OBJECTIVES/SPECIFIC AIMS: We aimed to develop an assay to measure new protein synthesis after Antisense Oligonucleotide treatment, which we hypothesized to be the earliest biochemical identification of RNA-targeting therapy efficacy. METHODS/STUDY POPULATION: We treated 2 transgenic animal models expressing proteins implicated in neurodegenerative disease: human tau protein (hTau) and human superoxide dismutase 1 (hSOD1), with ASO against these mRNA transcripts. Animals received isotope-labeled 13C6-Leucine via drinking water to label newly synthesized proteins. We assayed target protein synthesis and concentration after ASO treatment to determine the earliest identification of ASO target engagement. RESULTS/ANTICIPATED RESULTS: hTau ASO treatment in transgenic mice lowered hTau protein concentration 23 days post-treatment in cortex (95% CI: 0.05%–64.0% reduction). In the same tissue, we observed lowering of hTau protein synthesis as early as 13 days (95% CI: 29.4%–123%). In hSOD1 transgenic rats, we observed lowering of 13C6-leucine-labeled hSOD1 in the cerebrospinal fluid 30 days after ASO treatment compared with inactive ASO control (95% CI: 12.0%–48.4%). DISCUSSION/SIGNIFICANCE OF IMPACT: In progressive neurodegenerative diseases, it is crucial to develop measurements that identify treatment efficacy early to improve patient outcomes. These data support the use of stable isotope labeling of amino acids to measure new protein synthesis as an early pharmacodynamics measurement for therapies that target RNA and inhibit the translation of proteins.

OBJECTIVES/GOALS: The Building Up Study tests the effectiveness of an intervention aimed to diversify the workforce using a two-arm cluster randomized trial. We examined how underrepresented (UR) participants’ perceptions of institutional inclusion affected burnout, intent to continue training, and perceived stress. METHODS/STUDY POPULATION: Building Up was conducted at 25 institutions with 225 UR post-doctoral fellow or early-career faculty participants. To assess perceived institutional inclusion, participants completed a 28-item survey in the first year of follow-up. We used descriptive statistics to describe age, race/ethnicity, and gender. We used exploratory factor analysis to extract factors or domains (survey questions that grouped together). We calculated mean domain scores and used correlations to assess associations between each domain and each dependent variable (burnout, intent to continue training, and perceived stress). Demographics, correlation coefficients and associated p-values are presented. RESULTS/ANTICIPATED RESULTS: 130 of 144 eligible participants completed all questions. The mean age was 39 years (SD = 6), 83% were female, 35% identified as non-Hispanic Black, and 36% identified as Hispanic. Greater inclusivity was associated with lower burnout across 5/6 identified domains: policies (-0.3, p DISCUSSION/SIGNIFICANCE: These findings suggest that institutional inclusion is associated with differences in capacity to function among UR postdocs and early-career faculty. Inclusivity of leaders was only associated with intent to continue training. Inclusion coupled with employee support and development are important for positive outcomes.

OBJECTIVES/GOALS: To describe an Honest Broker (HB) tool and workflow integrated with the Institutional Review Board (IRB) to automate requests, approvals and delivery of both de-identified and identified data extractions from a clinical research data warehouse (CRDW). METHODS/STUDY POPULATION: The HB tool has predefined domain tables and is closely integrated IRB for quick and easy review and approval. Investigators can access patient data using query tools, barcodes from biospecimens or build a query in TriNetX and provide the patient list as an input for the HB tool. For de-identified data extraction, the required data domain tables and date ranges can be selected and submitted in the HB tool. For identified data extractions, investigators with an approved IRB protocol can enter the protocol number and the approved date range in the HB tool. This request is automatically forwarded to the IRB for review. RESULTS/ANTICIPATED RESULTS: For de-identified data extraction, an email alert is automatically sent to the investigator once the data extract is completed. For identified data extraction, if IRB approves the request, an HB is immediately notified to release the data. Data release triggers two emails to the investigator: (1) a link to an encrypted zipped file with the requested data, and (2) a password to unlock the encrypted file. If the request is denied, the IRB sends an email to the investigator with the reason for denial and options for remediation. The entire HB workflow is accomplished in a secure environment with an audit trail from the initial data request to data download by the investigator. Since the launch of the HB tool, the time from data request to delivery is approximately an hour for deidentified data and 24 hrs for identified data. DISCUSSION/SIGNIFICANCE: The HB tool has increased successful data delivery in support of publications, grant submissions, and clinical trial recruitment. Optimization of data extraction from the CRDW through automation and integration with the IRB can minimize interaction with data analysts and IRB staff, thus accelerating the conduct of clinical research.

