ABSTRACT IMPACT: Specific recommendations will be suggested in this presentation as to how a health equity lens can be applied to implementation science frameworks. OBJECTIVES/GOALS: This systematic review consolidated literature on how implementation science (IS) frameworks (e.g., RE-AIM) have been used in cancer prevention services (e.g., screening, tobacco cessation programs) to reduce health disparities. METHODS/STUDY POPULATION: The systematic review was conducted in accordance with PRISMA and registered with PROSPERO. Searches were conducted in Ovid MEDLINE, PubMed, PsycINFO, CINAHL, and EMBASE between January-May 2020. Search strategies used the combinations of terms related to implementation science frameworks, cancer prevention and/or intervention, and all search algorithms were validated by a public health librarian. RESULTS/ANTICIPATED RESULTS: A total of 1,025 articles were screened and 84 were deemed eligible for full-text screening. After full-text screening, n=27 articles were included for data abstraction and synthesis. Of the 27 studies that used an implementation science framework, only one-third of studies (N=9, 33.3%) used an IS framework to address cancer-related health disparities. Of those nine studies, six of them used the Consolidated Framework for Implementation Research (CFIR) to guide, inform, and/or adapt the implementation of a cancer prevention intervention to target health disparities. However, the variability in how this framework was applied remains a challenge. DISCUSSION/SIGNIFICANCE OF FINDINGS: Recommendations for how various IS frameworks can be used to address cancer prevention disparities will be presented, such as, guiding principles on how to intentionally select domains within the CFIR that will capture input from key stakeholders in health disparities populations.

OBJECTIVES/GOALS: This work-in-progress aims to: 1) identify and differentiate symptom pattern trajectories in a sample of older adult heart failure (HF) patients over 24 weeks, and 2) examine associations between sociodemographic/clinical/physiological characteristics, dyadic health, and symptom trajectories. METHODS/STUDY POPULATION: ENABLE CHF-PC, a palliative care RCT (NCT02505425), was conducted at a Southeastern US medical center. Between 2016-2018, 415 older adult HF patients and 159 family caregivers were randomized to receive a psychoeducational intervention or usual care. Baseline sociodemographic information (age, gender, rurality, etc.) were collected. Outcome variables of interest include symptoms (Kansas City Cardiomyopathy Questionnaire (KCCQ), Functional Assessment of Chronic Illness Therapy-Palliative 14, Hospital Anxiety and Depression Scale (HADS)) and dyadic health (PROMIS-SF Global Health). We have calculated baseline descriptive statistics. Future work includes latent growth mixture modeling to identify distinct symptom trajectories and univariate associations with patient level factors. RESULTS/ANTICIPATED RESULTS: Of 415 patient participants, mean age was 64, 53% were male; 55% were African American; 26% were rural dwellers; 46% had +15.8) and low anxiety (6.7+3.6) and depressive symptoms (5.7+4.3) on the HADS. Of 159 family caregivers participants, the mean age was 57.9, 85.4% were female, 51.9% were African-American, and 65.2% were the patient’s spouse/partner. DISCUSSION/SIGNIFICANCE OF IMPACT: Limited data describes HF symptom pattern trajectories.How co-occurring symptoms affect quality of life or are affected by personal or situational factors are not well-understood. This study will help to identify factors and symptom phenotypes that may serve as targets for future interventions.

