Collaboration Roundtable February 2, 2009 POSTER ABSTRACTS Submitted by: Thomas Adamkiewicz, Morehouse School of Medicine Hemoglobin, nutrition, inflammation and the environment: at the crossroads of global health. Thomas Adamkiewicz, Jacqueline Hibbert, Beatrice E Gee, Adel Driss, Kwaku Asare, Jonathan Stiles. Morehouse School of Medicine - Postdoctoral Training in Genomics and Hemoglobinopathies Program (MTGHP). Hemoglobinopathies affect disproportionately minorities in the US and significant portions of the global population, mostly residing in countries with low incomes. The MTGHP, funded by NIH/Fogarty, recruits and trains postdoctoral fellows from underrepresented US minority populations, particularly those affected by hemoglobinopathies over a period of two- three years. MTGHP includes international (University of Ghana; Sickle Cell Trust, Jamaica) and local collaborators (Emory and Medical College of Georgia). Members of the MTGHP group conduct laboratory, clinical and population- based studies that examine interactions between Sickle Cell Disease (SCD) and nutrition, inflammation, vascular biology, susceptibility to infection and possible therapeutic interventions. Recent studies examined the relationship of resting energy expenditure with inflammation in patients with SCD, allocation of the increased metabolic demand, as well effect of high protein diet on the inflammatory response in SCD mouse models. Determinants of vascular injury are being elucidated, with demonstration, for the first time, of the enhanced vasculogenic potential at steady-state in patients with SCD. These may serve as markers of disease severity. Population based studies examined the nature of increased susceptibility to pathogens, methods of prevention, and their possible global impact. In addition to the effect of nutrition,[1-3] other therapeutic modalities explored include stem cell translation modalities, and interaction between chronic transfusion iron overload toxicity, inflammation and hemolysis. With the participation of fellows, the program is currently laying the groundwork for SCD population based screening to determine reliable markers of disease severity in the context of complex and diverse environments, including hitherto seldom examined populations (Tunisia) as well as in Ghana. In summary, the aim of this program is to cultivate outstanding researchers who will strive to improve care of individuals both burdened by hemoglobinopathies and resource disparities, while exploring critical, but neglected interactions of human biology that possibly affect large segments of the global population. 1. Hibbert, Hsu, Bhathena, et al. Proinflammatory cytokines and the hypermetabolism of children with SCD. Experimental Biology & Medicine 2005 2. Hibbert, Creary, Gee, Buchanan, Quarshie, Hsu. Erythropoiesis and myocardial energy requirements contribute to the hypermetabolism of childhood SCD. Journal of Pediatric Gastroenterology & Nutrition 2006 3. Archer, Stiles, Newman, et al. C-reactive protein and interleukin-6 are decreased in transgenic sickle cell mice fed a high protein diet. Journal of Nutrition 2008 4. Gee BE, Manlove-Simmons JM, Huang Y, Wilson N, Stiles J, Ofori-Acquah S. Dominant Role for SDF-1 in the Vasculo- Angiogenesis Phenotype in Children with SCD. ASH/Blood 2008 5. Adamkiewicz, Silk, Howgate, et al. Effectiveness of the 7-valent pneumococcal conjugate vaccine in children with SCD in the first decade of life. Pediatrics 2008 6. Adamkiewicz, Szabolcs, Haight, et al. Unrelated cord blood transplantation in children with SCD: review of four-center experience. Pediatric Transplantation 2007 7. Adamkiewicz, Abboud, Paley, et al. Iron Overload in Children with SCD on Prophylactic Chronic Transfusion. Submitted 2009 Submitted by: Holly Avey, Georgia State University, Georgia Health Policy Center Georgia Health Policy Center: Founded in 1995 and housed within the Andrew Young School of Policy Studies, the Georgia Health Policy Center is focused on providing the best possible quality of research and information. Competencies: Core competencies include: knowledge creation and management; consensus building; grants management; health systems change; and knowledge transfer. Because of these core competencies, our staff has extensive experience, skills and knowledge in conducting evidence-based research and program evaluation, convening and engaging diverse stakeholders, empowering local communities, providing targeted technical assistance and strategic support, and disseminating research and best practices information through briefs, reports, and publications. Our Work: The Center provides evidence-based research, program development and policy guidance on local, state and national levels to improve health status at the community level. Projects have focused on: • Public and private insurance coverage • Long-term care and end-of-life care improvement • Children‘s health and well-being • Rural and community health system development • Social determinants of health Research Initiatives: Strengthening Public Health Infrastructure through Public Health Institutes - examine the overall capacity of existing Public Health Institutes (PHIs), assess the potential for mature PHIs to provide technical assistance to emerging institutes, and explore the contextual conditions in states without statewide PHIs. Collaborators: Centers for Disease Control and Prevention, National Network of Public Health Institutes PeachCare for Kids Evaluation - conduct the annual evaluation of Georgia's health insurance program to serve low-income children. Collaborator: Collaboration Roundtable Poster Abstracts P. 2 Georgia Department of Community Health Cancer Regional Programs of Excellence Evaluation - assess the cancer control planning work carried out by nine grantees seeking designation by the Coalition as Regional Programs of Excellence. Collaborator: Georgia Cancer Coalition Program Efforts: HRSA National Technical Assistance – provide technical assistance to 198 community network and outreach grantees in 49 states. Collaborator: Health Resources and Services Administration‘s Office of Rural Health Policy Building Strong Families - help couples strengthen their relationship, achieve a healthy marriage if that is the path they choose, and thus enhance child and family well-being. Collaborators: Annie E. Casey Foundation, Association for Child and Family Services Policy Initiatives: Finding the Voice of Public Health in the National Health Reform Dialogue - explore ways that public health issues might become part of the reform debate. Extensive research, interviews and focus groups, and convenings throughout the country resulted in a model that engages stakeholders at every level as instruments of reform. Collaborator: Centers for Disease Control and Prevention Legislative Education Initiative –developed the Legislative Health Policy Certificate Program, a comprehensive, policy-relevant, educational initiative to improve health policy decision making capacity. A system dynamics model for childhood obesity was developed to enable more rigorous discussions of policy alternatives. Collaborator: Robert W. Woodruff Foundation Partners and Collaborations: We recognize the evolving nature of our work and experiences. We learn from our clients, our communities, and partners. We actively seek partners to further the Center‘s mission of improving health status. We are open to new ideas, approaches and partnerships and want our work to reflect our emergent knowledge and experiences. Submitted by: Bernard Beall, CDC This is perhaps a non-conventional approach, but if allowed, our poster will probably simply consist of a panel of recently published and submitted abstracts from the CDC Division of Bacterial Diseases Streptococcus Lab. We feel that this would probably be the most convenient and efficient way convey our current research interests. Submitted by: Elizabeth Buffalo, Emory University School of Medicine HIPPOCAMPAL ACTIVITY REFLECTS RECOGNITION MEMORY ON A TRIAL-BY-TRIAL BASIS M. J. JUTRAS1,2, P. FRIES3, E. A. BUFFALO2,4 1Neurosci. Program, Emory University, Atlanta, GA; 2Yerkes National Primate Research Center, Atlanta, GA; 3FC Donders Center For Cognitive Neuroimaging, Nijmegen, Netherlands; 4Department of Neurology, Emory University School of Medicine, Atlanta, GA Recognition memory depends on the integrity of the medial temporal lobe (MTL). Although previous neurophysiological studies have reported recognition memory signals in the monkey MTL, it has been difficult to examine whether these signals correlate with performance because monkeys are typically overtrained to perform at high levels, resulting in very few error trials. To address this issue, hippocampal spikes and local field potentials (LFPs) were recorded from multiple electrodes in two monkeys performing the Visual Preferential Looking Task (VPLT). This task relies on the monkey‘s innate preference for novelty, and therefore requires no specific training. Additionally, this task elicits variations in performance that allow for an examination of the relationship between trial-to-trial fluctuations in recognition memory and neuronal activity. Out of 131 single units, 100 (76%) responded significantly to stimulus presentation, and the firing rate of 31% of these neurons was significantly modulated by stimulus novelty. Importantly, this modulation was positively correlated with trial-to-trial variations in performance, such that increased neuronal responses to novelty predicted better memory performance (median correlation coefficient = .40, p<.001). We also examined phase synchrony in the gamma- frequency band, which has previously been associated with successful memory performance (Fell et al., 2001). Across trials in a session, we found a significant positive correlation between gamma-band spike-field synchrony during encoding and subsequent memory performance (median correlation coefficient = .25, p<.001). Taken together, these results provide direct evidence linking hippocampal activity with recognition memory performance on a trial-by- trial basis. Submitted by: George Carlone and Sandra Steiner, CDC Research Interests and Capabilities in the Immunology Laboratories George Carlone, Sandra Steiner, Jacquelyn Sampson, Gowrisankar Rajam, Cheryl Elie, and Edwin Ades Immunology Laboratories, Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, NCIRD Abstract: The Immunology Laboratories, (1) Integrates laboratory and epidemiologic approaches to enhance the diagnosis and surveillance of agents causing respiratory, meningococcal and other priority bacterial infections, (2) Develops, evaluates, implements, and improves serologic, immunologic and molecular biologic methods, techniques and strategies, (3) Develops and evaluates vaccines and vaccine candidates that protect against priority bacterial diseases, (4) Conducts, participates, and collaborate in vaccine clinical trials, (5) Develops, standardizes and validates correlates of protection and applies to the evaluation of new and developed priority bacterial agents, (6) Develops new diagnostic reagents and methods including the development, maintenance and evaluation of hybridomas, (7) Develops and evaluates immunizing Collaboration Roundtable Poster Abstracts P. 3 agents and studies the role of immunologic mechanisms in disease processes, (8), Operates and maintains a research laboratory at the Good laboratory Practice (GLP) compliance level in support of vaccine clinical trials, (9) Maintains the World Health Organization Collaborating Center for Research and Reagents for Human Immunoglobulin Subclasses, and (10) Supports global access to vaccines by providing reference materials, standardized protocols training, and consultative support to other government agencies, international collaborators including domestic and international reference laboratories, vaccine manufactures, academic institutions, The World Health Organization, and the Pan American Health Organization. Submitted by: Corinne Crammer, American Cancer Society Cancer Survivors‘ Spiritual Well-Being and Use of Mind-Body Complementary Therapies: The Effects of Race and Gender Corinne Crammer PhD, MDiv, MM; Kevin Stein, PhD; Chiewkwei Kaw, MS; George Fitchett,DMin; Youngmee Kim, PhD; and Cristina Stephens, PhD PURPOSE: Little is known about the relation between cancer survivors‘ spirituality and their use of complementary therapies, specifically, mind-body methods (MBM). We examined this association and explored the effects of race and gender on this association. METHODS: We analyzed data from 3,903 cancer survivors who completed the American Cancer Society‘s Study of Cancer Survivors-I, a population-based, longitudinal study of quality of life. Participants completed this survey approximately 1.25 years after diagnosis. Three aspects of spirituality – Meaning, Peace, and Faith – were assessed using the FACIT-Sp. Mind-body methods (MBM) were divided into spiritual/religious (MBM-S) and non-spiritual/religious (MBM-NS). The race by gender moderating effects were tested for four groups: Black Male (BM), White Male (WM), Black Female (BF), and White Female (WF). Demographics, cancer severity, and health status served as covariates. RESULTS: Generalized linear model revealed that survivors who were younger, more educated, had more severe cancer, or poorer general health were more likely to use MBM. Meaning and Faith were positively associated with overall MBM use, whereas Peace was negatively associated. Meaning was significantly related for BM (OR=1.287) and WF (OR=1.057); Faith, for BM (OR=1.247), WM (OR=1.221), and WF (OR=1.255); and Peace was negatively associated for Whites only (WM, OR=0.916; WF, OR=0.931). For MBM-NS use, Meaning was positively related for females (BF, OR=1.250; WF, OR=1.051), and Faith, for