OBJECTIVES/SPECIFIC AIMS: Our primary objective is to determine the mechanism of action of myostatin on osteoblasts by measuring markers of osteoblast differentiation. With these experiments we will evaluate the effects of myostatin on an osteoblastic cell line (MC3T3 cells) and primary murine osteoblasts during baseline and hyperglycemic conditions and assess whether these effects are altered in the presence of a hyperglycemic environment. METHODS/STUDY POPULATION: Primary osteoblasts from calvaria of WT mice will be isolated and cultured per previously published protocol. MC3T3 cells (murine pre-osteoblast cell line) and primary osteoblasts will be plated in 6-well plates until they reach confluency. They will subsequently be stimulated with or without myostatin at various concentrations under control and hyperglycemic conditions. Additional experiments will assess myostatin stimulation during cell differentiation/maturation in the presence of osteogenic induction medium. Subsequently, cells will be lysed and processed for gene analysis with qPCR. Genes of interest (e.g., myostatin, RUNX2, osteocalcin etc.) will be assessed. Additionally, cells will be collected and processed for protein quantification with western blot to assess myostatin-related pathways, such as Smad2/3 and MAPK signaling. RESULTS/ANTICIPATED RESULTS: We have demonstrated that the receptor for myostatin (Activin receptor 2b, AcvR2b) is present in MC3T3 cells and we have evidence of Smad2 phosphorylation in MC3T3 cells as a result of myostatin stimulation, confirming that myostatin can exert intracellular signaling events in bone cells (Fig 1). We anticipate to observe negative effects of myostatin on differentiation of primary osteoblasts and MC3T3 cells. Specifically, we anticipate suppression of Runt-related transcription factor 2 (RUNX-2), a transcription factor known as the “ master regulator” of osteogenic gene expression and programming, as a result of signaling downstream of Smad 2/3. Additionally we anticipate downregulation of osterix and osteocalcin, two essential genes for osteoblast differentiation and activity. We anticipate that hyperglycemia will potentiate the negative effects of myostatin on osteoblastogenesis. DISCUSSION/SIGNIFICANCE OF IMPACT: We have demonstrated that myostatin can directly act on osteoblastic cells. As myostatin is a negative regulator or bone mass, its direct effects on bone cells can be detrimental to the bone health of patients with elevated myostatin levels and/or activity. There is evidence suggesting that myostatin is elevated in Type 1 diabetes, and its effects might be potentiated in a hyperglycemic environments. Future experiments will be evaluating the role of myostatin on a diabetic animal model and in humans. Our experiments provide an additional mechanism by which muscle-bone interactions could be contributing to the development of diabetic bone disease.

OBJECTIVES/GOALS: Health inequities represent complex structural and systematic processes that lead to disparate outcomes for populations or subgroups within populations. This project aims to improve the available structural and systematic approaches to the study of such inequities at the population level. METHODS/STUDY POPULATION: Using examples from diabetes research, two critical factors that may impact the validity or utility of health equity models will be examined; and proposed methodological approaches to offsetting potentially resulting biases will be offered. The factors include: (1) inequitably missing and misclassified data in large datasets and (2) the presumed positioning of socially constructed variables such as race, ethnicity, and gender within modeled structural and systematic mechanisms. This examination intersects theories and praxis in epidemiological modeling and health equity promotion with the goal of advancing rigorous, equity-focused epidemiological methods. RESULTS/ANTICIPATED RESULTS: Inequitably missing and misclassified data are generally expected to obscure inequities. Treatment of missing or misclassified data as informative measures of inequity is expected to partially offset this bias. The implicitly modeled components of socially constructed variables are expected to be non-uniform across structural and systematic mechanisms of inequity. Models that apply these variables as informatively heterogeneous constructs, using multi-phase analyses to test modeling assumptions and to assess intersectionality, may provide better context about the mechanisms by which inequity has been distributed and, perhaps, by which equity may be achieved. DISCUSSION/SIGNIFICANCE: Equitable epidemiological methods are essential to the advancement of evidence-based health equity on the population level. Potential structural or systematic inequities in large-scale datasets and traditional data analyses should be thoughtfully reviewed through a health equity lens.

