Despite the increased emphasis on formal training in clinical and translational research and the growth in the number and scope of training programs over the past decade, the impact of training on research productivity and career success has yet to be fully evaluated at the institutional level. In this article, the Education Evaluation Working Group of the Clinical and Translational Science Award Consortium introduces selected metrics and methods associated with the assessment of key factors that affect research career success. The goals in providing this information are to encourage more consistent data collection across training sites, to foster more rigorous and systematic exploration of factors associated with career success, and to help address previously identified difficulties in program evaluation.
clinical research; translational research; research careers; research success; evaluation; CTSA; graduate training; research training; mentoring; collaboration; team science
Only one LDL-C GWAS has been reported in African Americans. We performed a GWAS of LDL-C in African Americans using data extracted from electronic medical records (EMR) in the eMERGE network. African Americans were genotyped on the Illumina 1M chip. All LDL-C measurements, prescriptions, and diagnoses of concomitant disease were extracted from EMR. We created two analytic datasets; one dataset having median LDL-C calculated after the exclusion of some lab values based on co-morbidities and medication (n = 618) and another dataset having median LDL-C calculated without any exclusions (n = 1249). Rs7412 in APOE was strongly associated with LDL-C at levels of GWAS significance in both datasets (p < 5 X 10−8). In the dataset with exclusions, a decrease of 20.0 mg/dl per minor allele was observed. The effect size was attenuated (12.3 mg/dl) in the dataset without any lab values excluded. Although other signals in APOE have been detected in previous GWAS, this large and important SNP association has not been well detected in large GWAS because rs7412 was not included on many genotyping arrays. Use of median LDL-C extracted from EMR after exclusions for medications and co-morbidities increased the percentage of trait variance explained by genetic variation.
GWAS; LDL; electronic medical records
Mentors play important roles in training new investigators. This study was designed to determine characteristics of NIH mentored K award recipients and their mentors, their interpersonal interactions, and the factors, which influence satisfaction within this relationship.
A survey of 3027 NIH mentored K recipients and 1384 mentors was conducted in 2009. Nine hundred twenty-nine (30.7%) of the K recipients and 448 (32.4%) mentors completed the survey.
The gender of K respondents was evenly divided while the mentors were 72.1% male. The overall rating of their mentors was positive. Ideally, both thought the mentor should be important in research training; however, in actual practice, both rated the importance as lower. A total of 88.2% of recipients were satisfied with their relationship. Although the number of black K recipients was low, this group was more likely to be dissatisfied with the mentor relationship (6/29 or 20.7%) than their white counterparts. The frequency of meeting or communicating was correlated with K recipient satisfaction.
Overall K recipients are satisfied with their mentor relationships. Although the number of black K recipient respondents was small, the higher level of mentor dissatisfaction should be further evaluated. Qualities of mentors, including the frequency of interactions and accessibility, can influence satisfaction.
Ethics; Translational research; Trials; Mentor
Cocaine is the most frequently used illicit drug among individuals seeking emergency-room care, with fatal outcome most often attributable to the cardiovascular manifestations of drug abuse. While the symptomatic presentations of cocaine toxicity are increasingly understood, the molecular determinants that define outcome remain largely unknown. Here, we report that the susceptibility to cocaine-induced cardiotoxicity is genetically regulated. Targeted deletion of the KCNJ11-encoded Kir6.2 pore-forming subunit of sarcolemmal KATP channels resulted in amplified vulnerability to the toxic effects of chronic cocaine abuse. Under the hyperadrenergic stress, imposed by daily 3-week-long intraperitoneal administration of 30 mg/kg cocaine in Kir6.2-knockout mice, failure to maintain cardiac homeostasis translated into decreased exercise tolerance revealed by poor treadmill stress performance, and dilated hypokinetic left hearts with aggravated cellular hypertrophy and pathognomonic characteristics of chronic cocaine-induced cardiac toxicity. This study therefore reveals a previously unrecognized role of Kir6.2-encoded KATP channels in determining cardiovascular outcome in chronic cocaine abuse, identifying a novel molecular determinant of cocaine cardiotoxicity.
ATP-sensitive K+ channel; disease; genetics; heart; Kir6.2; SUR2A
Usage data for research networking systems (RNSs) are valuable but generally unavailable for understanding scientific professionals’ information needs and online collaborator seeking behaviors. This study contributes a method for evaluating RNSs and initial usage knowledge of one RNS obtained from using this method. We designed a log for an institutional RNS, defined categories of users and tasks, and analyzed correlations between usage patterns and user types and query types. Our results show that scientific professionals spend more time performing deep web searching on RNSs than generic Google users and we also show that retrieving scientist profiles is faster on an RNS than on Google (3.5 vs. 34.2 seconds) while organization-specific browsing on a RNS takes longer than on Google (117.0 vs. 34.2 seconds). Usage patterns vary by user role, e.g., faculty performed more informational queries than administrators, which implies role-specific user support is needed for RNSs.
Medical Informatics; Online Systems; Information Networks; User-Computer Interface; Social Interaction
Preeclampsia is a common and potentially lethal pregnancy disorder with lifelong increased risk of cardiovascular disease in survivors. Our prior global gene expression microarray analysis led to a novel set of 36 candidates in first trimester placentas of women who subsequently developed preeclampsia. In this report, we present preliminary studies demonstrating biomarkers of genotype and methylation variations in a subset of these candidate genes in maternal leukocyte and fetoplacental DNA of 28 case and 27 control dyads. We tested 84 single nucleotide polymorphisms (SNPs) using MassArray iPLEX and 50 CpG sites using EpiTYPER assays. Promising prediction modeling was identified with 25 SNPs selected using Fisher's exact tests (p≤0.05) and 20 CpG sites selected on fold change. Genotype Distribution Analysis identified SNP variations that differed between 9 paired cases versus paired controls. The findings validate the examined candidate genes and support feasibility of methods for further biomarker development. The integrative approach that was implemented begins to translate the 36 candidates toward clinical utility as a screening modality for preeclampsia.
Hypoferremia is a marker of disease severity in cystic fibrosis (CF). The effect of systemic antibiotics on iron homeostasis during CF pulmonary exacerbation (CFPE) is unknown. Our central hypotheses were that, by the completion of treatment, serum iron would increase, serum concentrations of interleukin-6 (IL-6) and hepcidin-25, two mediators of hypoferremia, would decrease, and sputum iron would decrease. Methods: Blood and sputum samples were collected from 12 subjects with moderate-to-severe CF (median percent-predicted forced expiratory volume in one second (FEV1%) = 29%; median weight = 56 kg) within 24 hours of starting and completing a course of systemic antibiotics. Results: After treatment, subjects showed median FEV1% and body weight improvements of 4.5% and 2.0 kg, respectively (p <0.05). Median serum iron rose by 2.4 μmol/l (p <0.05), but 75% of patients remained hypoferremic. Median serum IL-6 and hepcidin-25 levels fell by 12.1 pg/ml and 37.5 ng/ml, respectively (p <0.05). Median serum erythropoietin (EPO) and hemoglobin levels were unaffected by treatment. We observed a trend toward lower sputum iron content after treatment. Conclusions: Hypoferremia is a salient characteristic of CFPE that improves with waning inflammation. Despite antibiotic treatment, many patients remain hypoferremic and anemic due to ineffective erythropoiesis.
iron; hepcidin; cystic fibrosis; interleukin-6; exacerbation
Fetal cells enter the maternal circulation during pregnancies and can persist in blood and tissues for decades, creating a state of physiologic microchimerism. Microchimerism refers to acquisition of cells from another individual and can be due to bi-directional cell traffic between mother and fetus during pregnancy. Peripartum cardiomyopathy, a rare cardiac disorder associated with high mortality rates has the highest recovery rate amongst all etiologies of heart failure although the reason is unknown. Collectively, these observations led us to hypothesize that fetal cells enter the maternal circulation and may be recruited to the sites of myocardial disease or injury. The ability to genetically modify mice makes them an ideal system for studying the phenomenon of microchimerism in cardiac disease. Described here is a mouse model for ischemic cardiac injury during pregnancy designed to study microchimerism. Wild-type virgin female mice mated with eGFP male mice underwent ligation of the left anterior descending artery to induce a myocardial infarction at gestation day 12. We demonstrate the selective homing of eGFP cells to the site of cardiac injury without such homing to nonfinjured tissues suggesting the presence of precise signals sensed by fetal cells enabling them to target diseased myocardium specifically.
This research sought to better understand how clinical and translational research is defined and perceived by community service providers. In addition, the research sought to elicit how the perspectives of service providers may hinder or facilitate collaborative research efforts. The study employed a qualitative methodology, focus groups. A non probability sampling strategy was used to recruit participants from three neighborhoods in the Tufts University’s catchment area. Focus group findings add to the nascent body of literature on how community partners view clinical and translational research and researchers. Findings indicate that cultural disconnects, between researchers and community partners exist, as does mistrust, all of which serve as potential barriers to community research partnerships. This article suggests rethinking the business of community engagement in researcher, particularly as it relates to building research capacity to approach, engage and partner with communities.
Community Engaged Research; Community-based Participatory Research, CBPR; Translational Research; Partnerships; Focus Group Research
Mentorship is crucial for academic productivity and advancement for clinical and translational (CT) science faculty. However, little is known about the long-term effects of mentor training programs. The University of California, San Francisco (UCSF), Clinical and Translational Science Institute launched a Mentor Development Program (MDP) in 2007 for CT faculty. We report on an evaluation of the first three cohorts of graduates from the MDP. In 2010, all Mentors in Training (MITs) who completed the MDP from 2007 to 2009 (n=38) were asked to complete an evaluation of their mentoring skills and knowledge; all MITs (100%) completed the evaluation. Two-thirds of MDP graduates reported that they often apply knowledge, attitudes, or skills obtained in the MDP to their mentoring. Nearly all graduates (97%) considered being a mentor important to their career satisfaction. Graduates were also asked about the MDP’s impact on specific mentoring skills; 95% agreed that the MDP helped them to become a better mentor and to focus their mentoring goals. We also describe a number of new initiatives to support mentoring at UCSF that have evolved from the MDP. To our knowledge, this is the first evaluation of the long-term impact of a mentor training program for CT researchers.
The goal of this paper is to review the evaluation of mentors with a focus on training new investigators in clinical translational science. These scholars include physicians and PhD scientists who are generally assistant professors in clinical departments. This white paper is one of a series of articles focused on the programmatic elements of effective mentoring practices and the “current state of the art”. Evaluating mentor performance and providing formative feedback can lead to stronger mentoring and ultimately lead to increased success of new clinical and translational investigators. While there is general agreement that mentor evaluation can be helpful, the process is difficult. Trainees are reluctant to share negative experiences and to rate their mentors. Mentors are not sure they want to be evaluated. Program leaders are not sure how to effectively use the information. This white paper provides mentees, mentors and program leaders with new perspectives on mentor evaluation and ideas for future research.
evaluation; translational science; research training
Research over the last decade has uncovered roles for bile acids (BAs) that extend beyond their traditional functions in regulating lipid digestion and cholesterol metabolism. BAs are now recognized as signaling molecules that interact with both plasma membrane and nuclear receptors. Emerging evidence indicates that by interacting with these receptors BAs regulate their own synthesis, glucose and energy homeostasis, and other important physiological events. Herein, we provide a comprehensive review of the actions of BAs on cardiovascular function. In the heart and the systemic circulation, BAs interact with plasma membrane G-protein coupled receptors, e.g. TGR5 and muscarinic receptors, and nuclear receptors, e.g. the farnesoid (FXR) and pregnane (PXR) xenobiotic receptors. BA receptors are expressed in cardiovascular tissue, however, the mechanisms underlying BA-mediated regulation of cardiovascular function remain poorly understood. BAs reduce heart rate by regulating channel conductance and calcium dynamics in sino-atrial and ventricular cardiomyocytes, and regulate vascular tone via both endothelium-dependent and -independent mechanisms. End-stage-liver disease, obstructive jaundice and intrahepatic cholestasis of pregnancy are prominent conditions in which elevated serum BAs alter vascular dynamics. This review focuses on BAs as newly-recognized signaling molecules that modulate cardiovascular function.
Community engagement is an innovative and required component for Clinical and Translational Science Awards (CTSAs) funded by the National Institutes of Health (NIH). However, the extent of community engagement in NIH-funded research has not been previously examined. This study assessed baseline prevalence of community engagement activities among NIH-funded studies at a large Midwestern university with a CTSA. An online survey was e-mailed to principal investigators of recent NIH-funded studies (N = 480). Investigators were asked to identify what types of community engagement activities had occurred for each study. Responses were received for 40.4% (194/480) of studies. Overall, 42.6% reported any community engagement activities. More collaborative types of engagement (e.g., community advisory board) were less common than activities requiring less engagement (e.g., sharing study results with community members). Studies with more collaborative community engagement were less likely to be described as basic or preclinical research compared to all other studies. Given NIH’s inclusive call for community engagement in research, relatively few NIH-funded studies reported community engagement activities, although this study used a broad definition of community and a wide range of types of engagement. These findings may be used to inform the goals of CTSA community engagement programs.
community engagement; practice- and community-based research; translational research; CTSA
Classical drug exposure: response studies in clinical pharmacology represent the quintessential prototype for Bench to Bedside-Clinical Translational Research. A fundamental premise of this approach is for a multidisciplinary team of researchers to design and execute complex, in-depth mechanistic studies conducted in relatively small groups of subjects. The infrastructure support for this genre of clinical research is not well-handled by scaling down of infrastructure used for large Phase III clinical trials. We describe a novel, integrated strategy, whose focus is to support and manage a study using an Information Hub, Communication Hub, and Data Hub design. This design is illustrated by an application to a series of varied projects sponsored by Special Clinical Centers of Research in chronic obstructive pulmonary disease at the University of Pittsburgh. In contrast to classical informatics support, it is readily scalable to large studies. Our experience suggests the culture consequences of research group self-empowerment is not only economically efficient but transformative to the research process.
institutional management teams; organization and administration; information services; information storage and retrieval
Translational research is expanding, in part, because Evidence-Based Programs or Practices (EBPs) are not adopted in many medical domains. However, little translational research exists on EBPs that are prevention programs delivered in non-clinical, community-based settings. These organizations often have low capacity, which undermines implementation quality and outcomes. Rigorous translational research is needed in these settings so within a single study, capacity, implementation quality, and outcomes are measured and links between them tested. This paper overviews the study Enhancing Quality Interventions Promoting Healthy Sexuality (EQUIPS), which tests how well a community-based setting (Boys & Girls Clubs) conducts an EBP called Making Proud Choices that aims to prevent teen pregnancy and sexually transmitted infections, with and without an implementation support intervention called Getting To Outcomes®. The study design is novel as it assesses: Getting To Outcomes’ impact on capacity, implementation quality, and outcomes simultaneously and in both study conditions; will assess sustainability by measuring capacity and fidelity a year after the Getting To Outcomes support ends; and will operate on a large scale similar to many national initiatives. Many studies have not incorporated all these elements and thus EQUIPS could serve as a model for translational research in many domains.
It is well recognized that an interdisciplinary approach is essential in the development and implementation of solutions to address the current pediatric obesity epidemic. In two half-day meetings that included workshops and focus groups, faculty from diverse fields identified critically important research challenges and gaps to childhood obesity prevention. The purpose of this white paper is to describe the iterative, interdisciplinary process that unfolded in an academic health center setting with a specific focus on under-represented minority groups of Black and Hispanic communities, and to summarize the research challenges and gaps related to pediatric obesity which were identified in the process. Although the research challenges and gaps were developed in the context of an urban setting including high risk populations (the northern Manhattan communities of Washington Heights, Inwood, and Harlem), many of the issues raised are broadly applicable. The processes by which the group identified research gaps and methodological challenges that impede a better understanding of how to prevent and treat obesity in children has resulted in an increase in research and community outreach collaborations and interdisciplinary pursuit of funding opportunities across units within the academic health center and overall University.
pediatric obesity prevention; interdisciplinary; research priorities
CTSA-IP (http://www.CTSAIP.org) is a web-based, open access intellectual property (IP) search tool that aggregates and promotes technologies from member institutions of the National Institutes of Health’s (NIH) Clinical Translational Science Awards (CTSA) consortium. Its ultimate aim is to stimulate collaborative research activity by encouraging the formation of public-private partnerships with CTSA institutions and the NIH. First launched in 2009, CTSA-IP has grown rapidly and met its first objectives of developing wide member institution participation and site usage. This article will discuss the strategy employed in the initiative of aggregating IP across institutional boundaries, the promise that lies therein, as well as the challenges encountered and lessons learned in promoting CTSA-wide engagement.
To determine the Community-Based Participatory Research (CBPR) training interests and needs of researchers interested in CBPR to inform efforts to build infrastructure for conducting community-engaged research.
A 20-item survey was completed by 127 academic health researchers at Harvard Medical School, Harvard School of Public Health, and Harvard affiliated hospitals.
Slightly more than half of the participants reported current or prior experience with CBPR (58%). Across all levels of academic involvement, approximately half of the participants with CBPR experience reported lacking skills in research methods and dissemination, with even fewer reporting skills in training of community partners. Regardless of prior CBPR experience, about half of the respondents reported having training needs in funding, partnership development, evaluation, and dissemination of CBPR projects. Among those with CBPR experience, more than one third of the participants wanted a mentor in CBPR; however only 19% were willing to act as a mentor.
Despite having experience with CBPR, many respondents did not have the comprehensive package of CBPR skills, reporting a need for training in a variety of CBPR skill sets. Further, the apparent mismatch between the need for mentors and availability in this sample suggests an important area for development.
Prediction of mortality in severely burned patients remains unreliable. Although clinical covariates and plasma protein abundance have been used with varying degrees of success, the triad of burn size, inhalation injury, and age remains the most reliable predictor. We investigated the effect of combining proteomics variables with these three clinical covariates on prediction of mortality in burned children. Serum samples were collected from 330 burned children (burns covering >25% of the total body surface area) between admission and the time of the first operation for clinical chemistry analyses and proteomic assays of cytokines. Principal component analysis revealed that serum protein abundance and the clinical covariates each provided independent information regarding patient survival. To determine whether combining proteomics with clinical variables improves prediction of patient mortality, we used multivariate adaptive regression splines, since the relationships between analytes and mortality were not linear. Combining these factors increased overall outcome prediction accuracy from 52% to 81% and area under the receiver operating characteristic curve from 0.82 to 0.95. Thus, the predictive accuracy of burns mortality is substantially improved by combining protein abundance information with clinical covariates in a multivariate adaptive regression splines classifier, a model currently being validated in a prospective study.
Community engagement has become a prominent element in medical research and is an important component of the Clinical and Translational Science Awards program. Area Health Education Centers engage communities in education and workforce development.
Engaging Communities in Education and Research(ECER) is a successful collaboration among the Colorado Area Health Education Center (AHEC), the Colorado Clinical Translational Science Institute (CCTSI), and Shared Network of Collaborative Ambulatory Practices and Partners (SNOCAP)—Colorado’s practice-based research collaborative. The ECER Conference is an annual conference of community members, health care providers, clinical preceptors, AHEC board members, university faculty, primary care investigators, program administrators and community organization leaders.
300–440 participants each year representing all regions of Colorado. Several projects from the “new ideas” break out session have been developed and completed. Six-month follow-up provided evidence of numerous new collaborations, campus-community partnerships, and developing research projects. Several new collaborations highlight the long-term nature of building on relationships started at the ECER Conference.
Discussion and Conclusion
Engaging Communities in Education and Research has been a successful collaboration to develop and support campus-community collaborations in Colorado. While seemingly just a simple 3-day conference, we have found that this event has lead to many important partnerships.
Practice-based Research; Continuing Education; Translational Research