OBJECTIVES/GOALS: To identify empiric neuropsychiatric symptom (NPS) clusters in behavioral variant frontotemporal dementia and to determine the role of early anxiety/depression on functional progression. METHODS/STUDY POPULATION: Analyses were conducted using data from the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, an established consortium with an ongoing cohort study of FTD patients across 18 clinical sites which includes comprehensive cognitive, neuropsychiatric, and structural neuroimaging data. A polychoric cluster analysis was performed on subjects from the ALLFTD cohort [applewebdata%3A//044E463E-34DA-4677-9EDC-B8309D14C337#_msocom_1] with early-stage disease (N=145, male 61%, median age 62 years) in order to identify empiric NPS clusters. Cox proportional hazard regression was then used to examine the association between early affective symptoms in bvFTD and subsequent functional disabilities adjusted for age, sex, level of education, and FTLD CDR global score. RESULTS/ANTICIPATED RESULTS: We identified a four-factor model as the best fit for the data: (1) an affective cluster with prominent depression, anxiety, agitation, and irritability, (2) a disinhibited symptom cluster with prominent elation and disinhibition, (3) an obsessive symptom cluster with prominent obsessive/ritualistic behavior and hyperorality, and (4) a psychotic symptom cluster with prominent delusions and hallucinations. The hazard of developing impairments in transactions, language, self-care, meal preparation, and incontinence was significantly elevated in those with early affective symptoms (depression/anxiety). DISCUSSION/SIGNIFICANCE: In this study we show that, NPS cluster into four discrete groups: (1) affective symptoms, (2) disinhibited symptoms, (3) obsessive symptoms, and (4) psychotic symptoms. Anxiety and depression are prominent within the affective symptom cluster and are associated with accelerated functional decline in a number of domains.

OBJECTIVES/GOALS: The study aims to utilize event-related potentials (ERPs) coupled with observable reports of symptoms to comprehensively understand neurological and symptomatic profile of individuals at risk for developing psychosis. The study is a short-term longitudinal design which allows for examination of course as well as structure of illness. METHODS/STUDY POPULATION: This study uses a combination of well-validated ERPs (P300, N400, ERN) and symptom data to predict variation in symptoms over time. We parse heterogeneity within a high-risk group to create innovative profiles and predict variation in course of symptoms. Data collection is ongoing (n = 35; target N = 100). Methods include a battery of ERP tasks tracking neural processes associated with attention, language processing, and executive function (P300, N400, ERN), along with assessment of symptom type and severity. Analyses include how ERPs correlate with severity of risk and symptom dimensions (positive, negative, disorganized). We examine whether individual versus global ERP aberrations (P300, N400, ERN) predict individual versus global symptom domain severity (positive, negative, disorganized), or vice versa. RESULTS/ANTICIPATED RESULTS: Symptom domain scores were elevated compared to general population on positive (M = 1.65, SD = .36), negative (M = 1.9 SD = .42), and depressive (M = 1.94, SD = .40) domains. Small to medium effect sizes emerged for P300 profile (r’s = −.001 to −.41) and ERN profile (r’s = −.03 to −.37), though small effect sizes for N400 profile (r’s = −.06 to .29). Analyses were run to determine the degree to which profiles of risk were similar: P300/ERN (r = −.09), ERN/N400 (r = −.39), and N400/P3 (r = −.20). Additional analyses suggest potential mediating effects of cognition on neural activity and symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: We use a combination of well-validated ERPs (i.e. P300, N400, ERN) with behavioral and symptom data to predict variation in symptoms over time. A “fingerprint” physiologic aberration may be exhibited within high-risk individuals and can be used as biomarkers to identify those at risk even before onset of observable symptoms.

