BCHS 2526 Health Disparities Research: Methods and Interventions

This course will examine the challenges and methods in the implementation of health disparities research and interventions. It is intended to both complement and expand the knowledge gained in other BCHS courses by focusing specifically on minority/underserved populations. The course will explore readings and foster discussions that will include: ethics and research in minority/underserved communities; issues, barriers and facilitators to engaging minority/underserved communities in health research; examining basic research questions in minority health; understanding the application of research findings to program development; how to integrate theory and research, and issues and challenges of program implementation. An overarching goal is to increase awareness and knowledge of research on minority health, as well as unique issues to consider when engaging in public health research and practice in these communities. The purpose of this class is to introduce basic issues, challenges, and opportunities that are encountered in health disparities research and interventions. Current research and resources from minority health and health disparities literature will provide the background for student assignments

CrY2H-seq: a massively multiplexed assay for deep-coverage interactome mapping.

Broad-scale protein-protein interaction mapping is a major challenge given the cost, time, and sensitivity constraints of existing technologies. Here, we present a massively multiplexed yeast two-hybrid method, CrY2H-seq, which uses a Cre recombinase interaction reporter to intracellularly fuse the coding sequences of two interacting proteins and next-generation DNA sequencing to identify these interactions en masse. We applied CrY2H-seq to investigate sparsely annotated Arabidopsis thaliana transcription factors interactions. By performing ten independent screens testing a total of 36 million binary interaction combinations, and uncovering a network of 8,577 interactions among 1,453 transcription factors, we demonstrate CrY2H-seq's improved screening capacity, efficiency, and sensitivity over those of existing technologies. The deep-coverage network resource we call AtTFIN-1 recapitulates one-third of previously reported interactions derived from diverse methods, expands the number of known plant transcription factor interactions by three-fold, and reveals previously unknown family-specific interaction module associations with plant reproductive development, root architecture, and circadian coordination

Attributes of researchers and their strategies to recruit minority populations: Results of a national survey

Despite NIH mandates for inclusion, recruiting minorities is challenging for biomedical and public health researchers. Little is known about how attributes of researchers affect their choice of recruitment strategies. The purpose of this study was to address this gap by examining how use of recruitment strategies relates to other researcher characteristics. To do this, we conducted an online survey from May to August 2010 with researchers (principal investigators, research staff, and IRB members) in which we measured the number and types of recruitment strategies utilized, along with other characteristics of the researchers and their research. We identified two clusters of researchers: comprehensive researchers who utilized a greater number and more diverse and active recruitment strategies, and traditional researchers, who utilized fewer and more passive strategies. Additional characteristics that distinguished the two groups were that comprehensive researchers were more likely than traditional researchers to 1) report racial and ethnic differences as one of their specific aims or hypotheses, 2) receive federal (CDC and NIH) funding, 3) conduct behavioral or epidemiological research, and 4) have received training in conducting research with and recruiting minorities. Traditional researchers, on the other hand, were more likely to conduct clinical research and a greater (though non-significant) percentage received funding from pharmaceutical sources. This study provides a novel description of how researcher attributes are related to their recruitment strategies and raises a number of future research questions to further examine the implications of this relationship.http://dx.doi.org/10.1016/j.cct.2012.06.01

Synchronous clear cell renal cell carcinoma and tubulocystic carcinoma: genetic evidence of independent ontogenesis and implications of chromosomal imbalances in tumor progression

Seven percent of renal cell carcinoma (RCC) cases are diagnosed as "unclassified" RCC by morphology. Genetic profiling of RCCs helps define renal tumor subtypes, especially in cases where morphologic diagnosis is inconclusive. This report describes a patient with synchronous clear cell RCC (ccRCC) and a tubulocystic renal carcinoma (TCRC) in the same kidney, and discusses the pathologic features and genetic profile of both tumors. A 67 year-old male underwent CT scans for an unrelated medical event. Two incidental renal lesions were found and ultimately removed by radical nephrectomy. The smaller lesion had multiple small cystic spaces lined by hobnail cells with high nuclear grade separated by fibrous stroma. This morphology and the expression of proximal (CD10, AMACR) and distal tubule cell (CK19) markers by immunohistochemistry supported the diagnosis of TCRC. The larger lesion was a typical ccRCC, with Fuhrman's nuclear grade 3 and confined to the kidney. Molecular characterization of both neoplasms using virtual karyotyping was performed to assess relatedness of these tumors. Low grade areas (Fuhrman grade 2) of the ccRCC showed loss of 3p and gains in chromosomes 5 and 7, whereas oncocytic areas displayed additional gain of 2p and loss of 10q; the high grade areas (Fuhrman grade 3) showed several additional imbalances. In contrast, the TCRC demonstrated a distinct profile with gains of chromosomes 8 and 17 and loss of 9. In conclusion, ccRCC and TCRC show distinct genomic copy number profiles and chromosomal imbalances in TCRC might be implicated in the pathogenesis of this tumor. Second, the presence of a ccRCC with varying degrees of differentiation exemplifies the sequence of chromosomal imbalances acquired during tumor progression

