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.

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.

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.

Contactless photoplethysmography (cPPG) is a method of physiological monitoring. It differs from conventional monitoring methods (e.g., saturation probe) by ensuring no contact with the subject by use of a camera. The majority of research on cPPG is conducted in a laboratory setting or in healthy populations. This review aims to evaluate the current literature on monitoring using cPPG in adults within a clinical setting. Adhering to the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA, 2020) guidelines, OVID, Webofscience, Cochrane library, and clinicaltrials.org were systematically searched by two researchers. Research articles using cPPG for monitoring purposes in adults within a clinical setting were selected. Twelve studies with a total of 654 individuals were included. Heart rate (HR) was the most investigated vital sign (n = 8) followed by respiratory rate ((n = 2), Sp02 (n = 2), and HR variability (n = 2). Four studies were included in a meta-analysis of HR compared to ECG data which demonstrated a mean bias of –0.13 (95% CI, –1.22–0.96). This study demonstrates cPPG can be a useful tool in the remote monitoring of patients and has demonstrated accuracy for HR. However, further research is needed into the clinical applications of this method.

Clinical trial participation among historically underrepresented populations remains low in large part due to mistrust of academic institutions and research investigators. Mistrust may be ever greater today given misinformation related to COVID-19. The Research Ambassador Program is an interactive educational workshop delivered by Promotoras de Salud/Community Health Workers and designed to both address common myths, fears, and concerns about research and encourage research participation among underrepresented populations. An evaluation conducted with 819 Latino and Black participants demonstrated a change in behavior and intention to participate in a clinical trial, with half of participants enrolling in a clinical trial research registry.

OBJECTIVES/SPECIFIC AIMS: To complete a needs assessment and action planning process that engaged clinical and translational research network members in identifying needs through survey feedback, characterizing the needs in small group sessions, and developing recommendations for action at the network’s annual scientific meeting. METHODS/STUDY POPULATION: The project included (1) a survey of 357 members across partner institutions from the Great Plains IDeA CTR Network, (2) 6 - 90 minute brainstorming sessions to characterize needs identified through survey assessment, and (3) 6 - 60 minute sessions to develop recommendations for network improvement based on the characterization activity. Approximately 75 members participated in the characterization and recommendation sessions. RESULTS/ANTICIPATED RESULTS: Seven areas of need from the survey were identified based upon the frequency of identification by network members (support to move research across the translational spectrum, database design and management, data access and sharing, data analysis, recruitment and retention of subjects, support for members who have submitted grants but were repeatedly unsuccessful, mentoring). Members indicated which characterization sessions they were interested in attending and based on the enrollment numbers needs related to unsuccessful grant submitters and mentoring were combined as were needs related to database design and data access-sharing. Sessions resulted in 8 inter-related recommendations for network action that included to (1) develop GP-CTR directory/registry of clinicians, researchers, system partners, that can be used to identify people that want to be involved in research partnerships or mentoring, (2) create a GP CTR Navigators Program to will provide support to network members throughout the collaborative research and grant preparation process, (3) identify and disseminate information about assets (funding, databases/registries) that exist amongst network partners that can be leveraged by member, (4) develop a searchable repository of evidence-based interventions for T3/T4 efforts, (5) review GP CTR supported professional development, and technological resource offerings and identify potential gaps, (6) facilitate opportunities for peer support/networking, (7) provide guidance to GP CTR network institutions looking to adopt policies that will support translational research collaboration, and (8) identify potential barriers to GP CTR network engagement (i.e., infrastructure, communication, marketing). DISCUSSION/SIGNIFICANCE OF IMPACT: This process allowed for a wide range of network members to contribute to actionable recommendations for CTR leadership to move into action and improve the scientific network’s ability to conduct clinical and translational research.

