Child Neurodevelopmental and Behavioural Problems are Intercorrelated and Dimensionally Distributed in the General Population

The Autism – Tics, AD/HD, and other Comorbidities inventory (A-TAC) is a comprehensive interview for evaluating problems related to autism spectrum disorders (ASD), tic disorders, attention-deficit/hyperactivity disorder (AD/HD), and common comorbid conditions in children and adolescents. A-TAC telephone interviews were administered to parents of 2,957 children aged nine- or twelve-years, representing one in each twin pair included in the populationbased Child and Adolescent Twin Study in Sweden (CATSS). A total of 16.4% were screen-positive for one or several of the targeted disorder, 1.3% for ASD and 5.6% for AD/HD. All types of problems were more common among boys, with the exception of those related to “eating habits”. They were all dimensionally/continuously distributed, highly inter-correlated, and overlapped across types. They aggregated in three basic factors corresponding to externalizing/disruptiveness, socio-communicative problems, and compulsiveness. Population-based data on problems in children thus challenge current categorical diagnostic definitions, calling for dimensional and complementary models of problem descriptions

Predictive properties of the A-TAC inventory when screening for childhood-onset neurodevelopmental problems in a population-based sample

Background: Identifying children with childhood-onset neurodevelopmental problems (NDPs, defined here as autism spectrum disorders [ASDs], attention-deficit/hyperactivity disorder [AD/HD], tic disorders [TDs], learning disorders [LDs] and development coordination disorder), using easily administered screening instruments, is a prerequisite for epidemiological research. Such instruments are also clinically useful to prioritize children for comprehensive assessments, to screen risk groups, and to follow controls. Autism-Tics, ADHD, and other Co-morbidities inventory (A-TAC) was developed to meet these requirements; here the A-TAC's prospective and psychometric properties are examined, when used in a population-based, epidemiological setting. Methods: Since 2004, parents of all Swedish twins have been asked to take part in an ongoing, nation-wide twin study (The Child and Adolescent Twin Study in Sweden). The study includes the A-TAC, carried out as a telephone interview with parents of twins aged 9 or 12. In the present study, screen-positive twins from three birth year cohorts (1993-1995) were invited to a comprehensive clinical follow-up (blinded for previous screening results) together with their co-twins and randomly selected, healthy controls at age 15 (Total N = 452). Results: Sensitivity and specificity of A-TAC scores for predicting later clinical diagnoses were good to excellent overall, with values of the area under the receiver operating characteristics curves ranging from 0.77 (AD/HD) to 0.91 (ASDs). Among children who were screen-positive for an ASD, 48% received a clinical diagnosis of ASDs. For AD/HD, the corresponding figure was also 48%, for LDs 16%, and for TDs 60%. Between 4% and 35% of screen-positive children did not receive any diagnosis at the clinical follow-up three years later. Among screen-negative controls, prevalence of ASDs, AD/HD, LDs, and TDs was 0%, 7%, 4%, and 2%, respectively. Conclusions: The A-TAC appeared to be a valid instrument to assess NDPs in this population-based, longitudinal study. It has good-to-excellent psychometric properties, with an excellent ability to distinguish NDPs (mainly ASDs) from non-NDPs at least three years after the screening evaluations, although specific diagnoses did not correspond closely to actual clinical diagnoses

A supernova constraint on bulk majorons

In models with large extra dimensions all gauge singlet fields can in principle propagate in the extra dimensional space. We have investigated possible constraints on majoron models of neutrino masses in which the majorons propagate in extra dimensions. It is found that astrophysical constraints from supernovae are many orders of magnitude stronger than previous accelerator bounds. Our findings suggest that unnatural types of the "see-saw" mechanism for neutrino masses are unlikely to occur in nature, even in the presence of extra dimensions.Comment: Minor changes, matches the version to appear in PR

Nanoscale structural and chemical analysis of F-implanted enhancement-mode InAlN/GaN heterostructure field effect transistors

We investigate the impact of a fluorine plasma treatment used to obtain enhancement-mode operation on the structure and chemistry at the nanometer and atomic scales of an InAlN/GaN field effect transistor. The fluorine plasma treatment is successful in that enhancement mode operation is achieved with a +2.8 V threshold voltage. However, the InAlN barrier layers are observed to have been damaged by the fluorine treatment with their thickness being reduced by up to 50%. The treatment also led to oxygen incorporation within the InAlN barrier layers. Furthermore, even in the as-grown structure, Ga was unintentionally incorporated during the growth of the InAlN barrier. The impact of both the reduced barrier thickness and the incorporated Ga within the barrier on the transistor properties has been evaluated theoretically and compared to the experimentally determined two-dimensional electron gas density and threshold voltage of the transistor. For devices without fluorine treatment, the two-dimensional electron gas density is better predicted if the quaternary nature of the barrier is taken into account. For the fluorine treated device, not only the changes to the barrier layer thickness and composition, but also the fluorine doping needs to be considered to predict device performance. These studies reveal the factors influencing the performance of these specific transistor structures and highlight the strengths of the applied nanoscale characterisation techniques in revealing information relevant to device performance.</jats:p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment