OBJECTIVES/GOALS: This work-in-progress aims to: 1) identify and differentiate symptom pattern trajectories in a sample of older adult heart failure (HF) patients over 24 weeks, and 2) examine associations between sociodemographic/clinical/physiological characteristics, dyadic health, and symptom trajectories. METHODS/STUDY POPULATION: ENABLE CHF-PC, a palliative care RCT (NCT02505425), was conducted at a Southeastern US medical center. Between 2016-2018, 415 older adult HF patients and 159 family caregivers were randomized to receive a psychoeducational intervention or usual care. Baseline sociodemographic information (age, gender, rurality, etc.) were collected. Outcome variables of interest include symptoms (Kansas City Cardiomyopathy Questionnaire (KCCQ), Functional Assessment of Chronic Illness Therapy-Palliative 14, Hospital Anxiety and Depression Scale (HADS)) and dyadic health (PROMIS-SF Global Health). We have calculated baseline descriptive statistics. Future work includes latent growth mixture modeling to identify distinct symptom trajectories and univariate associations with patient level factors. RESULTS/ANTICIPATED RESULTS: Of 415 patient participants, mean age was 64, 53% were male; 55% were African American; 26% were rural dwellers; 46% had +15.8) and low anxiety (6.7+3.6) and depressive symptoms (5.7+4.3) on the HADS. Of 159 family caregivers participants, the mean age was 57.9, 85.4% were female, 51.9% were African-American, and 65.2% were the patient’s spouse/partner. DISCUSSION/SIGNIFICANCE OF IMPACT: Limited data describes HF symptom pattern trajectories.How co-occurring symptoms affect quality of life or are affected by personal or situational factors are not well-understood. This study will help to identify factors and symptom phenotypes that may serve as targets for future interventions.

OBJECTIVES/GOALS: The goal of this mixed methods project is to develop a comprehensive framework of the personal and care-related needs of informal caregivers of people with dementia. This model can be used to enhance targeted delivery of evidence-based services to caregivers in need. METHODS/STUDY POPULATION: To create a model of the personal and care-related needs of family caregivers of people with dementia, we conducted semi-structured in-depth interviews with current caregivers (N = 12) and conducted a content analysis of materials related to government reports and evidence-based interventions (N = 28) and existing measures of dementia caregiver needs (N = 54). Content analysis is a systematic qualitative methodology that is used to distill complex source material into content-related categories and is well-suited for both interview data and document data (Elo & Kyngäs, 2008). We identified themes related to caregiver needs through examination of materials within and across source categories. RESULTS/ANTICIPATED RESULTS: We propose a framework of five inter-related need categories: Environmental needs (e.g., transportation, health-care access, financial resources, time), psychological needs (e.g., emotional wellbeing, identity/autonomy, perceived preparedness), social needs (e.g., social support, family dynamics), health-related needs (e.g., health behaviors, sleep), and needs related to the care and functioning of the person with dementia. We also consider how needs and background characteristics transact to influence which services may be of greatest use. In the future, we plan to test this model empirically with a nationally representative sample of caregivers. DISCUSSION/SIGNIFICANCE OF IMPACT: Evidence-based services exist to meet the needs of dementia caregivers. A dearth of models clearly defining caregiver needs limits empirically-based plans for dissemination of services. We have identified a framework of the needs of family caregivers from which to create targeted dissemination plans.