Whites (WM, OR=1.065; WF, OR=1.052). For MBM-S use, Meaning was positively related for BM only (OR=1.338), whereas Faith was strongly and positively associated for all gender-racial groups. Peace was negatively associated with MBM-S for Whites only (MW, OR=0.852; FW, OR=0.882). The p- values for all reported ORs were <0.05. CONCLUSIONS: Spiritual well-being is associated both positively and negatively with the use of MBM. Associations differ based on gender and race. RESEARCH IMPLICATIONS: Causality between variables and the mechanism for differential effects of race and gender on the spirituality and MBM use should be further explored. CLINICAL IMPLICATIONS: Survivors‘ spirituality impacts the likelihood of their use of MBM. White survivors using spiritual MBMs may be experiencing low levels of spiritual peace, but this association was not found for Black survivors. ACKNOWLEDGEMENT OF FUNDING: ACS intramural. Submitted by: Edward Timothy Davies, Dept. of Biochemistry, University of Georgia The Bioexpression and Fermentation Facility is a molecular biology, protein and biomass production facility offering services and training to the University of Georgia research community, academic researchers, and private industry. The BFF provides custom services in molecular biology; vaccine development; antibody and protein expression and purification; process development; and production of biological materials and metabolites, from laboratory to pilot- scale. The BFF comprises the BioXpress laboratory, providing molecular biology, small scale protein expression and purification services; the Fermentation Research Facility, which is equipped with 23 bioreactors ranging from 1L to 800L and is designed to cover aspects of the biomanufacturing from process development through scale up and production; the Protein Purification Laboratory, which conducts large scale protein purification process development and production; and the BSL3 Cell Culture Laboratory which is designed for the production of proteins using mammalian cells in a high quality high containment setting. Our mission is to provide researchers with state of the art instrumentation and expertise to accelerate research from gene identification through process development, scale-up, and manufacturing. Our services include confidential fee-for-service research tailored to your exact research needs, utilization of BioXpress equipment by your research personnel, and training in our academic laboratory setting. Submitted by: Gene Demchuk, ATSDR, CDC Computational Toxicology in Public Health: the Present and the Future The Agency for Toxic Substances and Disease Registry (ATSDR) Computational Toxicology and Method Development Laboratory implements the full range of methods in support of ATSDR mission to protect human populations from exposure to environmental contaminants. These include benchmark dose, chemical-specific adjustment factor, physiologically-based pharmacokinetic/pharmacodynamic, quantitative structure-activity relationship, genetic-susceptibility- and meta- Collaboration Roundtable Poster Abstracts P. 4 analysis modeling, and modeling the toxicity of chemical mixtures. Computational toxicology methods are used as an integrated systematic approach in the development of ATSDR Minimal Risk Levels to be used as health guidance values to protect populations exposed to toxic chemicals at hazardous waste sites. These methods are also used in the development of ATSDR Toxicological Profiles, to support environmental health consultations and prioritization of environmental chemical hazards, when experimental information is insufficient, and to improve study design, when filling the priority data needs as mandated by the Congress. Also, the Laboratory is engaged in the development of response strategies to new emerging chemical threats, such as toxicology of nano-materials, and emerging techniques in the area of hazard identification and risk assessment, including characterization of personalized biomarkers, personalized and population genomics, and immunotoxicology. Submitted by: Andrew Dent and Stephanie Foster, Geospatial Research, Analysis and Services Program, CDC Background: The Geospatial Research, Analysis, and Services Program (ATSDR/CDC) provides expert advice and assistance with the application of geospatial science and spatial analysis tools. GRASP scientists utilize US Census data, health outcome data, and environmental data to evaluate geospatial relationships between health outcomes and risk factors. Highlighted Projects: > Avian Influenza Surveillance Collaborators: NCZVED GRASP is tracking animal H5N1 cases compiled from the Office International des Epizooties (OIE) and other reports for DEOC briefings to senior leadership. >Population Vulnerability Index (PVI) Collaborators: NCEH/ATSDR, Office of Terrorism Preparedness and Emergency Response PVI is designed to assess the vulnerability of populations to all-hazard events based on a combination of economic, household, transportation, and language Census attributes. >Patna, India Hospital Service Area Assessment Collaborators: NCIRD, Global Immunization Division GRASP is estimating population within hospital service areas of Patna, India to enable the efficient distribution of health services. >Modular Photographic Observational Device (ModPOD) Collaborators: NCEH/DEEHS/International Emergency and Refugee Health Branch, Georgia Tech Research Institute GRASP/GTRI developed the ModPOD, a low-cost, high resolution imaging device that produces georeferenced images for rapid assessment of complex humanitarian emergencies. >Barriers to Mammography Clinic Access in Metropolitan Atlanta Collaborators: NCCDPHP/Division of Cancer Prevention and Control, Susan G. Komen For the Cure GRASP is using MARTA route data to evaluate time and distance barriers confronting disadvantaged populations attempting to access mammography screening facilities in metropolitan Atlanta. >Emergency Preparedness and Response Collaborators: Director‘s Emergency Operations Center GRASP provides maps and consulting on the use of geospatial data to respond to public health emergencies. >Systems Integration and Applications Collaborators: Multiple GRASP develops and/or supports web/desktop applications that facilitate the investigation and analysis of disease dispersion, environmental exposure, and health care access. Conclusion: With expertise in demographic analyses, medical geography, epidemiology, exposure assessment, contaminant modeling, and emergency preparedness/response GRASP is poised to engage in new collaborative ventures that integrate a geospatial component into public health research. Submitted by: Duc Do, Mercer University Novel Nanotechnology Platform for Oral Delivery of Vaccines Martin J. D‘Souza, Tuhin Bhowmik, Bernadette D‘Souza, Neil J. Patel, Naser M. Uddin, Prathap Nagaraja Shastri, Lipika Chablani, Archana Akalkotkar, Duc Do, Suprita Tawde Mercer University, Nanotechnology, Cancer & Vaccine Laboratory, Atlanta, GA 30341 We, at the Nanotechnology, Cancer and Vaccine Laboratory at Mercer University, Atlanta, have developed a platform technology using nanospheres and microspheres to deliver vaccines by the oral route of administration, specifically in the form of a capsule containing the bead-like encapsulated vaccine antigens. This formulation technology enables us to prepare microspheres and nanospheres containing biologically active compounds, such as vaccine antigens and protein drugs, without loss of their biological activity during the formulation process. We can also encapsulate multiple antigens, targeting agents and drugs in a single particle. Using our novel method, the vaccine prepared exists in a dry stable form. These bead-like particles containing the antigen can be administered either orally or systemically. When administered orally, these spheres have an enteric coating to protect from the acidic environment of the stomach. The enteric coating dissolves in the basic environment of the intestine and the vaccine is targeted to the Peyer‘s patches and the general mucosal immune system. Since these particles are particulate in nature, ranging between 0.05-2.0 microns in size, they are taken up by phagocytic antigen presenting cells (APC's), such as M cells and macrophages in the Peyer's patches of the intestines, and the antigen is presented to the lymphocytes, which are responsible for antibody production. Since these nanospheres/microspheres release the antigen (payload) intracellularly into the APC's, a higher antibody response to the encapsulated antigen is obtained. Of particular interest in this formulation is the fact that the microspheres release the antigen in a slow and sustained manner over a prolonged time period, resulting in strong mucosal and systemic immunity after oral administration, without the need for adjuvants. Since no needles are required, this method of vaccine delivery is inexpensive and suitable for the Collaboration Roundtable Poster Abstracts P. 5 developing world as well as for the developed world. Preliminary studies conducted in our laboratory with TB, typhoid, melanoma, and hepatitis B vaccine antigens suggest that this delivery system is highly suitable for antigens to be used for protective immunity. This method of vaccine delivery enables us to address a wide spectrum of vaccines for prophylactic and therapeutic use. Melanoma tumors are widespread in the southeastern United States. We have been working on the ―Evaluation of an oral encapsulated melanoma tumor vaccine‖ as a collaborative research project, funded by the Georgia Research Alliance, with Dr. Periasamy Selvaraj from Emory University. We are currently also working on another grant funded by the Georgia Research Alliance in collaboration with Dr Sang-Moo Kang from Emory University on the ―Formulation and testing of oral nano-encapsulated influenza vaccines‖. We have also just received a grant from the Georgia Cancer Coalition for ―Nanosphere based targeted oral vaccines for breast cancer‖. We hope to obtain some encouraging results specifically in terms of generating a strong immune response after oral vaccination. Submitted by: Anne Fitzpatrick, Emory University Severe asthma in children is a complex disorder characterized by ongoing symptoms and extreme morbidity despite aggressive treatment with high-dose inhaled and oral corticosteroids. Although the pathophysiology of severe asthma is complex and not well understood, symptoms are thought to result from persistent airway inflammation and oxidant stress, with respiratory infection as a major trigger. Once infected, asthmatics have more severe lower respiratory tract infections with greater symptom persistence. The underlying biological mechanisms responsible for this aberrant response to respiratory infection in asthmatic children are unclear. Through clinical and translational research studies, my research program is focused on the cellular and biochemical derangements in the lung that are associated with severe asthma in children. We have previously demonstrated unique differences in the airway environment of children with severe asthma characterized by increased reactive oxygen species formation, lipid peroxidation, and loss of the protective antioxidant, glutathione (GSH). We have further shown impairment of alveolar macrophage (AM) function in children with severe asthma evidenced by decreased phagocytosis of pathogenic bacteria and increased AM apoptosis which are restored by GSH treatment. These data suggest that oxidant stress and GSH depletion may regulate the response to respiratory infection in children with severe asthma. While the broad, long- term goal of this research is to better understand the molecular mechanisms associated with respiratory infection, airway symptoms and AM dysfunction in children with severe asthma, we also hope to utilize these data to develop novel antioxidant therapies to improve airway innate immune defenses in this population. Submitted by: Stephanie Foster and Andrew Dent, Geospatial Research, Analysis and Services Program, CDC See poster abstract listed previously for Andrew Dent Submitted by: Eric Gilbert, Georgia State University Constructing Polymicrobial Biofilms with Defined Cell Compositions Bryan Stubblefield, Kristen Howery, Wendy Cardenas and Eric Gilbert Biology Department, Georgia State University, Atlanta, GA 30303 Multiple antibiotic resistant biofilms may potentially develop from bacteria that benefit one another via complementary antibiotic detoxification. We determined that two strains of Escherichia coli could establish a biofilm by simultaneously inactivating inhibitory concentrations of ampicillin (Amp) and spectinomycin (Spt). An asymmetry existed in the detoxification efficiency of the two strains; thus we predicted that varying their ratios at the substratum would influence the ability of a biofilm to form. To test this hypothesis, the areal cell density of each strain at the onset of biofilm formation must be controlled. To accomplish this, we recirculated cells suspended in 50 mM phosphate buffer for up to 4 h through parallel plate flow cells and enumerated cells attached to the substratum by confocal microscopy. Amp-resistant cells were labeled with green fluorescent protein and were visually distinct from red- stained Spt-resistant cells. A linear relationship was observed between the cell density of the recirculated suspension and the areal density for each strain alone. Following the reproducible attachment of the initial population, the second strain of cells could be linearly introduced into the flowcell, forming a monolayer at the biofilm substratum with defined cell composition. We will use this approach to investigate the effect of substratum cell composition on the development of mature polymicrobial biofilms. Submitted by: Jason Goldstein, Centers for Disease Control, Division Scientific Resources/NCPDCID The Biologics Branch within the Division of Scientific Resources provides the CDC Laboratories with expertise devoted to Quality System Essentials (QSE) and current Good Manufacturing Practices (cGMP) in development, production, and distribution services. In addition to a large variety of services and products (cell lines, Collaboration Roundtable Poster Abstracts P. 6 commercial/custom buffers and growth media), the Branch provides reagents that are customized to infectious organisms and agents. These include 1) biologics inventory management and distribution services, 2) pilot-scale reagent and in-vitro diagnostic device production, and 3) the development and manufacturing of novel gene products, protein reagents and diagnostic assays. We provide a custom service for the development of novel polyclonal and monoclonal antibodies through our Hybridoma Facility. The Protein Science Team provides and characterizes antigen preparations for selective immunizations as well as screening for selection of clones. Our expertise is focused in the affinity purification and biochemical characterization of immunoglobulin classes from mouse, rabbit, goat and human sources. Within the Laboratories for Gene Expression, Protein Production and Analytical Biochemistry, we focus on recombinant antigen and protein projects through various prokaryotic and eukaryotic expression systems. We employ new and classical biochemical methods for the isolation, purification and characterization of antibodies, recombinant proteins and native antigens. Our biochemical analysis elucidates protein structure and functionality, post-translational processing, and macro-molecular complexes. We maintain a Biosafety Level 3 Laboratory with clinical, diagnostic, training, research and production capabilities where work is performed on microorganisms that may cause serious or potentially lethal disease. The Quality Assurance Program within DSR has developed and implemented Quality Manufacturing Systems for the production of biological reagents and in-vitro diagnostics. Under the Program‘s guidance our laboratories ensure the highest quality services and reagents for our collaborators and clients. Submitted by: Gerardo Gutierrez-Sanchez, University of Georgia The molecular mechanisms that determine survival, differentiation and movement in multicellular organisms are dependent on interactions with the extracellular matrix (ECM). Cells in tissues are structurally and functionally integrated with their surrounding ECM via numerous dynamic connections. This matrix is composed of a variety of macromolecules that are secreted locally and assembled into an organized meshwork in close association with the surface of the cell that produced them. Two main classes of extracellular macromolecules make up the matrix: (1) polysaccharide chains of the class called glycosaminoglycans (GAGs), which are usually found covalently linked to protein in the form of proteoglycans, and (2) fibrous proteins, including collagen, elastin, fibronectin, and laminin, which have both structural and adhesive functions. The most common GAG structures are chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), hyaluronic acid (HA), and heparin. A major function of cell surface proteoglycans is in cell adhesion and migration, dynamic processes that are mediated through interactions between the proteoglycans GAG chains and extracellular matrix components, such as laminin, collagen, and fibronectin. Proteoglycans also occur as integral components of basement. Substantial evidence has accumulated over the last decades, indicating that GAG chains can impact cancer progression either positively or negatively. GAG chains, through binding and regulation of a formidable number of ligands, are important mediators of tumor cell and normal cell behaviors such as proliferation, differentiation, migration and adhesion. Therefore, many researchers are interested in this class of carbohydrates because of their roles in various cell surface phenomena such as cell– cell interactions, cell adhesion, and tumor metastasis. To elucidate these phenomena, it is essential to identify the biological molecules that recognize these carbohydrates and characterize quantitatively the interaction between the carbohydrates and their recognition molecules. To do so requires immobilization of carbohydrates, often on microtiter plates. We believe that immobilization on SPR chips provides a route to a much more quantitative of GAG-receptor interactions. The importance of the chemistry chosen to immobilize heparin to perform protein binding experiments using SPR has been previously demonstrated (Osmond et al., 2002). Results suggest that immobilizing heparin to a surface via multiple intrachain modifications of the heparin molecule can affect the binding of particular heparin-binding proteins. In our laboratory we have developed an appropriate method by which the pectin or GAG is biotinylated through the reducing end and bound to the surface of the SPR chip. This provides a surface with a relatively ―native‖ presentation of the GAG chains. Using this approach, we have successfully biotinylated different types of GAGs for conjugation to SPR chips. We present some examples of the use of SPR technology and this GAG immobilization chemistry to study protein-GAG interactions. Submitted by: Brantley Herrin, Emory University The jawless vertebrates, lamprey and hagfish, possess a second type of adaptive immunity that utilizes variable lymphocyte receptors (VLRs) composed of leucine-rich repeat (LRR) modules for antigen recognition, rather than immunoglobulin-based receptors. In the germ-line configuration, the two VLR genes (VLR-A and VLR-B) contain only invariant N-terminal and C-terminal sequences separated by a non-coding intervening sequence, however, they are flanked by hundreds of LRR gene segments. During lymphocyte development, the LRR gene segments are randomly and sequentially copied into the incomplete VLR gene to assemble a potential repertoire of >10^14 distinct antigen receptors. Immunization with particulate antigens induces VLR-B+ lymphocytes to divide and differentiate into plasmacytes that secrete multivalent VLR-B ‗antibodies‘ composed of 8 – 10 disulfide-linked uniform subunits. Antigen-specific VLR-B clones are isolated by screening the tissue culture supernatants of HEK-293T cells Collaboration Roundtable Poster Abstracts P. 7 transfected with VLR-B cDNA library plasmids for antigen binding. Monoclonal VLR-B antibodies can distinguish between antigens with 90% sequence identity and retain antigen binding capability after exposure to extremes of temperature and pH. Sequence analysis, mutagenesis, and crystal structure analysis have demonstrated that the antigen-binding site resides in the beta-sheets of the LRR subunits and a loop contributed by the LRR-CT region. The specificity, avidity, and stability of these unusual LRR-based monoclonal antibodies suggest they will have many biomedical uses. Submitted by: Robert (Jeff) Hogan, University of Georgia Significance of caveolin 1 and clathrin in SARS coronavirus replication T. Jelesijevic1, E.W. Uhl1 and R.J. Hogan2. 1Department of Pathology, 2Department of Radiology and Anatomy, University of Georgia Athens, Georgia Severe acute respiratory syndrome (SARS) is characterized by influenza-like symptoms and severe disease of the lower respiratory tract. It is caused by a positive-sense, single-stranded RNA virus (SARS coronavirus, SARS-CoV). SARS- CoV replication cycle is highly complex, and the mechanism(s) of pathogenesis remain unclear. With this in mind, we employed an RNA interference (RNAi) based approach to investigate which cellular proteins are involved in successful viral replication. The gene silencing was based on activation of polyprotein complex Ribonuclease Inducing Silencing Complex (RISC) with double stranded small interfering RNAs (siRNAs). The RISC, guided by sense/antisense sequences of siRNAs, bind and cleave cellular mRNAs and results in decreased translation of targeted cellular genes. Using siRNAs targeting 125 membrane trafficking and 50 nuclear receptor genes, we performed a set of experiments in vitro using Vero E6 cells and 3 different strains of SARS-CoV. Our initial results identified several cellular genes that may be important for viral replication. Among the genes identified, caveolin1 and clathrin appeared to be critical in the virus life cycle. When transfected with both caveolin1 and clathrin siRNAs, between 60% - 80% of Vero cells survived while the survival rate for infected, non-siRNA treated cells was from 10- 20%. Ongoing studies are aimed at investigating whether failure of SARS-CoV replication is at the point of entry or during the final stages of viral assembly and release. Submitted by: Baoming Jiang, CDC Rotavirus is the most common cause of severe dehydrating diarrhea in young children and is responsible for over 500,000 deaths per annum. The two newly licensed live oral vaccines (LOV), RotaTeq® and Rotarix®, have been demonstrated effective against severe rotavirus diarrhea among children in developed and mid income countries. However, the efficacy of neither vaccine has been demonstrated among children in resource-poor countries where a vaccine is needed most. Preliminary results of the ongoing immunogenicity and efficacy trials of the two vaccines in Asia and Africa have raised concern that either vaccine may not provide adequate protection in these settings. In addition, safety of these vaccines (e.g., intussusception and pneumonia) remains a concern as well. We have pursued inactivated rotavirus vaccine (IRV) as a backup strategy for LOVs. IRVs have several potential advantages. They are more uniformly reliable than oral vaccines when used in different settings. They would be less costly to test since intussusception is not an issue. They could be combined with other parenteral EPI vaccines and more easily delivered to children throughout the world. Finally, they do not replicate so their efficacy should be free of interference from maternal antibody in the gut, a problem that may inhibit the take of LOVs. We have conducted studies in monkeys and children and demonstrated that serum IgG is either an effector or a proxy against rotavirus infection and disease. These studies have established proof of principle for the protective role of serum antibody. We have developed human rotavirus vaccine pre-seed strains with specificity to major serotypes and demonstrated robust growth in cell culture and high yields. We have developed a novel, safe and robust method that effectively inactivates rotavirus but maintains the integrity of virus particles. Our IRV when formulated with adjuvant aluminum and administered intramuscularly induces a strong serum antibody response in mice and macaques and protects against oral challenge in gnotobiotic piglets. Currently we are looking for a jointly collaborative effort to examine and compare the immunogenicity and protective efficacy of intramuscularly and subcutaneously administered IRV in animal models. Submitted by: Alison Kelly, CDC/Coordinating Office for Global Health CDC is currently developing a global health research agenda to complement and support its global health strategic plan. Input is being sought on high-priority, high-impact research questions which are evidence-based, cross-cutting, relevant, unique, scientifically feasible, and actionable. Categories of research under development include: intervention scale-up, maternal and newborn health, global public health capacity development, policy change, surveillance system enhancement, social determinants of health, technology development, epidemiologic and etiologic. Participants in this poster session will have an opportunity to review CDC's work to date on the development of its global health research agenda and provide input to further develop and refine the agenda. Collaboration Roundtable Poster Abstracts P. 8 Submitted by: Kim Klonowski, University of Georgia An effective long-term vaccine against influenza virus has not yet been achieved. One problem contributing to the ineffectiveness of flu vaccines is the deterioration of memory CD8 T cells from the lung airways early after infection. While a secondary pool of memory cells continue to be recruited to the site, these cells represent inferior replacements. IL-15 is a cytokine important for the maintenance of CD8 memory cells and in other systems can induce lymphocyte migration. We believe that deficiencies in the levels of IL-15 or the types of cells recruited by IL-15 is responsible for the lack of protection in the airways. Our studies using IL-15-/- mice demonstrate that IL-15 is important for maintenance of flu-specific memory CD8 T cells in distinct locales. In vitro migration studies suggest that IL-15 may be important for migration of CD8 T cells. RT-PCR studies also confirm that IL-15 is differentially regulated after flu infection. Together these data suggest a role for IL-15 in controlling multiple aspects of memory CD8 T cell responses to flu infection. (NIH grant AI077038 (KDK)). Submitted by: Zsuzsanna Kuklenyik, CDC/NCEH Division of Laboratory Science On-line coupling of a microfluidic enzyme reactor with reverse phase chromatography and mass spectrometry detection for quantitative measurement of protein toxins Zsuzsanna Kuklenyik,a Shyam Aravamudhan,b Anne E. Boyer,a Paul Joseph,b and John R. Barra Centers for Disease Control and Prevention, Division of Laboratory Sciences Georgia Institute of Technology, Micro Electronics Research Center Atlanta, GA The enhanced sensitivity and speed is a well established inherent feature of miniaturized sample preparation platforms because of increased specific