OBJECTIVES/GOALS: To determine if current U.S. HPV vaccination rates have decreased dysplasia prevalence enough to decrease the positive predictive value (PPV) of abnormal cervical cytology. METHODS/STUDY POPULATION: This retrospective cohort study comprised a chart review of all patients 21-35 years of age who had at least 1 Pap test result within MHealth/Fairview 2016-2018. HPV vaccination data, cervical cancer screening data and dysplasia results were abstracted. Vaccinated was defined as receiving at least 1 dose of HPV vaccine, with subgroup analyses performed for those completing vaccination per ACIP guidelines and by age of initiation dichotomized as 21+ years versus <21 years. RESULTS/ANTICIPATED RESULTS: 49,764 patients meeting study criteria were identified. Among the entire study population, 10% had abnormal cytology results during the study period. Among the 4,928 patients with abnormal cytology, PPV for CIN2+ was lower among vaccinated individuals (13% vs. 18%; p < 0.0001). Among vaccinated individuals, PPV was lower among those completing vaccination (12% vs. 16% for incomplete vaccination; p = 0.04) and among those initiating vaccination at <21 years of age (9% vs 26% for 21+y; p < 0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: Among a population with low HPV vaccine coverage, the decrease in dysplasia prevalence among vaccinated individuals is resulting in a subsequent decrease in PPV of cervical cytology, particularly in those initiating vaccination prior to 21 years of age and among those completing the series. Confirmation of these results will call for changes in screening strategies for vaccinated individuals. CONFLICT OF INTEREST DESCRIPTION: Acelity: Industry grant for an investigator-initiated industry-sponsored clinical trial. Tesaro: Site PI for industry-sponsored clinical trial. NOTE: Funding from the industries above are unrelated to the research presented in the abstract.

Objectives/Goals: 1) Determine the association between wildfire smoke-driven PM2.5 and risk of persistent respiratory symptoms and repeated asthma exacerbations after the acute wildfire period among adults with asthma. 2) Examine how measures to reduce personal exposure to wildfire smoke, including avoiding outdoor activities, modify this association. Methods/Study Population: This is a retrospective study of adults with asthma in WHAT-NOW, a cohort study of people living in Northern California during the 2018 Camp Fire. Daily smoke-driven PM2.5 was estimated for each participant based on their home address or evacuation location. We examined the association between mean PM2.5 exposure and the presence of respiratory symptoms at both the time of the survey (6–16 months post-wildfire) and at least one other post-wildfire time-period, as well as whether they had a medically attended respiratory illness (saw a doctor, visited the ER, or were hospitalized for a respiratory symptom). We examined the interaction of PM2.5 with spending time outdoors during the wildfires. Poisson regression models with robust standard errors were adjusted for age, sex, race, smoking, allergies, and education. Results/Anticipated Results: Among 337 adults with asthma in the WHAT-NOW cohort, one standard deviation higher smoke-driven PM2.5 was associated with higher risk of any persistent respiratory symptom (risk ratio (RR) 1.38, 95% CI 1.07 – 1.78) and having at least one medically attended respiratory illness (RR 1.33, 95% CI 1.07 – 1.65), but not significantly associated with repeated asthma exacerbations (RR 1.30, 95% CI 0.92 – 1.81). However, there was a significant interaction between PM2.5 and outdoor activities during the wildfire on the outcomes of any persistent respiratory symptoms (p = 0.041) and repeated asthma exacerbations (p = 0.028). The association between PM2.5 and repeated asthma exacerbations was greater among people who spent time outdoors (RR 3.36, 95% CI 1.47 – 10.23) than those who did not (RR 1.00, p = 0.99). Discussion/Significance of Impact: This study provides evidence that exposure to wildfire smoke increases respiratory morbidity among adults with asthma beyond the acute wildfire period. Additionally, it suggests that avoiding outdoor activities on smoky days can significantly decrease the risk of future repeated asthma exacerbations associated with smoke exposure.

