OBJECTIVES/GOALS: Navigating the NIH Single IRB Policy has been challenging for investigators, study teams, and Human Research Protection Programs (HRPP). In response, the Indiana Clinical and Translational Sciences Institute (CTSI) created an innovative Single IRB Project Manager role (sIRB PM), uniquely placed within the Indiana CTSI. METHODS/STUDY POPULATION: The Single IRB Project Manager role was created in 2018 by the Indiana CTSI in response to the NIH Single IRB Policy for Multi-Site Research. The role of the sIRB PM is to serve as a liaison between the Indiana University HRPP, lead site, coordinating center, and participating sites when Indiana University serves as the Single IRB. This model has proven useful to both the IRB and lead site, notably in the following ways:

• At study start-up, the sIRB PM can handle complicated communications among sites and the IRB at the same time the lead site is responsible for many other administrative tasks related to start-up. By absorbing the workload of IRB approval for multiple sites, the sIRB PM provides the lead site more capacity to handle other essential tasks.

• The sIRB PM translates new terminology and facilitates processes that are new for sites.

RESULTS/ANTICIPATED RESULTS: Early assessment of this program is predominantly positive. The sIRB PM currently supports 24 external sites. In an NIA-funded 13 site study, all sites were added within 9 months of initial IRB approval of the protocol. This role fills a gap that benefits:

• IRB staff by allowing them to fulfill their duties of screening and review while leaving some of the reliance organization to the sIRBPM.

• Lead PI by allowing them to focus on conducting the research instead of the many administrative tasks required for single IRB review.

• Participating sites by having a liaison to enter their amendments and reportable events into an otherwise closed IRB software system.

• All parties by having the sIRB PM manage document organization, storage, and distribution study-wide.

DISCUSSION/SIGNIFICANCE OF IMPACT: The CTSI sIRB PM role effectively shifts administrative work caused by the sIRB mandate by merging research coordinator experience with regulatory experience while building upon an existing strong relationship with the HRPP. Future focus is on process education, standardizing pricing structure, and ensuring sufficient budget support in grants.

OBJECTIVES/GOALS: Clinical research is the backbone of the medical community. However, there are few regulations to ensure clinical trial participants can understand their results, leading to volunteers feeling unvalued and unlikely to enroll in trials1. This study examines the need of lay summaries METHODS/STUDY POPULATION: To understand the current landscape of clinical trial summaries, literature searches were conducted using the University of Southern California Library database with keywords Title contains “lay language” OR “lay summary” AND any field contains “Trial” OR “clinical”, and Title contains “natural language processing” AND “clinical trial” OR “Summary”. Studies were deemed relevant if they discussed lay language summaries for health care realms or using Natural Language Processing (NLP) to increase comprehension. Papers published by the Center for Information and Study on Clinical Research Participation (CISCRP) were reviewed and their Associate Director was interviewed. RESULTS/ANTICIPATED RESULTS: Of 67 total results, 14 were determined to be relevant. Ten of the relevant results examined lay language summaries and their regulation and 4 were NLP studies. The European Medicines Agency set regulations mandating clinical trial summaries. However, researchers have difficulty validating to an appropriate reading level2. Difficulty and potential bias halted a U.S. mandate of lay summaries3. The nonprofit CISCRP has partnered with industry to develop unbiased clinical trial summaries resulting in all volunteers feeling appreciated and 91% understanding clinical trial results post summary1. Similarly, NLP software for annotating Electronic Health Records increased comprehension for 77% of patients4. DISCUSSION/SIGNIFICANCE OF IMPACT: In the U.S., a lack of regulations mandating lay summaries may be related to concerns by regulatory agencies that summaries in plain language may introduce bias3. Future looks into integration of NLP systems to clinical trials may create unbiased summaries and allow for FDA regulation.