OBJECTIVES/GOALS: We aim to identify and characterize anti-Sox2-specific CD8+ T cell responses in stable MUGS patients expressing HLA class I alleles-A*02:01 and /or -B*07:02. METHODS/STUDY POPULATION: Cross sectional study of patients with stable MGUS defined as stable serum paraprotein for ≥ 12 months from the MM Research Clinic at the Abramson Cancer Institute. Sox2 T cell reactivity will be assessed by IFN-γ ELISPOT assays. Rested PBMC will be pulsed with candidate Sox2-derived peptides predicted to display high affinity to HLA class I alleles and known to be processed and presented as determined by “targeted MS/MS” (mass spectrometry). The presence of anti-Sox2-specific CD8+ T cells will be confirmed in peptide/HLA multimer assays using flow cytometry. Anti-Sox2-specific CD8+ T cells will be characterized for HLA restriction and TCR αβ composition. RESULTS/ANTICIPATED RESULTS: Our work is still in progress. From Aug to Dec 2019, 22 MGUS subjects have been analyzed, 11 of which were found to have the HLA of interest. Positive Sox-2 reactivity by ELISpot was found in 3 subjects. DISCUSSION/SIGNIFICANCE OF IMPACT: Anti-Sox2 immune responses may maintain MGUS in a clinical indolent state by eliminating Sox2-expressing clonogenic MM cells. A detailed characterization of anti-Sox2 T cells followed by in-vivo assessment of their anti-myeloma activity could provide the foundation for a Sox2 based immunotherapy approach in MM.

OBJECTIVES/GOALS: Neuroblastoma (NB) is the most common extra-cranial solid tumor with outcomes varying from spontaneous regression to metastatic with high mortality rates. The tumor immune microenvironment (TIME) may play a significant role in this disease. In this study we analyze the TIME comparing high-risk (HR) and low-risk (LR) NBs using multiplex platforms. METHODS/STUDY POPULATION: Two tissue microarrays (TMAs) with 2mm cores were created from 41 patients treated at Columbia University Irving Medical Center. Five micron TMA slides were stained for Digital Spatial Profiling (DSP, nanoString) and multiplex immunofluorescence (mIF). For DSP, a 24-patient subset including 11 HR, 8 LR and 4 intermediate risk patients was analyzed for 34 proteins. Protein expression among risk groups was compared using Mann-Whitney t-test. For mIF, TMA FFPE slides were stained for DAPI, CD3, CD8, CD68, HLA-DR, PDL1 and Chromogranin A. Whole TMA cores were captured as 9 -20X multispectral images (MSIs) stitched into a 3x3 MSI using Vectra (Akoya). MSIs were processed with inForm and qualitative analysis performed comparing HR and LR tumors. RESULTS/ANTICIPATED RESULTS: With DSP, we find significantly more HLA-DR in HR compared to LR tumors (p = 0.016). When controlling for immune cells with CD45 we find HLA-DR/CD45 to be higher in HR than LR tumors (p = 0.026). We found increased PD1 and PDL1 expression in all groups without significant difference between LR and HR (p = 0.778 and p = 0.310, respectively). Preliminary analysis of mIF on 9 patients (4 HR and 5 LR) finds HR tumors appear to have more immune cells than LR tumors, specifically more CD3+CD8- T cells while total CD8+ cells may be similar. There may be less macrophages in the HR compared to LR tumors. Completion of image processing and quantitative analysis of mIF data is underway. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased expression of immune markers in NB TIME correlates with higher risk, which is unlike many other tumors. We compared TIME in HR and LR NB using multiplex platforms, DSP and mIF. We find that HLA-DR is more expressed in HR NB while PD1 and PDL1 expression is consistently high and not different between risk groups. Further analysis is underway. CONFLICT OF INTEREST DESCRIPTION: Robyn D. Gartrell-Corrado received grant support from nanoString for Digital Spatial Profiling and received honoraria and travel support from Northwest Biotherapeutics and PerkinElmer, respectively.

