Objectives/Goals: This research aims to harness electronic health records (EHR) combined with machine learning (ML) to predict necrotizing enterocolitis (NEC) in preterm infants using data up to their first 14 days of life. We aim to provide interpretable results for clinical decisions that can reduce infant mortality rates and complications from NEC. Methods/Study Population: Through a retrospective cohort study using data from the University of Florida Integrated Data Repository and One Florida, we will develop machine learning models suitable for sequential data to predict NEC. Our inclusion criteria include very low birth weight (VLBW; <1500g) infants born <32 weeks gestation and EHR data availability from the first 14 days of life. We will include infants with NEC and infants without NEC to train our ML model. Exclusion criteria include infants diagnosed with spontaneous intestinal perforation and severe congenital anomalies/defects requiring surgery. Results/Anticipated Results: We anticipate that our model will provide an accurate and dynamic prediction for the risk of NEC in neonates using data up to the first 14 days of life. Our model will be interpretable to identify key risk factors and can integrate real-world clinical insights to increase early detection and improve patient outcomes. Discussion/Significance of Impact: The development of a model to predict NEC could be used in neonatal intensive care guidelines and protocols and could ultimately decrease mortality, reduce complications, improve the overall quality of care, and lower healthcare costs associated with NEC.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to assess differences in outcomes between African Americans (AAs) and whites along the HCV care cascade. Primary outcome was retention in the HCV care cascade, measured in two ways. For viral RNA confirmation, retention was a percentage of those having screened antibody reactive. For hepatic ultrasound, primary care, HCV specialty clinic, treatment initiation, and sustained viral load (SVR), retention was a percentage of those found chronically infected by positive RNA viral load. Secondary outcome was time to follow-up from antibody screening to each subsequent step in the care cascade. METHODS/STUDY POPULATION: A retrospective cohort study was performed. AA and white patients who tested HCV antibody reactive from March to October 2015 at the University Medical Center (UMC) Emergency Department in New Orleans, LA were included in this study. Outcomes were assessed using the HCV Continuum of Care model, delineating successive stages of care from identification to cure. RESULTS/ANTICIPATED RESULTS: A total of 728 patients screened HCV antibody reactive, including 446 AAs and 282 whites. AAs (53.5 years, SD 10.2) were disproportionately older than whites (46.7 years, SD 11.9) (p <0.001), more likely to be insured (89.2% vs 78.7%, p<0.001), had higher rates of Medicare (28.0% vs 12.1%, p<0.001), and less frequent history of intravenous drug use (IVDU) (32.3% vs 46.1%, p<0.001). For AAs, retention in the treatment cascade was 96.2% for viral RNA confirmation, 50.9% for hepatic ultrasound, 26.8% for primary care, 35.2% for HCV specialty clinic, 14.5% for treatment initiation, and 9.6% for sustained viral response (SVR). Among whites, retention in the treatment cascade was 96.8% for viral RNA confirmation, 37.8% for hepatic ultrasound, 16.1% for primary care, 23.3% for HCV specialty clinic, 8.8% for treatment initiation, and 7.8% for SVR. AAs had a higher likelihood of receiving a hepatic ultrasound (OR=1.70; CI=1.19-2.25; p<0.005), following up with primary care (OR = 1.91, CI=1.21-3.02, p<0.005), and attending the viral hepatitis specialty clinic (OR=1.79, CI=1.20-2.68, p<0.005), as compared to their white counterparts. After adjusting for age, insurance, and history of IVDU, AAs did not have a higher likelihood of receiving a hepatic ultrasound (aOR=1.09, CI=0.995-1.19) or seeking primary care (aOR=1.05, CI=0.98-1.14). AAs had attenuated odds of attending viral hepatitis specialty clinic (aOR=1.09, CI = 1.01-1.19). There was no statistically significant difference in follow-up time in the treatment cascade for AAs versus whites. DISCUSSION/SIGNIFICANCE OF IMPACT: Race alone cannot explain differences in achievement along the care cascade. Significant differences in retention along the HCV care cascade appear to be related primarily to differences in age and insurance status. In our population, older AAs are disproportionately insured through Medicare, thereby expanding their access to health resources. Their white counterparts are younger and more uninsured, leading to decreased access to care and ability to attend HCV follow-up appointments. ED HCV screening programs are still in their infancy and have opportunities to improve their linkage to care rates. Additional interventions are needed to better connect patients screened positive in the ED to HCV specialist care, preserving equity across racial groups.

