The University of California (UC) Davis Clinical and Translational Science Center has established the “Join the Team” model, a Clinical Research Coordinator workforce pipeline utilizing a community-based approach. The model has been extensively tested at UC Davis and demonstrated to generate a viable pathway for qualified candidates for employment in clinical research. The model combines the following elements: community outreach; professional training materials created by the Association for Clinical Research Professionals and adapted to the local environment; financial support to trainees to encourage ethnic and socioeconomic diversity; and internship/shadowing opportunities. The program is tailored for academic medical centers (AMCs) in recognition of administrative barriers specific to AMCs. UC Davis’s model can be replicated at other locations using information in this article, such as key program features and barriers faced and surmounted. We also discuss innovative theories for future program iterations.

OBJECTIVES/SPECIFIC AIMS: By combining clinical knowledge of hoarding disorder (HD) with qualitative methods from cultural anthropology, we hope to build a patient-centered approach that will allow us to better understand the clinician perspectives on patient motivations and explanatory models of individuals with HD, and improve treatment outcomes. We describe the ways that these methodologies are productively merged in this project as a result of TL1 collaboration, and present a preliminary picture of methodological and theoretical issues uncovered as part of this processes. We further describe the analytical methods used for this project, and explore issues raised through the combination of psychological and anthropological data and insights. METHODS/STUDY POPULATION: This study represents an attempt to combine the qualitative methodologies of cultural anthropology with the clinical knowledge of psychology and psychiatry in order to better understand gaps between provider and patient beliefs and knowledge about hoarding disorder. This study will present preliminary methodological issues arising from interviews with hoarding experts. RESULTS/ANTICIPATED RESULTS: This study will discuss preliminary issues including shared language, strengths and limitations of both disciplines, and factors for consideration when combining these disparate methodologies. It will close with recommendations for consideration when moving forward with similar collaborations. DISCUSSION/SIGNIFICANCE OF IMPACT: This project seeks to unite psychological and social factors that may contribute to the lived experience of individuals with HD in order to better understand the way that HD is manifested. It also unites disparate methodologies to provide us with a more holistic and complete picture of the experience of HD. While HD has been studied within psychiatry, it has never been assessed using the qualitative methods of anthropology. These methods provide the possibility of expanding knowledge about the ways that this disorder is experienced by individuals and their families, and potentially impacted by shared beliefs and cultures. Furthermore, qualitative data of this nature provides a patient perspective on the experience of HD as a psychiatric illness. This patient perspective can be used to better inform treatment, improve patient outcomes, and to allow providers and researchers to gain a fuller understanding of this complex population.

OBJECTIVES/GOALS: The characterization of the zebrafish as an animal model for Cockayne Syndrome may guide us towards role of Transcription-Coupled Nucleotide Excision Repair (TC-NER) defects in sensorineural hearing loss. METHODS/STUDY POPULATION: To examine our model, we have developed a zebrafish line with a 9+1 base-pair deletion in the ercc6 gene using TALENs. Mutation has since been confirmed by PCR and subsequent restriction digest with StuI. A series of assays evaluating hair cell morphology, structure and function, as well as ribbon synapse structure, will be used to analyze potential differences between the ercc6 mutant zebrafish line a their wild-type siblings. Additionally, electron microscopy will be used to assess differences in hair cell ultrastructure between the ercc6 mutant zebrafish line a their wild-type siblings. Finally, UVC exposure assays will be used to determine the role TC-NER plays in our novel zebrafish model, and evaluate its potential implications in sensorineural hearing loss. RESULTS/ANTICIPATED RESULTS: We anticipate that biallelic loss of function mutations in the zebrafish ercc6 gene will result in abnormalities in hair cell structure, mechanotransduction, or cell number. Additionally, we anticipate that hair cell ultrastructure and ribbon synapse structure will be impacted by loss of ercc6 expression. DISCUSSION/SIGNIFICANCE: Hearing loss mechanisms associated with defects in TC-NER are yet to be described. We believe our model will provide the tools for a faster and efficient way to carry out Cockayne Syndrome studies while laying the groundwork for the association between TC-NER and hearing loss.

OBJECTIVES/GOALS: Using a natural canine model of kidney stone disease, we previously identified a pathogenic variant in the uromodulin gene (UMOD) that imparts a dramatic risk for calcium oxalate (CaOx) stones. This study was designed to characterize the effects of the pathogenic variant on uromodulin processing, specifically polymerization and peptide excretion. METHODS/STUDY POPULATION: Uromodulin polymerization status and peptides were measured in random urine samples from CaOx stone-forming dogs with the pathogenic UMOD variant and breed-, sex-, and age-matched healthy control dogs. Polymerization status was determined using an ultracentrifugation protocol and Western blotting in 6 CaOx cases and 3 controls; relative abundance of the polymerizing and nonpolymerizing forms was evaluated. Uromodulin peptide abundances were measured by LC-MS/MS with 4 dogs per group; results were summed to determine total uromodulin peptide excretion for each dog, and individual peptide abundances were calculated as a percentage of the total. Polymerization status and peptides were compared between groups. RESULTS/ANTICIPATED RESULTS: Dogs with the pathogenic UMOD variant had abnormalities in both uromodulin polymerization and peptide processing. The polymerization data showed that the polymerizing form of uromodulin was abundant in all healthy controls but absent or severely reduced in most dogs with the variant. In contrast, nonpolymerizing uromodulin was detected in all dogs with no observed difference between those with and without the variant. The peptidomics data showed that stone-forming dogs with the pathogenic UMOD variant lacked a peptide cleavage site, resulting in the loss of two common peptides that terminate at that site and the presence of longer peptides that span the site. DISCUSSION/SIGNIFICANCE: These findings implicate uromodulin polymerization and peptide processing defects in kidney stone risk. Future studies will define the mechanisms through which these defects affect stone formation, ultimately informing development of novel preventative therapies.

OBJECTIVES/SPECIFIC AIMS: To identify characteristics of counties with persistently high opioid-overdose rates and low capacity to deliver medications for OUD (MOUD). METHODS/STUDY POPULATION: Setting: County-level opioid-overdose death data, 2013-2016, and 2017 publicly-available treatment provider data for MOUD: buprenorphine-waivered providers, opioid treatment programs (OTPs), and extended-release naltrexone providers. Participants: Populations in 3,142 U.S. counties. 24,851 buprenorphine-waivered providers; 1,517 OTPs; and 5,222 extended-release naltrexone providers. Measurements: The outcome variable, “opioid high-risk county”, was a binary indicator of high (above average) opioid-overdose rates with low (below median) MOUD availability rates. We used spatial logistic regression models to determine correlates of being a high-risk county. RESULTS/ANTICIPATED RESULTS: 46.4% of all counties, and 71.2% of rural counties, lacked a publicly-available MOUD provider in 2017. In adjusted models, rural counties had 53% greater odds of being high-risk than urban counties. Counties in the East South Central, West South Central, and South Atlantic divisions had over twice the odds of being high-risk than counties in the West North Central division. Primary care provider density, greater traversability, and a higher proportion of the population under age 25 were all protective against a county being opioid high-risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Counties with both low MOUD provider availability and high opioid-overdose death rates are significantly more likely to be rural, have less primary care providers per capita, and in the southern regions. Strategies to increase MOUD must account for these factors.

