Project description:ObjectiveDimensional approaches are gaining scientific traction. However, their potential for elucidating developmental aspects of psychopathology has not been fully realized. The goal of this article is to apply a multidimensional, developmental framework to model the normal-abnormal spectrum of preschool disruptive behavior. The Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB), a novel measure, was used to model dimensional severity across developmental parameters theorized to distinguish the normative misbehavior of early childhood from clinically salient disruptive behavior. The 4 MAP-DB dimensions are Temper Loss, Noncompliance, Aggression, and Low Concern for Others.MethodParents of a diverse sample of 1,488 preschoolers completed the MAP-DB. Multidimensional item response theory (IRT) was used for dimensional modeling.ResultsThe 4-dimensional, developmentally informed model demonstrated excellent fit. Its factor loadings did not differ across demographic subgroups. All dimensions provided good coverage of the abnormal end of the severity continuum, but only Temper Loss and Noncompliance provided good coverage of milder, normatively occurring behaviors. The developmental expectability and quality of behaviors distinguished normative from atypical behaviors. The point at which frequency of behaviors was atypical varied based on dimensional location for Temper Loss, Noncompliance, and Aggression.ConclusionThe MAP-DB provides an innovative method for operationalizing developmentally specified, dimensional phenotypes in early childhood. Establishing the validity of these dimensional phenotypes in relation to clinical outcomes, neurocognitive substrates, and etiologic pathways will be a crucial test of their clinical utility.
Project description:ObjectiveDisruptive mood dysregulation disorder (DMDD) in DSM, characterized by severe, chronic irritability, currently excludes children <6 years of age. However, capitalizing on a burgeoning developmental science base to differentiate clinically salient irritability in young children may enable earlier identification. The objective of this study was to advance an empirically derived framework for early childhood DMDD (EC-DMDD) by modeling and validating DMDD patterns in early childhood and generating clinically informative, optimized behaviors with thresholds.MethodData (N = 425) were from 3 longitudinal assessments of the MAPS Study, spanning preschool (means = 4.7 and 5.5 years) to early school age (mean = 6.8 years). The Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB) Temper Loss scale captured irritability, the Family Life Impairment Scale (FLIS) assessed cross-domain impairment at the preschool time points and the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) was used to assess clinical status at early school age. Latent transition analyses differentiated children with EC-DMDD from children with low, transient, or nonimpairing irritability.ResultsDevelopmental patterning of irritability proved important for normal:abnormal differentiation. Of children, 27% had initially high irritability, but only two-thirds of these were persistently highly irritable. Thus, "false positives" based on a single screen would be substantial. Yet, "false negatives" are low, as <1% of children with baseline low irritability demonstrated later high irritability. Based on the sequential preschool-age time points, 6.7% of children were identified with EC-DMDD, characterized by persistent irritability with pervasive impairment, similar to prevalence at older ages. Specific behaviors included low frustration tolerance; dysregulated, developmentally unexpectable tantrums; and sustained irritable mood, all of which sensitively (0.85-0.96) and specifically (0.80-0.91) identified EC-DMDD. EC-DMDD predicted irritability-related syndromes (DMDD, oppositional defiant disorder) at early school age better than downward extension of DSM DMDD criteria to preschool age.ConclusionThese findings provide empirical thresholds for preschool-age clinical identification of DMDD patterns. The results lay the foundation for validation of DMDD in early childhood and inform revision of DSM criteria.
Project description:People with schizophrenia are enriched for rare coding variants in genes associated with neurodevelopmental disorders, particularly autism spectrum disorders and intellectual disability. However, it is unclear if the same changes to gene function that increase risk to neurodevelopmental disorders also do so for schizophrenia. Using data from 3444 schizophrenia trios and 37,488 neurodevelopmental disorder trios, we show that within shared risk genes, de novo variants in schizophrenia and neurodevelopmental disorders are generally of the same functional category, and that specific de novo variants observed in neurodevelopmental disorders are enriched in schizophrenia (P = 5.0 × 10-6). The latter includes variants known to be pathogenic for syndromic disorders, suggesting that schizophrenia be included as a characteristic of those syndromes. Our findings imply that, in part, neurodevelopmental disorders and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology, and support the hypothesis that at least some forms of schizophrenia lie on a continuum of neurodevelopmental disorders.
