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/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.

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/Goals: Although the Deepest Vertical Pocket (DVP) method is increasingly used to assess amniotic fluid volume due to its simplicity and lower intervention rates, its relationship with neonatal outcomes remains underexplored. This study aims to determine if DVP measurements are associated with Apgar scores at 1 and 5 minutes in low-risk term pregnancies. Methods/Study Population: An IRB-approved retrospective cohort study of 171 singleton term pregnancies delivered at Penn State Hershey Medical Center between 2019 and 2024 was performed. Inclusion criteria included delivery at ≥37 weeks, birth weight between the 10th and 90th percentiles, absence of fetal anomalies, spontaneous labor or scheduled Cesarean, and classification as low risk based on ACOG 2019 Levels of Maternal Care guidelines. A single second-trimester DVP measurement was obtained from anatomy ultrasounds. Apgar scores at 1 and 5 minutes were abstracted from delivery records. Statistical analysis included ANOVA and Spearman correlation to assess relationships between DVP and Apgar scores. Results/Anticipated Results: Among 171 patients, the mean DVP was 4.79 cm (SD 0.94). Apgar scores at 1 minute were most commonly 8 (73%) or 9 (15%), and 94% of neonates had a score of 9 at 5 minutes. There was no statistically significant correlation between DVP and Apgar scores at 1 minute (Spearman r = –0.11, p = 0.14) or 5 minutes (r = 0.10, p = 0.19). ANOVA results also revealed no significant differences in DVP across Apgar score categories at 1 minute (p = 0.12) or 5 minutes (p = 0.41). Discussion/Significance of Impact: In this cohort of low-risk term pregnancies, DVP was not significantly associated with Apgar scores at 1 or 5 minutes. This study is one of the few to isolate DVP rather than AFI and to apply it to routine obstetric care. These findings support the use of DVP as a non-invasive, reliable fluid assessment method without concern for adverse neonatal outcomes.

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: 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: 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: 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/Goals: Our study’s primary objective is to develop a multivariate random effects meta-analysis model that estimates risk ratio at a series of clinically relevant time points. Our goal in doing so is to address gaps in traditional hazard ratio (HR) meta-analyses due to observed time-varying treatment effects. Methods/Study Population: Our model estimates pooled risk ratios (RRs), the ratio of cumulative event probabilities, at predefined timepoints (e.g., 12, 24, 36 months). We derive the variance of the log-RR for each trial at each time point by applying the delta method to the Kaplan-Meier (KM) estimator function. Furthermore, we will derive the covariance to account for the correlation between RR estimates at different time points within the same trial. We would then like to incorporate these derivations of within-trial variance and covariance at each available time milestone into our multivariate model to increase the precision of our pooled RR estimated for both Overall Survival (OS) and Progression-Free Survival (PFS). Results/Anticipated Results: We identified 7 trials by consulting 5 systematic reviews published through 2021-2025 to ensure use of updated data. We reconstructed the pseudo-Individual Patient Data of these trials by applying PDFs of published KM curves to a validated survival curve reconstruction algorithm. For the outcome of overall survival, the max amount of follow-up time recorded is 108 months. On the other hand, there are 96 months of available follow-up for the outcome of progression-free survival. In a univariate random effects meta-analysis of HR for OS, the pooled HR was found to be 0.81 (CI: 0.74 – 0.89). Additionally, the pooled HR for PFS was found to be 0.68 (CI: 0.59 – 0.79). For both outcomes, we anticipate the multivariate random effects analysis of Risk Ratio to yield more precise confidence intervals than those of HR. Discussion/Significance of Impact: The proposed multivariate meta-analysis model will improve precision of treatment effect estimates which will add to the ongoing evaluation of immunotherapies as a current standard of care. This is significant to translational science as it provides time-specific treatment effect estimates that could be more interpretable in a clinical setting.

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/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: 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.