OBJECTIVES/GOALS: Load sharing across the arc of knee flexion of the medial knee ligaments (MKLs) is not well understood. The goal of this research is to characterize ligament engagement and in-situ force within the deep and superficial medial collateral ligament (dMCL, sMCL) and the posterior oblique ligament (POL) in response to externally applied multiplanar loads. METHODS/STUDY POPULATION: Ten human cadaveric knees, 5 male and 5 female, age 32±7 (25-42) [mean±SD (range min-max)] years, were mounted to a force sensor and a 6-degree-of-freedom robotic arm. Knee kinematics, before and after serial dissection of the sMCL, dMCL, and POL, were recorded from 0-30 degrees during applied isolated external rotation, valgus angulation, and anterior tibial moments, and the force (Newtons, N) borne by each structure was measured via the principle of superposition. Loads in the dMCL, sMCL, and POL will be compared across each knee and at each flexion angle with paired t-tests and repeated-measures analysis of variance with Tukey post hoc testing. Ten knees will provide >99% power to detect differences of 5N ± 3% at p=0.05, which is considered the threshold for clinically meaningful force differences. RESULTS/ANTICIPATED RESULTS: Our anticipated results include characterization of the means and standard deviations of the in-situ forces within the dMCL, sMCL, and POL in response to externally applied valgus angulation, tibial external rotation, and anterior-directed tibial loading at 0, 15, and 30 degrees of knee flexion. Our statistical analysis will determine if there are clinically meaningful differences (5N ± 3%) in the loads within each ligament at different knee flexion angles and will also provide data regarding differential relative ligament engagement for each applied force scenario, which is an indication of the percentage of contribution that each structure contributes to knee stability during application of forces and torques to the knee. DISCUSSION/SIGNIFICANCE: Data on ligament engagement and in-situ forces will help clinicians better diagnose potentially injured ligaments when they observe pathological knee laxity in an injured patient. Our results will also inform future computer modeling studies on injury mechanisms, individual anatomical variability, and surgical planning.

Objectives/Goals: This study assesses the feasibility of a human-to-swine lung transplant model for the evaluation of bioengineered organs. Given the critical organ shortage, this research explores bioengineered organs as a potential solution by evaluating early lung function, immune responses, and technical aspects to develop a model for bioengineered lungs. Methods/Study Population: The study employs a non-survival human-to-swine left lung transplant model in an immunosuppressed Yorkshire swine. A combination of cobra venom factor pretreated with methylprednisolone and Benadryl with scheduled dosing of tacrolimus and mycophenolate over a 24-hour period will be administered. The transplanted human lung is assessed over a 24-hour post-transplant period, with hourly pulmonary vein gas sampling and lung tissue resections. The proposed model will assess the immunological response of swine to human lung tissue as well as the efficacy of the immunosuppression model. Tissue samples are taken at intervals to evaluate for signs of rejection, cellular damage, and the overall function of the transplanted lung. All tissues are preserved in formaldehyde for subsequent immunohistology evaluation. Results/Anticipated Results: We anticipate a successful non-survival swine transplant model with pulmonary function sustained for the full 24-hour study using our proposed immunosuppression regimen. Initial testing with a standard human lung will lay the groundwork to assess the effectiveness of the human-to-swine transplant model. Hourly pulmonary vein gas analyses and tissue biopsies are expected to show minimal immune rejection, supported by the preoperative immunosuppression regimen. Early data indicate that the swine tolerates both the surgical procedure and immunosuppressive therapy well, with manageable hemodynamic stability. This model is expected to yield critical insights into lung viability and will identify areas for optimization for long-term survival studies to test the efficacy of bioengineered organs. Discussion/Significance of Impact: This non-survival swine model offers valuable insights into the acute-phase immune response and functional viability of human-to-swine lung transplant model. The findings will support the development of long-term survival models that will allow the evaluation of bioengineered organs based solely on their functionality as engineered organs.

Objectives/Goals: The objectives of the study were to evaluate end-user feedback regarding usefulness and compliance with the revised DoD PRA-CR. The PRA-CR utilizes symptom-guided management strategies to advance service members with acute concussion through 6 stages of gradually increased activity prior to their Return to Duty (RTD). Methods/Study Population: Clinical providers previously trained on the PRA-CR were invited via email to participate in an online survey-based study to examine their opinions and utilization of the revised PRA-CR. Participants who responded to the initial email invitation were provided an electronic Microsoft Forms based survey. Of the 83 total responders, 36 met inclusion criteria and advanced to the end-user survey. Six items were designed to assess inclusion–exclusion criteria (i.e., credentialed medical provider trained in the PRA-CR with experience treating concussion over the previous 2 years). Four items gauging utilization required yes/no responses; 20 opinion items on a 7-point Likert scale ranged from strongly disagree to strongly agree; 5 explanatory items were multi-select; and 1 item allowed free text responses. Results/Anticipated Results: Overall, 87% of respondents who had used the revised CR indicated that it helped them treat patients with acute concussion and 73% rated, “ease of use” favorably. Of the newly added elements to the CR, utilization of the Patient Leadership Guide (PLG) was the highest at 78%, with the majority of the providers rating the PLG as useful in communicating with patients and command. In contrast, only 35% of participants reported using the Physical RTD screening section and 22% indicated using the Cognitive RTD screening tool. Those not utilizing the Physical screening identified a lack of support staff (67%) or setting barriers (47%) as the primary reasons. Those not utilizing the Cognitive RTD screening tool identified multiple barriers to use including availability (72%), inexperience (39%), and baseline data access (33%). Discussion/Significance of Impact: This study sought end-user (provider) feedback regarding the revised PRA-CR’s usability and utility, in addition to their confidence in the tool itself. Overall results were generally positive, except for the updated Physical RTD and newly introduced Cognitive RTD screenings.