OBJECTIVES/GOALS: Burst suppression is a neurophysiological marker associated with severe hypoxic-ischemic injury following cardiac arrest. The goal of this study is to identify the anatomical regions of the brain associated with burst suppression post-cardiac arrest. METHODS/STUDY POPULATION: 86 comatose patients post-cardiac arrest admitted to the neurological-ICU from Massachusetts General Hospital and Brigham and Women’s Hospital were included in this study. EEG data after return of spontaneous circulation were preprocessed and artifact was rejected. Burst segments were extracted for source localization analysis from epochs with burst suppression. Four bursts for each patients were manually selected. The source of the bursts were obtained using the Champagne algorithm and mapped on the Desikan-Killiany atlas. The source for each burst was defined as any region of interest (ROI) with power > = 75th percentile relative to all ROIs. The power of the bursts at each source was correlated with the burden of brain injury measured using apparent diffusion coefficient (ADC) per ROI. RESULTS/ANTICIPATED RESULTS: 48 (56%) patients had burst suppression. 5 (10.4%) of patients with burst suppression were independent at the time of hospital discharge. Preliminary analyses was performed on 6 patients (24 bursts in total). ROI’s determined to be sources in a majority of the burst (>=13) were bilateral superior frontal, rostral middle frontal, parstriangularis precentral, superior parietal, inferior parietal, right post central, superior temporal, lateral occipital, and left middle temporal ROI. A lower mean ADC intensity was associated with a higher EEG power in the bilateral superior frontal (r = -0.80, p < 0.0001; r = -0.677, p < 0.001, respectively), left superior parietal (r = -0.53, p = 0.009), left middle temporal (r = -0.43, p = 0.042) ROI. DISCUSSION/SIGNIFICANCE: The source of bursts in patients post-cardiac arrest experiencing burst suppression is not well defined. This study will improve our understanding of how burst suppression is a measure of cortical injury, how it may relate to the burden of injury found on ADC imaging, and patient outcomes.