ABSTRACT IMPACT: Leveraging partnerships with faith-based institutions and community centers in at-risk NYC neighborhoods, the H2H Program breaks down barriers to engaging with the medical establishment and addresses the increasing burden of diabetes and CVD risk factors in the most vulnerable individuals. OBJECTIVES/GOALS: Screening for modifiable risk factors is critical for cardiovascular disease (CVD) risk reduction. Low-income, urban communities often encounter barriers to care. Community-academic outreach partnerships are vital in addressing such disparities and promoting health equity and culturally targeted interventions among high-risk populations. METHODS/STUDY POPULATION: In 2010, the Weill Cornell Clinical and Translational Science Center along with Weill Cornell Medicine (WCM) and Hunter-Bellevue School of Nursing (HBSON) launched Heart to Heart (H2H), a community outreach program partnering with faith-based centers to offer free health screenings and education to some of New York City’s (NYC) most vulnerable communities. Participants work with undergraduate, nursing, medical and dietician students to complete a demographics and health questionnaire followed by vital signs and point-of-care blood testing. Participants then receive personalized health education, nutrition and lifestyle counseling by student volunteers, precepted by WCM Primary Care and HBSON faculty. Participants are provided information on local free or low-cost clinics as necessary for follow-up. RESULTS/ANTICIPATED RESULTS: To date H2H held 125 events and 5,952 screenings. Mean age of the participants was 54.3 (SD 39.6) and 3,682 (63.1%) were female. 74.2% identified as non-white. 42.1% were uninsured. 32.3% reported annual income of less than $20k. 18.3% of participants reported not having seen a doctor in the past year. 40.7% reported preexisting hypertension, of which 74.5% were on medication and 78% with sub-optimal control. 15.7% had been previously diagnosed with diabetes, of which 75.8% were on medication and 41.4% with sub-optimal control (HbA1c <7). 37.7% had been diagnosed with dyslipidemia previously, of which 47.4% were on medication and 62.1% with sub-optimal control. Screenings revealed, 56.9% had undiagnosed hypertensive blood pressures, 4.7% had an elevated HbA1c >6.5, and 49.2% had dyslipidemia. DISCUSSION/SIGNIFICANCE OF FINDINGS: H2H screening revealed significant cardiovascular health disparities, many of which were poorly controlled or newly discovered. Cross-institutional academic partnerships can empower communities with knowledge of their health status and help facilitate access to medical care to further address health risk factors.

OBJECTIVES/GOALS: We aim to characterize how Heligmosomoides polygyrus bakeri (H. poly) alleviates murine allergic asthma which shares many characteristics of human asthma. This approach of has already identified helminth-produced human immune cell ligand “mimics” that hold great potential for next-generation clinical biologics METHODS/STUDY POPULATION: We examined the lung tissue of C57BL/6 mice infected with H. poly for changes in the pulmonary microenvironment. At ten days post infection, four infected mice and two co-housed uninfected mice were sacrificed, and their lung tissue harvested for examination of RNA via RT-qPCR. This design allows for the comparison between the lung microenvironments of infected and naīve mice. In future experiments, we intend to characterize what small molecules produced by the helminth drive changes in the lung using germ-free models of H. poly infection. RESULTS/ANTICIPATED RESULTS: We found key differences in lung chemokines between mice infected with H. poly and naīve mice. Using a student t-test with naīve correction for variance, we were able to show significant differences in the expression of E cadherin (p = 0.0355), CXCL10 (p = 0.0025), CX3CL1 (p = 0.0029), CCR2 (p = 0.017), and IDO1 (0.0078). We also found that differences in the expression of CCL5 bordered on significant with a p-value of 0.066. The expression of most of these markers (CXCL10, CCR2, CCL5, and IDO1) was elevated in the lungs of infected mice compared to naīve controls. In contrast, E cadherin and CX3CL1 showed the opposite trend with naīve mice showing greater expression. These clear differences in lung tissue gene expression underscore the connection between the gastrointestinal and pulmonary mucosal immune compartments. DISCUSSION/SIGNIFICANCE: The changes are unexpected for an infection that has been shown to attenuate allergic inflammation in the lung with increases in the IFN-Y responsive genes IDO1 and CXCL10 and inflammatory lung markers, CCL5 and CCR2. In contrast, there were decreases in inflammatory lung marker CX3CL1 and the tight junction protein E cadherin in infected mice.

