OBJECTIVES/GOALS: METHODS/STUDY POPULATION: This study utilizes the IeDEA W. Africa cohort to evaluate the prevalence and burden of hypertension and diabetes type II among people living with HIV (PLWH) in sub-Saharan Africa (SSA), and to assess how sex and aging impact the development of these NACM. The cohort is a large, international collaboration across eight countries and 19 treatment centers. Established by the National Institute of Allergy and Infectious Diseases in 2006, the W. Africa cohort is now in its fourth renewal (2021-2026). Participating countries include Senegal, Mali, Cote d’Ivoire, Burkina Faso, Ghana, Togo, Benin, and Nigeria. Data are collected from affiliated cohorts in the regional data center every 24 months. The cohort currently includes >65,000 adult PLWH on anti-retroviral therapy. RESULTS/ANTICIPATED RESULTS: The prevalence of several NACM, such as hypertension and cardiovascular disease, have significantly increased among PWH over time, surpassing prevalence observed in the general population. We therefore expect similar patterns in the W. Africa IeDEA cohort and a high prevalence and burden of both hypertension and diabetes type II in this sample. Additionally, evidence suggests that increasing age and female sex serve as independent risk factors for the development of NACM in PLWH. We anticipate that both increased age and female sex, separately and synergistically, are associated with increased prevalence and burden of hypertension and diabetes type II in this cohort. DISCUSSION/SIGNIFICANCE: With more than 37 million people currently living with HIV, the HIV/AIDS epidemic continues to pose a serious threat to global public health. SSA bears a disproportionate burden of the epidemic with greater than two-thirds of global cases. NACM are now driving morbidity and mortality among PLWH, and increased age and female sex may modify this effect.

OBJECTIVES/SPECIFIC AIMS: Chromosome 22q11.2 deletion syndrome (22q) has a prevalence almost as common as Down syndrome. 22q is well known for medical complications, including congenital heart disease and immune dysfunction. However, children with 22q also have borderline cognitive abilities, are at high risk for ADHD and anxiety, and have poor independent living skills (adaptive function). Parenting is one modifiable factor that has been found in typically developing populations to promote independent functioning and protect against the development of anxiety disorders. This study investigates the associations between parenting, anxiety, and adaptive functioning in 22q. METHODS/STUDY POPULATION: Parent-child (ages 4–11) dyads participated in an ongoing study involving observed parenting during challenging tasks plus questionnaires of parenting, child anxiety, and child functioning. In total, 52 dyads [22q=25; typical development (TD)=27] have enrolled to date. Parents completed questionnaires, including the Parenting Styles and Dimensions Questionnaire (PSDQ), Spence Children’s Anxiety Scale, and Adaptive Behavior Assessment System for Children (ABAS-II). PSDQ dimensions of interest included Parental Psychological Control (PPC: the management of child behavior through the manipulation of emotions, expectations, and independence), Authoritative, Authoritarian, and Permissive, and the subscales of these broad dimensions. Scores were compared using t-tests and multiple regression models were used to investigate the relationships between 1-parenting and anxiety and 2-parenting and adaptive function. RESULTS/ANTICIPATED RESULTS: Mean age was 7.8+2.1 years. Full Scale IQ (TD: 112.3 vs. 22q: 82; p<0.001) and ABAS-II Global Adaptive Composite (TD: 102.7 vs. 22q: 69.2; p<0.001) were significantly higher in the TD group. Parents in the 22q group reported higher levels of PSDQ PPC (22q: 2.3 vs. TD: 2.1; p=0.06), specifically overprotection (22q: 3.7 vs. TD: 3.3; p=0.04), and lower Authoritative parenting (22q: 4.1 vs. TD: 4.4; p=0.03), across the subscales. There were no differences in Authoritarian or Permissive parenting. Children with 22q had higher Spence Total Anxiety scores (22q: 62.5 vs. TD: 47.4; p<0.001). Self-reported PPC and group (R2=0.3, F3,48=8.1, p<0.001) predicted child anxiety with a main effect of PPC (β=16, p=0.02). Group tended to moderate the association between PPC and anxiety (β=−17.5, p<0.10), with PPC predicting anxiety for the 22q group (r=0.35, p<0.09), but not the TD group (r=−0.08, ns). At this time, a relationship between PPC and child ABAS-II GAC in 22q (r=−0.14; p=0.5) is not identified. DISCUSSION/SIGNIFICANCE OF IMPACT: Children with 22q are at high risk for anxiety and poor adaptive outcomes. These results suggest that parents of children with 22q use higher levels of PPC, which is correlated with increased child anxiety. These analyses also provide support for parenting interventions to improve anxiety in children with 22q and possibly mitigate the serious mental health risk in this population.

OBJECTIVES/GOALS: Writers with high self-efficacy perform better than writers with low self-efficacy regardless of writing ability. We investigated whether Shut Up & Write® (SUAW), a less-intensive writing intervention, produced gains in writing self-efficacy similar to those reported by intensive, longer-term interventions. METHODS/STUDY POPULATION: Meetings were held 2x/wk for 5 wks via Zoom, for 1 hour. Participants were encouraged to attend at least 1x/wk. The 1st few mins were devoted to a discussion of what each person planned to work on. Then, a timer was set and each writer muted themselves, shuttered their webcam, and wrote. When the alarm sounded, everyone returned to the group, and discussed what was accomplished. We measured writing self-efficacy before & after participating in SUAW using a pre-post survey design and used two-tailed paired t-tests to test for significant differences between pre- and post-test means. SUAW participants (n=23) were in 1 of 2 categories: 10 were self-selected LEADS scholars from MSIs, and 13 were medical students in a palliative care program. 86% were URB, 78% were female. RESULTS/ANTICIPATED RESULTS: Seven (30%) SUAW participants completed both the pre- and post-survey. Individuals showed significantly higher agreement from pre-to-post on the self-efficacy item “I have a generally positive attitude toward writing” (p=0.047) using a 5-point Likert scale from “completely agree” to “completely disagree.” Most other items did not indicate significant change between pre- and post-survey. The mean of the question “How satisfied were you with this Shut Up & Write activity?” which appeared only on the post-survey (n=10) was 1.10 (1=extremely satisfied, 5=extremely dissatisfied). Anticipated result: We suspect that the benefits of SUAW are best actualized by ongoing attendance, and that benefits are cumulative. DISCUSSION/SIGNIFICANCE: We found that participation in SUAW promotes writing self-efficacy in early-career URB researchers. This is an exciting finding because publishing ones research is essential for academic advancement, and research supports a relationship between writing self-efficacy and writing production. This may curtail URB scientists’ rate of attrition.

OBJECTIVES/SPECIFIC AIMS: Identify objective neurological substrates of cognitive fatigue in Parkinson’s disease and in aging. METHODS/STUDY POPULATION: Structural and diffusion MRI. Behavioral assessments for aged adults and Parkinson’s disease. RESULTS/ANTICIPATED RESULTS: Gray and white matter deficits that correlate with deficits in the basal ganglia for fatigued Parkinson’s disease patients Versus anterior cingulate cortex in healthy aged adults with fatigue. DISCUSSION/SIGNIFICANCE OF IMPACT: Over 50% of patients with Parkison’s disease and 38% of healthy older adults suffer from cognitive fatigue. However, diagnostics are limited to subjective surveys and there are no treatments for either population. Therefore, objective measures are greatly needed for better diagnosis and development of treatment targets.

