OBJECTIVES/GOALS: The CDC estimates that Influenza infections account for an average of 420,000 hospitalizations and 34,700 deaths in the U.S. each year. This project explores the underlying mechanisms of the infectious process of Influenza A in human lung organoids by examining the differential transcriptomic expression compared to uninfected controls. METHODS/STUDY POPULATION: Lung organoids were cultured from differentiated human bronchial epithelial cells from lung transplant donors on an air-liquid interface until they were confirmed to contain both mucous producing and ciliated cells. Lung organoids are ideal models in translational science due to their structural and functional characteristics which closely mimic those of in vivo human epithelial tissue. Half the organoids were exposed to Influenza A pH1N1 for 72h; the other half served as uninfected controls. RNA was isolated from both groups and sequenced using the Oxford Nanopore MinION which generates full length reads. Reads were aligned to the human reference genome (GRCh38.p14) using Minimap2. RESULTS/ANTICIPATED RESULTS: The MinION sequenced an average of 3.24m reads per sample and a total of 13,128 genes were relevantly expressed (defined as greater than 1 read per million in at least half the samples). ANOVA with a 5% false discovery rate (Benjamini and Hochberg correction) revealed 5,417 differentially expressed genes between infected and control groups. Within this subset, we identified downregulation of mucociliary clearance, mitochondrial and ß-oxidation, peroxisome, and glutathione replenishment genes. We further identified upregulation in inflammatory markers, lactate dehydrogenase enzymes, and several s100 proteins. The downregulation of mitochondrial and β-oxidation markers and the upregulation of lactate dehydrogenase enzymes revealed a Warburg-like phenotype which has not previously been reported. DISCUSSION/SIGNIFICANCE: This study reveals a novel Warburg-like phenotype in Influenza A infection alongside downregulated mucociliary clearance and upregulated inflammatory processes. These findings improve our understanding of Influenza A infection and point to potential therapeutic targets to advance precision medicine approaches to treatment.

OBJECTIVES/GOALS: Face transplant can offer functional and aesthetic restoration to patients who have exhausted reconstructive options. Ethical issues in face transplant still abound, including that of patient selection. The goal of this study was to assess ethicists’ viewpoints on face transplant. METHODS/STUDY POPULATION: A large-scale online survey of attendees of the International Conference on Clinical Ethics Consultation (N = 401) was performed to assess ethicists’ opinions on issues in face transplant. Questions were asked regarding the risk-benefit ratio of immunosuppression, permissibility of face transplant for more recipient subpopulations (including children and blind patients), donor-recipient age, gender, and ethnicity mismatches, and ethics committee make-up. RESULTS/ANTICIPATED RESULTS: Among 84 respondents, 84% agreed it is permissible to perform a face transplant on an adult with no medical contraindications. The majority of respondents agreed that it is permissible to perform a face transplant on a child or blind recipient. An issue of continued concern was risk of immunosuppression. Respondents had a high threshold of permissibility for ethnic mismatches between donor and recipient, and 43% reported it is permissible to have a gender mismatch. A 10 year age difference between donor and recipient was the most commonly accepted. Questions regarding the ideal composition of a face transplant ethics committee demonstrated consensus on the roles that should be represented. DISCUSSION/SIGNIFICANCE OF IMPACT: This study provides insight into ethicists’ viewpoints on face transplant, which demonstrates a high level of permissibility towards the procedure. This may be due to the early success of face transplants and the shifting ethical issues in the field to practical aspects of the procedure. This research also provides guidance to programs regarding questions of donor and recipient selection, ethics committee composition, and offers insight into strengthening the ethical framework of the field.

ABSTRACT IMPACT: This research shows that physical intimate partner violence was associated with never testing for HIV while verbal intimate partner violence was associated with increased testing for HIV suggesting that HIV testing interventions should consider intimate partner violence prevention. OBJECTIVES/GOALS: HIV incidence is higher among women who experience intimate partner violence (IPV). However, few studies have assessed the association between HIV testing (regardless of the result) and the experience of IPV. Our objective was to assess the relationship between IPV and HIV testing among women from rural southwestern Uganda. METHODS/STUDY POPULATION: We conducted a whole-population, cross-sectional study including women ?18 years of age who were permanent residents in 8 villages of Rwampara District, southwestern Uganda from 2011-2012 who reported having a primary partner in the past 12 months. We surveyed participants to assess their exposure to 12 different forms of verbal, physical, and/or sexual IPV, and whether they had ever been tested for HIV. We used three separate modified Poisson regression models, clustering by village, to estimate the association between each type of IPV and ever testing for HIV, adjusting for categorical age, completion of more than primary education, and any food insecurity measured by the nine-item Household Food Insecurity Access Scale. RESULTS/ANTICIPATED RESULTS: Among 496 women with a primary partner (>95% response rate), 64 (13%) had never tested for HIV, 297 (60%) reported verbal IPV, 81 (16%) reported physical IPV, and 131 (26%) reported sexual IPV. Further, among these women, 208 (42%) were aged <30 years, 378 (76%) had a primary or no education, and 390 (79%) experienced food insecurity. Never having been tested for HIV was positively associated with physical IPV (adjusted risk ratio (ARR): 1.61, 95% confidence interval (CI): 1.02-2.56) and negatively associated with verbal IPV (ARR: 0.67, 95% CI: 0.44-0.99), but not sexual IPV (ARR: 1.05, 95% CI: 0.51-2.12). DISCUSSION/SIGNIFICANCE OF FINDINGS: Among this population of adult women with partners in Uganda, physical IPV was associated with never testing for HIV while verbal IPV was associated with increased testing for HIV. Evidence suggests that HIV testing interventions should consider IPV prevention, and future studies should focus on why certain IPV types impact HIV testing rates.

OBJECTIVES/GOALS: Patients with multiple myeloma (MM) experience significant disease- and treatment-related symptom burden, especially with higher lines of therapy (LOT). We used a remote symptom monitoring app to characterize overall symptom profile, symptom bother, and quality of life (QOL) among patients with MM across LOT and longitudinally. METHODS/STUDY POPULATION: We used Carevive PROmpt, a symptom monitoring app for cancer patients. From 11/10/22 to 9/27/23, we enrolled 84 adult patients with MM of any stage and anywhere in the treatment continuum from Duke Health MM clinics. Participants received weekly symptom surveys while on active treatment. Per prior studies, we defined heavily pretreated patients as those on current LOT ≥4. Our sample had a mean (SD) age of 63.7 (10.8) years and was 56.0% male; 73.8% had a prior bone marrow transplant, 40.5% were on LOT ≥4 (53.6% on LOT <4, 6.0% missing), 58.3% were on triplet therapy or higher. For 14 symptoms, we described the prevalence of moderate to very severe (MOD-VS) symptoms based on LOT overall and over time. We also described responses to “How bothersome are treatment side effects?” and “Overall QOL over the past week” based on LOT. RESULTS/ANTICIPATED RESULTS: Surveys continued for a mean (SD) of 14.9 (9.6) weeks (range: 44). The top 5 MOD-VS symptoms ever experienced were fatigue (66.7% of patients), neuropathy (48.8%), muscle pain (44.0%), insomnia (39.3%), and general pain (38.1%). Patients on LOT ≥4 had most of these symptoms more often than LOT <4 (fatigue: 70.6% of patients vs. 60.0%, neuropathy: 71.8% vs. 40.0%, muscle pain: 47.1% vs. 42.2%, insomnia: 35.3% vs. 40.0%, general pain: 47.1% vs. 33.3%). For those on LOT ≥4, 42.9% of survey responses endorsed “somewhat”, “quite a bit”, or “very much” symptom bother compared to 32.7% for LOT <4. QOL was similar between groups. Over many months, patients on LOT ≥4 had several persistent symptoms (neuropathy, sadness, insomnia), but even those on LOT <4 had unmet symptom needs (fatigue, general pain, constipation). DISCUSSION/SIGNIFICANCE: Evidence shows that treatment selection at higher LOT in MM often underrates the impact of cumulative symptom burden. Our study reveals significant longitudinal unmet needs regarding symptom and distress management in MM; understanding this can help guide treatment decisions and palliative care for MM patients with escalating treatment demands.