OBJECTIVES/GOALS: To test if a machine learning algorithm could predict a person’s capacity to binge drink and explore what measures might be important for identifying individuals at risk for high-intensity binge drinking behaviors. METHODS/STUDY POPULATION: The sample included 1177 (474 female) non-treatment-seeking drinkers (age: 18-91 years), that were assigned to a group based on their heaviest drinking day reported in a 90-Day Alcohol Timeline Followback questionnaire. The groups were Non-Bingers (female: 12 drinks, male:>15 drinks). The sample was divided into a training sample (N = 884) and a testing sample (N = 293). A machine learning algorithm called random forest was then used to generate a predictive model based on measures of substance use, personality traits, and trauma. The model was applied to the testing sample to determine accuracy. RESULTS/ANTICIPATED RESULTS: The first model correctly assigned 190 out of 293 subjects, giving it a total error rate of 0.35, with lowest rates for non-binge (0.19) and high-intensity (0.18), while medium-intensity had the highest error rate (0.86). The most important variables for the accuracy of the model included: total score on the Alcohol Use Disorder Identification Test, first five sub-score of the Self-Reported Effects of Alcohol, Compulsive Drinking subscale, and presence of a current psychiatric diagnosis. As a follow-up analysis, we built and tested another random forest model without the use of drinking dependence measures. This model had a total error rate of 0.39, and introduced other important variables such as smoking behaviors, perceived stress, IQ, and number of negative life events. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study showed that it was possible for a machine learning algorithm to predict binge drinking intensity better than chance. Drinking patterns were the most robust predictors, and stress, IQ, and psychiatric diagnoses were also useful in predicting binge drinking intensity.

OBJECTIVES/SPECIFIC AIMS: To introduce CCTS to the clinical and translational research community. METHODS/STUDY POPULATION: Established in the summer of 2017, the Center for Clinical and Translational Science (CCTS) fosters cooperative clinical and translational sciences between the University of Mississippi School of Pharmacy (UMSOP) and the University of Mississippi Medical Center (UMMC). CCTS facilitates the translation of basic research discoveries into clinically validated therapies to improve the health of populations in Mississippi and beyond. Priority areas of investigation in CCTS include Cardiometabolic disorders, Cancer, Neuroscience, Infectious diseases, Precision Medicine, and Community-Based Research. To accomplish CCTS mission three overarching goals have been defined: I) Develop progressive and sustainable capacity for clinical and translational research in Mississippi; II) Promote interprofessional engagement in clinical and translational science; and III) Foster research collaboration among stakeholders in and outside of Mississippi. RESULTS/ANTICIPATED RESULTS: To carry its CCTS’s mission three research units have been established: 1) The Pre-clinical Research Unit: Develops processes to move basic science discoveries towards translation into research in humans. This unit provides guidance in the development of Investigational New Drug (IND) applications; and identifies and pursues opportunities to develop progressive capacities for in vitro, ex vivo, in vivo, and in silico approaches for evaluating new pharmaceutical and therapeutic agents. 2) The Clinical Research Unit: Transitions projects that have received IND approval into the first phase of clinical trials. It also transitions clinical trials from Phase I to Phase II and to Phase III; develops standard operating procedures (SOPs), personnel training plans, and policies to guide clinical research; works with industry sponsors and governmental funding agencies; and assures compliance with regulatory requirements. 3) Community/population Research Unit: Develops, coordinates, and facilitates research activities and translation between clinical and community/population research stages. To do so, this unit works closely with community partners and Population Health programs on the Oxford and Jackson campuses. DISCUSSION/SIGNIFICANCE OF IMPACT: Since its inception, the CCTS has surpassed 1.5 million dollars in competitive funding. This early success positions the CCTS well to promote research collaboration between UMSOP and UMMC and to progress in becoming a national leader in clinical and translational investigation.

OBJECTIVES/GOALS: This study aims to develop objectively scored histological characteristics of early oral leukoplakia, which may be correlated with molecular pathways predictive of progression into proliferative verrucous leukoplakia (PVL). The secondary aim is to develop a biomarker profile to be used in diagnosis, staging, and management of PVL. METHODS/STUDY POPULATION: Clinical and pathology records of 120 patients with oral leukoplakia and/or PVL were reviewed. Eight patients were selected—all had serial biopsies over time leading to PVL suspicion. Specimens were deidentified and subjected to blinded examination by a board certified oral pathologist, then scored relative to the extent of each of the commonly accepted histologic characteristics of PVL: hyperkeratosis, acanthosis, blunt rete ridges, hyperchromatic nuclei, increased nuclear-cytoplasmic ratio, dyskeratosis, and surface corrugation. Given these results, a larger subset of patient samples will be labeled and assayed for expression of epidermal growth factor receptor tyrosine kinases and downstream pro-oncogenic signaling mediators. Expression of these factors will be tested against progression to PVL. RESULTS/ANTICIPATED RESULTS: Histologically, in scoring the specimens from eight subjects, the characteristics of acanthosis, dyskeratosis, and blunted rete ridges had the strongest correlation with eventual progression to PVL. These criteria will therefore be recommended as an objective histopathologic method of identification of patients with high risk of development of PVL, and therefore malignant potential. We expect the results of the biomarker assay to provide a molecular basis for predicting PVL pathogenesis. Particularly, we anticipate pro-oncogenic targets such as EGFR, PI3K, Akt, and mTOR pathways will show increased expression as leukoplakic lesions progress. These results would then provide the basis for testing patient samples for expression of these markers in a longitudinal study of PVL emergence and progression. DISCUSSION/SIGNIFICANCE: The aggressive nature of PVL, with a rate of malignant transformation of 61% and mortality rate of 40%, requires close clinical monitoring in order to improve patient outcomes. Therefore, well defined objective clinical, histologic, and molecular criteria are critical for early detection of sites likely to progress to PVL and subsequent malignancy.

OBJECTIVES/GOALS: Prior studies suggest that transgender individuals are at greater risk of mental health problems. This study aims to determine the mental health care needs of the adult transgender population seen at a tertiary referral hospital in the Midwest region of the United States and assess necessary resources to provide optimal care. METHODS/STUDY POPULATION: This descriptive, retrospective, cross-sectional study included all new transgender patients > 18 years old, seen at the Washington University Transgender Center since December 2019 through May 2022. Electronic medical record data obtained from their initial and subsequent follow-up visits include 1) Demographics: date of birth, age, race, ethnicity, sex assigned at birth, gender identity, zip code of residency 2) Mental health diagnosis: Previous mental health diagnosis, mental health history 3) Mental health care access: mental health providers, mental health treatment, previous mental health admission, resources provided in clinic. RESULTS/ANTICIPATED RESULTS: 487 patient records were reviewed. Median age at initial visit was 24 years (18 - 75 yr), with 46% identify as woman, 37% as man. Predominantly white (84%), 11% were black. 93% had primary health insurance At the first visit, 81% reported having some mental health diagnosis: depression (88%), anxiety (71%), attention deficit disorder (21%). Prior suicide attempt reported on 12% and 5% with self-harm behavior. Only 48% had a therapist and 22% had an established psychiatrist First follow up occurred with a median of 4 months (1-22 months). 4 patients reported new suicide attempt, 3 reported new self-harm behavior. 9 patients required a hospital admission due to a psychiatric condition. 4% reported a new mental health diagnosis (most common: depression and anxiety). No changes noted on access to therapist or psychiatrist DISCUSSION/SIGNIFICANCE: Our study shows that adult transgender individuals have high rates of depression, anxiety, and overall psychological distress which is exacerbated by poor access to mental healthcare. This indicates a critical need to include mental healthcare professionals during the evaluation of adult transgender individuals