Polarization and Belief Dynamics in the Black and White Communities: An Agent-Based Network Model from the Data

Public health care interventions—regarding vaccination, obesity, and HIV, for example—standardly take the form of information dissemination across a community. But information networks can vary importantly between different ethnic communities, as can levels of trust in information from different sources. We use data from the Greater Pittsburgh Random Household Health Survey to construct models of information networks for White and Black communities--models which reflect the degree of information contact between individuals, with degrees of trust in information from various sources correlated with positions in that social network. With simple assumptions regarding belief change and social reinforcement, we use those modeled networks to build dynamic agent-based models of how information can be expected to flow and how beliefs can be expected to change across each community. With contrasting information from governmental and religious sources, the results show importantly different dynamic patterns of belief polarization within the two communities

Safety of Levetiracetam in paediatrics: a systematic review

Objective To identify adverse events (AEs) associated with Levetiracetam (LEV) in children. Methods Databases EMBASE (1974-February 2015) and Medline (1946-February 2015) were searched for articles in which paediatric patients (≤18 years) received LEV treatment for epilepsy. All studies with reports on safety were included. Studies involving adults, mixed age population (i.e. children and adults) in which the paediatric subpopulation was not sufficiently described, were excluded. A meta-analysis of the RCTs was carried out and association between the commonly reported AEs or treatment discontinuation and the type of regimen (polytherapy or monotherapy) was determined using Chi2 analysis. Results Sixty seven articles involving 3,174 paediatric patients were identified. A total of 1,913 AEs were reported across studies. The most common AEs were behavioural problems and somnolence, which accounted for 10.9% and 8.4% of all AEs in prospective studies. 21 prospective studies involving 1120 children stated the number of children experiencing AEs. 47% of these children experienced AEs. Significantly more children experienced AEs with polytherapy (64%) than monotherapy (22%) (p<0.001). Levetiracetam was discontinued in 4.5% of all children on polytherapy and 0.9% on monotherapy (p<0.001), the majority were due to behavioural problems. Conclusion Behavioural problems and somnolence were the most prevalent adverse events to LEV and the most common causes of treatment discontinuation. Children on polytherapy have a greater risk of adverse events than those receiving monotherapy

Expert range maps of global mammal distributions harmonised to three taxonomic authorities