ABSTRACT IMPACT: Advanced cardiac magnetic resonance imaging techniques can help to protect cancer patients from cardiotoxicity from immunotherapy with a more sensitive assessment of cardiac function with strain imaging for detection of abnormal cardiac function in the setting of normal left ventricular ejection fraction. OBJECTIVES/GOALS: Immune checkpoint inhibitors (ICI) are associated with fatal cardiotoxicity. Cardiac magnetic resonance (CMR) imaging can assess ICI-associated cardiotoxicity, but the utility of CMR strain imaging is unknown. We present a study of patients with ICI-associated cardiotoxicity evaluated with fast strain-encoded (fast-SENC) CMR. METHODS/STUDY POPULATION: This prospective study was approved by the institutional IRB and informed consent was obtained from 15 patients (5 patients with ICI-associated cardiotoxicity, 10 controls patients) between August 2018 and January 2020. All patients with ICI-associated cardiotoxicity had abnormal troponin values and evidence of cardiotoxicity on T2-weighted and/or delayed enhancement CMR images. All patients underwent standard CMR assessment with steady state free precession cine images, T2-weighted imaging, and delayed gadolinium enhancement imaging. Additionally, free-breathing SENC images were obtained and then processed by a team of blinded cardiovascular imaging specialists using Myostrain software (Morrisville, USA). RESULTS/ANTICIPATED RESULTS: Left ventricular ejection fraction (LVEF) was normal in both groups (ï,³53%). Global longitudinal LV strain was significantly depressed in the ICI cardiotoxicity group versus controls (-12.8 ±3.2% vs. -16.6 ±1.9%, p=0.028). The average global circumferential LV strain was mildly abnormal (defined as strain > -17) in the ICI cardiotoxicity group and trended towards a higher value compared with controls (-16.0 ±2.6% vs -17.8 ±1.7%, p=0.103). The average number of dysfunctional segments (defined as strain > -10) was significantly higher in the ICI cardiotoxicity group (6.8 ±4.2 vs. 1.0 ±1.7, p=0.017). The proportion of abnormal myocardium was higher in the ICI cardiotoxicity group (66 ±21% vs. 45 ±18%, p=0.050), as well as the proportion of myocardium found to be dysfunctional (26 ±22% vs. 3.0 ±6.0%, p=0.041). DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite having preserved LVEF, patients who met criteria for ICI-associated cardiotoxicity had both global and regional abnormal LV strain. Fast-SENC imaging may provide a sensitive tool for detection of early cardiotoxicity in this population. This study is limited by its small cohort and a larger prospective study would be of value.

OBJECTIVES/GOALS: Phagocytes, diverse cells that ingest material, are the primary cell type infected by Mycobacterium tuberculosis (Mtb) and the executors of protective mechanisms. T cells play a critical role by helping phagocytes control the infection. Understanding the precise T cell-dependent mechanisms by which phagocytic cell types contain Mtb is critical. METHODS/STUDY POPULATION: To determine the impact T cells have on different phagocyte cell populations’ host defense mechanisms, groups of wild–type and T cell deficient TCRa-/- mice were infected with an Mtb strain expressing fluorescent mScarlet protein. At four weeks post-infection, a time when T cell help contributes to control of Mtb, lungs were homogenized and cells sorted based on detection of mScarlet, indicating Mtb-infected cells. Cell suspensions from each mouse background were underwent single-cell RNA sequencing analysis to reveal the heterogenous cellular transcriptional response of different phagocyte populations. RESULTS/ANTICIPATED RESULTS: We found that Mtb-infected phagocytes from wild-type and TCRa-/- mouse lungs contain the same dominant cell phenotypic clusters, but these have different patterns of gene expression. Without T cells, phagocytes are prone to a more inflammatory phenotype. DISCUSSION/SIGNIFICANCE: This will translate fundamental biological data to test the hypothesis that Mtb encounters different environmental stresses exerted by different phagocytic cell types. This work could reveal host intracellular niches that enable bacterial persistence and elucidate new pathways that could be targeted for traditional antibiotic therapies for TB.

OBJECTIVES/SPECIFIC AIMS: Objectives: To examine the differences in health outcomes of adolescents and young adults treated for malignancy at a pediatric cancer center compared to an adult cancer center. To determine the differences in receipt of supportive care for adolescents and young adults with malignancy who are treated at a pediatric cancer center compared to an adult cancer center. METHODS/STUDY POPULATION: Methods: This will be a retrospective cohort study of patients from the ages of 15 to 39 years who are diagnosed with a malignancy common between adult and pediatric facilities within 2013-2017. Data will be abstracted from an existing database at MCW containing patient information at the adult and pediatric centers. Study population: Patients ages 15-39 years of age who are categorized as young adolescent and adult patients (AYAs). Patients are eligible for the cohort if they have a diagnosis that is common between adult and pediatric oncology centers and that is made within the years 2013-2017. These diagnoses will include ALL, AML, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Germ cell tumors, Osteosarcoma, Ewing Sarcoma, other sarcomas, and CNS tumors. RESULTS/ANTICIPATED RESULTS: There will be a difference in health care utilization, clinical trial enrollment and toxicity of therapy in AYAs with malignancies treated at an adult facility than AYAs treated for similar malignancy at pediatric facility. DISCUSSION/SIGNIFICANCE OF IMPACT: There will be a difference in receipt of supportive care referrals, including psychology, social work, sperm banking, initiation of palliative care, in AYAs treated at a pediatric facility compared to AYAs treated at adult facility.

OBJECTIVES/GOALS: Clinical translational studies inform clinical practice patterns through dissemination of clinical practice guidelines (CPG). In EM practices change to rapidly for timely local EHR implementation. We test the OMG BPM+Health specification for rapid deployment of best practices relevant to EM. METHODS/STUDY POPULATION: The OMG Business Process Management for Healthcare (BPM+Health) specification combines BPMN™ with Case Management Model and Notation (CMMN™) and Decision Model and Notations (DMN™) to “disseminate and leverage evidence-based best-practices at the point of care.” The American College of Emergency Physicians (ACEP) Board-certified Emergency Physicians modeled practice guidelines in the BPM+ modeling language during on-line meetings. Two common emergency conditions were selected for initial pilot testing: 1) evaluation and treatment of first trimester bleeding in pregnant patients, and 2) the evaluation and treatment of non-traumatic low back pain. RESULTS/ANTICIPATED RESULTS: The protocols were successfully modeled during four on-line meetings in less than 2 months. Process steps from initial evaluation to disposition were implemented using BPMN™. When clinicians need to evaluate the patient to collect data for decision making the inputs and outputs were modeled in CMMN™. Decision logic is represented as DMN™. The software tool linked the components for easy browsing and authoring the logic. The Physicians easily followed the displayed logic. The practice recommendations from each policy were successfully modeled, using the standard BPM+ notation to support rapid implementation in EHRs. Detailed implementation specifications will be shared. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot project demonstrated the feasibility of the OMG approach to solving Clinical Practice Guideline Implementation and Dissemination Barriers. Ongoing work by involved specialty societies will be necessary to demonstrate the scalability and sustainability of this approach.

This paper describes the development and validation of a new 32-item test of knowledge of good clinical practice (GCP) administered to 625 clinical research coordinators. GCP training is mandated by study sponsors including the US National Institutes of Health. The effectiveness of training is rarely assessed, and the lack of validated tests is an obstacle to assessment. The GCP knowledge test was developed following evaluation of two existing widely used GCP tests to ensure it accurately reflects the content of current training. The final GCP knowledge test demonstrated good reliability (α = 0.69). It is a valid and reliable instrument for measuring knowledge of GCP. The test will be useful in assessing the effectiveness of GCP training programs as well as individuals’ mastery of GCP content.

This study presents an individualized coaching approach tailored to the stages of proximity of promising scientists interested in becoming independently funded researchers in the context of a minority-serving institution. This strategy defined the participant’s stage of proximity by their number of first-author publications in peer-reviewed journals and their track record in submitting research grants. We argue that coaching tailored by stages is an asset to maintain the enthusiasm, persistence, and positive attitude of promising scientists as they try to reach independent investigator status. Furthermore, this valuable educational approach supports the development of management and leadership skills in defined scientific domains.