ABSTRACT IMPACT: Better understanding how clinicians make decisions about pain management, particularly since our prior research has demonstrated that opioids prescribed at discharge is the strongest predictor of opioids taken, is critical to decrease high-risk medication prescribing while preserving high-quality care. OBJECTIVES/GOALS: (1) Identify major biological, psychological, and social determinants of medical and surgical residents’ pain management decisions; (2) Determine salient themes regarding the experience of residents in the management of acute and chronic pain METHODS/STUDY POPULATION: Focus groups of internal medicine and general surgery residents at an academic, tertiary care training hospital located in an urban setting were conducted. Due to the COVID-19 pandemic, all focus groups were conducted virtually and occurred during required didactic sessions to facilitate participation. All interviews were recorded and transcribed. Two reviewers independently reviewed and coded the data following the principles of constructivist grounded theory. RESULTS/ANTICIPATED RESULTS: 42 residents participated in ten focus groups ranging in size from two to five individuals. Six themes emerged demonstrating salient BPS factors in pain management decisions: (1) patient and clinician expectations determine what is considered normal/acceptable; (2) inability of pain scales to reliably capture patient pain; (3) desire for more objective methods of pain assessment, while simultaneously recognizing that pain is an inherently subjective experience; (4) difficulty in determine when pain is 'real’ or 'legitimate'; (5) lack of education and protocols regarding pain management; (6) the importance of engaging other services such as acute pain service or nurse educators in complicated situations. Junior residents often expressed doubt in the appropriateness of their approaches and decisions. DISCUSSION/SIGNIFICANCE OF FINDINGS: Surgical and medical trainees routinely treat pain and may struggle, particularly in the early phases of training, to determine if pain levels are appropriate. There is also a lack of education and/or best practices for assessing and managing pain. These areas represent high-value, clinician-focused targets for future interventions to improve care.

OBJECTIVES/GOALS: The goal of this study was to develop a clinically applicable technique to increase the precision of in vivo dose monitoring during radiation therapy by mapping the dose deposition and resolving the temporal dose accumulation while the treatment is being delivered in real time. METHODS/STUDY POPULATION: Ironizing radiation acoustic imaging (iRAI) is a novel imaging concept with the potential to map the delivered radiation dose on anatomic structure in real time during external beam radiation therapy without interrupting the clinical workflow. The iRAI system consisted of a custom-designed two-dimensional (2D) matrix transducer array with integrated preamplifier array, driven by a clinic-ready ultrasound imaging platform. The feasibility of iRAI volumetric imaging in mapping dose delivery and real-time monitoring of temporal dose accumulation in a clinical treatment plan were investigated with a phantom, a rabbit model, and a cancer patient. RESULTS/ANTICIPATED RESULTS: The total dose deposition and temporal dose accumulation in 3D space of a clinical C-shape treatment plan in a targeted region were first imaged and optimized in a phantom. Then, semi-quantitative iRAI measurements were achieved in an in vivo rabbit model. Finally, for the first time, real-time visualization of radiation dose delivered deep in a patient with liver metastases was performed with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the radiation dose deposition during treatment. DISCUSSION/SIGNIFICANCE: Described here is the pioneering role of an iRAI system in mapping the 3D radiation dose deposition of a complex clinical radiotherapy treatment plan. iRAI offers a cost-effective and practical solution for real-time visualization of 3D radiation dose delivery, potentially leading to personalized radiotherapy with optimal efficacy and safety.