OBJECTIVES/GOALS: Intravenous immunoglobulin (IVIG) is used for infection prevention in pediatric B-cell acute lymphoblastic leukemia (B-ALL), but evidence for this is lacking. We describe the prevalence of hypogammaglobulinemia in pediatric B-ALL, predictors of IVIG use and its efficacy for infection prevention. METHODS/STUDY POPULATION: We will conduct a retrospective review of children age 1-21 years with B-ALL treated at Aflac Cancer and Blood Disorders Center from 2010 to 2017. The cohort was identified through the cancer registry. Demographics, disease factors, laboratory values, medications and infection outcomes were linked between the electronic medical record and an institutional database. Outcomes of interest include emergency department (ED) visits, hospitalization days, and episodes of infection. Descriptive statistics will be performed. Outcomes will be compared between IVIG recipients and non-recipients. Univariate and multivariate logistic regression models will assess predictors of IVIG administration. RESULTS/ANTICIPATED RESULTS: We identified 443 patients with B-ALL during the study period who met inclusion criteria. Exclusion criteria included receipt of IVIG or hematopoietic stem cell transplant prior to diagnosis. The average age at diagnosis is 6.5 years (standard deviation 4.8 years); 52.6% are male; 61.6% are white; 61.0% are standard risk per National Cancer Institute criteria. Among eligible patients, 137 (31.1%) received IVIG. We hypothesize that IVIG initiation is associated with hypogammaglobulinemia and history of severe infection. We also anticipate that frequency of emergency department visits, hospitalization days, and episodes of infection will decrease after IVIG initiation. DISCUSSION/SIGNIFICANCE OF IMPACT: The immunological profile of children with B-ALL and factors influencing their susceptibility to infection are still incompletely understood. The benefits of IVIG are unknown. This study will provide evidence for IVIG prophylaxis recommendations in pediatric leukemia patients.

OBJECTIVES/GOALS: Lung cancer is the leading cause of cancer-related mortality in the United States for both men and women. African Americans are disproportionately affected with lung cancer, having higher incidence and mortality rates compared to Caucasian men and women. African American smokers are diagnosed with lung cancer at a lower age with lower cumulative smoking history. Differences in socioeconomic and environmental factors likely contribute to lung cancer disparities, but less is known about acquired biologic alterations that can promote initiation and progression of lung cancer, particularly in African Americans. This is of interest because there may be other biological, genetic, or environmental factors contributing to lung cancer outcomes as it relates to differences in gender and race. One potential biologic variable may be in the DNA repair capacity (DRC), which describes a cell’s ability to repair damage to DNA caused by carcinogens, oxidants, and radiation. Altered DNA repair is a hallmark of cancer, leading to mutations and malignant transformation. We hypothesize that DRC is decreased in African Americans with lung cancer compared to Caucasian Americans with lung cancer, contributing to the disparity that exists in this racial group. We will 1) perform a retrospective chart review to determine demographic differences between African Americans and Caucasians at three central Indiana hospitals and 2) determine the impact of race and lung cancer on DRC amongst African Americans and Caucasians with and without lung cancer. METHODS/STUDY POPULATION: Lung cancer patients are identified in 3 central Indiana hospitals with different payer source and patient populations using ICD codes. Collected demographics include age, gender, pack-years, lung cancer histology, treatment, and mortality. DRC is measured by host-cell reactivation (non-homologous end-joining and nucleotide excision repair pathways) by flow-cytometry. Measurement of DRC is performed on PBMCs obtained from 120 patients (male and female, African Americans and Caucasians with and without lung cancer). Correlation of DRC and lung cancer will be determined by comparing lung cancer diagnosis to quartile DRC, and adjusted for confounders (measured demographics). Correlative measures will include measures of DNA damage and genomic instability. RESULTS/ANTICIPATED RESULTS: 3450 lung cancer patients were diagnosed with lung cancer at Indiana University Hospital between 1/1/2000 – 5/31/2015. Of these, 48.2% were female and 92.7% smokers. African Americans, Caucasians and Other ethnicities represented 12%, 86% and 2%, respectively. Of smokers, 11.4% were African American. The primary payer source was Federal/Medicare. Retrospective review of lung cancer patients from two additional health systems (county and VA hospitals) will be performed as above with outcomes measured. DRC and additional correlative measures will be performed as in Methods. DISCUSSION/SIGNIFICANCE OF IMPACT: If present, altered DRC in African Americans compared to Caucasians may contribute to the disproportional impact of lung cancer on African Americans. If DRC is decreased in African Americans with lung cancer, future studies will focus on identifying potential genetic, epigenetic and environmental causes for this decrease.