Aim: Comprehensive, global information on species' occurrences is an essential biodiversity variable and central to a range of applications in ecology, evolution, biogeography and conservation. Expert range maps often represent a species' only available distributional information and play an increasing role in conservation assessments and macroecology. We provide global range maps for the native ranges of all extant mammal species harmonised to the taxonomy of the Mammal Diversity Database (MDD) mobilised from two sources, the Handbook of the Mammals of the World (HMW) and the Illustrated Checklist of the Mammals of the World (CMW). Location: Global. Taxon: All extant mammal species. Methods: Range maps were digitally interpreted, georeferenced, error-checked and subsequently taxonomically aligned between the HMW (6253 species), the CMW (6431 species) and the MDD taxonomies (6362 species). Results: Range maps can be evaluated and visualised in an online map browser at Map of Life (mol.org) and accessed for individual or batch download for non-commercial use. Main conclusion: Expert maps of species' global distributions are limited in their spatial detail and temporal specificity, but form a useful basis for broad-scale characterizations and model-based integration with other data. We provide georeferenced range maps for the native ranges of all extant mammal species as shapefiles, with species-level metadata and source information packaged together in geodatabase format. Across the three taxonomic sources our maps entail, there are 1784 taxonomic name differences compared to the maps currently available on the IUCN Red List website. The expert maps provided here are harmonised to the MDD taxonomic authority and linked to a community of online tools that will enable transparent future updates and version control.Fil: Marsh, Charles J.. Yale University; Estados UnidosFil: Sica, Yanina. Yale University; Estados UnidosFil: Burguin, Connor. University of New Mexico; Estados UnidosFil: Dorman, Wendy A.. University of Yale; Estados UnidosFil: Anderson, Robert C.. University of Yale; Estados UnidosFil: del Toro Mijares, Isabel. University of Yale; Estados UnidosFil: Vigneron, Jessica G.. University of Yale; Estados UnidosFil: Barve, Vijay. University Of Florida. Florida Museum Of History; Estados UnidosFil: Dombrowik, Victoria L.. University of Yale; Estados UnidosFil: Duong, Michelle. University of Yale; Estados UnidosFil: Guralnick, Robert. University Of Florida. Florida Museum Of History; Estados UnidosFil: Hart, Julie A.. University of Yale; Estados UnidosFil: Maypole, J. Krish. University of Yale; Estados UnidosFil: McCall, Kira. University of Yale; Estados UnidosFil: Ranipeta, Ajay. University of Yale; Estados UnidosFil: Schuerkmann, Anna. University of Yale; Estados UnidosFil: Torselli, Michael A.. University of Yale; Estados UnidosFil: Lacher, Thomas. Texas A&M University; Estados UnidosFil: Wilson, Don E.. National Museum of Natural History; Estados UnidosFil: Abba, Agustin Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Aguirre, Luis F.. Universidad Mayor de San Simón; BoliviaFil: Arroyo Cabrales, Joaquín. Instituto Nacional de Antropología E Historia, Mexico; MéxicoFil: Astúa, Diego. Universidade Federal de Pernambuco; BrasilFil: Baker, Andrew M.. Queensland University of Technology; Australia. Queensland Museum; AustraliaFil: Braulik, Gill. University of St. Andrews; Reino UnidoFil: Braun, Janet K.. Oklahoma State University; Estados UnidosFil: Brito, Jorge. Instituto Nacional de Biodiversidad; EcuadorFil: Busher, Peter E.. Boston University; Estados UnidosFil: Burneo, Santiago F.. Pontificia Universidad Católica del Ecuador; EcuadorFil: Camacho, M. Alejandra. Pontificia Universidad Católica del Ecuador; EcuadorFil: de Almeida Chiquito, Elisandra. Universidade Federal do Espírito Santo; BrasilFil: Cook, Joseph A.. University of New Mexico; Estados UnidosFil: Cuéllar Soto, Erika. Sultan Qaboos University; OmánFil: Davenport, Tim R. B.. Wildlife Conservation Society; TanzaniaFil: Denys, Christiane. Muséum National d'Histoire Naturelle; FranciaFil: Dickman, Christopher R.. The University Of Sydney; AustraliaFil: Eldridge, Mark D. B.. Australian Museum; AustraliaFil: Fernandez Duque, Eduardo. University of Yale; Estados UnidosFil: Francis, Charles M.. Environment And Climate Change Canada; CanadáFil: Frankham, Greta. Australian Museum; AustraliaFil: Freitas, Thales. Universidade Federal do Rio Grande do Sul; BrasilFil: Friend, J. Anthony. Conservation And Attractions; AustraliaFil: Giannini, Norberto Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Gursky-Doyen, Sharon. Texas A&M University; Estados UnidosFil: Hackländer, Klaus. Universitat Fur Bodenkultur Wien; AustriaFil: Hawkins, Melissa. National Museum of Natural History; Estados UnidosFil: Helgen, Kristofer M.. Australian Museum; AustraliaFil: Heritage, Steven. University of Duke; Estados UnidosFil: Hinckley, Arlo. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Holden, Mary. American Museum of Natural History; Estados UnidosFil: Holekamp, Kay E.. Michigan State University; Estados UnidosFil: Humle, Tatyana. University Of Kent; Reino UnidoFil: Ibáñez Ulargui, Carlos. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Jackson, Stephen M.. Australian Museum; AustraliaFil: Janecka, Mary. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Jenkins, Paula. Natural History Museum; Reino UnidoFil: Juste, Javier. Consejo Superior de Investigaciones Científicas. Estación Biológica de Doñana; EspañaFil: Leite, Yuri L. R.. Universidade Federal do Espírito Santo; BrasilFil: Novaes, Roberto Leonan M.. Universidade Federal do Rio de Janeiro; BrasilFil: Lim, Burton K.. Royal Ontario Museum; CanadáFil: Maisels, Fiona G.. Wildlife Conservation Society; Estados UnidosFil: Mares, Michael A.. Oklahoma State University; Estados UnidosFil: Marsh, Helene. James Cook University; AustraliaFil: Mattioli, Stefano. Università degli Studi di Siena; ItaliaFil: Morton, F. Blake. University of Hull; Reino UnidoFil: Ojeda, Agustina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Ordóñez Garza, Nicté. Instituto Nacional de Biodiversidad; EcuadorFil: Pardiñas, Ulises Francisco J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Pavan, Mariana. Universidade de Sao Paulo; BrasilFil: Riley, Erin P.. San Diego State University; Estados UnidosFil: Rubenstein, Daniel I.. University of Princeton; Estados UnidosFil: Ruelas, Dennisse. Museo de Historia Natural, Lima; PerúFil: Schai-Braun, Stéphanie. Universitat Fur Bodenkultur Wien; AustriaFil: Schank, Cody J.. University of Texas at Austin; Estados UnidosFil: Shenbrot, Georgy. Ben Gurion University of the Negev; IsraelFil: Solari, Sergio. Universidad de Antioquia; ColombiaFil: Superina, Mariella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Tsang, Susan. American Museum of Natural History; Estados UnidosFil: Van Cakenberghe, Victor. Universiteit Antwerp; BélgicaFil: Veron, Geraldine. Université Pierre et Marie Curie; FranciaFil: Wallis, Janette. Kasokwa-kityedo Forest Project; UgandaFil: Whittaker, Danielle. Michigan State University; Estados UnidosFil: Wells, Rod. Flinders University.; AustraliaFil: Wittemyer, George. State University of Colorado - Fort Collins; Estados UnidosFil: Woinarski, John. Charles Darwin University; AustraliaFil: Upham, Nathan S.. University of Yale; Estados UnidosFil: Jetz, Walter. University of Yale; Estados Unido

