bluuebunny/crossref_metadata_2025 huggingface dataset:
2043
Authors: Hertz Daniel L. , Kidwell Kelley M. , Vangipuram Kiran , Sun Duxin , Henry N. Lynn
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Peripheral neuropathy is the dose limiting toxicity of paclitaxel treatment. Paclitaxel pharmacokinetics (PK), specifically the Cmax and amount of time the concentration remains above 0.05 µM (Tc>0.05), have been associated with occurrence of severe, clinician-documented neuropathy. The objective of this study was to confirm that paclitaxel PK predicts progression of patient-reported neuropathy. METHODS/STUDY POPULATION: This observational trial enrolled breast cancer patients receiving weekly 1-hour paclitaxel infusions (80 mg/m2×12 cycles) at the University of Michigan Comprehensive Cancer Center. Paclitaxel concentration was measured via LC/MS in plasma samples collected at the end of (Cmax) and 16–24 hours after (Tc>0.05) first infusion. Patient-reported neuropathy was collected (EORTC CIPN20) at baseline and each cycle. The rate of neuropathy severity increase per treatment cycle is being modeled for each patient. Cmax and Tc>0.05 values will be introduced into the model to confirm that PK independently contributes to neuropathy progression. RESULTS/ANTICIPATED RESULTS: PK and neuropathy data have been collected from 60 patients for ongoing analysis. Our initial model will characterize the expected severity of neuropathy after each cycle of paclitaxel treatment. The PK-neuropathy model will include either PK parameter to validate their contribution to the progression of neuropathy severity during treatment. We anticipate, based on our preliminary analysis of the first 16 patients, that both PK parameters will significantly contribute to the model but Tc>0.05 will be more strongly associated with neuropathy progression. DISCUSSION/SIGNIFICANCE OF IMPACT: This project will generate a model that can be used to predict a patient’s neuropathy severity throughout treatment using a single, conveniently collected and easily measured PK sample during their first cycle. The next steps of this project include identifying genetic and metabolomic biomarkers that predict which patients experienced more severe neuropathy than would be anticipated based on their paclitaxel PK, and a planned interventional trial of personalized paclitaxel dosing to enhance efficacy and/or prevent neuropathy.
2272
Authors: Zapolski Tamika , Aalsma Matthew C. , Salyers Michelle , Watson Dennis
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Engagement in risky behaviors is not uncommon among adolescents. Two factors associated with risk taking are difficulty regulating emotions and impulsivity. Moreover, youth who exhibit higher scores on impulsivity-like personality traits (ie, negative urgency, positive urgency, sensation seeking, lack of premeditation, and lack of perseverance) are at even heightened risk. An effective intervention decreasing risk-taking behavior among adolescent populations in clinical settings is Dialectical Behavioral Therapy for Adolescents (DBT-A), which teaches skills on emotion regulation, distress tolerance, and mindfulness. However, DBT-A has yet to be tested as an intervention for youth in a nonclinical setting. The current study aimed to fill this gap in the literature. METHODS/STUDY POPULATION: A 9-week DBT-A skills group was implemented in a public high school classroom (7th-8th graders; N=41) and an alternative high school for at risk youth (7th-12th graders; n=21). Of the 41 youth from the public high school classroom participated, with preintervention and postintervention data provided by 30 participants (retention of 73%). RESULTS/ANTICIPATED RESULTS: Results found a significant increase in mindfulness skills and marginally significant increase in emotion regulation skills. Although there was not an overall change in risky behavior among participants, those who were higher on lack of premeditation and positive urgency showed steeper improvements on the skills. The second study at the alternative high school is currently underway, with no current results to report. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will demonstrate that DBT-A skills training is feasible in a school-based setting and shows promising preliminary evidence of decreasing risk of engagement in risky health behaviors among adolescents, particularly among high-risk youth.
2390
Authors: Canada Justin M. , Billingsly Hayley , Buckley Leo , Carbone Salvatore , Kadariya Dinesh , Van Tassell Benjamin , Abbate Antonio , Siddiqui Mohammad
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) affects 1 in 3 Americans and can exist in 2 histological subtypes: simple hepatic steatosis (SHS) and nonalcoholic steatohepatitis (NASH), a clinically aggressive variant. Fatigue is the most common complaint in patients with NAFLD but the etiology of fatigue is unknown. Thus, the goal of this study was to objectively evaluate fatigue via maximal cardiopulmonary exercise testing and identify determinants of exercise intolerance in NAFLD. METHODS/STUDY POPULATION: In total, 14 subjects with histologically confirmed NAFLD were prospectively enrolled. Subjects with cirrhosis or those with known history of heart failure (systolic or diastolic) were excluded. Fatigue was quantified via the Duke Activity Status Index (DASI) questionnaire. A symptom-limited treadmill cardiopulmonary exercise test was performed in all subjects to measure exercise time (ET) and peak oxygen consumption (peak VO2). Doppler-echocardiography was performed to measure systolic and diastolic function. RESULTS/ANTICIPATED RESULTS: The DASI score and ET was significantly reduced in patients with NASH (n=10) when compared to those with SHS [40.2 (IQR=24.2–50.7) vs. 58.2 (IQR=50.7–58.2), p=0.04]; [9.1 (IQR=6.4–12.2) vs. 13.1 (IQR=12.5–13.1) min, p=0.02, respectively] reflecting moderate fatigue and impaired overall exercise capacity. The ET was directly linked to peak VO2 (R=+0.79, p<0.001), VO2 at anaerobic threshold (R=+0.73, p=0.003), and inversely to ventilatory efficiency index (R=−0.785, p=0.001) suggesting impaired cardiorespiratory fitness in those with reduced ET. ET was also linked to several parameters of diastolic dysfunction including left atrial volume index (R=−0.798, p<0.001), and the ratio of early transmitral pulse-wave Doppler flow velocity (E) to early mitral annulus tissue Doppler velocity E’ (E/E’) (R=−0.608, p=0.036), suggesting a role of diastolic dysfunction in patients with NAFLD with exercise intolerance. DISCUSSION/SIGNIFICANCE OF IMPACT: Cardiac abnormalities drive cardiorespiratory fitness and exercise intolerance in patients with NAFLD. These findings are exaggerated in patients with NASH suggesting a link between disease severity in NAFLD, exercise intolerance and diastolic dysfunction.
2431
Authors: Lin Andrea , Mathews Clayton , Haller Michael , Brusko Todd , Atkinson Mark , Flynn Ryan
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Understand the immunomodulatory effects of anti-thymocyte globulin (ATG) and granulocyte colony stimulating factor (G-CSF) on type 1 diabetes patients using samples and in the preclinical model, the nonobese diabetic mouse. METHODS/STUDY POPULATION: Flow cytometry analysis of phase 1 peripheral blood samples treatment of nonobese diabetic mouse with ATG and GCSF and flow cytometry analysis of immune organs (spleen, lymph nodes, blood, bone marrow). RESULTS/ANTICIPATED RESULTS: Changes in both innate and adaptive immune cell subsets including plasmacytoid dendritic cells, naive, memory, effector CD4+ and CD8+ T-cells, and CD4+ T-regulatory cells and CD8+ T-regulatory cells DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding of immune cell targets for immunotherapy in new-onset type 1 diabetes patients.
2432
Authors: Huang Yuan , Brown Sheldon T. , Ma Shuangge , Kyriakides Tassos
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Effective HIV therapeutic options for persons with advanced HIV disease whose regimens have failed multiple times are limited. Current clinical practice utilizes regimens comprised of combinations of anti-retroviral (ARV) drugs. Despite the widespread use of ARV medications, optimization of initial treatment composition and subsequent management remains challenging. The goals of this study are (a) to better understand the ARV treatment structuring using prior clinical and patient information including virtual phenotype data and measures of viral load and CD4 cell count. We evaluated the potential impact of ARV strategies on AIDS-defining events and mortality; (b) to assess and understand differences of treatment composition and management when comparing standard ARV strategy (<5 ARVs) with an intensive ARV strategy (at least 5 ARVs). METHODS/STUDY POPULATION: OPTIMA was a tri-national (United States, Canada, and United Kingdom) randomized open label of alternative ARV treatment strategies for patients with advanced HIV disease (CD4≤300 cells/mm3) and evidence of resistance to 3 classes of ARV medications. OPTIMA used a 2×2 factorial design where the 2 factors were an ARV-free period Versus not; and standard Versus intensive ARV regimen. In this study, we focus on participants enrolled in OPTIMA at US participating sites and utilize demographic and clinical data including baseline virtual phenotype, ARV-related data (initial assignments and changes with drugs and dosages), follow-up lab data, AIDS-defining events, and vital status. RESULTS/ANTICIPATED RESULTS: Among 278 US-OPTIMA participants, 146 were randomly assigned to the standard ARV strategy and the rest were assigned to the intensive ARV strategy. Although not the sole factor, baseline virtual phenotype was used in selecting ARV medications within each assigned strategy. Participants in the standard arm exhibited better agreement between virtual phenotype results and the individual drugs selected for their regimen compared with participants in the intensive arm. This agreement had an almost statistically significant impact on survival time. No significant difference was detected in the frequency of ARV changes between standard and intensive ARV groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Even though per design, OPTIMA assigned participants to an ARV strategy using a binary factor (standard vs. intensive ARV) and assessed its effect on HIV-related disease at a coarse level, the trial’s design and rich database allowed for a closer examination of the ARV drug initial selection and subsequent management. Our findings summarize the patterns and discuss the effects of ARV and their management, on AIDS-defining events and survival. Such findings could provide preliminary, yet important insight, in understanding ARV use practice and could inform the conduct of future HIV treatment trials. Since the trial’s randomization was at the ARV strategy level and not the individual ARV drugs, findings cannot be described in terms of causal pathways for specific ARVs.
2208
Authors: Gruca Martin , Lyden Angela K. , Kumar Anjana M. , Jackson Elizabeth A.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: This project has 2 overarching objectives: (1) to investigate the acceptability of the Michigan Surgical and Health Optimization Program (MSHOP) among referred patients, and to describe individual motivations behind enrollment Versus nonenrollment; and (2) to identify patient and program related factors associated with adherence and LOS and readmission rates. METHODS/STUDY POPULATION: Hypothesis—(1) MSHOP participants will report overall satisfaction with the program. Individuals that are satisfied with the program will be likely to perceive the program as effective. Subjects that declined MSHOP will be more likely to perceive their outcomes as immutable. (2) MSHOP patients will have shorter hospital stays and fewer readmission compared with patients who declined MSHOP. Methods—this study will use both qualitative and quantitative methods to investigate patient experiences and program efficacy. First, a convenience sample of patients who were referred to the MSHOP within the previous 12 months will participate in structured interviews to assess program acceptability, patient satisfaction with individual components of MSHOP, and perception of program efficacy. Interviews will also include patients who declined to enroll in MSHOP. Interviews for these subjects will include questions that assess why patients chose to decline enrollment. Second, there will be a retrospective cohort study comparing hospital outcomes among patients who enrolled in MSHOP Versus those who chose not to enroll. Analysis—interviews will be recorded and transcribed for thematic analysis to identify patterns associated with satisfaction or dissatisfaction with the MSHOP. Multivariate regression will be used to determine effect of MSHOP participation on postsurgical length-of-stay and 30-day readmission rate. Demographics and procedure type will be included as covariates. RESULTS/ANTICIPATED RESULTS: In total, 28 interviews have been transcribed, and are in the initial stages of thematic analysis. Interviews have thus far suggested that patients have been satisfied with MSHOP and would recommend the intervention to other patients. Retrospective data regarding hospital length of stay for MSHOP patients from September 2014 to December 2016 has been acquired and is being processed. The characteristics of patients that tend to participate more actively in MSHOP will be explored. We anticipate that active participation in the MSHOP will be associated with shorter hospital stays and fewer readmissions. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will be one of the first to characterize patient perception of MSHOP, in particular its use of tracking step counts and breathing exercises to promote a form of prehabilitation that is easier to integrate into daily life. This project will investigate MSHOP’s effect on patient outcomes, as well as explore factors that may associate with better patient adherence and outcomes. This would help further optimize the MSHOP as an intervention.
2069
Authors: Hornung Carlton , Thomas Jones Carolyn , Hinkley Terri , Ellingrod Vicki , Calvin-Naylor Nancy
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Clinical research in the 21st century will require a well-trained workforce to insure that research protocols yield valid and reliable results. Several organizations have developed lists of core competencies for clinical trial coordinators, administrators, monitors, data management/informaticians, regulatory affairs personnel, and others. While the Clinical Research Appraisal Inventory assesses the self-confidence of physician scientists to be clinical investigators, no such index exists to assess the competence of clinical research professionals who coordinate, monitor, and administer clinical trials. We developed the Competency Index for Clinical Research Professionals (CICRP) as a general index of competency (ie, GCPs) as well as sub-scales to assess competency in the specific domains of Medicines Development; Ethics and Participant Safety; Data Management; and Research Methods. METHODS/STUDY POPULATION: We analyzed data collected by the Joint Task Force on the Harmonization of Core Competencies from a survey of research professionals working in the United States and Canada. Respondents reported how competent they believed themselves to be on 51 clinical research core competencies. Factor analyzes identified 20 core competencies that defined a Competency Index for Clinical Research Professionals—General (CICRP-General, ie, GCPs) and 4 subindices that define specialized research functions: Medicines Development; Ethics and Participant Safety; Data Management; and Research Concepts. RESULTS/ANTICIPATED RESULTS: Factor analysis identified 20 core competencies that defined a Competency Index for Clinical Research Professionals—General (CICRP-General, ie, GCPs) and 4 subindices that define specialized research functions: Medicines Development; Ethics and Participant Safety; Data Management; and Research Concepts. DISCUSSION/SIGNIFICANCE OF IMPACT: These indices can be used to gage an individual’s readiness to perform general as well as more advanced research functions; to assess the education and training needs of research workers; and to evaluate the impact of education and training programs on the competency of research coordinators, monitors, and other clinical research team members.
2200
Authors: Lynn Murphy Susan , Byks-Jazayeri Christy , Eakin Brenda , Hahn Jordan , Lynn Brandon , Samuels Elias M. , Ennever Fanny , Peyre Sarah , Dubocovich Margarita L. , Bajwa Wajeeh
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To conduct a preliminary evaluation of the Social and Behavioral Research Best Practices Course. METHODS/STUDY POPULATION: Learners are sampled from 5 institutions: University of Michigan, University of Rochester, University of Florida, Boston University, and University of Buffalo. Learners who take the course and consent to be in the study receive a web link to a survey immediately after course completion and at 2–3 months follow up. In addition to demographic information, learners will report their perceptions of usefulness and relevance of the course to their job, their satisfaction with the course and associated job aids, and at follow-up, if and how the course impacted their work. Additional information will be collected from the learning management systems which host the course at each institution. The data collected will include the number of participants who take the course, the number who complete, how many times the course was attempted, and pass rates. RESULTS/ANTICIPATED RESULTS: We anticipate that several hundred learners will take the course by the end of our project. Of learners who agree to participate in the survey, we anticipate that they will find the course useful and relevant to social and behavioral clinical trials and will be satisfied with the course. Information including suggestions about missing content, items or content that were not extremely clear, or any other comments will be collected to iterate and expand the course. DISCUSSION/SIGNIFICANCE OF IMPACT: This course was developed to fill a gap in training in good clinical practice for social and behavioral research. An evaluation of how the training provided in the course impacts the jobs of learners is needed both to ensure that the most relevant information is included in the course as well as to identify ways that the training may contribute to the quality and safety of social and behavioral clinical trials.
2379
Authors: Freel Stephanie A. , West Miranda , Snyder Denise
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Our objectives are to provide opportunities for graduate students, clinical interns, and postdoctoral fellows in traditional training programs to have immersive experiences in clinical research conduct from a CRP perspective. In addition, we aimed to address common causes of job dissatisfaction by providing professional development and networking opportunities for the existing CRP workforce. METHODS/STUDY POPULATION: In collaboration with the CTSA workforce development group, the Duke Office of Clinical Research hosted a site visit for 19 PhD scientists interested in nontraditional career pathways and a short lecture series on project management careers in clinical research. Additionally, we crafted specific clinical research training electives for 20 masters students and 10 dietetic interns. Finally, in collaboration with UNC-CH, we combined Research Professional Networks to provide a pilot joint professional development event for 109 CRPs from both schools. RESULTS/ANTICIPATED RESULTS: The number of Masters students enrolling in the CRP elective grew from 7 students in year 1 to 13 students currently enrolled. A retro-pre/postprogram adapted CRAI survey was issued following program completion. Students self-reported increases in competence across all 24 skills measured. Largest increases were seen in areas specific to CRP roles such as consenting patients, understanding the IRB, and reviewing key study documents. A baseline culture survey issued at the joint Duke/UNC CRP event garnered a 65% response rate and indicated that the principal gaps in professional training are in communications, teamwork, leadership, and professionalism. Moreover, respondents indicated that creating a sense of community and providing networking opportunities were the most important outcomes for future CRP collaborations. Future evaluations of both of these programs will allow us to tailor training to be most effective in strengthening our CRP workforce. DISCUSSION/SIGNIFICANCE OF IMPACT: These initiatives lay the groundwork for the development of a robust training pipeline into CRP careers. Future initiative will apply lessons learned toward creating internship programs aimed at improving diversity and inclusion within these careers. In addition, by addressing the professional development needs of the existing workforce, we create a sustainable environment for well-trained professionals. By evaluating these primary initiatives, we can better define the critical elements that must be included in CRP educational, development, and support programs and subsequently apply these to ultimately improve the clinical and translational research being conducted in academic research settings.
2523
Authors: Merrifield Angela , Lamere Michelle , Lim Kelvin , Larson Megan , Ingbar David H.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The NIH states, “The training of the biomedical workforce has always been an integral part of the NIH mission… It takes just one good mentor to influence the career of a new investigator; it takes a robust culture of mentorship across the research community to strengthen, sustain and diversify the entire biomedical research enterprise.” The University of Minnesota’s CTSI-Education core strives to build and maintain a strong culture of mentoring by providing CTSI KL2 scholars an opportunity to mentor an undergraduate student participating in the Pathways to Research Program (PReP). Using this mentoring model, participants gain valuable benefits and CTSI’s culture of mentoring is strengthened. METHODS/STUDY POPULATION: Participating KL2 scholars are matched with a promising PReP scholar for a 12-week mentored research project. The PReP program selects top candidates through a highly competitive application process. Students work in their mentor’s lab full-time, funded by CTSI-Ed. They engage in additional activities together including a mentor/mentee, an interview activity and 2 social events. Junior faculty scholars are asked to participate as judges at CTSI’s Poster Session and are invited to present at PReP seminars. The program culminates with the announcement of the Junior Mentor of the Year, in which scholars nominate their mentors for the award. Junior faculty mentors receive support through a training course, Optimizing the Practice of Mentoring, mentor orientation and a roundtable discussion with the program director and other mentors. The program’s infrastructure is designed to foster mentee/mentor relationships through faculty and staff support. Junior faculty receive one-on-one coaching when faced with difficult mentoring situations and are recognized for their mentoring successes. RESULTS/ANTICIPATED RESULTS: Junior faculty mentors highly rate the program on the following points; the experience was a good use of time, I am satisfied with my experience, I would recommend this program to faculty colleagues and students. Undergraduates and Professional students rated their mentoring relationship as 1 of 3 best outcomes of the program. In exit surveys, their highly rated program successes include having a network that helps move their career forward, and confidence to persist through training to become a successful researcher. DISCUSSION/SIGNIFICANCE OF IMPACT: Creating a culture of mentoring is important to the strengthen, sustain and diversify the biomedical research workforce. This mentoring model contributes to the mission while vertically integrating CTSI-Ed’s KL2 and PReP programs. On an individual level, junior faculty improve communication and management skills, develop leadership qualities, increase their network, provide a sense of fulfilment and personal growth, and reinforce their own skills and knowledge of subject. They are also provided a top undergraduate student worker fully funded by the program.
2030
Authors: Moore Tina , James Laura P. , Holland Jennifer , Paal Edith , Hadden Kristie
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Develop a plain language informed consent template that met IRB and regulatory requirements. Evaluate the effectiveness of the template at improving the readability of informed consents. Field test the informed consent with low health literacy. METHODS/STUDY POPULATION: We conducted a retrospective analysis of over 200 UAMS IRB approved, investigator initiated informed consents from 2013 to 2015 to determine the readability before intervention. The mean grade level readabilities were derived from the results of 3 readability formulas (Flesch-Kincaid, SMOG, and Fry) using open-source readability tools. A plain language informed consent template that meets IRB and regulatory requirements was developed, adhering to health literacy best practices for written communication. The template was made available to investigators as an optional resource, and IRB committees were trained on use of the template. In addition, a focus group will be conducted to qualitatively assess understandability of the template with study participants identified as having inadequate health literacy. Data analysis will include readability assessment of IRB approved informed consents post intervention with and without use of the plain language template, as well as qualitative feedback from focus group participants. RESULTS/ANTICIPATED RESULTS: The retrospective analysis revealed a mean readability of 10th grade for IRB approved informed consents from 2013 to 2015 (n=217). The readability of the developed plain language template was 5th grade. Preliminary post-intervention results show adoption of the template by investigators (n=16) resulted in informed consents with a mean readability of 7th grade (range 6–9th grade), compared to a mean of 10th grade (range 7–11th grade) for the comparator (“no adoption” group, n=24). Data collection will continue through May 2017. The focus group is forthcoming and results will be included in the poster. DISCUSSION/SIGNIFICANCE OF IMPACT: Low health literacy is common in individuals with healthcare disparities and can limit their participation in clinical research. Few studies have examined interventions to address this barrier to research. Preliminary results of this study support the utilization of a plain language informed consent template in investigator-initiated research. Moreover, this study demonstrates the importance of stakeholder engagement among CTSA leadership, health literacy experts, the institutional review board, investigators, and research subjects in the development and testing of this intervention to make informed consents “understandable to the subject” while containing all required elements.
2084
Authors: Otado Jane , Thomas Veronica , Callier Shawneequa , Rockcliffe Faun , Johnson Dietrich , Scott Denise
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The purpose of this descriptive study is to explore knowledge, attitudes, and behaviors related to genetics and genetic research in a sample of persons of African descent. METHODS/STUDY POPULATION: Data were generated using a cross-sectional survey design. A nonprobability sample of 272 persons of African descent, ages 18 and older, were recruited from the Washington, DC metropolitan area through public advertisement and word-of-mouth. Participants had diverse backgrounds with most born in the United States (93%), female (71%), some college or above education (57%), household income under $40,000 (54%), and some with a reported disability (38%). Before survey recruitment and administration, this study was reviewed and approved by the Howard University Institutional Review Board. RESULTS/ANTICIPATED RESULTS: The majority (79.8%) of the participants considered themselves as having a “fair” to “good” knowledge of genetics. The sample had a 2.24 (SD=77) mean score on the 5-item genetics knowledge questionnaire with total possible mean scores ranging from 0 (no correct responses) to 5 (all correct responses). Most (53.3%) participants believe it is important for persons of African descent to participate in genetic research. However, almost one-half (46.7%) felt that information from genetic research can be used to discriminate against minorities. In terms of behaviors, 83.4% of the participants never had genetic testing conducted. However, an overwhelming majority reported that they would be willing to participate in a genetic research project specifically for detection of risk factors such as cancer (87%), diabetes (89.3%), Alzheimer disease (88.6%), and alcohol use disorder (75%). DISCUSSION/SIGNIFICANCE OF IMPACT: This investigation suggests that persons of African descent generally view participation in genetic research as important and are willing to have their genetic profile analyzed to detect susceptibility to certain diseases. However, ethical issues, such as misuse of genetic research to discriminate against minorities, remain a prominent concern. Further studies are needed to illuminate KABEs and to help identify the role these factors may play in this population’s willingness to participate in testing and research. Such information could provide invaluable insight to the development and implementation of more ethical and culturally competence strategies for recruiting minority participants into genetic research.
2533
Authors: Croisant Sharon A. , Arcari Christine , Prochaska John , Anthony Amber , Wallace Brittany , Singleton Chantele , Wiseman Lori , Ruffner Rob , Gonzalez Tino , Jones Dwayne , Marie Brown Fredia , Purser Julie , Brasier Allan
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The Institute for Transnational Sciences (ITS) has developed novel methods to ethically engage stakeholders across the transnational research spectrum, up to and including public health practice and policy. METHODS/STUDY POPULATION: In 2014, the ITS co-founded The Research, Education, And Community Health (REACH), the mission of which was to facilitate communication, collaborative research, and service activities between faculty and scientists and area community leaders. The intent was to identify and meet the needs of our communities without gaps and/or redundancies, thus better leveraging time, funding, and efforts. RESULTS/ANTICIPATED RESULTS: REACH now boasts 23 Centers, Departments, and Institutes, as well as 39 community organizations, including public and mental health agencies, clinicians, policy makers, family service centers, cultural and faith-based organizations, business, and local schools/colleges. We offer 3 methods for consideration as best practices: (1) a comprehensive community health needs assessment, (2) an “Offer and Ask” community/campus partnership mechanism, and (3) Community Science Workshops, based on the European Union’s Science Shops. DISCUSSION/SIGNIFICANCE OF IMPACT: Results of REACH’s work have been used to provide guidance for enhanced, data-driven programs and allocation of resources for local and statewide initiatives. The organization has evolved into an independent coalition seeking 501(c)3 status and is planning to expand its scope to 5 counties. REACH thus serves as model for successful replication across applicable CTSA hubs.
2543
Authors: Delva Jorge , Paberzs Adam , Piechowski Patricia , Calhoun Karen , Carr Diane , Spiroff Meghan , Buyuktur Ayse , Weatherwax Kevin
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To describe how Michigan Institute for Clinical & Health Research (MICHR) has engaged communities in its leadership and governance structure. This presentation will describe these practices, how they are being evaluated, and future plans for institute-wide engagement of communities in translational research. METHODS/STUDY POPULATION: Engaged partners from various communities across Michigan in various ways within MICHR’s Community Engagement Program. RESULTS/ANTICIPATED RESULTS: MICHR has utilized participatory practices in the development of the CAB to strengthen existing relationships and build new ones with potential partners. DISCUSSION/SIGNIFICANCE OF IMPACT: MICHR-wide Community Advisory Board (CAB) will ensure community voices are heard and utilized in leadership and strategic decisions for CTSA activities.
2064
Authors: Riley Timothy P. , Mendoza Juan , Garcia K. C. , Baker Brian M.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The off-target and organ-specific toxicities observed in cancer immunotherapy present an obstacle to T-cell-based therapeutics. A recent clinical trial underscored the need for improved methods to define TCR specificity after melanoma patients treated with TCR engineered T-cells suffered from fatal cardiovascular toxicity arising from the unpredicted recognition of a muscle-specific peptide. METHODS/STUDY POPULATION: To address this drawback to T-cell-based immunotherapies, we developed a novel protein engineering approach to define the peptide specificity of a given TCR. Here, directed evolution in a yeast display system produced a large scale peptide library, where recognition by the melanoma reactive DMF5 TCR acted as the guiding selective pressure. After this technique identified a panel of putative cross reactive peptides, sequence analysis and computational modeling followed by kinetic binding experiments and structural analysis determined the DMF5 TCR recognizes 2 distinct classes of peptides through chemically distinct mechanisms. RESULTS/ANTICIPATED RESULTS: This information led to the rational, structure-based design of additional cross reactive peptides and introduced a unique approach to screen the human proteome and identify the TCR targets which triggered undesired autoimmunity when this molecule was used in clinical trials. DISCUSSION/SIGNIFICANCE OF IMPACT: The distinct chemical nature of the 2 peptide classes suggest TCRs are more cross reactive than previously thought, presenting an obstacle to cell-based immunotherapy. Defining the peptide specificity of TCRs is of high interest to the immunology community, and will lead to improved approaches to designing engineered TCRs for cell therapy.
2109
Authors: Davis Stephanie , Huang Jeffrey
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The overall objective of this proposal is to establish and modulate the inflammatory profile of individuals across the spectrum of multiple sclerosis (MS), with a focus on determining the potential of interleukin 4-induced protein 1 (IL4I1) as a possible marker of progression and modulator of inflammation in human blood samples. METHODS/STUDY POPULATION: The proposed experimental approach involves isolating plasma and peripheral blood mononuclear cells (PBMCs) from individuals across the spectrum of MS phenotypes, and analyzing these samples primarily by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) methods. Specifically, study groups include: (1) actively relapsing-remitting MS (a-RRMS), (2) non-actively relapsing-remitting MS (n-RRMS), (3) non-active secondary-progressive MS (SPMS), (4) other autoimmune diseases (OAD), (5) healthy controls (HC). RESULTS/ANTICIPATED RESULTS: We expect that IL4I1 treatment increases regulatory cytokine (eg, IL10, TGFb) expression while decreasing Th1 and Th17-derived cytokines (IFNg, IL17), as well as increasing relative composition of regulatory cells (Th2, Treg, M2) as compared with Th1, Th17, M1 (aim 1). Preliminary data on healthy control cells support this prediction. Our central hypothesis is that IL4I1 level indicates the body’s ability to repair itself. As such, we anticipate that all MS groups are deficient in IL4I1, to varying degrees, such that HC>n-RRMS>a-RRMS>SPMS. HC have full repair capacity. RRMS>SPMS as remission indicates existent repair capacity, which is lost in SPMS. n-RRMS>a-RRMS since both, as RRMS, capable of repair response, but a-RRMS triggered this response more recently in response to more recent relapse. In all groups, we expect IL4I-treatment to mitigate inflammation (aim 2). Finally, we expect that H2O2 production by IL4I1 is a key player in IL4I1 function, and that H2O2 will preferentially induce oxidative stress to pro-inflammatory subsets of PBCMs (aim 3). DISCUSSION/SIGNIFICANCE OF IMPACT: MS is a chronic inflammatory neurodegenerative disease of the central nervous system that, with an average age of onset of 34, afflicts over 2.3 million individuals worldwide during many of the most productive years of their lives. The pathogenesis of MS, which involves autoimmune destruction of myelin, is poorly understood. Accurate biomarkers, which could predict disease progression, are yet to be identified and would provide valuable information to patients and their treating clinicians. Likewise, effective treatments are few and in high demand. IL4I1 is a promising candidate for both roles.