interface, reduced diffusion distance and reduced diffusion time. These inherent features can be exploited for ―micro total analysis systems‖ or ―laboratories-on-chips‖ where all components of sample analysis, analyte purification, liquid handling, analyte detection, and data analysis can be performed in an integrated and automated fashion on microfabricated chips. The purpose of this on-going project is the development of an integrated microfluidic platform that is capable of performing sensitive and specific enzymatic assays for detection of protein toxins. The platform is designed to capture the protein toxins using antibodies cross linked to magnetic beads. The magnetic beads are loaded into chambers containing NiFe micro strips. The alignment of the beads inside the channels along the NiFe strips prevents clogging and high back pressure, avoiding a major drawback of packed bed microfluidic reactors. At the current proof-of-concept stage, the microfluidic reactor was connected in-line with a liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis system, where the enzyme reaction products are continuously collected on a HPLC column. Following the enzyme reaction, the products are automatically eluted from the HPLC column and detected by MS/MS. This project is collaboration between the Microelectronics Research Center at Georgia Institute of Technology where the fabrication work was performed, and the Division of Laboratory Sciences at National Center for Environmental Health where the prototypes were tested for measurement of anthrax lethal factor. Submitted by: Amrita Kumar, Emory University School of Medicine Commensal enteric bacteria, which can also be used as probiotics, positively affect epithelial barrier integrity after injury. Restoration of epithelial barrier functions following injury requires epithelial cell migration also referred to as restitution. Cell migration in turn is dependent on dynamic turnover of focal cell-matrix adhesions (FACs). The mechanisms by which commensal bacteria regulate cell migration after injury are however not understood. Thus, our objective was to define such mechanism(s). We show that in vitro interaction of cultured model epithelia with the commensal bacterial strain Lactobacillus rhamnosus, resulted in significant increase in cell adhesion, spreading and wound closure. This was associated with phosphorylation/activation of key FAC proteins, focal adhesion kinase (FAK) and paxillin within 5 minutes of bacterial contact. Furthermore, bacterial colonization of cultured epithelial cells resulted in rapid and reversible generation of reactive oxygen species (ROS), that mediated oxidative inactivation of a FAK phosphatase, PTEN, thus inducing sustained FAK activation. These observations demonstrate that commensal/probiotic bacteria modulate epithelial barrier recovery by stimulating ROS production that consequently modulates the phosphorylation of FAK. Submitted by: Anh Le, Emory University BIOMARKERS OF CARDIOVASCULAR DISEASE Ngoc-Anh Le, PhD Associate Professor of Medicine Director, Emory Lipid Research Laboratory Emory University and Atlanta VAMC The research interest of our group in biochemical markers of cardiovascular disease. In addition to original research, our laboratory has the capacity to provide core laboratory services for other investigators as well as multicenter trials. We provide basic Collaboration Roundtable Poster Abstracts P. 9 lipid/apolipoprotein measurements including lipoprotein subclasses by NMR as well as specialized assays of inflammatory markers (hsCRP, Lp- -associated oxidation (oxLDL, TBARS, nitrotyrosine-modified proteins, oxidative susceptibility of isolated lipoproteins). In addition to working with human plasma, our laboratory can also support lipid/lipoprotein research in animals. Using a semi-automatic FPLC plasma. We are currently supporting research in patients with CAD, diabetes mellitus, obesity, NAFLD, CKD, stroke, and HIV. In our research, we are focus on meal-induced changes in oxidative stress in humans. Using a number of different assays we have reported in vivo evidence for the direct generation of oxidatively modified epitopes in the plasma of patients with documented CAD following the consumption of a standardized fat-containing meal. We have subsequently demonstrated that this response is specific for the highly oxidizable polyunsaturated fatty acids and could not be demonstrated with meal enriched in saturated or monounsaturated fatty acids. We are currently evaluating interventions that may modulate meal-induced oxidative stress in humans. Submitted by: Keri Lubell, CDC Background: CDC‘s risk communication strategy for public health emergencies is developed by CDC‘s Emergency Communication System (ECS) as health threats are emerging and/or emergency response is required. ECS strategy is based on communication science and rapid assessment of public knowledge, attitudes, and behaviors (KABs) related to both the nature of the emergency and the particular health threat. Assessing public concerns and beliefs about the threat is critical to development of an effective communication response. During emergency health threats, ECS‘ Research Team conducts daily scans of traditional news media stories (print, internet, and television), blogs, and public inquiries to CDC INFO (phone calls and e-mails). Based on our analysis of these materials, we identify key news themes that may affect public perceptions of the emergency and influence adherence to public health recommendations. We also highlight critical information gaps, points of possible confusion or misinformation, pressing public information needs, and potentially important issues likely to emerge in coming days. A daily report summarizing this assessment is used by ECS leadership as the foundation for CDC‘s emergency communication strategy development. Process: The poster presents 1) the overall data collection approach we use to identify relevant news stories from multiple media outlets in each 24-hour cycle, 2) how we tailor the process to focus more on local outlets where affected groups are most likely to look for credible information and health guidance, 3) how we conduct a systematic ―content analysis‖ to generate the findings summarized in the daily report, and 4) examples from recent events and activations. Conclusion: The rapid and ongoing nature of the assessments compiled in the daily report helps ensure that agency messaging is responsive to the public‘s information needs as the situation evolves. It thereby enhances ECS‘ ability to create effective emergency communication messages that can influence public beliefs, attitudes and knowledge related to health threats. Submitted by: Marguerite Madden, University of Georgia GIS and Remote Sensing for Infectious Disease Studies Marguerite Madden, Thomas Jordan, Janna Masour Center for Remote Sensing and Mapping Science (CRMS) Department of Geography, UGA and Joseph Corn, David Stallknecht Southeastern Cooperative Wildlife Disease Study College of Veterinary Medicine, UGA The University of Georgia‘s (UGA) Center for Remote Sensing and Mapping Science (CRMS) has worked cooperatively with the UGA Southeastern Cooperative Wildlife Disease Study (SCWDS) on a number of projects involving the use of remote sensing, geographic information systems (GIS) and Global Positioning System (GPS) technologies in support of wildlife infectious disease studies. All projects involve the visualization of disease occurrences or landscape analysis including vegetation mapping, 3D terrain analysis and landuse change to assess environmental factors influencing disease outbreaks. Specific examples include: • Mapping distributions of exotic ticks known to be the vectors of diseases to animals and humans; • Assessing U.S. feral swine distributions and spatial coincidence with domestic swine populations; • Spatial patterns of wildlife associated with dairy farms for Johne‘s Disease in Georgia and Wisconsin; • Deriving spatial data sets for logistic regression linking West Nile virus live bird surveillance in Georgia to environmental and climatic variables; and • Spatio-temporal analysis and modeling of a 20-year database of nation- wide county surveys on reports on hemorrhagic disease in white-tailed deer (Odocoileus virginianus). Our current cooperative effort involves the development and implementation of a web-based mapping interface that allows state and regional wildlife experts to access and edit a map of U.S. feral swine distributions. Procedures were developed for wildlife managers to view the map of feral swine populations superimposed on satellite image data in Google Maps. The images provide a geographic reference for uses to add new populations, delete areas where feral swine have been removed and change map lines to reflect current swine distributions. The edited feral swine map is submitted to SCWDS for review and quality control checking via a password protected web site. As soon as the quality control is complete, the up-to-date map is quickly posted back to the website. The intent of this project is to provide local experts with easy-to-use geospatial tools to continually revise feral swine maps and assist farmers who Collaboration Roundtable Poster Abstracts P. 10 must take precautionary measures to prevent the spread of infectious diseases from feral swine to their domestic stock. Submitted by Michael McNeil, CDC Title: The Vaccine Analytic Unit (VAU): A Collaborative Vaccine Safety Research Infrastructure Using the Defense Medical Surveillance System (DMSS) Michael M. McNeil MD MPH1, Susan K. Duderstadt MD MPH1,2, Theresa M. Real PhD1,2, 1Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 2Logistics Health Incorporated Abstract Background: The VAU is a collaboration between CDC, DoD and FDA to assess unusual, longer term anthrax vaccine adverse events utilizing the DMSS. The VAU is a critical component of the CDC‘s Anthrax Vaccine Safety and Efficacy Research Program. Attributes: The DMSS is an active surveillance system administered by the DoD to integrate data from miltary treatment facilities, vaccination centers, and military personnel offices worldwide. Inpatient and outpatient diagnosis data are coded using ICD-9-CM codes. The DMSS is a valuable resource for investigating vaccine adverse events. The DoD also maintains a serum repository, which holds great potential for the assessment of specific identified adverse events for biologic plausibility and possible causative mechanisms. Population: All U.S. active duty and reservist service personnel. Project Description: The VAU‘s research agenda was established with input from the NVAC. Completed research activities include quality assessments of immunization data in DMSS, database hypothesis testing studies (optic neuritis, concurrent vaccinations, type 1 diabetes mellitus, and atrial fibrillation), and a pilot hypothesis generation/data mining study to evaluate a possible association of concurrent vaccinations and military hospitalizations. Ongoing and planned activities include hypothesis testing studies with medical chart diagnostic validation (Stevens Johnson syndrome, diffuse connective tissue diseases), database studies (unintentional injuries, autoimmune thyroid disease), data mining studies including an evaluation of Rapid Cycle Analysis for vaccine adverse event monitoring in DMSS, and a seroepidemiologic study of vaccine-associated Guillain Barré syndrome. Current Status: The VAU has increased understanding of the safety profile of anthrax vaccine and complements other post-marketing vaccine safety systems (Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink). Importantly, the VAU provides a platform for the conduct of timely investigations of vaccines administered in the DoD population which have critical implications for ―civilian‖ public health. Submitted by: Ross Molinaro, Emory University We have developed and validated a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the identification and quantitation of iothalamate in biological samples to better assess renal function by calculating glomerular filtration rate (GFR). Current methods using iothalamate to calculate GFR have long run times and lack the analytical sensitivity allowing a reduced iothalamate dosage. After the addition of iohexol as the internal standard, iothalamate is isolated from plasma by methanol extraction and urine by quick-spin filtration. Gradient chromatographic separations were performed on a reversed-phase dC18 column using an ammonium acetate/formic acid mobile phase. Iothalamate demonstrated a reproducible elution time of 0.8 minutes while iohexol, the more non- polar compound, consistently eluted from the column at 0.9 minutes. Both iothalamate and iohexol were monitored in the multiple-reaction monitoring (MRM) mode (Waters Quattro Micro) using the hydrogen adduct mass transitions. Primary (614.5>360.5, iothalamate; 821.6>652.3, iohexol) and secondary (614.5>486.5, iothalamate; 821.6>730, iohexol) ion ratios were calculated as an additional check of compound specificity. This method requires only a 3 minute run-time per sample. The iothalamate standard curve for plasma and urine displayed a wide measuring range with linearity up to 600 µg/mL and a limit of quantitation at 18.75 ng/mL. Acceptable precision (CVs ≤ 9.3 %) was demonstrated by both within-run and between-run experiments using drug-free plasma and urine spiked with known low, medium, and high concentrations of iothalamate. Ion suppression was tested by sample addition and infusion assays. Recovery from plasma and urine samples ranged from 93.6% to 104.1%. Accuracy was assessed using 50 urine and plasma samples tested by LC-MS/MS and an accepted capillary electrophoresis (CE) assay. The equations of the linear regression lines were; UrineLC/MS/MS = 