ABSTRACT IMPACT: We seek to determine which lymph nodes drain the human brain. OBJECTIVES/GOALS: Lymphatic vessels train lymphatic fluid from the central nervous system (CNS), but the specific lymph nodes that these vessels drain to remains unknown in humans. We intend on using technetium tilmanocept (TcTM)to map the draining lymph nodes of the CNSin humans. METHODS/STUDY POPULATION: Patients having a tumor resected are eligible for the trial. All patients will have TcTM injected intracranially after tumor resection. Six patients will be enrolled in Cohort 1 to define the time course of drainage to the lymph nodes. Patients in Cohort 1 will be imaged with planar LS within 7 hours of injection and the following day. Either 12 or 24 patients will be enrolled into Cohort 2 to localize the draining lymph nodes with SPECT-CT. The optimal imaging timepoint from Cohort 1 will be used for Cohort 2. Patients in Cohort 2 will be stratified depending on if their tumor is in the frontal, parietal, occipital, or temporal lobe. RESULTS/ANTICIPATED RESULTS: We anticipate that we will detect TcTMin the deep cervical lymph nodes after injection into the brain. It is unclear exactly which lymph nodes the tracer will go to. We hypothesize that the results among patients will be similar, but interindividual variation is a possibility. Furthermore, patients with disease in different lobes of the brain may have different lymph drainage patterns. DISCUSSION/SIGNIFICANCE OF FINDINGS: We seek to answer a fundamental question of human anatomy: what lymph nodes drain the human brain? Additionally, knowing which nodes drain the human brain could shape future research of immunotherapy in patients with brain cancer or autoimmune disease such as multiple sclerosis.

OBJECTIVES/GOALS: This project presents the Post-doctoral Master of Science in Clinical and Translational Research (MSc) program’s outcomes in 20 years of its implementation. This program is a joint offering between the Schools of Health Professions and School of Medicine of the University of Puerto Rico. METHODS/STUDY POPULATION: This study consists of secondary data analysis of academic and administrative documents. It also includes data from the Annual Evaluation retreats reports and an Alumni Follow-up Survey using an electronic questionnaire. All 121 Scholars admitted to the program from academic years 2003 to 2023 were included in the sample. Data analysis included descriptive statistical analysis of quantitative data and qualitative content analysis regarding recruitment/admissions, faculty composition, curriculum design, Scholars’ outcomes, and program’s financial support sources. Quantitative data were analyzed using the statistical software SPSS. RESULTS/ANTICIPATED RESULTS: Scholars of the program had been recruited from the UPR-MSC and several partner institutions with diverse backgrounds, disciplines, and research areas. Faculty and committee members have representation from the six MSC-Schools and partner institutions. The academic Program structure has changed over the years, and currently, more than 65% of the courses are offered online. Several financial sources have been identified to support the scholars. The Scholars’ portfolios of grant submission and publication productivity evidence the program’s success. Graduates have also been successful in advancing to positions that foster research impacting Hispanics. DISCUSSION/SIGNIFICANCE: The Post-doctoral Master’s in Clinical and Translational Research program (MSc) has contributed to the formation of committed Hispanic clinical and translational researchers impacting minorities and contributing to diversity in the research workforce.

OBJECTIVES/GOALS: Current approaches to drug development for the aggressive triple negative breast cancer rely on current 2D and 3D in vitro models which have limited capabilities. We have developed a translational microphysiological system that can maintain the human breast microenvironment to capture the complex interaction with the tumor microenvironment. METHODS/STUDY POPULATION: Three different TNBC cell lines were seeded in BC-MPS: MDA-MB-231 parental cell line, MDA-MB-231wiht the gene, LKB1 overexpressed, which is a tumor suppressor, and MDA-MB-231 with the enzyme, ERK5, an enzyme associated with increased metastasis and drug resistance, knocked out. These three TNBC cell lines were cultured in a standard 2D 96-well plate and in BC-MPS. Time-lapse videos were taken to track cellular mobility. RNA-sequencing was performed to compare different expression levels of various cancer related genes of the cell lines cultured in standard 2D and BC-MPS. RESULTS/ANTICIPATED RESULTS: The LKB1 overexpressed MDA-MB-231 and the ERK5-ko MDA-MB-231 cell lines are expected to have decreased mobility compared to the parental cells. The cell lines are expected to have increased expression of cancer related genes when cultured in BC-MPS than when cultured in standard 2D due to the presence of human breast tissue. DISCUSSION/SIGNIFICANCE: BC-MPS is a promising new translational MPS that facilitates studying long term interactions between real human breast tissue and cancer cells. The BC-MPS systems ability to support the growth of established cell lines has been demonstrated. Future studies will focus on developing the model for personalized medicine.

OBJECTIVES/GOALS: We developed a state-wide program to support early career faculty in preparing mentored career development awards, and connect them to resources, mentorship, and career development opportunities. We aimed to build self-efficacy along multiple axes, including research design and grantsmanship, and to facilitate networking with mentors and peers. METHODS/STUDY POPULATION: The program recruited four cohorts of faculty over the course of four years, for a total of 32 faculty participants (63% physician scientists). Participants were selected by a Steering Committee, and represented a variety of specialties from 19 departments across Brown University, University of Rhode Island, and affiliated hospitals. Participation required an institutional commitment of 20% minimum protected time to engage in research and a year-long curriculum that included biweekly didactic sessions, project development support, individual consultations, feedback on drafts, and internal study section review. Participants completed pre-, interim-, and final-assessments, which collected measures of self-efficacy, professional development needs, program satisfaction, and formative feedback. RESULTS/ANTICIPATED RESULTS: Over the first 3 years, 21 participants completed the program, 43% have received NIH or VA K/CDA awards so far, and 48% received other federal or non-federal awards. Over 25 faculty from across institutions participated in leadership and didactics, with even greater participation on mentorship teams, panels, and grant review. All cohorts showed improvements in measures of self-efficacy in grantsmanship and research and reported high satisfaction with program activities. Participants found individualized proposal feedback and internal study sections to be most valuable, and frequently cited the value of peer-learning opportunities. Challenges for scholars include mentorship challenges, competing priorities/protected time, and various external factors that impacted individual research progress. DISCUSSION/SIGNIFICANCE: The program has successfully supported cohorts of junior clinical and translational faculty from across the state in launching their independent research careers. The program may serve as a model for IDeA state inter-institutional collaboration in developing diverse faculty cohorts in the early stages of preparing their career development award.

OBJECTIVES/GOALS: The Association of Clinical and Translational Science (ACTS) chartered a Diversity, Equity, and Inclusion (DEI) Committee to prioritize activities to support, develop and report on metrics for measuring progress toward DEI goals. This poster aims to describe the formative process toward prioritizing DEI in society’s efforts. METHODS/STUDY POPULATION: In 2021, the ACTS chartered the DEI Committee. Two ACTS Board of Directors members chair the committee, and members represent 10 academic institutions committed to prioritizing DEI. Members participated in a Human-Centered Design process to develop the committee’s mission, goals, and activities. The committee determined areas of opportunity for ACTS to increase DEI by identifying challenges to support DEI in clinical and translational science. The chairs facilitated a discussion using Mural to foster an interactive strategy to engage members in conversations that respected individual experiences, promoted a discussion of actions that ACTS as a society, and determining metrics for measuring DEI. RESULTS/ANTICIPATED RESULTS: We plan to present the committee’s efforts to create the ACTS mission statement and strategies to priority to DEI. We will describe current and future activities to engage historically underrepresented members and academic institutions in ACTS programs. Based on the committee’s work, ACTS has taken systematic approaches toward social justice and is beginning to determine new ways of engaging members. DISCUSSION/SIGNIFICANCE: Scientific societies that prioritize DEI increases equity and belonging across members. ACTS is at the forefront of advocacy, policy, and social justice effort. The DEI committee is positioned to aid ACTS in increasing DEI across the clinical and translational science spectrum.

OBJECTIVES/SPECIFIC AIMS: Current practice frequently dictates hospitalization for TIA and minor stroke (TIAMS) in order to obtain comprehensive evaluation of stroke risk factors and mechanism. Inpatient hospitalization is often done to expedite workup and to coordinate care although may be associated with nosocomial risks and increased healthcare cost. However, a subset of these patients who do not have debilitating deficits may not require inpatient hospitalization. We conducted a pilot study to assess the feasibility of conducting rapid outpatient stroke evaluations in low risk patients with TIAMS without disabling deficits. METHODS/STUDY POPULATION: The rapid access clinic was initiated at a single-site urban tertiary care facility for outpatient evaluation of TIAMS within 24 hours of emergency department (ED) evaluation. Patients were selected using a decision tool identifying presumed low-risk TIAMS seen in the ED. Criteria included medical (e.g., no disabling deficit, no thrombolytic agent given, negative CT for hemorrhagic stroke) as well as social criteria (e.g., patient ability to follow-up as an outpatient). We evaluated rates of noncompliance with post-ED follow-up, need for hospitalization from clinic, and 90 day stroke and health outcome data. RESULTS/ANTICIPATED RESULTS: Between December 2016 and December 2017 a total of 93 TIAMS patients seen in the ED were recommended for the rapid access clinic utilizing the decision tool. Of these patients, 94.5% (86) were evaluated within 24 hours of ED discharge. Only 2 patients (2.4%) who received outpatient evaluation required hospitalization; 61 (71.8%) patients had TIAMS on final evaluation in clinic. DISCUSSION/SIGNIFICANCE OF IMPACT: Our pilot data suggests that for a subset of patients, rapid outpatient evaluation may be a feasible and safe strategy for TIAMS management. Future work exploring such strategies may help improve TIAMS outcomes and reduce ED crowding and unnecessary hospital admissions.

OBJECTIVES/SPECIFIC AIMS: Delirium, a form of acute brain dysfunction, characterized by changes in attention and alertness, is a known independent predictor of mortality in the Intensive Care Unit (ICU). We sought to understand whether catatonia, a more recently recognized form of acute brain dysfunction, is associated with increased 30-day mortality in critically ill older adults. METHODS/STUDY POPULATION: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Coma, was defined as a Richmond Agitation Scale score of −4 or −5. We used the Cox Proportional Hazards model predicting 30-day mortality after adjusting for delirium, coma and catatonia status. RESULTS/ANTICIPATED RESULTS: We enrolled 335 medical, surgical or trauma critically ill patients with 1103 matched delirium and catatonia assessments. Median age was 58 years (IQR: 48 - 67). Main indications for admission to the ICU included: airway disease or protection (32%; N=100) or sepsis and/or shock (25%; N=79. In the unadjusted analysis, regardless of the presence of catatonia, non-delirious individuals have the highest median survival times, while delirious patients have the lowest median survival time. Comparing the absence and presence of catatonia, the presence of catatonia worsens survival (Figure 1). In a time-dependent Cox model, comparing non-delirious individuals, holding catatonia status constant, delirious individuals have 1.72 times the hazards of death (IQR: 1.321, 2.231) while those with coma have 5.48 times the hazards of death (IQR: 4.298, 6.984). For DSM-5 catatonia scores, a 1-unit increase in the score is associated with 1.18 times the hazards of in-hospital mortality. Comparing two individuals with the same delirium status, an individual with a DSM-5 catatonia score of 0 (no catatonia) will have 1.178 times the hazard of death (IQR: 1.086, 1.278), while an individual with a score of 3 catatonia items (catatonia) present will have 1.63 times the hazard of death. DISCUSSION/SIGNIFICANCE OF IMPACT: Non-delirious individuals have the highest median survival times, while those who are comatose have the lowest median survival times after a critical illness, holding catatonia status constant. Comparing the absence and presence of catatonia, the presence of catatonia seems to worsen survival. Those individual who are both comatose and catatonic have the lowest median survival time.

OBJECTIVES/GOALS: To describe the prevalence of, and factors associated with, psychotropic medication use before cancer diagnosis (solid tumor cancer, lymphoma or leukemia) among AYAs 15 to 39 years of age in the US. METHODS/STUDY POPULATION: Retrospective cohort study in a 10% sample of claims from the IQVIA PharMetrics® Plus for Academics (2006-2020). We included AYAs with no prior cancer diagnosis codes 9 months before their index date – defined as the first of ≥2 ICD-9/10-CM primary diagnosis codes for cancer occurring ≤60 days apart. We defined psychotropic use as a claim for an antidepressant, anxiolytic/sedative-hypnotic, mood stabilizer, stimulant or antipsychotic medication. Prevalence of psychotropic use overall and by class, was estimated as the proportion of AYAs with at least one claim for a psychotropic in the 9-months prior to the index date. Using Chi-square and T-tests, we compared demographic characteristics, prevalence of mental health disorders, chronic pain and cancer type between psychotropic users and non-users. RESULTS/ANTICIPATED RESULTS: We identified 6,257 AYAs with cancer (thyroid 17%, breast 13%, melanoma 13%), 64% female, mean age 31 (SD 6) years. Twenty-four percent (n=1,506) used a psychotropic in the 9 months prior to the index date. Psychotropic classes used were antidepressants 15%, anxiolytic/sedative-hypnotics 11%, stimulants 3%, mood stabilizers 2% and antipsychotics 1%. Psychotropic use was higher among females than males (27% vs 19%, p <.001), older than younger AYAs (35 to 39 years-old: 26% vs 15 to 19 years-old: 16%, p <.001). Anxiety (25% vs 4%), depression (22% vs 3%) and chronic pain (17% vs 8%) were more common among those with psychotropic use pre-cancer diagnosis (all p <.001). The proportion of AYAs diagnosed with brain cancer was higher among psychotropic users than non-users (7% vs 5%, p <.001). DISCUSSION/SIGNIFICANCE: One in four US AYAs used a psychotropic medication prior to being diagnosed with cancer. Understanding psychotropic medication management patterns for these patients before cancer treatment may help inform comprehensive care.

OBJECTIVES/SPECIFIC AIMS: We set out to describe important associations and outcomes among those requiring maintenance renal replacement therapy with the patient volume per provider. METHODS/STUDY POPULATION: Through the combination of several large administrative datasets, including the United States Renal Data System (n=237,485), the American Medical Association Master file (n=6249), and Medicare data limited to 2012, we compared characteristics of patients, by quintile of patient/provider volume. χ2 and logistic regression, adjusted for various patient and provider factors for categorical and continuous variables, was used for baseline comparisons, respectively. Cox regression, adjusted for patient, provider, and socioeconomic variables, was used to calculate risks for important clinical outcomes such as kidney transplant listing, transplant receipt, and all-cause mortality. RESULTS/ANTICIPATED RESULTS: There is a threshold patient volume at which important clinical outcomes, including kidney transplantation and all-cause mortality, may be influenced. Higher patient volume is associated with adverse patient outcome. Those receiving care from providers with the highest patient volumes are less likely to receive kidney transplantation, live in a more rural area, and be non-White. DISCUSSION/SIGNIFICANCE OF IMPACT: There is a need to identify novel and potentially modifiable factors associated with patient outcome among those with end-stage kidney disease on maintenance renal replacement therapy. Provider level variables, such as patient volume, is one such variable. As nephrologists are often tasked with the care of variable numbers of patients on dialysis, a better understanding of this association is an unmet need.