OBJECTIVES/SPECIFIC AIMS: To establish an effective team of researchers working towards developing and validating prognostic models employing use of image analyses and other numerical metadata to better understand pediatric undernutrition, and to learn how different approaches can be brought together collaboratively and efficiently. METHODS/STUDY POPULATION: Over the past 18 months we have established a transdisciplinary team spanning three countries and the Schools of Medicine, Engineering, Data Science and Global Health. We first identified two team leaders specifically a pediatric physician scientist (SS) and a data scientist/engineer (DB). The leaders worked together to recruit team members, with the understanding that different ideas are encouraged and will be used collaboratively to tackle the problem of pediatric undernutrition. The final data analytic and interpretative core team consisted of four data science students, two PhD students, an undergraduate biology major, a recent medical graduate, and a PhD research scientist. Additional collaborative members included faculty from Biomedical Engineering, the School of Medicine (Pediatrics and Pathology) along with international Global Health faculty from Pakistan and Zambia. We learned early on that it was important to understand what each of the member’s motivation for contributing to the project was along with aligning that motivation with the overall goals of the team. This made us help prioritize team member tasks and streamline ideas. We also incorporated a mechanism of weekly (monthly/bimonthly for global partners) meetings with informal oral presentations which consisted of each member’s current progress, thoughts and concerns, and next experimental goals. This method enabled team leaders to have a 3600 mechanism of feedback. Overall, we assessed the effectiveness of our team by two mechanisms: 1) ongoing team member feedback, including team leaders, and 2) progress of the research project. RESULTS/ANTICIPATED RESULTS: Our feedback has shown that on initial development of the team there was hesitance in communication due to the background diversity of our various member along with different cultural/social expectations. We used ice-breaking methods such as dedicated time for brief introductions, career directions, and life goals for each team member. We subsequently found that with the exception of one, all other team members noted our working environment professional and conducive to productivity. We also learnt from our method of ongoing constant feedback that at times, due to the complexity of different disciplines, some information was lost due to the difference in educational backgrounds. We have now employed new methods to relay information more effectively, with the use of not just sharing literature but also by explaining the content. The progress of our research project has varied over the past 4-6 months. There was a steep learning curve for almost every member, for example all the data science students had never studied anything related to medicine during their education, including minimal if none exposure to the ethics of medical research. Conversely, team members with medical/biology backgrounds had minimal prior exposure to computational modeling, computer engineering and the verbage of communicating mathematical algorithms. While this may have slowed our progress we learned that by asking questions and engaging every member it was easier to delegate tasks effectively. Once our team reached an overall understanding of each member’s goals there was a steady progress in the project, with new results and new methods of analysis being tested every week. DISCUSSION/SIGNIFICANCE OF IMPACT: We expect that our on-going collaboration will result in the development of new and novel modalities to understand and diagnose pediatric undernutrition, and can be used as a model to tackle several other problems. As with many team science projects, credit and authorship are challenges that we are outlining creative strategies for as suggested by International Committee of Medical Journal Editors (ICMJE) and other literature.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Implementation assessment plans are crucial for clinical trials to achieve their full potential. Without a proactive plan to implement trial results, it can take decades for one-fifth of effective interventions to be adopted into routine care settings. The Veterans Health Administration Office of Research and Development is undergoing a systematic transformation to embed implementation planning in research protocols through the Cooperative Studies Program, its flagship clinical research program. This manuscript has two objectives: 1) to introduce an Implementation Planning Assessment (IPA) Tool that any clinical trialist may use to facilitate post-trial implementation of interventions found to be effective and 2) to provide a case study demonstrating the IPA Tool’s use. The IPA Tool encourages study designers to initially consider rigorous data collection to maximize acceptability of the intervention by end-users. It also helps identify and prepare potential interested parties at local and national leadership levels to ensure, upon trial completion, interventions can be integrated into programs, technologies, and policies in a sustainable way. The IPA Tool can alleviate some of the overwhelming nature of implementation science by providing a practical guide based on implementation science principles for researchers desiring to scale up and spread effective, clinical trial-tested interventions to benefit patients.