0.959×UrineCE – 1.351, (r = 0.98, SY/X = 11.2); PlasmaLC/MS/MS = 1.064×PlasmaCE – 0.317, (r = 0.89, SY/X = 0.94); GFRLC/MS/MS = 1.005×GFRCE – 5.264, (r = 0.92, SY/X = 10.3). GFR was calculated using the patient‘s urine flow rate and plasma and urine iothalamate values. We have developed and validated a fast, accurate LC-MS/MS assay to calculate GFR in patients that can serve to determine renal efficiency in potential kidney donors. In addition, the sensitivity of this assay holds promise for allowing a smaller dose of iothalamate to be administered to patients thereby reducing the chances of iothalamate hypersensitivity. Collaboration Roundtable Poster Abstracts P. 11 Submitted by: Teresa Morrison, CDC Asthma Prevalence by Urban-Rural Status — United States, 2005 Teresa A. Morrison, D. Callahan, J. Moorman, C. Bailey Background: Approximately 20 million persons in the United States have asthma. Identifying populations with high asthma prevalence focuses resources to reduce disease burden. Although geographically narrow studies suggest that asthma prevalence is higher in urban versus rural areas, a multi-state urban-rural comparison has not been done. We analyzed data from a national survey to determine prevalence by urban-rural status. Methods: We linked the 2005 Behavioral Risk Factor Surveillance System (BRFSS) to Urban Influence Codes (UIC) from the U.S. Department of Agriculture. BRFSS is an annual state-based telephone survey that uses a disproportionate stratified sampling plan to collect health data from non-institutionalized adults. In 2005, all 50 states asked about asthma. UICs categorize counties based on population size and adjacency to metropolitan areas. We classified these UIC categories into four groups (metropolitan, adjacent-metropolitan, micropolitan, and remote) to define urban-rural status. By using SUDAAN, we calculated weighted estimates for complex sample design and multivariate logistic regression to generate adjusted odds ratios (ORs) for the association between current asthma and urban-rural status while controlling for sociodemographic and health behaviors. Results: Overall asthma prevalence was 7.9% (95%CI=7.73–8.08). Although asthma prevalence was highest among micropolitan residents (8.6%; 95%CI=7.84– 9.36) and lowest among metropolitan residents (7.8%; 95%CI=7.65–8.05), prevalence across urban-rural categories was not statistically different (p<0.28). After we adjusted for sociodemographic and health behaviors, adjacent metropolitan (OR=0.91; 95%CI=0.85–0.97) and remote (OR=0.87; 95%CI=0.78–0.98) residents were less likely to report current asthma compared to metropolitan residents. Conclusions: Current asthma prevalence is as high in rural areas as in urban areas. Characteristics unique to residence impact disease burden. Allocating resources to address these environmental influences may reduce asthma prevalence. Submitted by: Mary Ohmer, Georgia State University Title: Building Community Capacity to Prevent Violence: Findings from a Pilot Project to Facilitate Collective Efficacy among Residents (Ohmer, M., Warner, B., & Beck, E.) Research demonstrates that collective efficacy, including social cohesion/trust and the willingness of neighbors to intervene in neighborhood problems and inappropriate behaviors, is associated with lower levels of community crime and violence (Morenoff, Sampson, & Raudenbush, 2001; Sampson, Raudenbush, & Earls, 1997). This poster presents findings from a training project designed to facilitate collective efficacy and informal social control among residents. The program taught residents skills to directly intervene in inappropriate neighborhood behaviors in a respectful and supportive manner, using the principles of restorative justice; and taught residents consensus organizing strategies for building trusting relationships with other residents and external stakeholders, thus enhancing social cohesion/capital; and helping residents identify and establish community norms supporting prosocial behavior and mutual trust. The program took place in Thomasville Heights, a low-income neighborhood in Atlanta, and consisted of six 90 minute sessions involving a combination of lecture, discussion, role plays and homework. Sixteen participants were recruited who were active in their community and/or were interested in gaining skills in community violence prevention. Data were collected using quantitative and qualitative methods, including a pre- and post training survey. Participants‘ average length of neighborhood residency was 6.5 years; most were African American (93%) and female (69%). Half completed high school/GED, 38% some college, and 12% a college and/or graduate degree. Only 25% were employed full-time, and the rest were retired or disabled (19%), and unemployed or full-time students (13%). Most participants also had low-incomes (65% earned less than $20,000/year). The survey asked participants about their attitudes toward intervening (@=.81), likelihood of and confidence in intervening in a variety of hypothetical situations, and what they were most likely to do when they intervened. Results were analyzed quantitatively using paired samples t-tests, and qualitatively according to themes. One way significance tests were conducted, as it was hypothesized that the training would improve participants‘ attitudes towards intervening and increase participants‘ likelihood of intervening and confidence in intervening. The t- test (N=15) demonstrated that the mean scores regarding participants‘ attitudes about intervening (p<.05) and their likelihood to intervene (p<.05) increased significantly from pre- to post-test; however, their mean scores regarding their confidence in intervening did not increase significantly (p=.29; p=.17). Participants who stated that they were ―very likely‖ or ―likely‖ to intervene in two of the hypothetical situations (a couple fighting, a neighbor having loud parties) were asked what they were most likely to do when they intervened. The results demonstrated that over half to most participants stated they would use only indirect intervention strategies (e.g., calling the police or 911) prior to the training; while afterwards most would use direct intervention (e.g., non-threatening strategies such as talking to the individuals) or a combination of direct and indirect intervention strategies. The results of this study contribute demonstrate the importance of facilitating collective efficacy and informal social control among residents as a strategy for building community capacity to prevent violence. Collaboration Roundtable Poster Abstracts P. 12 Submitted by: Chima Ohuabunwo, Grady Health System Health Outcomes Center & Department of Medicine, MSM ABSTRACT Title: Evaluating Telemetry Utilization in a Large Inner-city Academic Medical Center Background: Cardiac telemetry is costly and requires continuous human surveillance. Following its increasing use in non-critical care settings, the American College of Cardiology (ACC) published guidelines for in-hospital cardiac monitoring. Our institution and others adopted telemetry policies based on these criteria. Objective: Evaluate the appropriateness and outcomes of telemetry admissions, characterize the arrhythmias detected, and determine the use of cardiology consultations based on telemetry event as a surrogate for influence of telemetry findings on physician practice. Design and Setting: Medical records of all new telemetry admissions at the Grady Health System (GHS), a large inner-city academic medical center during a two-month period were prospectively studied for their entire telemetry stay. Two authors classified the patients using the ACC criteria and the GHS telemetry policy. Measurements and Statistical Methods: The appropriateness of telemetry admission based on the GHS telemetry policy and ACC classes I and II were determined along with other telemetry process and outcome measures. The degree of agreement between the ACC guideline and our institution‘s telemetry policy was computed as the kappa coefficient. Chi Square, or Fisher exact test compared categorical group parameters. Variation in telemetry LOS between groups was compared using the Mann-Whitney and the Kruskal Wallis non-parametric tests. Multiple regression analysis was done to ascertain predictors of telemetry LOS. Results Of the 120 patients, 58.3%, 23.3% and 18.3% were in ACC class1, II, and III respectively. The appropriate admissions rate was 81.6% per ACC criteria and 83% per the GHS telemetry policy. The degree of agreement or the interrater reliability between the ACC classification and our institution‘s policy was 0.89 (Kappa coefficient). The overall incidence of telemetry events was 32.3% with 5.8% being major and 27.5% minor events or arrhythmias. No major events occurred among the inappropriate admissions. Telemetry LOS was longer among the major than minor events group (7.8 versus 3.4 days, p=0.01). Type of telemetry event was a predictor of LOS (p=0.0001). The occurrence of major telemetry event was associated with cardiology consultation (p = 0.03). Conclusions: There was greater than 80% appropriate telemetry utilization and compliance with ACC guidelines at this site but opportunity for improvement remains. Agreement between ACC and GHS telemetry guidelines was very good. The low incidence of major telemetry events might question the effectiveness of current ACC criteria. Institutional measures alongside ACC guidelines are necessary for appropriate telemetry utilization Submitted by: Michael Powell, Morehouse School of Medicine Our lab group is involved in research to investigate the role of Nef in the pathogenesis of AIDS. We have found that Nef is secreted from infected cells in vesicular form and is present in patient plasma. Vesicular Nef can interact with uninfected T cells and induce apoptosis. Therefore, secreted Nef vesicles may play a key role in T cell depletion and dysregulation of the immune system. Submitted by: Mark Prausnitz, Georgia Tech Seasonal influenza causes up to 1.5 million deaths worldwide each year. Pandemic influenza killed up to 50 million people during the three pandemics of the last century. Our ability to deal with a future pandemic is limited in large part by inadequate methods to rapidly vaccinate against new threats. Hypodermic injection of vaccine by medical personnel is extremely time consuming, as seen during the prolonged and inefficient annual influenza vaccination campaigns. To expedite mass vaccination, this project seeks to develop microneedle-based vaccine patches that can be self-administered; do not produce sharp, biohazardous waste; and are low cost. Such patches could be rapidly distributed through pharmacies, fire stations or even the U.S. mail. Because microneedle patches target delivery to skin‘s dendritic cells, stronger mucosal and cellular immune responses can be achieved. To accomplish these goals, this project has two Specific Aims. Aim 1 seeks to design and characterize microneedle systems to deliver influenza vaccines to skin. Novel microfabrication techniques are being developed to make microneedles that easily insert into skin to rapidly deliver vaccine to targeted depths. Microneedle designs are studied using cadaver skin, living human skin explants, and human subjects to determine microneedle mechanical properties; stability during processing and storage; controlled dose targeting and kinetics of vaccine delivery; and safety. These studies are producing microneedles designed to meet the needs of mass immunization against pandemic influenza. Aim 2 seeks to evaluate the efficacy of influenza vaccines delivered using microneedles and determine the role of antigen presenting cells in immune activation. Virus-like particles, purified protein, and DNA vaccines against the H5 influenza strain are being delivered using microneedles to mice and hairless guinea pigs. Microneedle design and vaccination protocol are being optimized based on measuring humoral immune responses, cellular immune responses, memory B cell repertoire, and protection against virus challenge. Cellular pathways to immunity are evaluated by identifying the role of dendritic and other antigen-presenting cells in immune activation. Collaboration Roundtable Poster Abstracts P. 13 Submitted by: Mary Reynolds, CDC, Poxvirus and Rabies Branch Monkeypox: Applying Lessons Learned from Disease-specific Control Strategies to Overall Capacity Building Goals ABSTRACT: In the era immediately following smallpox eradication, relatively little research was performed to address basic issues relating to the pathogenesis and treatment of orthopoxvirus infections, including monkeypox, smallpox and vaccinia. It is only during the last decade—and principally as a consequence of bioterrorism concerns—that modern technologies have been applied to the development of rapid diagnostic assays, drugs and vaccines. Many of these technologies and medical advancements were conceived to combat smallpox but have likely additional utility in the context of extant, naturally-occurring orthopoxvirus infections of humans. Nevertheless, significant barriers exist to adapting and delivering new technologies to resource poor settings and communities in need. The public health infrastructure, vital for identification and prevention of orthopoxvirus-associated diseases such as monkeypox, has experienced declines in many parts of Africa, while at the same time smallpox vaccine-derived population-level immunity has eroded. Consequently, monkeypox, which is endemic to West Africa and the Congo Basin, may go unrecognized and undiagnosed while yet increasing in prevalence. This backdrop provides little opportunity to leverage newly developed technologies (vaccines, diagnostics, drugs etc.) that could have a positive impact on disease prevention. During the past five years, we, and others, have investigated several outbreaks of febrile rash illness suspected to be monkeypox in countries of the Congo basin; a serosurvey performed in the Republic of the Congo (RoC) in 2006 revealed evidence of recent foci of orthopoxvirus infections in several remote communities. To assist in strengthening recognition and prevention of monkeypox, we have initiated a multidisciplinary collaboration with representatives from the Ministries of Health, Research, and Natural Resources in RoC to enhance local diagnostic laboratory and outbreak investigation capacity (including promotion of ecologic and human disease surveillance). Difficulties encountered have included physical and supply-chain barriers which have impeded laboratory technology transfer, capacity deficits for scientific and ethical review of research protocols, and ineffective channels for communication with remote healthcare personnel, as well as among various partner agencies. Various strategies have been developed to deal with these issues, including increasing the number of partner face-to-face visits, and additional outreach to other agencies and organizations with appropriate expertise. This has for example led to the development of video based educational materials for health care workers designed to foster enhanced integration of clinical, epidemiologic and laboratory-based disease surveillance. We anticipate that partners are likely to benefit from this integrated approach, as it will ultimately promote use of systematic methodologies for disease identification and reduction, and will provide new opportunities to engage in useful and appropriate public health actions and clinical trial research. Submitted by: John Rose, University of Georgia Structural studies of the hepatitis B virus surface protein (HBsAg) aimed at developing next generation vaccines: a progress report John P. Rose1, Quentin Florence1, Hao Xu1, Jonny Yokosawa2, James Lara2 and Yury Khudyakov2, 1Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602 and 2Epidemiology & Bioinformatics, Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA 30333. The purpose of this study is to derive a 3-dimensional structure by X-ray diffraction of the HBsAg protein, which is the antigenic component of the currently licensed vaccine for hepatitis B virus (HBV). Despite its worldwide usage and its application as a carrier for epitope presentation, the tertiary structure of this important protein is still unknown. This lack of information has impeded the development of bivalent vaccines where HBsAg is used as a carrier for foreign antigenic epitopes. Additionally, the lack of this conformational information does not allow for understanding the effects of mutations, especially polymerase drug-resistance mutations in the region of the HBV genome overlapping with the HBsAg open reading frame, on antigenic properties of the HBsAg major neutralizing antigenic epitope. The first step in the X-ray structure determination process is the production of crystals of the protein under study. Initial crystallization trials on the HBsAg protein provided by the CDC have produced some promising hits. Results from the initial crystallization screen together with plans on crystal optimization will be presented. Work supported by a GRA/CDC Collaboration Planning Grant GRA.VAC09.G. Submitted by: Rebecca Rosen, Emory University/Yerkes National Primate Research Center Aβ multimers are structurally distinct in Alzheimer‘s disease and aged nonhuman primate brain R.F. Rosen1, A. S. Farberg1, B.J. Ciliax2,3, J.J. Lah2,3, M. Gearing2,3, J. Dooyema1, H. LeVine III4, J. A. Ghiso5, T.M. Pruess6,7, L.C. Walker3,6 1Graduate Program in Neuroscience, 2Ctr for Neurodegenerative Disease, Emory Univ, Atlanta, GA, 3Dept Neurology, Emory Univ, Atlanta, GA 4Sanders-Brown Ctr on Aging, Dept Biochemistry, Univ Kentucky, Lexington, KY, 5Dept Path and Psych, NYU Med Center, New York, NY, 6Yerkes Natl Primate Research Ctr, 7Dept Collaboration Roundtable Poster Abstracts P. 14 Path and Lab Med, Emory Univ, Atlanta, GA Aβ is a rapidly self-aggregating peptide that accumulates with age in both human and nonhuman primate brain. According to the amyloid hypothesis, the aberrant multimerization of Aβ is an upstream effector in Alzheimer‘s disease (AD) neurodegeneration. The Aβ peptide sequence is identical in humans and nonhuman primates. However, full spectrum AD has never been seen in an aged nonhuman primate. Because of their close biological relationship to humans, nonhuman primates are a unique model of nonpathologic Aβ accumulation. Clarifying the factors that govern the initiation and toxicity of Aβ aggregation in vivo could yield important clues to the uniquely human susceptibility to AD. To this end, we have extensively characterized cerebral Aβ populations in AD, aged chimpanzees, rhesus macaques, and squirrel monkeys. Using immunohistochemistry, ELISA, immunoprecipitation/ MALDI-TOF MS, Western Blot and in vivo Aβ-seeding assays, we found that Aβ populations are quantitatively and qualitatively similar in AD and nonhuman primate brain. To explain the pathological differences between humans and other primates, we hypothesized that higher-order structural features distinguish toxic Aβ in AD brain from the relatively benign Aβ in nonhuman primates. Recent reports show that Pittsburgh Compound B (PIB), a radioligand used for in vivo PET imaging of amyloid, binds with high affinity and stoichiometry to AD brain but with low stoichiometry to synthetic Aβ and to the Aβ deposits in transgenic mouse brain. We measured the binding of 3H-PIB to cortical homogenates from AD and nonhuman primate cases, all of which had been characterized for total soluble and insoluble Aβ levels. We found that 3H-PIB binds with low stoichiometry to Aβ in nonhuman primate cortical homogenates, even in cases with levels of Aβ equal to those in AD. These data suggest that cerebral β-amyloid deposits in aged nonhuman primates, which naturally develop cerebral β-amyloidosis over the course of many years, are structurally distinct from those in humans with AD, and that high-affinity PIB binding may be relatively selective for pathogenic Aβ in the AD brain. Supported by NIH RR-00165, P01AG026423, P50AG025688, Emory URC and a UK Faculty Research Support Grant. Submitted by: Don Rubin, University of Georgia The Southern Center for Communication, Poverty, and Health is a CDC-sponsored center for excellence in health marketing and communication. This center encompasses four major research studies as well as a public health workforce training unit, all focused on reducing health disparities through effective communication. One study examined lay understanding of genetics and disease and ways to reduce the resultant fatalism that can impede health behaviors. A second study examined resistance of minority youth to anti-smoking ads. People in poverty must often juggle multiple health risks. A third study examines the calculus people use to allocate concern and resources in dealing with those simultaneous demands. The fourth major study considered how many health recommendations can be optimally bundled in a single message, in this case in the context of prenatal health. Evidence-based lessons learned from these research projects include the following: (1) evoke empathy, (2) employ metaphors to render complex relations comprehensible, (3) thoroughly pretest messages with target audiences, (4) never mention genetic predisposition in isolation from behavioral determinants of disease, and (5) increase individual feelings of control over risks. Workforce training resources created include guidance on establishing liaison with Latino communities, strategies for pandemic flu planning with African American faith-based communities, and modules on working with the media and the public to be infused in MPH core classes. Submitted by: Kaori Sakamoto, UGA My research focuses on the host immune responses and pathology elicited by mycobacterial cell wall lipids in tuberculosis. Mycobacterial lipids are constantly produced and shed from phagocytosed bacilli, trafficking throughout the host cell and released in exosomes, making these lipids strong candidates for mediators of immunomodulation. We find that the mycobacterial lipid trehalose dimycolate (TDM) induces moderate cytokine responses, granulomagenesis, cachexia, and coagulopathies, while also inhibiting phagosome maturation. TDM synthesis is also upregulated in Mycobacterium tuberculosis after phagocytosis by macrophages. TDM in turn stimulates the up- and down-regulation of numerous macrophage genes involved in the immune response and tissue remodeling. A new research front is the investigation of the immunostimulatory properties of Mycobacterium avium paratuberculosis lipids, which may play a role in other granulomatous diseases, such as Johne‘s or Crohn‘s disease. My laboratory uses molecular, biochemical, cell biological, immunological, and histological methods to study the mechanisms by which mycobacterial lipids stimulate or inhibit the host immune response. We are also pursuing ways in which these lipids could be utilized prophylactically or therapeutically in the treatment of granulomatous diseases. The purpose of this poster is to present the techniques and analyses that my laboratory and collaborators can/will be capable of performing. Collaboration Roundtable Poster Abstracts P. 15 Submitted by: Kasumu Salawu, CDC-COTPER-DSNS-PPB [Demonstration on Laptop] Minimum Entropy Measure for Interobserver Agreement in Diagnosing Disease It is necessary to divide people in a population into one group that has a disease and another that does not, in order to understand how the disease develops and is transmitted. That initiates a search for appropriate and effective health care both in the clinical setting and in the public health arena where secondary prevention programs require early disease detection and intervention. As such, the quality – validity and reliability -- of diagnostic and screening tests is critical. The Kappa statistic is the most popular measure of interobserver percent agreement reported in medical literature. However, the debate continues as to the strength and biases of the method and several modifications have been proposed. In this paper, we borrow Shannon‘s Uncertainty Function from the field of Information Theory to join the debate and improve on a limitation of Kappa. Submitted by: Michael Schwartz, CDC Autism Spectrum Disorder (ASD) is thought to result from gene-environment interactions. Despite research progress in identifying candidate genes associated with ASD, no clear causative marker has been found, and as a result no directed search for a likely environmental trigger can be undertaken. We propose a novel computation approach to attempt to answer both questions at once. The purpose of our research is to develop a high-throughput computational toxicology methodology to screen for both the implicated gene variants and suspected environmental toxicants for further study using complementary laboratory screening of select candidate chemical-agent / genetic-variant combinations in the toxicology laboratory and through directed genetic association studies using biosample sets from ASD cohorts. The end result will be a high-throughput computational protocol which is available for screening of a wide range of neurodevelopmental and other disorders which have an implied gene-environmental basis. The method could be available for screening of a large number of gene and/or variant protein structures against an exhaustive database of toxicants when the causative mutation(s) are not known for a disease. High-Throughput Molecular Modeling (Docking) of ASD candidate gene products with common hazardous environmental agents will provide valuable and novel information concerning candidate genes and the potential environmental ligands implicated in disease pathogenesis. Identification of putative gene SNP variant(s) in ASD will facilitate rapid, directed genetic association studies of currently available databases of biosamples from known cohorts to validate the association of the SNP variant with the clinical phenotype. This would greatly reduce or obviate the need for large and costly Genome Wide Association Studies (GWAS). In addition to identification of a genetic marker associated with ASD, the environmental chemicals identified as scoring highly using our methodology could highlight those biologically plausible (based on biological target interaction) environmental triggers potentially responsible for the development or manifestation of the phenotype. Our research targets both genes and environmental agents; both treated as a unique pair of myriad possible combinations. Solution of combinatorial HTS problems of this kind is impractical using methods of traditional epidemiology. Thus, the current proposal provides an opportunity for the rapid identification of testable gene variant-chemical pairings implicated in a disease and an opportunity for Public Health Genomics to expand beyond the confines of conventional population studies with size-limited statistical power. Submitted by: Stuart Shapira, NCBDDD / CDC Effects of Stage of Reproduction, Nutrient Status, and Genes on Serum Homocysteine in Reproductive Age Women S.K. Shapira(1), A. Yesupriya(2), J. Robitaille(1), R. Fisk Green(1), H.C. Hamner(1), J.E. Kimmons(3), and K.S. Crider(1) (1) NCBDDD, CDC, Atlanta, GA; (2) NOPHG, CDC, Atlanta, GA; (3) NCCDPHP, CDC, Atlanta, GA Elevated serum homocysteine (Hcy) has been associated with adverse pregnancy outcomes, such as preterm birth, stillbirth, and low birth weight, as well as with cardiovascular disease and stroke. To evaluate genetic and environmental factors affecting Hcy, our study utilized survey data of 2,012 reproductive age women (17-44 years) from the NHANES III DNA Bank (1991-94). Associations between genetic variants (MTHFR 1298A-C, 677C-T, and 116C-T, MTRR 66A-G, and CBS 844ins68) and Hcy were tested using linear regression models that adjusted for demographic, reproductive, dietary, and environmental factors. To examine possible effect modification, models were stratified by race/ethnicity, reproductive stage in relation to pregnancy (never, currently, ≤2 years, >2 years), and total folate intake (―low‖ vs. ―adequate,‖ accounting for both folic acid from vitamins and food folate). Significant associations with mean Hcy were detected only for MTHFR 677C-T. Mean Hcy among TT women was higher compared with CC women (9.5 vs.7.1 μmol/L, p<0.001). When stratified by total folate intake, TT women with ―low‖ intake had higher mean Hcy, compared with CC women (16.7 vs. 7.6 μmol/L, p<0.001), while TT and CC women with ―adequate‖ intake had similar mean Hcy (7.1 vs. 6.8 μmol/L, p=0.44). Mean Hcy differed by genotype (TT vs. CC) for whites (17.9 vs. 7.7 μmol/L, p=0.003) and Mexican Americans (8.8 vs. 6.5 μmol/L, p=0.006) with ―low‖ total folate intake, although the difference was smaller for the latter. Models could not be stratified for blacks because of the low TT prevalence. A similar genotype effect was seen for women with ―low‖ total folate intake in all reproductive stages except currently pregnant, where TT women had lower mean Hcy compared with CC women (4.9 vs. 7.0 μmol/L, Collaboration Roundtable Poster Abstracts P. 16 p=0.003). These results suggest that the effect of total folate intake on the association between MTHFR 677C-T and Hcy is modulated by stage of reproduction and race/ethnicity. Therefore, adequate total folate intake appears to be important for reproductive age women, particularly those with the MTHFR 677TT genotype. Submitted by: Minoru Shinohara, Georgia Institute of Technology Impaired fine motor skills with heightened sympathetic nerve activity Minoru Shinohara (School of Applied Physiology, Georgia Institute of Technology) Manual dexterity is compromised in hypertensive individuals, heart transplant candidates, diabetics, the unaffected hand in stroke patients, and even healthy older adults. The impairment of manual dexterity in these individuals may precede a decrease in their quality of life and capacity for independent living. High levels of sympathetic nerve activity are observed in individuals with a variety of cardiovascular diseases including those listed above. It is possible therefore that an increase in sympathetic nerve activity is associated with impaired manual dexterity exhibited by the individuals described above. The purpose of the study was to test if heightened muscle sympathetic nerve activity increases fluctuations in motor output of a hand muscle in humans. Muscle sympathetic nerve activity was increased by applying lower body negative pressure (LBNP) while subjects performed low force isometric and anisometric contractions involving abduction of the index finger (5% of maximal force). The coefficient of variation of force during the isometric contraction increased with the application of LBNP. The standard deviation of acceleration during the eccentric contraction increased. There was no change in the standard deviation of acceleration during the concentric contraction. Discharge rate variability of motor units in the first dorsal interosseus muscle tended to increase with an increase in LBNP. The results indicate that heightened sympathetic nerve activity increases fluctuations in motor output during low force contractions, leading to impaired fine motor skills. Submitted by: Sarah Spencer, Georgia State University Microchip for Detection of Pathogenic RNA Detection of cellular messenger RNA is a useful diagnostic strategy for the detection of bacterial pathogens. A rapid and sensitive method for ―on site‖ detection of specific pathogens would be of great use for a number of fields. For example, simple and inexpensive method for the detection of Bacillus anthraces in train stations and airports is a useful system for national security. Rapid detection of pathogenic E. coli strains in food production would also be of great benefit in ensuring the safety and quality of our food supply. Here we present a method for the rapid detection of cellular mRNA. This system is based on the 3‘-labeling approach in which targeted RNA is simultaneously extended and labeled with the use of biotin labeled-dNTPs and DNA polymerase on an immobilized nucleic acid-base probe. The biotin is subsequently converted to an enzymatic label, which produces a detectable chemiluminescent reaction in the presence of the enzymatic substrate. Detection time of this system is very short (approximately 30 minutes) because there is no need for amplification by PCR, transcription, or fluorophore labeling. Furthermore, we have demonstrated detection sensitivity in the low femtomole range. This novel technology has been successfully demonstrated by selective detection of lac Z mRNA in a total RNA sample. Submitted by: Jason Stein, Section of Hospital Medicine, Emory University School of Medicine Automated, Real-Time Relay of Actionable Performance Data to Nursing Units: A Transferable Quality Improvement Strategy Jason Stein MD1, Bryce Gartland MD1, Laura Phillips2, Bruce Douglas2, Dee Cantrell2 1 Section of Hospital Medicine, Department of Medicine, Emory University School of Medicine 2 Emory Healthcare Information Services Background: Hospitals still have no readily transferable strategy to deliver optimal care consistently. Moreover, the regular data flow necessary to track and drive better performance is typically not available. Pilot work from our hospital medicine program suggests that daily relay of potential quality outliers enables front line staff to address oversights as they occur. Timely, actionable data relayed to the front line has significant value. Its acquisition represents a de facto performance tracking system, the strategy could apply to multiple hospital quality metrics, and could be transferred throughout a hospital or system if automated. Purpose: To examine the effect of automated, real-time relay of actionable performance data in nursing units across 5 separate Emory hospital facilities, hospitalists and health information specialists designed and developed a prototype aimed at improving the prevalence of venous thromboembolism (VTE) prophylaxis. Description: Features of the prototype were designed to overcome common quality improvement obstacles, accommodate clinical work flow, and positively influence provider behavior (Figure). To remove the necessity for manual acquisition of outlier data, we created an automated program to query our hospital system‘s electronic clinical database. To ensure real-time, geographic relevance of the information, the program runs every hour and presents the data by nursing unit. To make it readily accessible and useful to front line care givers, the data output is relayed to an aesthetically pleasing dashboard display that care team members can launch from any computer terminal. To emphasize actionable data while offering positive feedback, potential quality outliers are highlighted in red, but become green within an hour of being addressed. To leverage other drivers of Collaboration Roundtable Poster Abstracts P. 17 behavior, performance for every nursing unit is made fully transparent to all users across our hospital system. The prototype was introduced to over 40 nursing units in 5 separate Emory hospital facilities within a 3 week period. Conclusions: Automated, real-time relay of actionable performance data appears to be viable and transferable throughout a hospital system. As a strategy, it holds promise for improving the reliability and sustainability of quality hospital care. More research and development is needed to understand features of effective implementation and measure its impact on clinical, cost, and service outcomes. Submitted by: Sandra Steiner and George Carlone, CDC See poster abstract listed previously for George Carlone. Submitted by: Susan Sunay, Emory University, Department of Hematology Started in November 2006, the bank has collected and banked germ line and somatic DNA, RNA, and abnormal cells from patients with hematological disorders referred to Emory Healthcare. Plasma, serum and cerebrospinal fluid are also collected and stored for as additional material. Patients are banked at diagnosis, in remission and through the progression of their disease. Each de-identified sample is linked to a database which tracks extensive information for each study participant. This includes demographic information, patient history, pathology information and treatment outcomes. The Tissue Bank, located at Winship Cancer Institute of Emory University, is fully compliant with federal and institutional regulations to ensure patient confidentiality. Patients are enrolled at Emory University Hospital, the Winship Cancer Institute, Grady Memorial Hospital and the Hopital St. Antoine in Paris. As of January 2009 the bank has enrolled 375 patients into the study. Samples have been banked from various disorders including leukemia, lymphoma, myeloma, and chronic hematological conditions such as Essential Thrombosis and Polycythemia vera. This prospective project hopes to provide material for researchers to further investigate and identify genetic and other changes in blood cells that might occur to changes or progression in blood disorders. Understanding how these cancer genes and proteins work may help physicians predict prognosis and design new therapies for these diseases. Collaborative research has been carried out with other Winship Cancer Institute investigators, as well as with the Pathology Department at Emory University Hospitals and several outside institutions. Several of these studies have led to publications, posters, and grant proposals. Submitted by: Mitchell Tepper, Morehouse School of Medicine As part of Morehouse School of Medicine‘s (MSM) overall commitment to the elimination of health disparities among underserved and disadvantaged populations, MSM‘s Center of Excellence for Sexual Health (CESH), housed under the Satcher Health Leadership Institute (SHLI), has launched the Disabilities, Chronic Conditions and Sexual Health Program (DCCSHP). The mission of the DCCSHP is to be a catalyst and advocate for the development and implementation of monitoring, research, healthcare and support services, public and professional education, and policies to address the sexual health needs of persons with disabilities and persons with chronic conditions. The DCCSHP serves to address the disproportionate burden of sexual violence and abuse, sexually transmitted diseases, and sexual dysfunction resulting from the neglect of the sexual health of persons with disabilities and persons with chronic conditions. The DCCSHP also works to create equal opportunities to develop positive and life enhancing sexual relationships. The DCCSHP seeks to create an environment where there is substantial recognition of persons with disabilities and persons with chronic conditions wherever there are research, education, services and policies regarding sexual health and; conversely, an environment where there is substantial recognition of sexual health wherever there are research, education, services and policies regarding persons with disabilities and persons with chronic conditions. The specific aims of the DCCSHP are to: 1) improve monitoring and surveillance of indicators of sexual health and disability; 2) establish a prioritized national research agenda regarding the sexual health of persons with disabilities and persons with chronic conditions and conduct research in identified areas of need; 3) improve access to healthcare and support services in the area of disabilities, chronic conditions and sexual health; 4) develop curricula and competency standards to better prepare professionals to gain the knowledge, comfort, and skills necessary to understand and manage sexual health care needs of persons with disabilities and persons with chronic conditions, and; 5) work with Federal agencies to launch a major public information campaign to reduce stigma and counter stereotypes associated with the sexuality of persons with disabilities and persons with chronic conditions. The aims of the DCCSHP are consistent with the recommendations for improvement in the key areas of monitoring, research, access, and education identified in the Institute of Medicine‘s (IOM) report, The Future of Disability in America (2007). The aims also serve to further promote Dr. Satcher‘s Surgeon General‘s Call to Action to Promote Sexual Health and Responsible Sexual Behavior (2001) and parallel key areas of interest to CDC, including ending sexual abuse and violence, reducing STD transmission, promoting health and well-being of persons with disabilities and chronic conditions, and training, education and advocacy. The mission of CESH is to raise the level of national Collaboration Roundtable Poster Abstracts P. 18 dialogue on human sexuality, sexual health, and well-being in a sustained, informed, honest, mature, and respectful way and to link it to actions that reflect scientific evidence and deeply held beliefs. The DCCSHP will provide surety that the sexual health of persons with disabilities and persons with chronic conditions will be an integral part of the national dialogue on sexual health. Submitted by Charles Todd, CDC Evaluation of the TESA Immunoblot for inclusion in the algorithm for serodiagnosis of Chagas Disease in the USA. Debora R. Casandra1, Frank Steurer1, Eufrosina S. Umezawa2, Charles W. Todd1. 1Division of Parasitic Diseases, CDC, Atlanta, GA, USA, 2Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, Brazil Chagas disease, caused by the protozoan hemoflagellate Trypanosoma cruzi, is an increasing public health concern in the United States due to the migration of infected persons from endemic areas. There is no gold standard for diagnosis, therefore we are evaluating the utility of an immunoblot using trypomastigote excreted secreted antigens (TESA-IB) in order to improve the serodiagnostic algorithm that is currently in use at the CDC. Because T. cruzi is genetically polymorphic, TESA preparations from three strains, CL, Y and ―Mexico07‖ (a 2007 isolate from a Mexican patient) were evaluated in order to determine the most suitable for diagnostic use in the United States. Thirty sera that had been submitted for serodiagnosis were tested blindly. The TESA-IB results with all 3 TESA preparations were identical and concordant with previous serodiagnostic results by Immunofluorescence assay (IFA) and Wiener ELISA. The Y strain TESA was selected for further work because of its ease of production. A panel of sera with previously determined IFA and Wiener ELISA results were tested blindly by the TESA-IB. Of 43 sera that were IFA negative, 42 were negative by the TESA-IB. Similarly, of the 153 that were found positive by IFA, 136 were positive by the TESA-IB. Thus the TESA-IB shows concordance of 97.7% with IFA negativity and 88.9% with IFA positivity. Evaluating the TESA-IB against the Wiener ELISA, 75 were negative by the TESA-IB out of the 76 negative sera by the ELISA. Of 99 ELISA positive sera, 98 were positive by the TESA-IB, though the IB reactivity pattern of one serum was consistent with acute rather than chronic infection. Thus the TESA-IB has concordance of 98.7% with ELISA negativity and 99% with ELISA positivity. Studies with sera from parasitologically proven Chagas cases, Leishmaniasis and other specificity controls are in progress. Occasionally, the IFA and Wiener ELISA give discrepant results, either from assay values close to the respective diagnostic cutoffs or from non-specific cross reactivity. In such situations, the TESA IB shows promise to shift the weight of evidence to a clearer diagnosis. Submitted by: Maria Lucia Tondella, CDC The Pertussis and Diphtheria Laboratory (PDL) Current activities - Develops, evaluates, implements, and improves molecular biologic and serologic methods, techniques and strategies to enhance the diagnosis and surveillance of agents causing pertussis and diphtheria. - Pertussis outbreak response: PDL has worked closely with the health departments to determine the etiology of unknown respiratory outbreaks suspected to be caused by pertussis and has developed guidance for investigating suspected pertussis outbreaks - Clinical validation of pertussis diagnostics Areas Available for Collaboration - Development and evaluation of novel molecular and serologic assays to improve pertussis diagnostics. - Molecular typing of Bordetella and Corynebacterium species. - Study global epidemiology, population structure, and evolution of Bordetella pertussis. - Genomics and proteomics of Bordetella species including bioinformatics - Study virulence markers of Bordetella species Submitted by: Bi-Cheng Wang, University of Georgia Research Capabilities of The University of Georgia X-ray Crystallography Facility Bi-Cheng Wang and John Rose Department of Biochemistry and Molecular Biology University of Georgia, Athens, Georgia 30602 Obtaining structural information by X-ray crystallography requires considerable investment both in equipment and expertise. During the past decade, a world-class X-ray crystallography facility has been built on the University of Georgia campus with support from the GRA, NIH and UGARF. Using genes as a starting point, the proteins, including membrane proteins, may be expressed, purified, and crystallized, in addition to having their structures determined at the facility. Access to these local resources as well as the high-intensity X-rays and equipment at the Advanced Photon Source (APS), Argonne National Laboratory may be arranged either by collaboration or on a cost-recovery basis. The capabilities of the UGA and APS facilities, and mechanisms for accessing these resources will be presented. Collaboration Roundtable Poster Abstracts P. 19 Submitted by: Irene Weber, Georgia State University HIV Drug Resistance and Control of Apoptosis in Cancer and Neurodegenerative Disease Irene T. Weber and Robert W. Harrison Departments of Biology, Chemistry, and Computer Science, Molecular Basis of Disease Program, Georgia State University, Atlanta, GA, USA. We apply the techniques of biochemistry, bioinformatics, data mining and structural biology to assist in disease detection and therapy. Currently, two major projects address the challenges of drug resistance in HIV/AIDS and control of cell death in diverse diseases. Drug resistance is a major challenge for treatment of HIV infection. We are investigating the molecular mechanisms of drug resistance to inhibitors of HIV protease. This knowledge is applied in structure-guided designs for novel antiviral inhibitors with enhanced interactions with conserved regions of the protease structure. Daruanvir, which was approved in 2006 for AIDS salvage therapy, is a major success of this strategy. Several new antiviral inhibitors are in preclinical studies. Our insights into the mechanisms of drug resistance and novel strategies for drug design have wide impact in many diseases. Normal controls of cell death are disrupted in many diseases including cancer, stroke, heart disease, autoimmune diseases, neurodegenerative and neuromuscular diseases. We are studying the control and activity of caspase-3, -6 and -7 as the executioners of apoptosis. Our investigation of the substrate specificity of caspases was the first to reveal that caspase-3 and -6 differ from caspase-7 in their recognition of the P5 residue of protein substrates. Knowledge of the substrate specificity of caspases is vital for identifying signaling pathways leading to apoptosis in normal cells and disease states and for the rational design of selective therapeutic agents to control cell death. Acknowledgements: The research was supported in part by the Georgia State University Molecular Basis of Disease Program, the Georgia Research Alliance, the Georgia Cancer Coalition, the National Institute of Health grant GM062920, and the Center for Disease Control. Submitted by: Bruce Weniger, Centers for Disease Control and Prevention Phase I Safety Data from a Still-blinded Trial of Reduced-dose, Intradermal Influenza Vaccination by Needle-free Jet Injector in the Dominican Republic V. Gómez1, P.L. Moro2, G. Guzmán1, J. Feris1, J. Fernández1, C.B. Bridges3, M. Friede4, J.K. Iskander2, B.G. Weniger2 1 Department of Infectious Diseases, Hospital Infantil Dr. Robert Reid Cabral, Santo Domingo, Dominican Republic 2 Immunization Safety Office, Centers for Disease Control and Prevention (CDC) 3 National Center for Immunization and Respiratory Diseases, CDC 4 Initiative for Vaccine Research, World Health Organization, Geneva, Switzerland OBJECTIVE: Describe adverse events (AEs) following vaccination from a phase I trial comparing reduced-dose and intradermal vaccination for influenza. BACKGROUND: Intradermal (ID) delivery of influenza vaccine by disposable-cartridge jet injector (DCJI) may reduce antigen quantity needed for seasonal and pandemic protection and avoid drawbacks of ID vaccination by needle-syringe (N-S) Mantoux method. STUDY DESIGN: In a still-blinded trial, 48 children from 6.9-22.8 months of age (mean 13.9) received two doses 4 weeks apart of trivalent, inactivated Vaxigrip® (sanofi-pasteur) in 3 randomly-assigned groups: 0.1 mL ID by investigational spacer on Biojector® 2000 DCJI; 0.1 mL intramuscularly (IM) by N-S; or 0.25 mL IM by N-S (control). Parents and investigators were blinded; injecting nurses were not. AEs were assessed by investigators on days 0, 2, 7, and 28 after each dose and by parents in recorded diaries for prompted symptoms on days 0-7 and open-ended reports for days 8-28. RESULTS: After either dose, local mild pain (―light reaction‖) on touching injection site occurred in 8 (17%) participants, and moderate pain (―cries or protests‖) in 1 (2%). Mild local AEs of ≥10-<25 mm occurred for erythema (7, 15%), swelling (3, 6%), and hematoma (1, 2%). None had induration or nodules. All local AEs occurred within 2 days after a dose. Systemic AEs noted were diarrhea (20, 42%), loss of appetite (18, 38%), vomiting (14, 29%), fever ≥38.0°C (12, 25%), irritability (8, 17%), unusual crying (8, 17%), and sleepiness (7, 15%). None clustered temporally after doses. One febrile convulsion on day 24 after dose 1 was the only serious AE reported. CONCLUSION: Local AE‘s were mild. Most systemic AE‘s are likely unrelated to vaccination dose and route, but can only be determined after unblinding of phases I and II. Submitted by: Letitia Williams, CDC Translating Data into Action: Using PRAMS Surveillance Data for Public Health Programs and Policies The Pregnancy Risk Assessment Monitoring System (PRAMS) is an on-going state- and population-based surveillance system designed to monitor selected self-reported maternal behaviors and experiences that occur before, during and after pregnancy among women who deliver a live-born infant. PRAMS operates as a cooperative agreement between the Centers for Disease Control and Prevention and state health departments in 37 states, New York City, and the South Dakota Tribal Project. PRAMS represents approximately 75% of all U.S. births. The purposes of this presentation are to: (1) provide examples of how PRAMS surveillance data have been translated into state MCH policy initiatives; (2) demonstrate how state MCH programs collaborate with stakeholders to develop public health programs and identify funding sources; and (3) discuss some of the challenges associated with translation at the state level. Because of its utility in helping to address MCH health needs, programs and policies, PRAMS considers the use and translation of data to be vital. Analysis of surveillance data is essential in assessing state needs, Collaboration Roundtable Poster Abstracts P. 20 monitoring health status and gaps, developing health policies and programs, and evaluating and assuring the quality, efficacy and effectiveness of interventions. The development of data partnerships is indispensable in advancing the use of data. Submitted by: Guang-Jer Wu, Emory University School of Medicine Mechanisms leading to awakening (growth activation) of dormant tumor cells and outgrowth of manifesting metastases are not well understood. In addition to the genetic disposition (germ line polymorphisms) in the dormant cells, the altered expression of cell adhesion molecules (CAMs) may constitute the triggers by which the dormancy of cancer cells is maintained or broken. Since altered expression of CAMs changes cell motility and cellular invasiveness, alters angiogenesis, and affects cellular survival and growth (by crosstalk with various cellular surface receptors, which interact with the growth factors, cytokines, and various external stimuli in the surrounding microenvironment, which regulate secondary growth resulted in maintaining or awakening dormant metastatic tumor cells), altered expression of CAMs expressed on the surface of tumor cells may affect their interactions with extracellular matrix, temporarily control by the immune system, and pre-angiogenesis influences by the stromal cells in the surrounding micro-environment. Aberrant expression of METCAM/MUC18, a cell adhesion molecule in the immunoglobulin-like gene superfamily, often associates with the malignant progression of melanoma, prostate cancer, ovarian cancer, angiosarcoma, ostosarcoma, breast cancer, nasopharyngeal carcinoma, and haemangiomas. METCAM/MUC18 also plays a role in the angiogenesis of endothelial cells and some tumor cells. We have shown that increased expression of METCAM/MUC18 can increase the tumor-take and tumor proliferation and the metastasis of prostate cancer cells, melanoma cells, and ovarian cancer cells by increasing tumor angiogenesis. Evidence from other groups also suggests that METCAM/MUC18 may also play a similar role during the progression of angiosarcoma and osteosarcoma. On the contrary, some evidence supports the novel notion that METCAM/MUC18 may also serve as a tumor suppressor and perhaps also as a metastasis inhibitor for breast cancer, haemangiomas, and nasopharyngeal carcinomas. This is based on the findings that METCAM/MUC18 is expressed in all the normal breast and nasopharyngeal epithelium and endothelial cells, but only expressed in 18% of breast carcinomas and 13% of metastatic breast carcinomas, poorly expressed in all nasopharyngeal carcinomas (NPC), and lowly expressed in infantile haemangiomas. Furthermore, METCAM/MUC18 is not expressed or very weakly expressed in five luminal breast cancer cell lines and in ten established NPC cell lines. Moreover, over- expression of METCAM/MUC18 in the breast cancer MCF-7 cells actually suppresses the tumor growth in SCID mice. Over expression of METCAM/MUC18 in breast cancer cells may render them into a dormant state, thus manifests as a tumor suppressor or metastasis inhibitor. In addition, METCAM/MUC18 has been indicated as a marker for the mesenchymal stem cells and expressed in some activated T cells, suggesting that METCAM/MUC18 may also play a role in maintaining breast cancer cells in dormant state by rendering them to behave like stem cells as well as by subjecting them to negative control by the host immune system. We are in the process to test these effects in these two cancers. We further suggest that the role of METCAM/MUC18 in the progression of different types of cancers may be modulated by different intrinsic factors present in cancer cells derived from different organs.