ABSTRACT IMPACT: Our research would be the first therapeutic to both prevent and treat osteoarthritis - helping 27 millions U.S. citizens alone immediately. OBJECTIVES/GOALS: Our objective is to conjugate hyaluronic acid binding peptides (HABP) to anionic hollow nanoparticle (hNP), and allowing the HABP-hNP complex to penetrate into osteoarthritic cartilage, bind to exposed HA, prevent further degradation, and restore the compressive strength of articular cartilage. METHODS/STUDY POPULATION: N-isopropyl acrylamide, 2-acrylamindo-2-methyl-1-propanesulfonic acid, N,N’-bis(acryoyl)cystamine, and Acrylic Acid, in fluorescent batches rhodamine b isothiocyanate (RBITC), were polymerized via precipitation reaction. HA binding peptide, GAHWQFNALTVRGSG-Hydrazide (GAH-Hyd), was covalently bonded to the hNP using DMTMM chemistry. The reaction was halted by diluting the solution 10:1 with milliQ water and purified using tangential flow filtration. The dynamic viscosity of the six treatments were analyzed in a 70 kDa HA. Using a rheometer (Discovery HR-3) with a 20 mm parallel plate geometry, TA Instruments, New Castle, DE), a frequency sweep (0.01 -1000 Hz, 2.512 Pa) was conducted to measure the storage modulus of each solution. RESULTS/ANTICIPATED RESULTS: GAH-Hyd was successfully conjugated to the surface of the hNP and zeta-potential shows a significant increase in surface charge from -21.41 mV for unconjugated hNP to -8.94 mV for 65 GAH conjugated hNP, confirming conjugation. The hNPs need 65 ±10 GAH per nanoparticle to significantly bind to HA, shown by increasing the dynamic viscosity of the solution. The minimum concentration of 65 GAH-hNP required to significantly bind to HA is 313 µM. These data from our study display the ability to functionalized the surface of polymeric hNPs with site specific peptides and their ability to bind to diseased tissue. We expect the GAH-hNP system will restore the compressive strength of OA cartilage and prevent further HA degradation in ex vivo aggrecan depleted cartilage plugs. DISCUSSION/SIGNIFICANCE OF FINDINGS: Binding to exposed HA within the ECM of cartilage protects the HA from further degradation, halting the progression of OA. 65 GAH-hNP binds to HA at a 313 µM. Our system can be translated and used to treat a multitude of conditions by conjugating tissue specific peptides to the surface of our hNPs and delivery site specific therapeutics to diseases tissue.

OBJECTIVES/GOALS: Our team has developed a high-throughput 3D patient-derived muscle platform to study signaling pathways associated with skeletal muscle disease. This platform will be used to study pathologies of human muscle that arise from genetic mutations and processes of aging along with pharmacologic interventions to improve mass, function, and performance. METHODS/STUDY POPULATION: In the current study, 3D skeletal muscle is formed from young healthy male samples. Samples are treated with urocortin II (UCNII) or vehicle for ten days and evaluated for tissue performance. Functional assessments include real-time contraction magnitudes using digital image correlation (DIC) analysis of video collected during electrical pulse stimulation and end-point measures of initial and repeated tetanic force production. Functional measures provide indices of patient muscle synchronicity, strength, and endurance related to drug efficacy and toxicity which we will correlate to pro-growth protein signaling via Luminex. A subset of these samples will also be analyzed by histology and microscopy to assess muscle fiber density, type, and size, as well as myotube fusion index and sarcomere uniformity. RESULTS/ANTICIPATED RESULTS: We anticipate that healthy muscle treated with UCNII will have increased synchronicity and contraction magnitudes in DIC analysis throughout their seven-day electrical pulse stimulation protocol. We also expect to see sustained contraction magnitudes in DIC analysis at the end of electrical pulse stimulation indicating fatigue resistance in the drug treated group compared to no-drug control. Like our real-time DIC data, we anticipate increases to initial and sustained maximal force production in the drug treated group. We expect that drug treated muscle will present with an increased fiber density, fiber diameter, and fusion index with uniform sarcomeres. Finally, we expect heightened pro-growth signaling pathways in treated vs. controls. DISCUSSION/SIGNIFICANCE: The current study will serve as an initial investigation of the endogenous ligand UCNII for enhancing skeletal muscle mass and performance in human muscle laying the framework for future drug efficacy and toxicity studies. This platform will ultimately enhance the study of muscle diseases and translation of therapeutics to clinical settings.