OBJECTIVES/GOALS:

• To describe trends in fall risk screening and referrals to community-based programs among physical therapy professionals.

• To compare fall risk screening practices to clinical practice guidelines among

• To identify gaps in fall risk screening and referrals to community-based programs among physical therapy professionals.

METHODS/STUDY POPULATION: A panel of experts between the American Physical Therapy Association (APTA) - Geriatrics, and the National Council on Aging (NCOA) developed a web-based survey to identify practices among physical therapy professionals (PTs) for fall risk screenings and community-based referrals for older adults. The web-based survey was disseminated to PTs via email, e-blasts, and social media. The survey focused on questions related to knowledge of fall risk screening tools, fall risk management for older adults, and knowledge of and referrals to community-based interventions. RESULTS/ANTICIPATED RESULTS: To date, 453 PTs representing 50 states completed the survey. The majority of PTs (50.9%) had over 20 years of experience in various settings. Eighty-three percent regularly screen older adults for fall risk. Approximately 40% conduct community-based screenings. The majority (81.3%) were somewhat to very familiar with the CDC-recommended STEADI (Stopping Elderly Accidents, Deaths, and Injuries) screening toolkit. Despite familiarity, only 32% responded to the question if they used STEADI for screening. Of those, 83.4% used the tool. The majority (73.4%) of PTs were aware that NCOA recommends evidence-based programs to address health needs of aging adults and 59.6% refer. PTs did not refer due to lack of knowledge that programs existed (21.3%) or lack of knowledge of availability (33.3%). DISCUSSION/SIGNIFICANCE OF IMPACT: Although PTs are have some familiarity with the STEADI for fall risk screening, the tool is not common in practice. PTs are lacking awareness of local evidence-based community programs to address health needs of aging adults. Educational efforts should target these knowledge gaps and provide additional resources to improve referrals.

OBJECTIVES/GOALS: Incomplete mucosal healingand dysbiosis prevent long-term remission after colitis. IL4 may restore colon homeostasis through its action on immune cells and the microbiome. We will demonstrate this mechanism using genetically modified mice and molecular tools. This may result in target therapies that prolong remission in patients with IBD. METHODS/STUDY POPULATION: Mice were treated with 3% dextran sulfate sodium (DSS) in drinking water for 5 days to induce colitis. Mice were monitored daily for changes in body weight, and to monitor colitis severity. At each endpoint, mice were sacrificed and colon length was measured. For disease severity assessment, mouse colons were prepared in paraffin sections by the 'swiss-rolling' method. For flow cytometry, lamina propria mononuclear cell isolation was performed and cellular populations were stained with fluorophore-conjugated antibodies. IL4-eGFP-expressing (4get) mice were used to analyze the cellular expression of IL4 after colitis. Cell-specific IL4 deletion mice were generated using the cre-lox system. RESULTS/ANTICIPATED RESULTS: IL4-deficient mice had worse colitis compared with wild-type controls. Flow cytometry of lamina propria cells from 4get mice showed that most IL4-producing cells after colitis are eosinophils (CD11b+SiglecF+). Flow cytometry of C57bl6 mice showed an influx of IL4Ra+ monocytes (CD11b+Ly6C+) and macrophages (CD11b+F480+). IL4-stimulated bone marrow-derived macrophages demonstrated an increase in HB-EGF mRNA transcription. Myeloid-specific IL4R deleted mice had no difference in colitis severity compared with controls. Neutrophil-specific IL4R-deleted mice had increased colitis severity and mortality. Co-housing of littermate mice rescued recovery after DSS in IL4 deficient mice. DISCUSSION/SIGNIFICANCE: IL4 appears to play a role in restoring homeostasis after colitis. The mechanism depends on eosinophil-derived IL4, and action through neutrophils. However, the reparative function of IL4 can be shared with deficient mice through the microbiome. I will study the cellular and microbial mechanism by which IL4 restores homeostasis after colitis.

