This paper is part of the Environmental Scan of Adaptive Capacity and Preparedness of Clinical and Translational Science Award (CTSA) hubs, illuminating challenges, practices, and lessons learned related to CTSA hubs’ efforts of engaging community partners to reduce the spread of the virus, address barriers to COVID-19 testing, identify treatments to improve health outcomes, and advance community participation in research. CTSA researchers, staff, and community partners collaborated to develop evidence-based, inclusive, accessible, and culturally appropriate strategies and resources helping community members stay healthy, informed, and connected during the pandemic. CTSA institutions have used various mechanisms to advance co-learning and co-sharing of knowledge, resources, tools, and experiences between academic professionals, patients, community partners, and other stakeholders. Forward-looking and adaptive decision-making structures are those that prioritize sustained relationships, mutual trust and commitment, ongoing communication, proactive identification of community concerns and needs, shared goals and decision making, as well as ample appreciation of community members and their contributions to translational research. There is a strong need for further community-engaged research and workforce training on how to build our collective and individual adaptive capacity to sustain and improve processes and outcomes of engagement with and by communities—in all aspects of translational science.

OBJECTIVES/GOALS: Biliary tract cancer is an uncommon, aggressive malignancy. Incidence varies geographically and is highest in East Asia and South America and lowest in Western countries. Previous dietary risk evaluations have primarily been case-control studies. We evaluated associations of dietary intakes with BTC risk in three cohort studies in two countries. METHODS/STUDY POPULATION: We evaluated 638,860 adults in China and the United Kingdom enrolled in the Shanghai Women’s Health Study (SWHS), Shanghai Men’s Health Study (SMHS), or UK Biobank (UKB). Dietary intake information was obtained from study participants at baseline using food frequency questionnaires previously validated for these studies. Dietary intakes of major food groups and macronutrients were divided into low, middle, and high intake tertiles. Cox regression was used to estimate hazard ratios and 95% CIs for biliary tract cancer risk associated with major food groups in all three cohorts and macronutrients in the SWHS and SMHS. Participants were excluded if, at enrollment, they had a history of cancer, CHD, stroke, a total daily Kcal count below 500 or exceeding 3500, or developed cancer or died within one year after enrollment. RESULTS/ANTICIPATED RESULTS: The analyzed cohort includes 558,372 participants: 66,945 SWHS, 55,750 SMHS, and 435,677 UKB participants with median enrollment ages of 49, 52, and 57 years old and median follow-up times of 18.1, 12.3, and 10.3 years, respectively. The SWHS observed 205 eligible BTC cases, SMHS 97, and UKB 366. SWHS and SMHS participants were combined for dietary evaluation and the highest tertile of fruit intake showed an inverse association with biliary tract cancer risk when compared to the lowest tertile: HR 0.74 (95% CI, 0.55-0.99); p-trend 0.044. In UKB, the highest tertile of fish intake was associated with a reduced risk when compared to the lowest tertile: HR 0.76 (95% CI, 0.59-0.98); p-trend 0.034. DISCUSSION/SIGNIFICANCE: High dietary fruit intake was associated with a reduced risk of biliary tract cancer only in SWHS and SMHS. High fish intake was associated with a reduced risk of biliary tract cancer only in UKB. Our findings reflect geographic-based BTC risk variation which we will further explore in our next model accounting for population-specific risk factors.

OBJECTIVES/GOALS: Analysis and modeling of large, complex clinical data remain challenging despite modern advances in biomedical informatics. We aim to explore the potential of topological data analysis (TDA) to address such challenges in the context of COVID-19 outcomes using electronic health records (EHRs). METHODS/STUDY POPULATION: In this work, we develop TDA approaches to characterize subtypes and predict outcomes in patients with COVID-19 infection. First, data for >70,000 COVID-19 patients were extracted from the OneFlorida EHR database. Next, enhancements to the TDA algorithm Mapper were designed and implemented to adapt the technique to this type of data. Clinical variables, including patient demographics, vital signs, and lab values, were then used as input to conduct a population-level exploratory analysis with an emphasis on identifying phenotypic subtypes at increased risk of adverse outcomes such as major adverse cardiovascular events (MACE), mechanical ventilation, and death. RESULTS/ANTICIPATED RESULTS: Preliminary Mapper experiments have produced visual representations of the COVID-19 patient population that are well-suited to exploratory analysis. Such visualizations facilitate easy identification of phenotypic subnetworks that differ from the general population in terms of baseline variables or clinical outcomes. In this and subsequent work, we aim to fully characterize and quantify differences between these subnetworks to identify factors that may confer increased risk (or protection from) adverse outcomes. We also plan to validate and rigorously compare the efficacy of this TDA-based approach to common alternatives such as clustering, principal component analysis, and machine learning. DISCUSSION/SIGNIFICANCE: This work demonstrates the potential utility of TDA for the characterization of complex biomedical data. Mapper provides a novel means of exploring EHR data, which are otherwise difficult to visualize and can aid in identifying or characterizing patient subtypes in diseases such as COVID-19.

