronic GF were referred for surgical intervention particularly transplantation and comprised the study population. With a mean age of 45 ± 17 years, 477 (95%) were adults and 23 (5%) were children. Management strategy was guided by clinical status, splanchnic organ functions, anatomy of residual gut, and cause of GF. Surgery was performed in 462 (92%) patients and 38 (8%) continued medical treatment. Definitive autologous gut reconstruction (AGR) was achievable in 378 (82%), primary transplant in 42 (9%), and AGR followed by transplant in 42 (9%). The 84 transplant recipients received 94 allografts; 67 (71%) liver-free and 27 (29%) liver-contained. The 420 AGR patients received a total of 790 reconstructive and remodeling procedures including primary reconstruction, interposition alimentary-conduits, intestinal/colonic lengthening, and reductive/decompressive surgery. Glucagon-like peptide-2 was used in 17 patients. Results: Overall patient survival was 86% at 1-year and 68% at 5-years with restored nutritional autonomy (RNA) in 63% and 78%, respectively. Surgery achieved a 5-year survival of 70% with 82% RNA. AGR achieved better long-term survival and transplantation better (P = 0.03) re-established nutritional autonomy. Both AGR and transplant were cost effective and quality of life better improved after AGR. A model to predict RNA after AGR was developed computing anatomy of reconstructed gut, total parenteral nutrition requirements, cause of GF, and serum bilirubin. Conclusions: Surgical integration is an effective management strategy for GF. Further progress is foreseen with the herein-described novel techniques and established RNA predictive model.
Lay Abstract A stronger preference for high rates of stimulation when tested after feeding at four months of age has been reported in Neonatal Intensive Care Unit (NICU) graduates who later were diagnosed with autism relative to those who were not. This visual preference is typical of newborns, is likely mediated by arousal systems in the brainstem, and should no longer be present by four months. The fact that it was so persistent in babies who later developed autism suggested they may have had atypical brainstem development or functioning. There exists a group of newborns who initially fail Auditory Brainstem Response screens (ABRs; a measure of the integrity of their brainstem auditory pathways) but eventually recover by hospital discharge suggesting they have atypical brainstem development. We therefore examined the extent to which this problem with ABR functioning along with four-month-olds’ preference for high rates of stimulation predicts the later occurrence of autism in toddlers and preschoolers. We found that preference for higher rates of stimulation at four months was highly associated with later measures of autism severity and with language development problems but only in those who had initially abnormal ABRs. It was concluded that the joint occurrence of initially abnormal neonatal ABRs and preference for more stimulation at four months, both indices of early brainstem dysfunction, may be a marker for the development of autism. Scientific Abstract The authors evaluated the contribution of initially abnormal neonatal Auditory Brainstem Responses (ABRs) and four month Arousal Modulated Attention visual preference to later Autism Spectrum Disorder (ASD) behaviors in Neonatal Intensive Care Unit (NICU) graduates. A longitudinal study design was used to compare NICU graduates with normal ABRs (n=28) to those with initially abnormal ABRs (n=46) that later resolved. At four months post-term-age, visual preference (measured after feeding) for random check patterns flashing at 1, 3, or 8 Hz, and gestational age (GA) served as additional predictors. Outcome measures were PDD Behavior Inventory (PDDBI) scores at 3.4 (SD=1.2) years, and DQs obtained around the same age with the Griffiths Mental Development Scales (GMDS). Preferences for higher rates of stimulation at four months were highly correlated with PDDBI scores (all p values <.01), and the GMDS Hearing and Speech DQ but only in those with initially abnormal ABRs. Effects were strongest for a PDDBI social competence measure most associated with a diagnosis of autism. For those with abnormal ABRs, increases in preference for higher rates of stimulation as infants were linked to non-linear increases in severity of ASD at three years and to an ASD diagnosis. Abnormal ABRs were associated with later reports of repetitive and ritualistic behaviors irrespective of four month preference for stimulation. The joint occurrence of initially abnormal neonatal ABRs and preference for more stimulation at four months, both indices of early brainstem dysfunction, ma...
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