Persons with disabilities in Robeson County, North Carolina : an action-oriented community diagnosis : findings and next steps of action

The following document is a detailed report of an Action Oriented Community Diagnosis (AOCD) completed by a five-member team of graduate students at University of North Carolina at Chapel Hill, School of Public Health, Department of Health Behavior and Health Education. This AOCD was conducted in order to gain an understanding of the cultural, social, economic, and health experiences of persons with disabilities and their families in Robeson County, North Carolina. Through the AOCD process, the team and community participants identified resources, strengths, and challenges that exist in Robeson County for persons with disabilities and their families, and developed action steps to address several of the challenges. Over the course of seven months from October 2007 to April 2008, the team worked to learn more about the community. Through conducting secondary data, attending community events, and conducting 28 in-depth interviews with 20 service providers and eight community members and three focus groups with 13 community members, team members gained valuable insight into everyday life in this community. The team developed a coding system to analyze the data collected and to identify recurring themes related to living with disabilities in Robeson County. In April 2008, the team organized a community forum at the O.P. Owens Building in Lumberton, the county seat, to present findings from the AOCD process to over 43 community members and service providers. At the forum, participants had the opportunity to discuss major themes that emerged from the team‘s data analysis, and to work together in small groups to create specific action steps to address those themes. The themes and action steps discussed at the forum were: 1. Transportation: There is a lack of accessible, reliable, and affordable transportation options in Robeson County. This limits quality of life, access to services, and employment for people living with disabilities. Attend County Commissioner meetings. Attend Mayor‘s Committee for the Disabled meetings. Call SEATS to ask about safety procedures, weight limits, and wheelchair accessible vans. Research how other communities with similar demographics and geographies have addressed transportation for persons with disabilities. Look into recreating the voucher program. Create an education campaign for service providers, wheelchair vendors, persons with disabilities, and the general community about transportation issues faced by persons with disabilities. Talk to physicians and physical therapists about transportation issues faced by persons with disabilities, including how selection of wheelchair can affect opportunities for public transportation. 2. Services Communication and Information: Although many services exist for persons with disabilities in Robeson County, there is a lack of a centralized information system accessible to people with low literacy and without access to computer technology. There is also a lack of partnership between service providers. This causes confusion and limited knowledge about services for service providers, persons with disabilities and their families. Contacting the Healing Lodge in the county to facilitate a discussion with those members and connect them to disability resources. Service providers presenting at healthcare to educate the community about services available. Finding out more about the 211 telephone information service provided by United Way. Collaborate with other agencies on the Partnership for Community Health booklet by letting Partnership know about more providers. 3. Recreation: There is an interest among persons with disabilities to become physically active. There is a lack of recreational opportunities and facilities for persons with disabilities in Robeson County. This limits social and recreational interaction and creates barriers for physical fitness. Advertise and increase awareness of disabilities and recreational opportunities for persons with disabilities in the local newspapers. Form a support group for persons with disabilities to increase awareness of the need for recreation for persons with disabilities. Hold first meeting of support group where the ADA laws that ensure persons with disabilities access to accessible public recreational opportunities are explained. Organize monthly activities for persons with disabilities. 4. Awareness: There is limited awareness among community members and service providers about persons with disabilities, especially “invisible disabilities,” such as chronic illness and substance abuse. This contributes to feelings of isolation and disrespect that diminish the quality of life for persons with disabilities and caregivers. Train healthcare workers in disability awareness by having them use different assistance devices, such as wheelchairs, for a day. Be vocal as persons with disabilities and share experiences and perspectives with others. Advocate for disability awareness by integrating discussions of disability in other venues. Educate employers about ADA rights. 5. Paying for services: Although many people living with disabilities in Robeson County are supported by Medicaid, many others are uninsured and have difficulty paying for medical services. This causes people to delay seeking medical help and decreases the reach and effectiveness of existing resources. Action steps were not developed for this group as there were not enough attendees who participated in developing action steps around this theme. Following the forum, the team completed this final report with recommendations for the community based on their experiences throughout the process and the outcomes from the community forum. The final recommendations are summarized below: 1. Service providers for persons with disabilities in Robeson County should continue to update the resource list that the team has compiled and included in this document and should make it available in multiple formats designed for the those with vision loss, low literacy, and without access to computer technology. 2. Service providers for persons with disabilities in Robeson County should create a centralized referral system that could direct its users to different services, including medical and social services, as suggested by several service providers and community members. This could be started by further publicizing the existing 211 telephone directory. 3. Community members and service providers should advocate for the expansion of the county transit program (SEATS), including more accessible vans and drivers, affordable fares, and weekend routes. 4. Service providers should hold annual public events such as a community forum or health fair to increase awareness of disabilities and services and resources available to persons with disabilities in Robeson County. This can be hosted by a local health agency or an advocacy organization such as the Mayor‘s Committee for the Disabled. 5. Community members and service providers should advocate for the perspectives of persons with disabilities in public meetings about county development, including new and existing projects. Persons with disabilities and their supporters should be aware of local news, attend town, city or county meetings whenever possible, and share their views and ideas with the larger community. The Mayor‘s Committee for the Disabled should support persons with disabilities in these efforts by publicizing their meeting times and by helping persons with disabilities access schedules of other local government meetings and public hearings. The team hopes that this report, the action steps, community member and service provider connections, and the strong sense of initiative for change that emerged from this project and the community forum will continue to build on the strengths of this community. Ultimately, the team also hopes that the entire AOCD process and this final report contribute to future improvements not only for persons with disabilities, but for all residents of Robeson County.Master of Public Healt

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10$^{−35}$ and <10$^{−8}$ respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10$^{−6}$). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10$^{−20}$) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue

Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD

Peer reviewe

Fast demographic traits promote high diversification rates of Amazonian trees

The Amazon rain forest sustains the world's highest tree diversity, but it remains unclear why some clades of trees are hyperdiverse, whereas others are not. Using dated phylogenies, estimates of current species richness and trait and demographic data from a large network of forest plots, we show that fast demographic traits - short turnover times - are associated with high diversification rates across 51 clades of canopy trees. This relationship is robust to assuming that diversification rates are either constant or decline over time, and occurs in a wide range of Neotropical tree lineages. This finding reveals the crucial role of intrinsic, ecological variation among clades for understanding the origin of the remarkable diversity of Amazonian trees and forests

SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics

Rationale: Genetic studies suggest that SOX17 (SRY-related HMG-box 17) deficiency increases pulmonary arterial hypertension (PAH) risk. Objectives: On the basis of pathological roles of estrogen and HIF2α (hypoxia-inducible factor 2α) signaling in pulmonary artery endothelial cells (PAECs), we hypothesized that SOX17 is a target of estrogen signaling that promotes mitochondrial function and attenuates PAH development via HIF2α inhibition. Methods: We used metabolic (Seahorse) and promoter luciferase assays in PAECs together with the chronic hypoxia murine model to test the hypothesis. Measurements and Main Results: Sox17 expression was reduced in PAH tissues (rodent models and from patients). Chronic hypoxic pulmonary hypertension was exacerbated by mice with conditional Tie2-Sox17 (Sox17EC-/-) deletion and attenuated by transgenic Tie2-Sox17 overexpression (Sox17Tg). On the basis of untargeted proteomics, metabolism was the top pathway altered by SOX17 deficiency in PAECs. Mechanistically, we found that HIF2α concentrations were increased in the lungs of Sox17EC-/- and reduced in those from Sox17Tg mice. Increased SOX17 promoted oxidative phosphorylation and mitochondrial function in PAECs, which were partly attenuated by HIF2α overexpression. Rat lungs in males displayed higher Sox17 expression versus females, suggesting repression by estrogen signaling. Supporting 16α-hydroxyestrone (16αOHE; a pathologic estrogen metabolite)-mediated repression of SOX17 promoter activity, Sox17Tg mice attenuated 16αOHE-mediated exacerbations of chronic hypoxic pulmonary hypertension. Finally, in adjusted analyses in patients with PAH, we report novel associations between a SOX17 risk variant, rs10103692, and reduced plasma citrate concentrations (n = 1,326). Conclusions: Cumulatively, SOX17 promotes mitochondrial bioenergetics and attenuates PAH, in part, via inhibition of HIF2α. 16αOHE mediates PAH development via downregulation of SOX17, linking sexual dimorphism and SOX17 genetics in PAH

SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics

RATIONALE/OBJECTIVES: Genetic studies suggest SOX17 deficiency increases pulmonary arterial hypertension (PAH) risk. Based on pathological roles of estrogen and hypoxia inducible factor 2α (HIF-2α) signaling in PA endothelial cells (PAECs), we hypothesized that SOX17 is a target of estrogen signaling that promotes mitochondrial function and attenuates PAH development via HIF-2α inhibition. METHODS: We used metabolic (seahorse) and promoter lucifer assays in PAECs along with the chronic hypoxia murine model to test the hypothesis. MEASUREMENTS AND MAIN RESULTS: Sox17 expression was reduced in PAH tissues (rodent models and from patients). Chronic hypoxic PH was exacerbated by mice with conditional Tie2-Sox17 (Sox17EC-/-) deletion and attenuated by transgenic Tie2-Sox17 over-expression (Sox17Tg). Based on untargeted proteomics, metabolism was the top pathway altered by SOX17 deficiency in PAECs. Mechanistically, we found HIF-2α levels were increased in the lungs of Sox17EC-/- and reduced in those from Sox17Tg mice. Increased SOX17 promoted oxidative phosphorylation and mitochondrial function in PAECs, which were partly attenuated by HIF-2α overexpression. Rat lungs in males displayed higher Sox17 expression versus females, suggesting repression by estrogen signaling. Supporting 16alpha-hydroxyestrone (16αOHE, a pathologic estrogen metabolite)-mediated repression of SOX17 promoter activity, Sox17Tg mice attenuated 16αOHE-mediated exacerbations of chronic hypoxic PH. Finally, in adjusted analyses in patients with PAH, we report novel associations between a SOX17 risk variant, rs10103692, with reduced plasma citrate levels (n=1326). CONCLUSIONS: Cumulatively, SOX17 promotes mitochondrial bioenergetics and attenuates PAH, in part, via inhibition of HIF-2α. 16αOHE mediates PAH development via downregulation of SOX17, linking sexual dimorphism and SOX17 genetics in PAH. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Fast demographic traits promote high diversification rates of Amazonian trees

The Amazon rain forest sustains the world's highest tree diversity, but it remains unclear why some clades of trees are hyperdiverse, whereas others are not. Using dated phylogenies, estimates of current species richness and trait and demographic data from a large network of forest plots, we show that fast demographic traits--short turnover times--are associated with high diversification rates across 51 clades of canopy trees. This relationship is robust to assuming that diversification rates are either constant or decline over time, and occurs in a wide range of Neotropical tree lineages. This finding reveals the crucial role of intrinsic, ecological variation among clades for understanding the origin of the remarkable diversity of Amazonian trees and forests