Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOESpot). FTOESpot correlated with CSI, as did the change in FTOE during tilts, but CSI’s correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

Recent reports on the burden of cardiovascular disease (CVD) in the USA indicate that despite significant declines in CVD mortality in the late 20th century, this decline is now decelerating and may be worsened by inequalities in health care. Social factors contribute to most of the cardiovascular health disparities documented to date. Hispanics/Latinos and African-Americans share a higher prevalence of cardiovascular risk factors and experience higher rates of poverty and social stressors than non-Hispanic Whites. We propose that the use of social and behavioral data beyond basic and sometimes loose identifiers of race/ethnicity, educational attainment, and occupation would inform clinical practice and greatly facilitate the provision of adequate guidance and support to patients regarding continuity of care, adherence to medications and treatment plans, and engagement of participants in future research. This perspective briefly highlights factors deemed to be critical for the advancement of Hispanic/Latino health and delineates pathways toward future applications.

OBJECTIVES/GOALS: The Association for Clinical and Translational Science (ACTS) offers important inter-institutional communities through Special Interest Groups (SIGs). New to the SIG ecosystem is the Justice, Equity, Diversity, and Inclusion (JEDI) SIG. METHODS/STUDY POPULATION: Formed in 2022, the JEDI SIG is a growing community of individuals seeking to develop papers and products relating to improving health equity and workforce diversity within the Translational Science Community. Within this context, diversity is broadly defined to include groups at a negative power differential within US society. RESULTS/ANTICIPATED RESULTS: Comprised of 54 individuals spanning 29 institutions as of our first meeting in October 2022, the JEDI SIG is a welcoming group for ACTS members looking to make a difference. We have developed working groups to develop SIG-directed projects, and we look forward to expanding our activities in the future. DISCUSSION/SIGNIFICANCE: In this poster we will share key information about the new JEDI SIG including monthly meeting times, current activities, and ideas for future work.

OBJECTIVES/GOALS: Environmental factors may significantly increase the risk of or buffer against Alzheimer’s disease and related dementias, yet strategies to address cognitive decline and impairment to date largely overlook the role of neighborhoods. This mixed-methods study is the first to examine potential links between access to eateries and cognitive function. The goal is to inform place-specific interventions to help aging individuals reduce risk for cognitive impairment through neighborhood community and design. METHODS/STUDY POPULATION: Following an exploratory sequential mixed-methods design, seated and mobile interviews with 125 adults aged 55-92 (mean age 71) living in the Minneapolis (Minnesota) metropolitan area suggest that eateries, including coffee shops and fast-food restaurants, represent popular neighborhood destinations for older adults and sources of wellbeing. To test the hypothesis that these sites, and the benefits they confer, are associated with cognitive welfare, we analyzed data from urban and suburban dwelling participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national racially diverse sample of older Americans followed since 2003 (n = 16,404, average age at assessment 72 years). RESULTS/ANTICIPATED RESULTS: Qualitative thematic analysis of how older adults perceived and utilized local eateries include sites of familiarity and comfort; physical and economic accessibility; sociability with friends, family, staff, and customers; and entertainment (e.g., destinations for outings and walks, free newspapers to read). Quantitative results from multilevel linear regression models demonstrate a positive association between density of eateries and cognitive functioning. Taken together, these results complicate our understanding of fast-food settings as possible sites of wellbeing through social interaction and leisure activities. DISCUSSION/SIGNIFICANCE OF IMPACT: The results contribute new evidence towards an emerging ecological model of cognitive health. Understanding whether and how retail food environments can help buffer against cognitive decline among older adults provides novel opportunities to promote wellbeing in later life through community interventions and neighborhood design.

Pragmatic trials aim to generate timely evidence while ensuring feasibility, minimizing practice burden, and maintaining real-world conditions. We conducted rapid-cycle qualitative research in the preimplementation period of a trial evaluating a community paramedic program to shorten and prevent hospitalizations. Between December 2021 and March 2022, interviews (n = 30) and presentations/discussions (n = 17) were conducted with clinical and administrative stakeholders. Two investigators analyzed interview and presentation data to identify potential trial challenges, and team reflections were used to develop responsive strategies. Solutions were implemented prior to the commencement of trial enrollment and were aimed at bolstering feasibility and building ongoing practice feedback loops.