OBJECTIVES/SPECIFIC AIMS: This study is part of a parent grant evaluating antidiabetic medications and risk for heart failure in an observational cohort of Veterans with type 2 diabetes (T2DM). Confounding by indication remains a concern in many observational studies of medications because difficult to measure confounders such as frailty may influence prescribing of different medications based on patient characteristics. Frailty is a multidimensional syndrome of loss of reserves (energy, physical ability, cognition, health) that gives rise to vulnerability to adverse outcomes. The objective of this study is to determine if frailty is a potential confounder in Veterans with T2DM, that is, independently associated with exposure to a specific antidiabetic medications and hospitalization for decompensated heart failure. METHODS/STUDY POPULATION: We conducted a cross-sectional study of patients with diabetes who were hospitalized within the Veterans Health Administration (VHA) Tennessee Valley Healthcare System from 2002 to 2012. Inclusion criteria were: age 18 years or older, receive regular VHA care (prescription fill or visit at least once every 180 d), a diagnosis of T2DM. A probability sample of HF and non-HF hospitalizations was collected. HF hospitalizations were selected on the basis of meeting either a primary diagnosis code (ICD-9) and/or disease related group (DRG) code for HF. For each hospitalization using a standardized chart abstraction tool, data was abstracted on: antidiabetic medication(s), patient frailty status, and reason for hospitalization (HF or non-HF). Antidiabetic medication regimens were categorized as follows: no medication treatment, metformin alone, sulfonylurea alone, insulin alone, insulin and one oral agent, and all other regimens. Patient frailty status was measured using a modified version of the Canadian Health and Aging frailty index (FI), which generates a score (range 0–1) by dividing the number of deficits present by the number of deficits measured. Established categories for FI scores are: non frail ≤0.10, vulnerable 0.10–0.21, frail 0.22–0.45, and very frail >0.45. Patient frailty status at the time of hospitalization was used as a surrogate for patient frailty at the time of prescription of antidiabetic medication; this is a limitation of this approach. Hospitalizations were classified as HF hospitalizations if 2 major or 1 major and 2 minor Framingham criteria were present. FI was compared across antidiabetic medication regimen categories and hospitalization type using analysis of variance (ANOVA) and Student t-test, respectively. RESULTS/ANTICIPATED RESULTS: Of the 500 hospitalizations reviewed, 430 patients had confirmed diabetes diagnosis, adequate data to calculate FI scores, and were included in this analysis. Patients were on average 66.9 (10.9) years old; 99% male and 75% were White. Overall, 268 patients (62.3%) were categorized as frail or very frail. The mean FI score was 0.23 (SD 0.07). FI scores were highest in patients receiving insulin alone (mean 0.26) compared with patients receiving metformin alone (mean 0.22), sulfonylurea alone (mean 0.23), or no medication (mean 0.22). The lowest mean frailty score was seen in patients taking all other drug combinations, 0.19. The differences across these patient groups were statistically significant with p<0.01. Further, 75% of patients on insulin alone were frail or very frail compared with 68% on sulfonylurea alone, 58% on metformin alone, and 58% on no medication. Framingham criteria for acute HF were present for 318 of 430 patients (74.0%). FI scores were higher in patients hospitalized for HF compared with non-HF hospitalizations (mean 0.24 vs. 0.21, p<0.01). A higher proportion of patients hospitalized for HF were classified as frail or very frail compared with those hospitalized for non-HF diagnosis (66.4% vs. 50.9%, p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that certain antidiabetic medications are associated with patient frailty. In addition, those patients admitted for HF have higher FI scores than those admitted for non-HF diagnoses. Further investigation is planned to assess the degree to which frailty is captured by traditional covariates used in observational studies.