2279
Authors: Cooper Paula , Wang Hsing-Hui , Broman Meaghan , Kaimakliotis Hristos , Elzey Bennett , Crist Scott , Cheng Liang , Ratliff Timothy
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The primary goal of this project is to verify murine findings in the human setting. METHODS/STUDY POPULATION: The methods include primary cell isolation and culture, FACS, adoptive transfer, 3D-cell culture, histology, immunofluorescence, xenograft, and tissue recombination. The study population includes patients undergoing radical prostatectomy due to hyperplasia or adjacent bladder or prostate cancer. RESULTS/ANTICIPATED RESULTS: Having verified similar sensitivities to androgen receptor (AR) inhibitors between naive murine and human basal prostate stem cells, we anticipate that autoimmune inflammation in humans affects the response of basal prostate stem cells in a manner similar to the murine setting as well. This includes increased proliferation, differentiation, and response to AR inhibitors. DISCUSSION/SIGNIFICANCE OF IMPACT: The identification of survival mechanisms used by basal prostate stem cells in an androgen deprived environment may give insight to the process by which prostate cancer becomes androgen independent. The effect of inflammation on proliferation, survival, and AR signaling in these cells may also provide information relevant to cancer initiation and progression.
2297
Authors: Nadella Sandeep , Smith Jill , Burks Julian , Al-Sabban Abdulhameed , Wang Juan , Tucker Robin , Inyang Gloria
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Epidemiologic studies have found that the incidence of pancreatic cancer is greatest in countries that consume diets high in fat. The gastrointestinal peptide cholecystokinin (CCK) is released from the duodenum in response to dietary fat. CCK has also been shown to stimulate growth of pancreatic cancer through the CCK receptor that is over-expressed on pancreatic cancer cells. The aim of this investigation was to determine if dietary fat promotes growth of pancreatic cancer through the actions of CCK at its receptor. METHODS/STUDY POPULATION: The effects of dietary fat on growth of murine Panc02 pancreatic cancer xenografts were studied in 3 different systems with immune competent mice: (1) pharmacologic blockade with a CCK receptor antagonist, (2) genetic knockout of the CCK receptor by CRISPR, and (3) in genetically engineered mice lacking the CCK peptide (CCK-KO). After injection of 2×106 Panc02 cells subcutaneously, mice were fed either a high-fat diet or a control diet for 37–42 days. Tumor volumes and weights were measured and histology performed. RESULTS/ANTICIPATED RESULTS: Dietary fat significantly increased the size of pancreatic cancer xenografts and this effect was reversed by CCK receptor blockade. Receptor antagonist therapy also significantly reduced tumor-associated fibrosis and increased the influx of CD8+ lymphocytes in the micro-environment. Panc02 cancer cells lacking CCK receptors failed to respond exogenous administration of CCK in vitro and to dietary fat in vivo. Dietary fat did not stimulate Panc02 tumor growth in CCK-KO mice. DISCUSSION/SIGNIFICANCE OF IMPACT: The mechanism by which dietary fat stimulates growth of pancreatic cancer is by CCK and this effect is independent of obesity. This is a significant finding because of the potential beneficial effects of medications which can block the effects of CCK in populations at risk for pancreatic cancer consuming a high-fat diet.
2442
Authors: Fink Brandi , Claus Eric D. , Cavanagh James F. , Hamilton Derek A. , Salway Sarah
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The objective of this research was to investigate the effect of alcohol and evocative stimuli on heart rate variability (HRV) in partners with a history of intimate partner violence in a placebo-controlled alcohol administration study with an emotion-regulation task. METHODS/STUDY POPULATION: In total, 17 partners (9 females, 8 males) with a history of partner violence participated in a placebo-controlled alcohol administration study with an emotion-regulation task during which HRV measures were collected. In the alcohol condition, participants were administered a mixture of 100 proof vodka and cranberry juice calculated to raise their blood alcohol concentration (BAC) to 0.08%. In the placebo condition, participants consumed a volume of juice equivalent to that consumed in the alcohol condition, but without alcohol. Alcohol and placebo conditions were counter-balanced across participants as were the presentation the blocks of evocative and neutral partner stimuli. RESULTS/ANTICIPATED RESULTS: Controlling for baseline HRV, there was a significant main effect of stimuli (evocative vs. neutral partner stimuli) on HRV in intoxicated partners, F1,16=16.28, p=0.004. There was also a significant main effect of regulation on HRV under conditions acute alcohol intoxication, F1,16=23.55, p=0.001. These effects tell us that intoxicated partners experienced reduced HRV when exposed to evocative stimuli from their partners. These effects also tell us that under acute alcohol intoxication, partners were less able to regulate their emotion when exposed to evocative stimuli than when they consumed a placebo beverage. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that increases in intimate partner violence under acute alcohol intoxication may be the result of reduce HRV. This reduction in HRV would contribute to partners’ inability to response with adaptively in conflict when intoxicated. They also suggest that HRV may be an important target for intervention with partner with a history of intimate partner violence. One method may be Heart Rate Variability Biofeedback which has been shown to increase parasympathetic nervous system functioning, autonomic stability, and emotion regulation.
2493
Authors: Berman Brian , Shelton Erika , Miao Yubin
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Determine whether GABA-A receptor binding is abnormal and linked to dystonia symptoms in cervical dystonia (CD). METHODS/STUDY POPULATION: There is increasing evidence that a key pathophysiological mechanism in adult-onset focal dystonia is a reduction in inhibitory control over the sensorimotor network. Results from a recent 11C-flumazenil PET imaging study suggest that abnormal inhibitory signaling in genetic and sporadic forms of dystonia may be due to reduced GABA-A binding. It remains unknown whether CD, the most common form of adult-onset focal dystonia, is associated with abnormal GABA-A binding. The goal of this research is to determine if GABA-A receptor binding is abnormal and linked to dystonia symptoms in CD. RESULTS/ANTICIPATED RESULTS: We investigated whole brain GABA-A binding in 15 CD patients (11F; 64±8 y) and 15 healthy controls (10F; 64±9 y) using 60-minute dynamic 11C-flumazenil PET scans. GABA-A receptor binding potential (BP) was estimated using a simplified reference tissue model. A 2-sample t-test was used to identify voxel-wise GABA-A BP differences between groups, and a regression analysis used to test for correlations between GABA-A BP and disease severity as measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). A conventional region of interest analysis was also conducted to quantify BP changes within the sensorimotor network using the automated anatomical labeling atlas. DISCUSSION/SIGNIFICANCE OF IMPACT: CD patients have reduced GABA-A receptor binding compared with healthy controls, with the greatest reduction seen within the sensorimotor region of the thalamus. Furthermore, reductions in GABA-A binding in brain regions associated with coupling sensory and motor information predict motor severity. These findings support that reduced GABAergic signaling within sensorimotor integration regions is a key mechanism underlying dystonic symptoms in CD and could help inform the development of better, more targeted treatment options.
2529
Authors: Suarez Dagmar Fredy Hernandez , Melin Kyle , Lopez-Candales Angel , Duconge Jorge
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To determine the association between clinical characteristics and platelet reactivity in Hispanic patients on clopidogrel therapy. METHODS/STUDY POPULATION: A cross-sectional pilot study was performed in 58 Puerto Rican patients diagnosed with any type of vascular disease and actively receiving a maintenance dose of clopidogrel for at least 7 days. The study population was divided into 2 groups: Group I with non-high on-treatment platelet reactivity (TPR); Group II with high TPR. To determine the platelet function, P2Y12 reaction units (PRU) were obtained by VerifyNow® P2Y12 assay (Accumetrics, USA). RESULTS/ANTICIPATED RESULTS: We studied a heterogeneous cohort of patients with coronary artery disease (57%), peripheral artery disease (30%), carotid artery stenosis (7%), cerebral artery aneurysm (3%), and stroke (3%) on clopidogrel therapy for secondary prevention of thromboembolic events. The mean TPR was 205±49 PRU (range: 61–304), with a prevalence of 28% patients with high TPR (PRU≥230). No significant clinical differences were found between the non-high TPR and high-TPR groups (p>0.05). However, multivariable logistic regression analysis showed that both diabetes mellitus (OR=7.5; CI: 1.01–51.9) and proton-pump inhibitors (OR=13.6; CI: 1.3–142.0) were independently correlated with high TPR (p<0.05) after adjusting for other clinical variables. DISCUSSION/SIGNIFICANCE OF IMPACT: These results provide new insight into the importance of clinical characteristics on platelet reactivity in this Caribbean population. Further studies are warranted to determine whether important clopidogrel pharmacogenes are related with platelet function in Hispanics, as well as the role of TPR in guiding antiplatelet therapy and predicting future adverse cardiovascular events in this population.