OBJECTIVES/GOALS: Team science competencies are not well-defined for nonfaculty staff of Clinical Research Professionals (CRPs) who conduct research. Using an existing framework, our work has determined skills associated with team science competencies as related to CRPs. Our team also outlined examples of those skills on a fundamental, skilled, and advanced level. METHODS/STUDY POPULATION: The team consists of both CRPs and those working in the Team Science space. This team used a modified Delphi approach to determine the skills and leveling examples of each team science competency. The team broke into four groups and was assigned 3-4 competencies each. Each group determined skills needed to support (exhibit, promote) each competency and then described an example of this skill at the fundamental, skilled, and advanced levels. Once each group was finished with their assigned competencies, they were re-assigned to a different group for review and changes. Finally, team science and CRP experts reviewed the skills and levels. RESULTS/ANTICIPATED RESULTS: Our results are a rubric that defines 3-5 practical skills per described competency. These skills are needed to support and promote each competency as a CRP. An additional outcome from this work includes examples of each skill at the fundamental, skilled, and advanced levels in a CRP’s career. Each leveled example is described in a concise, actionable way using Bloom’s taxonomy. This rubric is meant to be easily understood, very useable and able to be used in conjunction with existing CRP competency frameworks. By using Bloom’s taxonomy, we set the stage for future educational programming in Team Science skill-building for clinical research professionals. DISCUSSION/SIGNIFICANCE: Team science concepts and competencies have been increasingly integrated into translational science teams. However, team science competencies related to CRPs have remained largely undefined. Our work helps to define these competencies for CRPs in a practical way. Our rubric fills gaps in, and builds on, existing CRP competency frameworks.

OBJECTIVES/GOALS: The UCLA Clinical and Translational Science Institute’s Population Health Program is creating versatile scientists who can solve population health problems. This means building learning capability in health care and public health agencies, and fostering a cross-sector, outcomes-based, regional ecosystem for implementation and improvement. METHODS/STUDY POPULATION: A synthesis of achievements and lessons learned reveals the Program’s trajectory. It maps progress in science leading to sustainable interventions for target populations. PHP goals are predicated on networked team science, rather than disorganized assortment of individual studies and interventions, and emphasize design, modeling and iteration. Evolving metrics include network analysis to document collaborative impact; extent of integrating real-world application into systems science and learning system curriculum; legislative and institutional policies developed and adopted; evidence of system orientation, cross-sector focus, and implementation research in scientists’ portfolios; and demonstration of population health impact. Barriers offer the opportunity for iteration and improvement. RESULTS/ANTICIPATED RESULTS: The PHP has progressed in its envisioned shared university-public health stewardship of translation and transformation. Milestones included galvanizing activities such as annual regional dissemination, implementation, and improvement (DII) symposia and Public Health Science Summits; pre- and post-doctoral experiential learning of system science and learning system methods based in Los Angeles County Health Agency initiatives; development of a regional CTSA network for implementation science training; strengthened public health policy practice (e.g., establishing a new Office of Youth Diversion and Development); learning healthcare system capability; and prototypes of population learning systems focused on hypertension, food insecurity, tobacco/vaping, and complex care management. DISCUSSION/SIGNIFICANCE OF IMPACT: PHP is committed to advancing science for population health. Prototypes were an essential initial phase. New areas include use of methodological advances (e.g., artificial intelligence, rapid assessments) in health and public health systems; an academic home for full-time, population-focused clinicians; and social policy innovations.