ABSTRACT IMPACT: Increase understanding of the types of sponsors responding to the COVID-19 pandemic. OBJECTIVES/GOALS: The COVID-19 pandemic has impacted millions of lives globally. To learn more about this disease and find potential diagnostic, treatment, and preventative products, the healthcare community has initiated a staggering number of clinical trials. Clinicaltrials.gov was reviewed to determine the types of sponsors who are conducting COVID-19 studies. METHODS/STUDY POPULATION: Clinicaltrials.gov was searched using terms ‘COVID-19’ and ‘SARS-Cov-2’. Search results were further defined to include only ‘Interventional’ studies. Of these, only studies with sites located in the United States were selected and for which the ‘Condition’ included at least one of the following terms: ‘COVID’, ‘COVID-19’, ‘Coronavirus’, ‘SARS-Cov-2’, ‘SARS’, or ‘2019-nCoV'. Study sponsors were then categorized as: (1) commercial, (2) academic, or (3) other, based on ‘Sponsor’ information within each study listing. A Google search was conducted for any sponsor that was not easily categorized to obtain additional information to support the proper assessment of sponsor type. The types of sponsors were analyzed over time using the ‘First Posted’ date of each study listing. RESULTS/ANTICIPATED RESULTS: A total of 3662 studies were retrieved, of which 2075 were ‘Interventional’ studies. The studies were further reduced to 681 studies by including only United States sites and the desired ‘Condition’. The percentage of studies from this refined dataset, by sponsor type, were found to be 63% academic, 34% commercial, and 3% other. The relationship between time and sponsor type demonstrated that academic sponsors had the highest percentage of study postings in the first month (March) of the COVID-19 pandemic compared to commercial and other sponsors. Following this first month, academic study postings gradually declined, while commercial sponsors had an increase in postings per month into July, followed by a gradual decline. Few other sponsor type postings were made and occurred primarily in August. DISCUSSION/SIGNIFICANCE OF FINDINGS: The number and timing of listings may be a reflection of study intention and regulatory pathway requirements. Additional variables, such as inconsistent terminology, collaborators, funding, and study start date may influence results. Further analysis may reveal how modification of listing information may result in expedited pandemic response.

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

OBJECTIVES/GOALS: The overall goal is to provide tips and suggestions for designing a summer internship program for undergraduates at an institution that only offers advanced degrees. This poster seeks to highlight what worked well and items that can be improved upon from a program that ran for the first time at the University of Texas Medical Branch in Summer 2022. METHODS/STUDY POPULATION: In February 2022, we opened admissions to a summer internship program whose goals are to expose students to statistical design and analysis problems from real research, while providing them with the conceptual and technical tools to address these problems. As such, students should be able 1) to assess study designs for strengths and weaknesses in addressing specific biomedical questions, 2) to use the tools of statistical modeling, data science, and hypothesis testing along with state-of-the-art statistical software to work on problems as well as produce results and conclusions for these problems, and 3) to understand how developing these skills can lead to a wide variety of career opportunities both inside and outside of academia. We ultimately recruited 12 participants in the first summer. RESULTS/ANTICIPATED RESULTS: Based on feedback from participants, we have identified recruitment efforts that worked (and those that need improvement), teaching methods that worked (as well as those that need improving), and ideas for career development sessions (based on questions generated from current participants). Each participant was paired with another student on a research project. Each research project had both a biostatistics faculty mentor as well as a basic science/clinical faculty mentor. We will discuss what worked/what needs improvement from this sort of situation as well. The program culminated in a poster session which was very well received by participants and faculty alike. DISCUSSION/SIGNIFICANCE: This internship program is significant because developing a workforce knowledgeable in biostatistics and data science has been increasingly in demand to improve the efficiency and reliability of biomedical innovation. My providing guidance to others hoping to provide similar programs, we aim to develop such skills in the incoming workforce.