OBJECTIVES/GOALS: This research has two goals. The first is to establish the relationship between hypertension, discrimination, and social cohesion in the general populaiton. The hypotheses for these relationships are:

• Hypothesis 1: Self-reported discrimination will be positively associated with incidence of hypertension in all REGARDS participants.

• Hypothesis 2: Self-reported neighborhood cohesion will attenuate the effects of discrimination on the development of hypertension.

• Hypothesis 3: Increased levels of Self-reported social cohesion will moderate the effects of discrimination on the likelihood of being hypertensive by weakening the relationship between discrimination and the likelihood of being hypertensive.

• Hypothesis 4: Self-reported discrimination will be positively associated with prevalent hypertension in black REGARDS participants over and above the association between discrimination and hypertension in white REGARDS participants.

• Hypothesis 5: Increased levels of self-reported social cohesion for will not moderate the effects of discrimination on the likelihood of being hypertensive by weakening the relationship between discrimination and the likelihood of being hypertensive as strongly for black REGARDS participants as it does for white REGARDS participants

METHODS/STUDY POPULATION: The population under investigation will be respondents to The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study at UAB. REGARDS participants are 45+ years old, and come from across the United States. The study will use the second wave of in-home data to assess relationships between discrimination, hypertension, and social cohesion. First we will calculate descriptive statistics (means and standard deviations or N and %) for each of the main variables and covariates. Modified Poisson regression will be used to model the association between discrimination and likelihood of hypertension, as well as the moderating effects of neighborhood social cohesion. We will run additional modified Poisson models including 1) demographic covariates (age, gender, race, rurality, education), 2) demographic covariates plus lifestyle factors, such as smoking status, BMI, exercise frequency, and 3) demographic covariates, lifestyle factors, and social characteristics, including insurance status, social support, getting around. To understand the main effect of social cohesion on hypertension, we will run a second set of models, following the same series of steps. A final series of models will test the interaction between perceived discrimination*perceived neighborhood cohesion. This model will be followed by the same series of steps as the global hypertension models. If the interaction is significant, postestimation will be used to model how different levels of perceived discrimination and cohesion are expected to interact to affect the likelihood of hypertension. If any of the covariates violates assumptions about distributions, data transformations will be explored. After conducting an analysis on the effects of discrimination on hypertension, and the buffering effect of social cohesion on the full sample population, the sample will be stratified by race so that the associations between discrimination, social cohesion, hypertension, and race are fully explored, consistent with previous literature. The stratified samples will be run through the same series of models as the full sample, providing information on how race, hypertension, and social cohesion are associated in and unadjusted models, models adjusted for demographic characteristics, models adjusted for sociodemographic and lifestyle characteristics, and finally full models that adjust for sociodemographic, lifestyle, and social characteristics. These models will compare each of these sets of characteristics, as well as the interaction between perceived discrimination* perceived neighborhood cohesion for stratified samples. This will allow researchers to compare the effects of discrimination, and the buffering effect of neighborhood cohesion across models. RESULTS/ANTICIPATED RESULTS: We anticipate that in a general population, social cohesion will attenuate the positive association of discrimination and hypertension. For blacks, however, higher levels of lifetime discrimination as well as lower levels of social cohesion in primarily black neighborhoods are expected to lead to both higher rats of hypertension and a lower degree of attenuation of the relationship between discrimination and hypertension. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will help to elucidate the social nature of hypertension. By examining how perceptions of discrimination and social cohesion are associated with hypertension, interventions directed at improving heart health will be able to be effectively implemented at the community level by targeting specific social factors that can improve health outcomes. In addition, this research will provide insight into groups that may be particularly vulnerable to hypertension, advancing both the sociological and cardiology literature as it relates to discrimination, social cohesion, race and health.