ABSTRACT IMPACT: Through this research, I will transform the standard of care for infants with single ventricle physiology by incorporating the Capute Scales and General Movement Assessment into day-to-day clinical care for these infants, leading to early detection of neurodevelopmental disabilities and access to proven therapies. OBJECTIVES/GOALS: Our objective was to establish a new protocol to detect and quantify developmental delays in multiple domains in infants with single ventricle physiology, a type of congenital heart disease. This population is at high risk for neurodevelopmental disabilities. METHODS/STUDY POPULATION: We implemented a novel protocol using the Capute Scales and General Movement Assessment to evaluate early language, cognitive, and motor development in infants with single ventricle physiology. The infants were evaluated between 1-5 months of age in the cardiac neurodevelopmental program. We defined our primary outcomes as (1) language and (2) cognitive developmental quotients as per the Capute Scales and (3) results of the General Movement Assessment. We hypothesized that infants with single ventricle physiology would have typical language and cognitive development and normal General Movement Assessment results at their initial evaluation. RESULTS/ANTICIPATED RESULTS: We recruited ten infants with single ventricle physiology. All ten infants had typical language development, and nine of the ten had typical cognitive development, as measured by the Capute Scales. All of the infants had gross motor delay. Due to medical instability, we only evaluated four infants with the General Movement Assessment. All four of the infants had a normal result, suggesting that their central nervous system motor pathways were maturing appropriately. In future studies, we will track the neurodevelopmental outcomes of each participant as they mature. We expect to see a decrease in expressive language development and preserved receptive language and cognitive development. DISCUSSION/SIGNIFICANCE OF FINDINGS: The combination of General Movement Assessment and Capute Scales in the evaluation of infants with single ventricle physiology will provide early identification and intervention for these high-risk children, allowing access to proven treatments and therapies.

OBJECTIVES/SPECIFIC AIMS: The objective for the present study is to evaluate qualitatively the Team Leadership Assessment Center (LAC) at UTMB-Galveston. There has been much discussion about the need for leader development within team science (Börner, et al, 2010; Falk-Krzensinski, etal., 2011). The LAC was designed to examine the study participants’ beliefs and perceptions of and competencies in team leadership by means of a multi-trait multi-method approach. Our team competency model involves seven dimensions and twenty-five specific competencies. There were two complementary components to the evaluation: a quantitative survey and a series of qualitative interviews, to be discussed here. METHODS/STUDY POPULATION: The study population for the qualitative component consisted of seventeen volunteers from the pool of fifty-one LAC participants, including trainees (KL2 scholars, TL1 scholars) as well as assistant professors, and early career associate professors. Each volunteer respondent was engaged in a twenty to thirty-minute, recorded, conversational, telephone interview. They were asked to describe and evaluate their LAC experience in their own words, perceptions, and values. The study was reviewed by the Committee for the Protection of Human Subjects at UTMB. RESULTS/ANTICIPATED RESULTS: Major findings from respondents’ overall assessment of their Center experience include:. All respondents stated that the LAC was a worthwhile experience. All respondents stated they would be willing to participate in any follow-up LAC activity. Before the LAC experience, most respondents indicated that they perceived leadership as a condition or feature of a job, appointment, or profession and not an individualistic feature of personality or experience. Ideational or conceptual definitions of leadership were superseded by administrative or managerial tropes. Major categorical indexes were related to occupational status. The generally belief is one is not trained to be a leader, but to perform leadership tasks. Significant differences among respondents tended to cluster around occupational positions and statuses at UTMB, for example:. Surgeons feel they are team oriented and their work is organized according to necessary tasks. Assistant professors and post-docs generally perceive the design of leadership as defined by the demands of their specialized field, not determined institutionally or professionally. A general take-away was the sense that, although some participants did not consider themselves to be “leaders” before the training, most felt that the “pressure” to be or become a leader was relieved a bit by the LAC. One was only expected to develop leadership skills and strategies, not change one’s Self-Identity. DISCUSSION/SIGNIFICANCE OF IMPACT:. The more complex the job status, the less critical is the need to achieve the Self-Identity of “leader.” Complaints about the LAC were very few and non-modal in occurrence. A general recommendation would be for the facilitators of programs like LAC to take cultural differences more into consideration. The most highly rated feature of the LAC is the personal attention given to participants during the one-on-one evaluation profile.

ABSTRACT IMPACT: This study evaluates the long term effects of pharmacologic weaning therapy for opiate exposed infants. OBJECTIVES/GOALS: Infants born to chronic opioid users often suffer from neonatal abstinence syndrome (NAS), a condition characterized by tremors, diarrhea, hyperirritability and an inconsolable high-pitched cry. Symptoms are treated with pharmacologic weaning therapy, but long-term effects of this treatment have not been established. METHODS/STUDY POPULATION: A sample of infants born between 2011-2017 was obtained from a large metropolitan hospital system. All infants who were exposed to opioids and received a Finnegan score were included in the sample (N=1,807). The analysis utilizes three dependent variables to measure developmental delay: motor delay, language delay or any delay, which includes general/non-specific delay in addition to motor and language delay. The treatment is defined as receipt of pharmacologic therapy with methadone or morphine. Maximum Finnegan score was also included as a continuous measure of the extent of the infant’s withdrawal symptoms. Linear models were utilized to determine a relationship between pharmacologic therapy and developmental delay with Maximum Finnegan score as an interaction term. RESULTS/ANTICIPATED RESULTS: In the linear models examining the main effects of weaning therapy on developmental delay, there was no relationship between pharmacologic therapy and motor delay (p=.260), language delay (p=.542) or any developmental delay (p=.176). When maximum Finnegan score was entered into the model as an interaction term the relationships were not significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: These results suggest that while pharmacologic weaning is an appropriate treatment for withdrawal symptoms in infants, it is not a deterrent against developmental delays associated with NAS. This provides support suggest an increased focus on non-pharmacologic interventions such as breastfeeding as the first line of treatment for NAS infants.

OBJECTIVES/GOALS: This study seeks to elucidate the relationships between early life adversity (ELA), social learning, and empathic responding. Specifically, it aims to understand the impact of ELA on the expression of empathy and ability to adjust behavior after social observation. METHODS/STUDY POPULATION: 60 healthy participants ages 18-65 will be recruited from the greater Baltimore area. They will undergo a placebo manipulation paradigm with simultaneous EEG recording to capture neural oscillations in frontal and insular cortices and event-related potentials. Participants will observe a demonstrator who indicates pain relief in response to the application of an inert cream. Then, while undergoing heat pain stimulations, the participant will receive the same inert cream and rate their physiological and psychological pain experience using a visual analog scale. The heat stimulations will be lowered without their knowledge to measure placebo response. Participants will also answer a battery of questionnaires which assess personality, psychological factors, life history, empathy, and current social life. RESULTS/ANTICIPATED RESULTS: It is expected that ELA will result in decreased placebo response, interpreted as deficits in social learning. Further, we expect that this effect is moderated by state empathy, empathy in a specific context or moment. We predict that individuals with lower state empathy and exposure to adversity will have greater deficits in social learning. We also expect to see more robust event-related potentials preceding painful stimulations at electrodes corresponding to the medial and ventral prefrontal cortex and insula in ELA-exposed participants. Because these brain regions are connected to anticipatory and predictive circuits, this would indicate that the individual has not adjusted their expectations according to the social information gained via observation. DISCUSSION/SIGNIFICANCE: Results of this study will expand our understanding of how ELA impacts behavior throughout life. Individuals with a history of ELA often face social difficulties and a higher risk of psychiatric disorders. This study will illuminate possible neural correlates of these differences in social behavior and, more generally, the expression of empathy.

OBJECTIVES/GOALS: To compare the effects of dietary fiber supplementation based on fermentability and viscosity on phosphorus fractional absorption and the gut microbiome in a rat model of chronic kidney disease-mineral and bone disorder (CKD-MBD). METHODS/STUDY POPULATION: 25-week-old Cy/+ male rats (CKD hereafter) will be randomly assigned to receive one of four fiber treatments (10% w/w each) based on fermentability and viscosity: 1) Cellulose (-fermentability, -viscosity), 2) inulin (+fermentability, -viscosity), 3) psyllium husk (-fermentability, +viscosity), or 4) pectin (+ fermentability, +viscosity). Diets will be formulated with a semipurified diet containing 0.7% phosphorus. Treatments will last for 10 weeks, and rats will be euthanized at 35 weeks of age, where animals have reached kidney failure. Intravenous and oral 33P will be used for intestinal phosphorus fractional absorption and cecal/fecal samples will be obtained at euthanasia for microbiome assessment using shotgun metagenomics. RESULTS/ANTICIPATED RESULTS: Our preliminary data show that fermentable dietary fiber (inulin) impacted phosphorus homeostasis by increasing the circulating levels of fibroblast growth factor-23 (a bone-derived hormone that increases phosphorus excretion in urine) and lowering circulating levels of phosphorus in the Cy/+ male rat model of progressive chronic kidney disease. We hypothesize that dietary fiber impacts phosphorus absorption in gut microbiome-dependent and independent mechanisms. For example, fermentable fiber enhances the production of short-chain fatty acids, lowering the intraluminal pH, and enhancing mineral solubility and absorption. Meanwhile, viscous fibers may encapsulate minerals limiting their absorption if these fibers are non-fermentable. DISCUSSION/SIGNIFICANCE: Hyperphosphatemia, or high circulating phosphorus, is a major factor in the pathogenesis of CKD-MBD. Treatment of hyperphosphatemia is focused on reducing intestinal absorption. However, available therapies vary in their efficacy and focus on phosphorus absorption in the small intestine, ignoring the possible impact of the large intestine.

