ABSTRACT IMPACT: Glucocorticoid steroids are commonly used despite known dose-dependent cardiovascular toxicity, yet little is known about a) how patients with other cardiovascular risk factors use glucocorticoids, and b) how risks of glucocorticoid treatment might vary depending on a patient’s baseline cardiovascular risk. OBJECTIVES/GOALS: Up to one-third of RA patients use long-term glucocorticoids (GCs) despite a known, dose-dependent association with increased risk of major adverse cardiovascular events (MACE). We aim to evaluate patterns of GC use among RA patients with other MACE risk factors (i.e. diabetes, smoking), and examine how GC use may potentiate these risk factors. METHODS/STUDY POPULATION: We used claims data from Veterans Health Administration to identify 6,090 RA patients with ≥1 rheumatology clinic visit during 2013-2017. We used logistic regression to evaluate associations between incident MACE between 2013-2018, recent long-term GC use, and 5 MACE risk factors: hypertension, diabetes, hyperlipidemia, smoking, and prior MACE. We included two-way interaction terms between GC use and each risk factor. We used a claims-based algorithm to define MACE as any of acute MI, ischemic stroke, TIA, sudden death, or coronary revascularization, between index date and 12/31/2018. We defined index date as first rheumatology visit after meeting RA diagnostic criteria, and recent long-term GC use as ≥90 days’ supply dispensed over 2 years prior to index date. RESULTS/ANTICIPATED RESULTS: Among 2,884 eligible patients,1,553 (54%) had MACE risk factors, and 97 (3%) had prior MACE (Table 1). Overall, 16% of patients recently used long-term GC, compared to 17% of patients with MACE risk factors, and 22% of patients with prior MACE. Incident MACE occurred in 308 (11%) patients, 24% of whom had recent long-term GC use. Recent long-term GC use was independently associated with increased incident MACE (Table 2). While no interaction term was statistically significant overall, differences in odds of incident MACE were seen across levels of recent GC use for several risk factors, particularly diabetes (OR 2.10, 95% CI [0.93-4.77]), tobacco use (OR 2.88, 95% CI [1.16-7.14]) and prior MACE (OR 2.41, 95% CI [0.73-7.95]). DISCUSSION/SIGNIFICANCE OF FINDINGS: Long-term GC use is common among RA patients with MACE risk factors. In this cohort, 25% of patients with incident MACE had recently used long-term GC. Long-term GC use may potentiate effects of comorbidities like diabetes and smoking, disproportionately increasing MACE risk in certain patients.

OBJECTIVES/SPECIFIC AIMS: The aim of this study is to understand how porosity and collagen filling impact cell proliferation and differentiation in 3D printed scaffolds. METHODS/STUDY POPULATION: 3 groups of scaffolds will be 3D printed using FDM: solid scaffold, porous scaffold and porous scaffold with collagen gel (n=10 for each group) Internal geometries and surface structure will be analyzed using micro CT and Scanning Electron Mi RESULTS/ANTICIPATED RESULTS: We hypothesize that porosity and collagen filler will increase signal from Picogreen assay and ALP assay when normalized to scaffold surface area, indicating enhanced cell proliferation and differentiation. DISCUSSION/SIGNIFICANCE OF IMPACT: 3D printing PCU is a relatively new technique with very little published in the literature. Previous work has focused on the mechanical properties and not the biological response to the polymer. Understanding how to optimize cellular proliferation and differentiation can lead to the development of better implants that will integrate into the host’s structure and facilitate tissue regeneration.

OBJECTIVES/GOALS: The need for mechanisms of ethical discourse and guidance has increased as translational research collaborations become more complex. The goal of this project is to analyze the stakeholder engagement and ethical issues our research ethics consultation service (RECS) conducted over a two year period. METHODS/STUDY POPULATION: We conducted a retrospective review of our RECS database from 2020 to 2022. We examined the nature of the research and ethical issues of concern from consult requestors, including whether or not consults were preventative. In addition, we assessed the educational outreach conducted during that timeframe as a measure of service awareness. RESULTS/ANTICIPATED RESULTS: There was a total of 42 consults conducted over the previous year. There were a wide variety of issues related to informed IRB-related processes (31%), consent (24%), QA/QI determination (12%), authorship (10%), confidentiality (7%), diversity/inclusion (7%), grant preparation (7%). Many of the consults (n=28, 67%) included secondary issues. A few consults (n=4, 10%) were preventative, meaning that the consult was requested in anticipation or consideration of a potential ethical issue. Outreach efforts extended to a diverse array of institutional stakeholders and trainees. DISCUSSION/SIGNIFICANCE: The RECS serves numerous constituencies throughout our institution on ethical issues spanning nearly all aspects of research design, conduct, and analysis. These data highlight initiatives to increase study efficiency (in collaboration with institutional research oversight) and helps to direct educational efforts and outreach.

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: The COVID-19 pandemic has impacted nursing frontline professionals. The aims of this study were to explore experiences of nursing professionals in Puerto Rico during the pandemic, examine the impact on their health and provide research development opportunities enhance research capacity. METHODS/STUDY POPULATION: This interpretative phenomenological study recruited graduate nurses who participated in one in-depth semi-structured virtual interviews. Interviews were audio recorded and transcribed. The data analysis process was guided using the following steps: 1. Reading and re-reading, 2. Initial noting, 3. Developing emergent themes, 4. Searching for connections across emergent themes, 5. Moving to the next case, 6. Looking for patterns across cases, and 7. Writing up. In addition, Van Manen's thematic structure of four foundations was used as a complement to guide reflection and interpretation. Faculty and students participated throughout the process. RESULTS/ANTICIPATED RESULTS: Seven nursing professionals’lived experiences caring for Covid-19 patients were gathered. Their ages ranged from 31 to 45 and had worked between 2 and 14 years providing direct care. Themes that emerged from narrations include compassion fatigue, teamwork, working beyond clinical role, and gratification. Nurses expressed dealing with a very difficult situation, fear of being infected , or infecting my family , and working together to get through it and better help patients . Nurses also expressed feelings of anxiety and lack of institutional support. Additionally, the impact of working with patients, feeling good for being there, good or bad and support from families. DISCUSSION/SIGNIFICANCE: Nurses’narrations point to the complexities of their experiences working during the pandemic. They had to transcend usual demands even though they often lacked needed support. We must recognize the value of nursing and reflect upon changes in healthcare that are essential to move nursing forward.

OBJECTIVES/SPECIFIC AIMS: Using national Medicaid claims, this retrospective cohort study aims to compare the outcomes of levetiracetam (LEV) versus phenobarbital (PHB) as initial monotherapy in infants with epilepsy aged one month to one year. We primarily analyzed health services outcomes, as follows: (1) Emergency Department (ED) visits: proportion of those with at least 1 ED visit, time to first ED visit, total number of ED visits, proportion leading to inpatient admission (2) Inpatient Admissions: proportion of those with at least 1 admission, time to first admission, total number of inpatient admissions, total length of stay (3) Treatment discontinuation: proportion of those who discontinued medication, time to discontinuation, proportion of those with prescription of second antiepileptic drug (AED) (4) Cost: total cost at 1 year from first prescription. METHODS/STUDY POPULATION: The project is a retrospective cohort study utilizing Medicaid claims from 2009-2012 from all states and DC. Inclusion criteria were: (1) Epilepsy diagnosis (ICD9 345.x) at age 1 month to 1 year (2) 1 year of continuous Medicaid enrollment Exclusion criteria were: (1) Neither LEV nor PHB monotherapy as initial treatment (2) Neither LEV nor PHB prescription within 45 days of epilepsy diagnosis (3) Less than 1 year of follow-up after first LEV or PHB prescription (4) Infantile Spasms diagnosis (5) Brain Surgery (6) Death within 1 year of follow-up Using R for statistical analysis, we analyzed outcomes including ED visits, inpatient admissions, treatment discontinuation, and total cost. In this abstract, we present our preliminary bivariate analysis. RESULTS/ANTICIPATED RESULTS: Demographics and Etiology: Compared to infants prescribed PHB (n = 1954), infants prescribed LEV (n = 1248) were older (median 6 months [IQR 3-9] vs 3[2-6]; p < 0.001), more likely to be white (44.2% vs 38.9%; p < 0.05) and not Hispanic (63.5% vs 58.9%; p<0.05). There were also important differences in epilepsy etiologies (p < 0.05). For example, infants prescribed LEV were more likely to have a diagnosis of tuberous sclerosis (1% vs 0.15%) or traumatic brain injury (12.8% vs 0.56%). Health Services Outcomes: After 1 year, infants prescribed LEV had more ED visits (2 [0-4] vs 1 [0-3]; p < 0.001) but shorter inpatient length of stay when admitted (3 days [2-5] vs 3 [2-6]; p < 0.001). They were less likely to discontinue the medication (46.6% vs 64.3%; p<0.001) but more likely to have a second AED prescription (53.3% vs 43.4%; p < 0.001). Other outcomes, including total cost, were similar. DISCUSSION/SIGNIFICANCE OF IMPACT: This preliminary analysis suggests that the healthcare trajectory of infants treated with LEV and PHB differ in complex ways. In ongoing work, we are conducting a multivariable comparative effectiveness analysis of LEV versus PHB using propensity score weighting to account for observable selection bias and multiple imputation to account for missing data.

Objectives/Goals: The second highest fear of the aging population is cognitive decline. Diet is associated with brain aging; therefore, the objective is to determine the effects of a Western diet (WD) on cognitive decline and the efficacy of a Mediterranean diet (MeDi) fecal microbiota transplant (FMT) in WD-induced cognitive deficit progression in aged rats. Methods/Study Population: For Study 1, 12-month-old Fischer344 rats (NIA Aging Colony) will be randomly assigned to a WD, MeDi, or control (positive control) for 6 or 12 months. Microbiota composition, blood pressure, and body composition (DXA Scan) will be longitudinally assessed. Groups will undergo a battery of neurobehavioral assessments to measure cognitive performance. At the end of the study, mitochondria bioenergetic assays in isolated cerebral microvessels will be used to determine changes in cerebrovascular function. For Study 2, 18-month-old Fischer344 rats (NIA Aging Colony) will be randomly assigned to a WD, MeDi, or control for 6 months. At month 4, the WD+ MeDi-FMT group will receive once weekly MeDi-FMT for two months. Assessments will be performed as described in Study 1. Results/Anticipated Results: It is anticipated that the WD-related gut dysbiosis will increase blood pressure, fat-free mass, neurovascular dysfunction, and induce cognitive impairment relative to a MeDi. When using a MeDi-FMT as an intervention, it is anticipated that there will be measurable improvements in cognitive function relative to a WD through the regulation of gut dysbiosis, blood pressure, fat-free mass, and neurovascular dysfunction. Discussion/Significance of Impact: These results are expected to have an important positive impact because they will provide insights into the WD-induced gut dysbiosis-associated cognitive impairments, and evaluate the roles and mechanisms of MeDi-FMT in the therapeutic intervention of aged rats.

OBJECTIVES/GOALS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern due to its increasing prevalence and association with type 2 diabetes mellitus. Non-invasive magnetic resonance-based biomarkers can aid in the monitoring of disease progression and identification of patients at risk for chronic liver disease. METHODS/STUDY POPULATION: Over 600 subjects will be recruited from the San Antonio Mexican American Family Study and from a second study, which consists of (i) T2DM patients diagnosed with either MASLD or metabolic dysfunction-associated steatohepatitis (MASH) or (ii) metabolically healthy controls. Hydrogen-1 MRS and diffusion-weighted MRI (DW-MRI) will be used to measure liver fat fraction and liver stiffness biomarkers, respectively. Several potential biomarkers of liver stiffness will be evaluated in vivo using the intravoxel incoherent motion (IVIM) model for DW-MRI. To further improve the diagnostic accuracy of patients with liver fibrosis, we will integrate MRI/MRS data with relevant clinical indicators of hepatic metabolism. Results will be compared to biopsy samples to evaluate the model’s diagnostic accuracy. RESULTS/ANTICIPATED RESULTS: Based on preliminary data, we predict that IVIM will be able to accurately diagnose hepatic fibrosis in patients with MASLD, allowing it to be implemented in clinics with high-field MRI units easily. Previous studies have shown correlations between IVIM estimates and fibrosis stages, however, none included additional clinical indicators of liver disease in their models. We have already found significant differences in metabolic measurements such as fasting plasma glucose and HbA1c levels. Additionally, the use of machine learning in developing these models has shown improvements in the ability to extract features from the data. The aim is to achieve high accuracy and robustness in the staging of liver fibrosis. DISCUSSION/SIGNIFICANCE: Over 100 million people in the US are affected by MASLD. Without treatment, it progresses from hepatic steatosis to MASH, fibrosis (liver stiffening), and ultimately to hepatic cirrhosis and hepatocellular carcinoma (HCC). Continued research efforts and clinical implementation of MRI and MRS are vital in combating the growing burden of MASLD.

Objectives/Goals: Bacterial dysbiosis has emerged as an accomplice in the progression of many cancers. The pancreas microbiome changes in pancreatic cancer patients. The mechanisms via which components of the microbiome regulate tumor growth is unclear. We seek to determine if bacterial dysbiosis influences cancer cell behavior thereby promoting tumor progression. Methods/Study Population: We performed immunohistochemistry for lipopolysaccharide and observed bacteria preferentially located in close proximity to cancer cells. We utilized an in vitro cell culture system and in vivo mouse models, in the presence and absence of gut bacteria, to assess the effect of bacteria and bacterial metabolites on pro-tumorigenic signaling and transcriptional changes in the cancer cell. We analyzed cancer cells and epithelial cells using RNA sequencing, flow cytometry, and enzyme-linked immunosorbent assay. We also used targeted metabolomics to identify bacterial and cancer cell produced metabolites. Results/Anticipated Results: We found microbial dysbiosis can induce proliferation, an inflammatory response and an increase in tryptophan metabolism via the kynurenine pathway in the pancreatic cancer cell. Along with upregulated expression of IDO1 in vivo, we observe an increase in nicotinic adenine mononucleotide. Also, we observe an increase in nicotinic acid in vitro and nicotinic adenine dinucleotide within the cancer cell compartment in the presence of bacteria and bacteria conditioned media. Due to the critical role in many vital pathways of cell survival, NAD+ production is thought to play a significant role in cancer progression. Nicotinic acid can stimulate NAD production to protect cells from cell death. Discussion/Significance of Impact: Pancreatic cancer is associated with a distinct tumor microbiome and ablation slows disease progression. Our data delineate mechanisms via which microbes modulate the pancreatic cancer cell and provide insight into therapeutic strategies for gut microbial modulation in treating pancreatic cancer.

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

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

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

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

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

Objectives/Goals: The extracellular matrix (ECM) of the sinoatrial node (SAN) is critical for maintaining automaticity in hiPSC-derived pacemaking cardiomyocytes (PCMs) under cyclic strain. We aim to determine the ECM ligands responsible for cell-ECM mediated mechanotransduction and the resulting phenotype in PCMs. Methods/Study Population: HiPSCs are differentiated to PCM and replated on substrate with 5 or 15 kPa PDMS that are coated with 5 or 25 ug/cm of either collagen I or fibronectin at sub-confluent density to restrict junction engagement to only costameres. Then, PCM are subjected to 10% cyclic mechanical strain at 1 Hz for 48 hours, with static culture as control. PCMs from all conditions are subsequently fixed and stained for cardiomyocyte-specific troponin T (TnT), pacemaking HCN4 channel, and pro-pacemaking transcription factors (Shox2, Isl1, Tbx3, Tbx18). Additionally, PCM cell size will also be assessed. Results/Anticipated Results: Considering the amount of hypertrophy and myofilament in CMs correlates with mechanical strain, we expect a reduced degree of mechanotransduction in hiPSC-PCM on collagen I with a stiffness 15 kPa to induce smaller cell size with fewer myofilament and an upregulation of HCN4 and pro-pacemaking transcription factors than those on 5 kPa and those on fibronectin of either 5 or 15 kPa after cyclic strain. This is because COL1 is reported to have a lower signaling threshold but a limited sensitivity to force which contributes to the diminished mechanotransduction signaling. Discussion/Significance of Impact: Effects of the microenvironment on hiPSC-PCMs via costamere mechanotransduction may provide insights for engineering biopacemakers with a suitable ECM, to potentially preserve automaticity in hiPSC-PCMs and sustain long-term pacemaking function, making biopacemakers a step closer to reality.

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

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