OBJECTIVES/GOALS: Development of interventions that improve social functioning (SF) in first episode psychosis (FEP) is hindered by a poor understanding of the neural mechanisms underlying SF deficits. This research aims to identify neural correlates of social functioning in FEP, and to evaluate whether this substrate is malleable in response to cognitive training. METHODS/STUDY POPULATION: This is a secondary data-analysis of participants in an ongoing randomized clinical trial investigating whether 12 weeks of targeted cognitive training is neuroprotective in FEP, versus treatment as usual. Baseline and post-training assessments include a brain MRI, three measures of SF, and a neurocognitive battery. Healthy controls complete MRI only. Differences in cortical thickness (CTh) and gray matter volume (GMV) in regions of interest between FEP and controls will be determined with ANCOVA. Multiple linear regression will be used to determine the relationship between neural substrate and SF in FEP. Linear mixed models will be used to examine the relationship between change in CTh and GMV and change in SF. Data collection is ongoing for this study. RESULTS/ANTICIPATED RESULTS: In preliminary data including 12 FEP and 9 healthy controls, FEP demonstrated cortical loss in the right superior frontal cortex and the right isthmus-posterior cingulate. Greater cortical thickness in the posterior cingulate cortex was associated with better social functioning across multiple measures when controlling for global cognition. Gray matter volume in the parahippocampal gyrus was also associated with better social functioning. Preliminary results evaluating whether targeted cognitive training is neuroprotective in these regions of interest in a manner that is associated with improved social functioning will also be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results link the posterior cingulate and parahippocampal gyrus to SF in FEP. Further research will investigate the contribution of changes in these brain regions to improved SF. The identification of biological treatment targets for SF may lead to development and optimization of novel interventions to alleviate SF deficits in FEP.

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

OBJECTIVES/GOALS: Patients who require a hematopoietic cell transplant (HCT) and dont have an HLA-matched related or unrelated donor may rely on a haploidentical donor. The optimal haploidentical donor and guidance for selection is limited. We aim to determine how donor characteristics affect outcomes following haploidentical-HCT for pediatric patients. METHODS/STUDY POPULATION: This is a retrospective cohort study evaluating the effect of donor age and relationship on post-HCT outcomes in children (0-18y) from 2008-2018. Multivariable logistic regression analysis will identify if donor age or donor relationship affect the development of graft-versus-host-disease (GVHD), while adjusting for other patient, donor, and transplant related variables. Two-year overall survival & event-free survival will be determined using Kaplan-Meier curves, stratified by donor age group and donor relationship, and compared by log-rank testing. Sub-analyses will be performed for myeloablative transplants and reduced intensity conditioning, as well as for malignant and non-malignant diseases. RESULTS/ANTICIPATED RESULTS: Our primary aim to is determine the effect of donor age and the effect of donor relationship to patient on the development of GVHD. We hypothesize that utilization of a younger donor will decrease the incidence of GVHD. Further, we hypothesize that utilizing a sibling haploidentical donor will result in less GVHD than a parental donor. Secondary aims include evaluating the effect of donor age and donor relationship on overall survival, event-free survival, non-relapse mortality, relapse, graft failure and time to engraftment. The results of this study will help us to develop criteria for optimal haploidentical donor selection. If donor selection is optimized, this could result in improved outcomes following haploidentical transplants. DISCUSSION/SIGNIFICANCE: Haploidentical donors are increasingly used as many patients, especially ethnic minorities, do not have an HLA-matched donor. This will be the largest study of haploidentical HCT in children. The data gathered will allow us to identify important donor characteristics to help guide physician decision-making when choosing a haploidentical donor.

OBJECTIVES/GOALS: Scholarly activity is a key component of most residency programs. To establish fundamental research skills and fill gaps within training curricula, we developed an online, asynchronous set of modules to introduce trainees to various topics that are germane to the conduct of research and evaluated its effectiveness in resident research education. METHODS/STUDY POPULATION: Research 101 was utilized by residents at the Brookdale Hospital Medical Center in Brooklyn, NY. Resident knowledge, confidence, and satisfaction were assessed using pre- and post-module surveys with 5-point Likert scaled questions, open-ended text responses, and a final quiz. RESULTS/ANTICIPATED RESULTS: Pre-module survey results indicated that residents were most confident with the Aligning expectations, Introduction to research, and Study design and data analysis basics modules and least confident with the Submitting an Institutional Review Board (IRB) protocol at UC and Presenting your summer research modules. Post-module survey responses increased significantly compared to pre-module results for all modules and learning objectives (p<0.0001). “This module met my needs” was endorsed 91.4% of the time. A final quiz of 25 multiple choice questions resulted in a median score of 23. Content analysis of open-ended post-module survey responses identified multiple strengths and opportunities for improvement in course content and instructional methods. DISCUSSION/SIGNIFICANCE: These data demonstratethat residents can benefit from completion of Research 101, as post-module survey scores were significantly higher than pre-module survey scores for all modules and questions, and final quiz scores were high and highlighted opportunities for additional resident learning.