OBJECTIVES/GOALS: This study proposes a pragmatic approach for tracking institutional changes in research teamwork and productivity in real time using common institutional electronic databases such as eCV and grant management systems. Dissemination of this approach could provide a standard metric for comparing teamwork productivity across different programs. METHODS/STUDY POPULATION: This study tracks research teamwork and productivity using commonly available institutional electronic databases such as eCV and grant management systems. We tested several definitions of interdisciplinary collaborations based on number of collaborations and their fields of discipline. Publication characteristics were compared by faculty seniority and appointment type using non-parametric Wilcoxon Rank Sum Test (p RESULTS/ANTICIPATED RESULTS: Interdisciplinary grants constitute 24% of all grants but the trend has significantly increased over the last five years. Tenure track faculty collaborated with more organizations (3.5, SD 2.5 vs 2.3, SD 1.1, p DISCUSSION/SIGNIFICANCE: This study provides empirical evidence of the benefits of interdisciplinary collaboration in research and identifies an important role that senior faculty may be playing in creating the culture of interdisciplinary teamwork. More research is needed to improve efficiency of interdisciplinary collaborations.

OBJECTIVES/GOALS: Cachexia is the involuntary and irreversible loss of muscle and fat and is a major cause of morbidity and mortality in head and neck cancer (HNC). It remains a poorly understood disease diagnosed by weight loss and a confluence of symptoms. We explored the metabolic and inflammatory mechanisms of cachexia symptoms via an multiomics network algorithm. METHODS/STUDY POPULATION: Prior to chemoradiotherapy, HNC subjects completed questionnaires and donated blood for untargeted (metabolites) and targeted (lipids and cytokines) assays. Metabolites and lipids were measured by liquid chromatography mass spectrometry. Cytokines were measured by multiplex assays. We plotted a multiomics network graph by estimating partial least squares correlations amongst metabolites, lipids, cytokines, and common cachexia symptoms—max percent weight loss over 1 year, baseline BMI, fatigue, performance, albumin, hemoglobin, and white blood cell count. To interpret the network, an algorithm identified highly correlated clusters of metabolites-lipids-cytokines-symptoms representing possible biological relatedness, which were functionally annotated via metabolic enrichment analysis. RESULTS/ANTICIPATED RESULTS: In 123 subjects (59 years of age, 72% male, 84% white, avg weight loss of 13%), we analyzed 186 metabolites, 54 lipids, 7 cytokines and 7 cachexia symptoms. We required a correlation >0.25 and P-value <.05 to be included in the network graph, resulting in 323 connections and 3 identified clusters. Max weight loss and baseline BMI were in a cluster enriched by unsaturated fatty acid biosynthesis (P<.0001) and arachidonic acid (P=.01) metabolic pathways but not linked to inflammation cytokines. The five other cachexia symptoms were in a cluster with 4 cytokines (C-reactive protein, interleukin 6, IL10, IL1, Tumor necrosis factor receptor 2) and enriched by aminoacyl tRNA (P<.01) and valine biosynthesis (P=.02). We observed no meaningful differences when we stratified the analysis by human papillomavirus. DISCUSSION/SIGNIFICANCE: Cachexia symptoms in head and neck cancer may be linked to specific metabolic dysregulation—weight loss and BMI were linked to fatty acids; fatigue, anemia and others were linked to amino acids and inflammation. This information may allow for the recognition of a cachexic-metabolic subtype or provide novel targets for metabolic intervention.

OBJECTIVES/GOALS: Twenty years of evidence show CHW home-visits for asthma improve population health and lower overall health care system costs by reducing costly Emergency Department (ED) visits. We built a model to communicate these results to decision makers and demonstrate how program modifications can improve CHW program sustainability and long-term cost savings. METHODS/STUDY POPULATION: This CHW program simulation model (CHWsim) examines program level outcomes of sustainability and costs. CHWsim is populated with individuals in an asthma registry with frequent ED visits. The simulation shows the uptake of the CHW program, and the less frequent use of ED visits based on empirical data from a recent randomized controlled trial (RCT). CHWsim is interactive, allowing for parameter adjustments to programming and robust quantitative evaluation of those changes. We study sustainability using parameters based on number of CHWs, case load, frequency and duration of program. For cost outcomes, we use empirical data from a published return on investment study to demonstrate the cost of CHW programming vs. health care systems savings from reduced ED visits. RESULTS/ANTICIPATED RESULTS: We demonstrate a basic model that successfully simulates a recent RCT (n = 551), replicating the primary outcome of reduced ED visits within the Confidence Intervals. The model is validated by reproducing results of other RCTs. Results will also be presented from an in-process expanded model that simulates the intervention in a broader population (n = 4000). We test two programmatic changes and demonstrate how these modifications might improve health outcomes (reduced ED visits) that translate into cost savings to the system. 1) In the original trial, we served only one household member; in the model, we treat the full household, serving several individuals at the same time. 2) We also consider the assumption that a short annual visit might sustain the known 12-month health effect across many years. DISCUSSION/SIGNIFICANCE OF IMPACT: CHWsim uses individual level local data and patient characteristics to demonstrate the impact of program efficiencies to improve CHW program sustainability and reduce health care system costs without expensive new RCTs. CHWsim has the potential to improve CHW program delivery and influence funders to provide support.