Every research study that includes volunteer participants requires safety assurances in proportion to the risks of the study. Investigator-initiated clinical research can present unique regulatory challenges particularly for studies with a risk profile that warrants more oversight than minimal risk but less than for large, commercial, or high-risk research. The use of an independent safety officer (ISO) offers a middle way of right-sizing oversight to match the risk. ISOs are clinicians or researchers with relevant expertise who are independent of the investigator and the research study. Their relationship to the study is defined by a formal charter which is aligned with the protocol and Data and Safety Monitoring Plan to address the oversight process, responsibilities of the ISO, and clearly describe the variables to be monitored. The ISO responsibilities include reviewing safety data, adverse events, recruitment, demographics, study progress, data quality, protocol changes, and any new scientific information that pertains to the trial. Finally, the ISO reports in their review on any significant findings may propose modifications to the study or a need to stop the trial.

OBJECTIVES/SPECIFIC AIMS: Our objective was to assess and compare the attitudes of patients with head and neck cancer and their clinicians regarding the commercialization of genetic research data. We explored whether such opinions changed when profits from such transactions were used to fund 1) cancer research, 2) academic research generally, or 3) if patients were given personalized genetic information in return. METHODS/STUDY POPULATION: This qualitative analysis was nested within a prospective precision oncology genomic sequencing study in an NCI-designated cancer center. We conducted paired, semi-structured interviews with enrolled participants with head & neck cancer and with their doctors (medical oncologists, surgical oncologists, and radiation oncologists). Interviews were recorded, transcribed, and coded for analysis. Codes were developed through an iterative process until saturation was reached, and all transcripts were double-coded (and discrepancies reconciled) to ensure reliability. RESULTS/ANTICIPATED RESULTS: We identified three main themes from the patients and clinicians: (1) Both clinicians and their patients were unclear about how the study protocol and informed consent form authorized patients’ genetic data to be used and commercialized in the future. (2) Patients with cancer were generally more comfortable than their clinician thought they were regarding the ongoing research use of their genetic data and commercialization thereof. (3) There is a strong interest among patients and clinicians in focusing academic medical center profits from commercialization back into the research program from which the data was acquired, rather than being invested into academic research more broadly. DISCUSSION/SIGNIFICANCE OF IMPACT: Given patients’ strong feelings about the commercialization of their data, our results highlight the need for greater transparency—both with patients and with their clinicians—about potential future use of research data. Clinicians appear inclined to be particularly cautious regarding access to and commercialization of patients’ data, however patients generally hope that their data may be used to help future cancer patients. Explicit discussions with patients about specific future uses of profits derived from commercialization of research data can ensure both transparency and participation in future primary and secondary precision health research programs.

OBJECTIVES/SPECIFIC AIMS: This study aims to evaluate potentially traumatic events (PTEs) and its relationship with posttraumatic stress symptoms (PTSS), posttraumatic growth (PTG), and resilience in a sample of help-seeking individuals in Puerto Rico. METHODS/STUDY POPULATION: This is an analytic, cross sectional design. Adults receiving health services will participate in the study. Recruited participants will provide informed consent during a visit to a community mental health clinic or community hospital. They will complete a demographic document and four retrospective questionnaires about the variables of study. RESULTS/ANTICIPATED RESULTS: We expect that a high rate of potentially traumatic events (PTEs) is associated with an increased rate of posttraumatic stress symptoms (PTSS). We also expect that a high rate of PTSS is associated with an increased rate of posttraumatic growth (PTG). We expect that a high rate of resilience is associated with low rates of PTSS and PTG. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a first step in the development of effective, clearly targeted interventions, specifically designed to treat negative effects, and also to facilitate positive change and resilience after PTE exposure.

OBJECTIVES/SPECIFIC AIMS: To identify the most frequently reported barriers/constraints and resources by junior faculty in achieving their goals at a large medical school in the Western United States. METHODS/STUDY POPULATION: We reviewed 222 individual development plans (IDPs) from 26 departments in an academic medical center for content regarding constraints and resources to achieve activities and barriers and/or resources to achieve new goals. The content and quality of the IDPs included was ascertained using quantitative data analysis as well a review of open-ended qualitative questions. In addition to analyzing the content, the quality and percent completion of data filled out for each field in the IDP was also assessed to help identify gaps with departments in successfully completing and submitting their IDPs. RESULTS/ANTICIPATED RESULTS: Junior faculty indicated the following barriers: time/time management (55%); work/life balance (32%); funding (8%) and other (5%). Junior faculty also indicated that they had resources to help them achieve their goals, including: mentors (60%); collaborators (26%); colleagues (6%); other (8%). DISCUSSION/SIGNIFICANCE OF IMPACT: The barriers in goal achievement (e.g., time/time management & work/life balance issues) at this academic medical setting suggest that further resources regarding time management and work - life balance need to be developed and disseminated in order to assist faculty in achieving their objectives. This project also reinforces the importance of having a robust mentor or mentoring team for junior faculty. Mentors and administrators should work collaboratively with junior faculty to identify resources to improve time management and work-life balance.

OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.

OBJECTIVES/SPECIFIC AIMS: Histones are nuclear proteins that associate with DNA to facilitate packaging into condensed chromatin. Histones are dynamically decorated with post-translational modifications (PTMs), which regulate such processes as DNA repair, gene expression, mitosis, and meiosis. Histone 3 Family 3 (H3F3) histones (H3.3), encoded by H3F3A and H3F3B, mark active genes, maintain epigenetic memory, and maintain heterochromatin and telomeric integrity. Specific somatic mutations in H3F3A and H3F3B have been strongly associated with pediatric glia and other tumors, but no germline mutations have been reported. The goal of our study was to further understand the functional effects of germline mutations of H3F3A and H3F3B. METHODS/STUDY POPULATION: We analyzed 32 patients bearing de novo germline missense mutations in H3F3A or H3F3B with core phenotypes of progressive neurologic dysfunction and congenital anomalies, but no malignancies. Patient histones were analyzed by quantitative mass spectrometry (qMS). RESULTS/ANTICIPATED RESULTS: qMS results revealed that the mutant histone proteins are present at a concentration similar to that of wild-type H3.3. qMS analysis showed strikingly aberrant PTM patterns that suggested local dysregulation. These patterns are distinct from the dominant negative somatic mutations, which cause more global PTM dysregulation. Patient cells also demonstrated upregulation of the expression of genes related to mitosis and cell division, and had a greater proliferative capacity. DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggests that the pathogenic mechanism of germline histone mutations is distinct from that of the published cancer-associated somatic histone mutations, but may converge on control of cell proliferation. Further clarification of the pathophysiology in these patients can elucidate the roles of histones and histone PTMs in human development and non-syndromic neurodegeneration. In addition, it provides a framework for targeted therapy development for this and related progressive neurologic disorders.

OBJECTIVES/SPECIFIC AIMS: Our study aims to create a novel state level HIV-ESRD dataset and compare patient-level characteristics on rates of transplant referral, evaluation, waitlisting, and transplantation for HIV-positive versus HIV-negative patients. Our main hypothesis is that HIV-positive patients in Georgia are less likely to be referred to kidney transplant compared with HIV-negative patients. METHODS/STUDY POPULATION: Three datasets will be merged in order to create the HIV-ESRD dataset. The datasets are United States Renal Data System (USRDS), a southeast Transplant Referral Dataset and patient-level Georgia Department of Public Health HIV Incidence Database. The resulting study population will include patients that are older than 18, but less than 70, are HIV-positive and are on dialysis in Georgia. This dataset will also identify those patients who have been referred to transplantation, have been waitlisted, and have received kidney transplants between January 2012 and December 2017. If within a 1-year period, the prevalence of HIV-positive patients referred to transplant was lower than the 1-year period prevalence of HIV-negative patients for 3 consecutive years, the dialysis facility will be classified as having a within-facility disparity. We will then characterize patient level and dialysis facility-level factors that may contribute to observed findings. Patient characteristics will include demographic, clinical data, proxies of socioeconomic status, and geospatial relationships to transplant centers and rural vs urban neighborhoods. Facility-level characteristics includes profit status (profit vs. nonprofit), total number of staff (including full-time and part-time employees), aggregate demographic and clinical facility characteristics, and total number of treated patients. RESULTS/ANTICIPATED RESULTS:. We anticipate the successful creation of the proposed dataset that will allow for accurate identification of HIV-positive patients on dialysis in Georgia.. This dataset will provide the ability to determine referral, waitlisting, and transplantation rates.. We predict the overall rate of referral, waitlisting, and kidney transplantation in HIV patients will be relatively low, and that dialysis facilities with a higher proportion of HIV-positive will have lower referral rates compared to dialysis facilities treating a higher proportion of HIV-negative patients. It is foreseen that among patient-level characteristics, the strongest predictor for decreased referral rates will be HIV serostatus and among dialysis facility factors, profit status will be associated with decreased referral rates. DISCUSSION/SIGNIFICANCE OF IMPACT: This pilot study offers the creation of the first regional dataset of HIV-ESRD patients that will include patient-level characteristic of HIV-positive patients and provide a model for other states to adopt. We will contribute improved state-level description of incidence data of HIV-positive patients on dialysis, current rates of transplant referral, waitlisting, and transplantation, and offer potential associated factors that influence these processes. This knowledge will be used to determine the next steps in improving access to care; conducting qualitative research to understand dialysis facility views on transplant in HIV patients, understanding HIV patient’s position on transplantation, providing education on the value of kidney transplant referral, and expanding the approach of combining patient level HIV data to the southeast.

