Developing a Business Plan for Sustaining School Mental Health Services: Three Success Storiess

Imagine an America where children arrive at their school desks, ready to learn and succeed. They have coping skills to address their everyday worries, concerns and stressors, as well as the more difficult challenges life may present. They have social skills to establish positive relationships with their peers, teachers and parents. They make healthy choices that allow them to focus on their education and prepare for future success. And if a problem arises, they have access to early intervention and treatment. Now, imagine having sustainable funding to make all of this a reality. Currently, however, barriers, particularly financing issues, restrict the expansion of existing programs and limit the growth of new ones that offer mental health and treatment services to students in a school setting. To shed light on successful models for sustaining school mental health services, the Center for Health and Health Care in Schools at George Washington University looked at three school mental health programs – in Pennsylvania, Washington, DC and Minnesota – that have crafted financial policies and processes that support their work. Their strategies include putting systems in place for billing Medicaid and other third-party payers and supplementing these patient-care revenues with public and private grant dollars and in-kind contributions. In short, they have developed and executed business plans that ensure longterm availability of services.] The hope is that by highlighting these three programs and sharing their business plans, we will shed light on some best practices that should be considered in searching for strategies to sustain school mental health services. Support for this publication was provided by a grant from the Robert Wood Johnson Foundation

Improving Access to Children\u27s Mental Health Care: Lessons from a Study of Eleven States

Implementation of the Patient Protection and Affordable Care Act (ACA) is well underway, creating long-overdue opportunities for growing the capacity of child and adolescent mental health systems and meeting children’s pressing needs. The good news is that as of January 1, 2014, coverage of mental health conditions and substance use disorders will be required as part of the broad Essential Benefits package of services under the ACA. While states will determine specific benefits, it is widely accepted that mental health and substance abuse coverage will substantially increase, though the details remain to be determined.1 Additionally, as a result of this new law, funding for prevention, early intervention, and treatment services and programs will likely expand. A challenge to capitalizing on the ACA opportunity, however, is the underdeveloped state of children’s mental health services across the United States. Unlike children’s physical health services, for which there is a robust private and publicly funded functioning system, management and delivery of mental health services are much less well developed or coherent. From significant disconnects among the multiple institutions that serve children and their families to chronic financial instability, the children’s mental health system is fragile and at-risk. Realizing the promise of the ACA for children and adolescents will require acknowledging systemic barriers that often lead to significant disparities and gaps in care. The following research, conducted by the George Washington University Center for Health and Health Care in Schools (CHHCS), identifies the systemic challenges to ensuring children’s access to mental health care common among many states and points to encouraging examples of success. The bright spots can serve as a guide for those responsible for implementing the ACA or developing other policies that strengthen children’s mental health. Support for this publication was provided by a grant from the Robert Wood Johnson Foundation

Anticholinergic Exposure During Rehabilitation: Cognitive and Physical Function Outcomes in Patients with Delirium Superimposed on Dementia

OBJECTIVES: We examined the association between anticholinergic medication exposure and subsequent cognitive and physical function in patients with delirium superimposed on dementia during rehabilitation. We also examined length of stay and discharge disposition by anticholinergic medication exposure. DESIGN: In this secondary analysis we used control group data from an ongoing randomized clinical trial. SETTING/PARTICIPANTS: Participants with delirium and dementia were enrolled at admission to post-acute care. These 99 participants had a mean age of 86.11 (±6.83) years; 67.6% were women; 98% were Caucasian; and 33% were positive for at least one APOE e4 allele. MEASURES: We obtained daily measures of cognitive and physical function using: Digit Span; memory, orientation and attention items from the Montreal Cognitive Assessment; CLOX; the Confusion Assessment Method; and the Barthel Index. Anticholinergic medication exposure was measured weekly using the Anticholinergic Cognitive Burden Scale. RESULTS: Using multilevel models for time we found that greater use of clinically relevant anticholinergic medications in the previous week reduced cognitive and physical function, as measured by Digit Span Backwards and the Barthel index, in the current week. There was no effect of anticholinergic medication use on delirium severity, and APOE status did not moderate any outcomes. Greater use of clinically relevant anticholinergic medications was related to longer length of stay but not discharge disposition. CONCLUSIONS: For vulnerable older adults, anticholinergic exposure represents a potentially modifiable risk factor for poor attention, working memory, physical function, and greater length of stay during rehabilitation

Evolution of a Bitter Taste Receptor Gene Cluster in a New World Sparrow

Bitter taste perception likely evolved as a protective mechanism against the ingestion of harmful compounds in food. The evolution of the taste receptor type 2 (TAS2R) gene family, which encodes the chemoreceptors that are directly responsible for the detection of bitter compounds, has therefore been of considerable interest. Though TAS2R repertoires have been characterized for a number of species, to date the complement of TAS2Rs from just one bird, the chicken, which had a notably small number of TAS2Rs, has been established. Here, we used targeted mapping and genomic sequencing in the white-throated sparrow (Zonotrichia albicollis) and sample sequencing in other closely related birds to reconstruct the history of a TAS2R gene cluster physically linked to the break points of an evolutionary chromosomal rearrangement. In the white-throated sparrow, this TAS2R cluster encodes up to 18 functional bitter taste receptors and likely underwent a large expansion that predates and/or coincides with the radiation of the Emberizinae subfamily into the New World. In addition to signatures of gene birth-and-death evolution within this cluster, estimates of Ka/Ks for the songbird TAS2Rs were similar to those previously observed in mammals, including humans. Finally, comparison of the complete genomic sequence of the cluster from two common haplotypes in the white-throated sparrow revealed a number of nonsynonymous variants and differences in functional gene content within this species. These results suggest that interspecies and intraspecies genetic variability does exist in avian TAS2Rs and that these differences could contribute to variation in bitter taste perception in birds

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