OBJECTIVES/GOALS: The Saint Georges Respiratory Questionnaire (SGRQ) is used as a patient reported outcome tool for clinical research in COPD and bronchiectasis. We established a registry and biospecimen repository of bronchiectasis patients with and without NTM and report associations between clinical phenotype and SGRQ scores. METHODS/STUDY POPULATION: Patients were recruited in a cross-sectional format from the Bronchiectasis, Cystic Fibrosis, and NTM clinics at our institution. All patients provided at least one sputum sample in the six months prior to inclusion. Clinical and epidemiologically relevant data was obtained, and blood specimens were processed and preserved. Patients were grouped based on clinical phenotype and differences in SGRQ scores were analyzed using ANOVA or Student’s t-test. Descriptive statistics are reported as means and standard deviations, p<0.05 considered significant. RESULTS/ANTICIPATED RESULTS: 72 NTM patients completed the SGRQ including 39 patients not on treatment (Colonized), 29 patients on NTM directed antibiotics, and 4 patients whose infection was cured in the past year. Among patients on treatment, 14 were treatment refractory (positive cultures beyond 12 months of therapy). The mean age of all NTM patients was 59.5±17.6 and 80.5% were female. Mean SGRQ Total scores were significantly higher among patients receiving treatment compared to patients considered colonized (35.7± 22.0 colonized group versus 48.8± 15.8 treatment group, p = 0.011). The SGRQ subdomain scores including Impacts (26.2± 26.2 colonized group versus 42.5± 17.0 treatment group, p = 0.01) and Activities (41.7± 31.8 colonized group versus 59.3± 24.5 treatment group, p = 0.018) were also significantly different between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed a cross sectional cohort of NTM patients and assessed associations between clinical phenotype and SGRQ score. Preliminary data suggests that female sex, treatment status, and therapeutic duration are associated with higher SGRQ scores. We intend to continue to assess the potential for specific SGRQ questions to be used for quantifying disease symptom severity for NTM patients.

OBJECTIVES/SPECIFIC AIMS: Low cancer clinical trial (CCTs) enrollment may contribute to the poor survival improvement for adolescents and young adults (AYAs, aged 15–39 years) with cancer. Treatment site is thought to exacerbate this problem. This study evaluated whether differences in CCT availability explain lower CCT enrollment depending on treatment site for AYAs. METHODS/STUDY POPULATION: This prospective, observational cohort study was conducted at an academic children’s hospital and an adult cancer hospital, 2 affiliated sites within a NCI-designated Comprehensive Cancer Center over 13 months. In consecutive AYA patients newly diagnosed with cancer at both site, it was determined whether an appropriate CCT existed nationally, was available locally, and if enrollment occurred. The proportions of AYAs in these categories were compared by site using the χ2 test. RESULTS/ANTICIPATED RESULTS: Among 152 consecutive AYA patients, 68 and 84 were treated at the children’s hospital and adult cancer hospital, respectively. AYAs treated at the children’s hospital had similar CCT existence nationally compared with AYAs treated at the adult hospital [36/68 (52.9%) vs. 45/84 (53.6%), p=0.938]. However, a significantly higher percentage of children’s hospital treated AYAs than adult hospital treated AYAs had an available CCT [30/68 (44.1%) vs. 14/84 (16.7%), p<0.001]. Enrollment percentages were similarly low in both groups [8/68 (11.8%) vs. 6/84 (7.1%), p=0.327]. DISCUSSION/SIGNIFICANCE OF IMPACT: Significantly fewer AYAs treated at the adult hospital had a CCT available, but national existence was similar at both sites. This suggests that institutional barriers to opening CCT have more importance at adult centers.

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

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

OBJECTIVES/SPECIFIC AIMS: Our goals were to understand the pattern, location, and extent of cardiac replacement fibrosis seen as late gadolinium enhancement on cardiovascular magnetic resonance imaging in a large cohort of cancer patients treated with anthracyclines and/or trastuzumab. METHODS/STUDY POPULATION: We performed a retrospective cohort study of consecutive adult cancer patients treated with anthracyclines and/or trastuzumab from 2004 through 2017. CMRs were analyzed for the presence, location, and pattern of LGE. RESULTS/ANTICIPATED RESULTS: Of 238 patients, 220/(92.4%) had no LGE. Among the 18/(7.6%) patients with LGE, 13/(72.2%) were ischemic in pattern (myocardial infarctions); 10 of these had known coronary artery disease (CAD). Of 5/(27.8%) patients with non-ischemic LGE, the etiologies were known for 4 – myocarditis, cardiac sarcoidosis, eosinophilic myocarditis, and acute myocardial calcification. Only 4/(1.7%) patients had unexpected LGE, of which 3 were unrecognized myocardial infarctions. DISCUSSION/SIGNIFICANCE OF IMPACT: The assessment of fibrosis helps to diagnose the cause of LVSD in cancer patients treated with potentially cardiotoxic medications. This is necessary because currently, the cause of LVSD in cancer patients cannot be established conclusively even though the cause is closely linked to patient outcomes. Our results demonstrate that cancer treatment-related LVSD is not associated with fibrosis. A minority of cancer patients with LVSD have fibrosis related to other reasons, most commonly CAD. Identification of the correct cause of LVSD in cancer patients treated with cardiotoxic medications allows for appropriate treatment. This, in turn, could improve patient outcomes.