OBJECTIVES/GOALS: The purpose of this study is to determine critical recovery support factors (SDOH, postpartum and post-discharge continuity of care), to optimize continuity of recovery and to determine the best intervention among postpartum and parenting women for treatment retention. METHODS/STUDY POPULATION: Through a mixed methods approach, we will review retrospective hospital discharge data to identify hospital-based gaps in treatment. We will conduct key informant interviews with postpartum women, treatment providers and stakeholders to broaden understanding of critical recovery factors from lived experiences and test a parent-centered evidence-based intervention for a comprehensive and targeted approach to recovery. RESULTS/ANTICIPATED RESULTS: This research will lead to new understanding of critical maternal recovery support factors for sustaining treatment retention for 6-12 months after childbirth and to improve long term maternal health outcomes. DISCUSSION/SIGNIFICANCE: The recovery journey and postpartum period are challenging and lack specific recovery support evidence. Recovery support and continuity of care protocols are unclear after childbirth. Maternal opioid-related overdose deaths occur 6-12 months after childbirth. Therefore, this study will impact and inform recovery retention strategies.

Expanded access (EA) provides a pathway for the clinical use of investigational products (drugs, biologics, and medical devices) for patients who are without satisfactory therapeutic options and for whom a clinical trial is not available. Academic medical centers (AMCs) are likely to encounter EA requests, but it is unknown what support is available at these institutions for physicians seeking EA for patients. Methods: A landscape assessment was conducted at AMCs, focused on those within the Clinical and Translational Science Awards (CTSA) consortium. Results: Forty-seven responses were evaluated including 42 CTSA hubs. The large majority (43 of 47 respondents) reported using single-patient EA, while 37 reported multi-patient industry sponsored EA and 37 reported multi-patient investigator-initiated EA. Only half reported central tracking of EA requests. Support was available at 89% of sites for single-patient EA but less often for multi-patient EA. Types of support varied and were focused largely on the initial submission to the FDA. Conclusion: Use of and support for EA is widespread at AMCs, with support focused on single-patient requests. Gaps in support are common for activities after initial submission, such as FDA reporting and data collection.

OBJECTIVES/GOALS: This study models a framework for integrating epidemiological and experimental approaches to investigate the effect of prenatal polycyclic aromatic hydrocarbon (PAH) exposure on mitochondrial function (mtDNAcn, superoxide production and membrane potential) as a potential mechanism of toxicity. METHODS/STUDY POPULATION: The epidemiological aim of this study characterizes mitochondrial outcomes in samples of umbilical cord tissue and blood from two Manhattan based birth cohorts. Prenatal PAH exposure is quantified using silicone wristbands worn for 48 hours during the third trimester of pregnancy. Experimentally, we are applying a PAH mixture designed to emulate the exposure profile of the human cohorts to mouse preimplantation embryos on various dosing schedules and quantifying the same mitochondrial outcomes. mtDNAcn is quantified using rtPCR while superoxide production and membrane potential are measured using fluorescence microscopy. The goal of this study design is to leverage the strengths of each approach to draw more robust conclusions than could be derived from either alone. RESULTS/ANTICIPATED RESULTS: Preliminary results of this study have found associations between higher levels of PAH exposure and increased mitochondrial superoxide production and hyperpolarization of the mitochondrial membrane potential in mouse preimplantation embryos. We anticipate these findings to persist across dosing schedules. We furthermore expect a decrease in mtDNAcn in association with higher PAH exposure in umbilical cord tissue samples and decreased mtDNAcn with exposure to the PAH mixture in mouse embryos. DISCUSSION/SIGNIFICANCE: Characterizing the effect of prenatal PAH exposure on the mitochondria is a critical step in understanding the mechanisms that underlie the toxicity of this exposure. By employing a similar exposure mixture and mitochondrial outcomes across epidemiological and experimental approaches, we offer a model of true interdisciplinary research design.

