Social and environmental determinants of health (SEDoH) are crucial for achieving a holistic understanding of patient health. In fact, geographic factors may have more influence on health outcomes than patients’ genetics. Integrating SEDoH into the electronic health record (EHR), however, poses notable technical and compliance-related challenges. We evaluated barriers to the integration of SEDoH in the EHR and developed a privacy-preserving strategy to mitigate risk of protected health information exposure. Using coded identifiers for patient addresses, the strategy evaluates an alternative approach to ensure efficient, secure geocoding of data while preserving privacy throughout the data enrichment processes from numerous SEDoH data sources.

Efforts to move community engagement in research from marginalized to mainstream include the NIH requiring community engagement programs in all Clinical and Translational Science Awards (CTSAs). However, the COVID-19 pandemic has exposed how little these efforts have changed the dominant culture of clinical research. When faced with the urgent need to generate knowledge about prevention and treatment of the novel coronavirus, researchers largely neglected to involve community stakeholders early in the research process. This failure cannot be divorced from the broader context of systemic racism in the US that has contributed to Black, Indigenous, and People of Color (BIPOC) communities bearing a disproportionate toll from COVID-19, being underrepresented in COVID-19 clinical trials, and expressing greater hesitancy about COVID-19 vaccination. We call on research funders and research institutions to take decisive action to make community engagement obligatory, not optional, in all clinical and translational research and to center BIPOC communities in this process. Recommended actions include funding agencies requiring all research proposals involving human participants to include a community engagement plan, providing adequate funding to support ongoing community engagement, including community stakeholders in agency governance and proposal reviews, promoting racial and ethnic diversity in the research workforce, and making a course in community engaged research a requirement for Masters of Clinical Research curricula.

Evidence-based psychotherapies (EBPs) are underused in health care settings. Aligning implementation of EBPs with the needs of health care leaders (i.e., operational stakeholders) can potentially accelerate their uptake into routine practice. Operational stakeholders (such as hospital leaders, clinical directors, and national program officers) can influence development and oversight of clinical programs as well as policy directives at local, regional, and national levels. Thus, engaging these stakeholders during the implementation and dissemination of EBPs is critical when targeting wider use in health care settings. This article describes how research–operations partnerships were leveraged to increase implementation of an empirically supported psychotherapy – brief Cognitive Behavioral Therapy (brief CBT) – in Veterans Health Administration (VA) primary care settings. The partnered implementation and dissemination efforts were informed by the empirically derived World Health Organization’s ExpandNet framework. A steering committee was formed and included several VA operational stakeholders who helped align the brief CBT program with the implementation needs of VA primary care settings. During the first 18 months of the project, partnerships facilitated rapid implementation of brief CBT at eight VA facilities, including training of 12 providers who saw 120 patients, in addition to expanded program elements to better support sustainability (e.g., train-the-trainer procedures).

OBJECTIVES/GOALS: To determine the prevalence of myocardial diastolic dysfunction (DD) and association of serum concentration of the cardiac biomarker serum soluble ST2 in HIV-infected as compared to uninfected Tanzanian adults at the time of HIV diagnosis. METHODS/STUDY POPULATION: In this cross-sectional study we consecutively enrolled HIV-infected participants and uninfected controls at a large, referral HIV clinic in Mwanza, Tanzania. Standardized history, physical examination, echocardiography and serum samples were obtained. The primary outcome was prevalence of myocardial diastolic dysfunction in HIV-infected as compared to uninfected adults. The secondary outcome was the association of baseline serum sST2 concentration with diastolic dysfunction prevalence. Regression models were used to quantify the associations. RESULTS/ANTICIPATED RESULTS: We enrolled 388 HIV-infected, ART naïve and 461 HIV-uninfected controls. Participants with HIV had a higher prevalence of DD (OR = 2.44, p = 0.001, controlled for age, sex, hypertension and BMI) and more severe dysfunction (66.7% vs 42.5%, p = 0.056) at an earlier age. Baseline serum sST2 concentration was significantly associated with DD in HIV-infected but not uninfected participants (p = 0.04 and 0.90, respectively). More HIV-infected adults with concurrent DD exceeded the threshold of 35ng/mL as compared to controls (15.7% vs 5.3%, p<0.0001). Additionally, a significant population level shift to higher sST2 concentration was observed in HIV-infected adults with dysfunction as compared to both HIV-infected without and HIV-uninfected adults with dysfunction (Kolmogrov-Smirnov test: p = 0.02 and 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: In a large population of HIV-infected adults in sub-Saharan Africa, HIV infection is associated with myocardial diastolic dysfunction. This dysfunction is associated with higher sST2 concentrations. Therefore, we conclude that the sST2 pathway may provide insight into the pathophysiologic mechanisms of dysfunction in HIV-infected adults.

