The Rockefeller Clinical Scholars (KL2) Program began in 1976 and transitioned into a 3-year Master's degree program in 2006 when Rockefeller joined the NIH Clinical and Translational Science Award (CTSA) program. The program consists of ~15 trainees supported by the CTSA KL2 award and University funds. It is designed to provide an optimal environment for junior translational investigators to develop team science and leadership skills by designing and performing a human subjects protocol under the supervision of a distinguished senior investigator mentor and a team of content expert educators. This is complemented by a tutorial focused on important translational skills.Since 2006, 40 Clinical Scholars have graduated from the programs and gone on to careers in academia (72%), government service (5%), industry (15%), and private medical practice (3%); two (5%) remain in training programs. 39/40 remain in translational research careers with 23 NIH awards totaling $23 million, foundation and philanthropic support of $20.3 million, and foreign government and foundation support of $6 million. They have made wide ranging scientific discoveries and have endeavored to translate those discoveries into improved human health.The Rockefeller Clinical Scholars (KL2) program provides one model for translational science training.
Retroviruses and herpesviruses are naturally occurring pathogens of humans and animals. Coinfection of the same host with both these viruses is common. We report here that a retrovirus can integrate directly into a herpesvirus genome. Specifically, we demonstrate insertion of a nonacute retrovirus, reticuloendotheliosis virus (REV), into a herpesvirus, Marek disease virus (MDV). Both viruses are capable of inducing T lymphomas in chickens and often coexist in the same animal. REV DNA integration into MDV occurred in a recently attenuated strain of MDV and in a short-term coinfection experiment in vitro. We also provide suggestive evidence that REV has inserted into pathogenic strains of MDV in the past. Sequences homologous to the REV long terminal repeat are found in oncogenic MDV but not in nononcogenic strains. These results raise the possibility that retroviral information may be transmitted by herpesvirus and that herpesvirus expression can be modulated by retroviral elements. In addition, retrovirus may provide a useful tool to characterize herpesviral function by insertional mutagenesis.
Abstract The ability to effectively lead an interdisciplinary translational team is a crucial component of team science success. Most KL2 Clinical Scholars have been members of scientific teams, but few have been team science leaders. There is a dearth of literature and outcome measures of effective Team Science Leadership in clinical and translational research. We focused our curriculum to emphasize Team Science Leadership, developed a list of Team Science Leadership competencies for translational investigators using a modified Delphi method, and incorporated the competencies into a quantitative evaluation survey. The survey is completed on entry and annually thereafter by the Scholar; the Scholar’s primary mentor and senior staff who educate and interact with the Scholar rate the Scholar at the end of each year. The program leaders and mentor review the results with each Scholar. The survey scales had high internal consistency and good factor structure. Overall ratings by mentors and senior staff were generally high, but ratings by Scholars tended to be lower, offering opportunities for discussion and career planning. Scholars rated the process favorably. A Team Science Leadership curriculum and periodic survey of attained competencies can inform individual career development and guide team science curriculum development.
Abstract Background: The Rockefeller University Center for Clinical and Translational Science (RU-CCTS) and Clinical Directors Network (CDN), a Practice-Based Research Network (PBRN), fostered a community–academic research partnership involving Community Health Center (CHCs) clinicians, laboratory scientists, clinical researchers, community, and patient partners. From 2011 to 2018, the partnership designed and completed Community-Associated Methicillin-Resistant Staphylococcus Aureus Project (CAMP1), an observational study funded by the National Center for Advancing Translational Sciences (NCATS), and CAMP2, a Comparative Effectiveness Research Study funded by the Patient-Centered Outcomes Research Institute (PCORI). We conducted a social network analysis (SNA) to characterize this Community-Engaged Research (CEnR) partnership. Methods: Projects incorporated principles of Community-Based Participatory Research (CAMP1/2) and PCORI engagement rubrics (CAMP2). Meetings were designed to be highly interactive, facilitate co-learning, share governance, and incentivize ongoing engagement. Meeting attendance formed the raw dataset enriched by stakeholder roles and affiliations. We used SNA software (Gephi) to form networks for four project periods, characterize network attributes (density, degree, centrality, vulnerability), and create sociograms. Polynomial regression models were used to study stakeholder interactions. Results: Forty-seven progress meetings engaged 141 stakeholders, fulfilling 7 roles, and affiliated with 28 organizations (6 types). Network size, density, and interactions across organizations increased over time. Interactions between Community Members or Recruiters/Community Health Workers and almost every other role increased significantly across CAMP2 ( P < 0.005); Community Members’ centrality to the network increased over time. Conclusions: In a partnership with a highly interactive meeting model, SNA using operational attendance data afforded a view of stakeholder interactions that realized the engagement goals of the partnership.