The Toll→NFκB Signaling Pathway Mediates the Neuropathological Effects of the Human Alzheimer's Aβ42 Polypeptide in Drosophila

Alzheimer's (AD) is a progressive neurodegenerative disease that afflicts a significant fraction of older individuals. Although a proteolytic product of the Amyloid precursor protein, the Αβ42 polypeptide, has been directly implicated in the disease, the genes and biological pathways that are deployed during the process of Αβ42 induced neurodegeneration are not well understood and remain controversial. To identify genes and pathways that mediated Αβ42 induced neurodegeneration we took advantage of a Drosophila model for AD disease in which ectopically expressed human Αβ42 polypeptide induces cell death and tissue degeneration in the compound eye. One of the genes identified in our genetic screen is Toll (Tl). It encodes the receptor for the highly conserved Tl→NFkB innate immunity/inflammatory pathway and is a fly homolog of the mammalian Interleukin-1 (Ilk-1) receptor. We found that Tl loss-of-function mutations dominantly suppress the neuropathological effects of the Αβ42 polypeptide while gain-of-function mutations that increase receptor activity dominantly enhance them. Furthermore, we present evidence demonstrating that Tl and key downstream components of the innate immunity/inflammatory pathway play a central role in mediating the neuropathological activities of Αβ42. We show that the deleterious effects of Αβ42 can be suppressed by genetic manipulations of the Tl→NFkB pathway that downregulate signal transduction. Conversely, manipulations that upregulate signal transduction exacerbate the deleterious effects of Aβ42. Since postmortem studies have shown that the Ilk-1→NFkB innate immunity pathway is substantially upregulated in the brains of AD patients, the demonstration that the Tl→NFkB signaling actively promotes the process of Αβ42 induced cell death and tissue degeneration in flies points to possible therapeutic targets and strategies

Expert range maps of global mammal distributions harmonised to three taxonomic authorities

AimComprehensive, global information on species' occurrences is an essential biodiversity variable and central to a range of applications in ecology, evolution, biogeography and conservation. Expert range maps often represent a species' only available distributional information and play an increasing role in conservation assessments and macroecology. We provide global range maps for the native ranges of all extant mammal species harmonised to the taxonomy of the Mammal Diversity Database (MDD) mobilised from two sources, the Handbook of the Mammals of the World (HMW) and the Illustrated Checklist of the Mammals of the World (CMW).LocationGlobal.TaxonAll extant mammal species.MethodsRange maps were digitally interpreted, georeferenced, error-checked and subsequently taxonomically aligned between the HMW (6253 species), the CMW (6431 species) and the MDD taxonomies (6362 species).ResultsRange maps can be evaluated and visualised in an online map browser at Map of Life (mol.org) and accessed for individual or batch download for non-commercial use.Main conclusionExpert maps of species' global distributions are limited in their spatial detail and temporal specificity, but form a useful basis for broad-scale characterizations and model-based integration with other data. We provide georeferenced range maps for the native ranges of all extant mammal species as shapefiles, with species-level metadata and source information packaged together in geodatabase format. Across the three taxonomic sources our maps entail, there are 1784 taxonomic name differences compared to the maps currently available on the IUCN Red List website. The expert maps provided here are harmonised to the MDD taxonomic authority and linked to a community of online tools that will enable transparent future updates and version control

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes