bluuebunny/crossref_metadata_2025 huggingface dataset:
2341
Authors: Vaughan Courtney , Stangl Bethany , Sinha Rajita , Ramchandani Vijay
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The objective of this analysis was to characterize the impact of stress, both early life and chronic, on intravenous alcohol self-administration (IV-ASA) in healthy non-dependent drinkers using the Computer-Assisted Infusion System (CAIS). Personality measures also have shown to impact drinking behavior, particularly impulsivity. Few studies have assessed the impact of stress and impulsivity on drinking behaviors in a non-dependent population. METHODS/STUDY POPULATION: Healthy non-dependent drinkers (n=28) completed a CAIS session, where they push a button adlib to self-administer standardized IV alcohol infusions. Participants completed the Cumulative Chronic Stress interview and the Early Life Stress Questionnaire (ELSQ) for stress measures. The Cumulative Chronic Stress interview was broken up into 4 sections: major life events, life traumas, recent life events, and chronic stressors. The number of endorsed events was added up to create 4 separate scores. Subjective response and craving measures were collected serially using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ). The Impaired Control Scale (ICS) assessed failed control over recent drinking in the past 6 months. Impulsivity was assessed using the NEO personality inventory, which included the N-impulsive sub-facet, as well as the UPPS-P Impulsive Behavior Scale. RESULTS/ANTICIPATED RESULTS: Results showed early life stress events (ELSQ) are related to more chronic stressors in the cumulative chronic stress interview (p=0.005). Participants with higher chronic stress scores showed lower subjective effects, as measured by the DEQ, following the priming exposure (p=0.036) but had more craving for alcohol as measured by the AUQ (p=0.009). A regression analysis showed the number of chronic stressful events predicted ICS failed attempts to control drinking (p=0.034), after covarying for sex. Participants with more chronic stressful events showed more impulsivity on the N-impulsivity measure (p=0.034) and the UPPS-P positive urgency measure (p=0.005). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-dependent drinkers with more early life stress tend to have a higher number of chronic stressful events. More chronically stressful events were associated with feeling less effects of alcohol and higher craving for alcohol. Participants with more chronically stressful events also appear to have more failed attempts at controlling their drinking. Future analysis will assess for mediation and moderation of these factors. Chronically stressful events and impulsive behaviors could serve as important areas for intervention for better treatment outcomes for alcohol use disorders.
2396
Authors: Youssof Sarah , Romero-Clark Carol
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Oculopharyngeal muscular dystrophy (OPMD) is a rare, late-onset muscular dystrophy that causes severe swallowing impairment (dysphagia). Although promising therapies are in the pipeline, validated dysphagia outcome measures for use in OPMD trials have not been established. Videofluoroscopic swallow studies (VFSS) are considered the clinical gold standard for dysphagia assessment, yet the optimal objective measure of VFSS in OPMD is not known. Our aim was to investigate the utility of the Modified Barium Swallow Impairment Profile (MBSImP) as an objective measure of VFSS in OPMD patients. METHODS/STUDY POPULATION: This was a single-center, prospective, cross-sectional study. In total, 26 individuals with OPMD underwent VFSS and other measures of dysphagia including 50-mL water swallow time (ST). Validity was assessed by examining correlations with an OPMD Global Severity Score (GSS) and with dysphagia duration. RESULTS/ANTICIPATED RESULTS: The MBSImP demonstrated moderate correlations with GSS (Pearson r=0.52, p=0.006) and ST (r=0.39, p=0.049). The relationship between MBSImP and dysphagia duration appeared nonlinear, and levelled off with long dysphagia duration. In contrast, ST did not correlate significantly with GSS (r=0.27, p=0.18), nor with disease duration (r=0.05, p=0.83). DISCUSSION/SIGNIFICANCE OF IMPACT: Objective measurement of VFSS is a promising outcome measure in OPMD. With long disease duration, the MBSImP may not be sufficiently sensitive to detect disease progression. More sensitive measures for scoring dysphagia severity on VFSS should be explored for application to future s of OPMD.
2438
Authors: Carbone Salvatore , Van Tassell Benjamin , Abbate Antonio , Canada Justin , Buckley Leo F. , Johns Sade , Kadariya Dinesh , Moeller F. Gerard
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Cocaine use is a significant health problem in the United States and associated with increased risk of adverse cardiovascular outcomes. Our goal was to evaluate the effects of rapid cocaine infusions on cardiovascular hemodynamics among patients with cocaine abuse disorder. METHODS/STUDY POPULATION: Patients with a history of cocaine abuse but no overt cardiovascular disease received 4 consecutive intravenous infusions of cocaine (0, 10, 20, 40 mg) given in randomized, double-blinded order. The infusion procedure was repeated on 2 consecutive days (4 infusions each day). Following each dose, patients underwent continuous monitoring via fingertip plethysmography for 30 minutes, followed by an additional 30 minutes washout procedure. Patients were surveyed throughout this timeline to record symptoms of cocaine response. Finger tracings were then used to calculate arterial pressure curves and parameters of heart rate, blood pressure, cardiac output, stroke volume, and systemic vascular resistance according to device-specific algorithms. Mean values were calculated over the entire 30 minutes follow-up and peak values were defined as the maximum value sustained over any 60-second interval during the follow-up period. RESULTS/ANTICIPATED RESULTS: Seven patients were enrolled and received cocaine infusions of 2 consecutive days. Cocaine dose was positively associated with mean cardiac output (R=0.489, p<0.001), peak diastolic blood pressure (R=0.435, p=0.001), mean heart rate (R=0.401, p=0.003), peak systolic blood pressure (R=0.399, p=0.003), peak mean arterial pressure (R=0.362, p=0.008), mean systolic blood pressure (R=0.399, p=0.003), +dP/dt (R=0.346, p=0.012), and peak heart rate (R=0.334, p=0.015). Hemodynamic parameters were also predictive of patient-reported symptoms of cocaine response. DISCUSSION/SIGNIFICANCE OF IMPACT: These data confirm the known pharmacologic effect of cocaine to prevent reuptake of neurotransmitters and demonstrate the feasibility of conducting a noninvasive assessment of cardiovascular hemodynamics as a measure of responsiveness to cocaine infusions. This procedure also provides a benchmark to evaluate the potential impact of pharmacologic treatments on cocaine-induced hemodynamic changes and patient perceptions of cocaine response.
2409
Authors: Murdy Steven , Steele Scott J. , Adamo Joan E.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To develop a regulatory science case study as an educational resource to inform the regulatory science considerations in medical product development for a range of scientific priority areas and emerging technologies. METHODS/STUDY POPULATION: Precision medicine represents one of the major regulatory science priority areas and the use of biomarkers holds promise for predicting the response to individual treatment strategies. Although progress has been made toward developing biomarkers, the development and validation of clinically useful biomarkers has presented significant regulatory science challenges, including the utilization of biomarkers in predicting responses to different cancer therapies. This case study reviews the technical, regulatory, and policy issues related to the development and use of lung cancer drugs Opdivo® and Keytruda® and an understanding of the codevelopment and utilization of their associated biomarkers. RESULTS/ANTICIPATED RESULTS: A detailed instructor guide with extensive resources such as diagrams and timelines will accompany the case study and will be used to highlight the development and approval process of 2 competing drugs and their associated biomarkers. The resources will provide a better understanding of their progression through the FDA regulatory process and opportunities and challenges for their use. DISCUSSION/SIGNIFICANCE OF IMPACT: Building on the case study framework we have developed, the detailed timelines and a collection of available resources, an extensive and modular case study will be finalized and made available to academic institutions, industry, regulatory agencies, and the public. The full case study and links to a series of resources will be disseminated as a standalone resource for integration into courses or programs interested in learning about specific regulatory science needs and opportunities to enhance medical product development and approval.
2433
Authors: Abiola Solomon , Akinwale Olaoluwa , Dorsey Earl , Kautz Henry
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: This study sought to develop a mHealth application which was capable of predicting the spread of infectious diseases during the height of the Ebola outbreak in Lagos, Nigeria. Following the success of this primary task, the research then sought to understand behavioral health issues which are indicative of chronic diseases, such as sedentary behaviors and where they occur at a geospatial level in real-time. The results of this study are now being used to develop a larger scale 500 person study in Rochester, NY, USA. METHODS/STUDY POPULATION: During a 3-month period individuals were asked to install a mobile health application known as Node onto the their android device. Consent was done remotely, individuals were recruited through the Lagos University Teaching Hospital, Nigeria Institute of Medical Research, and the University of Lagos. Participants were paid 50 USD/month for each month of study completion, while continuous location data was collected in addition to survey information about participants. RESULTS/ANTICIPATED RESULTS: During the study period 70 individuals enrolled, using this data we were able to create network based models which indicated that diseases were more likely to spread at the beginning of the week, and also indicated who would be most susceptible to being patient zero. In phase 2 we have started to look at behavioral patterns to determine the risk of chronic disease among our study population, by examining their human mobility patterns, since we can determine average sleep patterns, activity patterns using machine learning classifiers, and time spent in traffic—all of which we can visualize in a real-time geospatial manner with higher objectivity than traditional mechanisms for data collection. DISCUSSION/SIGNIFICANCE OF IMPACT: In developing countries, using Nigeria as our example most chronic disease and household studies only enroll a few thousand participants for a country numbering 150 million plus. Using our rapidly available application we were able within 1 week to enroll 70 participants on 1 year of funding, this creates a framework for larger scale public health studies which can be done in developing countries and also demonstrates the value in mHealth which can both answer questions of infectious disease and chronic diseases at the same time. Our results indicate that at an infectious disease level in city environments diseases may be prevented by targeting events early in the week. While at a chronic disease level the lack of reliable power results in less sedentary behavior as individuals seek locations to charge phones, while those with more stable western-like lifestyles have started to exhibit the conditions which cause such outcomes as obesity, which has begun to rise in developing countries. Ultimately, these results serve as a staging point to launch a more wide scale study both in the United States and Nigeria within the year, now that feasibility has been established.
2142
Authors: Namenek Brouwer Rebecca , Snyder Denise
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Describe the process used to develop job descriptions and how this translates into consistent hiring practices. Describe how competencies are used to provide transparency into professional development opportunities. Discuss planned incorporation of competencies into efforts to train the clinical research workforce. METHODS/STUDY POPULATION: These processes were developed at Duke, an academic medical center with over 2000 active clinical research protocols and 300 new clinical trials per year. Over 1000 employees were evaluated for mapping into clinical research positions, with 685 mapping into new research positions (makeup of workforce to be depicted). RESULTS/ANTICIPATED RESULTS: Prior to this initiative, the clinical research workforce was not well-defined. Through the mapping process, employees were mapped from over 80 different positions into 10 (figure), resulting in a workforce that allows for visible career ladders and greater opportunity for development. As the initiative evolves and grows to include competency-driven performance evaluations, training modules, and assessments, we anticipate the ability to see the relationship between the competencies and high-quality clinical research support. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of competencies in the context of workforce development is not new, yet in clinical research, they provide a much-needed framework for an ever-evolving profession. This comprehensive use of competencies throughout a workforce development initiative is key to ensuring strong support of high-quality clinical research.
2151
Authors: Kennelly Okraku Therese , Leone Sciabolazza Valerio , Vacca Raffaele , McCarty Christopher
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: We aim to leverage our analysis of the scientific collaboration network at a research university to design an innovative pilot program and foster scientific productivity. We test the impact of creating a new collaboration in a research community, which decreases the average network distance and accelerates the diffusion of information and expertise among the community’s investigators. METHODS/STUDY POPULATION: We mapped the whole network of co-authorship on publications and co-participation on extramurally awarded grants at the University of Florida (UF) between 2013 and 2015. We used network science methods to identify research communities of investigators who have consistently worked together and/or have other collaborators in common with at least one researcher based in the UF Health Science Center. We selected pairs of communities with (i) similar productivity levels, research interests, and network structures and (ii) no research projects in common. Communities in each pair were randomly assigned to a treatment or control group. In each treatment community, we selected 1 pair of investigators who had not collaborated in the past 3 years and whose connection would maximally reduce average network distance in the community. The pair was provided with an economic incentive to collaborate for the submission of a CTSA pilot proposal. RESULTS/ANTICIPATED RESULTS: We successfully identified 15 pairs of treatment/control communities. In each of 8 treatment communities, a pair of potential collaborators agreed to participate in the intervention. DISCUSSION/SIGNIFICANCE OF IMPACT: Network-informed Clinical Translational Science Awards (CTSA) pilot programs can identify research communities and create innovative collaborations. Statistical experiments can establish the programs’ causal effects on scientific productivity.
2235
Authors: Arwood Meghan J. , Rowe McDonough Caitrin , Cavallari Larisa H. , Elsey Amanda R. , Frye Reginald F. , Gong Yan , Johnson Julie A. , Weitzel Kristin W. , Langaee Taimour
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Compare effectiveness of a patient case-based, interactive teaching approach that included optional student genotyping with traditional didactic teaching strategies for increasing students’ knowledge and ability to effectively use pharmacogenomic data in clinical decision making. METHODS/STUDY POPULATION: The UF College of Pharmacy offers a required Personalized Medicine (PM) course for pharmacy students as well as an elective course, Clinical Applications of Personalized Medicine (CAPM). Students dual enrolled in the PM and elective CAPM courses comprised the intervention (INT) group, with interactive patient case-based teaching and the option to undergo personal genotyping, whereas students enrolled in PM alone comprised the control (CTR) group, which primarily used a traditional didactic teaching format and did not include personal genotyping. Both groups completed a pre- and post-course patient case-based test (15 questions/1 point each) to evaluate their knowledge and abilities to apply genotype and other patient-specific data to drug therapy recommendations. Pre- and post-course test scores for knowledge were compared between the INT and CTR groups using the Student t-test. RESULTS/ANTICIPATED RESULTS: In total, 52 students completed surveys (INT group, n=21; CTR group, n=31). Race was similar between groups, but there were fewer females in the INT compared with CTR group (8 vs. 22, p=0.02). Pre-course knowledge scores did not differ between INT and CTR groups (6.8±2.2 vs. 6.3±1.6 respectively, p=0.34), however, post-course scores were significantly higher in the INT Versus CTR group (10.0±2.3 vs. 7.5±1.7, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: There have been significant advancements in the clinical applications of pharmacogenomic and genomic data, however, barriers to routine clinical adoption of genomic medicine persist. Developing education and training methods that equip practitioners to effectively translate genomic data into evidence-based clinical recommendations has been identified as a key strategy to overcome such barriers. Our data suggest that a personalized medicine course that employs patient-centered, case-based teaching strategies and includes optional personal genotyping for students compared with traditional didactic instruction improves students’ knowledge and abilities to apply pharmacogenomic data in practice-based scenarios. These results can inform future strategies for educating healthcare professionals on the clinical use of pharmacogenomic and genomic data.
2315
Authors: LeClair Amy , Rubin Carolyn ,   Addressing Disparities in Asian Populations through Translational Research
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Addressing Disparities in Asian Populations through Translation research (ADAPT) is a community-research partnership funded by the Tufts Clinical Translational Sciences Institute (CTSI). Founded in 2011, this collaborative brings together 7 Chinatown-serving community-based organizations and academic researchers with the goal of improving health for the local Chinatown community and beyond. The goal of this research project was to document the best practices, lessons learned, and process through which ADAPT has developed and grown. The aim of this project is to disseminate the model to other CTSAs who are currently engaged in METHODS/STUDY POPULATION: We used a combination of qualitative interviews and content analysis to gather data on the evolution of ADAPT over the last 5 years. Current members from both community organizations and the university/medical center were interviewed about their experiences participating in ADAPT. When possible, interviews were recorded and transcribed verbatim. Deidentified transcripts and administrative documents including meeting minutes, conference summaries, bylaws, and mission statements were coded using Dedoose analytic software. RESULTS/ANTICIPATED RESULTS: Established community-based participatory research (CBPR) principles, including mutual respect, transparency, and commitment, are viewed as necessary, but not sufficient. Patience—both with other members and with the group as a work in progress—is highlighted as being a necessary characteristic of participants. Time and funding are 2 of the most important resources, and the majority of members agree that there is no substitute for “skin in the game.” Attempts at last minute, opportunistic engagement were provided as examples of what had not worked. One ongoing tension is the balance between process and product. Individual members are beholden to organizations to different degrees, and the need to produce something in the form of publications or grant money can limit the amount of time members can commit to the collaborative. At the same time, these products are unlikely to materialize if members are not invested in the process of growing and sustaining the collective. DISCUSSION/SIGNIFICANCE OF IMPACT: Out of the 7 community organizations who currently participate in ADAPT, only 1 is explicitly focused on health in the traditional sense. The others are primary service organizations, but because they understand the impact of the social determinants of health on the local community—including housing, employment, education, nutrition, among other factors—the research collaborative is able to leverage the knowledge and expertise of the academic researchers and the community partners to focus on health topics most salient to the local Chinatown community.
2530
Authors: McKinney Bernadette
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Discuss ethical and policy issues that will impact clinical research. Raise awareness of the need to understand internal policies at home institutions Encourage further examination of ways to facilitate clinical research participation. METHODS/STUDY POPULATION: Ethical and policy analysis. RESULTS/ANTICIPATED RESULTS: Ideally, clinical research participants should not be required to pay to participate in research. However, if we go with an equity model, as opposed to an equality model, policies should be changed to allow equal access to research participation. This is a matter of justice and also will enhance the quality of the science. DISCUSSION/SIGNIFICANCE OF IMPACT: Unless steps are taken to make participation in clinical research less burdensome financially for participants, research may slow or results may be biased, because only those who can pay will be able to participate.
2074
Authors: Moreira Alvaro , Winter Caitlyn , Balgi Saloni , Mustafa Shamimunisa , Winter Lauryn , Hornsby Peter
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To compare functional differences in WJ-MSCs-derived from term Versus preterm infants. METHODS/STUDY POPULATION: WJ-MSCs were enzymatically digested from umbilical cord tissue from Term (gestational age ≥37 wk, n=4) and Preterm (gestational age ≤32 wk, n=5) neonates. Cells were characterized by (1) surface antigen markers using flow cytometry, (2) ability to differentiate into adipogenic, chondrogenic, and osteogenic lineages following in vitro stimulation, (3) colony forming unit efficiency, (4) proliferation rates, and (5) cell motility assay. RESULTS/ANTICIPATED RESULTS: WJ-MSCs were successfully isolated from both Preterm and Term groups. Cells adhered to plastic and displayed characteristic spindle-shaped morphology when cultured under standard conditions. WJ-MSCs from both groups expressed surface antigen markers CD73, CD90, and CD146 (≥90%) and did not express hematopoietic markers HLA-DR, CD79, or CD117 (<5%). Preterm and Term cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. There were no significant differences between the groups when evaluated by colony forming efficiency, proliferation rates, or cell motility. DISCUSSION/SIGNIFICANCE OF IMPACT: These preliminary findings suggest that WJ-MSCs derived from full-term or preterm neonates have similar functional characteristics. Future studies will focus on the regenerative potential of WJ-MSCs from preterm and term infants following changes in the microenvironment (eg, oxygen tension, inflammatory stimulation).
2080
Authors: Moreira Alvaro , Archambault Jamie , McDaniel Dawn , Hornsby Peter
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To assess the efficacy of exogenous administration of MSCs in animal models of HIE. METHODS/STUDY POPULATION: Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed using MEDLINE, Web of Science, CINAHL, and Google Scholar. Search term items included mesenchymal stem/stromal cell, hypoxic ischemic encephalopathy, asphyxia, cerebral ischemia, and neonatology. We selected randomized and nonrandomized studies that examined in vivo neonatal models of induced HIE. We excluded studies that combined MSCs with an adjunct therapy. Data were collected on study specifics, MSC characteristics, and outcome measurements. The primary outcome was efficacy of MSC treatment, assessed by functional neurologic measures (cognitive, motor, sensory). Risk of bias was assessed using the SYRCLE’s risk of bias tool and we used the ARRIVE guidelines to describe the quality of study reporting. RESULTS/ANTICIPATED RESULTS: A total of 17 preclinical publications focusing on MSC therapy for HIE met our inclusion criteria. Fifteen of the studies (88%) induced HIE in rodents by ligating the common carotid artery followed by a period of hypoxic exposure. Nine (53%) studies derived their MSCs from rodent bone marrow, whereas the other investigators provided xenografts from human bone marrow or umbilical cord-derived MSCs. Range of MSC dose was between 0.25 and 3.5× 106 cells with 71% of the experiments transplanting the MSCs intranasally or intracerebral. Three studies (18%) administered multiple doses. The cylinder rearing test was the most common (73%) sensorimotor functional outcome performed in the first month following the establishment of HIE. All studies demonstrated a reduction in asymmetrical paw preference after receiving MSC therapy. Lesional size was assessed, using neuroimaging or histologic evaluations, and the majority of studies showed a decreased insult following MSC therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: MSC treatment demonstrates improved functional and structural outcomes that are encouraging for future translational studies.
2136
Authors: Qayed Muna , Arafat Dalia , Banskota Samridhi , Horan John , Waller Edmund , Gibson Gregory
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Aim 1: To compare microbiome diversity among patients who develop BSI post hematopoietic stem cell transplantation (HSCT) and patients without BSI. Aim 2: To compare microbiome diversity among patients who develop moderate to severe acute GVHD post HSCT and patients without GVHD. Aim 3: To describe alterations in specific bacterial orders (Enterobacteriaceae, Clostridia, and Lactobacillales) in pediatric patients undergoing HSCT. METHODS/STUDY POPULATION: Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from stool specimens collected at baseline (start of preparative regimen to transplant day), early (day 7–14 post HSCT), and late (day 21–28 post HSCT) from 46 children was performed. Microbiome diversity was assessed by the Shannon index as well as UniFrac analysis, and compared among patients with and without GVHD/BSI. Baseline bacterial diversity was compared among patients by primary diagnosis, race, timing of antibiotic introduction and method of supplemental nutrition. RESULTS/ANTICIPATED RESULTS: Median age was 9 years (range 0.5–19.2 years). There were 36 patients with hematologic malignancies. Patients with nonmalignant disease had a characteristic pattern of microbiome diversity (and microbiota order distribution) at baseline that persisted throughout the first month of transplant (p=0.004). Over all patients, there was an early and persistent drop in microbiome diversity throughout the transplant course. Early introduction of broad spectrum antibiotics (prior to transplant day) negatively impacted microbiome diversity (p=0.02). There was no difference in microbiome diversity among patients who developed BSI, when compared with patients without BSI. Similarly, we did not find an association between microbiome diversity and the development of moderate to severe acute GVHD. Ongoing analysis is examining the individual variations in microbiome at the species level, and their relation to transplant characteristics and clinical outcomes. DISCUSSION/SIGNIFICANCE OF IMPACT: In our analysis, microbiome diversity decreased during HSCT, but in contrast to published data, mainly in adult HSCT populations, we found no association between gut microbiome diversity and GVHD or BSI. There are ongoing clinical trials in children and adults using probiotics in HSCT with the aim of decreasing GVHD. Further analysis of our data at the species level may further inform the relationship between gut microbiome alterations and HSCT complications in children and guide clinical interventions.
2219
Authors: Kurani Shaheen , Madigan Nicolas , Clark Karl , Ekker Stephen , Staff Nathan , Windebank Anthony
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The current treatment for amyotrophic lateral sclerosis (ALS) includes systemic delivery of neurotrophic factors (NTFs). Although this approach may seem theoretically sound, NTF efficacy within the central nervous system (CNS) is largely limited by the blood-brain barrier. Thus, a cell-based approach, which allows for targeted delivery of molecular therapies locally from the CNS, could lead to a paradigm shift in the field. METHODS/STUDY POPULATION: The Windebank and Staff group at Mayo Clinic completed a Phase I dose-escalation safety trial of autologous, adipose-derived mesenchymal stem cells (adMSCs) in an effort to move toward personalized medical treatment of ALS. The adMSCs were injected into the intrathecal space by lumbar puncture in 27 patients and the results showed an excellent safety profile across a range of doses. The team is moving forward with this idea by using gene-editing technology to develop clinical-grade, genetically modified autologous MSCs. The patient-derived adMSCs are modified at defined “safe-harbor” regions of the human genome through transcription activator-like effector nuclease (TALEN) technology. RESULTS/ANTICIPATED RESULTS: Our results show that electroporating adMSCs with plasmid DNA leads to efficient GFP or TALEN transgene expression, but yields low cell survival and a low rate of genetic modification. DISCUSSION/SIGNIFICANCE OF IMPACT: It can be concluded that: (1) TALEN technology may be used to target safe harbor loci for gene integration to produce therapeutic adMSC for ALS. (2) Primary barriers to adMSC modification are inefficient TALEN and donor template uptake, low cutting efficiency, and poor cell survival after electroporation. Future directions include optimizing the protocol to obtain 48 base pairs in the homology arms and increasing transfection efficiency.
2249
Authors: Dinwiddie Darrell , Dehority Walter , Schwalm Kurt C. , Langley Raymond J. , Young Stephen A. , Kennedy Joshua L.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Respiratory viruses cause enormous medical burden, yet many of the specific virus and host genetic factors that impact pathogenesis are still largely unknown or poorly understood. To better understand the drivers of both acute clinical pathogenesis and long-term impacts, such as the development of asthma, we investigated the host response to respiratory syncytial virus (RSV) infections in pediatric patients. METHODS/STUDY POPULATION: We collected nasopharyngeal swabs from 32 pediatric patients with acute RSV infection. The swabs represented a mixed cell population including epithelial and immune cells at the active site of infection. Unbiased RNA sequencing with ribosomal RNA depletion allowed the simultaneous detection of host gene expression and RSV infection. We sequenced samples 2×75 bp on an Illumina NextSeq 500. Sequences were mapped to the human genome using the TopHat 2 aligner and FPKM estimation of reference genes and transcripts and assembly of novel transcripts were conducted with Cufflinks 2. RESULTS/ANTICIPATED RESULTS: During acute RSV infection we identified 7343 genes that were significantly expressed. Pathway analysis using KEGG revealed significant upregulation of pathways involved in innate immune response infection, ribosome function, oxidative phosphorylation, spliceosome and autoimmune disorders. We found high levels of innate immune response genes including CXCL8, IFITM1, IFITM2, IFITM3, IL1RN, and ISG15. In comparing RSV subtype A to RSV B we found significant differential expression of multiple noncoding RNAs. DISCUSSION/SIGNIFICANCE OF IMPACT: Examination of the host gene response during acute RSV infections, yielded important insight into the mechanisms that cause clinical pathogenesis and may provide understanding of the mechanisms that lead to known long-term impacts, such as the development of asthma. Together, this data may be used to guide clinical treatment and management decisions for children with severe RSV infections.
2299
Authors: O’Brien Kevin , Basso Michele , Schmiedeler James
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Incomplete spinal cord injury (iSCI) is a life-long disability that typically results in a profound loss of locomotion capability. Current rehabilitation methods rarely restore full community ambulation, which in turn limits quality of life. Most individuals with iSCI exhibit persistent deficits in eccentric muscle control and reach recovery plateaus below the levels necessary for independent community ambulation. Eccentric motor control is essential during the weight acceptance phase of gait, which is emphasized during downhill walking. METHODS/STUDY POPULATION: The overground locomotion of subjects with chronic iSCI was analyzed both prior to and following a 12-week downhill body-weight-supported treadmill training regimen and compared to that of matched healthy controls in terms of kinematics, kinetics, and EMG activation. RESULTS/ANTICIPATED RESULTS: We expect to find significant differences between the controls and subjects with iSCI, with deficits in eccentric motor control accounting for some of these differences. In addition, we expect the downhill training to yield significant improvement in eccentric muscle control that translates into improvements in functional, overground walking for the subjects with iSCI. DISCUSSION/SIGNIFICANCE OF IMPACT: The goal is to determine if downhill training can improve eccentric motor control and extend recovery beyond established plateaus. OpenSim modeling of the experimental data will help quantify changes in eccentric control of individual muscles to clarify where specific gains are made.
2370
Authors: Stojanovska Jadranka , Chenevert Thomas , Tsodikov Alex , Lumeng Carey , Burant Charles
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The goal is to understand the underlying mechanism of epicaridial fat biology and its response to cardiometabolic disease by using quantitative multi-echo Dixon (mDixon) of water and lipid sequence, T2* blood-oxygen-level-dependent (BOLD) sequence of iron content, and data analysis methods to determine the quantity of brown Versus white fat. To accomplish this goal, we propose to define the histological, genetic, and metabolite state of epicardial fat and to confirm the relationship between fat phenotype and magnetic resonance (MR) characteristics. We will then investigate whether MR is more effective in identifying patients with lower cardiovascular disease risk than computed tomography (CT). METHODS/STUDY POPULATION: We will recruit 100 patients undergoing open-heart surgery and will quantify mDixon (proton density fat fraction), BOLD (T2*), and T2/T1 maps of epicardial, extrapericardial, and subcutaneous fat before their surgery. We will then (a) validate MR findings by direct depot-specific tissue analysis for lipid content, histological, and genetic markers of inflammation and brown and white fat, (b) develop plasma and fat depot specific metabolite profiling of cardiovascular disease risk and correlate with imaging characteristics. We will categorize cardiovascular risk score (Cardiovascular Health Status) of our 100 patients on quartiles. We will then build models where the categorized cardiovascular risk score are regressed on MR measures (epicardial fat fraction, T2*, and T2/T1 maps) and CT measures (epicardial fat volume and coronary calcium score). RESULTS/ANTICIPATED RESULTS: We anticipate to learn about epicardial fat biology and the role of inflammation in cardiometabolic disease. We will validate proton density fat fraction, T2* and T2 map against histology of epicardial fat for lipid content, established markers of brown and white fat and inflammation, respectively, to help us translate imaging technique to clinical practice. In respect to our second aim we anticipate that MR identifies patients at lower cardiovascular risk quartile than CT. DISCUSSION/SIGNIFICANCE OF IMPACT: Interest in epicardial fat as a visceral fat of the heart and coronary arteries is rapidly growing as the scientific based evidence indicates that the anatomic specificity is an important contributor to the cardiovascular diseases. The transformation of epicardial fat from a cardioprotective phenotype to a pro-inflammatory, atherosclerosis-promoting state triggers inflammation that is coincident with the expansion of epicardial fat volume detected by anatomic imaging. This study will impact the management of patients at risk for cardiovascular disease because it will demonstrate that quantification of epicardial fat status by MR identifies fat tissue changes validated by histology at lower cardiovascular disease risk quartile than CT.