OBJECTIVES/GOALS: The objective of this study is to examine the relationship between gastro-intestinal (GI) patients’ health literacy levels and patients’ health outcomes (length of stay, readmission, complication). METHODS/STUDY POPULATION: A research team at the University of Alabama at Birmingham (UAB) ‘s Gastro-Intestinal (GI) surgical department collected inpatient GI patients’ health literacy data by distributing the Brief Health Literacy Screen (BRIEF) survey to patients are about to be discharged. Patients’ health outcomes data were gathered through Business Objects, an online platform that allows physicians and researchers to access and gather patients’ medical information with an IRB approval. After accounting for necessary control variables, logistic regression and multiple linear regression models will be run to assess whether there is a significant relationship between patients’ health literacy levels and patients’ health outcomes. RESULTS/ANTICIPATED RESULTS: Three specific hypotheses are proposed in this study. H1: GI patients’ health literacy levels will be negatively associated with their lengths of stay H2: GI patients’ health literacy levels will be negatively associated with their readmission status to the hospital H3: GI patients’ health literacy levels will be negatively associated with their complication status to the hospital DISCUSSION/SIGNIFICANCE OF IMPACT: This study allows us to further our understanding of patients’ health literacy level and its’ relationship with important health outcomes. By looking at a variety of diverse health outcomes, the impact of a patients’ health literacy level on that patients’ health outcomes will be observed more clearly.

OBJECTIVES/GOALS: Designed sampling from databases (DSD) methods have been used to cross-check electronic medical records for errors, structure study design, and, we hypothesize, can be used to make data collection for surgical quality metrics more efficient, particularly within national databases. We plan to apply statistical and DSD methods to accomplish the following aims:

1. 1. Identify the most important elements in managing post-operative pain

2. 2. Identify the most informative procedure or population-based targets to focus collection of additional, labor-intense detail surrounding adequacy of pain control (i.e., Patient Reported Outcome Measures (PROMs)).

METHODS/STUDY POPULATION: Our study population includes all children, ages 1-18 years, captured in the National Surgical Quality Improvement Project-Pediatric (NSQIP-P) from 2019 to 2021. We plan to apply statistical (regression modeling) and DSD methods to accomplish the aims listed above. RESULTS/ANTICIPATED RESULTS: For Aim 1, we expect to identify patient, procedure, and perioperative pain management practices that influence postoperative pain. For Aim 2, we will focus on outcomes such as PROMs that are challenging to obtain. By applying DSD methods, we will identify specific procedure and/or population-based cohorts to capture PROMs and decrease data collection burdens, while maintaining power, as the project is scaled nationally to all of NSQIP-P. DISCUSSION/SIGNIFICANCE OF IMPACT: Data from this study will inform expansion of NSQIP-P to collect novel outcomes of clinical and societal importance without prohibitively increasing data collection burden.

OBJECTIVES/GOALS: The aim was to examine whether nicotine patch was more effective in encouraging abstinence from cigarettes smoking compared to placebo. METHODS/STUDY POPULATION: Randomized controlled trials involving the general teenage age group smokers who were current smokers-“smoked less than 100 cigarettes over their lifetime and smoked at the time of the interview. Databases were searched for relevant studies reported in English that employed a randomized design published since 2000. Two authors extracted data and assessed quality. The primary outcomes and prioritization were continuous abstinence at 3, 6 and 12-month follow-up or more for the number of patients who responded to treatment, defined as a reduction/abstinence. Heterogeneity between studies did not preclude combined analyses of the data. RESULTS/ANTICIPATED RESULTS: 4 of 266 publications were included. Four studies reported positive effects on smoking cessation at end of treatment: (1) nicotine patches improved continuous abstinence at 6 weeks – 9 weeks months; (2) nicotine patch improved continuous abstinence at 3 to 6 months; (3) nicotine patches improved continuous abstinence 6 and 12 months; (4) nicotine patches improved continuous abstinence at 6 months – 12 and 24 months (5). All studies showed, continuous abstinence at follow up differed in percentage between groups both at 6 weeks through 24 months, with NRT (Nicotine patch) intervention groups achieving higher rates in most of the studies compared to placebo intervention group. Conclusions: NRT intervention methods seem to increase smoking abstinence in those treated for smoking cessation. Further and larger sample size studies are required to make stronger the base of evidence. DISCUSSION/SIGNIFICANCE OF IMPACT: Four randomized controlled trials investigating the effectiveness of smoking cessation interventions, for teenagers who smoke cigarettes were identified for inclusion in this review. Four of the studies reported significant effects on smoking cessation, providing evidence of effectiveness of NRT (nicotine patch), behavioral support and combinations of the two, although not all trials intervention treatments found an effect. The four studies reported important intervention effects at both the short and long follow-ups required: 6 weeks up to the 24 months, thereby, providing stronger evidence to support the effectiveness of NRT intervention on smoking cessation. All studies showed some evidence of improved smoking abstinence outcomes. The four studies had in common that the smoking cessation interventions provided a combination of intent to treat prevention, and of all the clinical trials none of them suggested a negative effect of smoking cessation treatment on substance use outcomes using NRT. However, the studies used reliable methods and reported their cases properly, but the small number of studies reviewed for the systematic review makes the conclusion about the effectiveness of these interventions uncertain. The papers visibly stated how the trials protected against bias, as indicated by the Yes (low risk). No (high risk) and U as “unclear risk.” All four studies conducted a random sequence generation of participants enrolled into the study sample.

OBJECTIVES/GOALS: Leveraging Patient’s Experience to improve Diagnosis (LEAPED) is our proposed method of measuring diagnostic error through seeking patient feedback on their understanding of their diagnosis and health status following emergency department discharge. To pilot test LEAPED’s feasibility, we deployed and determined patient uptake of LEAPED. METHODS/STUDY POPULATION: To test LEAPED, we employed a longitudinal cohort study design at emergency departments across one academic health system in the Mid-Atlantic region. Patients consented to complete questionnaires regarding their understanding of their diagnosis and/or follow-up steps and their health status at 2 weeks, 1 month, and 3 months following emergency department discharge. People aged 18 and older who were seen at the emergency department within the past 7 days with at least one chronic condition (hypertension, diabetes, history of stroke, arthritis, cancer, heart disease, osteoporosis, depression, and/or chronic obstructive lung disease) and one or more of the following common chief complaints: chest pain, upper back pain, abdominal pain, shortness of breath/cough, dizziness, and headache were eligible to join the study. RESULTS/ANTICIPATED RESULTS: Of those enrolled (n = 59), 95% (n = 53) responded to the two week post-ED discharge questionnaire (1 and 3-month ongoing). Of the 6 non-responders, 1 had died and 3 were hospitalized at two weeks. The average age was 50 years (SD 16) and 64% were female. Over half of participants (53%) were white and 41% were black. Almost one-third (27%) reported they were not given an explanation of their health problem on leaving the ED, and of those, a third did not have an understanding of what steps to take after leaving the ED. Participants reported a new health problem was identified after ED discharge (19%), worsening health status (12%), and health status stayed the same (16%). DISCUSSION/SIGNIFICANCE OF IMPACT: Patient uptake of LEAPED was high, which suggests that patient-report is a feasible method of evaluating diagnostic decision making and delivery to patients and yields insightful information beyond administrative data. The next steps are to validate the accuracy of patient-reported diagnostic error by comparing with administrative data.

OBJECTIVES/GOALS: This study evaluates the utility of self-reported quality of life measure in children with hearing loss. We will compare self-reported HEAR-QL scores with parent-reported HEAR-QL scores. We will then test the relationship between HEAR-QL scores and scores on a standardized assessment of cognition, the NIH Cognition Battery. METHODS/STUDY POPULATION: We will administer the HEAR-QL questionnaire to children with hearing loss and their parents. We will then administer the NIH Cognition Battery to the child. We will include in our population children ages 7 to 14 with hearing loss of any severity or side. We will exclude those with intellectual disability, disorders of speech or language, or those who would be unable to complete the questionnaires for any reason. Children will be recruited from Otolaryngology clinics at St. Louis Children’s Hospital based on ICD diagnosis of sensorineural hearing loss between 01/2015 – 03/2020. RESULTS/ANTICIPATED RESULTS: We will aim to recruit 44 patients in total, which is the sample size needed to detect a moderate correlation (r = 0.4) with a 1-sided α = 0.05 and 1-β = 0.8. HEAR-QL scores and NIH Cognition Battery scores will be reported using descriptive statistics. Linear regression as well as correlation analysis between HEAR-QL scores and cognitive testing scores will be performed using a 1-sided α = 0.05, with 1-β = 0.8. If recruitment is sufficient, we will adjust for demographics that are significantly correlated with the outcome on multivariate analysis. Finally, we will test for agreement between parent report and child report by calculating a Kappa statistic. DISCUSSION/SIGNIFICANCE OF IMPACT: There is little clarity on the necessity of amplification in children with hearing loss, yet the child’s perspective is not routinely assessed in clinical practice. This study employs self-report in a pediatric population with hearing loss to find out if children provide new and reliable information.

OBJECTIVES/GOALS: To determine the relationship among serum concentration of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and mortality in community-acquired pneumonia (CAP) patients. METHODS/STUDY POPULATION: This is a multicenter 2-year cohort study in Spain, designed to better understand the role of sTWEAK concentrations in CAP patients. CAP patients were prospectively enrolled in two University hospitals and sTWEAK was measured within the first 24 hours of ICU admission. Samples were collected and stored for laboratory analyses. To detect sTWEAK in human samples, we used a commercially available ELISA kit following manufacturer’s instructions. Demographic patients’ characteristics and ICU mortality were prospectively collected. Descriptive statistics and logistical regressions were used to assess the proposed aims. RESULTS/ANTICIPATED RESULTS: A total of forty-three patients were included in the study (10 healthy users, 10 uninfected controls and 23 CAP patients). In comparison to healthy volunteers, patients admitted to the hospital (both, infected and non-infected) had lower level of sTWEAK. During hospital admission, 7 (17%) patients died. Patients whom died during ICU stay due to CAP, had significantly lower levels of sTWEAK when comparing with patients whom survived (Median [IQR]; 509.35 [357.49, 953.92] Vs 1103.03 [716.93, 1663.16]; p = 0.015). In contrast, patients that developed shock did not have different concentrations of sTWEAK (Median [IQR]; 1008.04 [531.87, 1390.80] Vs 1062.29 [575.24, 1598.83], p = 0.84). DISCUSSION/SIGNIFICANCE OF IMPACT: Community-acquired pneumonia (CAP) is the first cause of death in underdeveloped countries. CAP is a pulmonary infection that creates a proinflammatory environment not just locally but also systemically, secondary to upregulation of molecular cascades with a wide variety of proteins being released perpetuating this inflammation and tissue damage. Several of these molecules have been described and linked to a greater risk of inhospital complications, longer length of hospital stay and mortality. TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF-alpha superfamily, involved in immune response, cell growth, angiogenesis, NF-kB activation and apoptosis induction in tumor cells. It is known that serum-TWEAK plays a role in inflammatory processes, however, its behavior is unknown in patients with CAP. Therefore, this study aims to identify whether there is a relationship between serum concentration of TWEAK and prognosis in CAP patients. To our knowledge, this is the first study to shown that concentration of sTWEAK within the first 24 hours of ICU admission is lower in patients with CAP. Moreover, patients whom died during ICU admission due to CAP, have lower sTWEAK levels. This biomarker may identify patients at higher risk of dying due to CAP and may represent severe CAP. However, further studies are needed to confirm these findings.

OBJECTIVES/GOALS: Asthma is a significant health concern that affects people of all ages worldwide. EAS demonstrates many of the pathophysiological characteristics of nonatopic human asthma, which has led EAS to be used as naturally occurring model. Previous work from our lab determined that MARCKS (Myristoylated Alanine Rich C Kinase Substrate) protein is an essential regulator of cellular inflammatory functions. In the current study, we hypothesized that MARCKS levels would be increased in BAL cell lysates from horses with EAS, and that inhibition of MARCKS in zymosan-stimulated BAL cells (ex vivo) would diminish respiratory burst. METHODS/STUDY POPULATION: Lysates were prepared from BAL cells isolated from horses with no, mild/moderate and severe EAS. Relative MARCKS protein levels were determined using equine specific MARCKS ELISA (MyBioSource). Cultured BAL cells were pretreated with a MARCKS inhibitor peptide (MANS), control peptide (RNS) or vehicle control and stimulated with zymosan for 5 hours. Reactive oxygen species levels were determined by luminescence to evaluate respiratory burst. Data were analyzed by One-way ANOVA (p<0.05). RESULTS/ANTICIPATED RESULTS: We determined that normalized MARCKS protein expression is significantly increased in BAL cell lysates from horses with mild/moderate or severe EAS, compared to horses with normal BAL cytology. Preliminary findings also suggest that MANS treatment of zymosan-stimulated equine BAL cells ex vivo attenuates levels respiratory burst. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings point to a possible role for MARCKS protein in the pathophysiology of EAS and support MARCKS inhibition as a potential therapeutic strategy.

OBJECTIVES/GOALS: The goal of this study is to better understand the homicide victim population who were institutionalized within 30 days prior to their death. Improved knowledge of this population can potentially prevent these future homicides. METHODS/STUDY POPULATION: A retrospective analysis of the 36 states included in the 2003-2017 National Violent Death Reporting System was performed. Demographics of recently institutionalized homicide victims (RIHV) in the last 30 days were compared to homicide victims who were not recently institutionalized. Circumstances of the homicide, such as suspected gang involvement, were also compared. Parametric and non-parametric statistical analyses were performed. Significance was set at p<0.05. RESULTS/ANTICIPATED RESULTS: There were 81,229 homicides with 992 (1.2%) RIHV. The majority of RIHV were Black (49.6%) and older than victims who were not recently institutionalized (37.2 vs. 34.8, p<0.001). RIHV had a high school degree or higher in 54.8% of cases and the primary homicide weapon was a firearm in 67% of the deaths. They were more likely to be homeless (3.1% vs. 1.5%), have a mental health diagnosis (9.2% vs. 2.3%), abuse alcohol (6.1% vs. 2.2%), or abuse other substances (15.2% vs. 5.8%) [all p <0.001]. These victims were most commonly institutionalized in a correctional facility or a hospital compared to other facilities such as nursing homes. Homicide circumstances for RIHV were more likely to involve abuse/neglect (4.3% vs. 2.2%, p<0.001), gang violence (7.6% vs. 5.6%, p = 0.002), or a hate crime (1.0% vs. 0.1%. p<0.001). DISCUSSION/SIGNIFICANCE OF IMPACT: Contact with an institution such as a hospital or prison provides high-risk patients the opportunity to potentially participate in violence intervention programs. These institutions should seek to identify and intervene on this population to reduce the risk of violent homicides.