OBJECTIVES/SPECIFIC AIMS: The objective of the present study is to determine if decreased adiponectin and increased leptin levels are associated with the development of MetS and identifiable endothelial dysfunction in a cohort of Hispanic pre-pubertal children. To do so we propose the following aims: (1) To measure expression of adiponectin and leptin levels in a Hispanic pre-pubertal cohort and determine their correlation with features of the MetS. (2) To perform proteomic analysis in a Hispanic pre-pubertal cohort. (3) Evaluate early onset of endothelial dysfunction and its correlation with expression of adiponectin and leptin levels in a Hispanic pre-pubertal cohort. METHODS/STUDY POPULATION: A cross-sectional pilot study will obtain a random representative sampling of children aged 6–12 years from all geographical areas of Puerto Rico. Children will be assessed regarding pre-pubertal status through Tanner staging and later divided into pre-MetS Versus MetS groups as well as controls. MetS will include children meeting 3 or more of the current International Diabetes Federation (IDF) criteria. Pre-MetS will include children with at least 1 criterion for MetS. Anthropometric data, blood pressure readings, ultrasound-based noninvasive testing for endothelial dysfunction, and laboratory assays will be performed to the study population and data analyzed for correlation. Total adiponectin and leptin levels will be measured using a commercially available quantitative sandwich enzyme-linked immunoassay test. The study will be submitted to the University of Puerto Rico Medical Sciences Campus’ Institutional Review Board (IRB) for approval. Written consent and assent will be obtained from parents and children respectively to ensure patient anonymity. RESULTS/ANTICIPATED RESULTS: We hypothesize that low levels of adiponectin and high levels of leptin will correlate with features of the MetS as defined by the IDF consensus statement, as well as with clinical features of MetS in undiagnosed Hispanic pre-pubertal youth. We also hypothesize that non-invasive testing of endothelial function will correlate both with clinical features of the MetS and with low levels of adinopectin and high levels of leptin. DISCUSSION/SIGNIFICANCE OF IMPACT: The correlation of findings suggestive of endothelial dysfunction and biomarker expression (mainly adiponectin and leptin levels) in a pre-pubertal cohort has yet to be established and could also provide information regarding early atherogenesis in otherwise unidentified youth at risk. Therefore, by using a proteomic approach, this study aims to measure associations between clinical features of the MetS and expression of proteins associated with an adverse cardiometabolic profile in a Hispanic pre-pubertal population. We will concurrently measure the degree of endothelial dysfunction and evaluate whether a correlation exists between previously mentioned protein expression and early onset of dysfunction.

The University of Michigan created the Practice-Oriented Research Training (PORT) program and implemented it between 2008 and 2018. The PORT program provided research training and funding opportunities for allied healthcare professionals. The program consisted of weekly didactics and group discussion related to topics relevant to developing specific research ideas into projects and funding for a mentored research project for those who submitted a competitive grant application. The goal of this evaluation was to assess the long-term impact of the PORT program on the research careers of the participants. Ninety-two participants (74 staff and 18 faculty) participated in both phases of the program. A mixed-methods approach to evaluation was used; 25 participants who received funding for their research completed surveys, and semi-structured interviews were conducted with eight program participants. In addition, data were collected on participants’ publication history. Fifteen out of the 74 staff participants published 31 first-authored papers after participating in PORT. Twelve out of 15 staff participants who published first-authored papers did so for the first time after participating in the PORT program. Results of quantitative and qualitative analyses suggest that the PORT program had positive impacts on both participants and the research community.

OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classification and regression tree analysis found that age, BMI, serum glucose, and femorotibial angle explained 31% of the variability between those who did and did not develop AKOA. Including structural measurements as candidate variables yielded a model that included effusion, BMI, serum glucose, cruciate ligament degeneration and coronal slope and explained 39% of the variability. DISCUSSION/SIGNIFICANCE OF IMPACT: Knee structural measurements improve classification of participants who developed AKOA Versus those who did not. Further research is needed to better classify patients at risk for AKOA.