OBJECTIVES/GOALS: Primary Objective: To evaluate the safety of venetoclax plus tazemetostat in patients with relapsed and refractory (R/R) Follicular lymphoma (FL) or Diffuse large B-cell lymphoma (DLBCL) Secondary Objectives: 1. To evaluate the tolerability of the combination of T+V using patient reported outcomes (PROs) 2. To evaluate the efficacy of T+V METHODS/STUDY POPULATION: Study design: A phase I trial in two parts: Part 1: a single-arm, open-label sequential dose escalation (3+3) of venetoclax in combination with tazemetostat, given at its recommended phase II dose (RP2D) of 800mg BID, to determine the maximum tolerated dose (MTD) of venetoclax. Part 2: two expansion cohorts (R/R DLBCL and R/R FL) to further characterize the safety and tolerability of the combination, and to estimate the preliminary efficacy. We will perform additional exploratory studies to determine if there are biologic features that correlate with responses. Eligibility: up to 38 patients aged >/=18 years old with histologically confirmed diagnosis of FL or DLBCL who have received at least 2 prior lines of therapy for lymphoma with evidence of disease progression and meet inclusion criteria RESULTS/ANTICIPATED RESULTS: Primary Endpoints: 1. Incidence and severity of adverse events as per CTCAEv5 2. Dose-limiting toxicity (DLT) of T+V, and to establish the maximum tolerated dose (MTD) of V plus fixed dose T Secondary Endpoints: 1. Incidence and Severity of toxicity and quality of life as per PRO-CTCAE and FACT-Lym 2. Overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, as per Lugano criteria 3. Duration of response (DOR), progression-free survival (PFS), overall survival (OS)Exploratory Endpoints: 1. Characterization of tumor cells pre-treatment (including EZH2 mutations and BCL2 translocations) 2. Phenotypic analysis (including BCL2 expression) and quantification of the tumor microenvironment in pre-treatment samples (using image mass cytometry)Explorato DISCUSSION/SIGNIFICANCE: There is a need for novel therapeutic approaches to improve the prognosis for patients with R/R NHL. Preclinical data suggests synergism between the pair.5 Importantly, this represents a chemotherapy-free, oral regimen. If well tolerated, this could present an alternative therapeutic option for patients ineligible for more intensive therapies.

OBJECTIVES/GOALS: The goal of this mixed methods project is to develop a comprehensive framework of the personal and care-related needs of informal caregivers of people with dementia. This model can be used to enhance targeted delivery of evidence-based services to caregivers in need. METHODS/STUDY POPULATION: To create a model of the personal and care-related needs of family caregivers of people with dementia, we conducted semi-structured in-depth interviews with current caregivers (N = 12) and conducted a content analysis of materials related to government reports and evidence-based interventions (N = 28) and existing measures of dementia caregiver needs (N = 54). Content analysis is a systematic qualitative methodology that is used to distill complex source material into content-related categories and is well-suited for both interview data and document data (Elo & Kyngäs, 2008). We identified themes related to caregiver needs through examination of materials within and across source categories. RESULTS/ANTICIPATED RESULTS: We propose a framework of five inter-related need categories: Environmental needs (e.g., transportation, health-care access, financial resources, time), psychological needs (e.g., emotional wellbeing, identity/autonomy, perceived preparedness), social needs (e.g., social support, family dynamics), health-related needs (e.g., health behaviors, sleep), and needs related to the care and functioning of the person with dementia. We also consider how needs and background characteristics transact to influence which services may be of greatest use. In the future, we plan to test this model empirically with a nationally representative sample of caregivers. DISCUSSION/SIGNIFICANCE OF IMPACT: Evidence-based services exist to meet the needs of dementia caregivers. A dearth of models clearly defining caregiver needs limits empirically-based plans for dissemination of services. We have identified a framework of the needs of family caregivers from which to create targeted dissemination plans.

ABSTRACT IMPACT: Study findings can guide improvements of the Summer Food Service Program to maximize the program’s desired effects on child summer nutrition and related health outcomes. OBJECTIVES/GOALS: The Summer Food Service Program (SFSP) addresses food insecurity during summer months. Project specific aims are to: 1. Describe characteristics of children participating in the SFSP. 2. Determine the nutritional quality of the SFSP foods. 3. Evaluate changes in children’s food insecurity, diet quality, and body mass index by SFSP participation. METHODS/STUDY POPULATION: A single group, prospective, staggered cohort design will be used for the proposed study. Two cohorts of 30 (N=60) elementary students and their parents will be recruited during the 2021-22 and 2022-23 school year. Each participant will complete a measurement session at three time-points: Baseline (spring), Post-Program (program end), and Follow-Up (following spring). Parents will complete an online survey about household food insecurity and family socio-demographic characteristics. Children will complete three 24-hour dietary recall interviews, and their heights, weight and percent body fat will be measured. The menus of at least ten SFSP sites will be analyzed to determine the nutritional adequacy of the site menus by using the Healthy Eating Index-2015. RESULTS/ANTICIPATED RESULTS: Study hypotheses are as followed: Aim 1. Not all of the children participating in the SFSP are from food-insecure or low-income households. Aim 2. Meals served at the SFSP will be higher in sugar and fat and lower in fruits and vegetables compared to recommendations in the 2015-2020 Dietary Guidelines for Americans. Additionally, the Healthy Eating Index-2015 score of the SFSP menus will be lower than that of the National School Lunch Program menus. Aim 3. Consistent SFSP participation will have a positive effect on reducing food insecurity, but not on increasing diet quality and reducing body mass index and percent body fat in children. DISCUSSION/SIGNIFICANCE OF FINDINGS: Program user information will determine if the program is reaching the target audience. Program managers will utilize menu analysis results to improve their menu nutritional quality. Changes in food insecurity, diet quality and anthropometric measures will inform whether the program needs to be improved to prevent any untoward excess weight gain.