OBJECTIVES/GOALS: To explore the patterns, sequence, quantity, frequency and duration of poly substance use among adults for back translation of information to rodent models. METHODS/STUDY POPULATION: From May –December 2019, we conducted 13 focus group discussions with adults 19 to 63 years of age who reported concurrent use of cocaine with alcohol and/or marijuana in the past 30 days. All participants were recruited from the community through community outreach activities. Written informed consent was obtained and all focus group discussions were audio recorded, transcribed and analyzed using the qualitative data analysis software Atlas Ti™. RESULTS/ANTICIPATED RESULTS: A total of 34 cocaine users, (68% male, and 59% minority) participated. The majority reported cocaine as the drug of preference, while marijuana and alcohol were used to extend or control the ‘highs’, or ‘to take the edge off’ after cocaine use. All participants reported when they used alcohol with cocaine, they could keep drinking a large amount of alcohol without feeling its effect. Participants also reported using marijuana throughout the day while driving, at work, or in class. Frequent patterns noted for the study included using two drugs at the same time or right before or after each other with alcohol used throughout the day. Participants also gave feedback on our Poly Substance Use (PSU) assessment that captures exact patterns so that the most common can be translated for the rodent models. DISCUSSION/SIGNIFICANCE OF IMPACT: Our focus group discussions provided detailed information on patterns, sequence, quantity, and types of poly substance use that could be useful for developing a poly substance use assessment in the collection of data for rodent models to understand effects of poly substance use.

OBJECTIVES/GOALS: In this study, we implemented deformable medial modeling as a morphometric approach in first trimester placentas to characterize morphometric differences between fully automated and manual segmentations. METHODS/STUDY POPULATION: Twenty placentas from singleton pregnancies between 11-14 weeks’ gestation were manually and automatically segmented from 3D ultrasound volumes. Automated segmentations were produced by a trained convolutional neural network pipeline. Dice overlap scores and volumes were computed between manual and automated segmentations. Deformable medial modeling was applied to both manual and automated segmentations to produce the following metrics: maternal and chorionic surface areas (SA), thickness, circumference, and diameter along the generated medial surface. Placental non-planarity was also determined as the greatest medial surface height difference. A paired t-test and simple linear regression was performed between manual and automated segmentations for each shape metric. RESULTS/ANTICIPATED RESULTS: Mean placental volume measurements between manual and automated segmentations were similar, with a percent difference of 3.28% and a mean Dice overlap score of 0.85 ± 0.07. There were strong, statistically significant (p <0.01) linear correlations with chorionic and maternal SA, SA difference, thickness, circumference, medial surface diameter, and medial surface height difference. No significant differences were noted with chorionic SA, thickness, circumference, maximum medial surface diameter, or medial surface height difference. However, statistically significant differences (p <0.01-0.03) were noted in maternal SA, SA difference, and mean medial surface diameter. Despite these differences, mean percent difference for all morphometric parameters was less than or equal to 10%. DISCUSSION/SIGNIFICANCE: A deformable medial model evaluate unique global and regional shape placental features with highly correlated values between manual versus automated placental segmentations. However, clinical studies are needed to determine if minor differences would impact the clinical utility of these features as potential indicators of placental function.