OBJECTIVES/GOALS: Introduction: Between 2014 and 2019 the National Institute of Health (NIH) through the National Center for the Advancement of Translational Science (NCATS) has awarded about $2.7 billion to U.S. Academic Medical Centers to build a national network of clinical and translational science program hubs that serve to meet their key goals and initiatives. Today there are about 60 Clinical and Translational Science Award (CTSA) program hubs. Each CTSA program hub has a corresponding website highlighting its clinical and translational science centered programs and activities. These websites are a critical communication gateway to promote NCATS goals and initiatives. Objective: The objective of this research is to evaluate the NIH funded Clinical and Translational Science Award (CTSA) program hub websites for NCATS goals and initiative content alignment, navigability, and interactivity. METHODS/STUDY POPULATION: Methods: Each CTSA program hub website was systematically evaluated for information or tools that align with the five NCATS / CTSA Goals and eight CTSA nationally identified program initiatives. Each NCATS goal and CTSA initiative was subsequently ranked by information diversity level (text, tool, interactivity) and navigation level (click distance from the home page). RESULTS/ANTICIPATED RESULTS: Results: Four of the five NCATS goals are thoroughly and consistently represented among the CTSA Consortium with workforce development, patient and community engagement, and quality and efficiency of research being the top three. Informatics is thoroughly and consistently represented, but not always clearly identified on the home page. The most underrepresented goal is integration of special and underserved populations which was identified on only 60% of CTSA program hub websites. The most common focus of the eight CTSA program initiatives is the Trial Innovation Network in CTSA program hub websites. The Smart IRB comes in a distant second. The remaining six initiatives are severely underrepresented. DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion: The identification of these gaps among the CTSA program hubs presents an understanding of content management and website functionality among the consortium from 3 principal approaches. First it creates an understanding of CTSA program hub content alignment with its funding source goals and initiatives. Such an understanding presents an opportunity to promote ways to create a better aligned consortium with improved collaboration pathways by the funding source through program hub website content standards. Second, it creates an opportunity for program hubs to understand and respond to the messaging their websites are presenting as it relates to the funding source. Third, it provides an opportunity to identify specific program initiatives and goals the CTSA institutions independently chose to highlight which can open a dialog to the better understanding the value of the program initiatives as they relate to the needs of CTSA program hubs. Ultimately, CTSA websites through content alignment should lead to an improved user experience.

OBJECTIVES/GOALS: Guided by the health belief model and social identity theory, we aim to identify socio-cultural and psychological factors that influence rural tobacco users a) participation in research and b) quitting tobacco use. We also explore how citizen scientists are perceived as disseminators of messages. METHODS/STUDY POPULATION: In Phase I of this multi-stage project, we are conducting in-depth interviews with approximately 30 tobacco users. Interviews are on-going, and have been conducted with 16 participants thus far from four rural counties in Florida. The interview consists of semi-structured questions and multiple validated questionnaires. Specifically, we ask a series of questions about participants’ barriers to participating in research, tobacco use history, and internet use and message preferences. Additionally, we include questionnaires on participants’ substance use, nicotine dependence, motivation to quit, and willingness to participate in research studies. RESULTS/ANTICIPATED RESULTS: Initial findings suggest that rural tobacco users have an overall positive perception of research, and many choose to participate in research for altruistic reasons (i.e. they want to help others). Further, participants noted described feeling stigmatized due to their tobacco use. Although most began smoking to fit in with their community, many now feel on the outs. Participants also reported logistical barriers to participating in research, including lack of transportation. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings can inform the development of recruitment materials to resonate with rural adults, including by emphasizing the collective potential to help by participating. This interdisciplinary highlights areas for collaboration to enhance the reach of health education and public health messages.

OBJECTIVES/GOALS: There is universal recognition of the importance of team science and team leadership. We have developed a semi-quantitative translational science specific team leadership competency assessment tool and have begun implementation studies to assess the impact of personalized feedback on the team science leadership skills of KL2 Clinical Scholars. METHODS/STUDY POPULATION: To create the instrument, we employed a modified Delphi approach by conducting a thorough literature review on Leadership to concretize the relevant constructs, then used these extracted constructs as a springboard for the Rockefeller Team Science Educators (TSE’s) to discuss and refine the leadership domain areas, collectively create domain-specific survey items. Further discussion helped refined the number, grouping, and wording. Scholars also contributed feedback in item development. We piloted the Leadership Survey by having all of the Rockefeller TSEs rate Clinical Scholars, and having each Scholar rate themselves. Each item was answered using a six-point Likert scale where a low score indicated poor expression and a high score represented excellent expression of the specific leadership attribute. RESULTS/ANTICIPATED RESULTS: Incorporation into a REDCap data base made consenting and rating process by TSE’s and the Scholars straightforward. The a priori domains (Foundational Leadership Competencies, Professionalism, Team Building and Team Sustainability, Appropriate Resource Use and Study Execution, and Regulatory Accountability) had high internal validity and good internal factor structure. The congruence between TSE and Scholar self-ratings were uniformly high, and discordance was often a function of “confidence” and “modesty” on the part of the scholar, rather than deficiency. Supporting comments were informative about performance barriers and mechanisms for improvement. Return of results allowed for the exploration of training gaps. Scholars were surveyed to gauge their reaction to the formal feedback. DISCUSSION/SIGNIFICANCE OF IMPACT: This quantification of team science leadership constructs has allowed for A)- the articulation of constructs essential for successful Translational Scientists to acquire during their training, B)- identification of gaps in that training and skill set, and C)- mechanisms for bolstering any identified gaps in these essential leadership constructs. CONFLICT OF INTEREST DESCRIPTION: None