OBJECTIVES/SPECIFIC AIMS: Objective: The Rockefeller University Center for Clinical and Translational Science (RU-CCTS), Clinical Directors Network (CDN), and Carter Burden Network (CBN), a multisite senior services organization serving East Harlem, NY, formed a community-academic partnership to examine the use of a simple validated surrogate measure of overall health status and frailty in this population. Many CBN seniors are racial/ethnic minorities, low-income, and suffer from multiple chronic conditions, depression and food insecurity. Multiple biological, musculoskeletal, psychosocial and nutritional factors contribute to frailty, which has been defined variously in senior health outcomes research. The CTSA-funded Pilot Project aims to: (1) Engage CBN seniors and stakeholders in priority-setting, joint protocol development, research conduct, analysis, and dissemination; (2) Characterize the health status of the CBN seniors using validated measures; (3) Establish database infrastructure for current and future research; (4) Understand how health and senior activities information can be used to create programs to improve senior health. METHODS/STUDY POPULATION: Methods: (1) CEnR-Navigation, a collaborative program/process that consists of semistructured meetings and activities facilitated by expert Navigators, was used for partnership development and to engage Carter Burden seniors to refine priorities and research questions, provide feedback on study design and conduct, and analyze and disseminate results. (2) Standard physical measurements and validated survey instruments were used to collect health information; target enrollment is 240 seniors across 2 sites (1 hosted within a subsidized housing facility and Social Model Adult Day Program). (3) A REDCap-based platform was designed for data capture and import. Individual attendance at senior activities for the prior year was extracted from existing records. The primary outcome is frailty, as measured by validated walk/balance tests (Short Physical Performance Battery). Secondary outcomes include measures of engagement, and association of use of services/activities with the primary outcome. RESULTS/ANTICIPATED RESULTS: (1) In total, 29 residents and 14 other stakeholders engaged in partnership-building, study design and implementation. (2) From May to November 2017, 98 participants were enrolled from site 1 (a residential site). Enrollment at site 2 (a senior center), begun in November, is projected for February completion. Characteristics of site 1 participants: median age=63.6 years; Hispanic, 44.90% (44); White, 13.89% (10), Black, 62.50% (45); Asian, 4.17% (3); American Indian or Alaskan Native, 2.78% (2), and Other, 16.67% (12). Educational attainment: 51.04% (49) had not completed high school; 19.79% (19) were high school graduates; 18.75% (18) completed some college, and 10.42% (10) were college graduates. For the 85 participants reporting annual income: 64.71% (55) reported <$10,000; 28.24% (24) reported $10,000–$15,000; 7.06% (6) were among the ranges from $15,000 to $50,000. The average body mass index (BMI) was 30, which is obese. For 83.67% (82) of site 1 participants, the BMI was in the range of overweight or obese. Half of participants (49) reported health literacy barriers in the Single Item Health Literacy Survey. Demographics and Frailty assessments (walk and balance tests) for participants enrolled at both sites will be reported. (3) Activity participation data for July 2016–November 2017 were recovered for 507 sessions at site 1 and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: Here we report progress in developing a sustainable community-academic partnership, infrastructure and research capacity with the CBN senior services organization, and characterizing this at-risk population, of whom 71% have a high school education or less, 93% live in extreme poverty, and 84% are overweight or obese. A simple validated frailty measure in seniors will enable the acceleration of community-based translational research addressing senior health, and examine changes in this measure in relationship to the utilization of senior services.