OBJECTIVES/GOALS: Acidity and the lactate-to-pyruvate ratio correlate with immunotherapy resistance. AcidoCEST MRI and hyperpolarized magnetic resonance spectroscopy (HP-MRS) measure extracellular pH and lactate-to-pyruvate ratio. We will establish a baseline for these biomarkers then observe changes after combination esomeprazole and immunotherapy. METHODS/STUDY POPULATION: We used multiple melanoma models created via serial in vivo passage under immunotherapeutic pressure (FVAX, CTLA-4, PD-1, PD-L1). We used four of these corresponding to 25%, 50%, 75% and 100% resistance (TMT, F2, F3, and F4, respectively). HP-MRS was performed two weeks post implantation in male BL6 mice with AcidoCEST MRI 2-3 days later. Tumors were implanted in additional mice and grown for 1 week. We used esomeprazole as a possible immunotherapy sensitizer. Esomeprazole (or PBS) alone and in combination with immune checkpoint blockade (ICB; αCTLA-4, αPD-1) was then conducted every 3 days for 3 doses. ICB was administered 3h after esomeprazole. AcidoCEST MRI was performed the day after the final dose of combination therapy and 3h after esomeprazole (or PBS) alone. HP-MRS was performed 2-3 days after acidoCEST MRI. RESULTS/ANTICIPATED RESULTS: There was a statistical increase in the lactate-to-pyruvate ratio of the F4 group compared with TMT, F2, and F3 groups (p < 0.05). The TMT, F2, and F3 groups did not differ significantly. The extracellular pH (pHe) of the TMT group was statistically lower than the F2 and F4 groups (p < 0.05). The pHe did not differ significantly between the TMT and F3 groups nor the F2, F3, and F4 groups. The lactate-to-pyruvate ratio and pHe after combination treatment with esomeprazole and ICB did not differ compared to PBS+ICB control. Treatment with esomeprazole alone generated higher lactate-to-pyruvate ratio compared with PBS alone. Tumor volume curves and survival curves of mice bearing F4 tumors treated with esomeprazole combination with ICB showed no difference compared with PBS+ICB, PBS alone, and esomeprazole alone. DISCUSSION/SIGNIFICANCE: We differentiated between the 100% and 25% resistant models with both pHe and lactate-to-pyruvate ratio, although the pHe was counterintuitive. Esomeprazole was ineffective, but other potential sensitizers exist. A non-invasive clinical imaging tool and sensitizer would permit more personalized treatment plans so treatment is more effective.

ABSTRACT IMPACT: Successful implementation of this control strategy will result in a commercially available ivermectin-treated birdfeed that the public can use to protect themselves from infection with West Nile virus (WNV) by reducing mosquito survival and thereby suppressing WNV transmission around their homes. OBJECTIVES/GOALS: We assessed the efficacy and feasibility of ivermectin (IVM)-treated birds as a mosquito control strategy for local reduction of West Nile virus (WNV) transmission. We conducted a randomized field trial in backyard chickens and developed a mathematical model informed by field data to predict the impact of treated wild birds on transmission. METHODS/STUDY POPULATION: We placed 48 chickens in four treated and four untreated control flocks in backyards coops across Davis, CA and administered IVM daily in feed to treated flocks (Jul-Sep 2019). We assessed entomological indices weekly (i.e. Culex mosquito abundance, WNV infection prevalence, and parity rate) around each coop, monitored serum IVM levels in treated chickens, and tested for WNV antibodies in all chickens. Shifting our focus to wild birds, we developed a spatially-implicit mathematical model of WNV transmission near IVM-treated birdfeeders. Model parameters for bird movement were based on our telemetry of 27 birds in Fort Collins, CO (Aug-Sep 2020). Using the model, we predicted optimal deployment of treated feeders to provide local WNV control. RESULTS/ANTICIPATED RESULTS: WNV seroconversions were reduced in treated vs. untreated flocks, indicating a reduction in WNV transmission intensity at treated coops (P = 0.03). A sustained, but insignificant reduction in number of infected mosquitoes was observed near treated coops (P = 0.59); small sample sizes and below normal WNV prevalence in the study area limited our power. We anticipate that optimal spacing and number of IVM-treated birdfeeders required for effective WNV control in neighborhoods will depend on feeder usage rates by common bird species irrespective of WNV competence; broad availability of IVM-treated bloodmeals to mosquitoes will be more effective in reducing transmission than targeting the few species responsible for viral amplification. DISCUSSION/SIGNIFICANCE OF FINDINGS: IVM is a novel method for controlling zoonotic pathogens in the US and has the potential for targeted mosquito control to reduce pesticide usage. Evaluating spatial deployment of IVM-treated bird feed for local reduction in WNV transmission is a stepping stone to commercial deployment of this WNV control strategy.