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to investigate whether RF-RDN attenuates renal fibrosis and inflammation in SHR with established hypertension. METHODS/STUDY POPULATION: Twenty-two-week-old SHR received bilateral RF-RDN or Sham-RDN (Biosense Webster Stockert 70 generator and RF-probe). Four weeks later, SHR were sacrificed and paraffin sections of kidneys were stained for fibrosis by Masson’s trichrome staining. Kidney tissue were homogenized for measurement of cytokines levels by ELISA. RESULTS/ANTICIPATED RESULTS: The results showed that Sham-RDN treated SHR had extensive fibrosis as demonstrated by moderate thickening of Bowman’s capsule, collagen deposition in glomerulus, extensive tubulointerstitial fibrosis, and segmental glomerulosclerosis. In contrast, RF-RDN significantly reduced each of these pathological components of fibrosis in kidney cortex and medulla as compared with Sham-RDN treated kidneys. In other studies, RF-RDN decreased B cells, CD4+ T cells, and CD8+ T cells in the kidney of SHR as measured by flow cytometry. Meanwhile, kidney tissue levels of IL-17, INF-γ, MIP-3a, TNF-α, and TGF-β were decreased as compared with respective levels in Sham-RDN. DISCUSSION/SIGNIFICANCE OF IMPACT: Together, these findings demonstrate that removal of the influence of heightened renal sympathetic activity by RF-RDN decreases kidney inflammatory markers and attenuates renal fibrosis in hypertensive SHR.

OBJECTIVES/SPECIFIC AIMS: Increased retinal protein O-GlcNAcylation occurs in response to hyperglycemia and contributes to diabetic retinopathy. Renin-angiotensin system (RAS) blockers reduce the incidence of diabetic retinopathy. Beneficial effects of RAS blockers are often attributed to production of angiotensin-(1-7) (Ang1-7). The objective here is to determine the impact of Ang1-7 on retinal protein O-GlcNAcylation. METHODS/STUDY POPULATION: C57/BL6 mice were fed a high-fat diet for 8 weeks and then treated for 3 weeks with either a vehicle control, the RAS blocker captopril, or captopril and the Ang1-7 receptor antagonist A779. R28 cells were used to assess levels of O-GlcNAcylated proteins in response to Ang1-7, and the role of cAMP was investigated with addition of forskolin, 6-Bnz-cAMP-AM, and 8-pCPT-2-O-Me-cAMP-AM to cell culture medium. RESULTS/ANTICIPATED RESULTS: Captopril attenuated retinal protein O-GlcNAcylation in mice fed a high-fat diet. This effect was reversed by A779. Ang1-7 attenuated protein O-GlcNAcylation and increased cAMP levels. Forskolin and the EPAC selective cAMP analog 8-pCPT-2-O-Me-cAMP-AM, but not the PKA selective cAMP analog 6-Bnz-cAMP-AM, attenuated O-GlcNAcylation. Inhibiting EPAC blocked the effect of forskolin, whereas inhibiting PKA did not. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates a novel role for Ang1-7 in the retina and identifies a potential EPAC-dependent mechanism that regulates protein O-GlcNAcylation. Thus, future therapeutics targeted at an Ang1-7/EPAC axis in retina may be used to address DR.

OBJECTIVES/GOALS: Observational studies suggest unequal effects of COVID-19 on the population of the U.S. distinguished by race and ethnicity. Our primary research question: what are the demographic differences among patients identified with concurrent ischemic stroke and COVID-19 positivity? METHODS/STUDY POPULATION: The National Covid Cohort Collaboration (N3C) data was used to identify patients with concurrent COVID-19 and stroke, operationally defined as those with a COVID diagnosis and inpatient admission for ischemic stroke 1 week before or 6 weeks after their COVID diagnosis. The data was further age restricted (18-65 years) and a categorical variable was created representing payer plans (Medicaid, Medicare, Other insurance). Data on patients race/ethnicity, comorbidities, treatments administered (Remdesivir and ECMO) and insurance information was analyzed using various exploratory data methods and visualizations. Logistic regression was implemented to model the relationship between variables (dependent/independent) in the cohorts. Model complexity was analyzed using the F test of significance. RESULTS/ANTICIPATED RESULTS: Taken as a whole, the data contained over 7 billion rows and around 6.4 million persons (~ 2.15 million of whom were COVID+). The main cohort of individuals with concurrent COVID positivity and ischemic stroke made up around 0.29% of the original COVID+ group, and the payer plan sub-cohort consists of around 29.26% of our main cohort. Black/African American (AA) and the Hispanic/Latino any Race have younger distributions (median ~ 65 years), while the White Non-Hispanic group has the oldest distribution (median ~ 70 years). Black/AA had the highest average number of comorbidities per patient (4.49), compared to white non-Hispanic (3.39) and Asian non-Hispanic (2.59). In our analysis, Medicaid patients had lower odds of obtaining ECMO (p < .01), there was no significant difference in Remdesivir treatment. DISCUSSION/SIGNIFICANCE: We found the N3C data to be useful in studying a distinct group of patients, and exploring COVID-19 and ischemic stroke treatment across patients’ race/ethnicity identities and insurance status. Our exploratory analysis provides a foundation for further insight into demographic trends and discrepancies in apportionment of treatment.