OBJECTIVES/GOALS: The goal of this project is to identify new therapeutic targets and biomarkers to treat or prevent cocaine toxicity by investigating proteomic, transcriptomic and epigenetic signatures of cocaine exposure in human subjects. METHODS/STUDY POPULATION: Cocaine is a highly addictive neurotoxic substance, and it is estimated that 1.9 million Americans are current users of cocaine. To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem dorsolateral prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine-exposed subjects and 17 controls. Future directions for this project include RNAseq and DNA methylation analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF IMPACT: Neuronal signatures found with this analysis can help us understand mechanisms of cognitive decline in long-term cocaine users as well as the acute effects on the brain of cocaine taken in overdose. With this work and future proposed studies, we can discover novel clinical biomarkers for cocaine neurotoxicity in patients with cocaine use disorder and determine readouts for future therapeutic development on cocaine addiction and overdose.

OBJECTIVES/GOALS: A particularly debilitating consequence of stroke is alexia, an acquired impairment in reading. Cognitive models aim to characterize how information is processed based on behavioral data. If we can concurrently characterize how neural networks process that information, we can enhance the models to reflect the neuronal interactions that drive them. METHODS/STUDY POPULATION: There will be 10 unimpaired adult readers. Two functional localizer tasks, deigned to consistently activate robust language areas, identify the regions of interest that process the cognitive reading functions (orthography, phonology, semantics). Another task, designed for this experiment, analyses the reading-related functional-connectivity between these areas by presenting words classified along the attributes of frequency, concreteness, and regularity, which utilize specific cognitive routes, and a visual control. Connectivity is analyzed during word reading overall vs. a control condition to determine overall reading-related connectivity, and while reading words that have high vs. low attribute values, to determine if cognitive processing routes bias the neural reading network connectivity. RESULTS/ANTICIPATED RESULTS: The localizer analysis is expected to result in the activation of canonical reading areas. The degree of functional connectivity observed between these regions is expected to depend on the degree to which each cognitive route is utilized to read a given word. After orthographic, phonologic, and semantic areas have been identified, the connectivity analysis should show that there is high correlation between all three types of areas during reading compared to the control condition. Then the frequency, regularity, and concreteness of the words being read should alter the reliance on the pathways between these area types. This would support the hypothesized pattern of connectivity as predicted by the cognitive reading routes. Otherwise, it will show how the neural reading network differs from the cognitive model. DISCUSSION/SIGNIFICANCE OF IMPACT: The results will determine the relationship between the cognitive reading model and the neural reading network. Cognitive models show what processes occur in the brain, but neural networks show how these processes occur. By relating these components, we obtain a more complete view of reading in the brain, which can inform future alexia treatments.

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.

OBJECTIVES/GOALS: Pancreatic cysts are comprised of both precancerous mucinous lesions and non-mucinous lesions with minimal malignant potential. Our goal is to improve our ability to classify the type of cyst using a combination of novel radiomic features and cyst fluid proteolytic activity. METHODS/STUDY POPULATION: Preoperative pancreatic protocol CT images from 30 patients with proteolytic assay characterization, followed by surgical resection with a pathologically confirmed pancreatic cyst diagnosis between 2016-2019 will be used in this study. We will contour images using the widely available software 3D Slicer, and extract radiomic features using IBEX software. We will analyze area under the ROC curves to identify the radiomic features that best differentiate mucinous from non-mucinous cysts, and identify features to be cross validated. The predictive ability of identified radiomic features combined with proteolytic assay will be determined by performing multiple logistic regression analysis and comparing AUROC analysis. We will determine sensitivity and specificity for individual, as well as combinations of, analytes to determine the optimal classifier. RESULTS/ANTICIPATED RESULTS: We anticipate that the predictive ability, sensitivity, and specificity of utilizing radiomic features combined with proteolytic assay data will exceed the performance of any individual test. DISCUSSION/SIGNIFICANCE OF IMPACT: This work is designed to provide a predictive radiomic model that will enable us to better identify mucinous cysts that require further evaluation, and potentially prevent unnecessary surgery in other patients. Ultimately, we would like to improve the accuracy of noninvasive radiographic evaluation using radiomic markers. CONFLICT OF INTEREST DESCRIPTION: Dr. Charles Craik is a co-founder of Alaunus Biosciences, Inc.

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.

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.