How changes at the local health department level are associated with improvements in health outcomes at the state level

The empirical evidence for guiding the resourcing of local public health departments (LHDs) and for what these agencies should be funded to do is limited primarily to cross-sectional studies of health department performance and effectiveness. There is relatively little published evidence showing an association between LHD activities or performance and health outcomes, and there is a lack of information from longitudinal studies on LHDs. The purpose of this study was to explore the association between changes in LHD resources and activities, and changes in health outcomes. A retrospective cohort design was used to analyze changes in LHD resources and changes in health outcomes at the state level. The National Association of County and City Health Officials (NACCHO) has collected data on LHD resources, such as expenditures and staffing, through multiple surveys. This study made use of a dataset which linked LHD responses in surveys conducted in 1997 and again in 2005. LHD data were aggregated to the state level, producing usable data for 42 states. Data for health outcomes were available through the America's Health Rankings reports for the same time period. Significant associations were found between overall LHD inputs and changes in state health rankings. In particular, increases in LHD expenditures were significantly associated with decreases in infectious disease morbidity at the state level (p = 0.037), and increases in full-time equivalent staff per capita were significantly associated with decreases in cardiovascular disease mortality (p = 0.014), when controlling for other factors. These results add to the empirical evidence that local public health activity is associated with improved health outcomes. These findings can be used to advocate for LHD support and may have policy implications for developing evidence-based standards for a National Public Health Accreditation Program

The Association of Changes in Local Health Department Resources With Changes in State-Level Health Outcomes

We explored the association between changes in local health department (LHD) resource levels with changes in health outcomes via a retrospective cohort study. We measured changes in expenditures and staffing reported by LHDs on the 1997 and 2005 National Association of County and City Health Officials surveys and assessed changes in state-level health outcomes with the America’s Health Rankings reports for those years. We used pairwise correlation and multivariate regression to analyze the association of changes in LHD resources with changes in health outcomes. Increases in LHD expenditures were significantly associated with decreases in infectious disease morbidity at the state level (P=.037), and increases in staffing were significantly associated with decreases in cardiovascular disease mortality (P=.014), controlling for other factors

Information-Seeking Behaviors and Other Factors Contributing to Successful Implementation of Evidence-Based Practices in Local Health Departments

The objective of this article is to describe factors which contribute to successful translation of science into evidence-based practices and their implementation in public health practice agencies, based on a review of the literature and evidence from a series of case studies. The case studies involved structured interviews with key informants in four health departments and with four corresponding partners from academic institutions. Interviews were recorded and transcribed, coded by two independent, trained coders, using a standard codebook. A thematic analysis of codes was conducted. Coding was entered into Atlas TI software for further analysis

Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14–15 September 2015

This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this ‘may be difficult for cell-based medicinal products’. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates

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

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

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

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation