FACILITIES AND OTHER RESOURCES (BOSTON UNIVERSITY HUB)

Boston University OverviewThe Boston University Clinical and Translational Science Institute (BU CTSI), the BU hub of the national CTSA network, is part of an integrated environment that supports the entire spectrum of translational research. From the Center for Nanoscience and Nanotechnology to the Framingham Heart Study, Boston University’s breadth of translational science encompasses the spectrum from T1 through T4.

BU CTSI was formed in 2008 with funding from the NIH CTSA program as well as substantial support by Boston University (BU), our applicant institution, and Boston Medical Center (BMC), our major partner and the chief teaching hospital of BU School of Medicine. In 2008, in addition to BU and BMC, our BU CTSI hub included three affiliates: the BMC-affiliated Boston HealthNet network of community health centers, the Boston VA Healthcare System, and the Edith Nourse Rogers Veterans Hospital.

Our institutional letters of support confirm the strength of these associations, as does the active participation of faculty at each site in the leadership and organization of the BU CTSI. These relationships and the complementary resources at each site allow us to implement high impact solutions that streamline translational research processes, create transformative and disruptive innovations, educate current and future translational scientists and bring products to commercialization. This section is a synopsis of the resources and the environment of the BU CTSI.

Boston University (BU) (the applicant institution) is a large urban, private undergraduate and graduate university with Colleges and Programs in all of the major arts and sciences. The University has two campuses separated by about 2 miles—the Charles River Campus (CRC) is the home for unique translational research resources in Engineering, Chemistry, Physics, Biology, and the home for the Photonics Center and the Center for Nanoscience and Nanobiotechnology. The BU School of Engineering has two world-renowned departments: its Biomedical Engineering Department is the only recipient of both Coulter and Fraunhofer endowment programs that support nationally recognized programs in point of care diagnostics, microfluidics, and photonics, among others. Boston University hosts one of the first interdisciplinary PhD programs in computational mathematics, renamed Bioinformatics, which gave birth to the bioinformatics revolution of which the BU CTSI has taken advantage. Unique programs in chemical synthesis in the department of Chemistry in the School of Arts and Sciences complement strong research in cancer biology in the Biology Department. Boston University’s College of Health & Rehabilitation Sciences, Sargent College, is a unique entity that fosters programs in physical rehabilitation medicine and research. The university financially supports core laboratories and facilities, as well as houses centers and institutes that participate in a vast array of research. Selected ones include: Biology Core (PICF) Biomedical Optics Laboratory, Center for Chemical Methodology & Library Development, Center for Nanoscience and Nanobiotechnology, Chemical Instrumentation Center, Electronic Design Facility (EDF), Engineering Product Innovation Center (EPIC), Fraunhofer Center for Manufacturing Innovation, High Performance Computing & Communications Facilities (Supercomputing), Photonics Center and Scientific Instrument Facility. The University is in the process of building a new 170,000 sq. foot Center for Integrated Life Sciences and Engineering (CILSE) which will house several new Centers, including the Center for Systems Neuroscience and the Biological Design Center that will bridge work in synthetic biology and cellular and tissue engineering. CILSE will contain several key core facilities including a Cognitive Neuroimaging Center that will be outfitted with a 3T MRI.

We describe here only a few of the highly interactive translational research centers and resources pertinent to this application.

BU Center for Molecular Discovery (BU-CMD). The BU CMD is focused on the discovery of new methodologies to produce novel chemical libraries of unprecedented complexity for biological screening. The goal of the CMLD-BU is to explore and expand the diversity of small-molecule libraries by creating general,

useful protocols for stereo-controlled synthesis. This process involves the creation of novel chemical libraries that uniquely probe three-dimensional space by employing stereochemical and positional variation within the molecular framework as diversity elements for library design. A major objective of the CMLD-BU is also to provide information and chemistry protocols to the public on parallel and chemical library synthesis. The CMLD-BU has also organized the Chemical Library Consortium (CLC) to provide members of the biology community with access to its chemical libraries. To facilitate the use of these libraries in biological screens, the Boston University Chemical Library Consortium (CLC) has been established, which consists of a group of investigators who will be evaluating these compound libraries in biological screens. The BU-CMD builds upon a foundation developed over a twelve-year period by the Center for Chemical Methodology and Library Development at Boston University (CMLD-BU). The CMLD-BU focused on the production of novel chemical libraries of unprecedented complexity for biological screening.

The BU-CMD has inherited several important CMLD-BU resources, including the small molecule screening collection. We will continue to make our compound libraries available for screening free-of-charge to interested researchers in both academia and industry.

The CMLD-BU is directed by Prof. John Porco.

BU Nanoscience and Nanobiotechnology (BU-CNN). The BU-CNN was formed to advance academic and technological research and development by extending discoveries in nanoscale materials and platforms into diagnostics and therapeutic areas of biomedicine. The center serves as a hub for nanoscience researchers from BUMC and BUCRC to build interdisciplinary research and training. CNN connects scientists and engineers from disparate disciplines in seminars, meetings, joint visitor programs, interdisciplinary courses, industrial collaborations, and seeded projects. CNN has three core functions: First, to develop interdisciplinary research and education in nanoscience and nanobiotechnology, second, to develop and run an industrial liaison program that partners researchers with external companies for mutual benefit and third, to connect researchers to resources for technological commercialization. BUMC researchers have successfully competed to set up a training program in nanosciences for cancer. Bennett Goldberg, PhD collaborating with Douglas Faller MD, PhD, Director of the Cancer Center at BUSM, and Katya Ravid, PhD, Director of the ARC program were awarded a five-year, $2 million grant from the NCI’s Alliance for Nanotechnology in Cancer to create the BU Cross-disciplinary Training in Nanotechnology for Cancer (BU-XTNC) program. Projects are carried out by trainees supervised by a mentor based in the CNN and a clinical co-mentor. CNN is directed by Mark Grinstaff, Distinguished Professor of Translational Research, Professor of Biomedical Engineering and Chemistry & Materials Science and Director of the BU CTSI Pilot Awards Program.CNN is directed by Mark Grinstaff.

The Boston University Nanotechnology Innovation Center (BUnano) is a collaborative research center that includes faculty members from ten departments from the Colleges of Engineering and Arts and Sciences and the School of Medicine. The Center’s mission is to promote a vibrant and dynamic community for nano-related disciplines at BU. Our objectives are to advance research and education in nanoscience and nanotechnology and to achieve significant growth in research support. We achieve these objectives by: Providing seed funding for collaborative research and development; Developing large, interdisciplinary grant proposals; Funding graduate students; Organizing targeted workshops and symposia.To accelerate the development and deployment of nanotechnology innovations that be used to meet key challenges in medicine, energy and materials science, the Center builds linkages between researchers and technology commercialization resources at BU, including the Photonics Center, the Center for Future Technologies in Cancer Care (CFTCC) the Cancer Research Center, the Evans Center for Interdisciplinary Biomedical Research, the Clinical and Translational Science Institute, and the Fraunhofer Center for Manufacturing Innovations. The BUnano Center also serves as focal point for interactions with peer universities, Boston-area hospitals, industry, and government to accelerate advances in the field of nanoscience.

BU Center for Future Technologies in Cancer Care. Catherine Klapperich, PhD, in the Department of Biomedical Engineering (and member of our Workforce Development, K and T programs) has established this center with a large award under the NIH Point of Care Technologies Research Network (POCTRN) program to

develop novel point-of-care diagnostics and monitoring for cancer (www.bu.edu/cftcc). Their work involves assessing early stage technologies in terms of clinical needs, market demands, setting appropriateness and commercialization strategies. An integrated multidisciplinary center consisting of engineers, clinicians, public health practitioners, and technology transfer experts is evaluates technologies in various stages of development for suitability across a range of primary care and non-traditional healthcare settings. The Center comprises an Administrative Core, a Clinical Needs Assessment and Impact Analysis Core, a Training Core and a Prototype Development and Testing Core. Over 20 emerging technologies have been funded in the last 5 years of the Center. Examples include point of care technologies for the early detection of cervical cancer and oral cancer, new devices to monitor the effectiveness of chemotherapy during infusion, and mobile health applications to enable pain management and nutrition in patients undergoing therapy.

Translational Research Commercialization. Boston University offers a rich source of research, intellectual property, proprietary know-how, and novel methodologies and then supports faculty to bring to the patient new therapeutics, devices and diagnostics. These “assets” often have tremendous commercial value if appropriately evaluated and supported. However, new venture creation can be confusing for those unfamiliar with the process. As a result, we offer our faculty, students, and staff these outstanding services: Technology Development. Technology Development’s main focus is to commercialize the inventions and discoveries that emerge from Boston University research. The objective is to ensure the development of our groundbreaking research and discoveries by facilitating collaborations with the entrepreneurial and industrial ecosystems through licensing, sponsorship, and new ventures. Primary services include patenting, licensing and new venture creation.

The Ignition Award program is a gap funding program managed by Technology Development that provides competitive grants to faculty interested in further developing their discoveries for future commercial applications.

Innovate@BU. INNOVATE@BU is an all-university initiative designed to foster a creative community. The program connects all of the ongoing curricular and co-curricular efforts in innovation and entrepreneurship throughout Boston University. It operate a new university-wide student innovation center – the IDG Capital Student Innovation Center Build Lab, where undergraduate and graduate students can develop the skills to express their creativity, prototype their ideas, create enterprises, team up with like-minded students and find mentors. Finally, it strengthens our connections to entrepreneurial peers, the Boston business community, and the world.

The power of Innovate@BU lies in no one person or program, but in the diverse network of skills, concentrations, and passions spread across the entire University. BUild Lab is a central hub where you can attend hands-on workshops, make connections with mentors, find funding sources, and collaborate with other students on a project that plays to your passions. Affiliated programs include:

The Faculty Innovation Network (FIN), is comprise of over 40 BU faculty. Year-round, FIN members serve as innovation ambassadors and extend the Innovate@BU mission throughout their schools, colleges, departments, and classrooms. Individually and as working groups, members contribute their time and expertise for Innovate@BU projects and initiatives including research, creating resources for students and faculty, mentorship, and curriculum development.

The Innovate@BU Summer Accelerator is a full-time summer program that guides BU students and alumni teams through the startup process and provides all of the perks that an early-stage venture needs.

The Mentoring Program provides a unique opportunity for seasoned entrepreneurs and business executives to have direct and meaningful interaction with the BU community. The mentoring program educates faculty, students, and alumni to facilitate early-stage business formation.

BU Spark! is an initiative to support student driven innovation and entrepreneurship in computer science, computer engineering and related disciplines. Housed at Boston University’s Hariri Institute for Computing, BU Spark aims to help students realize their entrepreneurial potential by providing access to resources, knowledge, and expert networks to support their innovation journeys.

The Entrepreneurship and Intellectual Property Clinic and the Technology & Cyberlaw Clinic is a collaborative program between BU Law and MIT that brings together law students with student entrepreneurs looking to launch new businesses and advance technological innovations while adhering to legal and regulatory requirements. The clinic provides free consults and legal services related to company formation and intellectual property rights.

The Engineering Product Innovation Center (EPIC). EPIC is a 15,000-square-foot, $9 million pioneering facility in the heart of the Boston University’s Charles River Campus that helps address a critical need in the US: the training of prospective engineers who understand how to develop and manufacture innovative new products. EPIC features teaching space, demonstration areas, laboratories and a product fabrication facility, all in a reconfigurable layout that is easily adaptable to future technologies and educational needs. The facility includes:

o Hardware and software for computer-assisted design, including an $18.8 million in-kind gift of product design and lifecycle management software from PTC Rapid 3D prototyping

o additive manufacturing toolso a full machine shop, featuring multi-axis CNC machines, mills, lathes, and other standard industrial

tools, electronics design and fabrication capability, including test, PCB fabrication and surface mount soldering, an automated, robotic, manufacturing line

o a materials characterization laboratoryo a metals foundryo a complete carpentry shop

Business Incubation. Boston University’s Business Incubators host up to fifteen technology start-up companies. The mix of companies includes Life Sciences, Bio-tech, Medical Devices, Photonics, Clean Energy, and Engineering.

Corporate Relations. Corporate Relations builds strategic long-term relationships with industry, creating road maps that identify areas of mutual opportunity. Faculty can work with Corporate Relations staff to understand the landscape of potential corporate partners to synergize and accelerate the application of their discoveries into commercial products and services.

CELL-MET. The NSF Engineering Research Center in Cellular Metamaterials – CELL-MET – is designed to stimulate translation of research to practice by facilitating worldwide corporate, clinical, and institutional partnerships. CELL-MET—with Boston University as the lead institution— aims to transform cardiovascular care by combining breakthroughs in nanotechnology and manufacturing with tissue engineering and regenerative medicine, while also developing areas of expertise in education, diversity, administration, and outreach.

CELL-MET will use the latest multiscale 3D printing technologies to engineer scaffolds that guide cells to assemble into complex tissues that exhibit desired behaviors. The scaffolds will incorporate actuators to apply dynamic electrical and mechanical signals as well as cellular “glues” that include biological signaling molecules, all of which can be chosen to foster desired activity of the cells and tissue. The researchers will also employ optogenetics and other imaging techniques to monitor and control cellular activity. The ultimate goal is to fabricate personalized heart tissue that could be used in the shorter term to test the efficacy of drugs and eventually to replace diseased or damaged muscle after a heart attack.

CELL-MET will be housed at Boston University, the lead institution on the grant. David Bishop, an ENG professor of electrical and computer engineering, a College of Arts & Sciences professor of physics, and head of ENG’s Division of Materials Science & Engineering, will direct the center. Two partner institutions—the University of Michigan and Florida International University—as well as six affiliate institutions—Harvard Medical School, Columbia University, the Wyss Institute at Harvard, Argonne National Laboratory, the École

polytechnique fédérale de Lausanne in Switzerland, and the Centro Atómico Bariloche/Instituto Balseiro in Argentina—will offer additional expertise in bioengineering, nanotechnology, and other areas.

Institute for Health System Innovation and Policy. The Institute for Health System Innovation and Policy was created by Boston University in September of 2016, to develop solutions to address the critical challenges of health and healthcare, both in the United States and globally. Its goal is to transform healthcare through integration and innovation across science and technology, system design and management, leadership, and policy development.

Dr. Jonathan Woodson is the founding Director of the Institute. He brings an exceptional ability to bridge research, education, management, business, clinical practice, and public policy. His integration of arenas that typically function in isolation underlies the unique approach of the Institute to creating positive impact.

The Institute is truly a university-wide organization, drawing upon the diversity of the Boston University community’s constituent schools and faculty, as well the greater Boston bio-technology and medical ecosystem, to leverage the development of leaders and solutions for the complex current and future problems in healthcare.

The Institute is committed to research and education to support the development and deployment of capabilities to produce effective and efficient healthcare delivery, optimal health outcomes, and better population health. It uses analytic tools and evidence-based study to improve the value creation across all elements of the healthcare system.

Center for Integration of Medicine & Innovative Technology (CIMIT). In a joint membership with Boston University (BU) and Boston Medical Center (BMC) the Center for Integration of Medicine & Innovative Technology (CIMIT), the Cambridge, Massachusetts-based consortium brings together clinicians, scientists and engineers to solve complex medical problems using novel technologies. The BU/BMC collaboration forms a highly integrated academic medical center that combines the highest standards of patient care, medical training, and biomedical engineering and research.

Boston Biomedical Innovation Center (B-BIC). B-BIC is a consortium of eleven institutions across Boston. Harvard Medical School and the two founding members of Partners Healthcare, Brigham and Women’s Hospital and Massachusetts General Hospital have a long, productive history of bringing innovation to commercialization. In addition, through their participation as key Harvard-affiliated institutions, Beth Israel Deaconess Medical Center and Boston Children’s Hospital, and the VA Boston Healthcare System are intimately linked via the Harvard Catalyst and through CIMIT. BWH, MGH, BIDMC, BCH, and VABHS now have common regulatory panels and approved inter-institutional policies involving confidentiality and the handling of intellectual property. Four other partnering institutions that are currently active members of CIMIT also hold membership in B-BIC: Boston Medical Center, Boston University, the Draper Laboratory, and Northeastern University. These four institutions provide numerous additional innovators as well as complementary expertise in bioengineering and drug development. Boston University, through its School of Engineering and Department of Bioengineering, provides a computational simulation laboratory, a micro- and nano-imaging facility, a micro and nano-fabrication facility, and a bio-interface technology core. The Boston University-Fraunhofer Alliance for Medical Devices, Instrumentation, and Diagnostics, and the materials characterization core and prototyping core of the Harvard Medical School-based Wyss Institute for Biologically Inspired Engineering, all of which were created to accelerate the development and deployment of medical innovation from the laboratory to patient point-of-care, offer unparalleled resources to B-BIC for rapid realization of essential prototype device and diagnostic technologies. The Draper Laboratory is a not-for-profit research and development laboratory focused on the design, development, and deployment of advanced technological solutions for challenging problems. Northeastern University has a long-standing focus on use-inspired research, engendering a research culture that is intrinsically collaborative and interdisciplinary.

Fraunhofer Center for Manufacturing Innovation (CMI). In collaboration with Boston University, CMI conducts advanced research and development leading to engineering solutions for a broad range of industries, including biotechnology/biomedical, photonics, manufacturing and renewable energy. The BU Alliance was created to accelerate the development and deployment of medical innovation from the laboratory to the patient point-of-care.

Massachusetts Green High-Performance Computing Center (MGHPCC) in Holyoke, MA, founded in 2012 by BU and several university and industry partners. The Massachusetts Green High Performance Computing Center (MGHPCC) is a data center dedicated to research computing. It is operated by five of the most research-intensive universities in Massachusetts: Boston University, Harvard University, MIT, Northeastern University, and the University of Massachusetts. It serves the growing research computing needs of the five founding universities as well as other research institutions.

Boston University Medical Campus (the applicant institution) is located in the historic South End of Boston, two miles from the Charles River Campus but connected by continuously running shuttles, free cross-campus parking and robust webinar resources. It comprises the Boston University School of Medicine, the School of Public Health, the Henry M. Goldman School of Dental Medicine, and the Division of Graduate Medical Sciences of the School of Medicine. Boston Medical Center is the primary teaching affiliate of the School of Medicine embedded intimately within the Schools of Medicine, Public Health and Dentistry. All schools and the hospital are within a 3 block area connected by walkways to provide easy access and easy interaction for teaching, patient care and research. The accompanying map graphically shows how the facilities of the medical campus are completely physically integrated.

Renowned for the quality of teaching and research, and for service to the community, these schools provide education and training in the most current thinking and techniques in their fields, with a particular focus on serving disadvantaged, underserved, and indigent populations. The Medical Campus/Hospital in 2013 received $366M in sponsored research funding. The offices of the CTSI are within the centrally located medical school main building. The Provost of the Medical Campus and Dean of the School of Medicine is Karen Antman, MD.

Boston University School of Medicine (BUSM). Boston University School of Medicine is dedicated to the educational, intellectual, professional and personal development of a diverse group of exceptional students, trainees, and faculty who are deeply committed to the study and practice of medicine, to biomedical research, and to public health. As a community, we place great value on excellence, integrity, service, social justice, collegiality, equality of opportunity, and interdisciplinary collaboration.

Boston University School of Medicine is ranked 32nd in Research on the 2015 list of Best Medical Schools by the US News and World Report and 30th in the world for Clinical Medicine among clinical, pre-clinical and health universities. In the autumn of 2014, BUSM's first year medical students were 52% female, and 19% were of an ethnicity that is under-represented in medicine. Out of the 178 matriculated students, 120 are in the traditional Doctor of Medicine (MD) program. Seven were enrolled in the MD/PhD program, and the remaining students were in some other type of non-traditional MD track. BUSM also offers joint degrees with other Boston University graduate schools, allowing the medical students to earn an MD degree with a Master of Business Administration (MBA), Master of Public Health (MPH), or PhD.

The Division of Graduate Medical Sciences (GMS) at Boston University School of Medicine (BUSM) is a recognized leader in research and graduate education in the biomedical sciences. Students can choose from 33 fields of study, with interdisciplinary programs available in many areas. Students may pursue PhD or MD/PhD degrees in 15 different departments and programs.

The school contains more than 550,000 square feet of research space in multiple buildings (See Appendix-Overall). The School of Medicine financially supports many core laboratories, and houses centers and institutes that participate in a vast array of research. The campus possesses an impressive array of basic research cores with state-of-the art equipment vital for early stage translational research. They include: analytical instrumentation, biomedical and cellular imaging, biospecimen archive, experimental pathology, flow cytometry, high throughput screening, Illumina sequencing, microarray analyses, mass spectrometry, immunohistochemistry, metabolic phenotyping, and animal imaging including IVIS, MRI, and infrared imaging.

We also have extensive animal facilities. The Laboratory Animal Science Center (LASC) has been an AAALAC accredited animal care program since 1971. LASC has 35,000 square feet and cares for most species of research animals annually under the direction of the Attending Veterinarian. The Institutional Animal Care and Use Committee (IACUC) reviews all protocols prior to ordering of animals.

Boston University is a major academic research institution conducting high-quality research as part of its mission of advancing human health. Animal research has been, and continues to be, a critical component of the efforts in advancing our understanding of cancer, heart disease and neurodegenerative diseases such as Alzheimer’s and Parkinson’s to name a few.

We recognize and embrace the fundamental interdependence of humans and animals and are committed to the core value of humane care in the use of any animals. The institutional committee that oversees the use of animals at Boston University is vigilant in meeting their commitment to animal welfare. The Institutional Animal Care and Use Committee (IACUC) reviews every proposed research protocol.

The Boston University Clinical and Translational Science Institute (CTSI)

Transforming biomedical discoveries into clinical diagnostics and therapeutics is a highly complex, expensive, and cumbersome task that takes many years.

The Boston University Clinical and Translational Science Institute (CTSI) is a partnership between Boston University and Boston Medical Center launched in 2008 with funding from the National Institutes of Health, which has been tasked with the mission of expediting this process.

CTSI is funded by a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences, National Institutes of Health, and grant UL1TR001430.

The CTSI serves as a center of expertise which provides tools, services, and resources to clinical and translational investigators to maximize the impact of their discoveries and speed the translation of their research to the bedside. In particular, we are committed to improving the health of vulnerable populations through novel discovery approaches and by engaging this population in the research enterprise.

Our vision is shaped and supported by CTSI’s two unique strengths: our long history of a caring and scientific relationship with a diverse patient population and the rich scientific enterprise within the BU community.

We have noted that individual and incremental local and national solutions to the inefficiencies in translational science have not had a lot of impact. On the contrary, we find our greatest successes occur when we employ team approaches to problems. As a result, the CTSI has succeeded in meeting many of the challenges of T1 through T4 translational science because we have bridged these environments through innovative collaborative processes. Figure 1 emphasizes the local, highly-integrated, interconnected, and interdependent nature of our network. As a result, every CTSI interaction with the CTSA Network brings to the collaboration the full strength of an expanded portfolio of our resources to expedite progress in translational research. While we present many types of solutions to barriers in translational science, we strongly endorse NCATS’ emphasis on multi-disciplinary team approaches to manage complexities and create innovative programs.

The CTSI’s vision is to be the strongest advocate for research that represents the needs of our diverse populations by creating superior resources that can reliably be transferred to the national CTSA Network.

In an effort to do better research and do research better, CTSI’s aims are centered around four key focus areas:

Discover, demonstrate, deploy, and disseminate novel TRAINING methods that will enhance our entire translational science workforce

Effect meaningful research relationships with all COMMUNITIES AND STAKEHOLDERS that empower bi-directional contributions to strengthen translational research across the lifespan

Use our unique, full-spectrum RESEARCH strengths to discover, develop, and disseminate improved treatments and diagnostics that address the problems of our community and nation

Share innovative best practices with other hubs in the national CTSA network, and COLLABORATE in the conduct of coordinated, multi-center, translational research

Leadership

BU CTSI leadership: Dr. David M. Center, MD, is the director of the CTSI. He is Gordon and Ruth Snider Professor of Pulmonary Medicine and associate provost for clinical translational research. Also the chief of the Division of Pulmonary, Allergy and Critical Care Medicine at BMC, Dr. Center has directed CTSI since its inception in 2008. An accomplished scientist, and clinical and research administrator and educator, his experience and qualifications include 34 years of individual and program research grants from NIH, focusing on the immunology of lung disease; a breadth of research approaches including cell-, animal-, and human-bases studies; over 150 manuscripts and 30 US patents. He is a former chair of both NIH and American Thoracic Society study sections and numerous national committees. As the Principal Investigator of an NHLBI T32 training program, he is deeply committed to multidisciplinary research and research training, including clinician scientists. In the past two years, he has been elected to the National Academy of Inventors, elected a Fellow of the AAAS and awarded the Edward Livingston Trudeau Medal of the American Thoracic Society, its highest honor for accomplishment in lung diseases and service to the society.

Dr. Center is assisted by two directors: Dr. David Felson, director of workforce development, and Dr. George O’Connor, director of clinical research.

Dr. Felson is professor of epidemiology and medicine and one of the world’s leading experts in osteoarthritis of the knee. He has over 450 publications and numerous patents on devices to decrease stress on the knee. He is the author of our K30 program and has mentored over three dozen MD clinical scholars.

Dr. O’Connor is an internationally known clinical researcher in the field of chronic lung diseases of adults and children. He is one of BU/BMC’s most experienced investigators, with more than 22 years of continuous NIH funding of both epidemiologic studies and randomized controlled trials. Dr. O’Conner headed the Framingham Heart Study Pulmonary epidemiology program.

BU CTSI General Clinical Research Unit (GCRU). The GCRU, located within BUMC, provides resources to BUMC faculty, including a controlled and optimal setting for clinical investigators, career development programs, and training for health professionals. The GCRU is currently the setting for over 50 different active protocols, it offers infrastructure and clinical investigation resources. Examples of resources provided by the GCRU include: The ability to conduct pharmacokinetic studies in a controlled environment with both adult and pediatric

inpatients and outpatients Resources for timed collection of specimens and other specialized testing (bone density, CT scan, etc.) A private environment to explore patterns of behavior A primary location for the education of future physicians, scientists, and nutritionists in patient-oriented

research

BU CTSI offers resources to investigators in medicine and dentistry funded by Federal and non-Federal sponsors, as well as those conducting innovative clinical research pilot studies before requesting funding. The

GCRU also assists projects funded in whole or in part by pharmaceutical and biotechnology companies. Experienced medical professionals facilitate the day-to-day research activities for physicians, trainees and subjects. The GCRU boasts a highly trained research staff of 7 people who support inpatient and outpatient, adult and pediatric, medical and dental studies that discover the cause, progression, prevention, control and cure of human diseases.

GCRU Nursing. Nurses at the Clinical Research Unit (CRU) are trained to make complex research observations and take precise specimen collections (i.e., Insulin Clamp). These skilled clinicians are able to participate in groundbreaking research while ensuring patients receive compassionate, quality patient care. The team also includes a certified medical assistant to assist in research methodologies. With an average of 30 years of experience, GCRU nurses are certified in Chemotherapy, Bone Densitometry and skilled in the following:o Bone densitometryo CT scan of the extremitieso EKGo Fat and muscle biopsieso IM/SC injection administrationo Inserting intravenous lines

o IV administrationo Lumbar punctureso Medication teachingo Performing pharmacokinetic drug studieso PK sampling o Research methodologies

GCRU Laboratory. The laboratory on the CRU is staffed with an experienced laboratory manager and laboratory assistant with years of experience in laboratory services and an average of 15 years of phlebotomy experience combined in pediatric and adult participants. The CRU laboratory provides the following services:o Bio-Repository Services (offers term storage of research samples by BUMC investigators)o Informational resource before and during the implementation processo Packaging and shipping (dry ice for shipping and transport)o Processing- Blood, Urine CSF, Sputum and o Storage of frozen samples with matching log.All laboratory personnel are certified in: o Lab safety (yearly)o Safety and Infection control (yearly, online) ando Shipping biologicals (every 2 yrs)

GCRU Facilities. The General Clinical Research Unit (GCRU) located on the 8th floor of the Evans building on 72 East Concord St. in Boston MA, is an ideal setting for outpatient research studies offering a variety of resources including:o Children’s play areao Conference roomo Exam roomso Extreme CT scano Investigator and Coordinator stationo Participant dining area

o Laboratoryo NEW bone densitometry w/fat distribution

analysiso Private interview and consultation roomso Private outpatient roomso Videotaping laboratories andoWaiting room

The GCRU also offers an inpatient setting for studies requiring overnight stays. Prior considerations and accommodations should be made with the Nurse Manager prior to the implementation process.

Dental Clinical Research Outpatient Facility. The dental clinical research outpatient facility is located on the 1st floor of the dental school at 100 East Newton Street, Boston, MA. The facility occupies 1,000 square feet and serves faculty in the dental school. The dental clinical research unit offers services that support multidisciplinary and long-term clinical studies and product trials. This state-of-the-art facility provides researchers with a centralized, controlled testing environment for oral health-related investigations. A ten chair conference room with audio-visual equipment is available for use by investigators. Every dental unit offers:o A centralized databaseo A patient reception areao A ten-chair conference room with audio-visual o Curing lights

o Foot and touch-pad controlo Four fully-equipped dedicated dental unitso High and low-speed hand pieceso Timers and large patient mirrors and equipment

o Ultrasonic systems (25,000 mh/sec)

Bone Density Facility. A new Hologic QDR 4500W bone density instrument was purchased in 2014. It is capable of doing bone densitometry, as well as fat distribution analysis in adults, children and infants. The QDR 4500W is a multiple detector, fan-beam Dual-energy X-ray Absorptiometry (DXA) bone densitometer. Hologic QDR 4500W Instruments allow regional and global measurements of the whole body. An advanced application of QDR technology can directly measure fat and skeletal mass and is useful in research and clinical studies.

Xtreme CT Scanning. The SCANCO MEDICAL AG Xtreme CT performs a quantitative computed tomography scan of the distal radius or distal tibia to provide measurements of volumetric bone density, which can be used as an aid to the physician in determining risk of fracture.

Pro-Form 505 CST Treadmill (Model #PFTL60910.1). This treadmill features a walking belt coated with high-performance lubricant. The console features 15 onboard workouts as well as allowing manual operation. The treadmill's speed and/or incline can be changed as desired. This particular model has an iFit feature that can be used if a subscription is purchased.

Observation and videotaping laboratories. Specialized areas are available for recording developmental behavior of children and adults.

BU National Emerging Infectious Disease Laboratory (NEIDL). A 192,000-square-foot, $128M, seven-story building located within BUMC, The NEIDL, funded by the NIH/NIAID, is one of the few laboratories in the U.S. that can support BSL-4 research on pathogens such as the Ebola virus. The containment area includes imaging, aerobiology, insectaries, animal facilities, GMP lab space and other specialized cores and support spaces to support basic research and vaccine development in emerging infectious diseases. In addition, the facility houses a state-of-the-art BSL-4 training simulator to provide hands-on training for research staff, faculty, and some support personnel.

The National Emerging Infectious Diseases Laboratories (NEIDL) is part of a national network of secure facilities studying infectious diseases that are—or have the potential to become—major public health concerns. The laboratories are dedicated to the development of diagnostics, vaccines, and treatments to combat emerging and re-emerging infectious diseases. In addition to BSL-2 and BSL-3 laboratories, the NEIDL houses a BSL-4 laboratory. The NEIDL adds to the growing life sciences industry in the region, throughout the Commonwealth of Massachusetts, and across the country.

The NEIDL uses state-of-the-art technologies designed to conduct research in safe and secure environments. In fact, the facility was designed and constructed with the highest attention to community and laboratory safety and security. The laboratories emphasize comprehensive core research facilities that enable basic, translational, and clinical research and the development of products related to emerging infectious diseases. Core support laboratories containing sophisticated facilities—including high-power microscopes, Magnetic Resonance Imaging (MRI) machines, and diagnostic tools to study new vaccines and drugs—are housed at the NEIDL.

The NEIDL represents a major step forward in advancing public health and solidifying the New England area’s reputation as the biomedical research hub of the nation. Supported by all local research institutions, the 192,000-square-foot, seven-story building serves as a venue and resource for training researchers in infectious diseases. The facility is located within BioSquare, a biomedical research and business park adjacent to the Boston University Medical Campus.

Scientific Environment: The National Emerging Infectious Diseases Laboratories (NEIDL) is housed on the Boston University Medical Campus within close proximity to the School of Medicine, School of Dental Medicine and School of Public Health and their associated research facilities. The Medical Campus also houses major Core facilities (http://www.bumc.bu.edu/busm/research/cores/) and includes an extensive Animal Science Center which includes animal facilities for BSL-2 and BSL-1 animal work. In addition to Basic Sciences and Clinical Departments, the Medical Campus also includes the Center for Regenerative Medicine, the Center for Network Systems Biology, and the Clinical and Translational Science Center. The Boston University Medical Campus is a short shuttle bus ride from the Boston University Campus on the Charles River. The BU campus includes the Engineering School including its Biomedical Engineering Department and its Biologic Design (“synthetic biology”) group. Major research programs in the Department of Chemistry and the Department of Biology are also of importance to the goals of the NEIDL, and the Bioinformatics Graduate Program is managed from the Charles River Campus. Boston University is a highly interactive and collaborative environment which is supported by the University administration to ensure that artificial barriers to success do not hamper innovation in research. Core activities are centered within the appropriate spaces of the NEIDL with support of the wider university offices that serve as resources for these Core activities.

Laboratory: The NEIDL contains extensive BSL-2, BSL-3 and BSL-4 laboratory facilities, as well as core facilities to support innovative infectious diseases research in high and maximum containment. There are extensive spaces for using animal models for infectious diseases research in BSL-3 and BSL-4.

Animal: The Laboratory Animal Science Center (LASC) at Boston University has been an AAALAC accredited animal care program since 1971. Animals are housed in state-of-the-art facility run by licensed veterinarians and supported by a large technical staff. All individuals involved in animal research are trained in proper animal handling, dissection, anesthetization and euthanasia techniques as described and approved by the Institutional Animal Care and Use Committee (IACUC) protocol(s). The Animal Services component of the NEIDL are integrated into the larger Animal Sciences Center, under the direction of the Attending Veterinarian. Each of the animal holding rooms in ABSL-3 and ABSL-4 includes dedicated procedure space for animal work. In addition, there are insectary spaces for studying vector transmission of pathogens localized near the animal facilities within the NEIDL.

Computer: All laboratories are serviced by the universities IS&T group, with the exception of those services that are uniquely required for work within the NEIDL and are managed by the IT Core staff dedicated to the NEIDL. This includes building automation systems and select agent inventory control which is managed in a safe and secure network environment.

Office: Office spaces within the NEIDL are provided near the relevant core activities. The Administrative Core is completely integrated into and supported by the administrative infrastructure of the University. All offices are accessible in an environment secured via proximity card and iris scan access.

Major Equipment: The major equipment within the NEIDL for operational support and services to scientific staff includes the following: Leica Confocal Microscope, 2 BD LSRII FACS analyzers, Biorad Bioplex 200 instruments, Beckman L90K ultracentrifuges, luminometers, Tecan Spark 20M multimodal microplate reader, Odyssey CLx infrared imager, -80C freezers, Biosafety cabinets, ELISA readers, refrigerated centrifuges, humidified CO2 incubators and all instrumentation required for conventional cell biology, virology and microscopy needs. For work with animals, instrumentation includes clinical chemistry and hematology systems (Drew Scientific Hemavet 950 FS multi-species automated hematology system, Abaxis Vetscan VS2 and Clinical Chemistry Analyzers, Abaxis Piccolo Xpress Chemistry Analyzer, Abaxis VSpro for coagulopathies and Diagnostica Stago Coagulation Analyzers. The NEIDL also houses a Bruker 4.7T MRI, CT scan and IVIS scan instrumentation for live animal monitoring. Extensive aerobiology suite with instrumentation for aerosol delivery of pathogens or therapeutics to animals from mice to non-human primates, including Class III glovebox biosafety cabinet and animal transfer modules are in the facility as well.

Interfacing with other support offices at Boston University. The operational core services offered in the NEIDL benefit from the additional infrastructure on the Boston University Campus, which not only provide significant expertise but also provide services that we do not need to duplicate. For example, the IT services in the NEIDL are supported by a large BU Information Services and Technology Team that provides IT services to the NEIDL, with the exception of the BSL-4 facilities. Similarly, our EH&S core is supported by a larger EH&S group within the University, and Emergency Response is supported by a University wide ER group which has long experience working with local, state, and national responders. The Community Relations Services are integrated with BU campus-wide services which include the Office of Government and Community Affairs, while our Occupational Medicine Program is supplemented by a larger Research Occupational Health Program at the University.

BU School of Medicine Centers and Institutes located within BUMC. These categorical homes for interdepartmental clinical and translational research that were developed to be organ- or disease- specific. They have been profound successes in the science they have generated since their inception in 1982. Selected ones are: Alzheimer’s Center Amyloid Treatment & Research Center Arthritis Center Cancer Center Cardiovascular Proteomics Center Center for Excellence in Sickle Cell Disease Center for Global Health & Development Center for Regenerative Medicine Center for the Study of Traumatic

Encephalopathy (see below) Data Coordinating Center

Evans Center for Interdisciplinary Biomedical Research

Framingham Heart Study (see below) Genome Science Institute Pulmonary Center Silvio O. Conte Center for Neuroscience Slone Epidemiology Center Spivack Center for Clinical and Translational

Neuroscience Whitaker Cardiovascular Institute Women’s Health Interdisciplinary Research

CenterOne high profile center, the BU Center for the Study of Traumatic Encephalopathy (CSTE) raised the national debate on athletes (and others) with a history of repetitive concussions. Launched in 2008 as a joint venture between the School of Medicine and the Sports Legacy Institute, the CSTE has been studying Chronic Traumatic Encephalopathy (CTE), a progressive degenerative disease of the brain that has been tied to cognitive and behavior disorders and eventually results in dementia. More than 200 athletes from various sports have committed to donate their brains to the center after death.

The CTE Center is an independent academic research center located at Boston University School of Medicine. Part of the Boston University Alzheimer’s Disease Center (BU ADC), it was established in 1996 as one of 29 centers in the United States funded by the National Institutes of Health to advance research on Alzheimer’s disease and related conditions.

In collaboration with the VA Boston Healthcare System, and nonprofits including the Concussion Legacy Foundation (formerly known as the Sports Legacy Institute), and other NIH funded ADC Centers the CTE Center conducts high-impact, innovative research on chronic traumatic encephalopathy and other long-term consequences of repetitive brain trauma in athletes and military personnel.

Ann McKee, MD, Neuropathologist and Neurologist, is Director of the CTE Center. Dr. McKee also directs the Neuropathology Core of the Boston University ADC and directs all the brain banks at VA Boston   Healthcare System, including the VA-BU-CLF brain bank and BU ADC brain bank. The neuropathologists, Thor Stein, MD, PhD, Bertrand (Russ) Huber MD, PhD   and Victor Alvarez, MD participate in the daily operations of the VA-BU-CLF brain bank and conduct neuropathological analyses and research for the CTE Center. Robert Stern, PhD directs the Clinical Research team. Michael Alosco, PhD and Jesse Mez, MD, PhD are active clinical researchers and participate in clinical neurological and neuropsychological data collection. Dr. Lee Goldstein, MD, PhD heads the molecular research team.

Research conducted at the CTE Center continues to lead the field in furthering the understanding of mild traumatic brain injury (mTBI) and Chronic Traumatic Encephalopathy (CTE). The VA-BU-CLF Brain Bank is the largest tissue repository in the world focused on traumatic brain injury (TBI) and CTE. The VA-BU-CLF Brain Bank contains more than 425 brains, including over 270 brains that have been diagnosed with CTE using the

recently defined NINDS criteria for the diagnosis of CTE (6). Dr. McKee and her team of neuropathologists and other investigators have published a large number of studies focused on CTE (see below).

The CTE Center is part of the Boston University Alzheimer’s Disease Center (BU ADC), established in 1996 as one of 29 centers in the US funded by the National Institutes of Health to advance research on Alzheimer’s disease and related conditions. In collaboration with other NIH-funded ADC’s and the non-profit, Concussion Legacy Foundation and CTE Center conducts high-impact, innovative research on Chronic Traumatic Encephalopathy and other long-term consequences of repetitive brain trauma in athletes and military personnel. The mission of the CTE Center is to conduct state-of-the-art research on CTE, including its neuropathology and pathogenesis, clinical presentation, genetics and other risk factors, biomarkers, methods of detection during life, and methods of prevention and treatment.

The nationally recognized NHLBI funded Boston University Framingham Heart Study (FHS) has been a leader in the field of population- based research, T3 and T4. Since 1948, careful monitoring of the Framingham Study three cohorts of FHS population participants has led to the identification of major cardiovascular disease (CVD) risk factors, as well as valuable information on the effects of these factors such as including blood pressure hypertension, blood triglyceride and cholesterol dyslipidemia levels, diabetes, and obesity, as well as the contributions of age, gender, sex, and psychosocial issues to CVD risk. Risk factors for other physiological health conditions such as dementia, lung disease, kidney disease, and bone disease have been and continue to be investigated also are under investigation. In addition, the relationships between physical traits and contributions of genetic patterns variation to CVD and other traits are now being studied through genomic analysis initiative using 500K chip technology whole genome sequencing of over 4000 FHS participants. The FHS population research informs current guidelines for the evaluation and management of hypertension and dyslipidemia. New molecular research from the FHS is used by physician scientists where to return to at the bench or to pose new clinical research questions and new basic research projects. A number of our CTSI scientists are full members of the FHS and use its data bases for their research and training programs, described in the body of the Grant where appropriate, including our new program in iPSC generation from the carefully phenotyped FHS subjects.

The Framingham Heart Study (FHS), a joint program of at Boston University and the National Heart, Lung, and Blood Institute, is one of the world’s most informative and longest running studies on cardiovascular disease (CVD). More than 3,000 articles based on the study’s FHS data have been published in peer-reviewed medical journals, including the New England Journal of Medicine, the Journal of the American Medical Association, Nature, Nature Genetics, Circulation, and the Lancet.

The Framingham Heart Study has been a partnership between the National Heart, Lung, and Blood Institute and Boston University since 1971.

Beginning in 1948, the family-based study provided much of the earliest scientific evidence of the relationships between cardiovascular disease and contributions of smoking, obesity, diabetes, high blood pressure, and high cholesterol to CVD.

Knowledge of the combined effects of these risk factors, and others, led to discoveries such as the Framingham Risk Scores Functions. Physicians and patients throughout the world currently use these functions to estimate, often decades in advance, individual risks for developing specific cardiovascular diseases.

Other landmark discoveries that came from the study include the protective role of HDL (or “good”) cholesterol and the adverse effect of hormone replacement therapy on women’s risk for stroke. See more of the study’s research milestones.

Today, the study remains a global epicenter for epidemiologic research. Current research focuses largely on identifying genes and proteins associated with various risk factors and cardiovascular diseases. In total, Framingham FHS investigators have identified hundreds of DNA sites associated with risk of coronary heart disease, hypertension, obesity, diabetes, dyslipidemia, stroke and dementia, atrial fibrillation, lung disease, valvular calcification, bone density, and other pressing health conditions.

The Framingham investigators also conduct ancillary studies targeting areas of research such as:• Heart and brain imaging• Cognition and stroke• Diet and physical activity

• Bone and sleep disorders

Scientists in 33 states and in more than a dozen countries use the study’s clinical and laboratory data resources. The Framingham Heart Study FHS welcomes collaboration and invites investigators throughout the world to apply to use Framingham data and specimens in their studies.

The Heart Study FHS has offices at the BU School of Medicine and at the main research center in Framingham, providing opportunities for students to attend lectures and chat interact with study investigators. BU also awards two postdoctoral fellowships each year.

Many of the study’s investigators hold physician and faculty appointments at:• Boston Medical Center• BU Department of Mathematics & Statistics• BU School of Medicine• BU School of Public Health• BU Statistics and Consulting Unit: Statistics in Medicine

The BMC/BU Medical Campus Institutional Review Board is a shared function between Boston University Medical Campus and Boston Medical Center. The IRB Office has a staff of 11, has four boards that each meet every two weeks, and annually reviews 600 protocols, 1200 continuing reviews, 2000 study personnel changes, and 850 amendments. See the body of the grant under Regulatory for our programs related to improving IRB function. The IRB is a portion of the Human Research Protection Program that was accredited by the Association for the Accreditation of Human Research Protection Programs in December 2017. Two unique components of the BU clinical and translational science setting are relevant to this application.

The program Affinity Research Collaboratives (ARCs) is co-supported by the Evans Center for Interdisciplinary Biomedical Research (ECIBR), based at the medical center, the Boston University (BU) Interdisciplinary Biomedical Research Office (BU IBRO), based at the Charles River Campus, and the BU CTSI. Katya Ravid is the ECIBR and BU IBRO Director and the Program Leader of the BU CTSI Collaboration and Multi-Disciplinary Team Science Program. Dr. Ravid has been instrumental in integrating the ARC program with CTSI pilots and Team Science initiatives. Much of the ECIBR ARC funding comes from the Evans Memorial Department of Medicine Endowment to provide, and together with the CTSI it provides seed opportunities for collaborations within ARCs--investigators-initiated groups, organized around foci of common research interests. The extraordinary strength in biomedical and physical sciences at BU, and the support and development of the ARCs create opportunities for new interdisciplinary approaches to both research and training in biomedical research. Other resources include an array of university-subsidized research cores available to all the faculty, ARC data gathered from 2009 to Jan 2017 show a total 337 participating faculty: 287 BU faculty and 50 outside of BU, active in 15 ARCs, of these faculty: 55 are from basic science and other departments at the medical campus, 10 from the dental school, 16 from the School of Public Health, 43 from Charles River Campus, and 163 from different section of the Department of Medicine. Of the 50 ARC collaborators outside of BU, 9 are from industry and the rest are from other academic institutions. Faculty of every rank is represented in each of the ARCs. 

The second component is centered on a NIGMS T32 grant in Pharmacology (Biomolecular Pharmacology). One of only four such pharmacological sciences training programs in New England, it is a model of Public-Private Partnerships, partnering with Pfizer to offer innovative internship and training opportunities so that students have an exposure to the industrial perspective early in their graduate career. It was ranked in the top echelon of PhD training programs for research productivity by the 2010 National Research Council report. There are 19 additional T32 programs, 25 P and U series awards and innumerable other interdisciplinary programs that cannot be described in this space.

Our department administers an NIGMS sponsored training program in Biomolecular Pharmacology that is directed toward preparing students for the pharmacology of the next generation. Advanced research in the translational sciences requires an understanding of the principles and precepts of a broad range of disciplines that come under the umbrella of pharmacological sciences.

From the behavior of atoms in macromolecules to the effect of molecules on the behavior of organisms, the pharmacologist must be trained to think in terms of several dimensions simultaneously. This need is reflected in the training partnership that we have developed among the Department of Pharmacology & Experimental

Therapeutics, the Department of BioMedical Engineering, and the Graduate Program for Neuroscience, as well as our industrial training partner Pfizer. Our central mission is to provide unique learning opportunities for all of our students.

Of the 61 appointees to the Biomolecular Pharmacology Training Grant in the last 15 years, 87% earned the Ph.D. degree (7% completed with an M.A. degree). The average time-to-degree has been 5.2 years for the 20 most recent graduates enrolled since September 2007. The current professional positions of graduates in the last 15 years reflect the diversity of opportunities available for PhDs with expertise in pharmacology. Thirteen graduates are employed in eleven pharmaceutical and biotechnology companies of varying sizes, from Pfizer (the world’s largest), Abbvie (a spinoff of Abbott Research Laboratories), and a variety of start-up companies. Graduates are also engaged in research within academic programs, including UPenn, Iowa State University, UCLA, University of Illinois, Harvard Medical School/Boston VA, Scripps Research Institute (FL), Brigham and Women’s Hospital (Boston), Kavli Institute (Norway), and BU. Among the MD/PhD graduates several are pursuing medical research, one at UCLA and another at UCSF. Other graduates are employed as: a reviewer at the FDA, medical writer, undergraduate biology professor, Program Manager at Jackson Laboratories, Senior Scientist at Abbvie, and ASPET Washington Fellow. Six graduates work in consulting firms, and several have positions as clinical trial coordinators.

There are three points of entry into the Biomolecular Pharmacology training program: PhD in Pharmacology, PhD in Biomedical Engineering, and PhD in Neuroscience.

Boston University School of Public Health (BUSPH). The Boston University School of Public Health is fundamental to the clinical research environment of the BU CTSI. It was established in 1976. Dean Sandro Galea, MD, DrPH, a physician and epidemiologist, has served as Dean of BUSPH since 2015. The Associate Dean for Research is Michael McClean, ScD. BUSPH has 333 faculty, 1,177 students, and approximately 9,000 alumni living and working in all 50 states and more than 100 countries. BUSPH is fully accredited by the Council on Education for Public Health (CEPH) and is ranked 10th in Public Health Graduate Schools by the U.S. News & World Report. It has over 65,000 square feet in dry bench research space and approximately $50 million in annual research awards. In addition to the MPH and DrPH degree programs, BUSPH offers four PhD degree programs (Biostatistics, Environmental Health, Epidemiology, Health Services Research), six MA and MS degree programs (Applied Biostatistics, Biostatistics, Environmental Health Data Analytics, Epidemiology, Health Services and Systems Research, Public Health Nutrition), and five dual degree programs (MBA/MPH, JD/MPH, MS/MPH, MD/MPH, MSW/MPH). The research focus areas of the school are Urban Living, Aging and Wellbeing, Health across the Lifecourse, and Health Systems, with a particular emphasis on disadvantaged, underserved, and vulnerable populations. The BUSPH services a number of unique large databases described in the application as resources for T4 research.

Two sections of the BUSPH are key services and programs of the BU CTSI:

The BUSPH Department of Biostatistics consists of 25 faculty members who are experts in the areas of statistical genetics, clinical trials, and observational studies. Embracing the multidisciplinary nature of biostatistics, faculty design and conduct important studies that span the continuum of public health. Biostatistics faculty is available to our investigators and the scholars program. The second, the Data Coordinating Center (DCC) is a data collection, management and analysis resource for the entire medical campus community. The Center’s staff provides assistance to members with study design and data processing at every stage of research.

Fundamental to public health research and policy, biostatistics is also one of the most interdisciplinary departments at Boston University School of Public Health. By designing studies,

developing new methodologies, and extracting and analyzing information from data, we help inform decisions to promote better health.

Biostatistics faculty members are internationally recognized for methodological innovations in clinical trials and observational studies, statistical genetics analysis, and Bayesian methods. They have a long history of collaborating to address some of the world’s most pressing public health concerns, as well as training the next generation of students to tackle emerging public health and medical issues with cutting-edge methods and technological skills.

Areas in which we are active include genetic studies of risk factors for breast cancer; safety and efficacy assessments of a new Alzheimer’s disease drug; comparisons of patient outcomes with different behavioral interventions; and studies to identify genetic and non-genetic factors of healthy aging and extreme human longevity.

The BUSPH Department of Global Health seeks to improve the health and well-being of underserved populations in low and middle-income countries through research, education and training of students, as well as technical assistance and service. Our 32 faculty members are involved in major research projects designed to identify and resolve health disparities across the lifespan in more than 24 countries, the majority of these activities are located in Africa and Asia. There are specific research studies focusing on improving reproductive health, pregnancy outcome, child survival and adolescent health, reducing the economic impacts of HIV/AIDS, tuberculosis and malaria, and improving the diagnosis and outcomes of non-communicable diseases. There is a new focus on developing point of care diagnostics that has relevance in the US and globally and the potential for diagnostic studies that could be conducted in the CRC. The research studies are funded by NIH, USAID, the Bill and Melinda Gates Foundation and many other Organizations. There are opportunities for CRC investigators to collaborate with our in country principal investigators on related studies.

Affiliated with the School of Public Health and the Sargent College, the Slone Epidemiology Center is a research organization that focuses on studying the possible health effects of medications and a wide variety of other factors in adults and children. Staff of approximately 100 includes specialists in epidemiology, adult and pediatric medicine, nursing, pharmacy, biostatistics, and computer science. Slone researchers use a variety of epidemiological tools, including case-control and follow-up studies, clinical trials, surveillance studies, risk management studies, and population-based surveys.

The School of Public Health provides the resources for the planning and implementation of clinical research across the range of research and communities.The Slone Epidemiology Center is a public health research organization which focuses on studying the possible health effects of a wide variety of factors in adults and children. The initial focus on medication use has over the years been expanded to include behavioral, psychosocial, socioeconomic, environmental, and genetic factors. Our staff includes specialists in epidemiology, medicine, nursing, pharmacy, biostatistics, and computer science. Slone researchers are typically involved in all aspects of the studies they conduct, including design, data collection, analysis, interpretation, and dissemination. They use a variety of epidemiological tools, including case-control and follow-up studies, clinical trials, surveillance studies, risk management studies, and population-based surveys.

Slone Epidemiology Center at Boston University (Slone) houses and/or provides access to all the facilities, resources, and services necessary for the successful execution and completion of the proposed research project. Since its founding in 1975, Slone has collected, managed, and maintained research data acquired directly from doctor offices, clinics, hospitals and over 900,000 patient interviews comprising of demographic information, pharmaceutical usage, and medical, dietary, and disease histories and biologic specimens for genetic analysis and analysis of biomarkers.

Boston University Goldman School of Dental Medicine (GSDM). The Henry M. Goldman School of Dental Medicine is the dental school at Boston University. Jeffrey Hutter, DMD, is the Dean, and Maria Kukuruzinska, PhD, is the Associate Dean for Research. GSDM is located in a six story building on the BUMC that is the center for teaching, patient care and clinical research. The Henry M. Goldman School of Dental Medicine (GSDM) offers the DMD (both the traditional four-year program and a two-year Advanced Standing program for internationally trained dentists) and advanced certificates and degrees in all recognized specialties. It offers a Doctor of Science in Dentistry (DScD), a Doctor of Science in Oral Biology (DSc), and a Doctor of Philosophy in Oral Biology (PhD). The School has faculty of 450 and 800 students. GSDM is also noted for its student and faculty research and is ranked highly in the nation. GSDM now ranks 12th out of 56 U.S. Dental Schools in research funds awarded by NIH. The GSDM is a strong component in pediatric clinical trials networks in URM as part of the BU CTSI.Jeffrey Hutter, DMD, is the Dean, and Maria Kukuruzinska, PhD, is the Associate Dean for Research.

Boston University Henry M. Goldman School of Dental Medicine offers state-of-the-art dental care through our teaching clinic and faculty practice. Emphasizing preventive and restorative dentistry, our experienced dentists, hygienists, and students provide a range of patient services at our Patient Treatment Centers.The scope of research at GSDM is broad, spanning areas of basic, clinical, public health, and translational sciences. Faculty research interests are in the fields of: Endodontics Health policy and health services Molecular and cell biology Oral and maxillofacial surgery Oral cancer

Oral health disparities Orthodontics Pediatric dentistry Periodontology and oral biology and Restorative sciences/ biomaterials.

The GSDM Center for Clinical Research provides clinical researchers with a location to see research subjects for studies of oral conditions and diseases, as well as oral complications of systemic diseases and facilitates collection of tissue specimens from the oral cavity including saliva, pellicle, scalpel and brush biopsies and swabs of oral mucosa.

The Boston University Henry M. Goldman School of Dental Medicine Office of Research provides research infrastructure for faculty, emerging scholars, and pre- and post-doctoral students. Its role includes the following activities: Identify and highlight collaborative research initiatives and provide administrative support for these

collaborations. Organize seminars and research retreats on a variety of research issues to promote collaboration and

interdisciplinary interaction. Host an annual Science Day to showcase the cutting edge research being conducted at the school. Run the Pre-doctoral Research program which provides research opportunities and enhances access to

cutting-edge investigation for students. Identify funding opportunities from federal and non-federal entities. Assist in the preparation of competing and non-competing grant applications. Ensure proposal compliance with Boston University and sponsor policies and procedures, as well as those of

subcontracting institutions. Prepare internal paperwork to be submitted with applications, such as the Proposal Summary Form and

Conflict of Interest form. Assist in all administrative aspects of applications, including downloading the grant mechanism, tracking

required materials, editing and formatting application pieces, preparing the budget, and submitting final proposal to the Office of Sponsored Programs.

Work with sub-awardees to gather forms required for BU and sponsor. Provide post-award support by submitting progress and final reports to the sponsor. Assist with the submission and administration of IRB proposals. Serve as a liaison to funders/sponsors. Serve as a bridge between GSDM researchers and BU offices such as the Office of Sponsored Programs,

Post-Award Financial Operations, the Office of Technology Development, the IRB and Research Compliance.

The Center for Clinical Research at the School of Dental Medicine is a virtual center, facilitating clinical research activities within all BU GSDM patient treatment centers. In addition to patient oriented research, the CCR provides support to investigators involved in epidemiologic and behavioral studies, as well as health outcomes and health services research.CREEDD is one of five national centers for oral health disparities research funded by the National Institute of Dental and Craniofacial Research (NIDCR). CREEDD’s mission is to improve oral, dental and craniofacial health through research, research training, and the dissemination of health information, with a focus on the elimination of oral health disparitiesCREEDD was created in 2001 with joint funding from the NIDCR and the National Center on Minority Health and Health Disparities (NCMHD; now the NIMHD). CREEDD was awarded a second grant from the NIDCR in 2008. This grant, totaling just over $14.5 million, will fund CREEDD from 2008 to 2015.The Northeast Center for Research to Evaluate and Eliminate Dental Disparities (CREEDD), based at Boston University, is committed to the elimination of oral health disparities through research, training, and action. Our efforts build on a strong foundation of early and continuous community engagement, community-based research interventions, integrated training and career development, broad dissemination of research findings, and targeted health policy initiatives.The CREEDD continues its regional collaborations today with partnering institutions in Massachusetts, Maryland, and Ohio. A diverse, multidisciplinary and multi-institutional team implements community-based intervention research projects aimed at reducing early childhood caries (ECC). The Center is led by Drs. Raul Garcia and Michelle Henshaw.Within the GSDM, social determinants of health are studied as part of the Office of Global and Population Health (GPH). GPH is funded by the following grants:o Community Based Dental Partnership Program (CBDPP): 13-year grant from the Health Resource and

Services Administration (HRSA) totaling just over $3.5 milliono Transformative Primary Care for Older Adults: Integrating URM Faculty Development and Retention/Dental

Faculty Development and Loan Repayment Program (LRP): 5-year grant from the Health Resource and Services Administration (HRSA) totaling just over $1.3 million

o Integrating Interactive Parent Text Messaging and Oral Health Guidelines into Pediatric Community Health Centers to Reduce Early Childhood Caries: Dr. Henshaw is currently a Co-PI on 5-year grant from the National Institute of Dental and Craniofacial Research (NIDCR) totaling just over $4.5 million

The overall mission is to improve oral, dental and craniofacial health through research, research training, and the dissemination of health information, with a focus on the elimination of oral health disparities.

Boston Medical Center (Participating Partner)A nonprofit institution, Boston Medical Center (BMC) was formed in 1996 by the merger of Boston City Hospital, Boston Rehabilitation Specialty Hospital, and Boston University Medical Center Hospital. BMC encompasses a 496-bed hospital with a Level I Trauma Center, the city’s busiest emergency department, and extensive ambulatory services, offering primary care and over 70 medical subspecialties. BMC is the largest safety net provider in New England, serving more than 200,000 patients per year. More than half are classified as low-income with an annual income below federal poverty level.

In 2014, BMC had over 874,770 outpatient visits, 128,840 emergency department visits, and 26,064 inpatient admissions. The BMC urban patient population is more than 60% minority, with African Americans accounting for 39% and Latinos for 15% of patients. More than 31% of BMC patients require interpreter services, available on-site in more than 240 languages. BMC operates 68 residency training programs with more than 702 resident and fellowship positions. Externally-funded research and educational grants to BMC grew from $47 million in 2000 to more than $118 million in 2014. At present, BMC researchers hold over 100 grants from the National Institutes of Health. These grants are for clinical research and basic research in infectious disease, pediatric AIDS, cardiology, cancer, Parkinson’s disease and addiction.BMC is a founding partner of Boston HealthNet, Inc., an affiliation of BMC, Boston University School of Medicine, and 14 community health centers (CHCs) located in Boston's most impoverished neighborhoods. The community centers are all within 8 miles of medical campus. The CHCs account for nearly one-third of admissions to BMC. Physicians from the CHCs provide inpatient rounds at BMC and BMC physicians provide a range of specialty care clinics in the CHCs. A shuttle bus system provides round-trip patient transportation. This integrated urban safety net system has garnered national attention.BMC hosts a health information exchange linking the CHCs to BMC across a common platform. With investments from BMC, the Health Resources and Services Administration, and private foundations, BMC and the CHCs have implemented a common electronic health record and exchange a range of clinical information. e-Prescribing and e-Referrals are used throughout the system. Data warehouses are in place for BMC and the CHCs and have been programmed to populate diabetes and immunization registries. The Clinical Data Warehouse and Health Information Exchange, which contain data from the emergency, inpatient, and outpatient electronic health records of BMC and Boston HealthNet patients, offers unlimited research opportunities on health services utilization, treatment decisions, and health outcomes of general and special populations across the lifespan. BMC promotes health care access of low-income populations through the BMC HealthNet Plan, a Medicaid managed care plan founded in 1995 with 240300,000 members statewide, and its companion plan, the CareNet Plan, which provides managed free care for people awaiting HealthNet Plan enrollment. Boston University School of Medicine and 15 14 Community Health Centers (CHCs) also participate in the Boston HealthNet. Together, these groups provide care for approximately 30% of all Boston residents. An integrated safety net health care delivery system, Boston HealthNet provides outreach, prevention, primary care and specialty care and dental services at sites located throughout Boston's low-income neighborhoods.BMC is an active partner in clinical research with BUSM, and supports the BU CTSI Hub. BMC co-supports key translational research functions including the IRB, IACUC, and LASC. BMC operates its own Office of Clinical Research and Office of Research Administration, which assists investigators with BMC-based and patient-oriented grants and contracts, assuring compliance with GCP including proper assignment of research and standard-of-care billing for patients participating in clinical trials. BMC provides substantial institutional support for the BU GCRU in services. Clinical research programs based at BMC have an exceptional track record of minority enrollment on clinical trials. For example, in 2014, the Cancer Clinical Trials Office screened 700 new cancer cases diagnosed or treated at BMC for participation in clinical trials. The overall enrollment onto trials was 19%, much higher than the national average (typically 5-10% of cancer patients). Furthermore, 59% of those patients enrolled onto clinical trials were minority patients: 140 out of 237 enrollments.For example, in 2013, the Cancer Clinical Trials Office screened 1244 new cancer cases diagnosed or treated at BMC for participation in clinical trials. The overall enrollment onto trials was 18%, much higher than the national average (typically 5-10% of cancer patients). Furthermore, 31% of those patients enrolled onto clinical trials were minority patients: 67 out of 216 enrollments. The 2013 data are consistent over more than 5 years, and reflect the institutional commitment to access to trials for minority, underserved, and low income patients. Clinical trials access is supported by a robust Patient Navigation Program, whose nationally recognized research has been led by Tracy Battaglia, MD, Program Leader of the BU CTSI Community Engagement component. At Boston Medical Center, all are welcome and treated equally. The best and brightest physicians, representing virtually every medical specialty, choose to work here for the opportunity to make a difference in their community and beyond. Unwavering in its commitment to the community, BMC is a private, not-for-profit, 487-bed, academic medical center located in Boston's historic South End. The primary teaching affiliate for Boston University School of Medicine, BMC is the largest safety net hospital and busiest trauma and emergency services center in New England.

Dedicated to providing accessible healthcare to everyone.

72% of patients are from under-served populations and 32% of patients do not speak English as a primary language.

Through its commitment to serve everyone, BMC offers numerous outreach programs and services such as: Health Screenings Smoking Cessation Preventive Food Pantry Interpreter Services in over 240 Languages, 24 hours a day

Seeing more than more than one million patient visits a year in over 70 medical specialties and subspecialties, BMC physicians are leaders in their fields with the most advanced medical technology at their fingertips and working alongside a highly-skilled nursing and professional staff. No matter who you meet at BMC – from the x-ray technologist to the critical care nurse, the admissions staff to the chief of surgery – everyone is committed to providing quality care to every patient and family member with respect, warmth and compassion.HealthCore/New England Research Institutes, Inc. (Participating Affiliate)HealthCore, Inc. acquired NERI, a full-service contract research organization, to strengthen its pre-approval research capabilities. Founded in 1986, New England Research Institutes, Inc. (NERI) continues to solidify and expand its place in the scientific community as a leader in producing impeccable scientific results while maintaining high quality standards. NERI was acquired by HealthCore, Inc in September 2017, who is an independently operating, wholly owned subsidiary of Anthem, Inc. Anthem is among the largest health benefits company in terms of medical enrollment in the United States. Herein our company is referred to as “HealthCore/NERI”.HealthCore/NERI sets itself apart from other independent research organizations by setting optimum goals and striving to exceed those goals. Over 45% of its Associates have advance degrees. Our scientists include experts in areas such as biostatistics, epidemiology, health services research, clinical trials, social and behavioral sciences, as well as business administration. Our professional and technical staff members are experienced in areas such as project management, site management, safety management, data collection, computer programming, data management, and both quantitative and qualitative data analysis.HealthCore/NERI research teams have access to all resources needed to successfully and efficiently undertake and complete proposed and funded research studies. HealthCore/NERI’s extensive experience and team approach ensures that timelines are met while maintaining established high-quality standards. Research teams are tailored for each study to create the best possible “fit” between skills and expertise and the needs of the study. The intellectual environment at HealthCore/NERI is rigorous yet highly supportive -- ideas are vigorously challenged and tested in order to identify potential weaknesses and promote the discovery of innovative solutions. In short, HealthCore/NERI provides a scientific environment that is strongly supportive of the proposed research and, therefore, success of the study. Facilities HealthCore maintains four offices in: Wilmington, DE (Philadelphia metro area), Alexandria, VA (Washington DC metro area), Watertown, MA and Andover, MA (Boston metro area). Staff members are assigned to a particular office but occasionally work from another office as necessary. To maintain the confidentiality of the PHI HealthCore uses in its research, access to these offices requires a dedicated access card, which is only provided to HealthCore employees and invited guests. All HealthCore/NERI offices are equipped for in-person meetings, teleconferences, and video conferencing capabilities. HealthCore/NERI also maintains a subscription to WebEx, a software application that allows documents to be shared in real time during meetings. This allows HealthCore/NERI to minimize expenses and travel time and still hold productive meetings between employees in its own offices and also clients in other sites. All offices are also equipped with necessary office hardware and supplies, including printers, copiers, fax machines, and other necessary equipment.HealthCore/NERI maintains access to on-line computerized literature search services including: MEDLINE, PaperChase, Dialog, HealthGate, MEDLARS, IQUEST, and PsychINFO. HealthCore/NERI’s location also

facilitates frequent in-person meetings with collaborators located at hospitals and universities in the Philadelphia, Washington DC, and Boston areas.Computers/TechnologyHealthCore/NERI maintains an information technology infrastructure that meets and exceeds its information technology needs. This redundancy in IT infrastructure allows project work to continue unimpeded even if there is a technical problem in one part of the system or a part needs to be taken offline for upgrading purposes.HealthCore/NERI maintains several larger servers, including a database server for the HIRD, SAS, SQL, Teradata, and Stata servers and electronic communication servers. All employees are provided with a laptop for work use. Employees are encouraged to maintain all their files on server drives, which are backed up on a daily basis, to mitigate the possibility of loss of data due to hard drive corruption on the employee’s personal laptop. Over the past several years HealthCore/NERI has significantly refreshed its financial and business information systems and related processes. The company has upgraded to current versions of software which are widely used in the services industry including Microsoft Dynamics SL (accounting system), Microsoft Project Server, Microsoft SharePoint. In addition, HealthCore/NERI has implemented Voice over IP telephony. These and other systems investments totaled more than half a million dollars, and are representative of HealthCore/NERI’s longstanding commitment to utilizing the best tools in delivering high quality and cost effective service to our clients.  HealthCore/NERI’s core business systems have been moved to a secure, solid state, cloud based platform to ensure high availability and redundancy.HealthCore Integrated Research Database (HIRD ® ) HealthCore combines clinical and scientific expertise with access to a robust data environment, to generate new knowledge that assists health plans, federal and state governments, and the pharmaceutical industry to make better health care decisions for the people they serve. The HealthCore Integrated Research Database (HIRD®) is a longitudinally integrated medical and pharmacy claims, enrollment, and electronic outpatient laboratory results database drawn from health care encounters of members enrolled in several commercial health plans. The HIRD is stored locally at HealthCore’s headquarters in Wilmington, DE. To help ensure that HealthCore is able to carry out its research with ethical and scientific integrity, HealthCore maintains a “firewall” between its scientific processes and, the individual health plans represented within the HIRD, as well as HealthCore’s parent company, Anthem, Inc. HealthCore maintains a separate, independently operating infrastructure, including its primary information technology systems, that are managed independently from Anthem. The logical and physical firewall, supports the segregation of duties and addresses any real or perceived conflicts of interest. HealthCore does not disclose the nature of its unpublished research projects with Anthem, other than when they are involved directly in the project. Our research expertise comes from nearly 20 years of experience transforming our raw materials – commercial health insurance claims data, electronic laboratory results data, and data collected from medical records, surveys, and registries – into a comprehensive research data environment for use in epidemiologic, health economics and outcomes, health services, and comparative effectiveness research. Further, our dedicated staff of scientific investigators with advanced degrees in medicine, pharmacy, health economics, health services research, mathematics, biostatistics and epidemiology adds a multidisciplinary scientific perspective to our offerings.The HIRD contains health benefit claims data, integrated across data sources and types (e.g. professional claims, facility claims, outpatient pharmacy claims, laboratory, and enrollment information) and across years (from 2006 through the most recent calendar quarter in 2017). Data is obtained from health plans in different parts of the United States and is classified by HealthCore into Northeastern, Southeastern, Mid – Atlantic, Mid – Western, Central, and Western regions of the United States. As of January 2018, the HIRD contained data from over 65 million researchable lives with medical coverage and about 48 million researchable lives with both medical and pharmacy coverage from January 2006 through September 2017. Individuals represented in the HIRD include fully – insured and administrative services only (ASO) lives from Anthem – affiliated health plans in 14 states and certain other non-Anthem plans in additional state(s). Anthem is an independent licensee of the Blue Cross and Blue Shield Association with affiliates that serve their members as the Blue Cross licensee for California; the Blue Cross and Blue Shield (BCBS) licensee for Colorado, Connecticut, Georgia, Indiana, Kentucky, Maine, Missouri (excluding 30 counties in the Kansas City area), Nevada, New Hampshire, New York (as the Blue Cross Blue Shield licensee in ten New York City metropolitan and surrounding counties and as the Blue Cross or Blue Cross Blue Shield licensee in selected upstate counties only), Ohio, Virginia (excluding the Northern Virginia suburbs of Washington, DC), and Wisconsin.

The HIRD also contains diagnostic laboratory testing results from two large national laboratories for Anthem-affiliated health plan members receiving outpatient laboratory services. Data include full ranges of hematologic, chemistry, immunologic and microbiologic (including culture and antibiotic sensitivity results) from over 22 million lives. The innovative HIRE is fully identifiable, and as necessary with proper protocols in place, we have the ability to link to supplemental data sources, including registries, obtain medical records for chart studies, and administer surveys to conduct direct outreach to members and providers. In addition to claims and enrollment data, information regarding current and historical medical and pharmaceutical policies, benefit designs, formulary processes, care management programs, and care coordination programs can potentially be accessed by HealthCore through our relationships with the individual health plans represented in the HIRD. Specific data in the HIRD include individual enrollment data, medical care, prescription drug use, and health care utilization that can be tracked for each individual throughout the course of their enrollment in the health plans. Diagnoses and procedures are identified by ICD – 9/10 diagnostic, ICD – 9/10 Procedure, Current Procedural Terminology (CPT), and Health Care Financing Administration Common Procedure Coding System (HCPCS) codes for both outpatient and inpatient visits/stays. Outpatient pharmacy claims are captured by National Drug Codes (NDCs). Physician, specialist, and emergency room visits, as well as hospital stays, are captured in the database through ICD – 9/10 diagnostic, CPT procedures codes, HCPCS, Uniform Billing Code of 1992 (UB – 92) revenue codes (e.g., room and board), and place of service codes.Demographic characteristics available in the HIRD include date of birth, and gender. In addition, each member represented in the HIRD is associated with a unique encrypted identification (ID) number. Standard procedures entail retaining each member’s unique ID number throughout the period of plan eligibility. Race and ethnicity are not available in the administrative claims database. However, these variables, in addition to socioeconomic status, can be obtained through several direct – ascertainment from medical charts or surveys – and indirect mechanisms – imputation based on US Census data and member zip code and/or US Census tract information in the context of certain research protocols. Electronic Data Capture SystemHealthCore/NERI has partnerships with various patient data capturing companies. Description of our main partner eClinicalOS is described below. 1. eClinicalOS IBM® Clinical Development, formerly eClinicalOS (eCOS), is one of NERI’s choice of programs for developing protocol specific, web-based, Electronic Data Capture (EDC) for studies including clinical trials, registries, and observational studies. eCOS allows the study to assess the mode(s) of collection for each type of data and provide the entry that is right for it.  Easy to design and use pages allow for data collection to be done by phone, medical record abstraction, interview, self-report or combination thereof. eCOS is a fully integrated product suite including EDC, eDiary, Interactive Web Randomization (IWR) and a Clinical Imaging Management System. eCOS can be used in a manner that is compliant with 21CFR11, FDA Guidance to Industry, HIPAA and EU Privacy regulations. eCOS runs on current versions of Internet Explorer, Firefox, Chrome, Safari and is mobile phone accessible.  eCOS provides: Real-time field level validation and skip-patterns Both inter- and intra- instrument data checks to ensure consistently high quality data Inconsistent or illogical values are flagged during entry and queries are automatically generated Integrated Electronic Data Capture (EDC) and paper based Case Report Form (CRF) data entry Electronic signatures supported Configurable double entry system Automated query management system Tracking and managing study documents Randomization Laboratory specimens and results tracking Protocol management  Standard and Ad Hoc data reports Implementation of protocol amendments SAS and XML study data exports Data Integrity and Security For Clinical sites: To gain access to eCOS, a user is sent an email from NERI data management. The email directs the user to go to a specific address and apply for an account. They must provide a password that is at

least 8 characters and contains 3 of the following: Upper case letter, Lower case letter, Number and Special Character.  Passwords expire every 90 days. Users supply answers to secret questions and control their account as it pertains to resetting their password and gaining access if they forget their password. A user entering an invalid password is locked out of the system after 5 incorrect tries.  Once the user has created the account, they can request access to a specific study. NERI will provide a study code, specific to the user’s protocol, in order to ask for access. NERI data management will review all requests and grant access when appropriate. A user working on multiple studies has access to all through one login.  Each user within a study is assigned a role. Each role in a study is granted specific privileges that allow the user to view and/or enter and/or delete, etc.  All movement within eCOS is tracked in an audit trail. For Participants: Once a participant has consented and is enrolled, clinical site staff will assign them an identification number in eCOS.  The ID is associated with a user ID that can be used by the participant to access the surveys that are pertinent to them in the time frame required by the protocol. The participant and only the participant retains control over both their password and their ‘Forgot My Password’ questions.  Data and Storage: All data in the eCOS database are stored by identification number only. No personal identifying information such as participant name or address are stored in the database.  For this project, the participant will supply the clinical site with their email address. This address will be used to send a reminder to fill out the follow up survey. No data is directly stored at NERI from eCOS. All data are stored in data bases at Merge’s hosting facility. Five levels of security are provided at PEAK-10 – eClinicalOS’ hosting facility. They include: Level 1: Proximity card access with PIN to enter the building (does not grant access to the data center) Level 2: Proximity card access with biometric scan required to enter the data center Level 3: Hardware is located in a secure cage or locked cabinet Level 4: Video surveillance throughout the facility Level 5: Staffed 24x7x365 Merge has a well-documented disaster recovery and business continuity plan which includes detailed checklists, forms, call lists and local maps with directions of what should be done in the first few hours of a crisis as well as an hour by hour breakdown. The plan is tested at two year regular intervals and documented. The most recent test successfully demonstrated that the databases would be successfully retrieved from the secondary center.  Online Document Sharing and Collaboration for External StaffHealthCore/NERI Connect is a Microsoft SharePoint based solution through which project team members external to NERI have secure access to project documents for both collaboration and review. Single point, secure access to the site is managed with an F5 gateway and access to specific sections and documents is managed by the project staff. The graphic below illustrates the general design of the system.Data Security and IntegrityHealthCore/NERI employees use a variety of statistical programs to conduct their statistical analyses, most notably Teradata, SQL, SAS and Stata. Dedicated SQL and SAS servers are maintained, which both permits analyses to be run quickly and allows associates to maintain analytic files and code on a central server. Associates also have access to a variety of other software packages, including: Maptitude and ArcGIS (for GIS applications), all Microsoft Office Suite products, and so on. In the event that an associate require software that is not currently available at HealthCore, it will be purchased.Statistical Design, Analysis, and InterpretationHealthCore/NERI currently employs statisticians with advanced degrees in statistics and biostatistics. Collectively, senior-level NERI statisticians have expertise in all aspects of research study design, statistical methodology, data analysis and interpretation of results in health, medical, or clinical research. NERI statisticians are knowledgeable collaborators, working well with clinicians, epidemiologists, and other researchers on study design and implementation, including sample selection, design of data collection instruments, data quality control and data management.

Senior statisticians have directed numerous large-scale multi-center clinical trials, both national and international. Together, statisticians work closely with the project team to provide study design and methodology guidance for IND/IDE applications, strategic planning for clinical development, contribute to annual reports and safety updates to the FDA, and post-market surveillance proposals. HealthCore/NERI statisticians are capable of contributing to marketing applications, integrated safety and efficacy summaries, and post-trial regulatory reports. In addition, not only do the statisticians perform analyses, generate stopping rules, and produce reports for Data and Safety Monitoring Boards (DSMBs), they also have served on independent DSMBs. Specific areas of expertise include, but are not limited to: clinical trial design genetics sequential monitoring of trials longitudinal analysis survival analysis

analysis of complex surveys reliability and validity assessment mixed model analytic methods methods for categorical data analysis propensity score

methodologyEpidemiologyHealthCore/NERI epidemiologists are well-versed in the design, conduct, and analysis of epidemiologic studies. HealthCore/NERI has conducted a wide variety of Observational Studies (Retrospective, Case/Control, Cross-Sectional, Prospective, Effectiveness Field, Post-Marketing Surveillance), as well as other types of studies, including Disease and Product Registries, Patient-Reported Outcome (PRO) Studies, and Pharmacoepidemiologic Studies. These studies have been conducted in a broad range of therapeutic areas. HealthCore/NERI epidemiologists have extensive experience with in-home biologic sampling, recruitment, and retention of hard-to-reach minority and inner-city populations, and with cross-validation of technologies (e.g., bone densitometry, assay dilution/change) that may evolve in the context of long-term cohort studies. Epidemiology Services Study quality assessment

Internal and external validity Exposure, confounder, endpoint definitions Statistical analysis

Analysis of large complex surveys or data sets (e.g., Medicare, NAMCS) Development and validation of patient-reported outcomes and other survey instruments Literature reviews and meta-analysis Publication strategy consulting Scientific publicationMedia and Technology HealthCore/NERI has a long history of developing high-quality media programs as products or components of larger research studies. Technology approaches include innovative video, audio, web, conference organization, social media and software development for providers, patients, and general consumers of health information. These products and programs address a wide range of topics including, CBT for PTSD, asthma, depression, schizophrenia, heart disease, pain, cancer, diabetes, behavioral and social science methods, ethics in clinical practice and understanding clinical research, pediatric conditions, among many others. HealthCore/NERI productions are the proud recipients of numerous awards from highly regarded agencies in the health communication industry, including the “Oscar” of health communication, the Freddie, several Telly awards for a web campaign on Children in Clinical Studies, CINE Gold Eagle, National Educational Media Award, Aesculapius Award, Gene Screen and International Rebrand. A full list of programs and awards is available on the neriscience.com website. HealthCore/NERI works with established top Continuing Medical Education/Continuing Education organizations to provide CME/CE credits for physicians, nurses, social workers and other providers through collaborating affiliates. Qualitative ResearchNERI has a long record of conducting qualitative research, with funding from numerous institutes within the NIH, the CDC and Prevention, the SAMHSA, the Centers for Medicare and Medicaid Services, and the pharmaceutical industry. Studies include a variety of topics and have been essential in the development of patient reported outcomes (PROs), and media products. In addition, qualitative methods have made significant contributions to research both to inform the development of quantitative studies, case studies for program evaluation, and assessment of population needs.

NERI’s is well-prepared to execute the full range of qualitative research including recruitment of appropriate study populations, development of discussion guides, translation and transcription services as appropriate. Our expertly trained staff conduct a variety of data collection methodologies including in-depth, open-ended interviewing; cognitive debriefing interviews; focus groups; participant observation; and archival document review. In addition, qualitative staff is trained to use a variety of systematic approaches to qualitative data analysis including thematic analyses, conversational or semantic analysis, and is well versed in the use of software packages for qualitative analysis. Regulatory AffairsNERI understands that a sound regulatory strategy must be built into any project from the beginning. NERI’s experienced regulatory team actively works in partnership to provide comprehensive regulatory support to our clients. Recent submissions include a drug for heart failure (CDER), carotid stents (CDRH), drug-eluting stents (CDRH/CDER), and blood-derived products (CBER). Our recognized regulatory department provides comprehensive support in regulatory intelligence, as well as: Regulatory Submissions - Strategic planning and representations at pre-IND/ pre-IDE meetings are only the beginning of the commitment and dedication NERI provides to ensure regulatory compliance. Discussion items range from orphan drugs/devices to drug development and CMC/bioanalytical issues to foreign clinical data and post-market strategies. Applications have been submitted to not only the FDA but also internationally (Canada, European Union, Central and Eastern Europe, Latin America, Australasia, and Japan) for investigational drugs, biologics, and devices, including orphan products and pediatric populations. The regulatory services include, but are not limited to, preparation and submission of applications (IND, IDE, NDA, BLA, PMA), 510(k) notifications, master files, supplements, annual reports, and response preparation (483 and warning letters). Adverse Event and Safety Reporting - The regulatory team works closely with each project team for safety surveillance, including unanticipated adverse device effects (UADE), suspected unexpected serious adverse reactions (SUSAR), serious adverse events (SAE), medical device reporting (MDR), and periodic safety update reporting (PSUR), using standardized coding. Decisions from Data Safety Monitoring Boards (DSMB), adjudication committees, and endpoint review committees are immediately relayed to the regulatory team for appropriate actions as required.Project ManagementNERI provides full service project management support for global Phase I through Phase IV trials in major therapeutic areas. Project Managers have a broad range of expertise and a history of delivering high-quality services to our clients. NERI project managers have sharpened their skills through formal training and more than 20 years of organizational experience managing epidemiological studies and clinical trials involving tens of thousands of patients. NERI assigns a dedicated project manager (PM) to each study as the primary point of contact for our clients and to manage all study activities. The PM works closely with our clients to understand their goals, needs, and expectations. Client service and satisfaction are incorporated into all project processes. NERI is particularly proud of its history in managing complex, international, multi-center clinical and health-related studies. Our project managers are trained to analyze the size, scope, and duration of new projects and evaluate the needed requirements to successfully execute them. Project Management Activities Include: Compliance with internal SOPs, GCP, regulations and ICH Guidelines Development of Project Plans and timeline schedules Establishment of a communication plan to include the client, NERI team, and third party vendors Execution of project plans and provision of key deliverables Monitoring the ongoing project activities against the Project Management Plan Managing study timelines, milestones, and deliverables Leadership in conducting internal & external team meetings Monitoring study budgets and managing variances to project scope Site Selection, Recruitment, Management, Training & MonitoringThe success of a clinical trial or research agenda often hinges critically on the selection of appropriate sites and the successful recruitment of study participants. NERI maintains an extensive global database of sites and investigators with proven track records of excellence in patient recruitment and protocol adherence. As part of its pre-study qualification responsibilities, NERI uses this database to identify the best sites for multi-center research studies. Included are thousands of sites throughout North America, South America, the European

Union, Eastern Europe, and research centers in the Middle East, Southeast Asia, Australia, and New Zealand. NERI’s stringent selection process assures our clients that their research goals will be achieved. Once site selection and participant recruitment have been completed, NERI uses its web-based Clinical Trial Management System to efficiently and effectively manage clinical sites. This system allows for ongoing management of recruitment, site performance, regulatory documentation, and site payments. The system also links a site database with the protocol database for each clinical study and monitors site performance via real-time reports. This ensures rapid identification and correction of problems at clinical sites.NERI maintains both in-house and regional Clinical Research Associates (CRAs) trained in numerous therapeutic areas. CRAs perform a variety of clinical monitoring activities to ensure regulatory and GCP/ICH compliance for all studies. NERI CRAs work closely with the Program/Project Managers to ensure that clients’ expectations and deliverables are met or exceeded. NERI prides itself in developing strong working relationships with each investigative site in order to help build lasting and trusting relationships, leading to high performance. NERI’s Clinical Monitors can provide all or a selection of the following services: Clinical monitoring plan development, including risk-based monitoring Site identification, qualification, and selection Site initiation, interim, and close-out visits (i.e. monitoring visits) Regulatory/study site documentation management Informed consent development Site payment management Investigator meeting coordination Site personnel training Study procedures manual development Clinical study supply accountability Specimen/image management Scientific Quality ReviewNERI maintains rigorous scientific standards in conducting research and performs ongoing reviews. This commitment is strengthened by periodically inviting nationally recognized experts with particular knowledge of research methodology to perform a thorough independent quality review. All work products (e.g., statistical reports, scientific manuscripts) must undergo independent review in accordance with NERI SOPs prior to submission. NERI's Quality System and SOPs are designed and implemented to be compliant with ISO 9001.

Edith Nourse Rogers Memorial Veterans Hospital (Participating Affiliate)

The Edith Nourse Rogers Memorial Veterans Hospital is a 400-bed VA hospital located in Bedford, Massachusetts. It is affiliated with Boston University and University of Massachusetts Medical School. It’s clinical and educational mission centers around strong programs in mental health, ambulatory, and long-term care. The research program is supported by over $12 million in VA research funding and is predominantly based in three Centers: a Health Services Research and Development (HSR&D) Center of Innovation, a Geriatric Research and Education Clinical Center (GRECC) and a Mental Illness Research and Education Clinical Center (MIRECC). Activities span the spectrum from basic science to translational research focused on improving health care. The program in translational research is strongly supported by the VA Quality Enhancement Research Initiative (QUERI) with specialized programs in e-health, HIV/hepatitis, and patient-centered care. Research activities at Bedford VA are supported by extensive facilities and resources.

The primary resource of the Bedford VA is the population of 18,000+ veterans with a broad range of complex medical and psychiatric comorbidities. This population is highly willing to take part in research

and studies have demonstrated consistently high retention rates for veterans involved in clinical trials. A full time PhD Clinical Trials Coordinator supports clinical research at the Bedford VA Hospital. The Bedford VA Hospital Pharmacy is available for participation in research activities and has been supportive of clinical trials for over 15 years.

Among the special populations available for clinical research is the GRECC Dementia Special Care Unit (DSCU) and Outpatient Clinics. The DSCU is a clinical research unit located at the Bedford VA Hospital in Building 62. The unit occupies two floors of the building, and has a capacity of 45-50 beds per floor. The new Women’s Unit is located on the lower level. Office space for clinical and clinical research staff is located in Buildings 62 (lowest level) and in the adjacent Building 61. The GRECC Outpatient Clinics provide service to hundreds of Veterans suffering from neurodegenerative diseases who have a strong history of research participation. This program also makes extensive use of home video-conferencing for care. The majority of patients and families associated with the DSCU are interested in participating in research including brain donation (historical rate exceeds 80%).

Clinical research is supported by several laboratories. The Evoked Response Potential (ERP) laboratory and ambulatory electroencephalography (EEG) laboratory is located in Building 62 basement. These laboratories are equipped with state of the art ERP and EEG rigs and supported by dedicated hardware and fully-equipped software for data analysis and imaging. The morgue was completely remodeled in 1993 and contains all required equipment for the performance of autopsies. A 400 square ft. tissue storage room with two ultra-low freezers is adjacent to the morgue. The neuropathology laboratory is currently expanding to additional facilities to accommodate the new VISN1 Regional Neuropathology Laboratory.

The Bedford VA has extensive capacity for studies making use of comprehensive VA databases. The network has eight Microsoft Windows based fileservers with over 16TB of storage space dedicated for research data analysis and storage. The servers and workstations are part of the VA Bedford domain and are behind the VA firewall. Attention to data security is very high study resources are stored in secure, restricted access data directories. Access to these directories is limited to study team members. A number of disease specific registries have been developed including the Diabetes Epidemiology Cohort (DEpiC) that has merged information from a wide variety of VA and CMS data sources.

Bedford VA also has an Animal Research Facility. This facility recently completed a major renovation of all environmental systems and of the cage-washing areas. The facility includes procedure rooms that are suitable for BL-2 research and all research is supervised by the Bedford VA Hospital IACUC, Safety Committee, and IBC.

Supporting basic science are a number of wet laboratories. Bedford VA Molecular pathology and biology laboratories are located in buildings 17, 18, and 70. The Spectroscopy Center and the Mass Spectrometry Center are located in Building 70. Labs offer shared space for tissue culture, microscopy, and a dark room. There are five PCR machines and designated areas for molecular biology and RNA processing. There are two Zeiss fluorescence microscopes, including a new Zeiss AxioImager Z fluorescent multichannel scanning microscope with Apotome motorized stage. There is one Leica SP5 confocal microscope. A stereological microscope with Microbrightfield Stereoinvestigator and Neuroleucida software is available for advanced stereological quantitation. There are multiple automated plate readers, including a Meso Scale Discovery Sector Imager, a water purification system, four cell incubators, and other basic equipment necessary for conducting cellular and molecular neurobiology.

Bedford VA human and mouse neuropathology laboratories include two wet laboratories with two hoods each for tissue processing. The neuropathology suite includes animal surgery/tissue processing labs, a brain documentation room with a hood and sink, a photo microscope/image analysis room, a graphics arts room, a conference room with a five-headed microscope and a data storage room. This lab was completely renovated in 1993.

The Mass Spectrometry Center at the Bedford VAMC has ca. 3400 sq. ft. of laboratory space organized in three sections in Building 70. Section one has three Mass Spectrometers, a newly purchased Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer for both discovery and quantitative studies, TSQ Quantiva

Triple Quadrupole Mass Spectrometer for ultra-sensitive quantification of target at an attogram level, and a Sciex QSTAR QTOF Mass spectrometer. Section one also has multiple components integrated with Mass Spectrometers, including a Matrix-assisted laser desorption/ionization source, a nano RSLC Liquid Chromatography System, and a standard LC system. Section two is a laboratory that has the facilities for sample preparation, including two high speed refrigerated centrifuge, refrigerated clinical centrifuge, centrifugal evaporation systems, refrigerators and a -90C freezer for samples currently being processed. Section 3 has three -80C freezers for sample archiving, preparation of samples under -60 C nitrogen atmosphere and archiving of intermediate sample preparations. A cryo device is in place to store frozen cells.

The Bedford VA Laser Spectroscopy Laboratory established at Bedford houses optical and spectroscopic instruments for basic and applied research in the optical spectroscopy of neurodegenerative diseases. The spectroscopy resources include optical absorption, light scattering, and laser induced fluorescence, from the near infrared to the ultra-violet, utilizing a state of the art imaging spectrograph, fiber optics and CCD detector. These facilities include Raman spectroscopy and fluorescence/Raman micro-spectroscopy, with acquisition of an additional imaging spectrograph, CCD detector, two laser sources, and fiber optic coupling. Data acquisition, storage and analysis using these resources are controlled using three dedicated computers. In addition to laboratory instrumentation, a transportable instrument for in situ brain tissue fluorescence measurements developed at the Bedford VA Hospital includes state of the art components whose modular design anticipates proposed modifications and updates. This system has a stabilized tungsten source, the fiber optic probe described above, and imaging spectrograph with cooled CCD detector. In addition to various optical components for coupling light into and out of the optical fibers and for filtering the source and collected light, there is also a dedicated computer for system control and data acquisition and analysis. The entire system can be mounted on a small cart so that it can be moved as needed. The optical design of this instrument has evolved to include the capability to acquire diffuse reflectance spectra.

VA Boston Healthcare System (Participating Affiliate)VA Boston possesses much scientific strength across all medical disciplines. Three areas are internationally recognized resources and will be highlighted in this section. First, the National Center for Posttraumatic Stress Disorder (PTSD) houses two unique divisions fully dedicated to research on post-deployment health and mental health: the Behavioral Sciences Division, and the Women’s Health Sciences Division. The scientific strengths are many and include behavioral scientists, cognitive scientists, neuroscientists, epidemiologists, and biostatisticians. In addition to the many intellectual resources represented here, there are data resources in terms of large scale data bases available for further analyses, laboratory space, powerful computer resources and data analytic expertise, and equipment dedicated to the research mission. Second, the Cognitive and Behavioral Neuroscience strength at VA Boston/BUSM dates to the origins of this medical facility in 1953. Often termed one of the founding sites for behavioral neurosciences, the group remains academically strong and very deep with newer generations of scientists assuming leadership roles in this scientific area. Third, the Massachusetts Area Veterans Epidemiological and Information Resources Center (MAVERIC) hosts the Million Veteran Program, an initiative to collect genetic information from one million veterans and match these data to information in the VA’s trend setting electronic medical record and additional interview based information. Also within MAVERIC and here at VA Boston is one of VA’s Biorepository that is processing and housing the genetic material in a building established expressly for this purpose. Finally, MAVERIC is also one of VA’s Cooperative Studies Coordinating Centers, often viewed as the jewel in VA’s research crown. This component of MAVERIC is responsible for the successful planning and execution of multi-site clinical studies. We will briefly discuss the scientific resources contained within these.VA Boston Overview of National Center for PTSD and Staffing. The National Center for PTSD is mandated by public law 98-528 as a specialized center within the Department of Veterans Affairs devoted to research and education in all aspects of traumatic stress and PTSD. The full National Center operation currently involves a

seven-site consortium of basic, clinical and implementation research. It also has extensive programs devoted to creation of educational materials and tools for both clinicians and patients, including white papers, web-based resources, and smart phone applications. The organizational units relevant to this competing continuation proposal, the Behavioral Science and Women's Health Sciences Divisions of the National Center, are both located at the Jamaica Plain Campus of VA Boston Healthcare System. The Behavioral Science Division has been active since 1989 and the Women's Health Sciences was initiated in 1992. Male and female veterans of military service are the most frequent consumers of National Center products and the most common populations under study. However, staff interests and activities are neither limited to the veteran population nor restricted to PTSD linked to combat. Community and domestic violence, sexual assault, and motor vehicular accidents are examples of traumatic experiences that also are the focus of research and clinical efforts.The combined National Center for PTSD divisions at Boston have typical staffing of approximately 75, anchored by more than 20 psychologist investigators along with psychiatrists, postdoctoral fellows, pre-doctoral interns, and over 20 junior-level research associates and assistants. The doctoral staff at the National Center have full faculty appointments at Boston University School of Medicine.The primary physical location of the program is the main building on the Jamaica Plain Campus of the VA Boston Healthcare System. The two National Center divisions occupy three vertically adjacent floors in one wing of the building. This area includes over 50 offices, 4 conference rooms, 6 lab rooms, a secure computing and printing room, testing rooms, storage areas, and two staff kitchens. The divisions also control 1700 linear feet of securely enclosed, track-mounted storage, located in the basement of the building, which is used for long-term retention of raw research data.The backbone of National Center computer operations is a fiber optic local area network that supports the more than 80 computer workstations in use by staff and support personnel. The LAN operates from a set of primary and secondary servers, running Windows operating systems that deliver a wide array of applications and support large-scale file storage and backup. The LAN is directly linked to the cluster of servers that service the facility, and thereby is linked to the wider network of servers across the VA system. The system also allows secure remote access capabilities through a virtual private network. The National Center maintains additional standalone T1 service for access to research-related resources that are difficult to reach due to the technical configuration of the VA network.Typical workstations for all VA-based faculty are Windows-based PCs of recent vintage based on a VA replacement plan that exchanges desktop IT systems on a rotating basis at intervals of approximately 3 years. Apple computers are used in specialized research contexts related to processing of brain images and digital video files. Printing involves a mix of individual desktop printers and centralized high-speed laser and color printers, and there are multiple scanners available for shared use. Windows-compatible software of various types is available to all staff via the network. Specific examples of the software include the full suite of Microsoft programs for word processing, spreadsheets, databases, and graphics. Adobe products are used for digital image and pdf document creation, and EndNote is used for bibliographic databases. SPSS, SAS, LISREL, Mplus, and HLM, are among the most frequently used resources for statistical analysis. Professional computer staff assist with custom programming to, for example, create stimulus displays, control data acquisition in the laboratory, and develop user-friendly methods for manipulating data sets. VA faculty and fellows make use of VA subscriptions for the PsycInfo service for literature searches and the PsycArticles service for full text electronic access to journals published by the American Psychological Association. Both of these can be accessed directly from the VA network. In addition, faculty and fellows have electronic access to an extensive collection of journals, books, and other scholarly resources through both the VA online system and Boston University School of Medicine, with the latter also offering physical access to the resources. The two divisions of the National Center maintain small libraries of books and materials addressing topics in traumatic stress, along with an extensive collection of tests, interviews, and manuals used for both clinical and research purposes.Psychophysiology Laboratory Resources. Each Division of the National Center has its own suite of three rooms devoted to psychophysiological recording, which is comprised of a central control room with subject rooms on each side. Each subject room is equipped with video equipment that is used both for monitoring participants and recording sessions. The Behavioral Science Division psychophysiological recording equipment is based around components and software purchased from Mindware Technologies, Inc. The hardware system is comprised of modules and amplifiers that can be configured to record a variety of peripheral physiological signals of interest, including heart rate, respiration, skin conductance, and electromyographic activity. Mindware BioLab Acquisition software interfaces with recording equipment and

operates through a computer interface that samples and stores the output from an A/D converter according to parameters specified by the experimenter. The Mindware data analysis suite interfaces with the acquisition software for quality control (e.g., artifact detection and correction) and scoring of physiological data. The laboratory also maintains user licenses for specialized software packages including E-prime and SuperLab that are used for event-related control and stimulus presentation (e.g., pictures and acoustic probes). The lab also has automated Dinamap (Critikon) monitors for measuring blood pressure and pulse rate via traditional auscultatory methods and two Finapres (Datex-Ohmeda) continuous blood pressure monitoring devices that offer capabilities not widely available with noninvasive procedures.The Women’s Health Sciences Division psychophysiological recording equipment is based around components and software purchased from Biopac. The hardware system is comprised of modules and amplifiers that can be configured to record a variety of peripheral physiological signals of interest, including heart rate, respiration, skin conductance, and electromyographic activity. Biopac Acquisition software interfaces with recording equipment and operates through a computer interface that samples and stores the output from an A/D converter according to parameters specified by the experimenter using Superlab software. The software packages supports several commonly used psychophysiological tasks including startle and physiological reactivity, differential fear conditioning, and script driven imagery. The WHSD laboratory also houses a Neuroscan Synamps2 system that allows for recording and measurement of electroencephalogram (EEG) and event related potential (ERP) activity. This system includes the requisite hardware and software required for stimulus presentation, data acquisition and amplification, and artifact detection. EEGs are recorded from 70 channels.Archival and Shared Data Resources. Staff investigators, fellows, and trainees have ready access to datasets from an array of behaviorally-oriented research studies, as well as others that include: (a) data from a clinical sample of approximately 300 veterans and a matching sample of over 2000 community members who completed inventories relevant to the assessment of DSM-5 PTSD; (b) data from a sample of 287 couples in which at least one member is a trauma-exposed veteran, all of whom have been extensively assessed for psychiatric conditions and conflict behaviors; (c) data from a nationally-representative cohort of over 800 trauma-exposed veterans who have completed a variety of self-report symptom assessments related to PTSD and dissociation; (d) data from an ongoing study on the utility of the MMPI-2 Restructured Form scales to assess DSM-5 PTSD and its subtypes, and to distinguish malingering from psychopathology; (e) data from a psychometric evaluation of the modified Deployment Risk and Resilience Inventory (DRRI) in a sample of 1048 OEF/OIF veterans (54% female); (f) data from a two-wave longitudinal study examining gender differences in the effects of deployment stressors on Veterans’ postdeployment functioning in both work and family domains, as well as use of a broad range of VA programs and services (i.e., health-care, employment, and education services); and (g) data from a multicenter, cluster randomized, parallel-group study comparing standardized with non-standardized PTSD-related disability assessment during a VA compensation and pension examination; and (h) data from the VA’s Corporate Data Warehouse (CDW), a system-wide database which draws from several VHA and administrative systems expressly to support research objectives (i) data from cohort of approximately 1800 male and female Marine recruits assessed longitudinally over 11 years, and (j) data from a cohort consisting of approximately 1500 active duty soldiers from Fort Drum, NY who participated in a randomized test of a brief mindfulness-based training for healthy coping with intrusive thoughts. Existing genetic datasets include genome-wide SNP data (2.5M SNPs) drawn from approximately 1,100 participants, genome-wide DNA methylation data (450K probes) drawn from a 600 person Caucasian subsample, and gene expression data (approx. 40K probes) from another 200 person subsample. There are several datasets focusing on genetic and epigenetic factors related to PTSD, eating disorders, and obesity. There also are genome-wide SNP and methylation data on approximately 300 members of a cohort who have completed neuroimaging protocols. The Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) has been funded by VA Office of Research and Development since 1997 with a mission to advance the health and care of veterans and the nation through development and national deployment of technological innovations and research methodologies that facilitate medical knowledge discovery. Initially established an epidemiology research center, MAVERIC has grown to incorporate centers with expertise in: population genomics; multisite national and international traditional and pragmatic trials clinical trials coordination; bio-banking; and informatics. The majority of the research performed at the center is intra-mural to the VA but significant collaborations with the National Institutes of Health, Department of Defense, Department of Energy, academia and industry exist. The center is located at the Jamaica Plain facility of the VA Boston HCS (13,500 square feet of office space; 8,300 square feet laboratory space) and has an offsite campus (8,300 square feet office space) located in close

proximity to the Boston University Schools of Medicine and Public Health. The MAVERIC staff includes project managers, biostatisticians, computer programmers, database managers, program and staff assistants, informatics personnel, medicine and data scientist fellows, physicians, quality assurance personnel, and administrative personnel who all contribute to the coordination of research.Since 2010, the Center has been funded to lead several major VA national research initiatives. These include: • The Million Veteran Program, a national program intended to enroll up to one million veterans into a high

quality research genomic medicine cohort. As of February 2018, over 640,000 participants have been enrolled, with close to 500,000 genotyped with imputation available for analysis.

• The Genomic Information System for Integrated Science (GenISIS) provides the MVP with informatics capability to enroll and track participants and a Scientific Computing Environment to store and analyze genomic and phenotypic data. The scientific compute environment includes a high performance computing cluster, access controlled datasets and tools for data analysis.

• The Point-of-Care Research Program which pioneers pragmatic methodologies to conduct clinical trials (primarily comparative effectiveness studies) within the ecosystem of the healthcare system. The program introduces randomization of equivalent treatments to patients at the time of their healthcare encounter and then monitors response and toxicity passively through the electronic medical record.

• The Research Precision Oncology Program (RePOP) enrolling patients with cancer to participate in a research program that aggregates their personal health information (including demographics, cancer features, tumor mutational status, medical images, text notes, treatments and outcomes) into a data repository for data sharing with investigators within and outside VA, allows for re-contact for research purposes and permits re-use of excess tumor specimens for research purposes. The principal aims of the research agenda are to match patients to clinical trials of targeted therapies, allow for biomarker discovery and validation and do predictive analytics to inform clinical management.

The VA New England Healthcare System’s (VISN 1) Clinical Trials Network (CTN) was established in 2013 by VISN1 leadership to create a collaborative clinical research network between all eight VISN1 medical centers, leveraged by MAVERIC’s core infrastructure, with the objectives of: 1) expanding access for veterans to state of the art care through participation in clinical trials; 2) supporting the VA mission to do research to improve veterans’ health care; 3) enhancing recruitment and retention of highly qualified clinicians; 4) enhancing the professional environment through opportunities to participate in innovative and world class scientific research; and 5) improving VA support of the scientific and educational mission of its academic affiliates. The network brings clinical providers and researchers together to conduct trial that address clinically compelling questions whose results can be translated into practice. Through establishment of disease-based consortium made up of clinician researchers trails are selected based on their scientific relevance and impact for our population. Infrastructure provided includes seed funds to support initial field staff at the sites to perform the work, core MAVERIC support of VISN-wide research activities, and leveraging existing resources and tools both at MAVERIC and at the sites in the VISN to conduct the trials.In fulfilling its mission to create a clinical research infrastructure and processes to promote and support multicenter trials among the 8 VISN1 facilities, the CTN has more than doubled the number of trials conducted in the VISN and allowed more than 8000 veteran an opportunity to participate in research. In addition, the CTN has gained the membership required for the VA to participate in NCI-funded trials and established relationships with groups such as the VA Central IRB and non-profit corporations to create efficiencies in trial initiation across multiple sites. The CTN is continuing to expand scientific consortium beyond cardiology, oncology and mental health, broadening NCI membership to include other VAs nationally, and expanding VA CSP-funded and Point of Care pragmatic trial.Center for Translational Cognitive Neuroscience. The core missions of Dr. Budson’s Center for Translational Cognitive Neuroscience (CTCN) is to use cognitive neuroscience research to improve the lives of individuals with cognitive and emotional brain disorders by using event-related potentials (ERPs) as an early diagnostic marker as well as to develop and incorporate behavioral strategies to reduce false memories and improve overall memory function in diagnosed individuals. The mission of CTCN also includes building bridges between cognitive neuroscience research and investigators using other research techniques, and to educate clinicians and scientists in cognitive neuroscience and how it can be applied to brain disorders.The laboratory occupies a 6-room suite, which consists of four offices, one room that is divided into separate assessment chambers, and a collaborative workspace area.The laboratory contains a 128-channel Biosemi Active Two data acquisition system. The ActiveTwo system uses active electrodes, and is capable of 24-bit continuous sampling at 4,096 samples per second. The ActiView software is a complete acquisition program that displays all ActiveTwo channels on screen and saves

all the data to a disk. Post-processing of the data is performed using the EMSE Suite 5.3 software (Source Signal Imaging). This allows display of the ongoing EEG, single epochs, and averages with high spatial resolution. The ERP laboratory includes 2 Windows-based computers, three high-resolution VGA monitors, headphones, CD-RW drives for saving data.The laboratory also contains two Cognision Apparatuses, an FDA approved ERP/qEEG device for the diagnosis of Alzheimer’s disease. This system is being utilized through the exploration of event-related potentials, which when used as a biomarker, have the potential to expand our current understanding of the pathophysiology of Alzheimer’s disease beyond the amyloid hypothesis, but also to facilitate earlier and more accurate diagnosis of AD.In addition to the ERP computers mentioned above, the P.I.'s laboratory includes: 4 Dell laptops, as well as 6 Dell workstations equipped with E-Prime, statistical software (SPSS), Adobe Acrobat, Microsoft Word, Excel, Power Point, and internet connections. Two Buffalo Linkstation Network Drives provide shared network drives access and back-up for personal computers. Office equipment also includes 1 Dell 2130cn Color LaserJet printer, 1 Dell M5200 LaserJet printer, and 1 HP 3030 LaserJet Facsimile.VA Boston Overview of National Center for PTSD and Staffing. The National Center for PTSD is mandated by public law 98-528 as a specialized center within the Department of Veterans Affairs devoted to research and training in all aspects of PTSD. The full National Center operation currently involves a seven-site consortium of clinical, research, and training programs devoted to theoretical, empirical, and clinical aspects of PTSD. The applicant organizational units for this competing continuation proposal--the Behavioral Science and Women's Health Sciences Divisions of the National Center are both located at the VA Boston Healthcare System/Jamaica Plain Campus in Boston. The Behavioral Science Division has been active since 1989 and the Women's Health Sciences Division joined the effort when it was initiated in 1992. Male and female veterans of military service are the most frequent consumers of National Center services and the most common populations of study. However, staff interests and activities are neither limited to the veteran population nor restricted to PTSD that results from combat. Community violence, sexual assault, and (with the recent arrival of Dr. Buckley), motor vehicular accidents are examples of traumatic experiences that are also the focus of research and clinical efforts.The National Center for PTSD divisions at Boston have a typical staff size of approximately 45, including 21 psychologists, 2 psychiatrists, 2 social workers, 5 postdoctoral fellows (4 associated with this program and 1 to be enrolled in the newly VA-funded clinical postdoctoral position, September 2000), 3 predoctoral interns, and perhaps 10-12 other junior-level research associates and assistants. The doctoral staff at the National Center have full faculty appointments at Boston University School of Medicine.VA Boston Equipment and Physical Resources. The backbone of National Center computer operations is a fiber optic local area network for the more than 50 computers in use by staff and support personnel. The LAN operates from a set of primary and secondary servers, running Windows NT, that provide security, deliver a wide array of applications, support large-scale file storage and backup, and offer four-port remote access capabilities. The LAN is directly linked to the mainframe cluster of computers which serve the Medical Center, and thereby is linked to the wider network of medical center computers across the VA system. This VA link connects to a gateway onto the Internet, as well as to a mirrored ftp server that allows secure transfer of large files to/from outside computers.All of the computers are PCs that were recently evaluated to insure Y2K compatibility. They range from a set of approximately 10 computers with 300 MHz Pentium II processors operating with 128 megabytes of memory, through a set with 500 MHz Pentium III processors operating with 256 megabytes of memory. Each year, we purchase approximately 10 new computers with the latest available features (e.g., processor speed) to maintain technological currency. Printing is largely centralized through six HP LaserJet high-speed printers. Windows-compatible software of various types is available to all staff via the network. Specific examples of the software include Word and WordPerfect for word processing, Excel for spreadsheets, Access and SQL Server for databases, PowerPoint for graphics applications, and SPSS, S-Plus, LISREL, M-Plus, EQS, AMOS, HLM, and Systat for statistical analysis. Teleforms software is used to create customized scannable forms for data collection and automated data entry. The National Center subscribes to the PsycLit service for literature searches, and to the electronic version of Current Contents for tracking the latest published research in the social sciences. Both of these can be accessed directly from the LAN. In addition, commercial software is available for functions such as creating and searching customized bibliographic databases, statistical power calculations, and modem and fax communication. Computer and data management staff provide custom programming to create, for example, stimulus displays, control data acquisition in the laboratory, and user-friendly ways to manipulate data sets. Most of this programming is being done in the Visual Basic language.

VA Boston Behavioral Science Division houses a suite of rooms devoted to psychophysiological, electrophysiological, and infrared eye movement recording. The psychophysiological recording equipment is based around components primarily purchased from Coulbourn Instruments. This system is comprised of a range of modules and amplifiers that can be configured to record virtually any peripheral physiological signal of interest. The most common measures to date have been heart rate, blood pulse, skin conductance, and electromyographic activity. In addition to blood pressure recorded via the traditional auscultatory methods, we also have two continuous blood pressure monitoring devices called Finapres (from Datex-Ohmeda) that offer capabilities not widely available with noninvasive procedures. Coulbourn Instruments recording equipment provides the backbone of the laboratory system. It operates through a computer interface that samples and stores the output from an A/D converter according to parameters specified by the experimenter. Software used to control this operation is Labtech Notebook and SuperLab, though other similar products are available commercially.One of VA Boston’s Behavioral Science Division psychophysiological labs has a state-of-the-art event-related potentials (ERP) system integrated with it. This 64-channel system operates from an amplifier designed and built by SA Instruments. It is linked to a set of components and software from InstEP Systems that controls stimulus presentation, data acquisition and filtering, waveform processing and display, and source localization. The key advantages of this technology include extensive error checking and filtering, rapid data processing, and advanced capability for identifying brain structures associated with signal differences. The link between ERP and psychophysiological equipment is currently being exploited to simultaneously examine PTSD information processing in terms of electrophysiology, autonomic responding, and startle. This type of multimodal physiological measurement is a rarity in existing research literature.A second VA Boston psychophysiological lab is integrated with infrared eye movement monitoring equipment from ISCAN. This system allows detailed tracking and recording of eye movement patterns, points of fixation, and pupillary diameter. It is completely unobtrusive and does not require any restraints or limitation on the subject other than the need to remain seated in a relatively fixed position. This technology is useful for examining aberrations in eye movement per se, as has been the case in the literature on schizophrenia. For our purposes, the main value of this measurement is its ability to provide direct evidence of viewing location and pattern when visual stimulus presentations are used in experimental protocols. This information is of interest as it relates to other measures of information processing and to the psychophysiological measures of emotion and arousal. Furthermore, pupillary diameter itself offers another index of autonomic functioning that can be considered with others in the psychophysiological domain.Yet a third VA Boston psychophysiological laboratory is housed in the Women’s Health Sciences Division and is available to postdoctoral fellows. This laboratory occupies a three-room suite that consists of a control room and two assessment rooms. The laboratory includes a computerized, remote-controlled system for audio-visual recording of individual participants, dyads, or groups, and a computerized system for recording and reducing psychophysiological data (ECG, EDA, finger pulse volume) from individual participants or dyads. The latter system is controlled by a Pentium PC and currently includes two Dinamap noninvasive blood pressure monitors. Full video-editing capabilities are also available. Outside the laboratories, equipment is available for ambulatory monitoring of psychophysiological activity including blood pressure, heart rate, temperature, and electromyograms. This equipment from SunTech Medical Instruments (Accurtraker), Pulse Metric (Dynapulse), VitaLog and Polar Instruments (Heart Watch), and each has storage and downloading capability so that recordings can be directly processed into a computer for analysis. Finally, there is a range of audiovisual equipment that includes video cameras, recorders, playback units, monitors, and mixers. Computer hardware and software specially designed for both analogue and digital video editing also is available.VA Boston Archival Databases Available for Analysis. Postdoctoral fellows will have ready access to several large archival databases for analysis, including several databases collected at the National Center or affiliated units at the VA Boston Healthcare System. Typical contents of these databases include demographic information comprehensive psychometric data on PTSD and other psychopathology structured clinical interviews measuring trauma, PTSD, and other psychopathology information on physical health and information on occupational and social functioning. Several databases contain extensive psychophysiological data, and databases from completed research projects contain the dependent measures from the study-specific experimental protocols. Examples of available databases include: (a) the database from the National Vietnam Veterans Readjustment Study, encompassing samples of veterans, their family members, and civilians controls, with a total of over 4000 participants altogether (b) the National Center clinical database, containing information on almost 700 male and female veterans evaluated for PTSD and other conditions (c) a clinical database consisting of information collected on 200 inpatients on a substance abuse unit (d) the

database from a nationwide Department of Veterans Affairs Cooperative Study on psychophysiological reactivity, with diagnostic and psychophysiological information on 1500 veterans evaluated at VA Medical Centers around the country (e) a research database containing extensive validity data on PTSD collected on 120 male Vietnam veterans (f) the Ft. Devens longitudinal database containing mental and physical health variables on approximately 2900 male and female Gulf War veterans over multiple time points and (g) the database on the effects of the Peacekeeping Missions in Somalia and Bosnia.VA Boston Integration of Departments and Disciplines. The National Center functions as an interdisciplinary clinical and research program. The two divisions of the Boston arm of the National Center complement one another in that their missions (and actual work performed) overlap to a degree, yet each offers a unique perspective on the study of trauma and its consequences. The Women’s Health Sciences Division is devoted to issues related to gender differences in stress and trauma research as well as a focus on the PTSD-physical health connection. It is also closely affiliated with the Women’s Health Clinic at the VA Boston Healthcare System. VA Boston Center for Behavioral and Cognitive Neurosciences. A second area of considerable research strength at VA Boston is behavioral and cognitive neurosciences. For forty-seven years (until 2014), VA Boston and BUSM hosted the NIH supported Harold Goodglass Aphasia Research Center which is considered to be one of the premier influences in the development of the field of behavioral neurosciences. VA Boston and BUSM also host the Center for Memory Disorders, headed by Mieke Verfaellie, PhD, who is a VA Senior Research Career Scientist and a Professor of Psychiatry at BUSM. More recently, the expertise in this area led to collaboration between the National Center and the cognitive neuroscientists at VA Boston in the form of a VA funded Center of Excellence to study the intersection of PTSD and mild Traumatic called TRACTS: Translational Research Center for TBI and Stress. This group forms the basis for the focus on genetics, neuroimaging, psychiatric evaluation, and life functioning. Aging research is also a critical part of the Neurosciences program with investigators examining aging, physical health status, brain/behavior variables, exercise, and diet as they contribute to learning, memory, attention, and related cognitive functions. Beginning in 2017 a new state of the art building on the VA Boston campus will bring all of these investigators to a single location with the capacity to conduct imaging, psychophysiological measurement, ERP, and related assessment tools. This will constitute a new, integrated Center for Behavioral Neurosciences. As one important component of this program is the development, construction, and implementation of a state of the art Exercise Physiology Laboratory located at VA Boston. This research laboratory is 800 square feet of new equipment that is available for precise measurement of exercise and related physiological parameters. Multiple investigators from a variety of disciplines now use this facility to understand the impact of exercises across many domains of functioning, to include cognitive, cardiovascular, pulmonary, and muscular levels of analyses. VA Boston Massachusetts Veterans Epidemiological Research and Information Center. The Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) was funded in 1997 with the mission of improving the health of Veterans and enhancing health care delivery in the Veterans Health Administration (VHA) by promoting the conduct of VA-based population research relevant to the needs of Veterans facilitating the transfer of vital epidemiological information to VHA providers and administrators and educating the next generation of population researchers. Over the past 12 years MAVERIC has expanded to five major programs: the Clinical Trial Coordinating Center (CC), the Epidemiology Research and Information Center (ERIC), the VA Central Biorepository, the Informatics Program, and the MAVERIC Training Program.VA Boston MAVERIC—Applied Research and Technology (ART) Research Core Facilities. Consisting of multiple components of important, interdisciplinary scientific research, the MAVERIC ART facilities incorporate the following capabilities that are widely available to collaborating investigators: Biostatistics Core. Biostatistical support is available to support local investigators and outside entities including consulting services, study design, preparatory to research analysis for grant support, statistical analysis plan development, biostatistical programming and analyses.Biorepository. The main objective of MAVERIC Core Laboratory is to support and enhance VA clinical research by providing both local and national VA researchers with a coordinated, quality-assured, and state-of-the-art facility for biological specimen collection, automated or manual processing, storage, and distribution. The laboratory provides both local and national VA researchers a convenient, high-quality, low-cost mechanism to include biological specimen processing, DNA extraction, aliquotting, sample storage and supplies.Study Management Services. MAVERIC is fully equipped to support local investigators in managing studies including protocol development, document tracking and management, study site coordination, system validations, study monitoring, and regulatory compliance consultation.

Informatics Core. The MAVERIC Biomedical Informatics Team specializes in the development of information technology and informatics methods. They conduct research and development to make information more useful for the science and practice of healthcare. Areas of applied research include natural language processing, machine learning, quality measurement & improvement, and scientific information infrastructure development. The Informatics Core provides support in electronic data capture, clinical trial management systems, genomic infrastructure services, recruitment and enrollment software interface, software development, information extraction, data mining, natural language processing, and data standards consultation.Study Design Expertise and Consulting. MAVERIC Investigators are available to provide expertise in study design for clinical trials, pharmaco-epidemiology, cohort studies and database studies. MAVERIC Investigators are on the cutting edge of research with experience in point of care or pragmatic clinical trials, translational research, and biomarker validation studies. Data Operations Core. The MAVERIC Data Operations Core supports local investigators and outside entities in VA data acquisition, forms design and development, data management, data reporting, and consulting services.

THE UNIVERSITY OF VERMONT

The University of Vermont (UVM), the Robert Larner MD, College of Medicine (COM), and associated UVM Health Network (UVM HN) are highly valuable resources for the proposed CSTA application. The physical and intellectual resources available to the proposed partnership ensure its feasibility and success in augmenting the clinical and translational research capabilities of BU CTSI Hub.

Scientific Environment. The University of Vermont is often called UVM—Universitas Viridis Montis, Latin for "University of the Green Mountains." Founded in 1791, UVM is a premier small research university with a reputation for excellence in biomedical research. It is Vermont’s flagship university and it’s only comprehensive research institution of higher education. Today, UVM is a Public Ivy and top 100 research university. It is the perfect size, large enough to offer a breadth of ideas, resources, and opportunities, yet small enough to enable close faculty-student mentorship across all levels of study, from bachelor’s to professional degree programs. A new Science Technology Engineering and Mathematics (STEM) Complex is currently in construction. In a four-year, three-phase project that began in Spring 2016, UVM is building a state-of-the-art teaching and research laboratory facility and a new classroom/office facility for Chemistry, Physics, Engineering, Mathematics, and Statistics and Computer Science. In addition to these significant infrastructure investments, a major strength of the UVM research enterprise is the collaborative and interactive nature of the scientific environment, which favors cooperation, rather than competition as a strategy for continued strengthening of scientific inquiry at the university. blends the academic heritage of a private university with the service mission of the land-grant tradition. UVM is home to over 10,500 undergraduates, 1,542 graduate students, 459 medical students and more than 1,500 full- and part-time faculty. Student educational experiences are enriched by our location – from the energy and innovation of Burlington, Vermont, to the forests, farm, and independent spirit of Vermont. Burlington is approximately 90 miles south of Montreal, 230 miles northwest of Boston, and 300 miles north of New York City.

The Robert Larner MD, College of Medicine (LCOM) was established in 1822 as the nation’s seventh medical school, it has earned a longstanding reputation for educating and training superb physicians and scientists, fostering groundbreaking research to improve patients’ lives, and actively engaging with the community of Vermont and the region. Today(2018) the LCOM enjoys over a robust annual extramural grant funding record, an award-winning integrated curriculum, and international recognition for research-based expertise, clinical and teaching excellence, and strong community partnerships. The UVM College of Medicine is organized into 16 academic and clinical departments and over 20 interdisciplinary centers, programs, and networks, including four NIGMS T32 programs, two NIGMS COBREs, two completed COBREs, and an INBRE that train the next generation of biomedical scientists. Over the past decade, the College of Medicine has built or renovated more than 100,000 ft2 of space for science education, research faculty offices and conference rooms, and laboratory and core space. In support of the research mission, the current extramural research support totals $69 million with an additional $4.5 million in support of clinical trials. On a per capita basis, this places LCOM in the top ten states for federal funding and similarly for population engaged as research participants. The faculty of LCOM published 1168 peer-reviewed publications last year. A major strength of the college is the collaborative and interactive nature of its environment, which allows for interdisciplinary, translational research that cuts across all disciplines.

The UVM College of Nursing and Health Sciences is an integral part of the UVM academic medical center that connects faculty practitioners, scientists, and scholars with the next generation of health care professionals. The Rowell Building in the UVM Health Sciences complex houses the College of Nursing and Health Sciences and is directly connected to the College of Medicine.

The UVM Medical Center, formerly Fletcher Allen Health Care, partners with the UVM College of Medicine and the College of Nursing and Health Sciences to form an integrated delivery system that provides high-value health care to surrounding communities and enhances the academic mission of UVM. The UVM Medical Center is Vermont's academic medical center—one of approximately such 130 centers in the US. All of the resources and opportunities of a major medical center are available to VT and upstate NY residents, providing patients with the breadth and depth of services they need and an array of specialists nationally acclaimed for their work in a wide range of medical disciplines. UVMMC, the only teaching hospital within a wide radius, trains approximately 300 residents and fellows in 16 residency and 23 fellowship programs. UVMMC consists of 562 licensed hospital beds and over 30 patient care sites. In the early 2010s, a new 550,000-ft2 Ambulatory Care Center and an adjoining 70,000-ft2 Medical Education Center and underground library were built to accommodate the clinical operations of the Medical Center, and Colleges of Medicine, and Nursing and Health Sciences. In July 2015, a $187 million project was approved to construct a new 180,000-ft2 inpatient building in the UVM Medical Center complex. The Clinical Research Center is located within the hospital and houses the outpatient and inpatient wards for clinical research trials. UVMMC, in conjunction with the LCOM, constructed a new educational facility that interconnects the hospital and clinical research center facility with the research buildings.

The UVM Health Network is the parent organization of a five-hospital, cross-lake partnership that includes the UVM Medical Center as its largest institution. The network establishes a highly integrated health care system serving the communities of Vermont and northern New York. The system includes more than 1,200 physicians, more than 2,700 nurses and countless other health care professionals. The six hospitals in the network provide 936 staffed beds, greater than 40,000 inpatient discharges, 172,00 ED visits, 4.6 million laboratory specimens and a total 1.8 million patient visits, The UVM Medical Center also works collaboratively with other health care organizations, including the Visiting Nurse Association and three smaller medical centers in upstate New York to strengthen the services available to patients in the catchment region. These mutually beneficial partnerships and affiliations allow patients at affiliate hospitals to receive diagnostic and follow-up care from UVM Medical Center specialists close to their homes. In addition it facilitates access to care from UVM Medical Center providers for populations in rural areas. Finally, affiliates can access the resources of the region’s academic hospital including cutting-edge therapies and technologies, specialists with advanced, research-based expertise. There is in place a strategic plan for academic integration that focuses on teaching and research across the network.

Core Clinical Facilities at the LCOM: The Office of Clinical Trials Research (OCTR) at the UVM Larner College of Medicine was established in 2002. The mission of the OCTR is to promote and enhance quality clinical research activities at UVM; to provide a wide range of trial support services allowing investigators to concentrate on their research; and to act as an institutional contact for sponsors facilitating identification of investigators whose clinical trial interests, experiences, and patients match a sponsor’s study requirements. Last year, OCTR provided clinical research nurse or coordinator services during over 2000 outpatient visits The OCTR provides study nursing services and fully-trained research coordinators on a fee-for-service basis. The OCTR provides centralized financial and legal review and approval of all industry-sponsored clinical trial research contracted at UVM Medical Center. Contracts are reviewed for consistency and compliance. The current services provided by OCTR to investigators include clinical coordinator and research nursing support, budget development and negotiation, preparation and submission of regulatory documents and audit preparation and support. The OCTR has functioned as a Contract Research Organization spearheading and overseeing clinical trials conduct and regulatory management at multiple research sites. The OCTR has assisted in the development and implementation of research standard operating procedures ensuring the smooth and compliant functioning of trials. The clinical staff of OCTR includes 6 FTE research nurse coordinators and 5 FTE research coordinators; their services are available at standard hourly rates to support industry-sponsored trials; there are 6 additional staff who are non-clinical.The Clinical Research Center (CRC) at the University of Vermont/UVM Medical Center had been in existence, until a few years ago with NIH support (as a GCRC), for more than 40 years, Presently, it is an institutionally supported CRC that provides infrastructure for the performance of high-quality, clinically oriented research with an emphasis on NIH-funded research. The CRC is both an Inpatient and Outpatient Unit with its own dietary

component, core laboratories that house Gas Chromatography and Isotope Ratio Mass Spectrometers and a staff statistician. The CRC employs 19 technicians and nurses and provides 9,290 sq. ft. of clinical research and laboratory space. Satellite labs include the Molecular Genetic Research Core Laboratory that is a fully equipped molecular genetics laboratory that carries out a wide range of research and diagnostic testing and the Cardiac Rehabilitation Facility that allows for exercise testing and training.

Nursing Equipment 12 Inpatient/Outpatient Rooms--Private or Semi-Private Capability--All Procedure-Ready Automated BP monitoring (Dinamap) Digital standing scales (Scale-tronix) Digital wheelchair scale (Detecto) Stadiometer (Harpenden) Electrocardiogram machine (GE MAC 5000) Telemetry system (HP Intellivue) GE Vivid 7 ultrasound unit Infusion pumps (Alaris) Syringe infusion pumps (IMED Gemini and various sizes of Harvard) Hand warming boxes to permit sampling of arterialized venous blood Glucometer (Precision) Doppler machine (Huntleigh Diagnostics) Pulse Oximeter (Nellcor) Gynecological exam table, pap testing supplies Video camera

Biochemistry Core Laboratory Two IEC refrigerated centrifuges Room temperature table top centrifuge -80 and -20 degree freezers for temporary storage YSI model 2300 Glucose analyzer (3) Micromedic Digiflex and multiple Rainin Pipetmen Fume hood lab bench equipped for sample processing or experimentation Sartorius balance

The Laboratory for Clinical Biochemistry Research (LCBR): Directed by Dr. Russell Tracy, the LCBR is CLIA-certified for certain testing and participants in external proficiency testing programs such as those offered by CAP and NGSP. The LCBR has two main locations. The laboratory itself is located in the Colchester Research Facility approximately three miles from the main University of Vermont campus. The LCBR includes ~ 3500 square feet for research divided into four areas: sample receipt and handling, general biomarker lab, DNA preparation and analysis lab, and a CLIA-certified clinical chemistry lab. In addition there is a 160 sq ft cold room, and ~1,000 sq ft of office, conference and workstation/computer space. At a second location, the Biological Sample Repository comprises about 10,000 sq ft of freezer storage space which is temperature-controlled, alarmed, and backed up with generator power.The LCBR Biological Sample Repository currently houses ~4,000,000 samples in more than 160 -80ºC or –145ºC freezers. This is actually a family of individual repositories, each with specifically labeled and databased sample sets. Samples include serum, various types of plasma, urine, cryo-preserved cells, and purified DNA. There is also LN2-based stored for specialized tissue samples. The facility has three separate power lines (ensuring that complete loss of power is exceedingly rare) and full generator backup. All freezers a fully alarmed and LCBR personnel and a certified freezer repair service are on call 24 hours a day. Freezer inspection, maintenance, and cleaning is performed frequently. Storage and location of repository samples are maintained and tracked in computer databases. All new studies use barcode technology to enhance sample tracking capabilities.MRI Center for Biomedical Imaging: The UVM MRI Center for Biomedical Imaging, a UVM College of Medicine Core facility, is a research dedicated facility that specializes in functional, quantitative, and static brain imaging. The facility has a full complement of multi-channel, parallel imaging “SENSE” coils for cardiac, orthopedic, abdominal, and all anatomic regions of the body. The MRI Center for Biomedical Imaging is co-directed by Drs. Joshua Nickerson and Richard Watts. It was established in 2007 with grant support provided by the US

Department of Energy. The facility houses a Philips 3T Achieva dStream MRI scanner, including 32-channel phased array head coil, and Dual Quasar gradients with up to 80mT/m strength and a slew rate of up to 200 T/m/s. dStream technology provides signal digitization at the coil to minimize noise, as well as an almost unlimited number of receive channels. This scanner was recently the first Philips scanner to be upgraded to a new spectrometer (DDAS) to support the use of multiband SENSE technology (simultaneous multislice imaging), enabling acceleration factors of up to 8 over conventional functional and diffusion MRI acquisitions with minimal loss of signal-to-noise. The UVM MRI Center for Biomedical Imaging is located in the McClure building of the University of Vermont Medical Center, UVM’s affiliated teaching hospital. The facility is available to investigators by appointment. Two senior MRI technologists, an MRI physicist, and a neuroradiologist staff the facility. In addition, the MRI Center has a research collaboration agreement with Philips Healthcare, Cleveland, OH, which provides an on-site MRI clinical scientist, who is also an adjunct associate professor of radiology at UVM. This relationship with Philips also allows access to various research software keys to perform scan sequences that are not yet available on commercial MRI systems.

MRI Center researchers have recently developed improved, specialized quantitative MRI methods such as: T1rho, pseudo-continuous arterial spin labeling (PCASL), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI). The MRI Center has been working on cutting edge techniques for quantifying brain tissue with T1rho MRI in Alzheimer's patients, Multiple Sclerosis patients, Mild Traumatic Brain Injury (MTBI) subjects, and in healthy individuals. The facility also has the ability to image rats and mice, and is able to accommodate a limited number of rodent studies.

Advanced Biostatistics Unit: Statistical consultation and analysis are also available through the Biostatistics Unit at UVM if needed to extend the capabilities of the BU BERD Core. The College of Medicine Biostatistics Unit develops and maintains a comprehensive coordinated program of research support covering biostatistics, statistical genetics, and epidemiology for biomedical and health-related research activities. The Faculty of the Medical Biostatistics Department includes biostatisticians, epidemiologists, and behavioral scientists, some of whom are affiliated with the Statistics Program of the College of Engineering and Mathematics or other academic units. The Department staff currently consists of 5 Ph.D. Biostatisticians, 3 M.S. Biostatisticians, and 2 Data Analysts. Data Analysts carry out data processing and analysis as well as assist in the development of databases. The UVM College of Medicine is currently searching for two additional biostatisticians for the Biostatistics Unit.

Special Purpose Computer and Software Systems: The Biostatistics CATI system server is a Dell PowerEdge with a 2.0 GHZ dual-core Xeon processor and 4 GB RAM running 2003 Windows Server. It utilizes WinCati (ver.4.2.4.1) by Sawtooth Technologies, Inc. with up to 12 possible interviewer seats and 1 supervisor that is part of the departmental work group. The IVR server and developmental platforms are Dell Optilex systems which are now configured to handle 4 incoming lines and uses Telesage SmartQ (ver.5.2.48). The Biometry Facility also maintains hardware and software for data form development and form scanning using Adobe Form Designer, AUTODATA Scannable Office software and Panasonic KV S2026C scanners. MATLAB is used for 2D image capture and for programming for feature extraction purposes using GUI interfaces.Biostatistics Software Inventory: Available software packages include SAS, SPSS, SUDAAN, BMDP, SYSTAT, STATA, Egret, EgretSize, EquivTest, HLM, Mplus, EQS, AMOS, MULTILOG, StatXact, LogExact, WinBugs, Comprehensive Meta-Analysis, nQuery, StatPower, PASS, SOLAS, ToxTools, DBMS Copy, StatTransfer, and other specialized software packages, macros, libraries and languages (FORTRAN, IMSL, R, S+), specialized server and developmental platform software for Computer Aided Telephone Interviewing (CATI) and Interactive Voice Response (IVR) systems. Standard office support and communication software includes MS Office Professional (Word, Excel, PowerPoint, Access), Word Perfect, Adobe Acrobat Professional, Mozilla Firefox and Thunderbird, and Open-Office, and GoToMeeting and GoToTraining.

Bioinformatics Shared Resource: The bioinformatics core, directed by Dr. Julie A. Dragon, provides computational and bioinformatics support in the form of experimental design and data analysis related to high throughput genomic and proteomic data. Services include consultation on experiment design and sample preparation, target preparation, target hybridization/scanning, library construction, quality assessment, calculation of probe set statistics, sequence reads, alignment to a reference genome, variant calls, linear modeling, multivariate analysis, text describing methodology/figures for manuscripts, and deposition of data in public databases. In addition to providing established resources, the core assists in implementing new bioinformatics tools to provide innovative solutions for bioinformatics challenges as they occur. Core personnel also support use of tools associated with the Vermont Advanced Computing Cluster (VACC), a multi-core cluster that will run computational intensive applications. The UVM College of Medicine is currently searching for two additional bioinformaticians for the Bioinformatics Shared Resource. In this role, they will help support the bioinformatics needs of the Rural Health Research and Delivery Core. The Bioinformatics Shared Resource is located in the Hills Building of the UVM Health Sciences complex.The Tissue Management and Analysis Core: This facility comprises UVM College of Medicine facilities that have been providing research services for more than two decades, including biobanking resources through the UVM Medical Center Surgical Pathology Department. Surgical Pathology provides specimen processing for surgical/biopsy samples received from the UVM Medical Center, Copley Hospital, Cottage Hospital, Littleton Hospital, North Country Hospital, Northeastern Vermont Regional Hospital, Porter Hospital, and a large number of outpatient samples from a diverse referral base. The Surgical Pathology Suite includes 8 gross evaluation and sectioning stations. Intraoperative assessment and rapid tissue assessment are managed in a dedicated adjoining suite. Once laboratory assistants receive specimens, the cases are reviewed grossly by a resident or pathologist assistant (overseen by an attending pathologist). Sections are taken and processed by histology in an overnight/early morning procedure from which glass slides of the tissues are produced. The attending staff in Surgical Pathology has expertise in both general anatomic pathology as well as specialty areas including gastrointestinal pathology, dermatopathology, gynecologic pathology, breast pathology, neuropathology, soft tissue pathology, pediatric pathology, hematopathology, renal pathology, genitourinary pathology pulmonary pathology, and cardiovascular pathology.

Biobank Core: The UVM Biobank Core contains more than 3,000 tumor samples from a wide range of anatomic sites in -80°C storage. Typically, 30–45 fresh surgical specimens are frozen for banking each month. The Biobank has a collaborative agreement with the University of Massachusetts Medical School Biobank (Director Stephen Lyle, MD) for mutual enhanced sample range access. Specimens are collected according to IRB compliance requirements. The Biobank is operated by standard operating procedures compliant with ‘NCI Best Practices for Biospecimen Resources’ and in accordance with College of American Pathologist ‘Biorepository Checklist’ requirements. Specimen storage and utilization is managed using Freezerworks Unlimited Sample Management software (Dataworks Development, Inc., Lynwood, WA). The Biobank utilizes two Revco -86°C freezers; in accordance with guidelines, these are located in separate buildings (HSRF and Given) that operate on unique power source inputs. Freezers are fully alarmed for remote notification of temperature control failure. One full time technician is employed by the Biobank.

Research Histology Laboratory: The Research Histology Laboratory occupies 300-ft2 and is part of the clinical histology laboratory in the UVM Medical Center. Support for histologic, histochemical, immunohistochemical and in situ hybridization applications is available through the laboratory. Abiy Ambaye, MD is the lab Medical Director; technical support is provided by two personnel; Mark Evans, PhD is a scientific consultant for the lab.Investigational Pharmacy Services: The UVM Medical Center Department of Pharmacotherapy oversees approximately 100 inpatient and outpatient investigational drug studies. The Investigational Pharmacy Services ensure full compliance with federal, state, and sponsor requirements regarding drug dispensing, monitoring, and accountability. SOPs are in place and include a comprehensive continuous quality improvement program that monitors all aspects of data acquisition and management of case and dosage report forms, and it provides oversight of final dosage and labeling for compliance with agency and sponsor requirements, ensuring patient safety. Health Economics Unit: The HEU are 3 faculty, 2 staff, and 5 affiliates. The impact of health and health care costs on economic growth is essential given the rising health care cost. Health economics as a service is receiving considerable attention. In its broad definition, health economics comprises an organized and systemic analysis of the trade-offs between costs and units of effectiveness. The goal of the unit is to introduce health economics methods to investigators and provide expert services for applying a wide range of health economic tools. Research areas amenable to these services are diverse and include: bench-to-bedside translation, clinical trials, health services delivery research, and health policy reform. The viewpoints of these evaluations may variously include the patient, hospital, healthcare budget or society as a whole. Key responsibilities of the unit include support to investigators who want to apply comparative effectiveness and health economics methodological tools to clinical and translational research, and assessment of research impact of health economics services. Resources & Services include: (1) Cost-Effective Analysis to measure consequences of interventions (or programs) held as comparators, using natural units such as “life years gained” or “hospitalizations avoided.” A special form of cost-effective analysis called cost-utility analysis accounts for the consequences of alternative interventions adjusted by health-state preference scores called utility weights; (2) Cost-Benefit Analyses assess cost consequences of health problems and are evaluated in a manner similar to cost-effective analysis, where both the numerator and denominator are placed in monetary terms; (3) Budget-Impact Analysis provides down-stream estimates of total financial consequences within a specific healthcare budget from which to assess affordability; and (4) Sensitivity Analysis uses extreme scenario analysis to test the extent to which results are robust following extreme changes in values, assumptions and sets of values and assumptions.

UVM Department of Psychiatry Addictions Research Program (Stephen T. Higgins, PhD, Director): There is a longstanding (> 30 years) and active program of addictions research within the UVM Department of Psychiatry. This program includes a rich array of NIH and other externally supported research ($49,142,323 in current total grant support excluding COBRE funding). Research interests span most licit and illicit drugs of abuse, although currently there is considerable focus on opioid addiction and tobacco control and regulatory science. This research center is also integrated with the UVM Medical Center’s outpatient clinical services for addictions. A Tobacco Centers of Regulatory Science (TCORS) is a particularly important component of this research program and supports two multi-site studies and a vibrant training program for 4 predoctoral and 4 postdoctoral fellows, along with 9 full-time research assistants, 5 hourly research assistants, 2-3 paid students hourly assistants, and 5-6 undergraduate students participating for academic credit. The TCORS training component is integrated with a longstanding NIDA-supported T32 training program in addictions research that supports an additional set of 4 predoctoral and 4 postdoctoral fellows. The TCORS area of study has primarily been on the influence of nicotine content of cigarettes on the addiction potential of cigarette smoking in vulnerable populations. This addictions program also supports clinical laboratory research on behavioral-economic, genetic, and neurobiological factors underpinning addiction vulnerability as well as treatment-outcome research on behavioral and pharmacological interventions for opioid, tobacco, and other addictions. The center occupies more than 10,000 sq ft of office, clinical laboratory, and treatment clinic space in the main outpatient building of the LCOM campus, which houses the central offices of the VCBH. Drug use toxicology testing is available onsite. The Chittenden Clinic Opioid Treatment Program: The Chittenden Clinic Opioid Treatment Program is the first and largest outpatient opioid treatment program in the State of Vermont. It is a joint venture between the University of Vermont, UVM Medical Center and the Howard Center for Human Services. The clinic is under the leadership, Dr. Stacey Sigmon, and is located in the ambulatory care building where the VCBH addictions research labs and clinics and administrative offices are located. The Chittenden Clinic includes therapists and staff offices, a dispensary, on-site urine toxicology lab, exam room, reception area, intake room, and a large

waiting room. The Chittenden Clinic has an integrated and automated methadone delivery system and buprenorphine- dispensing infrastructure. The clinic has an extensive on-site urine toxicology testing laboratory which includes a high-capacity Microgenics enzyme immunoassay VTwin analyzer, and this equipment is available for use at any time in the event of unforeseen equipment or scheduling problems in the addictions research program. The UVM Cardiac Rehabilitation (CR) Exercise Testing and Training Facility (Philip A. Ades, MD, Director): The UVM Cardiac Rehabilitation (CR) Exercise Testing and Training Facility is one of the preeminent CR research centers in the world. Research topics include resistance training in older cardiac patients and patients with chronic heart failure, methods of weight reduction in overweight cardiac patients, and methods such as financial incentives to increase CR participation in low SES cardiac patients. Behavioral counseling services for weight reduction and stress management are provided. The CR Facility is located in the UVMMC Outpatient Cardiology building. It includes both clinical areas for examining patients and exercise testing and training areas along with research space. Facilities available to VCBH investigators include a fully equipped exercise testing laboratory with a Mortara X-Scribe 7 ECG system, a treadmill, a Monarch ergometer and a MedGraphics expired gas analysis apparatus. In addition, there is a 2,000 sq ft exercise training facility including 10 treadmills, 6 concept II and Nu-step rowing ergometers, 6 cycle ergometers, a multi-station Bodyguard strength training set up, and free weights. An automatic defibrillator is on site as are ECG monitors. In addition to ample equipment for exercise there is dedicated facility space and equipment for individual and classroom education and counseling. This center brings an outstanding level of research and clinical expertise in physical activity, resistance training, and weight reduction among seriously ill clinical populations. IDEA-CTR: Northern New England Clinical and Translational Research Network (NNE-CTR) (UVM PI’s Gary S. Stein, PhD and Gordon Jensen, MD, PhD): The mission of the recently funded NNE-CTR Network is to develop and sustain a clinical and translational research infrastructure that supports improvement in rural and community health for inhabitants in the IDeA states of Maine, New Hampshire, and Vermont. This goal will be accomplished through complementary and synergistic collaborations of investigators at two lead institutions, UVM and Maine Medical Center, one participating institution, the University of Southern Maine, two collaborating organizations and the Dartmouth Primary Care Cooperative Research Network (Dartmouth CO-OP). The NNE-CTR efforts will emphasize chronic health problems endemic in the rural populations of Northern New England, including cancer, cardiovascular disease, and substance abuse, as well as the barriers that compromise rural health care delivery. To accomplish these goals, NNE-CTR aims to: (1) improve the infrastructure and support for clinical and translational research in Vermont, Maine and New Hampshire; (2) increase translational and clinical research capacity and efficacy by establishing collaborative and synergistic transdisciplinary research partnerships among the NNE-CTR institutions, aided by a vigorous Pilot Projects program; (3) establish innovative training, mentoring and professional development programs to develop clinical and translational scientists at the NNE-CTR institutions; and (4) provide the infrastructure to support community practices and practice-based primary care research networks, particularly in rural areas, to engage clinical, community, public health and other stakeholders in the development and conduct of research relevant to the clinical and population health needs of northern New England. Vermont Cancer Center (VCC): Housed in the LCOM, the Vermont Cancer Center (VCC) is a not-for-profit comprehensive clinical and research cancer center, the only such organization in the state. Founded in 1974, the VCC comprises more than 120 scientists and physicians engaged in a full range of basic, translational, clinical, and outcomes research. The Center is committed to innovative research, life-saving prevention and treatment programs, public education, scientific collaboration, and serves to influence standards of cancer prevention, screening, diagnosis, and care. An emphasis is placed on delivery of cancer screening and treatment to rural and underserved populations. A common thread of inquiry and discovery is epigenetics in cancer to better understand how cancer develops and how this process can be modified to achieve better treatment outcomes. Vermont Breast Cancer Surveillance System (VCBSS): The Vermont Breast Cancer Surveillance System (VBCSS) is a statewide registry of integrated patient, radiology, pathology, treatment, and outcomes data for all women undergoing breast imaging in the state of Vermont. Drs. Sprague and Weaver lead the VBCSS, which is a member of both the Breast Cancer Surveillance Consortium (BCSC) and the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. Since 1996, the Vermont Breast Cancer Surveillance System (VBCSS) has been continuously funded by research grants from the National Cancer Institute and PCORI to study breast cancer screening in community practice. The VBCSS integrates data from 15 radiology facilities, 10 pathology facilities, and the Vermont Cancer Registry, thus providing extensive longitudinal data from over 200,000 women undergoing breast imaging in Vermont since

1996. These data include over 1.2 million mammography exams (screening and diagnostic) and more than 50,000 breast specimen pathology records, including more than 10,000 breast cancer diagnoses. The breadth of data integrated in the VBCSS permits a wide range of research opportunities, such as studies of breast cancer risk, etiology of molecular subtypes, utilization of screening, screening performance, diagnostic pathways, breast cancer recurrence, and breast cancer mortality. The UVM Weight Management Research Program (Jean Harvey, PhD, RD Director): The UVM Weight Management research program located in the Department of Nutrition and Food Sciences has a significant web-based support/counseling system that accomplishes similarly effective weight management remotely or onsite. This program brings a unique expertise in remote, web-based treatment for weight loss for overweight and obesity that will be an innovative and important resource for the BU-UVM CTSI efforts to combat the obesity epidemic, but also to integrate current technology into expanding the reach of clinical interventions for cigarette smoking and other health-related behavior problems. The Vermont Center for Children, Youth and Families (James Hudziak, MD, Director): The Vermont Center for Children, Youth and Families is a center within the Department of Psychiatry that encompasses research at UVM and patient care at UVMMC, as well as information for primary care givers in the State of Vermont. Areas of research interest include, but are not limited to, genetic and environmental influences on developmental psychopathology and wellness, ADHD, aggression, depression, developmental psychopathology and wellness and physician education through telemedicine online education systems. This program brings an internationally recognized level of expertise in behavioral genetics that is already fostering NIH-supported research collaborations among VCBH members and will be an outstanding resource for the VCBH. This center supported one of our original five Project Directors (Dr. Althoff) and will continue to be available to him and other VCBH investigators. Vaccine Testing Center (VTc): The Vaccine Testing center is an investigator-initiated research team seeking new approaches to vaccine development. The Vaccine Testing Center and laboratories are housed on the main medical campus of the Robert Larner, MD College of Medicine at the University of Vermont and its affiliated hospital, UVMMC. Since its establishment in 2001, the Vaccine Testing Center has been dedicated to advancing knowledge in vaccine development, infectious diseases, and human immunology. With the goal of decreasing the global burden of infectious diseases, the VTC performs Phase I- III clinical trials of candidate vaccines and therapeutics against infections; laboratory-based research exploring human immune responses to vaccines and infections; and international/developing country field trials of vaccines and therapeutics for infectious diseases. The UVM VTc has successfully conceived, designed, written, and obtained funding for research proposals and worked with the Navy Medical Research Center, the National Institutes of Health, other academic centers and industry partners, and the Bill and Melinda Gates Foundation. The team is also one of only four U.S.-based academic centers that perform inpatient, human enteric challenge models (Campylobacter, cholera, Shigella). The VTc’s administrative, regulatory and financial “core” assures that all clinical work is performed to Good Clinical Practices standards and manages QA/QC and Quality Management Plans to assure full federal and international compliance, as well as audit-readiness for both the clinic and laboratory. The VTc team includes clinical (MD) and scientific (PhD, Dr. PH) faculty, clinical research study managers and coordinators, a statistician, administrators and recruiters, an operations/regulatory expert and laboratory technicians. The VTc team has recently worked on a 10-year federal contract with the NIH and Johns Hopkins to perform multiple clinical trials toward developing the NIH’s live attenuated tetravalent dengue vaccines; a multi-center grant with the Gates Foundation (in Bangladesh) to determine immunologic reasons for oral vaccine underperformance; and a phase III vaccine-challenge model of a single-dose oral cholera vaccine.

Vermont Child Health Improvement Program: VCHIP is a population-based maternal and child health services research and quality improvement program of UVM. The main goal of VCHIP's program evaluation effort is the systematic gathering and assessment of information to provide useful feedback about a program. Quality improvement initiatives are the hallmark of their work and provide the framework that VCHIP and their clinical partners use to improve the health outcomes of children, youth and families in Vermont and nationally. In addition, through its effective engagement with community-based medical practices, a network of state Improvement Partnerships has emerged as an effective way to advance quality and transform health care practice for children. VCHIP provides individual practice-level support, with a focus on identifying strategies for improvement that can be implemented system-wide. The program will benefit the proposed NNE-CTR as a model of effective healthcare delivery research and evaluation in Vermont and as a launching point for identifying community-based practices that could serve as collaborators in rural health research and delivery initiatives through the proposed network. Vermont Area Health Education Centers Program (AHEC): The Vermont AHEC Program is a statewide network of community and academic partners working together through three AHEC centers and a Program Office to improve the health of Vermonters. Through community-based initiatives, Vermont AHEC works to promote rural health educational opportunities and address health care workforce challenges unique to specific areas of the state. Dr. MacLean is PI for the Health Resources and Services Administration grant funding this program. Vermont Department of Health, Vermont Agency of Human Services: The Vermont Department of Health, part of the larger umbrella agency, the Vermont Agency of Human Services (which also contains departments such as Mental Health, Children and Families, Aging and Independent Living, and the Department of Vermont Health Access) is Vermont’s lead agency for public health. It has twelve district offices throughout Vermont, connecting public health to communities, health practitioners and hospitals. The environment is a collaborative one, and both Dr. Carney and Dr. MacLean have strong connections and ongoing work with these agencies, directly relevant to the NNE-CTR.

The Department of Health is home to data and surveys, including the Behavioral Risk Factor Surveillance System, chronic disease data, environmental and infectious disease tracking, substance abuse surveillance, vital records, hospital discharge databases, and health care provider surveys. The Department regularly reports on the health of the population for the entire state, and also has reporting capacity at the county, hospital and health services, and health department district levels.

The Vermont Blueprint for Health: The Vermont Blueprint for Health is a state-led, nationally recognized initiative that helps health care providers meet the medical and social needs of people in their communities.

Medical Homes are the foundation of the Blueprint, along with Practice Facilitators who help them continuously improve care, and Community Health Teams who expand available services to include free care coordination, counseling, substance abuse treatment support, health coaching and more. The Blueprint also helps design innovative interventions, like Support and Services at Home (SASH) for elders and Hub & Spoke Medication Assisted Therapy for individuals battling opioid addiction. All Blueprint work is closely integrated with health and human service organizations through Community Collaboratives that guide care delivery and payment reforms at the local level. Dr. MacLean serves as a member of the Provider Practice Workgroup, Evaluation Workgroup, and Executive Committees of the Vermont Blueprint for Health.

The Vermont Lung Center (VLC, Charles Irvin, PhD, Director): The UVM Vermont Lung Center is a thriving, self-sustaining research center, initially established through NCRR (now NIGMS) COBRE support. VLC Director, Dr. Charles Irvin, is a member of the steering committee for this application. The keystone to the VLC program is translational research. Over 15 years the center grew from 2-3 investigators to 32 investigators in three departments and $13.4 million (FY 2017) million dollars in extramural research support. The VLC enjoys an international reputation for research excellence in lung disease, lung cell biology, asthma, cystic fibrosis, stem cell biology, bioengineering, epithelial biology and the effect of obesity on the respiratory system. The training program is supported by an NHLBI T32 training grant. The program currently recruits participants in over 50 clinical research studies that are supported by the NIH, CF Foundation, industry and the American Lung ACRC program. VLC investigators are considered some of the best investigators in lung biology and disease-all made possible by fully capitalizing on the IDeA program. The VLC has offered grantsmanship workshops twice over the last 5 years for all UVM COBRE early-career faculty members. The Vermont Center for Immunobiology and Infectious Diseases (VCIID) (Ralph Budd, MD, Director): The Vermont Center for Immunobiology and Infectious Diseases (VCIID), a COBRE-supported center, now in Phase III, was established in 2006. VCIID combines the expertise of the UVM COM groups in Immunobiology,

Microbiology, and Infectious Diseases to promote collaborative studies into the immune response to infectious agents, including viruses, bacteria and parasites, as well as studies of microbial pathogenesis and autoimmune disorders. The VCIID currently has 25 faculty members in 8 departments and 4 colleges. The Center has an outstanding record of productivity including peer-reviewed publications, external grant support, and early-career faculty mentoring. The Center also supports core facilities in microarray, bioinformatics, proteomics, and flow cytometry. OTHER RESOURCESCore/Shared Facilities: Vermont Integrative Genomics Resource (VIGR): The VIGR is an overarching, umbrella core encompassing four distinct shared resources: DNA Analysis, Microarray Analysis, Massively Parallel Sequencing, and the Bioinformatics Shared Resource. The mission of the core is to comprehensively support research by providing direct services to research laboratories and by introducing emerging technologies to the broader University community. The facilities within the VIGR offer a wide breadth of services to facilitate research involving identification, quantification, and profiling of nucleic acids.Projects are reviewed using an integrated approach to experimental design in collaboration with University Bioinformatics Core Facilities to ensure high-quality, statistically relevant results. The facility offers multiple technologies including Sanger DNA sequencing, real-time quantitative PCR, DNA fragment analysis (microsatellite instability, haplotyping, SNP detection, nucleic acid extraction, global gene expression profiling, miRNA detection/profiling, and image analysis, and human cell line authentication). The VIGR is directed by Julie Dragon, PhD, a recognized leader in core facility best practices and management, who provides direct oversight, support and comprehensive education/training.DNA Analysis Facility: This facility is administered by the Vermont Cancer Center and is available to all investigators. The facility is located in the Health Science Research Facilities building and primary services offered include Sanger DNA sequencing, real-time quantitative PCR, DNA fragment analysis (microsatellite instability, haplotyping, AFLP, T-RFLP and SSCP), SNP detection, nucleic acid extraction, image analysis, analytical flow cytometry, and support for absorbance, chemiluminescence, and fluorescence assays. The facility contains an AB 3130 XL, 3130 Genetic Analyzers for automated sequencing and fragment analysis. Quantitative PCR analyses and biallelic discrimination assays are performed on an AB7500 FAST, or AB 7900HT using either dual-labeled probes or SYBR green methodology. Experiments using QPCR are not limited to gene expression analysis, but also include samples from chromatin immunoprecipitation assays. The facility also has a Bio-Rad Personal FX, Molecular FX, and Versa Doc 4000MP for image analysis and accurate quantification. The facility also offers several user driven pieces of equipment that include a Beckman Coulter Epics XL-MCL, BioTek Synergy H4 multi-plate reader, and a Transgenomic Wave DHPLC. Two NanoDrop spectrophotometers are available for quantification of nucleic acids and proteins. Microarray Facility: The Microarray Facility provides comprehensive support for gene expression profiling experiments and qualitative and quantitative quality control support services for nucleic acids. The Microarray Core utilizes the Affymetrix GeneChip system for microarray analysis. The facility also provides support for DNA identification, quantification, and profiling for DNA studies using the DNA mapping (SNP), Promoter, Phylochip, and custom arrays. The facility utilizes the NanoDrop spectrophotometer or Invitrogen Qubit for critical nucleic acid quantification, an Agilent 2100 Bioanalyzer for nucleic acid qualitative analysis, and a MP Biomedicals Fast Prep system for extracting nucleic acids from difficult tissues. Services offered include: global gene expression profiling using the standard 3’ arrays, gene and exon arrays for human and mouse, and DNA mapping studies, Phylochips™, and profiling with the Human, Mouse, and Rat Transcriptome Array 2.0. The facility has implemented and now offers the new Clariom S (surface) and D (deep) genechips. The most frequently requested genechip type is the miRNA used for both identification and profiling of miR’s. All microarray projects are reviewed using an integrated approach to experimental design in collaboration with the Bioinformatics arm of the VIGR to ensure high quality, statistically relevant results. The facility sponsors technology seminars, tutorials, general lectures, workshops, and an annual open house. Core staff provide advice on experimental design, RNA isolation methods, and just about any aspect of array hybridization. Massively Parallel Sequencing Facility: The MPS core was initiated by the Vermont Cancer Center and the Lake Champlain Cancer Research Organization, and established in 2011 in collaboration with the College of Medicine and College of Agriculture and Life Sciences to provide genome-scale DNA sequencing to the scientific community. This facility includes infrastructure that provides comprehensive support for the design, execution, and analysis of experiments involving Next Generation Sequencing (RNA Seq, Exome Seq, ChIP Seq, Methyl Seq, whole genome sequencing, and small RNA sequencing) through access and use of the Illumina HiSeq1500 sequencer. Services offered include: Experimental design consultation; Single End, Paired End, or Mate Paired End Library Construction for a variety of applications: RNA-seq (prokaryote or eukaryote),

Whole Genome DNA Sequencing, Methyl-Seq, ChIP-Seq, Metagenomics, and Amplicon Sequencing; Sequencing by Synthesis. The MPS facility has the ability to multiplex 16 samples/lane via indexing for prokaryotes and up to 48 for the standard Illumina TruSeq protocols. All next generation sequencing projects are reviewed using an integrated approach to experimental design, workflow, and sample collection in collaboration with the UVM bioinformatics core facilities to ensure high quality results.Flow Cytometry and Cell Sorting: The Harry Hood Bassett Flow Cytometry and Cell Sorting (FCCS) Facility at UVM provides state-of-the-art flow Cytometry to the UVM community as well as other Colleges nearby. The FCCS Facility provides analytical flow cytometry and sorting services. The facility is located on the third floor of the Given Medical Building. It is equipped with three cytometers: the BD LSRII and MACSQuant VYB analytical cytometers, and the BD FACS Aria III high-speed cell sorter. To analyze rare cell populations in human samples, a MACSQuant Cell Enrichment Unit concentrates cell populations prior to multiparametric flow cytometry. The FCCS provides professional consultation and assistance with equipment use, experimental design, and data interpretation. The FCCS is also approved for BSL2+ human clinical samples and provides full training to investigators. The FCCS is directed by Jonathan Boyson, PhD, a faculty immunologist with over 20 years’ experience in flow cytometry.Proteomics (Mass Spectrometry) Facility: The UVM Proteomics Facility is located in Marsh Life Science Building (MLS, Room 333-337) and is directed by Dr. Ying Wai Lam and managed by Dr. Bin Deng. An array of state-of-the-art mass spectrometry-based techniques is available to investigators who are performing proteomics experiments, ranging from routine protein identification to post-translational modification (PTM) characterization, and large-scale quantitative proteomics using stable isotopes. Since its inception in 2006, the facility has analyzed over 15,000 samples and facilitated data acquisition to support over 100 peer-reviewed publications. The proteomics facility is equipped with analytical HPLC systems, electrophoresis systems, Sutter P-2000 laser puller, Savant SpeedVac concentrator, and four mass spectrometers equipped with electrospray and nanospray ionization interfaces: Q-Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer (Thermo Scientific) that can perform accurate

mass measurements at 140,000 FWHM. The Q-Exactive is coupled to an EASY-nLC 1000 Liquid Chromatograph (Thermo Scientific).

Two Thermo-Finnigan LTQ linear ion trap mass spectrometers (Thermo Scientific), allowing mass separation by a linear ion trap (m/z = 50-2000 mass range), with electrospray ionization (ESI) and nanospray-ESI interfaces for liquid sample introduction. The mass spectrometers are each coupled to either a Shimadzu Prominence or a Thermo Surveyor HPLC system.

LTQ Orbitrap Discovery (Thermo Scientific) mass spectrometer for mass separation using a linear ion trap (m/z = 50–2000 mass range). This instrument can obtain accurate mass measurements (~ 1-3 ppm with lock mass function activated) at high resolution (30,000 FWHM at m/z 400). The LTQ-Orbitrap is coupled to a Thermo Surveyor HPLC system.

The Facility has a Data Processing Center (MLS, Room 333) offers a suite of software, including Proteome Discover with SEQUEST and MASCOT, SCAFFOLD, SIEVE, PEAKS, and SimGlycan to evaluate the datasets generated from MS-based experiments for peptide quantification and peptide-modification mapping. The proteomics facility works closely with the Vermont Genetics Network bioinformatics core to provide “tailored” bioinformatic solutions to investigators. The facility trains investigators in experimental design and proteomics methods, as well as provides assistance in data interpretation, manuscript preparation and grant submission.Microscopy Imaging Center (MIC): Services include transmission electron microscopy and confocal microscopy. MIC equipment includes JEOL 1210 transmission electron microscope, the Zeiss LSM 510 META confocal scanning laser microscope, which is a state-of-the-art multi-spectral imaging system consisting of a confocal scanning system attached to an Axiovert 200M inverted light microscope. Diode and argon lasers provide excitation lines of 405 nm, 458 nm, 477 nm, 488 nm, 514 nm, 543 nm and 633 nm. The MIC offers service levels from training and advice, or complete experimental design from sample preparation optimization to data acquisition services samples for TEM and confocal for possible tissue neutrophil/virus studies.The Vermont Advanced Computing Core (VACC): The Vermont Advanced Computing Core (VACC) is a university-wide research core facility that supports computationally-intensive research and high performance computing (HPC) services. The VACC is a cluster of nearly 3000 compute cores and associated memory support services maintained by UVM, and has the capacity to perform massively parallel computations to simulate processes that would be impractical or impossible on single desk-top computer systems. VACC's mission includes strategic support in three key areas: advancing high-impact, multidisciplinary research efforts; promoting advanced computing education and outreach across disciplines; and investing in next-generation, innovative and sustainable high-performance computing infrastructure models. The facility is headed by Dr.

Douglas J. Taatjes and staffed by four full-time, experienced laboratory technologists. It is administered by the College of Medicine and located in the Health Science Research Facility building. Imaging center staff provide guidance with experimental design, tissue sectioning, sample preparation, data analysis and interpretation, and optimal use of the instrumentation available in the facility.Animal Care Management (if needed for any animal studies): The University of Vermont (UVM) is committed to the humane care and use of animals in activities related to research, testing and teaching. UVM has fully staffed animal facilities operated under the supervision of the Office of Animal Care Management (OACM). The OACM is directed by the University Veterinarian, Dr. Ruth M. Blauwiekel, DVM, PhD, who provides oversight and clinical care for animals used in University research activities. Dr. Blauwiekel also serves on UVM's Institutional Animal Care and Use Committee (IACUC) and participates in the review and monitoring of all proposed or ongoing animal use. Animal facilities at UVM are AAALAC accredited. Construction of the facilities and animal husbandry are in compliance with the standards outlined in the NIH publication, "Guide for the Care and Use of Laboratory Animals." Mice are housed and maintained in pathogen-free barrier conditions in the HSRF animal care facility, currently administered and staffed by Priority One Services. This facility is managed by Priority One and contains complete HEPA-filtered in and out air supplies to individual bubble chambers that hold either 20 or 50 cages of five mice each, as well as Super Mouse 750™ Allerzone™ Micro-Isolator™ 10-tier, double-sided, high-density racks equipped with Enviro-Gard™ HEPA-filtered air supply units. These systems have been in use for over 10 years without a single infection outbreak. Mice have appropriate caging with sterile rodent food and acidified water ad libitum. All animals have 12 hour light/dark cycles. A digital Faxitron (MX-20) and a C-arm are available in the animal quarters. All investigators of this T32 training program will have access to and full use of the transgenic animal core and facility as well as the inhalation exposure facility. Transgenic/Knockout Mouse Facility: It is located within the Mouse Facility in the Health Science Research Facilities (HSRF) building at the University of Vermont and is directed by Dr. Mercedes Rincón. The transgenic facility is a strict barrier facility to maintain a pathogen-free environment. The facility has a mouse room with microinsulators and ventilated racks, a clean room that houses a microinjection laboratory, and a tissue culture room for embryonic stem cells. The Transgenic/Knockout mouse facility is separated from the rest of the Mouse Facility as an additional barrier. The microinjection laboratory is equipped with an invert Diaphot 200 microscope, an MF-9 microfuge, a Sutter horizontal pipette puller, a PLI188 Nikon picoinjector, M0188 hydraulic manipulator, a gooseneck light guide-coupled SMZ-U stereoscope, CO2 incubator, refrigerator, CCD B&W camera, Panasonic Monitor/VCR. It is equipped to perform both microinjection of DNA into isolated mouse fertile eggs, and microinjection of embryonic stem cells into blastocysts for generation of knockout mice. It is also equipped for performing embryo cryopreservation (embryo freezer) and re-derivation. Inhalation Facility: An inhalation facility as part of the Vermont Lung Center has been constructed at the Colchester Research Facility about 2 miles from the Larner College of Medicine. The facility consists of 2 large 300 sq. ft. rooms, one equipped with 2 large fume hoods for nose only exposures and 2 downdraft tables for nonhazardous particles (e.g., antigen) exposures. The second room has 2 whole-body, stainless steel, exposure chambers and a tissue culture hood for cell exposure experiments. Currently, we have the ability to expose animals to NO2, ozone, antigens, silica and acrolein, and the capability for other forthcoming agents.BSL3 Facility: A BSL3 facility was constructed at the Colchester Research Facility with funds provided by an NIGMS supplement grant to the parent COBRE grant for the Vermont Center for Immunology and Infectious Diseases. This facility initially provided research space for Dr. Jason Botten’s work on hantaviruses, but is available to all UVM faculty who need a BSL3 facility.

Instrumentation and Model Facility: For over forty years the UVM Instrumentation and Model Facility (IMF) has designed and fabricated custom instruments, models, and prototypes for academic research at UVM and other universities, product developers, and commercial enterprises. Facilities include a 3,500-ft2 machine, welding and electronics shop and 3,900-ft2 of office space and utilities. The facility can fabricate single custom parts or instruments, or conduct small-volume production runs. Reporting to the Vice President for Research and Graduate Studies, IMF actively supports academic researchers at UVM and the Technology Commercialization Office. In addition to research instrumentation for funded studies, IMF develops prototypes to help inventors make “real world” instruments. This experience is unique and valuable in working with emerging technology companies in their quest to rapidly get products to the marketplace.

IMF engineers and technicians employ technical aptitude in mechanical, electrical, optical, and programming disciplines to solve application problems for customers prior to fabrication at state of the art in-house facilities. Examples of the types of the problems IMF has solved for customers include an optomechanical “laser trap”

system first used to measure the contraction force between two muscle molecules, automobile simulators used in drunk driving studies, antibiotic bead molds used in the treatment of musculoskeletal infections, a high energy molecular measurement system for Argonne National Laboratory, and a high temperature, high pressure instrument developed for meteorite studies.

Medical Simulation Center: The Clinical Simulation Laboratory (CSL) is a collaborative effort of the UVM COM, the UVM College of Nursing and Health Sciences, and FAHC. It serves as a centralized hub for the training of health care professionals, with the ultimate goal of improving quality and safety of care. It brings together individuals, groups and teams for hands-on learning experiences designed to improve clinical, collaborative, and communication skills. Simulations are further enhanced by the integration of standardized patients and advanced technology in settings that reflect actual trauma, operating room, in-patient and ambulatory settings. Clinical research requires competency-based instruction that improves after training on simulated experiences to prepare learners for research care. The CSL enables trainees to use well-founded simulation principles to develop and maintain GCP and competencies to augment patient safety and improve patient care during the research experience. Through comprehensive practical team training and innovative skills programs, the CSL will serve as a valuable training resource for the NNE-CTR Net. CSL also supports the Vermont Army and Air National Guard, Emergency Medical Technicians and Paramedics, and health care providers across Vermont and throughout the region.Electronic Medical Record System: The UVM Medical Center has implemented the EPIC electronic medical record system. It is supported across the UVM Health Network by a specialized Patient Record and Information Systems Management (PRISM) team. A designated PRISM architect is dedicated to supporting clinical research. The state-of-the-art EPIC system was selected to help UVM Medical Center improve quality and enhance safety while protecting the security and confidentiality of patients’ health information.

In 2009, when the UVM Medical Center purchased EPIC, only 10.9% of U.S. hospitals had a basic electronic medical record system, and only 1.5% had implemented a comprehensive system like PRISM. Today, PRISM is an institution-wide system that electronically stores and provides instantaneous access to patient health records throughout all 32 UVM Health Network facilities in Vermont, including over 750 physicians. Most of these physicians practice in multiple locations in Vermont, making access to patient health records critical. UVMMC has developed quality improvement projects using PRISM, such as automatic checks that safeguard against specific common medical occurrences leading to improved patient safety. A rollout of EPIC across the UVM Health Network is being planned.

Shared Video Conferencing and Seminar Resources: The University of Vermont, College of Medicine has a variety of classroom and conference rooms within the medical school complex. In the Medical Education Center, there are 15 small-group classrooms that seat 14 students, a medium-sized class room that seats 40 and a large classroom that seats 120 students. In the adjacent Given, Health Science Research Facility and Given Courtyard buildings there are 5 conference rooms, each of which can support 20 attendees. 

Many of the classrooms are equipped with Polycom CX5000 Speakerphone with Video and CX5000 Satellite Microphone for teleconferencing or interactive distance teaching. Participants can see and hear each other, and when coupled with the SmartBoard technology, can share information, such as presentations, images and documents in real time. The college currently uses this technology for distance learning and shared classroom experiences.

College of Medicine Information Systems: The UVM College of Medicine Information System (COMIS) provides support for all computers with the College of Medicine system. The COMIS system includes 30+ Windows servers and affiliated desktop and laptop computers. Connectivity is through the UVM GB Ethernet backbone. All available Microsoft security patches are installed on the servers and clients. Virus protection includes Network Associates and McAfee Virus applications with DAT files updated as soon as new files are released. Full nightly backups are done to tape on a 30-day cycle. Full backups are done monthly and retained for 13 months. Available software includes the Microsoft Office suite, Adobe Acrobat Pro, SPSS, and SQL for large databases. COMIS computers are integrated with the UVM network and maintain connectivity to the information systems of the UVM Medical Center.

University Libraries: The combined collection of the libraries on the University of Vermont campus totals over 1.7 million books and over 65,000 journal subscriptions. The Charles A. Dana Medical Library serves the information needs of the Academic Health Center at the University of Vermont. The Academic Health Center comprises the faculty, staff and students at UVM's Larner College of Medicine, the College of Nursing and Health Sciences, as well as the physicians and other healthcare providers at the University of Vermont Medical

Center. The Library also meets the health sciences information needs of the University of Vermont’s undergraduate and graduate programs. Over 5,000 journals, including all major scientific journals, are available in the Dana Medical Library either as print or e-subscriptions. The library has access to a wide range of electronic and print literature, technical databases, and subject specialists to assist scientists in the development of their research and in the communication of relevant results. Investigators also have access to interlibrary loan for journals or books not housed within the University’s collection.

BU SummaryThe BU CTSI, the Boston University hub of the national CTSA network, encompasses translational research activities in two states and across four sites with complementary research resources and programs that have a demonstrated track record of collaboration.Together, this association of the Boston University Medical Campus including the Schools of Medicine, Dentistry, and Public Health, Boston Medical Center hospital, the BU Charles River Campus, the New England Research Institute (NERI), and our participating affiliates, the Edith Nourse Rogers Memorial Veterans Hospital (Bedford VA) and the VA Boston Healthcare System (VA Boston), provides the foundation for the BU CTSI as an academic home with an integrated research and training environment dedicated to quality, safety, efficiency and cost effectiveness of clinical and translational research.BMC provides a unique urban safety net population, with a proven track record of diversity and successful enrollment on clinical trials. BU provides expertise in training and research in biomedical engineering, informatics, nanosciences, photonics, etc. that supports innovative device development and a strong basic science foundation for our translational research programs. Our three participating affiliates provide respective areas of intellectual and functional expertise that will strategically support BU CTSI components’ aims.