OBJECTIVES/GOALS: The proposed study aims to improve physical and mental health outcomes among Hispanic older adults who live alone in a low-income San Juan, Puerto Rico community through weekly PA groups. Specific outcomes include measures of loneliness, social isolation, depression, physical mobility, metabolic indicators, and other health indicators. METHODS/STUDY POPULATION: Data will be collected at three time points: Pre (Week 1), Mid (Week 6), and Post (Week 12) intervention. Currently, the community has 50 residents over 65 years old who live under the poverty index and receive multiple social benefits. Various tools will be implemented to measure loneliness (University of California Los Angeles – Loneliness Scale-10 items), social isolation (Lubben Social Network Scale-6 items), depression (Geriatric Depression Scale-10 items), physical mobility (Time Up and Go Test), metabolic health indicators (hemoglobin A1c and glucose) and other health indicators (i.e., blood pressure, cholesterol, as well as body mass index (BMI)). These measurements will determine if participation in PA groups is associated with improvement of the variables measured. RESULTS/ANTICIPATED RESULTS: It is expected that the baseline scores of older Hispanic adults in terms of loneliness, social isolation, depression, physical mobility, metabolic indicators (i.e., cholesterol level and hemoglobin A1c), and other health indicators (blood pressure or BP and BMI) will be lower compared to those after participation in the Physical Activity Program. More frequent participation will be associated with more significant improvement in measured variables. DISCUSSION/SIGNIFICANCE: Results from this study will determine the effectiveness of community-based PA interventions in addressing loneliness, social isolation, depression, physical mobility, and metabolic factors (hemoglobin A1c and glucose) in elderly minority Hispanic populations as a means of improving their health outcomes and quality of life.

OBJECTIVES/GOALS: Studies have shown that cardiac arrest survivors have poor quality of life (QoL) secondary to neurologic injury. We hypothesized that poor provider-patient communication, lack of readiness for discharge, and perceived illness threat would be associated with QoL in cardiac arrest survivors. METHODS/STUDY POPULATION: We distributed an online survey to the Sudden Cardiac Arrest Foundation listserv. Survivors completed the Questionnaire for the Quality of Provider-Patient Interactions (QQPPI), Readiness for Hospital Discharge Scale (RHDS), and the Brief Illness Perception Questionnaire (B-IPQ). When completing the QQPPI and RHDS, survivors were asked to think back to their hospitalization and discharge. QoL domains (physical, psychological, social) were measured via the WHO-QOL BREF. Three multiple regression models examined associations between QQPPI, RHDS, and B-IPQ scores with QoL domains, adjusted for age, sex, months since arrest, and understanding of arrest and post-arrest symptoms at discharge. RESULTS/ANTICIPATED RESULTS: A total of 163 survivors (mean age 50.1 years, 50.3% women) provided complete survey data. Greater perceived illness threat (β: −.45, p < .001) and lower readiness for discharge (β: .22, p = .01) were associated with worse physical QoL; greater perceived illness threat (β: −.45, p < .001) was associated with worse psychological QoL; and greater perceived illness threat (β: −.3, p < .001) and poor provider-patient communication (β: .35, p < .001) were associated with worse social QoL. Our models explained 48%, 43%, and 30% of the variance in physical, psychological, and social QoL, respectively (p < .001). DISCUSSION/SIGNIFICANCE OF IMPACT: In-hospital interactions and perceived illness threat have important ramifications for cardiac arrest survivors attempting to return to daily life. Discussions regarding cardiac arrest sequelae, expectations, and specific treatment options during hospitalization could impact future QoL.