OBJECTIVES/GOALS: As part of the Cleveland CTSA, “Collaborative Working Retreats” have been developed for the purpose of being a catalyst to move groups of interdisciplinary investigators and stakeholders to collaborative research teams with feasible and actionable translational research projects. METHODS/STUDY POPULATION: Groups of interdisciplinary investigators with engaged stakeholder(s) were invited to apply. Selected groups participated in a 4-hour, professionally facilitated retreat, tailored to the unique needs of each team. In addition to the facilitator, a graphic recorder was utilized to capture ideas and aid in decision making by creating a visual narrative linked to the team’s overall vision. Teams were charged with generating three translational research projects and writing a formal Team Action Plan (TAP) by two months post retreat. Retreat participants were asked to complete a survey to evaluate the retreat, and structured interviews were conducted with team leaders 4-6 months post retreat. RESULTS/ANTICIPATED RESULTS: Six groups were awarded retreats, comprised of 48 investigators (representing all schools in the university and 3 of 4 affiliated hospital systems) and 28 stakeholders for a total of 76 participants. 45% completed the followup survey. 77% said they would recommend the service to other teams or would use it again themselves and 97% stated their team benefited from having a facilitator. At 2 month follow up, one team had completed the TAP and subsequently applied for federal funding. However, 4 of the remaining 5 teams indicated that they had made significant progress, attributing progress to their retreat time. Each teams’ progress is being tracked for 2 years, using a newly developed metric. DISCUSSION/SIGNIFICANCE OF IMPACT: Facilitated retreats appear to serve as an important catalyst for progression of translational research projects, providing needed time and support for brainstorming and planning. Lessons learned, pre-retreat work, and tools for tailoring retreat content and tracking progress will be presented.

OBJECTIVES/GOALS: Health care systems are complex, dynamic, and varied. Advances in artificial intelligence (AI) are enabling healthcare systems to use their own data to elicit patterns and design suitable interventions. To realize this potential, computer scientists and clinicians need an effective, practical, and replicable approach to collaboration METHODS/STUDY POPULATION: In this study, computer scientists partnered with clinicians to investigate predictors of avoidable emergency department use. The team sought an approach to computational medicine that could increase the relevance and impact of prediction to solve pressing problems in the health system. The team adopted an emergent architecture that engaged system leaders, computer scientists, data scientists, health services researchers, and practicing clinicians with deep ambulatory and inpatient knowledge to form the initial questions that shaped the prediction model; to understand nuances of coding and recording in source data and the implications for models; and to generate insights for promising points of intervention. The team recorded decisions and challenges as it progressed to analyze its function. RESULTS/ANTICIPATED RESULTS: Most avoidance models focus on a narrow time period around target events, or on high cost patients and events. This interdisciplinary team used their insights into the health system’s workflows and patient population to adopt a longitudinal approach to their prediction models. They used AI to build models of behavior in the system and consider prevention points across clinical units, time, and place. The holistic, systemwide focus enabled the team to generate insights that the system leaders and subsequently specific clinical units could apply to improve value and outcomes. A facilitated team process using learning system and cooperative network principles allowed a large and modular interdisciplinary team to build a transparent AI modeling process that yielded actionable insights into hypercomplex workflows. DISCUSSION/SIGNIFICANCE OF IMPACT: An architecture for involving diverse stakeholders in computational medicine projects can increase the relevance and impact of AI for solving care delivery problems in complex health systems. Translational science and computational medicine programs can foster this type of engagement and encourage a whole system perspective.

OBJECTIVES/GOALS: We examined how individual characteristics and characteristics of the socioeconomic and built environment were associated with care coordination’s effect on cardiovascular disease (CVD) risks to identify geographic areas that may benefit from supplementary clinic-community linkages. METHODS/STUDY POPULATION: We analyzed data with geocoded residential addresses and data from electronic health records for 9946 adults from a Centers for Medicare & Medicaid Services funded innovation project from 7/1/2013 to 3/30/2015. Variables included patient-level demographics, Elixhauser comorbidity index, total time with a nurse care manager, and neighborhood factors such as poverty indicators, walkability, and social capital index. Outcomes were change in CVD risk factors, hemoglobin A1C, blood pressure (BP), and low-density lipoprotein (LDL). Generalized linear models were used to assess the effect of nurse care management program on outcomes after controlling for confounding factors. RESULTS/ANTICIPATED RESULTS: We report preliminary models that include patient demographics (age, sex, race), health care utilization, nurse care manager contact time, Elixhauser comorbidity index, neighborhood education status, percent of population below 200% federal poverty level, median home value, walkability score of the residential address, and social capital index. After adjusting for all mentioned variables, in adults with HbA1C more than 7.5% at baseline, females had worsening HbA1C by 0.53% over the study period. Additionally, LDL values in females worsened over the study period by 4.8 mg/dL after adjusting for all variables. No clinically significant changes were noted for BP. DISCUSSION/SIGNIFICANCE OF IMPACT: Women’s HbA1C and LDL worsened despite nurse care management and may benefit from additional community-based interventions or interventionists. In future analyses, we anticipate that CVD risk will worsen for patients with higher fast food proximity and with greater geographic distance from their PCP.

OBJECTIVES/GOALS: Collaborations are at the core of translational science and team science. Differences by gender have been identified in various research contexts from recruitment to retention to promotion. This study assesses the relational associations of translational collaborations, and what role of gender. METHODS/STUDY POPULATION: In 2011 and 2013, clinical and basic sciences investigators at University of Rochester School of Medicine and Dentistry responded to an online survey nominating their research collaborators. Two study years were merged, and name lists were transformed into a collaboration network. Departments were classified into basic sciences (e.g. biochemistry) and clinical (e.g. urology). If respondent and partner were affiliated to different department classes, the collaboration was defined as translational. Multi-level GLM models were developed to assess the associates of the likelihood of translational vs. within discipline collaborations. Partner nominations were nested in respondents. RESULTS/ANTICIPATED RESULTS: 202 respondents were included in the multi-level GLM models. A collaboration was more likely to be translational if the respondent shared more collaborators with the partner (OR:1.13), and respondent was a central actor in collaboration network (OR: 1.2). Translational collaborations were less likely to be reported by clinicians (OR: 0.25). In the model to assess gender match, a collaboration was more likely to be translational if the respondent was male, and nominated a male partner. For both genders, collaboration with a partner of the opposite gender was more likely to be translational if respondent had more shared collaborators with the partner. DISCUSSION/SIGNIFICANCE OF IMPACT: Translational collaborations happen in teams. Gender homophily exits in translational collaborations, and is reduced by shared collaborators; implying the effect of personal connections and community membership. Community-building interventions may increase diversity in translational collaborations.

OBJECTIVES/GOALS: Vaginal delivery is typically avoided in extremely preterm breech fetuses due to the concern for head entrapment by the cervix. Development of a device to prevent head entrapment would be best addressed by a multidisciplinary approach incorporating engineering principles with clinical obstetrics. METHODS/STUDY POPULATION: Construction of a collaborative multidisciplinary team to address the clinical challenge of preventing head entrapment was initiated through a unique course at the Massachusetts Institute of Technology (Course 2.75, Medical Device Design). The course would provide a structured means by which students (senior undergraduate and graduate students in Mechanical Engineering) would be paired with a clinical advisor and faculty in their department. Weekly team meetings were scheduled to review the clinical context pertinent to the problem and review engineering principles needed to develop a solution. The course also provided a small monetary budget ($4K) for the students to purchase supplies. RESULTS/ANTICIPATED RESULTS: During the semester long course, several iterations of a prototype were designed. Each subsequent rendition was evaluated from both an engineering and manufacturing perspective, as well as clinical appropriateness. The weekly meetings allowed for rapid re-design and assured that all necessary parameters were considered by the entire team. Students also had access to lab facilities and additional mentorship that allowed for supplementary input beyond that generated by core team members. These interactions, along with those of their classmates working on other projects, provided a strong base for exploring subsequent device development. DISCUSSION/SIGNIFICANCE OF IMPACT: Successful medical device development requires a collaborative process and students can be ideal members of these teams as they reside in an environment that is conducive to exploration and novel idea generation. Course-based student led team science platforms can provide an excellent foundation for solving uniquely challenging medical problems.

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.

OBJECTIVES/GOALS: To determine whether length of stay (LOS) and opioid prescribing differ among patients who present to the emergency department (ED) with low back pain (LBP) and serious mental illness (SMI+) compared to patients without SMI (SMI−). METHODS/STUDY POPULATION: Eligible patients that visited the ED within the Mount Sinai Health Care System from 2016-2019 were identified from the Mount Sinai Data Warehouse. Data on patient demographics, number of medications prescribed, and length of stay (LOS) were compared between the groups. Patients were excluded if English was not their primary language and if the LOS exceeded 24 hours. The final dataset consisted of 940 patients (SMI+: n = 181; SMI−: n = 759). RESULTS/ANTICIPATED RESULTS: SMI+ cases included patients with a diagnosis of depression (n = 152), anxiety (n = 134), schizophrenia (n = 9), bipolar (n = 1), and/or post-traumatic stress disorder (n = 33); 26% of cases had a single diagnosis, 66% with two, and the remaining 8% had three diagnoses. There was no significant difference in pain scores between the two groups (SMI-: 7.0 ± 0.1; SMI+: 6.8 ± 0.3; p = 0.6). We found no significant differences in LOS between the groups (SMI-: 3.9 ± 0.1 hours; SMI+: 3.8 ± 0.2 hours; p = 0.8), nor was there a significant difference in number of medications prescribed (SMI-: 1.7 ± 0.9; SMI+: 1.7 ± 0.6; p = 0.4). Further analysis revealed that the odds of receiving an opiate prescription in the SMI- group was 0.92 (95% CI: 0.54,1.55). DISCUSSION/SIGNIFICANCE OF IMPACT: Comparable opioid prescribing and LOS exist in patients with and without serious mental illness who are seeking treatment for low back pain in the ED. Despite similarities in approaches to care, more information is needed to determine if other social determinants influence these practices.

OBJECTIVES/GOALS: We seek to develop a 3D perfusion culture imaging plate for human fecal bacteria co-culture with epithelial cells in a structure that mimics the gut epithelium. We will develop this system for use with patient fecal samples to characterize patient risk of developing cancer. METHODS/STUDY POPULATION: E. coli NC101, a strain that harbors the pks gene island, produces the genotoxin colibactin which causes DNA damage that can lead to colorectal cancer development. The genotoxic ability of this bacterium is dependent upon cell-to-cell contact. Here, we present 3D printed E. coli NC101 and intestinal epithelial cells (IEC-6) in a perfusion imaging plate, enabling visualization of the cytotoxic effects of the bacteria in real time using confocal microscopy, in combination with flow cytometry analysis for cell cycle arrest (a surrogate marker of DNA damage). RESULTS/ANTICIPATED RESULTS: 40,000 IEC-6 cells were 3D printed in a cylindrical layer in our triple well imaging plate. The cells were infected at an MOI of 100 for 18 hours and time lapse images of the infection were recorded by confocal microscopy. The cells were then harvested for analysis by flow cytometry for cell cycle arrest as a measure of DNA damage. Our images and flow cytometry data show that E. coli NC101 co-localizes with IEC-6 cells and causes cell cycle arrest in phase G2 (infected %G2 = 40.1), compared to uninfected cells (%G2 = 24.7, P = 0.034). Mutant strains lacking adhesion protein FimH or the ability to produce colibactin do not cause G2 cell cycle arrest (P = 0.844 and P = 0.644, respectively). DISCUSSION/SIGNIFICANCE OF IMPACT: We are able to recapitulate the DNA damage phenotype of E. coli NC101 in our 3D culture system. We show here that host-microbe interactions leading to cancer can be modeled in our 3D perfusion system, and we will next use patient fecal samples in our culture system.

OBJECTIVES/GOALS: Spinal cord stimulation (SCS) is an intervention for patients with chronic back pain. Technological advances have led to renewed optimism in the field, but mechanisms of action in the brain remain poorly understood. We hypothesize that SCS outcomes will be associated with changes in neural oscillations. METHODS/STUDY POPULATION: The goal of our team project is to test patients who receive SCS at 3 times points: baseline, at day 7 during the trial period, and day 180 after a permanent system has been implanted. At each time point participants will complete 10 minutes of eyes closed, resting electroencephalography (EEG). EEG will be collected with the ActiveTwo system, a 128-electrode cap, and a 256 channel AD box from BioSemi. Traditional machine learning methods such as support vector machine and more complex models including deep learning will be used to generate interpretable features within resting EEG signals. RESULTS/ANTICIPATED RESULTS: Through machine learning, we anticipate that SCS will have a significant effect on resting alpha and beta power in sensorimotor cortex. DISCUSSION/SIGNIFICANCE OF IMPACT: This collaborative project will further the application of machine learning in cognitive neuroscience and allow us to better understand how therapies for chronic pain alter resting brain activity.

OBJECTIVES/GOALS: Morehouse School of Medicine (MSM), TxTM is a scientific philosophy promoting interdisciplinary approaches towards exponential advances in community and population health. Objectives are to detail the model, pilot funding mechanism, early research findings and infrastructure investments. METHODS/STUDY POPULATION: The health research system has widely acknowledged challenges that can delay research translation to systems that advance health for chronically disadvantaged health disparity population groups. MSM’s vision is to lead the creation and advancement of health equity. The vision-aligned strategic plan prioritized formalization of a TX TM implementation priority. The study population was the institution’s research faculty and leaders, research administration, and communication arm. Through a cross-institutional working group, a plan was deployed to 1) assess the institutional landscape, 2) review the grey and peer reviewed literature on translational research and 3) invest in a pilot research funding mechanism. RESULTS/ANTICIPATED RESULTS: Over $700K has been invested in TX TM implementation. Over half of research faculty completed an institutional landscape assessment to identify translational research expertise, interests and points of interest in new collaboration. The most frequently cited collaborative research interests were clinical research with human subjects, patient-centered outcomes and laboratory-based research with human subjects/specimens. Funded multidisciplinary and/or community-engaged pilot studies investigate the role for circadian rhythms and shift work, cultural variables influencing mental health among Haitians living in the US and integrating prescription reconciliation telehealth in primary care. DISCUSSION/SIGNIFICANCE OF IMPACT: TX TM requires interdisciplinary collaboration across translational research spheres and beyond the academy. Institutional investment, infrastructure support and senior-level champions are central to awareness and rewarding such scholarship towards scaling approaches that advance health equity. CONFLICT OF INTEREST DESCRIPTION: Coined at Morehouse School of Medicine (MSM), Tx TM symbolizes an approach and scientific philosophy designed to intentionally promote and support convergence of interdisciplinary approaches and scientists to stimulate exponential advances for the health of diverse communities.

OBJECTIVES/GOALS: Peri-implantitis is the inflammation of peri-implant mucosa and subsequent loss of supporting bone. Its treatment is only <40% successful mainly due to persistent bacterial infection. The goal of this project is to increase success rates by developing a robust antibiofilm multi-biomolecular membrane that can be placed around implant surfaces. METHODS/STUDY POPULATION: A collagen membrane was soaked in the antimicrobial peptide GL13K solution overnight to form an interpenetrating fibrillary network. The nanostructure of the membrane was imaged with scanning electron microscope (SEM). The hydrophobicity of the membrane was analyzed by water contact angle (WCA) measurements. The biodegradability was tested in a 0.01 mg/mL Type I collagenase solution for up to 5 weeks. The antimicrobial activity of the membrane was assessed with Gram-positive oral bacteria Streptococcus gordonii. The cytotoxicity was evaluated by culturing human gingival fibroblasts (HGF), and the osteogenesis was assessed using preosteoblasts MC3T3. Pure collagen membrane was used as the control. Statistical significance (p<0.05) was determined by one-way ANOVA with Tukey’s HSD test. RESULTS/ANTICIPATED RESULTS: The antimicrobial peptide GL13K self-assembled to short fibrils (< 1 µm long), which entangled with the larger collagen fibers (around 200 nm in diameter). The collagen fibers presented characteristic periodic banding structures, which provided biomimetic cues for cell behavior as extracellular matrix. The interpenetrated GL13K fibrils turned the highly hydrophilic collagen membrane to a hydrophobic membrane (WCA = 135 °) and significantly reduced the rate of degradation by collagenases. The developed membrane was efficient in preventing the attachment of S. gordonii. A large portion of the attached bacteria was killed on the surface of the membrane. The incorporation of GL13K did not affect the cytocompatibility of the membrane for HGF. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed an antibiofilm membrane with interpenetrating collagen and antimicrobial peptide fibrils. The strong antimicrobial activity and low cytotoxicity support its further translational evaluation as scaffolds for increasing success rate in treating peri-implantitis.

OBJECTIVES/GOALS: Decision-making impairments in addiction can arise from dysfunction in distinct neural circuits. Such processes can be dissociated by measuring complex, computationally distinct behaviors within an economic framework. We aim to characterize computational changes conserved across models of addiction. METHODS/STUDY POPULATION: We used neuroeconomic tasks capable of dissociating neurally separable decision processes using behavioral analyses equally applicable to humans and rodents. We tested 12 human cocaine-users and 9 healthy controls on the Web-Surf task designed to match the rodent Restaurant Row task on which 27 mice were trained and then exposed to saline (n = 10), cocaine (n = 7), or morphine (n = 10). All subjects foraged for rewards (humans: entertaining videos; mice: food) of varying costs (1-30s delays) and subjective value (humans: genres; mice: flavors) by making serial accept or reject decisions while on a limited time budget, balancing the utility of wanting desirable rewards despite conflicting costs. RESULTS/ANTICIPATED RESULTS: When encountering unique offers for rewards with a delay above one’s willingness to wait, cocaine-treated mice like cocaine-exposed humans were less likely to appropriately reject economically disadvantageous offers. Furthermore, these mice and humans did so despite spending more time deliberating between future options. In contrast, morphine-treated mice displayed distinct impairments when given the opportunity to correct past mistakes, a process we previously demonstrated was uniquely sensitive to alterations in strength of synaptic connectivity of the infralimbic-accumbens shell circuit in mice. We anticipate human opioid-users will mirror these latter, computationally distinct findings. DISCUSSION/SIGNIFICANCE OF IMPACT: These data elucidate facets of addiction shared across species yet fundamentally distinct between disease subtypes. Our translational approach can help shed light on conserved pathophysiological mechanisms in order to identify novel diagnostic parameters and computational targets for intervention.

OBJECTIVES/GOALS: An evidence-based approach for childhood obesity is family-based treatment (FBT). Research supports that motivation and income level may impact treatment success; however, the relationship between the two is understudied. Therefore, the objective of this study was to examine whether motivation for beginning FBT is associated with income levels. METHODS/STUDY POPULATION: 459 parent and child dyads from the PLAN (Pediatric, Learning, Activity, Nutrition) with Families multisite study were included in this study. PLAN consists of FBT through personalized health coaching over the course of two years, focusing on nutrition, physical activity, and parenting skills. Parent and child also attend height and weight assessments every 6 months in the study. Outcomes of the study include weight change and mastery of behavioral skills. Motivation and income level were provided by self-report at the beginning of the study. Motivation was based on a scale from 1-10 (1 = no motivation, 10 = high motivation). Income levels were grouped into one of three broader categories- low income ($80,000/year). RESULTS/ANTICIPATED RESULTS: The mean level of motivation for the parent was 8.76 and for the child was 7.87. There was a significant difference in the mean level of motivation for the child and parent, t = 7.73, p = < .001. Post-hoc multiple comparisons using Tukey’s HSD test indicated that children in the high-income group had lower levels of motivation (M = 7.29, SD = 2.07) compared to children in the middle (M = 8.18) and low (M = 8.70) income groups. Level of motivation did not differ for children in the middle and low-income groups. Finally, parent motivation level did not differ significantly by income group. While there were significant differences between parent and child motivation levels, the motivation remained high for both groups. DISCUSSION/SIGNIFICANCE OF IMPACT: The data suggests a significant difference in mean child motivation and income level. Child’s high motivation may be from the idea of participating in something new, a rare opportunity for low-income children. To improve the implementation and efficacy of FBT, further study into the relationship between motivation and income level should be done.

OBJECTIVES/GOALS: The purpose of this 4-phase exploratory study is to create a human-centered protocol for a new program, CAPABLE-FAMILY, to address older adults with physical disability and dementia and their caregivers. METHODS/STUDY POPULATION: The Szanton-Gill Resilience Model, Verbrugge & Jett Disablement, and Life Span Theory of Control are theoretical frameworks guiding this study. Phase 1. Using qualitative research (n = 10 dyads) methods (ex. Photovoice) we seek to understand the context for older adults with dementia regarding disability. Phase 2. Using synthesis/ideation (n = 10 dyads) tools (ex. Journey Maps) we will synthesize the qualitative research during group ideation sessions with stakeholders. Phase 3. Using prototype testing (n = 3 dyads) methods (ex. Semantic Differentials, Storyboards), we will build the most promising prototypes. Phase 4. Using an open-label pilot (n = 3 dyads), we will test the interventions. RESULTS/ANTICIPATED RESULTS: We will assess disability (ADL, IADL), environmental changes pain, depression, polypharmacy, provider communication needs, and caregiver burden. We will interview the dyads and multiple CAPABLE Registered Nurses (RN), Occupational Therapists (OT), and Handymen (HM) about their prior experiences and perceptions of the pilot. CFQ, MocA, pain (BPI), and ZBI will be measured pre/post RN, OT, HM visit. While there are evidence-based programs to separately address cognitive impairment and physical disability, we anticipate this is the first study to develop a community-based goal-directed, human-centered approach for the maintenance of physical function for persons with dementia in the home. DISCUSSION/SIGNIFICANCE OF IMPACT: Persons with more cognitive impairment did not improve as much as those with less cognitive impairment in the original CAPABLE study, an evidenced based program which reduced disability. This suggests the need to adapt CAPABLE to reduce the burden of disability in persons with Alzheimer’s dementia. CONFLICT OF INTEREST DESCRIPTION: None