People with lived experience of incarceration have higher rates of morbidity and mortality compared to people without history of incarceration. Research conducted unethically in prisons and jails led to increased scrutiny of research to ensure the needs of those studied are protected. One consequence of increased restrictions on research with criminal-legal involved populations is reluctance to engage in research evaluations of healthcare for people who are incarcerated and people who have lived experience of incarceration. Ethical research can be done in partnership with people with lived experience of incarceration and other key stakeholders and should be encouraged. In this article, we describe how stakeholder engagement can be accomplished in this setting, and further, how such engagement leads to impactful research that can be disseminated and implemented across disciplines and communities. The goal is to build trust across the spectrum of people who work, live in, or are impacted by the criminal-legal system, with the purpose of moving toward health equity.

OBJECTIVES/GOALS: Non-alcoholic fatty liver disease increases with aging and may be associated with MCI. Thus, adults >65 years with NAFLD have a greater risk of MCI. Our objective is to associate NAFLD with MCI and, therefore, optimize the management of MCI through prevention strategies and early interventions. METHODS/STUDY POPULATION: We will recruit 100 patients >65 of all sexes from the GI and Geriatrics clinics of the University of Puerto Rico (UPR). NAFLD prevalence in aging adults will be estimated via ICD-10 codes and definition will be liver fat accumulation or steatosis (AASLD) without secondary causes. We will exclude patients RESULTS/ANTICIPATED RESULTS: We expect to find a higher NAFLD prevalence in aging adults >65 years old compared to younger ones. Furthermore, we aim to elucidate an association of NAFLD with MCI in aging adults. Besides, as the literature has shown, we anticipate that the main cognitive domains affected by NAFLD will be the visuospatial and executive functions. As the population ages, this study will help identify future targets for early interventions in people diagnosed with NAFLD that could have a greater risk for cognitive impairment. DISCUSSION/SIGNIFICANCE: To our knowledge, no study has determined the association of NAFLD with MCI in Hispanics >65 in PR. Raising awareness of NAFLD as a possible treatable or preventable risk factor for MCI by screening NAFLD patients for MCI may improve not only their global health but their quality of life as well.

OBJECTIVES/GOALS: The goal of this presentation is to highlight the role of and challenges to the Biostatistics, Epidemiology and Research Design (BERD) Core as it transitions into (i) the resources and services module (ii) and also possibly a regional center of translational science. METHODS/STUDY POPULATION: BERD cores play key roles in translational research missions, often in the form of long-term collaborative relationships focusing on project conception and design, interim monitoring and review, analysis and dissemination. The resources and services module encourages consolidation of all resources and services under the single modular umbrella, which can pose challenges to BERD autonomy and function. CTSAs transitioning from local to regional centers can also threaten to overwhelm BERD workloads and resources. Our CTSA planned an outsource-insource model to make the BERD a central feature of the new module and transplant its functionality to partner institutions. RESULTS/ANTICIPATED RESULTS: The team has planned a centralized, web-based entry-point for both self-guided inquiry and electronic requests of all resources and services, which aides project database creation and provides notification for review. The review process adds two new approval types: guided assistance to help navigate connections to relevant resources, and triaged referrals to training modules for remediation and skills development. Our BERD has added a Consulting Laboratory for projects of sufficient but non-priority merit that would otherwise be waitlisted, and established connections with regional partner institutions to whom they can refer investigators. DISCUSSION/SIGNIFICANCE: We have consolidated all resources and services into a single, accessible location, emphasizing tailored guidance to maximize limited resources. We also planned a transportable regional model that accounts for local resources and capacity to keep from overstretching the BERD and other hubs.

COVID-19 reinforced the need for effective leadership and administration within Clinical and Translational Science Award (CTSA) program hubs in response to a public health crisis. The speed, scale, and persistent evolution of the pandemic forced CTSA hubs to act quickly and remain nimble. The switch to virtual environments paired with supporting program operations, while ensuring the safety and well-being of their team, highlight the critical support role provided by leadership and administration. The pandemic also illustrated the value of emergency planning in supporting organizations’ ability to quickly pivot and adapt. Lessons learned from the pandemic and from other cases of adaptive capacity and preparedness can aid program hubs in promoting and sustaining the overall capabilities of their organizations to prepare for future events.

OBJECTIVES/GOALS: While the current management of single ventricle repairs has drastically prolonged life expectancy, the repair fails over time primarily through pathologic inflammation and fibrosis. Our goal is to demonstrate that cardio-omentopexy can decrease inflammation and fibrosis in swine after cryoinjury. METHODS/STUDY POPULATION: A cryoinjury is created using a liquid nitrogen cooled probe to the right ventricle of 20kg swine. In half the groups the omentum is attached to the heart over the area of the injury. The swine are recovered and monitored for 4 or 8 weeks at which time they are euthanized. The injured area is evaluated via histological and immunohistochemical testing for markers of inflammation and scarring including collagen type, scar area, macrophage activity. RESULTS/ANTICIPATED RESULTS: We anticipate that the addition of omentopexy to cryoinjury will decrease scar area, fibrosis and markers of chronic inflammation. Additionally, we expect an increase in myocytes in the area of injury. We expect that this will occur through the anti-inflammatory and protective mechanism of the omentum. DISCUSSION/SIGNIFICANCE: Cardio-omentopexy, if able to decrease fibrosis and preserve myocytes, may provide a useful adjunct to the treatment of single ventricle repair by prolonging the longevity of the repair. Additionally, as these repairs often require a ventriculotomy, decreasing the operative scar may preserve myocardial function.

The COVID-19 pandemic had an immediate impact on the lives and work of early-career researchers. We leveraged a cluster-randomized trial and compared survey data collected over two timepoints to explore whether these impacts persisted. Although more than a year had passed, 74% of participants reported that their research was affected in multiple ways in both 2020 and 2021. These data suggest that the effects of the pandemic on early-career researchers may be prolonged. Our findings additionally serve as an impetus to identify and implement solutions to early-career challenges that undoubtedly existed before the pandemic, but which COVID-19 brought into the spotlight.

OBJECTIVES/GOALS: Cadmium is a widespread neurotoxic metal pollutant; however prior study results of Cd and later-life cognition are mixed. We investigated association of urinary cadmium on Alzheimer’s Disease (AD) mortality risk, accounting for key co-pollutants smoking and lead, in the presence of competing risks. METHODS/STUDY POPULATION: We included 5692 persons, 60 years old from the 1998-2018 National Health and Nutrition Examination Survey. Underlying cause of death was determined via linked 1999-2019 National Death Index data. Urinary cadmium (UCD) reflects prolonged exposure and was adjusted for creatinine. We used multiple imputation (5 iterations) to recapture substantial model observation drop-out (N=782). We used three Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence interval (CI) per unit increase in UCD and time to AD mortality: a competing risks model, a survey-weighted model, and a baseline model including neither, all adjusted for demographic characteristics, lead, and smoking. RESULTS/ANTICIPATED RESULTS: Follow-up ranged from 0 to 20.8 years (mean 8.2 years), with a total of 1,987 individuals deceased (14,232 person-years at-risk), including 88 individuals dying from AD. Mean UCD was 0.50 μg/g creatinine (standard error=0.01). In baseline and survey-weighted models fully adjusted for NHANES cycle, poverty income ratio, age, race/ethnicity, sex, marital status, education, smoking status, and blood lead levels, a per unit increase in UCD was associated with approximately twice the rate of AD mortality (baseline model HR: 1.92, 95% CI: 1.28, 2.89; survey-weighted model HR: 2.08, 95% CI: 1.42, 3.06). In the competing risks model, this association was attenuated (HR: 1.58, 95% CI 1.06 2.36). DISCUSSION/SIGNIFICANCE: Our study finds chronic cadmium exposure associated with AD mortality even after accounting for competing risks of AD mortality and confounding effects of cigarette smoking and lead exposure, strengthening the evidence that long-term cadmium exposure adversely affects later-life cognitive health.

Racially and ethnically minoritized populations have been historically excluded and underrepresented in research. This paper will describe best practices in multicultural and multilingual awareness-raising strategies used by the Recruitment Innovation Center to increase minoritized enrollment into clinical trials. The Passive Immunity Trial for Our Nation will be used as a primary example to highlight real-world application of these methods to raise awareness, engage community partners, and recruit diverse study participants.

OBJECTIVES/GOALS: The preclinical stage of Alzheimer disease (AD) is a clinically silent period that can be detected through neuroimaging and biofluid biomarkers. The goal of this study was to determine whether performance of complex daily tasks is associated with plasma biomarkers of brain amyloidosis or neuroaxonal injury in cognitively normal (CN) older adults. METHODS/STUDY POPULATION: This is a cross-sectional analysis of an ongoing longitudinal cohort study. CN older adults performed three complex daily tasks (shopping, checkbook balancing, medication management) from the Performance Assessment of Self-Care Skills in their home. Tasks were scored for independence, with more assistance required indicating worse performance. Participants had a plasma sample obtained within two years of completing the tasks. Plasma amyloid (Aβ42 and Aβ40) were evaluated by high precision immunoprecipitation mass spectrometry assays and neurofilament light (NfL) was measured with single molecule array (Simoa) assays. Nonparametric partial correlations were used to quantify the associations between task performance and plasma AD biomarkers, controlling for age and gender. RESULTS/ANTICIPATED RESULTS: 105 CN participants (mean age 74.7 years, 55% female, 88% white) were included. After controlling for age and gender, worse performance of complex daily tasks (more assistance required) was associated with increased plasma NfL (Spearman’s: 0.23, p=0.04) but not plasma Aβ42/Aβ40. DISCUSSION/SIGNIFICANCE: This study suggests that worse performance of complex daily tasks in CN older adults may be associated with increased plasma NfL a marker of neuroaxonal injury, but not with plasma amyloid. These findings could lead to a better understanding of clinical changes that may occur prior to the onset of noticeable memory symptoms in AD or related dementias.

OBJECTIVES/GOALS: Multiple induction agents can facilitate rapid sequence intubation (RSI) in management of refractory status epilepticus (rSE), many which have anti-seizure properties. We examine the anti-seizure efficacy and safety of induction agents used during RSI in the management of rSE. METHODS/STUDY POPULATION: We conducted a single-center retrospective review of patients admitted to the neuro-ICU intubated for management of rSE. Propofol, ketamine and benzodiazepines were considered anti-seizure medication (ASMs), etomidate was not. Patients were treated with propofol or midazolam following intubation. Our primary outcome was clinical or electrographic recurrence of SE within 12 hours of intubation. Exploratory outcomes included time to recover command following, duration of mechanical ventilation (MV) and complications related to intubation. We used multivariable logistical regression to evaluate outcomes between patients induced with ASMs and etomidate. A Fisher exact test was used to compare rSE cessation in a subset of patients with continuous electroencephalography (cEEG) at the time of intubation. RESULTS/ANTICIPATED RESULTS: We identified 149 induced for RSI in management of rSE: 88 patients intubated using ASMs (propofol,n=56; ketamine,n=14; benzodiazepines,n=18) and 61 patients intubated with etomidate. Forty-one patients had recurrence (29.9% ASMS, 24.6% etomidate). The induction agent was not associated with recurrence of SE, time to command following, or duration of MV. Twenty-seven patients had cEEG monitoring at the time of intubation. Sixteen of the 22 patients induced with ASMs had cessation of rSE with induction, while 1 of 5 intubated with etomidate had cessation (Fisher exact test, p=0.047). There were 34 patients with post-induction hypotension (22.9% ASMs, 22.9% etomidate (Fisher exact test, p=1)). DISCUSSION/SIGNIFICANCE: Induction with an anti-seizure medication during intubation was more likely to halt rSE, but did not decrease the likelihood of clinical or electrographic recurrence of rSE and may not affect time to recovery of command following or duration of MV.