Problem Engaging basic scientists in community-based translational research is challenging but has great potential for improving health. Approach In 2009, The Rockefeller University Center for Clinical and Translational Science partnered with Clinical Directors Network, a practice-based research network (PBRN), to create a community-engaged research navigation (CEnR-Nav) program to foster research pairing basic science and community-driven scientific aims. The program is led by an academic navigator and a PBRN navigator. Through meetings and joint activities, the program facilitates basic science–community partnerships and the development and conduct of joint research protocols. Outcomes From 2009–2014, 39 investigators pursued 44 preliminary projects through the CEnR-Nav program; 25 of those became 23 approved protocols and 2 substudies. They involved clinical scholar trainees, early-career physician–scientists, faculty, students, postdoctoral fellows, and others. Nineteen (of 25; 76%) identified community partners, of which 9 (47%) named them as coinvestigators. Nine (of 25; 36%) included T3–T4 translational aims. Seven (of 25; 28%) secured external funding, 11 (of 25; 44%) disseminated results through presentations or publications, and 5 (71%) of 7 projects publishing results included a community partner as a coauthor. Of projects with long-term navigator participation, 9 (of 19; 47%) incorporated T3–T4 aims and 7 (of 19; 37%) secured external funding. Next Steps The CEnR-Nav program provides a model for successfully engaging basic scientists with communities to advance and accelerate translational science. This model's durability and generalizability have not been determined, but it achieves valuable short-term goals and facilitates scientifically meaningful community–academic partnerships.
In 2000, the National Center for Research Resources mandated that general research centers create a research subject advocate (RSA) position. In 2008, the Clinical and Translational Science Award (CTSA) consortium endorsed a new advocacy model based on four RSA Best Practice Functions. The authors surveyed CTSA centers to learn about their implementation of programs to fulfill the RSA functions.In 2010, the RSA taskforce developed a two-part online survey to examine leadership, organizational structure, governance, scope, collaboration and integration, and funding and evaluation of RSA activities implemented at CTSA centers.Respondents from 45 RSA programs at 43 CTSA centers completed the survey. Senior university or CTSA officials led all programs. Ninety-six percent (43/45) of programs were funded by a CTSA core. Eighty percent (36/45) designated an individual "RSA." Ninety-eight percent (44/45) provided diverse services either in collaboration with or complementary to other departments, including development of data and safety monitoring plans (16/45; 36%), informed consent observation (10/45; 22%), training responsive to audit findings (12/45; 27%), and direct advocacy services to participants (11/45; 24%). Eighty-six percent (24/28) reported qualitative evaluation methods for these activities.RSA programs conduct both collaborative and unique research protection activities. This survey, an initial step in developing a more robust mechanism for evaluating RSA programs, collected valuable feedback. The authors recommend defining and developing outcome-based evaluation measures that take the heterogeneity of the individual RSA programs into account while advancing their value and effectiveness in protecting human research subject participants.
The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed alpha1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that alpha1 circle numbers in blood remain high for the first 10-15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, alpha1 circle numbers in HIV-1-infected adults were significantly reduced; however, there were many individuals with normal alpha1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on alpha1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in alpha1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as alpha1 circle numbers are normal in a substantial subset of HIV-1-infected individuals.
Adolescent obesity, a risk factor for cardiorenal morbidity in adulthood, has reached epidemic proportions. Obesity-related glomerulopathy (ORG) has an early reversible stage of hyperfiltration. Age-appropriate formulae for eGFR, which are standardized to ideal body surface area (BSA) and provide assessment of kidney function in ml/min/1.73 m2, may underestimate prevalence of early ORG. We investigated whether adjusting eGFR to actual BSA more readily identifies early ORG.We studied a cohort of 22,417 young individuals, aged 12-21 years, from a New York metropolitan multi-institutional electronic health records clinical database. eGFR was calculated in two ways: BSA-standardized eGFR, and absolute eGFR. Hyperfiltration was defined above a threshold of 135 ml/min per 1.73 m2 or 135 ml/min, respectively. The prevalence of hyperfiltration according to each formula was assessed in parallel to creatinine clearance.Serum creatinine values and hyperfiltration prevalence according to BSA-standardized eGFR were similar, 13%-15%, across body mass index (BMI) groups. The prevalence of hyperfiltration determined by absolute eGFR differed across BMI groups: underweight, 2%; normal weight, 6%; overweight, 17%; and obese, 31%. This trend paralleled the rise in creatinine clearance across BMI groups.Absolute eGFR more readily identifies early ORG than the currently used formulae, which are adjusted to a standardized BSA and are not representative of current population BMI measures. Using absolute eGFR in clinical practice and research may improve the ability to identify, intervene, and reverse early ORG, which has great importance with increasing obesity rates.