2477
Authors: Wilder-Smith Petra , Ajdaharian Janet , Golabgir Anbarani Afarin , Ho Jessica , Sahni Karan , Mittal Richa , Potma Eric
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The specific objectives of this project are (1) identify, test, and validate the parameters for a simplified NLOM imaging probe that will provide specific research and point-of-care information on biofilm presence, therapeutic need and response of individual wounds to treatment. (2) Identify specific proteomic and metabolomic biomarkers of (i) wound susceptibility to infection, (ii) wound response to the most commonly used antibacterial measures in wounds, and (iii) establish criteria for more effective interventions. METHODS/STUDY POPULATION: First, optimal use parameters for NLOM including illumination, field of view, focal length, linear Versus concentric image acquisition, detection and filter wavelengths were identified. Parameters for evaluation included ease and speed of imaging, ability to map diagnostic criteria. Next, using the optimised NLOM imaging modality in bacterial biofilm isolates and subsequently a rabbit ear model of biofilm wound infection, proteomic and metabolomic biomarkers of susceptibility to infection were identified. The effects of 2 standard debridement and anti-infective treatments, polyvidone-iodine solution or cetrimide 15%+ chlorhexidine gluconate 1.5% were mapped in situ for up to 10 days using the NLOM probe. RESULTS/ANTICIPATED RESULTS: Using the novel custom NLOM probe, high resolution mapping of wound biofilm infection, as well as the underlying tissue was performed throughout the onset, development, treatment, and resolution of wound biofilm infection. Specific microbiological, microstructural, oxygenation, and pH parameters were mapped at defined surface and subsurface locations and time-points. Findings included the determination that some standard antimicrobial formulations provide a supportive environment for wound infection, and that micro-channels within the biofilm and their interface with the tissues serve as an important predictor and indicator of wound infection establishment, progression, and response. DISCUSSION/SIGNIFICANCE OF IMPACT: The novel multimodality in vivo NLOM imaging approach establishes an important tool for earlier and more specific diagnosis of wound infection risk, virulence, and invasiveness along with markers of successful treatment, and a simple clinical imaging tool for improving wound infection prevention and treatment.
2058
Authors: Gleason Kelly , Himmelfarb Cheryl Renee Dennison
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: (1) Determine person (sex, age, education level), environment (marital status, living alone, insurance), and health and illness (BMI, type of AF, comorbidities) characteristics that are associated with outcomes (QOL, symptom severity, and emotional and functional status). (2) Determine the association of symptom management strategies (ablation, cardioversion, and rate and rhythm control medications) and outcomes (QOL, symptom severity, and emotional and functional status). (3) Test person (sex, age, and education level) and environment (marital status, living alone, insurance) characteristics as moderators of the effect of symptom management strategies (ablation, cardioversion, and rate and rhythm control medications) on outcomes (QOL, symptom severity, and emotional and functional status). METHODS/STUDY POPULATION: AF patients (≥18 years of age) already enrolled in the PaTH study will be included. To date, 1026 total participants have been enrolled. Based on the enrolled participants, 92% (945) of our study population are Caucasian and 36% (362) are female. The age range of the enrolled participants is: 2% (16) 18−39, 4% (42) 40−49, 11% (108) 50−59, 33% (343) 60−69, 34% (353) 70−79, and 16% (162) 80+. Participants are recruited through in-person, email, phone, patient portal messaging and post mail techniques to ensure a representative sample. The PaTH study integrates electronic health record and insurance claims data with patient-reported outcome measures collected through online surveys. RESULTS/ANTICIPATED RESULTS: We hypothesize that sex, older age, low education level, living alone, absence of partner, absence of insurance coverage, high BMI, and a high number of comorbidities will be associated with lower QOL, high symptom severity, and low emotional and functional status. We further hypothesize that symptom management strategies will be associated with higher QOL, low symptom severity, and high emotional and functional status, and that these associations will be moderated by person and environment characteristics. DISCUSSION/SIGNIFICANCE OF IMPACT: The proposed research is an important first step in determining potential causes of person and environment differences in symptom severity. It will lead to tailored symptom management interventions for individuals most at risk for experiencing high symptom severity.