OBJECTIVES/GOALS: Pregnant African American (Black women) have higher rates of adverse pregnancy outcomes compared to other races and routine monitoring of lipid levels is not currently in practice in prenatal care. We hypothesized that lipid profiles would show variation across pregnancy indicative of specific requirements during gestation and fetal development. METHODS/STUDY POPULATION: We used an untargeted lipidome analysis approach to investigate lipid metabolism with the progression of pregnancy. Pregnant Black women were recruited at prenatal clinics in Midwest (Metro Detroit, Michigan and Columbus, Ohio), women under 18 or above 45 years of age were not enrolled due to metabolic changes associated with these age groups. Women signed the consent forms and plasma samples were collected at 8-18 weeks at (T1), 22-29 weeks (T2) and 30-36 weeks (T3) of pregnancy. Samples from sixty-three women (mean age 27.41 ± 5.61 years) who had term birth (completed 37 weeks of pregnancy) were subjected to “shotgun” Orbitrap high resolution/ accurate mass spectrometry. Mixed-effects models were used to quantify systematic changes in relative lipid abundances over time using R lme4 and ggplot2 packages. RESULTS/ANTICIPATED RESULTS: Total lipids and some major lipid classes showed a significant increase with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase throughout pregnancy, while sphingolipids and total sterol lipids displayed a more pronounced increase at the T3 timepoint. Acylcarnitines, hydroxy acylcarnitines and Lyso phospholipids levels significantly decrease from T1 to T3. One of the interesting finding was that non-esterified fatty acids decreased from T1 to T2 and increased again from T2 to T3, suggesting a possible role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids- Linoleic Acid, Arachidonic Acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, Docosahexaenoic acid. DISCUSSION/SIGNIFICANCE: Mapping lipid trends during pregnancy could lend support to a precision health approach to reduce perinatal health disparities among pregnant Black women. The findings from this study will be used to identify biomarkers and study associations with social and environmental factors responsible for adverse perinatal outcome in pregnant Black women.

OBJECTIVES/SPECIFIC AIMS: Many CTSA network activities aim to promote collaboration. Who should we target, and how should we evaluate short-term success? This study examined the validity of recently developed collaboration readiness indices among early career scholars, an important and understudied portion of the translational workforce. METHODS/STUDY POPULATION: Participants were 107 scholars within 10 years of completing terminal degree or residency (mean age = 38; 69% female; 29% MD) who applied to one of two week-long NCATS-funded Innovation Labs (www.buffalo.edu/innovationlabs.html). Measures included the MATRICx (Mallinson etal., 2016), which assesses 17 collaboration motivators and 31 threats; the Transdisciplinary Orientation Scale (TDO; Misra etal., 2015), an assessment of attitudes and behaviors theorized to predict effective collaboration; and a brief measure of one’s perceived ability to succeed in different aspects of collaboration (i.e., self-efficacy; see teamscience.net). RESULTS/ANTICIPATED RESULTS: Factor analyses of individual measures and evaluation of cross-scale correlations suggest that collaboration readiness is multi-dimensional. Factor analysis of the MATRICx suggests 3 moderately-correlated facets of motivators (benefits to world, self, and others rs = +.50 to +.62) and threats (process concerns, external barriers, and leadership style, rs = +.29 to +.53). Most correlations between motivator and threat scales (except process concerns) were modest, suggesting they reflect relatively independent aspects of collaboration readiness. The TDO scales seemed to capture a different aspect of collaboration readiness; correlations with MATRICx motivator and threat scales were mostly modest (rs = -.26 to +.43). As expected, collaboration self-efficacy was positively related to collaboration motivators and TDO (rs = +.41 to +.59) and negatively related to collaboration threats (particularly process threats, r = -.47). Participants typically scored in the upper half of the TDO, MATRICx motivator, and collaboration self-efficacy scale ranges, and in the lower half of the MATRICx threat scale ranges. DISCUSSION/SIGNIFICANCE OF IMPACT: Collaboration readiness is a reasonable short-term target of efforts to promote collaboration. However, this work suggests that no single scale captures the entire conceptual space, and multiple measures should be assessed. The implications for efforts to enhance collaboration are intriguing. In samples already high in collaboration readiness, these measures will have limited ability to detect positive change. However, assessment of collaboration readiness may be particularly useful in identifying scholars who could most benefit from collaboration-enhancement programs (i.e., scholars with moderate scores on one or more of these metrics) and in personalizing intervention (e.g., selectively targeting TDO, collaboration motivators, and/or collaboration self-efficacy, and/or perceived threats to collaboration).