OBJECTIVES/SPECIFIC AIMS: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to help concretize the relevant constructs, and then usied these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively creating domain-specific survey items, and then further discussed and refining the number, grouping, and wording of the items. METHODS/STUDY POPULATION: We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars. Each item was answered using a six-point Likert scale where a low score indicated poor expression of the specific leadership attribute and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Means, medians, standard deviations, and ranges of each item were calculated and tabulated. A complete (Pearson) correlation matrix was computed so that the raw inter-item relationships can be observed. For each a priori Domain an equal weighted summary scale was created and tabulated for review. The internal consistency of each a priori scale was assessed by calculating Cronbach’s Alpha (α). Items with low Item to Construct coefficients were candidates for elimination or modification, and overall scales with low’s will undergo further discussion. To challenge our assumptions of the construction and integrity of each domain, we employed exploratory Principal Components Analysis (PCA), followed by orthogonally rotated Factor Analysis (FA). We also forced the PCA / FA analysis to extract the a priori dimensions that allowed us to compare if the empirical and a priori structures match. DISCUSSION/SIGNIFICANCE OF IMPACT: We are partnering with the CTSA programs at Penn and Yale to assess issues of generalizability and scalability. We are working with Vanderbilt to install survey onto REDCap for ease of dissemination. Will continue to assess psychometric properties and refine as we receive more input.

OBJECTIVES/SPECIFIC AIMS: Cesarean delivery is typically performed in the extremely preterm period (23 to 28 weeks) when the fetus is in breech presentation to avoid the potential risk of head entrapment by an insufficiently dilated cervix during a vaginal delivery. Assessment of the prevalence of extremely preterm breech cesarean delivery would help to appropriately guide future clinical interventions designed to increase the feasibility of vaginal delivery for this sub-group of patients. METHODS/STUDY POPULATION: We performed a cross-sectional study of the 2106 U.S. National Vital Statistics birth certificate database to estimate the prevalence of cesarean deliveries performed during the period of gestation from 23 to 28 weeks with a fetus in breech presentation. RESULTS/ANTICIPATED RESULTS: An analysis of the total births in the 2016 registry (3,945,875) was performed. The gestational age was limited to the target range of 23 0/7 to 27 6/7 weeks. Multiple gestation deliveries were excluded. This yielded 16,092 births of which 4,849 were noted to have breech presentation. The proportion of cesarean deliveries performed for singleton breech fetuses at this gestational range was 87% (4,203/4,849). DISCUSSION/SIGNIFICANCE OF IMPACT: The probability of undergoing a cesarean delivery for an extremely preterm fetus in breech presentation is notably higher (87%) when compared to an overall cesarean delivery rate of 31.9%. Specific interventions to allow for vaginal delivery in this particular sub-group of the obstetric population would be useful to reduce maternal morbidity by increasing vaginal deliveries. Future work will attempt to address innovative solutions to prevent head entrapment by the cervix in this particular population and ultimately avoid cesarean delivery.

ABSTRACT IMPACT: Mobile app may help improve the depression symptoms among underserved patients OBJECTIVES/GOALS: Depression is one of most common mental health conditions and the leading cause of disability worldwide, affecting about one in 10 adults in the US. The aim of this study was to explore the factors that affect feasibility of incorporating mobile app self-management tools for depression in integrated primary care settings. METHODS/STUDY POPULATION: This was a cross-sectional questionnaire study of depressed patients at two primary care clinics in a Midwest academic medical center. Adult patients (≥19 years) who had an active or previous diagnosis of depression were included in the study. A self-administered survey collected information pertaining to demographics, smartphone ownership, data plan type, smartphone application usage, mobile app self-management interest, health literacy, and patient activation. Chi-square analysis was conducted to compare the patient demographic characteristics, the smartphone ownership, phone plan, smartphone use for health information between two clinics. Multinominal logistic regression analysis was conducted to examine the association between the patient activation and patient characteristics. RESULTS/ANTICIPATED RESULTS: Over 80% of patients owned a smartphone, 80.5% were willing to use data for depression management, and 68.9% believe an app can help in depression management. A higher literacy level was significantly associated with higher level of patient activation (Chi-square=8.5453; p=0.0360). These results suggest that planning interventions that use mobile apps within this patient population is likely feasible and the intended underserved patients at these clinics have an interest in using depression related apps which is similar to findings found by other studies exploring app interest. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding patient activation levels within a given population can help to shape corresponding needs. The use of depression related self-management mobile apps will likely require the development of educational materials to facilitate patient use and engagement which means understanding the literacy needs of this population as well.

OBJECTIVES/SPECIFIC AIMS: We sought to solicit and synthesize stakeholders’ ideas for how the Advance-CTR program can best increase the quality and quality of clinical and translational research in Rhode Island, and to apply these findings to address barriers and strengthen research capabilities across our partner institutions. METHODS/STUDY POPULATION: We utilized a Group Concept Mapping approach, involving university and Institution-based researchers and administrators. The process was conducted using the web-based concept mapping application CS Global Max (Concept Systems, Inc). Respondents were asked to provide their best ideas for promoting clinical and translational research in RI. These ideas were then organized by our project team into a set of unique items for consideration by attendees of an Advance-CTR retreat. Participants were tasked with sorting these ideas by theme (cluster), and were also asked to rate each idea according its importance and feasibility. Using the online software, these clusters and ratings were analyzed to identify key themes and to explore differences among sub-groups. RESULTS/ANTICIPATED RESULTS: The Group Concept Mapping exercise yielded 150 statements that were edited down to 78 unique ideas, and clustered into nine themes (e.g., institutional collaboration, training). Fifty-seven retreat participants completed the sorting and rating tasks of the concept mapping exercise. Overall, ideas rated as highly important and highly feasible included “providing seed grants to encourage new collaborations across basic science,” and “connecting researchers with common interests.” Top rated items varied across institutions and according to respondent demographics, allowing us to consider the unique issues relevant to particular groups. Relative rankings of clusters across groups revealed notable differences, such as higher importance placed on community engagement among administrators as compared with researchers, and differences in needs for internal support for research between universities. DISCUSSION/SIGNIFICANCE OF IMPACT: Group Concept Mapping was an effective and insightful participatory approach to engage our program’s stakeholders in developing ideas and identifying challenges to enhancing clinical and translational research in Rhode Island. Our results have implications for project decision-making and initiatives to facilitate translational research in RI. Thus, results have been presented to the Advance-CTR community via webinar, as well as Advance-CTR project leadership and advisory committees.

Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.

OBJECTIVES/SPECIFIC AIMS: Over 80% of CTSA programs have a community advisory board (CAB), an effective strategy to increase community engagement (CE) in research. Little is known about how the research discussed with CABs aligns with community priorities (i.e., bi-directionality). This program evaluation assessed the health topics presented by researchers to the CABs linked to our CE Program at all three Mayo Clinic sites (MN, AZ, and FL) for relevance to local community needs. METHODS/STUDY POPULATION: Two coders classified Mayo researcher presentations to our CABs from 2014-2018 for relevance to needs identified in the local 2013 and/or 2016 County Health Needs Assessments and specific topic(s); with high levels of agreement (Kappa=0.90). RESULTS/ANTICIPATED RESULTS: Overall, of the 65 presentations 41 (63%) addressed one or more local health needs (47% MN, 60% FL, 80% AZ). Cross-cutting health topics addressed at 2 sites were physical activity/obesity/nutrition and mental health. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings were shared with our CABs to obtain input on future directions. The FL and AZ CABs are systematic in seeking out or initiating research projects that address local health needs, an approach the MN site is interested in adopting. Ultimately, it is important to demonstrate improved health outcomes with CTSA-based CE research strategies. Understanding community health needs and depth of researchers in those areas may help to focus priorities for demonstrating such outcomes.

ABSTRACT IMPACT: Human exhaled breath is rich in metabolomic content that represents pulmonary function and gas exchange with blood, which can provide insights into an individual’s state of health. OBJECTIVES/GOALS: Human exhaled breath is rich in metabolomic content that represents pulmonary function and gas exchange with blood. It contains a mixture of compounds that offer insight into an individual’s state of health. Here, we present two novel non-invasive breath sampling devices for use in basic medical practice. METHODS/STUDY POPULATION: The two breath samplers have a disposable mouthpiece, a set of inhale and exhale one-way flap valves to allow condensation of exhaled breath only, and a saliva filter. The housing is constructed out of Teflon®, a chemically inert material to reduce chemical absorbance. The first device condenses exhaled breath into a frozen condensate using dry ice pellets and the other is a miniaturized design that liquifies exhaled breath on a condenser surface with micropatterned features on a cooling plate. Both designs have individual strategic and analytical advantages: frozen exhaled breath condensate (EBC) has high retention of analytes and sample volume; EBC collected in liquid phase offers facilitated sample collection and device portability. RESULTS/ANTICIPATED RESULTS: We investigated if breath aerosol size distribution affects the types or abundances of metabolites. We modified the geometry of the first device to redirect aerosol trajectories based on size. The trapping of larger aerosols increases with filter length, thus altering the aerosol size distribution although no significant changes in the metabolite profiles were found. With the miniaturized device, metabolite abundances were measured in a small cohort of healthy control and mild asthmatic subjects. Differences among subjects were found, as well as main differences between control and asthmatic groups. All analyses of EBC were performed with liquid chromatography - mass spectrometry. Inflammatory suppression found in asthmatic subjects can be explained by prescribed daily use of inhaled corticosteroids. DISCUSSION/SIGNIFICANCE OF FINDINGS: Breath collection devices can be used in intensive care units, outpatient clinics, workplaces, and at home. EBC analysis has been used to monitor asthma and chronic obstructive pulmonary disease. It can be applied to infectious respiratory diseases (e.g. influenza, COVID-19) and for monitoring environmental and occupational chemical exposures.

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.

OBJECTIVES/GOALS: To facilitate the development of innovative injection products by providing translational researchers with a regulatory and manufacturing road map for producing small batch sterile products for Phase 1 research use. To leverage recent AMC investments in facility improvements and pharmacy training in the areas of sterile product production, testing, and environmental controls, that can be used to support production of phase 1 clinical trial supplies METHODS/STUDY POPULATION: Searching and organizing relevant data and information from web portals and databases in the following: areas: FDA, EMA, USP regulations, regulatory science, pharmaceutical formulation and analytics, supply vendors, analytical testing laboratories, and product testing laboratories. Present the information using a user friendly format including flow charts and development timelines, taking the perspective of the translational investigator. RESULTS/ANTICIPATED RESULTS:

• Choosing AMC resources vs outside consultants and vendors, leveraging local resources where possible

• Qualifying and monitoring suppliers, testing laboratories, in-house departments, and Contract Drug Manufacturing Organizations (CDMO)

• Bringing together the deliverables for the IND CMC section

• Where and how to leverage available products and science to simplify safe and reliable production

DISCUSSION/SIGNIFICANCE OF IMPACT: Use and utility of injectable drug products, both small molecule and biologics, is growing rapidly, and is projected to continue to escalate well into the next decade. This is due not only to advances in medicine, but also to improvements in AMC-based sterile product production, and a better understanding of small batch manufacturing methods. All three trends align in academic medical centers (AMC) and can be utilized by translational researchers, if they can understand the potential and regulatory requirements.

OBJECTIVES/GOALS: Empowering the Participant Voice (EPV) is a Rockefeller-led 6-CTSA consortium that aims to collect research participant feedback through new Research Participant Perception Survey (RPPS)/REDCap infrastructure and data aggregation to a national database. Here we describe diverse Use Cases and launch dissemination to other hubs. METHODS/STUDY POPULATION: The EPV team refined the RPPS-S and developed fielding and data standards, a multi-lingual RPPS/REDCap project XML, At-a-Glance Dashboard, EPV Consortium Database, and Use Cases to align with local initiatives and stakeholder input. Sites ran full thread tests of the infrastructure before launch. To demonstrate RPPS/REDCap, 5 sites implemented Use Cases, surveyed diverse populations via email, patient portal or SMS, and analyzed results using the At-a-Glance Dashboard External module (which provides visual analytics and enables filtering by participant/study characteristics). Sites continue to collect, synthesize and respond to actionable data. To disseminate infrastructure, we will invite early adopters to implement the RPPS/REDCap infrastructure locally, joining the EPV learning collective. RESULTS/ANTICIPATED RESULTS: To date, 5 sites surveyed 10,199 research participants, at post-consent or end of study. 2833 (26%) research participants responded, from diverse demographic groups. More than 90% gave the Top Box score response regarding courtesy, respect for cultural background, privacy, and lack of pressure to join a study. Disparities were apparent in the informed consent experience, with a Top Box score range of 38-78% in different demographics. Dissatisfaction with out-of-pocket research costs was a recurring theme. Top Box scores varied for feeling like a valued partner in research (69-93%), would recommend research participation to friends or family (56%-81%), and Overall Experience (64%-90%) questions. Sites identified actionable findings in areas of consent, communication, partnership, and study conduct. DISCUSSION/SIGNIFICANCE: The EPV RPPS/REDCap infrastructure enabled sites to broadly collect participant feedback, identify actionable findings and make inter-institutional comparisons. Collaborators are designing local initiatives to increase response rate and diversity, address disparities in research participation experiences, and discover better practices.

OBJECTIVES/SPECIFIC AIMS: Stakeholder engagement has been proposed to help realign clinical and translational research with the needs of clinicians, patients, and policymakers. Increasingly, funders and researchers seek to partner with stakeholders to inform study design, execution and dissemination of results. Kids and families Impacting Disease through Science (KIDS) is a program of the American Academy of Pediatrics that seeks to engage youth in clinical research. United States KIDS programs participate in International Children’s Advisory Network activities. The Chicago KIDS Advisory Board program at Walter Payton College Preparatory School, a Chicago Public School, was initiated in 2015 to foster and develop interest in careers in science, research and healthcare and provide youth perspectives to academic and industry researchers on the design and development of pediatric research studies. This project engaged youth advisors in creation and evaluation of a video explaining clinical research and informed consent for Ann & Robert H. Lurie Children’s Hospital, a clinical partner of the Northwestern University Clinical and Translational Sciences Institute. METHODS/STUDY POPULATION: The Payton program advisory board sessions are 1.5hr interactive seminars held on 1–2 school days each month. During the 2016–2017 school year, students participated in 3 stakeholder sessions, led by Lurie Children’s hospital researchers, to advise development of a script, storyboards, and ultimately an animated video that informs children and families about participation in clinical research to aid in the decision-making process. Qualitative research methods were used to examine attitudes towards clinical research and assess the video on content objectives, clarity of concept, and appropriateness for a pediatric audience. Following production, students from the 2017–2018 advisory board viewed the final video and presurvey and postsurvey were administered to assess the effect of video on the comprehension of 8 key concepts of informed consent on a 5-point Likert scale. The Wilcoxon signed-rank test was used to compare median pretest and post-test ranks. Results of this analysis were reviewed in seminar and students provided written contribution to this abstract. RESULTS/ANTICIPATED RESULTS: In total, 11 Walter Payton high school students participated in video development and 27, who were naïve to development, participated in the pre and post evaluation sessions. Students ranged from Freshman to Seniors and reflected the diverse ethnic and racial background of Chicago. A positive change from pre to post-test survey was observed in all questions presented assessing comprehension of key concepts of informed consent. The median post-test ranks were statistically significantly higher than the median pre-test ranks for all questions (p<0.01 in all). DISCUSSION/SIGNIFICANCE OF IMPACT: Chicago KIDS youth advisors were engaged in all aspects of the design of the research tool and gained experience in stakeholder contribution from study design to evaluation and publication. The students will next be involved in the design of a prospective randomized study to test the efficacy of the video compared with standard recruitment and consent practices. Given the difficulty of recruiting youth for clinical trials, development of effective engagement practices in is critically important. Our findings demonstrate the feasibility of utilizing youth advisors in a public school based setting.