The Effects of the State of Tennessee Immunization Policy Change of 2011 - 2012 on Vaccination Uptake in East Tennessee

In the United States, funding for the purchase of vaccines depend on annual Congressional allocations. These allocations fluctuate from year to year as Congress responds to changes in national needs for immunizations. The Affordable Care Act requires first dollar coverage of immunizations and other preventive care, allowing a reduction in federal funding for vaccine purchase and a reallocation of funds to other uses such as infrastructure development. In fiscal year 2012, the loss of funds allocated from the American Recovery and Reinvestment Act required action by states to ensure appropriate use of remaining funds. In Tennessee, the response was a policy change that redefined the population who would receive immunizations at health departments

The Effects of the Changes in Section 317 Rules for Administration of Federally Purchased Vaccines

Section 317 of the Public Health Services Act is a federal program that provides funds for the purchase of vaccines. These annual Congressional allocations fluctuate from year to year as Congress responds to changes in national needs for immunizations. The Affordable Care Act requires first dollar coverage of immunizations and other preventive care, allowing a reduction in federal funding for vaccine purchase and a reallocation of funds to other uses such as infrastructure development. In fiscal year 2013, Section 317 rules redefined the population eligible for immunization with Section 317 purchased vaccines. In Tennessee, the response was a policy change that redefined the population who would receive immunizations at health departments

A Case Study of Cross-Jurisdiction Resource Sharing: The Merger of Two Tuberculosis Clinics in East Tennessee.

Cross-jurisdiction resource sharing is considered a possible means to improve efficiency and effectiveness of public health service delivery. A merger of the Tuberculosis (TB) clinics of a rural and a metropolitan jurisdiction in East Tennessee provided an opportunity to study service provision changes in real time. A mixed methods approach was used, including quantitative data on latent TB treatment outcomes and qualitative data from staff interviews, as well as documentation of changes in staffing time in TB services. Results showed a mix of efficiency changes, indicating probable increased pressure on key service providers after the merger, in addition to expected improvements of economies of scale such as a reduction in overall staff time. Mechanisms found beneficial in coping with the merger, such as face-to-face meetings between coworkers and management of the different jurisdictions were identified at interview. The clinic merger was associated with a balance of efficiency changes, problems and advantages, and this balance is likely to change as new working arrangements become more routine

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation

Abstract Background Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. Methods We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. Results We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 × 10−03; FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten “CNV positive” trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. Conclusions Our findings suggest that rare CNVs may contribute to the etiology of OCD.http://deepblue.lib.umich.edu/bitstream/2027.42/134675/1/11689_2016_Article_9170.pd

Is the onset of disabling chronic conditions in later childhood associated with exposure to social disadvantage in earlier childhood? a prospective cohort study using the ONS Longitudinal Study for England and Wales

Background: The aetiology of disabling chronic conditions in childhood in high income countries is not fully understood, particularly the association with socio-economic status (SES). Very few studies have used longitudinal datasets to examine whether exposure to social disadvantage in early childhood increases the risk of developing chronic conditions in later childhood. Here we examine this association, and its temporal ordering, with onset of all-cause disabling chronic later childhood in children reported as free from disability in early childhood. Methods: The study comprised a prospective cohort study, using data from the Office for National Statistics Longitudinal Study (ONSLS) for England and Wales. The study sample included 52,839 children with complete data born between 1981–1991 with no disabling chronic condition/s in 1991. Index cases were children with disability recorded in 2001. Comparison cases were children with no recorded disability in 1991. A socio-economic disadvantage index (SDI) was constructed from data on social class, housing tenure and car/van access. Associations were explored with logistic regression modelling controlling sequentially for potentially confounding factors; age, gender, ethnicity and lone parenthood. Results: By 2001, 2049 (4%) had at least one disability. Socio-economic disadvantage, age, gender and lone parenthood but not ethnicity were significantly associated with onset of disabling chronic conditions. The SDI showed a finely graded association with onset of disabling chronic conditions in the index group (most disadvantaged OR 2·11 [CI 1·76 to 2·53]; disadvantaged in two domains OR 1·45 [CI 1·20 to 1·75]; disadvantaged in one domain OR 1·14 [CI 0·93 to 1·39] that was unaffected by age, gender and ethnicity and slightly attenuated by lone parenthood. Conclusion: To our knowledge, this is the first study to identify socio-economic disadvantage in earlier childhood as a predisposing factor for onset of all-cause disabling chronic conditions in later childhood. Temporal ordering and gradation of the response indicate socio-economic disadvantage may play a causal role. This suggests that targeting preventative efforts to reduce socio-economic disadvantage in early childhood is likely to be an important public health strategy to decease health inequalities in later childhood and early adulthood

Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance

This white paper provides updated International Transporter Consortium (ITC) recommendations on transporters that are important in drug development following the 3rd ITC workshop. New additions include prospective evaluation of organic cation transporter 1 (OCT1) and retrospective evaluation of organic anion transporting polypeptide (OATP)2B1 because of their important roles in drug absorption, disposition, and effects. For the first time, the ITC underscores the importance of transporters involved in drug-induced vitamin deficiency (THTR2) and those involved in the disposition of biomarkers of organ function (OAT2 and bile acid transporters)

Why Should Ecosystem Services Be Governed to Support Poverty Alleviation? Philosophical Perspectives on Positions in the Empirical Literature

In light of trade-offs related to the allocation of ecosystem services we investigate the prevalent norms that are drawn upon to justify why ecosystem governance should prioritise poverty alleviation. We are specifically concerned with poverty alleviation because we consider this an urgent problem of justice. We review empirical literature on social trade-offs in ecosystem services governance in order to identify the prevalent conceptions of justice that inform scholarly assessments of current practice. We find that empirical studies do present specific notions of justice as desirable benchmarks for ecosystem services governance but that they rarely attempt to spell out the precise meaning of these notions or what makes them desirable. For those notions of justice that we identify in this literature - sufficientarianism, egalitarianism and participatory approaches - we draw on philosophical justice literature in order to better articulate the normative arguments that could support them and to be more precise about the kind of actions and expectations that they invoke. Moreover, we point to some striking normative silences in the ecosystem services literature. We conclude that the ecosystem services justice discourse would benefit from more conceptual clarity and a broader examination of different aspects of justice

Research Ethics Recommendations for Whole-Genome Research: Consensus Statement

Interest in whole-genome research has grown substantially over the past few months. This article explores the challenging ethics issues associated with this work

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression