February 2016, Vol. 4 Num. 2

Looking for collaborations: The Hispanic Community Health Study/ Study of Latinos: Overview, Key Findings, and Research Opportunities Larissa Avilés-Santa, MD, MPH, FACP, FACEHCHS/SOL Project Director & Medical Officer

Inside this issue 1. The Hispanic Community Health Study 2. Puni Ke Ola – Pilot Project 3. Se premian los mejores “Hacks” de Salud 5. Welcome our new collaborators 9. Translation in Data Mining 10. Scientific Highlights/Science Advance

11. Arts of Granstmanship 12. Upcoming Events

Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH Project Period: 06/01/2013–05/31/2019 Contact: Dr. Larissa Avilés-Santa The Hispanic Community Health Study/Study of Latinos external disclaimer (HCHS/SOL) (https://www2.cscc.unc.edu/hchs ) is a multi-center epidemiologic study in Hispanic/Latino populations designed to describe the prevalence of cardiovascular and pulmonary disease and other select chronic diseases, their protective or harmful factors, and changes in health over time, including incidence of fatal and non-fatal cardiovascular disease events, exacerbation of pulmonary disease and all-cause mortality. In addition, the role of sociocultural factors (including acculturation) on Hispanic/Latino health is of interest. The initial study period was funded between October 2006 and May 2013. Over 16,400 Hispanics/Latinos, aged 18-74 years at enrollment, and representing different groups of origin (Central Americans, Cubans, Dominicans, Mexicans, Puerto Ricans and South Americans) were recruited and examined between March 2008 and June 2011, and are currently followed at four centers affiliated with San Diego State University, University of Illinois at Chicago, Albert Einstein College of Medicine in the Bronx area of New York, and the University of Miami. A research Coordinating Center at the University of North Carolina in Chapel Hill provides additional scientific and logistical support, and an Echocardiography Reading Center at Brigham and Women's Hospital at Harvard University will provide the reading and interpretation of echocardiograms to be performed during this cycle. In this second study period, study participants will undergo a second examination, and will continue to be followed annually to determine changes in health and health outcomes of interest. Baseline study findings are being analyzed, and publication of the results in scientific journals, and their dissemination to the communities involved in the study is ongoing. The study is currently funded by the National Heart, Lung, and Blood Institute and the National Institute Diabetes, and Digestive, and Kidney Diseases.

Puerto Rico Clinical and Translational Research Consortium Newsletter

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Abstract The broad purpose of this translational (T3) research is to improve rural Native Hawaiian health by improving access to a community-based model of drug prevention. We have developed such an intervention, called Puni Ke Ola. Given the scale of the small grant program, we will implement a single month-long module, and our aims are to study both the process and outcomes of Puni Ke Ola as an initial step in preparing for a larger scale intervention study. Our long-term goal is to eliminate substance use/abuse and related health disparities in Hawaiian populations and communities. Narrative Substance use and abuse represent significant and persistent health disparities among minority and indigenous populations, including Native Hawaiians. Further, substance use contributes to co-morbid health problems ranging from diabetes to cardiovascular diseases to cancer. While substance use among Hawaiian youth tends to start younger and use rates tend to be higher than among their non-Hawaiian peers in the State of Hawai`i, evidence-based drug prevention interventions have not been based on cultural and community assets grounded in Native Hawaiian values, beliefs, practices, and places. Our intervention, Puni Ke Ola, has

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been developed in this way, which we believe is critical for sustained effectiveness. The lack of cultural relevance in existing evidence-based community interventions targeting rural Native Hawaiian communities limits their use and effectiveness. We hypothesize that a culturally relevant intervention (intervention design and evaluation design) developed with rural Native Hawaiian communities will reduce youth substance use in such communities. A single module of Puni Ke Ola will be implemented with a small purposive sample of youth. Each module features a specific cultural practice. Modules are implemented following the lunar cycle, which structures a series of activities for community-based experiential learning with classroom-based individual and group reflection. Youth will participate in a photovoice project through which they will document (photo) the hands-on cultural immersion learning, and reflect (voice) on its role in promoting individual & community health and preventing substance use and related youth health risks (Aim 1: document implementation). The main product of the proposed research is to develop a tool for evaluation that aligns with the implementation strategy and includes both standard and novel culturally relevant items (Aim 2: develop outcome measure). We will collaborate with the RTRN DCC to migrate the tool to an online web based platform for use in future intervention studies.

Puni Ke Ola – Pilot Project PI: Susana Helm, PhD/University of Hawai`i RTRN Collaborator: Edna Acosta-Perez, PhD/University of Puerto Rico

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Noviembre 25, 2015. San Juan, Puerto Rico. El Simposio de Informática de la Salud en América Latina y el Caribe (SHILAC), se llevó a cabo este pasado fin de semana en un hotel de San Juan, con el fin de facilitar los datos para la creación de herramientas tecnológicas en la mejora de la calidad de la salud en América Latina y el Caribe. Por primera vez, Puerto Rico fue sede de este importante evento en el cual participaron más de 150 profesionales de la salud y desarrolladores de tecnología durante los dos días y medio. “En SHILAC se juntaron equipos multidisciplinarios para ver soluciones reales a los problemas más comunes que tienen los servicios sanitarios, especialmente en contextos de escasos recursos tanto tecnológicos como humanos”, detalló Carol Hullin, ejecutiva de bioinformática del Banco Mundial para América Latina y el Caribe y presidenta del Comité de Programa de SHILAC. "El hackathon, fue dirigido por el conocido grupo MIT Hacking Medicine formado en el Instituto de Tecnología de Massachusetts (MIT), quien celebro el primer hackathon relacionado con la salud en Puerto Rico y la primera vez que MIT Hacking Medicine realiza un hackathon en el Caribe y América Latina", describió Patricia Ordóñez, profesora auxiliar en el departamento de Ciencias de Cómputo de la UPR-RP y presidenta del Comité Organizador de SHILAC. Con MIT Hacking Medicine más de 10 equipos se formaron para desarrollar proyectos y programar en un espacio de 24-horas

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consecutivas. Los proyectos ganadores fueron: - Primer lugar: Plataforma digital para determinar el nivel de riesgo en la calidad de aire para asmáticos y personas que padecen de alergias. - Segundo Lugar: Un “tracking bracelet” que ayuda en prevenir que pacientes de enfermedades neurodegenerativas se pierdan. - Tercer Lugar: Una plataforma digital dirigida a padres de adultos jóvenes con autismo para conectarlos con información, servicios o ayudas para pacientes por región geográfica. - Mejor Hack auspiciado por AARP: Una plataforma digital para conectar a los cuidadores de personas mayores con la comunidad envejeciente. - Mejor Hack auspiciado por Varmed Management Corp.: EMPATE: a. Visualización de data sobre los Super Utilizers en Puerto Rico, b. Sistema para la “limpieza” de los datos de los Super Utilizers para una mayor precisión en el análisis. Entre los equipos premiados había estudiantes del Recinto de Ciencias Médicas, UPR-Río Piedras, Universidad Metropolitana, UPR-Humacao, Universidad del Turabo, UPR-Mayagüez y la Universidad Inter-Americana (Metro). El jurado estaba compuesto por Carlos Díaz Vélez, MD, del Colegio de Médicos Cirujanos, Dra. Carol Hullin Del Banco Mundial, Ing. Marlene Pierce de Varmed, Sr. José Vargas de Varmed, Sr. Antonio Fernández de Ponce Health Sciences University, Sr. Archer Lebrón de Tranxcend y la Asociación de Industriales y Kenneth Paik, MD, de MIT. Algunos temas incluyeron tratados en los trabajos técnicos y posters

COMUNICADO DE PRENSA SE PREMIAN LOS MEJORES “HACKS” DE SALUD

Puerto Rico Clinical and Translational Research Consortium Newsletter

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científicos incluyeron: · Aplicaciones para reducir el tiempo de los pacientes en las oficinas médicas · Utilización de la tecnología en la detección de jóvenes en riesgo de embarazos precoz · Iniciativa en la telemedicina en la preparación para los desastres naturales · No solamente marketing: Usando las métricas de los medios sociales para determinar los riesgos en una población expuesta a la infección del HPV La conferencia contó con ponentes de reconocido prestigio procedentes de América Latina y América del Norte, representando a Chile,

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Colombia, Ecuador, Jamaica, Estados Unidos y Puerto Rico. Además hubo representación de MIT, Escuela de Medicina de Harvard, Universidad de Pittsburgh, Universidad de California-San Diego, y un representante de la División de Informática de la Casa Blanca, Washington, DC. Contó además con paneles de la Asociación de Hospitales, Asociación de Industriales, Ponce Health Sciences University, Instituto de Estadísticas de Puerto Rico, Edwards Lifesciences, Puerto Rico Health Information Network, entre otros.

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Antonio Fernandez, MBA is our liaison for the Biomedical Informatics Core

(BIC). He will work closely with the BIC Leader to provide guidance and

service for the PRCTRC investigators at Ponce Health Science University

(PHSU).

Mary S. Rodriguez-Rabassa, PsyD, is an Associate Professor in the Clinical

Psychology Program at the Ponce Health Science University. She is our

Research Subject Advocate for the Regulatory Knowledge and Support Core

(RKS) for Ponce. She will provide guidance on IRB compliance to PRCTRC

investigators. Dr. Rodriguez is part of the RCMI Program as a junior

researcher. This year she was accepted into the CRECD’s mentored clinical

research and career development program, which is part of the Master of

Science in clinical research (MSc) program at UPR-MSC.

Our New Collaborators

Cynthia M. Pérez, Ph.D., is a full-time Professor of Epidemiology at the

University of Puerto Rico, Graduate School of Public Health, Medical

Science Campus. She holds MS (Statistics) and PhD (Epidemiology)

degrees from Purdue University in Indiana. She has directed efforts in

mentoring and training public health students, medical students, residents,

fellows, and faculty in the fields of epidemiology and biostatistics for the

past 20 years. She is our new Leader for the Professional Development

Core (PDC).

Puerto Rico Clinical and Translational Research Consortium Newsletter Juan Orengo MPH, MD, PhD, is a Professor in the Public Health at the

Ponce Health Science University. He is our Co-Leader for the Research

Design and Biostatistics Core (RDB), providing service to PRCTRC

investigators in the areas of methodology, analysis, data management and

clinical research ethics.

Deana Hallman, M.D, is a Hematologist. She is the Leader for our new

External Funding & Scientific Writing Resources Unit, under the

Administrative Core. She will assist PRCTRC identified investigators in

scientific writing, submission and resubmission of proposals for external

funding, manuscripts, posters and others.

Vanessa Rivera, PhD is an Associate Professor from the Department of

Microbiology at Ponce Health Sciences University. She is the Co-Leader for

Technologies Resources and Core Laboratories (TRCL). She is responsible

for coordinating all PRCTRC Lab services, training and activities at the PHSU.

On July 10, 2015, the Journal of Virology & Antiviral Research published an

article by our own Dr. Vanessa Rivera. The title of the article is Longitudinal

Analysis of Cerebrospinal Fluid and Plasma HIV-1 Envelope Sequences

Isolated From a Single Donor with HIV Asymptomatic Neurocognitive

Impairment. Click on the following link to check it out:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498488/?tool=nihms

Dr. Kenira J. Thompson is an Associate Professor in Basic Sciences,

President of the Ponce Research Institute (PRI) and Dean of Research at

the Ponce Health Sciences University (PHSU). Dr. Thompson completed

her doctoral work and postdoctoral training in Behavioral Neuroscience.

She has been Co-Leader for the CPC during the past two years; she is

now our Program Director for the PRCTRC at PHSU. Dr. Thompson

oversees the PRCTRC Pilot Project Program and Technologies

Resources and Core Laboratories.

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Patricia Casbas-Hernandez, PhD, MPH, is an assistant professor with a

joint appointment in epidemiology (Public Health Program) and

biochemistry (basic sciences). She also serves as the laboratory

coordinator of the Puerto Rico Tissue Biobank (U54 PSM–MCC

partnership). Recently, she was awarded a two-year pilot project from the

U54 Moffitt–PSM partnership for the amount of $62,500 per year. Her

pilot project is titled Infiltrating Immune Cells in Breast Cancer Subtypes.

Eida Castro, PsyD, MSc, assistant professor (Psychology Program and

Psychiatry Department) and participant in the CRECD’s mentored clinical

research and career development program, part of the Master of Science

in clinical research (MSc) program at UPR-MSC, recently received funding

through the U54 Moffitt–PSM partnership for a two-year pilot project in the

amount of $62,500 per year. Her project’s title is Educational Intervention

to Increase Genetic Counseling Use in Hispanic Breast Cancer Survivors

• Dr. Castro has published an article in the world’s first multidisciplinary open access journal, PLOS ONE. The article is titled A Social-Ecological View of Barriers and Facilitators for HIV Treatment Adherence: Interviews with Puerto Rican HIV Patients. You can access this article at the following link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125582

Julie Dutil, PhD, is an associate professor in the Department of Basic

Sciences. Her areas of interest are breast cancer genetics, genomics, and

population genetics. She has recently received funding for her two-year

pilot project, which is entitled Uncovering Breast Cancer Predisposition

Factors in Puerto Rico. Awarded through the U54 Moffitt–PSM

partnership, the for the amount of the funding is $125,000 per year.

Puerto Rico Clinical and Translational Research Consortium Newsletter Luisa Alvarado, MD, FAPP, is a professor in the Department of Pediatrics.

Dr. Alvarado was recently awarded with a continuance of her Centers for

Disease Control and Prevention (CDC) grant, amounting to $3,402,283.00.

Her project’s title is Sentinel Enhanced Dengue Surveillance System

(SEDSS) Sites to Evaluate the Epidemiology and Prevention of Dengue

and Other Acute Febrile Illnesses in Puerto Rico.

Annelyn Torres-Reveron, PhD, is an assistant professor of physiology and

pharmacology in the Department of Basic Sciences. She was awarded

with an NIH-K07 grant. You can view an interview (in Spanish) about her

research by clicking on the following link: http://www.primerahora.com/yo-

soy-ph/yo-soy-ph/nota/queorgulloparanuestraisla-1097442/

We are pleased to introduce Dr. Guillermo N. Armaiz-Peña, PhD, to the

PHSU team. He was a post-doctoral fellow at the University of Texas MD

Anderson Cancer Center. He is currently an assistant professor of

pharmacology in the Department of Basic Sciences at PHSU–PRI. His

research area of interest is cancer as it relates to women's health and

reproductive biology. You can contact him via email at garmaiz@psm.edu.

Also new to the PHSU team is Dr. Harold Saavedra, PhD. He is an R01

investigator who joins us from Emory University. His background is in the

study of the cell and centrosome cycles as applied to breast cancer

biology. He is currently an associate professor of pharmacology in the

Department of Basic Sciences. His general area of interest is cancer. You

can contact him via email at hsaavedra@psm.edu.

New Personnel at PHSU-PRI

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Translation in Data Mining to Advance Personalized Medicine for Health Equity In their recent publication, Translation in Data Mining to Advance Personalized Medicine for Health Equity, Dr. Estela S. Estape, former Lead for the Professional Development Core, Dr. Mary Helen Mays, Lead for the Biomedical Informatics Core of the PRCTRC, and their colleague, Dr. Elizabeth Sternke, Adjunct Professor of the MSc program, explore translational research and personalized medicine through the lens of biomedical informatics and data mining. What impact could personalized medicine have on patient care and treatment choices? One example is seen in Kathy Halamka’s case [1]. Diagnosed at the age of 49 with Stage III breast cancer, Kathy was faced with the choice of the conservative, standard-of-care protocol of mastectomy followed by chemotherapy. As a patient of Beth Israel Deaconess Medical Center, Kathy’s medical team was able to query the clinical data repository comprised of data from the EMRs of five Harvard-affiliated hospitals, using the i2b2 platform. By searching for patients with certain characteristics (e.g., 50-year old, Asian females, stage III breast cancer, medications, outcomes), the medical team was able to identify variables, which indicated that a different treatment protocol was more appropriate for Kathy. Choosing to not have surgery as a first treatment step, Kathy began with chemotherapy drugs that targeted the estrogen-sensitive tumor cells. By the completion of chemotherapy, the tumor was no longer visible on radiographs. Her treatment ended with a lumpectomy and a continuation of estrogen-blocking medication. In 2015, US President Barack Obama announced the Precision Medicine Initiative, to focus attention and resources towards the development of innovative technologies and infrastructure designed to improve individual and societal health and treatment of disease [2]. Precision medicine, also referred to as personalized medicine, enables physicians and other care providers to treat individuals as unique, using observations from the individual patient as well as harnessing the power of aggregated data drawn from millions of other patients’ data [3]. Reaching this ideal requires bringing together diverse data sources into an analytic paradigm. A resource to clinicians in the development and application of personalized medicine is largely facilitated, perhaps even driven, by the analysis of “big data”. Data used in creating a personalized medicine treatment plan are already routinely collected in day-to-day healthcare settings, including primary and specialty care offices, laboratories, imaging centers, pharmacies, and hospitals. Other healthcare and health-related data that are increasingly available include clinical trial data, claims data from health insurance providers, and research study data. Data, such as those available in electronic medical records (EMRs), will be in both structured and unstructured formats [4, 5]. In short, there is now a superabundance of data, which may be mined and analyzed to identify and support better clinical decisions as well as new treatment discoveries. These data, collectively recognized as “big data”, are keys that can unlock doors to the potential of personalized medicine. These large, complex datasets will house structured data (e.g., numerical data for height, weight, blood pressure, glucose levels; categorical data such as yes/no for marital status; etc.) as well as unstructured data (e.g., physician notes). Such systems will need to be able to effectively aggregate and normalize data from across data sources (e.g., genomic data, patient data from EMRs, radiologic images, etc.). Systems such as those built on the “informatics for integrating biology and the bedside (i2b2)” framework are particularly useful and effective for integrating clinical and research data that may be used by investigators [6]. These clinical data repositories (i.e., databases) are often de-identified and anonymized, allowing researchers to generate hypotheses and identify cohorts for study. These “big data” repositories can be queried by clinicians, using specific questions, with data used to gain an understanding of challenges in patient care and treatment.

Puerto Rico Clinical and Translational Research Consortium Newsletter

Project Title: “Longitudinal Analysis of Cerebrospinal Fluid and Plasma HIV-1 Envelope Sequences Isolated From a Single Donor with HIV Asymptomatic Neurocognitive Impairment” Institution: Ponce Health Sciences University PI Name: Rivera-Amill, Vanessa, PhD Background: Combined antiretroviral treatment (cART) has changed the clinical presentation of HIV-associated neurocognitive disorders (HAND) to that of the milder forms of the disease. Asymptomatic neurocognitive impairment (ANI) is now more prevalent and is associated with increased morbidity and mortality risk in HIV-1–infected people. HIV+ subjects with ANI have a greater likelihood of symptomatic neurocognitive decline, a prognosis that seems to be overrepresented in females and in subjects with low nadir CD4+ levels.HIV-1 envelope (env) genetic heterogeneity has been detected within the central nervous system (CNS) of individuals with ANI. Changes within env determine co-receptor use, cellular tropism, and neuropathogenesis. Findings from previous studies highlight the importance of studying the genetic variability within HIV-1 env as an additional risk factor of neurocognitive impairment. The researchers of this study hypothesize that compartmental changes are associated with HIV-1 env (C2V4 region) during ANI and sought to analyze paired HIV-1 env sequences (C2V4 region) from plasma and cerebrospinal fluid (CSF) of a female subject undergoing long-term cART. The phylogenetic analysis of paired study samples consistently showed genetic variants unique to the CSF. Phenotypic prediction showed CCR5 (R5) variants for all CSF-derived sequences and showed minor X4 variants (or dual-tropic) in the plasma at later time points. Viral compartmentalization was evident throughout the study, suggesting that the occurrence of distinctive env strains may contribute to the neuropathogenesis of HAND. Advance: This study presents interesting viral evolution data from a Hispanic woman with mild ANI and provides new insights about the genetic characteristics within the C2V4 of HIV-1 env that persist after long-term cART and during the course of persistent ANI. The C2V4 region of HIV-1 env isolates in matched CSF and plasma samples (collected at 12-month intervals for 3 years) from a female subject diagnosed with ANI was successfully amplified and characterized. This is the first study that describes the mean viral diversity in matched plasma and CSF sequence from a Hispanic female subject with ANI who is undergoing long-term cART. How NIMHD Grant Enabled Advance: The Technological Resources for Core Laboratories from the PRCTRC (#U54MD007587) supported this study. Public Health Impact Statement: This study found that CSF variants were genetically unique within their C2V4 region during the setting of long-term suppressive cART and persistent ANI. In sum, probing the functional phenotypes of CSF-derived HIV-1 env variants will allow for the identification of putative mutations present in the subjects with ANI and for the identification as well of potential for neurotoxic properties that are associated with the C2V4 region. Grant Support (all grant numbers): U54MD007587, P20RR11126, G12-MD007579, R01-MH08316-01, U54 NS3011, and GM082406. Publication Citation and Link: Vázquez-Santiago, F., García, Y., Rivera-Román, I., Noel, R.J., Wonja, V., Melendez, L.M., and Rivera-Amill, V. (2015) Longitudinal Analysis of Cerebrospinal Fluid and Plasma HIV-1 Envelope Sequences Isolated From a Single Donor with HIV Asymptomatic Neurocognitive Impairment. Journal of Virology & Antiviral Research, 4(1). doi:10.4172/2324-8955.1000135 PMID: 26167513; PMCID: PMC449848

SCIENTIFIC HIGHLIGHTS/SCIENCE ADVANCES

Upcoming events February 2016 Vol. 4 Num. 2

The Art of Grantsmanship: A Hands-On, Intensive Workshop

Applications are being accepted now Spring 2016 Session

The Professional Development Core of the Puerto Rico Clinical and Translational Research Consortium (PRCTRC) is pleased to announce the schedule for the Spring 2016 session of The Art of Grantsmanship: A Hands-On, Intensive Workshop.

+ Sessions Start: February 23, 2016

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• Ponce Health Sciences University: Dr. Jose Torres (jtorres@psm.edu) • Universidad Central del Caribe: Dr. Robert Hunter (robert.hunter@uccaribe.edu) • University of Puerto Rico Medical Sciences Campus: Dr. Mary Helen Mays (mary.mays@upr.edu)

Upcoming events February 2016 Vol. 4 Num. 2

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