ABSTRACT IMPACT: Our results reveal a limited amount of breast cancer survivorship print materials as both understandable and actionable, and indicate a need to supplement material with personalized teaching. OBJECTIVES/GOALS: Using educational print material for young women breast cancer survivors (YBCS) is considered a best practice in patient teaching. Little is known about how well YBCS understand or act upon the material. The purpose of this study was to assess the understandability and actionability of commonly distributed breast cancer survivorship print materials. METHODS/STUDY POPULATION: We used an environmental scan approach to obtain breast cancer survivorship print materials available in eight outpatient oncology clinics and one electronic medical record used in a Midwestern state. Print materials were included if they were freely available to patients, were specific to breast cancer, provided detailed information about survivorship, and were directly given to patients by physicians or nurses. Print materials were excluded if topics were related to treatment, diagnosis, or prevention. All brochures, drug advertisements, and advertisements for support services were excluded. The understandability and actionability analyses of the breast cancer survivorship print materials were analyzed using Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). RESULTS/ANTICIPATED RESULTS: The environmental scan resulted in 82 individual print materials. After applying the inclusion and exclusion criteria, eight breast cancer survivorship print materials were included in the final sample. The final sample included two books, two patient education handouts from the electronic medical record, two multi-page booklets, and two pamphlets. The overall mean understandability score of the print materials was 68.9% ? 11.3 with a range of 47% to 80%. Five materials scored above the recommended 70% in understandability. The overall mean actionability score of the print materials was much higher at 81.3% ? 21.6 with a range of 67% to 100%. Five materials scored above 70% in actionability. However, only three of the eight materials scored above the recommended 70% in both understandability and actionability. DISCUSSION/SIGNIFICANCE OF FINDINGS: Limited breast cancer survivorship print materials exist as both understandable and actionable. Personalized instruction provided by oncology team members may be indicated to supplement the material. This additional teaching may help ensure survivors comprehend messages and act upon specific tasks as indicated in survivorship print material.

OBJECTIVES/SPECIFIC AIMS: We present an alternative strategy to retain NTFs at an injected CNS tissue site by endowing them with binding affinity for carbohydrates that are abundant on the cell surface and within extracellular matrices. METHODS/STUDY POPULATION: We are creating recombinant fusions in which glial cell-derived neurotrophic factor (GDNF) is linked to galectin-3 (G3), a human protein that binds to extracellular beta-galactoside glycans and glycosaminoglycans. GDNF-G3 fusion proteins will circumvent major therapeutic shortcomings of early GDNF human trials by anchoring GDNF to the midbrain in a preclinical animal model of PD over a therapeutically-relevant timescale in order to achieve DA neuron rescue. Further, in PD patients, we have detected significantly dysregulated dopamine signaling in peripheral, blood-derived monocytes, suggesting a systemic dopamine signaling change in PD. RESULTS/ANTICIPATED RESULTS: Based on results from published human NTF administration trials, we anticipate that a successful intervention using GDNF-G3 will result in rescue or delayed degeneration of midbrain dopaminergic neurons in a murine PD model. Outcome measures include behavioral PD phenotype testing via rotarod and pole descent compared to non-parkinsonian control animals, as well as corroborating immunohistological evidence from immunohistochemical examination of post-mortem brain tissue from the same animals to examine degree of degeneration. DISCUSSION/SIGNIFICANCE OF IMPACT: Current treatments for PD, whether pharmacological or surgical, center on alleviating movement symptoms that impair daily function - in other words, largely palliative care. Little has been accomplished by way of rescue of dopaminergic neurons or slowing disease progression using standard-of-care therapy. If successful, GDNF-G3 constructs administered intracranially at the site of degeneration would represent a milestone on the path to treating the basic pathology associated with PD, while addressing major shortcomings in earlier NTF-delivery attempts, namely NTF diffusion away from target site.