OBJECTIVES/GOALS: This study examines faculty mentor experiences in a summer research program for students traditionally underrepresented in translational research. The objectives are to understand mentor perspectives of the program and how their views were impacted by the pandemic-related pivot to a remote format. METHODS/STUDY POPULATION: During the summer research program, students work with a faculty mentor on an ongoing research project. Program staff pair students with diverse faculty members who share their research interests. Our program has traditionally been offered as a residential in-person program but in 2020 we moved swiftly to a fully remote learning format. Students continued to work on research projects remotely and interacted virtually with their faculty mentors. For the past five cohort years, we have collected comparable data about faculty perspectives of their program experience, which allows us to evaluate the impact of the remote format on the faculty experience compared to that of the in-person format. RESULTS/ANTICIPATED RESULTS: For this study, we will examine data from five cohort years (2017-2021). A survey questionnaire was administered to mentors each year at the end of the summer research program. Data were collected on faculty satisfaction with the quality and amount of student work, the amount of time students spent on their projects, and how mentors communicated with students. In 2020 and 2021, three questions were added regarding satisfaction with the remote format. Quantitative data collected from both the in-person and remote cohorts will be compared using independent samples t-tests. Select quotes from open-ended qualitative questions will be used to illustrate mentors attitudes toward the program. DISCUSSION/SIGNIFICANCE: This study addresses a gap in the literature about summer research programs, as previous work has primarily focused on trainees. As many training programs continue to remain remote or adopt hybrid models, these results have implications for the design of similar mentored research programs.

ABSTRACT IMPACT: Plasma and CSF are not reliable estimates of drug exposure in tissue compartments relevant for treatment and prevention of infectious diseases. OBJECTIVES/GOALS: Globally, high dose fluconazole is widely used in the management of cryptococcal meningitis. While it is known to readily penetrate into cerebrospinal (CSF), less is known about drug concentrations in brain parenchymal tissues. Similarly, distribution of fluconazole into gynecological tissues has not been robustly characterized. METHODS/STUDY POPULATION: With informed consent from next-of-kin, we conducted autopsies within 24h of death for hospitalized Ugandans receiving fluconazole for treatment or secondary prophylaxis of cryptococcal meningitis. Dosing history was abstracted from medical chart and caregiver interviews. Fluconazole concentrations were determined using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS) in plasma, CSF, 10 brain compartments (frontal, parietal, and occipital lobes, corpus callosum, globus pallidus, hippocampus, midbrain, medulla oblongata, spinal cord, and choroid plexus) and 4 female genital compartments (cervix, vagina, ovary, and uterus), depending on tissue availability. Descriptive statistics of tissue to plasma ratios were used to describe concentrations relative to plasma. RESULTS/ANTICIPATED RESULTS: Fluconazole concentrations were measured in available tissues of 21 individuals with detectable fluconazole in plasma. Daily doses of fluconazole were 200 mg (n=4), 400 mg (n=1), 800 mg (n=4), 1200 mg (n=9) or unknown (n=3). CSF concentrations (n=10) ranged from 93-1380% (median 100%) of plasma while brain concentrations (n=3) across all 10 compartments ranged from 45% to 89% (median 69%) of plasma. In the female genital tract, cervical concentrations (n=10) were 9-78% (median 65%) of plasma and in the 2 individuals with available tissue, concentrations in vaginal, ovarian, and uterine tissues were similar to cervix, ranging from 63-105% of plasma. DISCUSSION/SIGNIFICANCE OF FINDINGS: Measuring drug concentrations directly in tissues, the presumed site of action, improves estimates of drug efficacy. While fluconazole concentrations in CSF were similar to plasma, actual brain tissues were consistently lower. Concentrations were similar between upper and lower female genital tracts, but were consistently lower than plasma.