2152
Authors: Ortiz Ana I. , Jorge Juan C. , Guerrios Lourdes
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The goal of this pilot study is to provide a reliable anatomical algorithm for the measurement of adipose tissue within the pelvic cavity as a predictor of prostate cancer aggressiveness and recurrence after radical prostatectomy. METHODS/STUDY POPULATION: We will conduct a retrospective analysis of men treated with radical prostatectomy between 2012 and 2016 at the VA Caribbean Health Care System. Clinical variables, pathology reports, and computed tomography will be reviewed. Pelvic and periprostatic fat (PF) will be measured to determine association between PF and cancer aggressiveness and recurrence. RESULTS/ANTICIPATED RESULTS: We expect a positive association between PF and cancer aggressiveness and recurrence among patients who underwent radical prostatectomy. DISCUSSION/SIGNIFICANCE OF IMPACT: Measurement of subcutaneous and PF within the pelvic cavity can provide a reliable anatomical measure which can be used as a proxy measure to identify those with higher risk of recurrence and develop better prevention and treatment strategies, especially in Hispanic men.
2162
Authors: Anderson Alyce J. M. , Ramos-Rivers Claudia , Click Benjamin , Cheng Debbie , Koutroubakis Ioannis , Al Hashash Jana , Dunn Michael , Schwartz Marc , Swoger Jason , Barrie Arthur , Regueiro Miguel , Binion David
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Inflammatory bowel disease (IBD) patients are at an increased risk of Clostridium difficile infection (CDI) but the impact of CDI on disease severity is unclear. The aim of this study was to determine the effect of CDI on long-term disease outcome in a cohort of IBD patients. METHODS/STUDY POPULATION: We analyzed patients enrolled in a prospective IBD natural history registry. Patients who tested positive at least once formed the CDI positive group. We generated a 2:1 propensity matched control cohort based on risk factors of CDI in the year before infection. Healthcare utilization data (emergency department use, subsequent hospitalizations, telephone encounters), medications, labs, disease activity, and quality of life metrics were temporally organized. RESULTS/ANTICIPATED RESULTS: A total of 198 patients (66 CDI, 132 matched controls) were included [56.6% female; 60.1% Crohn’s disease (CD), 39.9% ulcerative colitis (UC)]. Groups were not significantly different in the year before infection in all metrics but in the year of infection, having CDI was significantly associated with more steroid and antibiotic exposure, elevated C-reactive protein or erythrocyte sedimentation rate, and low vitamin D (all p<0.01). Infection was associated with increased disease activity metrics (UC: p=0.036, CD: p=0.003), worse disease-related quality of life (p=0.003), and increased healthcare utilization (p<0.001). In the next year after infection those with prior CDI continued to have increased exposure to vancomycin or fidaxomicin (p<0.001) and all other antibiotics (p=0.01). They also continued to have more clinic visits (p=0.006), telephone encounters (p=0.001), and worse disease-related quality of life (p=0.03), but disease activity and biomarkers of severity were not significantly different between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: CDI infection in IBD is significantly associated with various surrogate markers of disease severity, increased healthcare utilization and poor quality of life during the year of infection. CDI patients continue to experience poor quality of life after infection with increased clinic visits and antibiotic exposure while disease activity is no longer significantly increased. These findings suggest that CDI infection may have a lasting effect on healthcare utilization beyond the acute treatment period.
2283
Authors: Campbell Kelsey , Lin Joanne C. , Brunner Robert C. , Novack Thomas A. , Younger Jarred W.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: In this pilot study, we are testing a new approach for detecting neuroinflammation in individuals who have sustained a traumatic brain injury (TBI). We hypothesize that many long-term adverse consequences of TBI are driven by abnormal inflammatory processes in the brain that occur secondary to the original neural injury. This inflammation can spread well beyond the damaged tissue and cause profound fatigue, widespread pain, cognitive impairment, and depressed mood. METHODS/STUDY POPULATION: Using a technique based on magnetic resonance spectroscopy, we can obtain precise and accurate temperature measurements throughout the human brain, which may serve as a proxy for neuroinflammation. In this study, we examine 20 men who have sustained a moderate-to-severe TBI and 10 age-matched healthy men without history of TBI. Temperature is assessed on a voxel-by-voxel basis throughout the entire brain. Cognitive ability is measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Information on pain, fatigue, and mood is collected through questionnaire. RESULTS/ANTICIPATED RESULTS: We anticipate that (1) average whole-brain temperature will be significantly higher in the TBI group than the healthy control group; (2) severity of (a) pain, (b) fatigue, and (c) mood symptoms will be correlated with brain temperature; and (3) severity of cognitive impairment will be correlated with brain temperature. DISCUSSION/SIGNIFICANCE OF IMPACT: If the hypotheses are confirmed, this tool will fill a need for objective tests of TBI pathology that can be used to improve diagnostic and treatment decisions and predict long-term functioning. This test would be the first completely noninvasive tool for detecting neuroinflammation, and will allow for safe and inexpensive longitudinal testing. Ultimately, we hope this noninvasive scanning technique will accurately track neuroinflammation in TBI, leading to more targeted and effective treatments.