Objectives/Goals: Using secure systems for sharing documents with external collaborators is essential for all researchers. These documents may include protected health information (PHI) or sensitive materials like protocols, study reports, DSMB reports, publications, presentations, abstracts, and statistical analysis plans (SAPs). Methods/Study Population: We surveyed the ACTS Biostatistics, Epidemiology, and Research Design Special Interest Group (BERD-SIG) to gather information about the systems they are currently using or have used in the past for document sharing with external collaborators. The survey focused on the security of these systems, particularly in relation to sharing documents containing PHI. In addition, the survey included questions about various system features of interest. These features included version control, simultaneous editing by multiple users, and access rights management, such as the ability to assign different permissions (e.g., read-only, write, and download) to different individuals. We also invited participants to provide feedback on any additional positive or negative aspects of the systems they use. Results/Anticipated Results: We received 28 completed survey responses. Respondents had an option for choosing more than one system. The top current systems reported were Microsoft Teams (OneDrive, SharePoint) (n = 16), Box (n = 11), Google Docs/Drive (n = 10), and Dropbox (n = 6). Among other systems listed individually were Filelocker, REDCap, Slack, Website, Significant Media Shuttle, and Zulip. Notably, 15 responses indicated the respondents were unsure if their system is secure for sharing documents containing PHI. Respondents also offered feedback on both the positive and negative aspects of these systems. For example, a key advantage of Box was its password-controlled access. However, its incompatibility with office tools and the challenges for external collaborators attempting to access the system were noted as drawbacks. Discussion/Significance of Impact: Utilizing secure institutional document-sharing systems and understanding their features significantly affects the effectiveness and security of collaborations among researchers, particularly with external partners. This knowledge is especially crucial when sharing documents containing sensitive patient and study data.

ABSTRACT IMPACT: This study provides public health and K-12 school districts with a pragmatic, flexible, adaptable model showing COVID-19 transmission dynamics, using local data and program elements that are modifiable and with an online model for easy use, to enable safe and equitable re-opening and maintenance of in-person learning. OBJECTIVES/GOALS: School closures resulting from the COVID-19 pandemic disrupt student education and health and exacerbate inequities. Public health agencies and school districts currently lack pragmatic models to assess the effects of potential strategies for resuming and maintaining in-person learning on outcomes such as transmission and attendance. METHODS/STUDY POPULATION: This study explored how various combinations of transmission-mitigating interventions affect health and learning outcomes in a range of underlying epidemiological conditions. The CTSA science team developed a conceptual framework and an agent-based simulation model with parameters including prevalence, transmission, testing, preventive and responsive actions, infection control, population behavior and awareness, and the potential impact of vaccine adoption and exemption policies. The team partnered with a large school district to ensure relevance of the program components to decision-making. RESULTS/ANTICIPATED RESULTS: The model shows that no single program element or condition ensures safety. Combining interventions can result in synergy in the mitigation efforts. Even without testing, an efficient health screening process with forthcoming risk reporting, combined with on-campus infection control, can reduce on-campus transmission. The resulting model is accessible online to enable exploration of likely scenarios. It is adaptable as COVID-19 science evolves, including for testing and vaccines. DISCUSSION/SIGNIFICANCE OF FINDINGS: This research provides public health agencies and school districts with a model that couples local conditions with programmatic elements to help inform the local COVID-19 response, recognizing that decisions about the school community are often complex politically, technically, and operationally when it comes to addressing a health crisis.