Monitoring Success in Choice Neighborhoods: A Proposed Approach to Performance Measurement

Offers a framework and tools for performance management in the initiative to transform poor neighborhoods into revitalized, sustainable mixed-income communities. Proposes system components, logic model, management reports, and performance indicators

Building Environmentally Sustainable Communities: A Framework for Inclusivity

Reviews literature on past inequitable and unsustainable urban development and visions for linking sustainability, opportunity, and inclusion. Analyzes possible metrics for measuring sustainability and access as well as next steps for policy

Zebulon, Wake County : a community diagnosis including secondary data analysis and qualitative data collection

This document was created to identify and clarify points of interest and concern that are of significance to community members of Zebulon, North Carolina. The document is divided into two main sections. The first is a compilation of secondary data collected for Zebulon, and when possible, for Wake County and the State of North Carolina to use as comparisons. The second section addresses various topics brought to light during interviews with both community members and service providers within the Town. In essence, this document examines the congruence and differences between secondary data and the community’s perceptions concerning various topics of interest. Over the course of the interviewing process, many members of the Zebulon community shared their thoughts, beliefs, and experiences to help illuminate the most salient issues. The subsequent characteristics were identified as some of the most important, and hence, contributed greatly to the completion of this document: Community Characteristics: The small town of Zebulon is known as “The Town of Friendly People” and does a great deal to live up to its name. Many of the Town residents have lived there for a long period of time. Consequently, many residents enjoy familiarity with one another, close family ties, and a sense of history and community in the area. There is widespread community support within the Town from both individuals and community organizations such as churches, civic groups, and service agencies. Although Zebulon is a rural town, it now faces some issues more typical of urban centers. These issues are rapid and expansive growth, ethnic and language diversity within the population, public housing, increased crime and drugs, and growing industry and commercialization. The rapid change and growth that Zebulon has experienced in the last several years brings with it many needs and challenges, many demanding the attention of the Town and County governments. There is significant interest among residents and Town officials in handling the change and growth in Zebulon, especially concerning meeting the needs of the community through the provision, improvement, and assurance of services. Directions and Challenges: Zebulon is in the midst of a period of growth and change that the Town never before experienced. The recent annexation of Wakefield is an example of the community’s expansion, and one that illustrates some of the concerns facing Town Hall. The addition of more people means an increase in need for existing services and perhaps the development of new services. While growth is a welcomed sight for some members of Zebulon, many see it as a movement away from the traditionally held values and familiarity that come from living in a small town. The adjustment period has already started for some individuals in the community, but many steps have yet to be taken to make the Town accessible to everyone who calls it home. Several of the churches and civic organizations have offered their services to help new members to the community feel welcome, namely the growing Hispanic population. In addition, the new police chief has made a commitment to actively involving the police department in the community, thus showing one example of how the Town and its residents can work together to make Zebulon a better place for everyone. As continued growth and change face the Town, community members and service providers are preparing to address the challenges these bring. Many of the people interviewed have strong feelings and opinions about their Town and the direction in which it is moving. The greatest endeavor for Zebulon may focus on communication among Town officials, services providers, and community members to ensure a future that benefits all living and working within Zebulon.Master of Public Healt

Development of a UK core dataset for geriatric medicine research: : a position statement and results from a Delphi consensus process

Funding AS and MW are funded by the Newcastle National Institute for Health (NIHR) Biomedical Research Centre, which also funded the initial meeting of academic clinicians in geriatric medicine during the Delphi process. The views expressed in this article are those of the authors and not necessarily those of the NIHR, the NHS, or the Department of Health. Acknowledgements The authors acknowledge the contributions of members of the UK Geriatric Medicine Core Dataset Extended Working Group.Peer reviewedPublisher PD

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer

Purpose: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. Methods: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics. Results: The ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive. Conclusions: We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling

Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”

We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≥0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus

Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci

Background: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors (TFs) critical to somatic tumorigenesis. Methods: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery), and combined (9627 cases/30 845 controls; including additional individuals). Results: The PAX8-target gene set was ranked 1/615 in the discovery (PGSEA&lt;0.001; FDR=0.21), 7/615 in the replication (PGSEA=0.004; FDR=0.37), and 1/615 in the combined (PGSEA&lt;0.001; FDR=0.21) studies. Adding other genes reported to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P&lt;10−5 (including six with P&lt;5 × 10−8). The pathway was also associated with differential gene expression after shRNA-mediated silencing of PAX8 in HeyA8 (PGSEA=0.025) and IGROV1 (PGSEA=0.004) SOC cells and several PAX8 targets near SOC risk loci demonstrated in vitro transcriptomic perturbation. Conclusions: Putative PAX8 target genes are enriched for common SOC risk variants. This finding from our agnostic evaluation is of particular interest given that PAX8 is well-established as a specific marker for the cell of origin of SOC