Objectives/Goals: Motivational deficits are associated with depression and poorly treated by current therapeutics. We sought to identify more effective therapeutics for these deficits using a mouse model of early-life exposure to SSRIs, a developmental risk factor identified for depression in humans. Methods/Study Population: Mice were administered the SSRI, fluoxetine (FLX), or a vehicle control from postnatal day P2-P11, a window that mimics brain development occurring during the third trimester in a human pregnancy. Motivation and hedonic perception were assessed in adulthood using the progressive ratio and lickometer tasks, respectively. Behavioral testing was repeated after chronic adult administration of either an SSRI (fluoxetine), an atypical antidepressant and mu-opioid receptor agonist (tianeptine), or a mu-opioid receptor antagonist (methocinnamox). Results/Anticipated Results: Mice administered FLX in early-life showed motivational deficits in the progressive ratio task, while hedonic perception, as measured by the lickometer task, remained intact. Chronic administration of FLX in adulthood did not improve motivational deficits and did not alter hedonic perception. Chronic administration of tianeptine (TIA) slightly improved motivational behavior without altering hedonic perception. In contrast, chronic administration of the mu opioid antagonist methocinnamox (MCAM) markedly improved motivational deficits in mice, even while blunting hedonic perception. The ability of MCAM to enhance motivation was selective to early-FLX exposed mice Discussion/Significance of Impact: Our results reveal that unexpectedly opioid receptor antagonism is effective at improving motivation in mice exposed to SSRIs in early life. This suggests potential novel treatment approaches in individuals with motivational impairments and a history of in utero exposure to SSRIs.

Preparing investigators to competently conduct community-engaged research is critical to achieving Clinical and Translational Science Award (CTSA) program goals. The purpose of this study is to describe the perspectives of members of a long-standing community engagement advisory board (CEAB) on investigators’ readiness to engage communities and indicators of investigator competence in community-engaged research, in order to suggest core competencies to guide the development of CTSA-sponsored educational programs. Two 90-minute focus groups were conducted with a subset of members of a CEAB (n=19) affiliated with the Center for Clinical and Translational Science at the University of Illinois at Chicago. CEAB members identified a range of investigator skills and practices that demonstrate readiness to engage in community-engaged research. Eight competencies were identified that should be incorporated in providing education to enhance the readiness and competency of CTSA-affiliated researchers planning to engage communities in research. CEAB observations demonstrate the necessity of developing competency-based educational programs that prepare clinical and translational scientists at all levels for the important work of community-engaged research.

Single institutional review board (IRB) review of multisite research increased in frequency over a decade ago with a proliferation of master IRB reliance agreements supporting statewide and regional consortia and disease- and population-specific networks. Although successful, the increasing number of agreements presented significant challenges and illuminated potential benefits of a single, nationwide agreement. Anticipated changes in federal regulations highlighted the need to systematize and simplify IRB reliance. To address these challenges, the NIH National Center for Advancing Translational Sciences funded a project to establish a national IRB reliance network that would support national adoption of single IRB (sIRB) review. The Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB Platform launched in July 2016 to facilitate dissemination, adoption, and implementation of a collaboratively developed master IRB reliance agreement and supportive tools and resources. More than 580 institutions have joined SMART IRB’s Master Common Reciprocal Institutional Review Board Authorization Agreement and begun using the SMART IRB platform to support sIRB arrangements. Here, we describe the tenets of the agreement and operational benefits and challenges of its use. SMART IRB’s early success affirms the utility of collaborative, flexible, and centralized approaches to supporting sIRB review while highlighting the need for further national harmonization.