OBJECTIVES/SPECIFIC AIMS: To determine the association of participant’s characteristics and socio-cultural factors including acculturation, community identity and discrimination with the adherence to cancer screening guidelines and participants’ quality of life. METHODS/STUDY POPULATION: As part of the Cancer Disparities Research Network pilot cohort, the study recruited 333 participants across four sites: Boston Chinatown, African American communities in Philadelphia, and Hispanic communities in Columbus, and rural white communities in Appalachia, Ohio. Enrolled participants were eligible if they were 40 to 74 years old, did not live in a nursing home or other facility, and had no prior invasive cancer diagnosis. Additionally, each participant met at least one of the following criteria: living in a medically underserved area, having low literacy, low income (defined as 100% of the 2015 Federal Poverty Level FPL according to 2015 FPL Guidelines), or being uninsured or receiving subsidized health insurance coverage. Participants completed a baseline survey of demographic data, health status, including health behaviors and risk factors to cancer, Primary Care Physician (PCP) status and most recent breast, cervical, prostate, skin and colorectal cancer screenings. Information related to discrimination, acculturation or adaptation, and sense of belonging to their community was collected using validated instruments. RESULTS/ANTICIPATED RESULTS: Of the 333 participants enrolled in the study, 65.5% were women, 14.1% were 40-50 years of age, 59.8% were 51-64 years, and 26.1% were 65-74. The cohort was racially and ethnically diverse: 8.4% of participants identified as Hispanic, 30.3% as non-Hispanic White, 31.2% as non-Hispanic Black, 29.4% as non-Hispanic Asian, and 0.6% as Other. 62.2% spoke English, 8.1% Spanish, and 29.7% Chinese as their primary language. Low incomes were common: 33.6% reported incomes $15,000 or less, and 25.8% reported incomes between $15,000 and $24,999. Overall adherence to USPSTF guidelines on cancer screening rates was 77.9% for breast cancer, 71.1% for cervical cancer, and 67.7% for colorectal cancer. Analyses will present the association of acculturation, community identity, and discrimination with cancer screening and quality of life measures. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will promote the increase of cancer disparities research, and reinforce the importance of inclusion and increased recruitment of diverse populations in future studies. By determining the potential factors associated with cancer disparities among minority populations, it may provide new information for clinicians to have more cultural sensitivity addressing potential disparities in the clinical setting. It will also promote the creation of more tailored interventions and programs to deliver adequate healthcare among these populations.

OBJECTIVES/GOALS: Evidence suggests that individuals with generalized joint hypermobility (GJH), or excessive joint range of motion, are at higher risk of developing chronic neck pain. The objective of this study is to determine the prevalence and clinical presentation of chronic neck pain in GJH and investigate its associations with other measures of spine health. METHODS/STUDY POPULATION: Data was collected at the Driven to Discover Research Facility at the 2022 Minnesota State Fair. Individuals 18 years and older were invited to participate. All enrolled participants completed Phase 1, which included: the Beighton Score (measure of GJH), the 5-Point-Questionnaire (self-report survey for current or historical GJH), and a custom self-report survey for demographics and musculoskeletal pain. A subset of participants was also asked to complete Phase 2 of the study. Phase 2 consisted of additional self-report surveys (Neck Disability Index (NDI) and PROMIS-10 Global) and the following physical measures: neck range of motion in all planes, neck strength in flexion-extension and lateral bending, and grip strength. RESULTS/ANTICIPATED RESULTS: A total of 559 participants were enrolled in the study. All participants completed Phase 1, and 285 of those individuals completed Phase 2. Those with a Beighton Score≥4 were categorized as having GJH. The overall prevalence of GJH was 23.8% for females and 9.1% for males. Consistent with previous studies, multiple linear regression analysis (R2=0.20, F(2,552) = 69.37, p DISCUSSION/SIGNIFICANCE: This is one of the largest studies investigating GJH, pain, and physical measures of neck function in the general population. The results highlight the higher prevalence of chronic neck pain in those with GJH and will form the basis for a subsequent study to identify mechanisms and potential therapeutic targets for individuals with GJH and chronic pain.

OBJECTIVES/GOALS: The objective of this study was to determine whether residential radon and proximity to horizontal oil and drilling (fracking) are risk factors for the development of multicentric lymphoma in pet dogs, a spontaneous, immunocompetent model for non-occupational risk for NHL in humans. METHODS/STUDY POPULATION: Two case-control populations of dogs with multicentric lymphoma were utilized, with a focus on two dog breeds at high risk for lymphoma. Control dogs were matched for age, breed, and sex. Home addresses were collected for 54 Golden retrievers with lymphoma and 108 Golden retriever controls, and for 56 boxer dogs with lymphoma and 84 unaffected boxer controls. Counties of residence were matched to radon zones and percentage of home radon tests that exceeded the actionable level of 4 pCi/L, available by county through the EPA and the CDC National Environmental Public Health Tracking Network from 2008 to 2017. Locations of horizontal oil and gas wells were obtained from the Enverus Database, and distances from dog homes to the closest well, and well density by county, were calculated for each case and control. RESULTS/ANTICIPATED RESULTS: We found no significant differences in radon zones, county level radon measurements, or residential proximity to active fracking wells between dogs with lymphoma and unaffected controls in either the Golden Retriever or boxer populations. DISCUSSION/SIGNIFICANCE: Canine multicentric lymphoma resembles human NHL and is a valuable model of non-occupational environmental risk for NHL in people. Although we did not find geographic associations between radon and fracking wells, follow-up studies will measure household radon, as well as household air, water, and dog urine for potentially genotoxic chemicals.