OBJECTIVES/GOALS: Cervical cancer is the fourth most common cancer among women worldwide, with approximately 570,000 newly diagnosed cases and 311,000 related deaths among women in 2018.In the United States, approximately 13,000 new cases of cervical cancer are diagnosed annually with approximately 4,000 women dying each year from cervical cancer. Nearly all cervical cancer is caused by oncogenic strains of the human papillomavirus (HPV). Prevention strategies to reduce cervical cancer after HPV exposure entail treatment of cervical dysplasia at the premalignant state, specifically low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL), along with the eventual clearance of HPV.The most common treatment for persistent LSIL or HSIL is the loop electrical excisional procedure (LEEP). This procedure is unfortunately not widely available in resource-limited countries and is associated with potential significant morbidities, including decreased fertility, preterm birth, premature rupture of membranes and cervical incompetence. Despite undergoing standard of care treatment, in certain high-risk populations, specifically HIV-infected women, there is a higher rate of premalignant HPV-related cervical disease persistence, progression and recurrence.There is a paramount need for novel nonsurgical treatments to stabilize or treat precancerous lesions of the cervix and to decrease the persistence of HPV infection. Medical treatment with the natural herb curcumin may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Curcumin is a major active component extracted from turmeric with anti-inflammatory, anti-infectious, and anti-cancer properties.Topical intravaginal curcumin has the promise of delivering this drug directly to the site of disease, ensuring adequate concentrations at the site of disease while avoiding systemic side effects. This proposed study will determine if there are higher rates of HPV clearance after curcumin administration among women with and without HIV who have premalignant HPV-related cervical disease, specifically LSIL or recently treated (with a LEEP) HSIL. METHODS/STUDY POPULATION: We are proposing a prospective double-blind randomized control trial to investigate the utility of topical intra-vaginal curcumin in increasing rates of HPV clearance and mitigating the high rates of disease recurrence in women with and without HIV. A sample of approximately 200 women with and without HIV who have biopsy-proven LSIL or recently treated HSIL will be randomized to one of two arms: 2000 mg of curcumin powder in capsules or placebo inserted intravaginally at bedtime once weekly for 20 weeks (excluding the time of menses). Cervical cytology and HPV testing will be performed at baseline and 6 months post-randomization. If a participant has abnormal cytology or a positive high-risk HPV test 6 months post-randomization, they will be scheduled to undergo a colposcopy with biopsies of all suspicious cervical lesions. If biopsy results are HSIL or greater, subjects will be referred back to routine clinical treatment, which may include a LEEP. Clinicians performing the colposcopies and the study participants will be blinded since the placebo has the same appearance as the curcumin capsules. At the end of the study, study participants will be offered the opportunity to participate in 2-3 hour focus groups to discuss acceptability of the product as a treatment for premalignant HPV-related cervical disease until data saturation is achieved. Power and sample size calculations are based on the primary outcome of interest, which is clearance of HPV at 6 months. Basu et al (2013) documented HPV clearance in as many as 80% of subjects with topical curcumin. To account for an expected lower success rate in HIV-infected women, who will also be included in the study, we intend to power our study to determine a more conservative 20% improvement in clearance rate at 6 months with curcumin treatment, assuming an expected clearance rate of HPV in HIV-infected women of 25%. In order to detect a 20% difference of HPV clearance among those treated with intravaginal curcumin vs. placebo at 6 months, about 80 patients per arm would achieve 80% power at the 5% significance level. To account for up to 20% loss to follow-up or discontinuation, the total sample size in each arm would be 100 subjects with a total of approximately 200 subjects enrolled in both arms. RESULTS/ANTICIPATED RESULTS: We are currently in the process of collecting data for this study. We hypothesize that intravaginal curcumin will have a 20% higher rate of HPV clearance at 6 months as compared to placebo. Primary outcome measures will include clearance of HPV at 6 months in curcumin vs. placebo. Secondary outcomes measures will include recurrence of disease by either cytologic or histologic abnormality requiring further surveillance or treatment at 6 months. We also hypothesize that intravaginal curcumin administered once weekly at bedtime for 20 weeks will be safe, acceptable, and well tolerated. This is based off of previous findings from the Phase 1 trial of intravaginal curcumin that we performed. During this Phase 1 trial, we explored daily intravaginal administration of 2000 mg of curcumin to further understand curcumin’s tolerability. Our focus group participants displayed an overwhelming consensus that daily administration affected quality of life, specifically due to the yellow-colored vaginal discharge from the medication. Study participants expressed that once or twice weekly administration was more tolerable and feasible. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. The primary outcome measure will be the proportion of study participants who discontinue treatment for any reason (acceptability) and the proportion of study participants who discontinue treatment due to adverse effects (tolerability). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-surgical treatments that decrease the morbidity and risk of progression of premalignant HPV-related cervical disease are greatly needed, especially in low-resource settings and among women experiencing barriers to care and/or at high risk for disease progression. Medical treatment with the natural herb curcumin is an emerging strategy that may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Several preclinical and clinical studies have shown curcumin’s ability to reduce tumors and precancerous lesions in animal and human cancer cells. Curcumin can suppress the activation of transcription factor NF-κB and the expression and activity of VEGF and p16INK4a, biomarkers known to be elevated in premalignant HPV-related cervical disease.Studies have also shown that curcumin alters HPV-associated molecular pathways in cancer cells, suppressing cervical cancer growth by inhibiting the transcription of oncoproteins HPV16 and HPV18 (designated as E6 and E7) and restoring p53 and retinoblastoma function. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. Our results will generate novel data as to what is an acceptable and well-tolerated dosing regimen of intravaginal curcumin, which would be crucial in designing further curcumin intervention studies. The results of our proposal will explore the effect of intravaginal curcumin as a standalone and adjuvant therapy to a LEEP among women with premalignant HPV-related cervical disease. The potential to not just excise diseased tissue, but to directly augment the clearance of the causative agent HPV, would have profound long-term ramifications in resource-limited settings and among women experiencing barriers to care and/or at high risk for disease progression.