OBJECTIVES/SPECIFIC AIMS: The primary objective of this study is to determine the prevalence of maternal GBS colonization and demographic risk factors associated with maternal GBS colonization in Latin America. Secondary objectives include: To determine if there is an association between maternal colonization with GBS and stillbirth or preterm birth in Latin America. To determine the effect of cesarean section (CS) on the incidence of neonatal sepsis with GBS in mothers colonized with GBS. METHODS/STUDY POPULATION: Study Population: Pregnant women who received prenatal care at sites that utilize the Perinatal Information System (SIP) from 1989 through 2015, and were screened for GBS between 35 and 37 weeks of gestation. Maternal exclusion criteria included spontaneous abortion, stillbirth before 35 weeks, and lack of screening for GBS. Methods: Estimated prevalence (and 95% confidence interval) of maternal GBS colonization for the entire data set, by region, and by country. The prevalence data for each country further stratified by maternal age, ethnicity, education, civil status and habitation. Descriptive statistics calculated for each clinical prenatal and clinical perinatal health indicator as well as for each clinical history variable for GBS colonized and non-GBS colonized women. Odds ratios will be calculated for each demographic and clinical risk factor. Fisher’s exact tests will be used to test hypotheses about the relationship between maternal GBS colonization and specific perinatal outcomes such as stillbirth or preterm birth. We will use multiple logistic regression models to test the hypotheses about the relationships between demographic variables, maternal GBS colonization and perinatal outcomes. RESULTS/ANTICIPATED RESULTS: Preliminary results: 712,061 records included in database. 98,852 records with data for GBS screening. o90.6% White, 7.4% Mixed, 0.6% Black, 0.3% Native Indian, 0.1% Other. GBS prevalence among screened women, 17.5% There was a significant association between maternal GBS colonization and ethnicity (X2 (4, N=97006)=569.901, p<0.01) o Prevalence rates by ethnicity: 20.5% Black, 18.4% White, 15.2% Native Indian, 8.8% Mixed, 3.3% Other. There was a significant association between maternal GBS colonization and age (X2 (4, N=98655)=119.901, p<0.01) o Prevalence rates by age group:. Age ≤ 20 - 15.2%. Age 21-34 – 17.8%. Age ≥ 35 – 19.6% Anticipated results:. GBS positive mothers will have an increased burden of stillbirth and preterm birth compared to GBS negative mothers. Neonates born to GBS colonized mothers who deliver via cesarean section will have a decreased incidence of sepsis compared to neonates born to GBS colonized mothers who deliver vaginally DISCUSSION/SIGNIFICANCE OF IMPACT: There have been no comprehensive studies to date that use the CLAP data to characterize the epidemiology of maternal GBS colonization and GBS disease and the burden of neonatal GBS disease in Latin America. Taking advantage of this unique database, this is the first region-wide study using systematically collected data. Our preliminary analysis indicates that GBS colonization status among pregnant women in Latin America is 17.5%, which is greater than previously reported. While there is evidence that maternal carriage of GBS is associated with stillbirth, this will be the first study to quantify the burden of GBS-associated stillbirth in Latin America. Additionally, previous work has been inconclusive in regards to maternal colonization with GBS and its association with preterm birth. This will be the largest study to evaluate the association of maternal GBS carriage with preterm birth. Findings from this study have the potential to inform public health policy and interventions by identifying the prevalence and risk factors.

Objectives/Goals: Safely and effectively translating AI classification models requires robust post-deployment monitoring. Yet there is little guidance about how to do so. Here, we outline how standard machine learning model development study designs are insufficient for post-deployment monitoring, and what specific study designs are needed. Methods/Study Population: We made original linkages between machine learning methodology and biostatistics, particularly to diagnostic testing, for study design guidance on post-deployment model performance and fairness assessment. Results/Anticipated Results: The kind of case–control sampling typically used for model development cannot give valid estimates of the Positive Predictive Value (precision) and may suffer from verification bias; in a pragmatic clinical trial, or under deployment, only the PPV can be measured, unless there is random confirmatory testing of predicted negatives. This is important for measuring sensitivity, specificity, and False Omission Rate as a fairness metric. Discussion/Significance of Impact: By linking well-understood biostatistics principles (e.g., diagnostic testing) to machine learning classifier evaluation, we show what is required for rigorous evaluation of models in clinical practice. This will establish clear guidance and rigorous standards of practice for study design and analytic aspects of post-deployment monitoring.