Intensifying Impact: State Budget Cuts Deepen Pain for Ohio Communities

Policy Matters Ohio looked at the size and scope of cuts in each county and in many municipalities. We talked with city and county administrators, local elected officials and residents. On our website, there is a link for each Ohio county that describes the loss in state funding and the impact on cities, towns and services within that county. Because local newspaper clips and quotes from local officials are used, this brief is an oral history as well as a presentation of charts and graphs. The insights of those interviewed add clarity and depth to a description of hard times

Conversations With Health Care Providers and Parents Before Autism Diagnosis: A Qualitative Study

Introduction The purpose of this study was to explore communication with health care providers from the perceptions of parents before their child\u27s diagnosis of autism spectrum disorder and provide some examples of how communication may contribute to the autism diagnosis. Method This study used a qualitative descriptive design with multiple individual structured in-person interviews. Results Three themes captured parents’ (n = 8) descriptions of the phases of communication during their children\u27s diagnoses including, (1) anguished questioning, (2) urgently seeking help, and (3) expecting a diagnosis. In addition, three themes characterized the communication style that parents needed, although not always received, in each of the periods of diagnosis including (1) compassionate curiosity, (2) acknowledgment and affirmation, and (3) engagement with parents. Discussion Results point to opportunities for pediatric providers to use a more empathic and engaging communication style during the diagnostic process with better identification of education and support needed by parents and families

Dependence of gene-by-environment interactions (GxE) on scaling:Comparing the use of sum scores, transformed sum scores and IRT scores for the phenotype in tests of GxE interaction

Estimates of gene–environment interactions (GxE) in behavior genetic models depend on how a phenotype is scaled. Inappropriately scaled phenotypes result in biased estimates of GxE and can sometimes even suggest GxE in the direction opposite to its true direction. Previously proposed solutions are mathematically complex, computationally demanding and may prove impractical for the substantive researcher. We, therefore, evaluated two simple-to-use alternatives: (1) straightforward non-linear transformation of sum scores and (2) factor scores from an appropriate item response theory (IRT) model. Within Purcell’s (2002) GxM framework, both alternatives provided less biased parameter estimates, and improved false and true positive rates than using a raw sum score. These approaches are, therefore, recommended over using raw sum scores in tests of GxE. Circumstances under which IRT factor scores versus transformed sum scores should be preferred are discussed

Social Difficulties in Youth with Autism With and Without Anxiety and ADHD Symptoms

Social difficulties inherent to autism spectrum disorder are often linked with co‐occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co‐occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co‐occurring symptom subgroups (Anxiety, ADHD, Both, Neither)—namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Lay Summary Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested

Social Difficulties in Youth with Autism With and Without Anxiety and ADHD Symptoms

Social difficulties inherent to autism spectrum disorder are often linked with co‐occurring symptoms of anxiety and attention deficit hyperactivity disorder (ADHD). The present study sought to examine the relation between such co‐occurring symptoms and social challenges. Parents of adolescents with autism (N = 113) reported upon social challenges via the social responsiveness scale (SRS) and anxiety and ADHD symptomatology via the Child Behavior Checklist. Results revealed differences in SRS scores across co‐occurring symptom subgroups (Anxiety, ADHD, Both, Neither)—namely, adolescents with autism and anxiety as well as those with autism, anxiety, and ADHD showed greater scores on the SRS than the other groups. Implications for research and clinical practice are discussed and recommendations are offered. Lay Summary Anxiety and attention deficit hyperactivity disorder (ADHD) symptoms are related to greater social challenges for adolescents with autism spectrum disorder. The present study found that autism with anxiety and autism with anxiety and ADHD, was related to greater social difficulties than autism alone. Findings provide further support for the intertwined nature of anxiety and ADHD symptoms in autism. What this may mean for research and clinical practice is considered and recommendations are suggested

Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues.

BACKGROUND: Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on the parent of origin and is typically regulated by differential DNA methylation inherited from gametes. Imprinting is pervasive in murine extra-embryonic lineages, and uniquely, the imprinting of several genes has been found to be conferred non-canonically through maternally inherited repressive histone modification H3K27me3. However, the underlying regulatory mechanisms of non-canonical imprinting in post-implantation development remain unexplored. RESULTS: We identify imprinted regions in post-implantation epiblast and extra-embryonic ectoderm (ExE) by assaying allelic histone modifications (H3K4me3, H3K36me3, H3K27me3), gene expression, and DNA methylation in reciprocal C57BL/6 and CAST hybrid embryos. We distinguish loci with DNA methylation-dependent (canonical) and independent (non-canonical) imprinting by assaying hybrid embryos with ablated maternally inherited DNA methylation. We find that non-canonical imprints are localized to endogenous retrovirus-K (ERVK) long terminal repeats (LTRs), which act as imprinted promoters specifically in extra-embryonic lineages. Transcribed ERVK LTRs are CpG-rich and located in close proximity to gene promoters, and imprinting status is determined by their epigenetic patterning in the oocyte. Finally, we show that oocyte-derived H3K27me3 associated with non-canonical imprints is not maintained beyond pre-implantation development at these elements and is replaced by secondary imprinted DNA methylation on the maternal allele in post-implantation ExE, while being completely silenced by bi-allelic DNA methylation in the epiblast. CONCLUSIONS: This study reveals distinct epigenetic mechanisms regulating non-canonical imprinted gene expression between embryonic and extra-embryonic development and identifies an integral role for ERVK LTR repetitive elements

CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials

Improved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of knowledge about patients’ lifestyle behaviors that may affect cancer’s progression and recurrence, and limited ability to compile and interpret the wide range of variables that must be considered in the cancer treatment. This lack of data integration limits the potential for patients and clinicians to engage in fully informed decision-making regarding cancer prevention, treatment, and survivorship care, and the translation of research results into mainstream medical care. Particularly important, as noted in a 2009 report on CER to the President and Congress, the limited focus on health behavior-change interventions was a major hindrance in this research landscape (DHHS 2009). This paper describes an initiative to improve CER for cancer by addressing several of these limitations. The Cyberinfrastructure for Comparative Effectiveness Research (CYCORE) project, informed by the National Science Foundation’s 2007 report “Cyberinfrastructure Vision for 21st Century Discovery” has, as its central aim, the creation of a prototype for a user-friendly, open-source cyberinfrastructure (CI) that supports acquisition, storage, visualization, analysis, and sharing of data important for cancer-related CER. Although still under development, the process of gathering requirements for CYCORE has revealed new ways in which CI design can significantly improve the collection and analysis of a wide variety of data types, and has resulted in new and important partnerships among cancer researchers engaged in advancing health-related CI

Multi-omics profiling of mouse gastrulation at single-cell resolution.

Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes1-5. Global epigenetic reprogramming accompanies these changes6-8, but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements at enhancer marks, driven by ten-eleven translocation (TET)-mediated demethylation and a concomitant increase of accessibility. By contrast, the methylation and accessibility landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or remodelled before cell-fate decisions, providing the molecular framework for a hierarchical emergence of the primary germ layers.CRUK, Wellcome Trust, MRC, BBSRC, EMBL, E