Project description:PurposeIt is well-established that victims and offenders are often the same people, a phenomenon known as the victim-offender overlap, but the developmental nature of this overlap remains uncertain. In this study, we drew from a developmental theoretical framework to test effects of genetics, individual characteristics, and routine-activity-based risks. Drawing from developmental literature, we additionally tested the effect of an accumulation of adverse childhood experiences (ACEs).MethodsData came from the Environmental Risk (E-Risk) Study, a representative UK birth cohort of 2232 twins born in 1994-1995 and followed to age 18 (with 93% retention). Crime victimization and offending were assessed through self-reports at age 18 (but findings replicated using crime records). We used the classical twin study method to decompose variance in the victim-offender overlap into genetic and environmental components. We used logistic regression to test the effects of childhood risk factors.ResultsIn contrast to past twin studies, we found that environment (as well as genes) contributed to the victim-offender overlap. Our logistic regression results showed that childhood low self-control and childhood antisocial behavior nearly doubled the odds of becoming a victim-offender, compared to a victim-only or an offender-only. Each additional ACE increased the odds of becoming a victim-offender, compared to a victim-only or an offender-only, by approximately 12%, pointing to the importance of cumulative childhood adversity.ConclusionsThis study showed that the victim-offender overlap is, at least partially, developmental in nature and predictable from personal childhood characteristics and an accumulation of many adverse childhood experiences.
Project description:BackgroundSagittal malalignment is associated with poor quality of life. Correction of lumbar lordosis through anterior column release (ACR) has been shown to improve overall sagittal alignment, however typically in combination with long posterior constructs and associated morbidity. The technical feasibility and radiographic outcomes of short-segment anterior or lateral minimally invasive surgery (MIS) ACR techniques in moderate to severe lumbar sagittal deformity were evaluated.MethodsConsecutive patients treated with short-segment MIS ACR techniques for moderate to severe lumbar sagittal deformity correction were retrospectively analyzed from a prospectively collected database. Clinical outcomes included perioperative measures of invasiveness, including operative time, blood loss, complications, and average length of stay. Radiographic outcomes included measurement of preoperative, immediate postoperative, and long-term follow-up radiographic parameters including coronal Cobb angle, lumbar lordosis (LL), pelvic incidence (PI), PI-LL mismatch, pelvic tilt (PT), T1 pelvic angle (TPA), T1 spino-pelvic inclination (T1SPI), proximal junctional angle (PJA), and sagittal vertical axis (SVA).ResultsThe cohort included 34 patients (mean age 63) who were treated at an average 2.5 interbody levels (range 1-4) through a lateral or anterior approach (LLIF or ALIF). Of 89 total interbody levels treated, 63 (71%) were ACR levels. Posterior fixation was across an average of 3.2 levels (range 1-5). Mean total operative time and blood loss were 362 minutes and 621 mL. Surgical complications occurred in 2 (5.9%). Average hospital stay was 5.5 days (including staging). At last follow-up (average 25.4 months; range 0.5-7 years), all patients (100%) demonstrated successful achievement of one or more alignment goal, with significant improvements in coronal Cobb, LL, PI-LL mismatch, PT, and TPA. No patient was revised for PJK.ConclusionsThese data show that short-segment MIS ACR correction of moderate to severe lumbar sagittal deformity is feasible and effective at achieving overall alignment goals with low procedural morbidity and risk of proximal junctional issues.
Project description:The present study aimed to evaluate the expression of neuro-oncological ventral antigen 1 (Nova1) in cerebral ischemia/reperfusion (I/R) insults by immunohistochemistry. The focal cerebral I/R model was induced by right middle cerebral artery occlusion (MCAO) for 120 min followed by 1 day, 7 days, and 14 days of reperfusion in Sprague-Dawley (SD) rats. The results showed that Nova1 was expressed in nearly the whole brain, although with higher density in hippocampus, hypothalamus, cingulate cortex, and medial habenular nucleus. The immunoreactivity of Nova1 neurons was increased dramatically, especially on both sides of the hippocampal CA(1) region, after 1 day of reperfusion. A strong response occurred at the ipsilateral CA(1) region between 1 day and 7 days of reperfusion. Likewise, strong compensatory responses of Nova1 expression were observed on the contralateral side of the striate cortex, dentate gyrus, and hypothalamus. Interestingly, more Nova1 neurons were observed to translocate to the dendrites and growth cones of the axons in the hypothalamus on the ischemic side after 7 days of reperfusion. In conclusion, our data suggest that Nova1 might mediate neuronal responsiveness, and its expression might positively correlate with neural repair after I/R insults in the rat brain.
Project description:Nanopore sequencing was recently made available to users in the form of the Oxford Nanopore MinION. Released to users through an early access programme, the MinION is made unique by its tiny form factor and ability to generate very long sequences from single DNA molecules. The platform is undergoing rapid evolution with three distinct nanopore types and five updates to library preparation chemistry in the last 18 months. To keep pace with the rapid evolution of this sequencing platform, and to provide a space where new analysis methods can be openly discussed, we present a new F1000Research channel devoted to updates to and analysis of nanopore sequence data.
Project description:Younger children have more difficulty in sharing attention between two concurrent tasks than do older participants, but in addition to this developmental change, we documented changes in the nature of attention sharing. We studied children 6-8 and 10-14 years old and college students (in all, 104 women and 76 men; 3% Hispanic, 3% Black or African American, 3% Asian, 7% multiracial, and 84% White). On each dual-task trial, the participant received an array of colored squares to be retained for a subsequent probe recognition test and then an easy or more difficult signal requiring a quick response (a speeded task, clicking a key on the same side of the screen as the signal or the opposite side). Finally, each trial ended with the presentation of the array item recognition probe and the participant's response to it. In our youngest age group (6-8 years), array memory was often displaced by the speeded task performed under load, especially when it was the opposite-side task, but speeded-task accuracies were unaffected by the presence of an array memory load. In contrast, in older participants (10-14 years and college students), the memory load was maintained better, with some cost to the speeded task. With maturity, participants were better able to adopt a proactive stance in which not only present processing demands but also upcoming demands were taken into account, allowing them to balance the demands of the two tasks. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Project description:Even if an animal matches its surroundings perfectly in colour and texture, any mismatch between the spatial phase of its pattern and that of the background, or shadow created by its three-dimensional relief, is potentially revealing. Nevertheless, for camouflage to be fully broken, the shape must be recognizable. Disruptive coloration acts against object recognition by the use of high-contrast internal colour boundaries to break up shape and form. As well as the general outline, characteristic features such as eyes and limbs must also be concealed; this can be achieved by having the colour patterns on different, but adjacent, body parts aligned to match each other (i.e. in phase). Such 'coincident disruptive coloration' ensures that there is no phase disjunction where body parts meet, and causes different sections of the body to blend perceptually. We tested this theory using field experiments with predation by wild birds on artificial moth-like targets, whose wings and (edible pastry) bodies had colour patterns that were variously coincident or not. We also carried out an experiment with humans searching for analogous targets on a computer screen. Both experiments show that coincident disruptive coloration is an effective mechanism for concealing an otherwise revealing body form.
Project description:BACKGROUND: Chromatin remodeling is crucial for proper programing of developmental gene expression. Recent work provides a dynamic view of post-translational histone modifications during differentiation; however there is little insight on the evolution of combinatorial genome-wide patterns of chromatin marks, excluding an essential aspect of developmental gene regulation. RESULTS: We report here a 15-chromatin state Hidden Markov Model which describes changes in chromatin signatures in relation to transcription profiles during differentiation of human pre-adipocytes into adipocytes. We identify nineteen modules of gene expression reflecting multiple waves of transcriptional up- and down-regulation which characterize adipogenic differentiation. From our model, we developed chromatin state matrices fitting each of these transcription modules to show how the complexity and dynamic nature of chromatin signatures relate to expression patterns. Spatial relationships between chromatin states underlie a high-order chromatin organization in differentiating adipocytes. We show the importance of gene expression level in generating diversity in chromatin signatures, and show that the hyper-dynamic nature of H3K4me2/H3K27me3-marked 'bivalent' promoter states underlies many of the gene expression patterns associated with adipogenic differentiation. CONCLUSIONS: Our results reveal the highly dynamic nature of bivalent promoter states within the adipogenic lineage. The data constitute a valuable resource enabling the assessment of possibilities to alter the adipogenic program.