OBJECTIVES/GOALS: Patients who have experienced conjunctive mild traumatic brain injuries (mTBIs) suffer from a number of comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation after mTBI and its contribution to long-term pain are still poorly understood. METHODS/STUDY POPULATION: Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes and their effects on TBI-related pain. Utilizing a recently developed transgenic caspase-1 luciferase reporter mouse, we characterized the bioluminescence signal evident in both in vivo and ex vivo tissues following repetitive closed head mTBIs. This allowed us to reveal the spatiotemporal dynamics of caspase-1 activation in individual animals over time. Furthermore, we utilize various proteomic and behavioral assays to evaluate the role of caspase-1 mediated inflammation in the development and progression of injury-associated chronic pain. Lastly, by blocking inflammasome caspase-1 activation with a specific inhibitor, we assess its clinical potential as the next therapeutic approach to pain. RESULTS/ANTICIPATED RESULTS: We established that there were significant increases in bioluminescent signals upon protease cleavage in the brain, thorax, abdomen, and paws in vivo, which lasted for at least one week after each injury. Enhanced inflammation was also observed in ex vivo brain slice preparations following injury events that lasted for at least 3 days. Concurrent with the in vivo detection of the bioluminescent signal were persistent decreases in mouse hind paw withdrawal thresholds that lasted for more than two months postinjury. Using MCC950, a potent small molecule inhibitor of NLRP3 inflammasome-caspase 1 activity, we observed reductions in both caspase-1 bioluminescent signals in vivo and caspase-1 p45 expression by immunoblotting and an increase in hind paw withdrawal thresholds. DISCUSSION/SIGNIFICANCE: Overall, these findings suggest that neuroinflammation in the brain following repeated mTBIs is coincidental with a chronic nociplastic pain state, and repeated mTBI-associated events can be ameliorated by a highly specific small molecule inhibitor of NLRP3 inflammasome activation.

Each year our Clinical and Translational Science Award pilot projects program awards approximately $500,000 in translational pilot funding to advance health in South Texas. We identified needs to improve the timeliness, transparency, and efficiency of the review process by surveying applicants. Lean six sigma methodologies, following a “Define, Measure, Analyze, Improve, Control” approach, were used to streamline the pilot project application and review by identifying and removing bottlenecks from process flows. We evaluated the impact of our reorganized review process by surveying applicants and reviewers. Process mapping identified pilot project review as the main source of delay, leading to the implementation of a study section-style review mechanism. After one cycle, 90.3% of pilot applicants and 100% of reviewers were highly satisfied with the new processes and time to award notice was reduced by 2 months. All reviewers familiar with both review processes preferred the study section. We demonstrated how lean six sigma, a methodology not commonly applied in research administration, can be used to evaluate processes in translational science in academic health centers. Through our efforts, we were able to improve timeliness, transparency, and efficiency of the review process.