Dynamics of Race, Culture and Key Indicators of Health in the Nation's 100 Largest Cities and Their Suburbs

Profiles the 2000 status of, and changes since 1990, in rates of health and health-related measures to identify patterns in race/ethnicity, foreign-born status, language use, poverty, income, low birth weight, teen births, prenatal care, and tuberculosis

Implications of the Patient Protection and Affordable Care Act for Health Inequities

To assess implications , opportunities, and challenges of health care reform for improving the health and health care of racially and ethnically diverse populations

PATIENT PROTECTION AND AFFORDABLE CARE ACT OF 2010: Advancing Health Equity for Racially and Ethnically Diverse Populations

Racial/ethnic disparities in health and health care in the United States are persistent and well documented. Communities of color fare far worse than their white counterparts across a range of health indicators: life expectancy, infant mortality, prevalence of chronic diseases, self-rated health status, insurance coverage, and many others.1 As the nation’s population continues to become increasingly diverse—people of color are projected to comprise 54% of the U.S. population by 2050 and more than half of U.S. children by 20232— these disparities are likely to grow if left unaddressed. Recent health care reform legislation, while not a panacea for eliminating health disparities, off ers an important fi rst step and an unprecedented opportunity to improve health equity in the United States. Reforming the nation’s health care system was President Obama’s top domestic priority when he was sworn into offi ce in January 2009. Th e road to reform was complex and unoffi cially started in summer of 2009 when House and Senate committees began to draft legislation. On November 7, 2009, the House of Representatives passed its health care reform proposal, Th e Aff ordable Health Choices Act of 2009 (H.R. 3962). On December 24, 2009, the Senate passed its own proposal for health care reform, Th e Patient Protection and Aff ordable Care Act (H.R. 3590)*, which was a merged version of the Senate Finance Committee’s America’s Health Future Act (S.1796) and the Senate Committee on Health, Education, Labor, and Pensions’ Aff ordable Health Choices Act (S. 1697).† Eff orts to reconcile diff erences between the Senate and House bills were stymied by the death of Senator Edward Kennedy (D-MA), a lifelong proponent of health care reform and critical force in securing a proposal’s passage in the Senate. Faced with limited options and expecting that a compromise bill could not get Senate support, the House passed the Senate’s proposal and Th e Patient Protection and Aff ordable Care Act (ACA) was signed into law by President Obama on March 23, 2010 (Pub. L. No. 111-148).‡ On March 30, 2010, the ACA was amended by Th e Health Care and Education Reconciliation Act of 2010 (H.R. 4872). According to Congressional Budget Offi ce (CBO) estimates, the ACA, as reconciled by H.R. 4872, will reduce the defi cit by $143 billion over the next decade and decrease the number of non-elderly uninsured by 32 million, leaving 23 million uninsured— approximately one-third of whom would be undocumented immigrants.3 Th is report provides a comprehensive review of general and specifi c ACA provisions with the potential to signifi cantly improve health and health care for millions of diverse populations and their communities. Th e narrative that follows identifi es these provisions, discusses why they are important, and considers challenges that may lie ahead in implementing them. We have organized this presentation in three major sections. Th e next section discusses provisions that explicitly address health disparities, such as those concerning data collection by race/ethnicity, workforce diversity, cultural competence, health disparities research, health disparities initiatives in prevention, and health equity in health insurance reform, and discusses their implications for racially and ethnically diverse communities. Section III describes general provisions, including health insurance reforms, access to care, quality improvement, cost containment, public health and social determinants of health, all of which are likely to have major implications for diverse communities. An accompanying appendix identifi es these provisions, provides a timetable and, where identifi ed in the legislation, the federal agencies responsible for implementation, as well as allocations as of June 30, 2010. Section IV discusses issues that will be critical in realizing the full potential of health care reform and highlights questions and directions for the future, particularly in context of important priorities for reducing racial/ethnic health disparities that were left unaddressed

Emergency Department Initiatives to Improve the Public Health *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71985/1/j.1553-2712.1998.tb02827.x.pd

Preparing racially and ethnically diverse communities for public health emergencies

Health Affairs, 26(5): pp. 1269-1279.The tragedy of Hurricane Katrina in New Orleans confirmed that effective implementation of public health preparedness programs and policies will require compliance from all racial and ethnic populations. This study reviews current resources and limitations and suggests future directions for integrating diverse communities into related strategies. It documents research and interventions, including promising models and practices that address preparedness for minorities. However, findings reveal a general lack of focus on diversity and suggest that future preparedness efforts need to fully integrate factors related to race, culture, and language into risk communication, public health training, measurement, coordination, and policy at all levels

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Genome-wide examination of the transcriptional response to ecdysteroids 20-hydroxyecdysone and ponasterone A in Drosophila melanogaster

<p>Abstract</p> <p>Background</p> <p>The 20-hydroxyecdysone (20E) hierarchy of gene activation serves as an attractive model system for studying the mode of steroid hormone regulated gene expression and development. Many structural analogs of 20E exist in nature and among them the plant-derived ponasterone A (PoA) is the most potent. PoA has a higher affinity for the 20E nuclear receptor, composed of the ecysone receptor (EcR) and Ultraspiracle proteins, than 20E and a comparison of the genes regulated by these hormones has not been performed. Furthermore, in <it>Drosophila </it>different cell types elicit different morphological responses to 20E yet the cell type specificity of the 20E transcriptional response has not been examined on a genome-wide scale. We aim to characterize the transcriptional response to 20E and PoA in <it>Drosophila </it>Kc cells and to 20E in salivary glands and provide a robust comparison of genes involved in each response.</p> <p>Results</p> <p>Our genome-wide microarray analysis of Kc167 cells treated with 20E or PoA revealed that far more genes are regulated by PoA than by 20E (256 vs 148 respectively) and that there is very little overlap between the transcriptional responses to each hormone. Interestingly, genes induced by 20E relative to PoA are enriched in functions related to development. We also find that many genes regulated by 20E in Kc167 cells are not regulated by 20E in salivary glands of wandering 3^rdinstar larvae and we show that 20E-induced levels of <it>EcR </it>isoforms <it>EcR-RA, ER-RC</it>, and <it>EcR-RD/E </it>differ between Kc cells and salivary glands suggesting a possible cause for the observed differences in 20E-regulated gene transcription between the two cell types.</p> <p>Conclusions</p> <p>We report significant differences in the transcriptional responses of 20E and PoA, two steroid hormones that differ by only a single hydroxyl group. We also provide evidence that suggests that PoA induced death of non-adapted insects may be related to PoA regulating different set of genes when compared to 20E. In addition, we reveal large differences between Kc cells and salivary glands with regard to their genome-wide transcriptional response to 20E and show that the level of induction of certain EcR isoforms differ between Kc cells and salivary glands. We hypothesize that the differences in the transcriptional response may in part be due to differences in the EcR isoforms present in different cell types.</p

Patient survival and tumor characteristics associated with CHEK2:p.I157T – findings from the Breast Cancer Association Consortium

Abstract Background P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. Methods We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. Results P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly enriched among genes, whose expression differed between p.I157T and non-carrier tumors. Conclusions Our analyses suggest that there are fundamental differences in breast tumors of CHEK2:p.I157T and c.1100delC carriers. The poor prognosis associated with c.1100delC cannot be generalized to other CHEK2 mutations