OBJECTIVES/GOALS: This team science pilot program aims to elevate the quality of Parkinson’s disease modeling initiatives by strengthening connections between clinical researchers and computational teams. As many data science projects in Parkinson’s research would benefit from deeper clinical expertise, many clinical engagements would be improved by upfront integration of computational requirements. These team science programs, developed from design thinking methodologies, provide structured, sustainable, and scalable means for multi-disciplinary teams to come together and co-create translational science in PD. METHODS/STUDY POPULATION: Design Thinking (DT) could help yield an effective learning experience. DT is grounded in ethnographic research strategies and prototyping, relying heavily on grantee interviews and feedback. This approach is commonly used to navigate and design amidst complexity; its applications range from product to healthcare to instructional design. The following is an overview of the process as applied to this project: Discover: Once the core team (MJFF and project designers) has refined the key question they would like to answer, the team will begin gathering both primary and secondary data. This phase may include focus groups, one-on-one interviews, expert interviews, and immersive data-gathering. The purpose of this phase is to capture complexity and lay the groundwork to understand grantees’ perspectives and lexicon around their work. The deliverables of this phase are primarily unstructured research findings, such as transcribed interviews and secondary sources. Define: When sufficient data has been gathered, the core team will move into an initial round of synthesis and sense-making (making connections and assumptions to explain emerging themes in the data). This phase may include one to two in-person engagements with the core team. The purpose of this phase is to define the guiding principles for subsequent prototypes. It will also help reveal potential opportunity areas, both latent or apparent. The deliverables of this phase are agreed upon key themes, insights, and an informed “How Might We” question that will anchor the ideation process. Develop: Armed with informed themes, the core team will begin to brainstorm potential solutions. Following a set of brainstorming techniques, they will initially aim for quantity versus quality in order to allow potentially innovative and/or risky solutions to surface. Eventually, these ideas will be distilled into three robust and unique prototypes. Like the prior phase, ideation may also require one to two in-person engagements. The deliverables here are three unique prototypes; the reason for three is the ensure that the team does not anchor themselves in just one solution, but rather remains in an exploratory mindset as they solicit feedback on these prototypes from the grantees. Deliver: In this final phase, the core team revisits the grantees and presents the three prototypes. This phase may include conducting three small-scale pilots or simply just explaining the prototypes. Either way, it is important to solicit another round of feedback to ensure the solutions are indeed addressing the needs and context of grantees. Once completed, the core team will iterate a final pilot design and identify any remaining questions and assumptions they would like the pilot to inform. RESULTS/ANTICIPATED RESULTS: The team science pilot identifies five main opportunities to tighten collaboration, communication, and expectations across clinical and computational teams. Firstly, in-person events, held regularly in a central location, can act as an incubating space for these teams to partner, ideate, and pitch for grant funding. Secondly, co-developed guidelines for research questions would ensure consistent availability of clinically-relevant, computationally-feasible research topics. Thirdly, increasing the presence of Parkinson’s cohort data resources at computational conferences could introduce more diverse data and genetics interest in Parkinson’s research. Fourthly, a standard suite of research-facing, educational content (focused on both disease background and data basics) would ensure a strong baseline and launch-pad for PD modeling projects. Lastly, a fellowship program focused on early-stage researchers could establish a unique foundation to ground both clinical and computations fellows to collaboratively work on PD research as well as iterate on the aforementioned solutions. DISCUSSION/SIGNIFICANCE OF IMPACT: This team science program has the potential to upend collaborative silos in Parkinson’s research, accelerating disease modeling projects which otherwise stagnate or over-emphasize clinical v. computational aspects. By more effectively connecting team members with diverse backgrounds across clinical and computational roles, PD disease patterns can be discovered and validated ultimately resulting in improved patient care and therapeutic development. CONFLICT OF INTEREST DESCRIPTION: Several authors are staff members at The Michael J. Fox Foundation for Parkinson’s Research, the sponsor of this Team Science grant. All author and non-author contributors are grant recipients from The Michael J. Fox Foundation.

ABSTRACT IMPACT: Effective robotic pedaling therapy would allow stroke survivors a precision, customized, and adaptable therapy to help recover lower extremity function. OBJECTIVES/GOALS: It has been observed that people post-stroke can pedal each limb individually but not simultaneously when the bicycle is split-crank. This implies that lower extremity movement difficulties are affected more by interlimb rather than unilateral coordination deficits. This work seeks to further develop a robotic split-crank pedaling therapy device. METHODS/STUDY POPULATION: This work uses a robotic split-crank pedaling device to facilitate rehabilitation of interlimb coordination, measured by continuous relative phase (CRP) and paretic neuromuscular output. The effects of three control schemes were tested: assist, resist, and assist+resist. Each limb was strapped to a pedal which was connected to a motor. The participants were asked to pedal forward while keeping the pedals antiphase. The robot aided or resisted according to the activated control scheme. Control schemes were tested on two stroke participants. The control schemes respond proportionally to phasing deviation from 180 degrees. The assist scheme assisted the lagging limb while the resist scheme resisted the leading limb. The assist+resist did both control actions. RESULTS/ANTICIPATED RESULTS: For the assist scheme, CRP improved for participant 1 (P1) and declined for participant 2 (P2). P1 increased paretic velocity while P2 decreased. Rectus Femoris (RF) and Biceps Femoris (BF) activity of both limbs lowered for P1. RF and BF activity of both limbs remained about the same but shifted for P2. For the resist scheme, CRP improved for P1 and declined for P2. P1 increased paretic velocity while P2 decreased. P1 increased BF activity of both limbs while RF activity remained constant. P2 increased paretic BF activity and non-paretic RF activity. For the assist+resist scheme, CRP improved for both participants. Both participants increased paretic velocity. P1 increased paretic BF activity and decreased RF activity. P2 better modulated paretic BF and RF. DISCUSSION/SIGNIFICANCE OF FINDINGS: All control schemes augmented performance, however the assist+resist scheme showed the most promise in terms of CRP and muscle activity. More participants are needed to determine true effects of each control scheme. The control scheme selected will be the foundation for further improvements such as adaptive control and extrinsic feedback.