OBJECTIVES/GOALS: The “hidden curriculum” is a set of unofficial rules outside of the formal curriculum that allows medical students to succeed. It is often not accessible to those who are first-generation in medicine. This study created a novel survey tool to directly evaluate the hidden curriculum, its contributing factors, and its effects on students. METHODS/STUDY POPULATION: Using available literature as a guide, a novel survey tool to evaluate different aspects of the hidden curriculum was created. This survey consists of 17 Likert scale questions on topics varying from sense of belongingness to dress code, self-guided studying, mentorship, and confidence in knowing how to succeed. This survey tool was embedded into a larger survey evaluating health disparities and diversity, inclusion, accessibility, and justice (DEIAJ) in the curricular and extracurricular spaces. This survey packet was administered to all medical students at a large U.S. medical school. RESULTS/ANTICIPATED RESULTS: 166 medical students from all years responded to this survey. 70% were female, 27% male, and 3% non-binary or prefer not to say. 67% of respondents agreed or strongly agreed that there is a hidden curriculum accessible to only those who have family members in medicine. 57% agreed or strongly agreed that the medical school gave them the adequate training and resources to succeed. 48% agreed or strongly agreed that they would perform better academically if they had more money with 11% stating they often feel embarrassed in a professional setting due to lack of money. Fellow classmen, faculty members, and upperclassmen were identified as the most useful resources to learn how to succeed in medical school. Students on average reported feeling like they knew what to do to succeed in medical school half of the time. DISCUSSION/SIGNIFICANCE: This data strongly supports the existence of a hidden curriculum and gives insight into the importance of financial support for low-income students and peer support groups for those who do not have family members in medicine. This data will be used to inform future interventions to address the hidden curriculum.

OBJECTIVES/GOALS: Women are twice as susceptible to ailments like anxiety, PTSD, and Alzheimer’s disease compared to men. The locus coeruleus (LC), the primary source of noradrenaline for the brain is implicated in these disorders, however physiological sex differences have never been assessed in the LC. METHODS/STUDY POPULATION: To address this gap, In vivo electrophysiology under anesthesia was used to measure single unit activity of noradrenergic LC firing patterns in 4-month-old wild-type Fischer male and female rats. Recordings measured neuronal activity under basal conditions and in response to a footshock stimulation which elicits burst firing in LC neurons. Single unit activity is sorted via automatic valley seeking scan PCA, additional manual sorting is done via line and template method. Analysis is done extracting interspike interval (ISI) and firing rate of single units, additional analysis is done to quantify properties of bursting patterns (burst duration, spikes per burst, interburst interval, etc…). RESULTS/ANTICIPATED RESULTS: This data shows that during LC burst firing, females have longer interspike intervals compared to males, supporting the inhibitory effect of E2 on LC firing. Additionally, females have significantly different waveform patterns than males, indicating possible differences in intrinsic properties, but further supporting sexually distinct physiology of the LC . Because female rats have been estrous cycle tracked via vaginal lavage, stratification into estrus groups and further analysis may uncover differences within females. These data suggest that estrogen acts as a potent neuromodulator of noradrenergic LC neurons, providing valuable insights into the physiology of this brain region. DISCUSSION/SIGNIFICANCE: This study is the first exploration of LC physiological sex differences. This work offers insights into a critical brain region implicated in many diseases, and may pave the way for future therapeutic approaches, particularly for women, who are at a higher risk of neurological disease developing.

ABSTRACT IMPACT: This work represents a novel way in which genetic information can be used to improve clinical decision making as it pertains to both treatment and management of congenital heart disease. OBJECTIVES/GOALS: Our lab found that MYH6 variants are both enriched in hypoplastic left heart syndrome (HLHS) and associated with decreased cardiac transplant-free survival. To elucidate the mechanisms of MYH6 variant pathogenicity, we are assessing their impact on atrial function during HLHS development and progression. METHODS/STUDY POPULATION: We are using 2D speckle-based tracking to retrospectively evaluate echocardiograms (echos) from 51 HLHS patients, 17 with MYH6 variants and 34 matched controls. Atrial function will be assessed by myocardial strain and strain rate at seven time points, beginning at the time of the patients’ earliest prenatal echo, and ending with their last available echo before death or cardiac transplant. Early left atrial function will examine the role of MYH6 variants in the development of HLHS in vivo, while longitudinal right atrial function will be assessed in order to look for differences that could be contributing to the decreased transplant-free survival seen in MYH6 variant carriers. RESULTS/ANTICIPATED RESULTS: We hypothesize that MYH6 variants cause HLHS by impairing early left atrial (LA) contractility, resulting in altered left ventricular hemodynamics and consequent hypoplasia. We therefore expect to find diminished prenatal LA function in HLHS patients with MYH6 variants. We also hypothesize that MYH6 variants continue to impair right atrial (RA) function in surgically-reconstructed HLHS hearts, necessitating earlier transplantation. Accordingly, we expect variant carriers to exhibit lower RA function at birth versus controls. We expect differences between groups to persist over time, and possibly increase in magnitude. In HLHS patients with MYH6 variants, we anticipate declining RA function will precede right ventricular function and therefore be an early indicator of transplant need. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study represents a novel way in which genetic information can inform clinical decision-making. Identifying MYH6 variants as an early cause of HLHS offers chances for intervention. Understanding long-term effects of MYH6 on right atrial function in HLHS may aid in cardiac transplant risk stratification, thus improving patient outcomes.

OBJECTIVES/GOALS: Patients suffering from respiratory failure have few options to support oxygenation and carbon dioxide removal aside from mechanical ventilation. Our objective was to test a novel extrapulmonary mechanism of gas exchange via peritoneal oxygenated perfluorocarbon (PFC) in a large animal model. METHODS/STUDY POPULATION: Using two 50 kg swine, hypoxia was modeled with subatmospheric oxygen and hypercarbia induced with acute hypoventilation. Through a midline laparotomy, cannulas were placed into the peritoneal space to allow for PFC infusion and circulation. After abdominal closure, these cannulas were connected to a device capable of draining, oxygenating, and infusing PFC. One animal was subjected to acute hypoxia (12% FiO2) and another animal to acute hypoventilation (4 breaths per minute). Primary outcomes were times for SpO2 to reach 75 mmHg, respectively. Trials were performed without PFC and with PFC dwelling or circulating through the peritoneal space, during which abdominal and bladder pressures were monitored and maintained under 20 mmHg by regulation of the PFC volume contained in the animal. RESULTS/ANTICIPATED RESULTS: In the animal subjected to acute hypoxia (12% FiO2), survival time improved from 5:55 to 20:00 (min:sec) after 2.5 liters of oxygenated PFC was instilled in the peritoneal space. Oxygen percent saturation of PFC before and after dwelling in the peritoneal space was measured at 100% before and 70% after dwelling in the animal during this hypoxic period corresponding with a gas transfer of 300 mL of oxygen over the 20-minute trial (i.e., 15 mL/min). Continual PFC circulation did not further extend the survival time during hypoxic conditions over PFC dwelling in the abdomen. In the animal that was acutely hypoventilated, there were no detectable differences in the rate of CO2 accumulation as measured by EtCO2 or direct blood pCO2 measurements with PFC dwelling or circulating through the peritoneal space. DISCUSSION/SIGNIFICANCE: Oxygenated PFC dwelling in the peritoneal space increased the duration of systemic arterial blood saturation remaining greater than 50% during normobaric hypoxic (12% FiO2) conditions but did not appreciably clear blood carbon dioxide during hypoventilation. Future experiments will focus on maximizing the rate of systemic oxygen uptake.

OBJECTIVES/GOALS: The desmoplastic reaction in PDAC involves a significant accumulation of immune cells and fibroblasts.The functional diversity of carcinoma associated fibroblasts (CAFs) remains largely unknown, and identification of immune regulating subsets would have a substantial impact in augmentation of immunotherapy efficacy. METHODS/STUDY POPULATION: Employing histology, FACs, multiplex immunohistochemistry, single cell RNA sequencing (sc-RNA-seq) and genetically engineered mouse models, we demonstrate that aSMA+ cells are a dominant CAF population in PDAC with tumor restraining properties (TS-CAFs), as opposed those of the FAP+ CAFs, which demonstrate tumor promoting activity (TP-CAFs). RESULTS/ANTICIPATED RESULTS: Analysis of bulk tumor depleted of either TS-CAFs or TP-CAFs showed that TS-CAFs predominantly modulate extracellular matrix (ECM) production, facilitate cell-ECM adhesion and regulate adaptive immunity, while TP-CAFs exhibit a lineage that is skewed towards a pro-inflammatory, chemokine secreting phenotype. Further, scRNA-Seq analyses demonstrate that CAFs share distinct gene expression profiles characteristic of lymphocytic and myeloid lineages. Together our data distinguish two populations of CAFs, one which is tumor suppressing with roles in ECM remodeling and another which is tumor promoting with roles in cytokine production, both with immune modulating capabilities. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study identifies a complex network of functionally heterogeneous fibroblasts during PDAC progression with significant immunotherapeutic implication. The identification of distinct fibroblast subsets will allow us to discriminately target fibroblast populations to augment immunotherapy efficacy in pancreatic cancer.

OBJECTIVES/SPECIFIC AIMS: o To review the community’s recommendations on how to rebuild trust in the Flint community. o To review effective community engagement strategies utilized with the Flint Special Projects for project conceptualization, participant recruitment, data analysis, project oversight, and dissemination. METHODS/STUDY POPULATION: The study population includes nearly two hundred residents representing seniors, youth and diverse ethnicities recruited to participate in eleven focus group meetings. The population also represents the general public who attended informational meetings in Flint, Michigan to learn about the crisis and allow residents to voice their opinions and concerns during the onset of the crisis. The project is a mixed methods community based participatory research effort that utilized community decision making in all phases of the effort such as pre-conception, implementation, dissemination and advocacy to encourage the community’s recommendations are adopted at policy and institutional responsiveness levels. It includes three community engaged research efforts: (project 1) A qualitative analysis of community sentiment provided during 17 recorded legislative, media and community events, and (projects 2-3) two mixed methods efforts utilizing purposive sampling of stakeholders whose voice may not have been heard. RESULTS/ANTICIPATED RESULTS: The project presents a qualitative analysis of the community’s voice during the onset of the man-made disaster when the community first became aware of the emergency manager’s plans to switch the water source. It also reflects current perspectives of community voice since the projects are scheduled to end late February 2019. Findings from a trust measure administered to nearly two hundred residents will be presented, along with a qualitative analysis of focus group findings among segments of the population (seniors, youth, and diverse ethnicities) who may have been left out of narratives on the water crisis. Finally, the project will compare empowerment and resiliency approaches being utilized in Flint, Michigan to recover from the disaster with other approaches grounded in literature and theory. DISCUSSION/SIGNIFICANCE OF IMPACT: Communities of color often experience social determinants of health which negatively impact their health, well-being and human rights. Some Flint citizens are experiencing negative health consequences (i.e., rashes, brain and behavioral sequelle, fertility, etc.) as a result of the disaster, and are uncertain of health outcomes in the future. This is the first project to rigorously document and analyze levels of trust and mistrust in the city of Flint since the water disaster occurred. The qualitative research will guide future clinical research that will benefit this traumatized community experiencing high levels of mistrust (i.e., government, elected officials, etc.). The community engaged methodology involved residents and study participants in all phases of the project including project oversight, validating and analyzing data, and dissemination. This methodology will contribute to existing literature and theory on community based participatory research, community engaged research, team science and citizen science. The approaches empowered a call to action among residents, for example, seniors who attended two senior focus group sessions shared “they are hopeful and have a purpose,” resulting in the creation of a council (with officers) at their housing complex to advocate for the well-being of seniors during the recovery process. Recruitment methodologies were extremely successful due to resident level trust in community leaders and community partner organizations. Finally, the project’s examination of approaches encouraging empowerment and resiliency will provide lessons learned for other communities challenged with crisis.

OBJECTIVES/GOALS: A stroke can impair neural communication between sensory and motor pathways thus compromising walking function. Paired associative stimulation (PAS) is a useful assay of sensorimotor integration (SMI) with limited use post-stroke. The objective of this study will be to determine lower extremity PAS effectiveness and reliability post-stroke. METHODS/STUDY POPULATION: This study will use a pre-post, cross-sectional design. Ten healthy controls and 10 individuals with chronic stroke (>6 months) will be recruited. PAS protocols will be individualized to account for between-subject variability in sensorimotor signaling by first measuring cortical sensory signaling using electroencephalography. Post-stroke participants will then receive PAS targeting the paretic tibialis anterior muscle; healthy controls will receive PAS targeting the non-dominant TA. Changes in cortically derived muscle responses will be characterized by absolute motor-evoked potential amplitude (MEPAmp) change, elicited by transcranial magnetic stimulation, over two sessions separated by >24 hours. Clinical measures of sensorimotor function and walking ability will also be performed. RESULTS/ANTICIPATED RESULTS: By individualizing PAS protocols, we expect to see significant increases in MEPAmp pre to post PAS, determined using paired t-tests. We also anticipate reliable PAS-induced increases in MEPAmp, which will be assessed using two reliability statistics: intraclass correlation coefficient and coefficients of variation of method error. Lastly, the increases in MEPAmp will be correlated with measures of sensorimotor function and walking ability, anticipating that greater increases in MEPAmp will be related to better walking ability and sensorimotor functioning. Correlations will be assessed via a Pearson’s correlation. A preset alpha = 0.05 will be used to determine significant findings. DISCUSSION/SIGNIFICANCE: The importance of this study is that establishing individualized PAS protocols could potentially provide a reliable and clinically relevant measure of SMI. Understanding post-stroke lower extremity SMI is necessary for furthering targeted and personalized interventions to combat walking deficits.

OBJECTIVES/GOALS: Thiswork is an evidential study that demonstrates the positive impactof integrating Community Health Workers (CHWs) and SocialDeterminants of Health on an important health outcome, notably in decreasing the 30-day unplanned hospital ED readmissions at Sinai Health Systems. METHODS/STUDY POPULATION: Using datafrom the Sinai Urban Health Institute (SUHI), we compare predictingthe readmissions of patients with and without data pertainingto Social Determinants of Health (SDoH). We thoroughly describe the data cleaning and data pre-processing, done in collaboration with experts in community health. We use a fundamental and ubiquitous classifier in Random Forest for its feature characterization capability in order to translate models results into insights and recommendations for the CHW program. RESULTS/ANTICIPATED RESULTS: We show that when patients are simply engaged byCHWs, regardless of the content of those conversations, we canincrease the predictive accuracy of our classifier by 5%. We usethis result to make recommendations for improving patient careand discuss limitations and future work. Importantly our workpoints directly to the human connection between patients andCHWs as an important feature in the readmission rate. DISCUSSION/SIGNIFICANCE: Our work shows that the predictive capabilities of the classifier increases with CHW logs and SDoH survey data, highlighting the benefit of collecting this information. This is the first step in early identification of such patients so that CHWs are focusing on and providing resources to patients who will most benefit from the program.

Objectives/Goals: This study looks to better understand and call attention to the inequalities found within medical treatment options for individuals suffering from preeclampsia during pregnancy in the USA. The goal is to map the terrain of clinical trials and evaluating existing medicare/medicaid covered services on a both national and state levels. Methods/Study Population: The study population for this research was limited to: pregnant women, ages 18–45, both pregnant and postpartum suffering from preeclampsia. We began looking at clinical trials targeting preeclampsia treatment conducted within the United States between 2019 and 2024. Using our study population parameters, we searched clinicaltrials.gov. These trials’ inclusionary and exclusionary factors were noted, along with participant race. The drug intervention medication used during these clinical trials was compared to those prescribed by doctors via the current national standard of care. We then looked at Medicaid coverage provided to expecting mothers on a state-to-state basis and nationally regulated level. These factors included coverage on ultrasounds, low-dose aspirin, blood pressure monitors, and more. Results/Anticipated Results: Preliminary findings demonstrate the need for more federally regulated policies and programs set in place to help combat the lack of resources faced by expecting mothers across the nation. This research will expose factors contributing to a lack of successful and completed clinical trials and lack of drug intervention innovations taking place to combat the rise in maternal deaths. This study will also focus on the importance of more education and awareness for communities such as African American mothers and those facing multiple gestational pregnancies who are at much higher risk of complications during their pregnancies. We also anticipate a large correlation between a lack of proper childbirth education and mothers who experience complications during birth. Discussion/Significance of Impact: Within the past two decades, rates of preeclampsia have grown 25% within the USA. It affects 5–8% of all pregnancies, and with maternal death rates rising, it is crucial to highlight the alarming lack of government regulation. It is imperative to provide awareness to mothers from disadvantaged backgrounds to treat this preventable condition.

OBJECTIVES/SPECIFIC AIMS: To examine maternal morbidity and its related social determinants among women experiencing homelessness during pregnancy. METHODS/STUDY POPULATION: This study will use an exploratory sequential mixed method design to explore and examine the structural, interpersonal and individual factors contributing to maternal morbidity among a convenience sample of 150 English speaking women experiencing homelessness during a pregnancy within the last 3 years in Baltimore. In the qualitative phase of the study, we will conduct semi-structured interviews with 15 women purposively sampled to refine the relationships between resilience, social determinants of health and multilevel factors that impact maternal morbidities. Factors of interest include prenatal care received, barriers and facilitators to receiving prenatal care, maternal morbidities, social support, and strategies used to manage their condition during this time. Using the findings from the qualitative phase, a quantitative survey will be developed to gather data on topics that emerged in the interviews. In addition, the Housing Instability Index will be used to measure the degree of homelessness as defined by the degree of housing instability in a 6-month period. Using the 25-item Connor-Davidson Resilience Scale, resilience levels among women in the sample will be assessed as a moderating factor in the examination of the relationship between a pregnant woman’s homeless status and maternal morbidity. Descriptive statistics and logistical regression tests will be used to analyze these relationships while controlling for other structural, interpersonal, and individual factors that may be associated with maternal morbidity. RESULTS/ANTICIPATED RESULTS: Qualitatively we expect to gain insight into the relationship between the extrinsic and intrinsic factors impacting maternal morbidities and the health behaviors and practices used by women to manage their pregnancy while homeless. These findings will inform the quantitative survey development and help generalize the quantitative findings. We expect to identify the common morbidities in this population we anticipate that there will be differences in maternal morbidity among the different types of homelessness. Maternal morbidity will be higher among women with a greater degree of homelessness. Resilience will have a moderating effect on the relationship between homelessness and maternal morbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: This study, to our knowledge, is the first to look at maternal morbidity in this population. Additionally, this study seeks to move current research from examining infant outcomes at birth among mothers experiencing homelessness to understanding the maternal morbidities during this period. Long term, good maternal health has significant implications for the health of a mother’s future pregnancies and a risk reduction of adverse chronic conditions. Study results will provide the preliminary knowledge needed to guide further research leading to clinical approaches that promote better maternal health in this population. Lastly, the study findings will inform policy by characterizing the quality and strength of evidence of the adverse maternal health effects associated with the experience of homelessness.

OBJECTIVES/GOALS: The goal was to develop foundational research knowledge and skills for clinicians interested in conducting clinical research. Emphasis was on the development of a research question and the iterative process necessary to transform a research question into a well-designed study and well-articulated research proposal for pilot grant funding. METHODS/STUDY POPULATION: The course took place over 10 sessions, May - September 2021. The application process required participants to provide an initial self-assessment of research skills and a proposed research question. 25 clinicians applied to the program, 11 were accepted, and 9 enrolled. All clinicians in the initial cohort were clinical faculty physicians. Because of the geographical distance of participants as well as the ongoing pandemic, the course used a blended learning approach with both synchronous and asynchronous learning. Participants viewed online lectures on core content coupled with live virtual sessions with opportunities for discussion and application of the content. Relevant CTSI and institutional resources were highlighted in each session. RESULTS/ANTICIPATED RESULTS: Of the 9 clinician participants who enrolled in Research 101, the average attendance per session was 67% or 6 people. 89% or 8 participants attended five or more sessions. 5 participants submitted a letter of intent for the annual CTSI Pilot grant program, and of the five, two were invited to submit a grant application. Formal evaluation of the program is currently ongoing and will close on November 30th, at which time full results will be available. Research competencies will be assessed through a pre-post comparison, each self-rated by course participants. Additionally, participants were asked to provide input on the most and least valuable components of the course, as well as any open-ended feedback. Research 101 leadership will use these results to improve the course for future participants. DISCUSSION/SIGNIFICANCE: A learning health system (LHS) is recognized as an essential means by which research evidence is translated into practice. Important to realizing the LHS vision is the engagement of clinicians into the generation and translation of research into practice. Research 101 is an important way to bolster clinician engagement in translational research.

Objectives/Goals: To present an asset-based approach to advance minoritized patients’ participation in clinical research by elevating experienced Black research participants’ motivations and decision-making processes, favorable sociocultural research contexts, and impactful research questions to reduce chronic disease burden and improve quality of life. Methods/Study Population: Data will be extracted from a pilot study to develop an asset-based approach to clinical research with young Black adults living with chronic pain. Participants will be Black patients at an academic medical institution on the West Coast, ages 21 to 44, currently or formerly have chronic pain, and current or previous electronic health record-captured enrollment in a clinical research study. Approximately 25 Black patients will participate in semi-structured focus groups with topics including: motivations for research participation, access to research, preferred research activities, perceived research benefits, favorable structural and cultural contexts, considerations of past ethical and trust violations, and alignment of research questions and patient needs. Data will be collected Fall ‘24 and analyzed in Winter ‘25. Results/Anticipated Results: We will examine experienced Black clinical research participants’ decision-making processes for participating in research, including access to studies, perceived value of research, community support, and alignment of study goals with their personal interests and needs. Results will illuminate the sociocultural, structural, and historical contexts under which Black patients have successfully participated in clinical research, and types of studies they have participated in, and recruitment procedures that have been effective. Also, we will examine the conditions for successful study completion. Investigators will also learn about the types of clinical research questions that minoritized patients believe will have an immediate and long term impact on their lived experienced with chronic illness. Discussion/Significance of Impact: The results will challenge deficit models of minority research participation that focus solely on barriers to participation, previous ethical harms, and violations of trust/trustworthiness by elevating the motivations, favorable contexts, and empirical priorities of experienced Black clinical research participants.

ABSTRACT IMPACT: As the number of poorly water-soluble drugs in development increases, our research will expand on the science behind improving drug solubility and absorption and ensuring that promising poorly-water solubility drugs do not fail drug development. OBJECTIVES/GOALS: Spray-dried dispersion (SDD) tablet formulation is an approach to increase oral drug solubility and absorption. Methods to predict SDD performance in humans are poorly developed. We aim to develop an in vivo in vitro correlation (IVIVC) between in vitro dissolution and in vivo absorption of itraconazole SDD tablets. METHODS/STUDY POPULATION: This research project involves tablet manufacturing, in vitro dissolution experiments, and a clinical study. We manufactured fast-, medium-, and slow-release SDD tablets containing amorphous solid dispersion of itraconazole (100 mg) and different grades of the polymer hypromellose acetate succinate (HPMC-AS). Tablets differed in slug pressure, tablet compression force, and formulation composition. Dissolution studies were performed using the United States Pharmacopeia (USP) type II apparatus. The clinical study is an ongoing randomized, cross-over, open-label, fasted, single-dose trial in healthy participants (n=12). An IVIVC will be created by comparing the rank order of drug in vitro dissolution with in vivo absorption. RESULTS/ANTICIPATED RESULTS: Tablet manufacturing was successful, and the tablets displayed the same dissolution rate ranking order as anticipated. Fast-release tablets showed the highest percentage of drug dissolved by 10 min (74%) compared to medium- (62%) and slow-release (1.2%) tablets. Percentage drug dissolved differs by at least 10% at all time points among the different release-rate tablets. The clinical study is currently ongoing, and we expect that the pharmacokinetic (PK) profiles differ among the different tablets. We predict that the rank order of tablet absorption in humans will agree with the order of drug dissolved observed in the dissolution experiments. DISCUSSION/SIGNIFICANCE OF FINDINGS: Spray-dried dispersions are a formulation method to try to improve drug solubility and oral drug absorption. This research will elucidate manufacturing parameters that can impact tablet performance and expand on the ability of in vitro dissolution to predict human PK and streamline drug development of poorly soluble drug candidates.