ABSTRACT IMPACT: This research will aid clinical and policy solutions on lessening the vast health disparities and overall access issues for low-income, type 1 diabetes patients. OBJECTIVES/GOALS: Identify key barriers to accessing continuous glucose monitors (CGMS) and care options for low-socioeconomic status (SES) patients on public insurance. Low-SES patients with type 1 diabetes (T1D) have lower utilization rates of effective diabetes management technologies and worse clinical outcomes. METHODS/STUDY POPULATION: A literature review was conducted to understand the current research landscape for T1D and lead to the identification of potential barriers which included socioeconomic status, low-income, health literacy, and racial/ethnic minority. Clinicaltrials.gov was searched using the keyword ‘type 1 diabetes’ in conjunction with the identified barriers (as well as the keyword ‘barrier’). A follow up review of each state’s Medicaid programs was conducted to analyze cost and access options for CGMs and the overall financial burden of the disease on low-SES T1D patients. States that offered CGM coverage were further analyzed to determine reimbursement rates and actual out-of-pocket cost for patients. RESULTS/ANTICIPATED RESULTS: Of 285 trials identified from Clinicaltrial.gov searches, only seven relevant trials examined barriers and T1D for low-SES patients. Additionally, many of these studies, both in and outside of the clinical trial space, seldom distinguished between type 1 and type 2 diabetes’‘ an important distinction given that T1D has a higher financial burden and a quicker onset of complications. Currently, 39 states offer various insurance coverage through their Medicaid programs, but have clinical restrictions and requirements such as pediatric coverage only or minimum blood glucose requirement checks. Additionally, there is vast variability in reimbursement rates between states ($0-$800). DISCUSSION/SIGNIFICANCE OF FINDINGS: Study results indicate less effective diabetes management for low-SES T1D patients and a need for more intersectional clinical trial research. Differences in state’s Medicaid CGM coverage, expressed in disparate clinical outcomes for these T1D patients, belies financial incentives to health improvements, as annual US T1D costs are $14.4 billion.

OBJECTIVES/GOALS: Our goal is to determine the structure of the CACHE domain of the Vibrio cholerae quorum sensing receptor CqsR as well as its autoinducer (AI). We are performing X-ray crystallography on the protein in its apo form, with the fractions containing the AI, and with known ligand ethanolamine (ETA). METHODS/STUDY POPULATION: We have transformed BL21(DE3) E. coli cells with a pTB146 vector to contain the gene for the CqsR CACHE domain. We grow these cells to high optical density and induce protein expression, at which point we harvest them and purify the protein. This entails lysing the cells, separating the protein with Ni-NTA resin, cleaving our protein tag, and column chromatography. With purified protein, high-throughput screens are set up to find crystallization conditions of apo CqsR, CqsR-ETA, and CqsR-AI. We then determine conditions that best lead to crystal formation and optimize them. Crystals are then diffracted with X-rays, process the data, and determine the structure of protein and AI. RESULTS/ANTICIPATED RESULTS: We anticipate finding the structure of the CqsR CACHE domain to a high resolution in addition to the identity of its autoinducer. Previous results found that the structure is homologous to another V. cholerae chemoreceptor, Mlp37, and we expect the results from this project to confirm this. In addition, we know that the autoinducer weighs approximately 62 daltons, the same as the known ligand, ethanolamine. Given that CACHE domains bind specifically to their ligands, we anticipate that the autoinducer will be structurally similar to ethanolamine. DISCUSSION/SIGNIFICANCE: The results will reveal the structure of the CqsR CACHE domain and its autoinducer. This knowledge will better allow researchers to treat cholera, as both autoinducer identity and receptor conformational changes will be uncovered, allowing for drug development to inhibit cell growth.