As part of their mission, Clinical and Translational Science Award (CTSA) hubs are charged with developing, testing, and disseminating evidence-based practices to other CTSA hubs. Over the past 7 years, the University of Wisconsin-Madison has answered this charge by implementing the facilitator training (FT) initiative for research mentors. Three elements to advance training across the CTSA hubs have been critical: (1) using an FT model to empower others to build research mentor training at their local institutions; (2) tracking implementation of training events across the CTSA hubs over time; and (3) partnering with implementation sites to build local capacity and evaluate the effectiveness and quality of training. Here we report that facilitators have been trained at 75% of CTSA hubs. These facilitators report high satisfaction with the training and increased confidence in their ability to implement mentor training, and plan to implement local mentor training. These findings demonstrate that the FT initiative can serve as a model for dissemination and implementation of other workforce development interventions across the CTSA hubs.

OBJECTIVES/GOALS: Lack of diversity within clinical trials is well known, but there is little data on the use of investigational products through other pathways, such as expanded access. This project sought to determine the demographic diversity of patients benefiting from expanded access at Michigan Medicine. METHODS/STUDY POPULATION: Previous quality improvement reviews provided the list of 271 patients for whom a single-patient, expanded access request had been approved by the FDA and University of Michigan IRBMED between 2005 and 2021. Demographic information was collected through the EMERSE tool, including age, legal sex, race, ethnicity, and zip code. These data were cross-referenced with available regulatory documentation on product requested, treatment area, and date of request. Descriptive statistics were performed using Excel. RESULTS/ANTICIPATED RESULTS: Patients who were approved to use an investigational product through expanded access at Michigan Medicine showed a wide geographic distribution, including 48 Michigan counties, 20 states, and 1 province. All age groups were served, with those between 30-49 underrepresented and those under 10 and over 60 overrepresented. Race data generally followed the proportions of the Michigan state census, including 76% white and 14% black or African American (expected: 79% and 14%) and 48% female (expected: 50%). On further breakdown, populations differed by specialty and county. DISCUSSION/SIGNIFICANCE: The distribution of Michigan Medicine patients with approved expanded access requests was similar to the population of Michigan with respect to age, sex, and race. Further research is needed to determine if this reflects equitable use or if these results are generalizable to other institutions.

OBJECTIVES/SPECIFIC AIMS: We intended to investigate the relationship between children’s genetic admixture proportions and the incidence of obesity at 12 months of age METHODS/STUDY POPULATION: 821 twelve month old children were included and their genetic admixture was estimated using the ancestry and kinship toolkit (AKT). Weight for Length Percentile (WFLP) at 12 months of age was categorized as <95th percentile and ≥95th percentile. Multiple logistic regression analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for association of admixture proportion including EUR, AMR, AFR, EAS and SAS with WFLP categories adjusting for maternal education, birth weight, frequency of breast feeding and juice consumption RESULTS/ANTICIPATED RESULTS: 821 children were included; WFLP <95th percentile = 671 (81.7%) and WFLP ≥95th percentile = 150 (18.3%). Crude odds ratios showed EUR admixture was protective (OR 0.45 (95% CI 0.27–0.74)) whereas AMR (OR 3.85 (95% CI 1.92 –7.70)) and AFR (OR 5.70 (95% CI 2.19 –14.85)) were positively associated with obesity. After adjusting for confounding variables, only AFR was associated with WFLP≥95th (OR 7.38 (95% CI 2.31 – 23.59)), AMR and EUR were no longer associated with WFLP≥95th DISCUSSION/SIGNIFICANCE OF IMPACT: The AFR admixture proportion remains associated with early childhood obesity after accounting for confounding variables, suggesting the ancestral genetic background may contribute to the differences seen in early childhood obesity