Storytelling is increasingly recognized as a culturally relevant, human-centered strategy and has been linked to improvements in health knowledge, behavior, and outcomes. The Community Engagement Program of the Johns Hopkins Institute for Clinical and Translational Research designed and implemented a storytelling training program as a potentially versatile approach to promote stakeholder engagement. Data collected from multiple sources, including participant ratings, responses to open-ended questions, and field notes, consistently pointed to high-level satisfaction and acceptability of the program. As a next step, the storytelling training process and its impact need to be further investigated.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the factors influencing engagement with out-patient services from pregnancy to 1 year postpartum among women in recovery from opioid use disorders (OUD). METHODS/STUDY POPULATION: We conducted semi-structured qualitative interviews and a brief survey with 20 mothers in OUD recovery recruited from health care and community organizations in Western MA. Transcripts were coded by two independent coders and analyzed using a qualitative descriptive approach. RESULTS/ANTICIPATED RESULTS: The average duration of any addiction treatment among the 20 participants was 5.6 years with 80% receiving medication-assisted treatment during a pregnancy. Approximately two-thirds experienced relapse during pregnancy or the first year postpartum. We identified 3 themes elucidating women’s experiences around service engagement: “How I see myself” (personal development), “How services see me” (service delivery quality), and “Are you with me?” Personal development included response to past trauma, coping strategies and self-advocacy, and adjusting to parenthood. Service delivery quality was influenced by service design, efficacy of individual providers, and cultural norms (organizational and societal). In the final theme, intersection of individual and service-level factors influenced the degree and quality of the women’s experience engaging with services. DISCUSSION/SIGNIFICANCE OF IMPACT: Women describe successful engagement when they experience service providers as being emotionally supportive, delivering relevant services, and advocating on their behalf. To best support and engage families affected by OUD, relevant and timely services should be linked with compassionate delivery.

OBJECTIVES/SPECIFIC AIMS: Because clinical trial results are instrumental in the approval of a new drug or changes to the practice of medicine, ensuring the accuracy and validity of collected data is critical in the clinical trial process. This function, routinely carried out by clinical trial monitors in industry-sponsored trials, is often lacking in investigator-initiated trials (IITs) conducted in academia. To address this challenge, we have developed a self-study module that can be used to cross-train academic researchers in essential concepts and practical approaches to monitoring. Furthermore, we are applying a framework drawn from implementation science in the development and launch of this initiative. This framework, as used in other educational programs, is employed here to close the gap between initiative and practice, thereby effectively disseminating this training would improve the quality of clinical trials in academia. METHODS/STUDY POPULATION: This research project applied exploration, installation and implementation stages of the implementation science process by 1) exploring the need for a new initiative, 2) disseminating results, 3) engaging stakeholders, 4) creating standard operating procedures (SOPs) for installation and implementation, 5) studying user satisfaction and effectiveness, 6) addressing feedback and 7) conducting implementation. RESULTS/ANTICIPATED RESULTS: From literature review and internet searches we determined that although numerous GCP training resources exist, most are too broad and lack the practical approaches to meet the complex requirements of monitoring. Moreover, most of the offerings identified are costly or inaccessible. With only about 65% of IITs reported as being monitored (Figures 1 and 2), it appears that there is a clear need for training tools that are easily available to a broader audience. And because monitoring skills are substantially different from those associated with research coordination, it is not surprising that research professionals believed that they would need additional training to become proficient. To address this need, we began developing a monitoring module. We engaged key stakeholders from academia and industry to gain insights into their needs. The results indicated that although our training module was effective, supplementary information on the fundamentals of clinical trials should be included for those new to the field. After incorporating suggested changes and completing the module, we conducted user testing to determine if our module is ready to be broadly disseminated (Figures 3 and 4). Following positive feedback from the group, we are currently in the process of disseminating our module and studying its impact. DISCUSSION/SIGNIFICANCE OF IMPACT: IITs are instrumental in translating academic research into product development. Deficiencies in the quality control of these trials can lead to inadequacies in data accuracy and validity that could lead to significant delays in bringing innovative therapies to patients. Recent NIH policies require data and safety monitoring for all of the trials it supports. The latest addendum to ICH GCP, E6(R2), discusses a need for quality management across the clinical trial lifecycle. As we continue to disseminate and share information during the development of our self-study monitoring module, we are engaging key stakeholders from academia, government, and private institutions to understand and address quality challenges in conducting clinical trials. Finally, this research informs dissemination and implementation research, specifically for creating training for academic research professionals.