OBJECTIVES/GOALS: Diabetes is a prevalent chronic illness that imposes health-related burdens including nephropathy, retinopathy and sleep disorders. The goal of this study was to examine the relation between both sleep disorders and sleep duration and diabetic chronic kidney disease (CKD) and retinopathy. METHODS/STUDY POPULATION: We analyzed data from the National Health and Nutrition Examination Survey 2005-2016 related to diabetic nephropathy and retinopathy, sleep disorders and duration, demographics, and risk factors among diabetics. The subjects were adults with diabetes type 2. Multiple logistic regression analysis was performed to look at the relationship between diabetic complications (CKD and retinopathy) and sleep disorders and sleep duration adjusting for demographics and risk factors. RESULTS/ANTICIPATED RESULTS: Of the 4087 diabetics, 45% had CKD, 19% had retinopathy, and 15% had sleep disorders. CKD and retinopathy were not associated with sleep disorders (p>0.05) but CKD was associated with sleep duration (Adjusted odds ration = 1.014, 95% confidence interval = 1.001-1.027, p<0.05). Cardiovascular disease was a predictor of both CKD and nephropathy (P<0.05). Other predictors of CKD and nephropathy were age >60 years, Non-Hispanic Black, hypertension, low education level, and living under 200% of the Federal Poverty Level (P<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT : Among diabetics, CKD and retinopathy were not associated with sleep disorders, and only CKD was associated with sleep duration. These findings may impact the management of diabetes in the future, since it has effects on a range of other health conditions.

OBJECTIVES/GOALS: In vitro models that mimic the human respiratory system are needed to assess the toxicity of inhaled contaminants. Therefore, our goal is to establish a Dosimetric Aerosol in-Vitro Inhalation Device (DAVID) that delivers aerosols in different patterns to human lung cells cultured at an air-liquid interface (ALI). METHODS/STUDY POPULATION: The collection unit of DAVID was modified in this study to accommodate different deposition patterns (spots, annular ring, rectangle & circle). CuO aerosols of varying concentrations were generated using a 6-jet Collison nebulizer for varying time periods to achieve different doses. To quantify the doses that were delivered to cells, the samples were digested with nitric acid & analyzed by Inductively Coupled Plasma-Optical Emission Spectrometry. Following the exposure of A549 cells to CuO aerosols, cytotoxicity and mRNA expression (i.e., HMOX1 & IL-8) will be assessed via LDH and RT-qPCR to determine the effect of regional (mass deposited/area of the pattern) and global (mass deposited/area of the cell culture insert) doses in cells. RESULTS/ANTICIPATED RESULTS: The deposition areas covered by rectangular, spot, annular ring, and circular patterns are estimated to be 6, 17, 27 and 85% of the insert’s surface area, onto which cells are cultured. Results for the patterns tested (spots and annular ring) show that both the regional and global doses were greater for spots than annular ring. Also, the regional doses were higher than global doses. Irrespective of the patterns, the global doses were the same for nebulizer suspensions of 0.1-1 mg/mL. Statistical analysis by ANOVA revealed there was no significant difference in doses between replicate inserts used in the same trial. We anticipate that regional doses with aerosol deposition to a larger surface area of the cell culture insert will correspond with higher cytotoxicity and mRNA expression of HMOX1 and IL-8 in cells. DISCUSSION/SIGNIFICANCE: There are limited in vitro exposure systems that can efficiently deliver aerosols to lung cells, while also mimicking inhalation by humans. In addition to addressing this knowledge gap, we will show the role of regional & global doses in studying cellular response & the ability of DAVID to deliver aerosols in different deposition patterns.