Objectives/Goals: Healthcare organizations must track electronic health record (EHR) activity at the user level, including logons, accessed records, and viewed or entered documentation. There is little standardization in EHR audit logs and nurse workload has not been explored using these data. In this project, we characterized nurse actions from EHR audit logs. Methods/Study Population: We performed an analysis of EHR audit log data collected from 8,149 nurses over 5 years at University of Utah Health. We preprocessed nursing-centric EHR audit logs from the Epic EHR by cleaning and preparing the data for analysis. We calculated basic statistics for the variables labeled user_id (nurse) and metric_id (action). We reviewed the actions used by nurses and categories the actions as navigation, view, and entry. To capture the clinical context of the actions, two nurses categorized each action. A third nurse resolved any discrepancies. Results/Anticipated Results: We found that of the 4,419 available metrics, nurses used 1,461 unique metrics during the timeframe. The actions most used by nurses were 1) report with patient data viewed, 2) inpatient system list, and 3) storyboard viewed. Most of the metrics were categorized as navigation. The number of nurses interacting with the EHR increased each year and on average, we found that 1000 unique metrics were used by each nurse user in a 24-hour period. The expected outcome is a set of actions that can be mapped to higher level nursing interventions and in the future contribute to models for nursing workload measurement. Discussion/Significance of Impact: We found great value in using EHR audit logs to provide insights into nursing actions. Information gleaned can benefit organizations that are crafting interventions to decrease workload. Ultimately, the goal is to ensure that nurses have an appropriate workload allowing for safe and high-quality patient care while maintaining their well-being.

OBJECTIVES/SPECIFIC AIMS: The aim of the present study is to explore the relationships between resilience, pain catastrophizing, and functional outcomes in pre-and post-operative TKR patients. The primary outcome is the ability of the Brief Resilience Scale (BRS) to predict function using the Knee injury and Osteoarthritis Outcome Score Joint Replacement (KOOS, JR.) and overall health on the Patient-Reported Outcome Measurement Information System Global Health (PROMIS GH). METHODS/STUDY POPULATION: Recruited patients will provide informed consent during in-person office visits. At the pre-surgery intake appointment, patients will provide demographic information and complete baseline questionnaires assessing resilience, pain catastrophizing, knee stiffness, pain, and function, and impression of overall health. In-person or electronic follow-up assessments will be administered post-surgery at 6-week, 3-month, and 6-month appointments. RESULTS/ANTICIPATED RESULTS: We aim to recruit 150 patients for this study. We do not expect a difference in sociodemographic characteristics of the patient sample. P-values will be based on t-tests and correlations calculated by comparing only non-missing values. Each outcome measure will be examined at each time point and trajectories will be calculated to determine the change in each outcome over time. Using latent class growth modeling we will examine individual change over time for each outcome (BRS, PCS, PROMIS GH, and KOOS JR.), and the association of resilience and pain with change in function (KOOS, JR. total score) and overall health (PROMIS GH). DISCUSSION/SIGNIFICANCE OF IMPACT: To our knowledge, this is the only known study that will compare resilience, pain catastrophizing and longitudinal health outcomes in a single paradigm. Results will hopefully inform the design and implementation of future studies that will assess the impact of preoperative treatment of vulnerable patients. The ultimate goal is to improve functional recovery by using pre-identified psychological constructs as intervention points. Ideally, the same measures would be implemented, however, details of this plan will be established following completion of this study.

OBJECTIVES/GOALS: Suicide is the second leading cause of death in teens. Substance misuse, including opioids, is a risk factor for suicidal thoughts and behaviors among teens. School-based approaches are promising, yet they lack evidence on their effectiveness. To fill this gap, we created supportED, a digital game to prevent suicide in youth who misuse substances. METHODS/STUDY POPULATION: We conducted focus groups and interviews to inform the development of the digital game and discuss approaches to enhance user experiences, acceptability, and feasibility of the intervention. A semi-structured focus group/interview guide was developed, pilot tested, and used in focus groups/interviews. The guides aligned with constructs from a safety planning intervention, a well-recognized, evidence-based suicide prevention intervention, to identify potential warning signs of emotional distress, coping strategies, and resources for seeking help to prevent suicidal thoughts and behaviors. Focus groups/interviews were led by a facilitator, who is also a certified school counselor and licensed professional counselor, and a co-facilitator who took field notes and provided debrief summaries. RESULTS/ANTICIPATED RESULTS: A total of 35 participants, including 10 high-school-aged teens [aged 16-19], 10 college-aged youth [aged 18-22], 10 school-based providers, and five interviews with adults who had experience with opioids in their youth informed the development stage. Of the focus group participants, 25.7% identify as female (n=23), 71.4% identify as male (n=6), and 2.9% do not identify as male or female (n=1); 60% identify as White (n=18), 20% identify as multi-racial (n=6), 10% identify as Black (n=3), 3.3% identify as Asian (n=1), and 6.7% identify as race unknown (n=2); and, 37.1% (n=13) identify as Hispanic/Latinx. Salient themes that emerged focused on opioids, substance misuse, mental health, bullying, grief, family, identity, and stigma to create six distinct narratives in the digital game. DISCUSSION/SIGNIFICANCE: Findings informed the development of a digital game to prevent suicide among adolescents who misuse substances. The digital game is currently being evaluated in a pilot RCT to assess the preliminary efficacy of the intervention, user experience, usability, and feasibility of delivering the intervention and protocols among 60 youth.

OBJECTIVES/GOALS: The goal of this study is twofold: To develop a method for an ex vivo hypofibrinolytic control and second to analyze patterns in standard and recently developed clinical coagulation assays for the detection of hypofibrinolytic states. METHODS/STUDY POPULATION: We analyzed blood samples from healthy patients first under normal conditions and then laced with human recombinant PAI-1 under three different concentrations. We then analyzed both samples using standard clinical assays (PT, aPTT, D-dimer, Fibrinogen), thromboelastography point-of-care tests (Hemosoncs- Quantra system), and with research assays of clot size and aggregation. Our previous research of diagnostic errors showed the patient group with the highest overall risk of these non-identifiable thrombotic complications was post-menopausal women with chronic diseases. We therefore focused our patient population to healthy post-menopausal women who were not using hormone replacement therapy. RESULTS/ANTICIPATED RESULTS: Research assays showed PAI-1 significantly increased clot size and aggregation. Preliminary results of clinical assays showed no detectable difference in hypofibrinolytic samples at any concentration. We anticipate ongoing testing will show similar results. Results on Quantra tests showed much larger differences between control and hypofibrinolysis samples, and we anticipate ongoing testing will achieving statistical significance. It is still unknown whether the mean value for hypofibrinolysis samples on the Quantra Clot Stability assay will be outside of the “normal” reference range. We theorize that this may be due to hypofibrinolytic changes in the overall structure and core density of the clots. DISCUSSION/SIGNIFICANCE: Cellular stress stimulates a concomitant activation of inflammation and coagulation, including decreased fibrinolysis. Unfortunately, current clinical assays do not assess clot breakdown. This connection would account for the increased rate of thrombosis in patients with chronic inflammation without detectable results on clinical tests.

OBJECTIVES/SPECIFIC AIMS: Our objective is to examine the relationship between depression, childhood asthma and family structure. METHODS/STUDY POPULATION: We analyzed data from The National Survey of Children’s Health 2011-2012 for the variables family structure, parent’s smoking, education, poverty, available emotional support, and children’s age, gender, race/ethnicity, asthma, physical/mental health, access to care, and insurance. Data were analyzed using multiple logistic regression in STATA 14 (sampling and weight). RESULTS/ANTICIPATED RESULTS: Of the 95,000 participants, 3.8% had depression, 5.1% had anxiety, 8.5% had emotional, developmental, or behavioral problem, 14.6% had asthma and 19% were single-parent family. Asthmatics had higher chance for depression relative to non-asthmatics (Adjusted Odds Ratio (AOR)=1.5, 95% confidence interval (CI)=1.2-1.8), p=0.001). Those living in a single-family home had higher chance for depression than those living in 2-parents homes (AOR=2.5, 95% CI=1.9-3.2), p=0.001). Other predictors were lack of emotional support, age, poverty <100%, poor health, and smoking parent (p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: We concluded that depression was associated with asthma in children from poor single family who lack an emotional support. Management of asthma should include screening and management of psychosocial factors.

ABSTRACT IMPACT: This study is providing a telehealth intervention for the first time in patients with sickle cell disease with the goal of improving cognitive functioning and preparing adolescents for successful transition of care to adult healthcare providers. OBJECTIVES/GOALS: There is a high prevalence of cognitive impairment in adolescents with sickle cell disease (SCD). The purpose of this study is to test the efficacy of an individualized cognitive remediation program designed to promote not just cognitive function, but also adaptive and self-management skills necessary for successful transition to independence. METHODS/STUDY POPULATION: 12 participants with SCD (5 males, ages 10-16) participated in an individualized program, Cognitive-Remediation of Executive and Adaptive Deficits in Youth [C-READY], consisting of three main components: individual goal-based therapy, parent training sessions, and home skill practice. C-READY sessions occur one-on-one with a trained therapist for 8 sessions conducted over 4 weeks. Weekly parent training sessions are also conducted as part of the C-READY program. All of these sessions occurred via telehealth video-calling between the therapist and the adolescent/parent. Participants were evaluated before and after the C-READY program using neuropsychological assessment measures and transition readiness questionnaires. Parents also completed ratings on telehealth delivery, content, and timing. RESULTS/ANTICIPATED RESULTS: Repeated measures ANOVA indicated significant improvement in transition readiness behaviors as rated by parents, including improved independence in medication management (p = 0.029) and in talking with their healthcare providers (p = 0.019). Significant improvement was also demonstrated on a neuropsychological measure related to executive function skills, specifically inhibition and switching (p = 0.012). Results from telehealth surveys (rated on a 5-point Likert scale) indicated overall satisfaction with services (4.2/5), including visual (4/5) and voice quality (4.3/5) of telehealth equipment. Ratings also indicated feeling that their privacy was respected (4/5) and that their interactions with their therapist were appropriate and sensitive (4.5/5). DISCUSSION/SIGNIFICANCE OF FINDINGS: These results provide support for interventions that focus on cognitive skills to improve behaviors necessary for successful transition of care in youth with SCD. Results are also promising for delivery via telehealth in order to address barriers related to access to care. Future results will continue to be reported, as this study is currently ongoing.

Objectives/Goals: Despite the documented link between ultraviolet (UV) exposure and skin cancer, the potential protective role of pigmentation in preventing skin carcinogenesis is not fully understood. This project will test the hypothesis that individuals with light skin tones are more susceptible to skin cancer due to a higher accumulation of somatic mutations from UV exposure. Methods/Study Population: Skin biopsies were collected from various anatomical sites of seven donors aged 70 to 80 years with dark skin tones and used to generate clones of normal skin cells. The clones were then subjected to whole-exome and RNA sequencing. We developed a workflow that allows us to accurately detect somatic mutations in clonal expansions of individual cells with high specificity and sensitivity. For comparison, we also analyzed mutations in skin cells obtained from individuals with light skin tones, who served as our control group. In the future, we plan to employ admixture analysis to clarify the impact of race on somatic mutations by examining ancestral genetic contributions. Results/Anticipated Results: Our preliminary analysis of the existing data supports our hypothesis. The average mutation burden in individuals with light skin tone was found to be 3.778 Mut/Mb, whereas in those with dark skin tones, was only 0.818 Mut/Mb. These findings align with the prevailing hypothesis that melanin acts as a protective factor against skin cancer, as it appears to reduce the mutagenic effects of UV radiation. This suggests that individuals with darker skin may have a lower cumulative mutational load, potentially contributing to their reduced risk of developing skin cancers such as melanoma. Similarly, our results showed variations in mutational burdens across different anatomical sites, which seemed to be influenced by differing levels of UV exposure, with the highest burdens observed in areas with the greatest exposure. Discussion/Significance of Impact: Understanding how skin cancer operates in darker-skinned individuals is imperative for tailoring effective screening and targeted therapies to meet their specific needs. In the long run, elucidating the mechanisms underlying skin cancer development in this demographic will help refine screening protocols and prevention recommendations.