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

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

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

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

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

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

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

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: Vanishing White Matter Disease (VWM), is a childhood neurodegenerative leukodystrophy that presents with motor deficits, neurologic decline, and seizures leading to death.There are no treatments. Herein we investigate adeno-associated virus serotype 9 (AAV9) gene addition therapy for VWM. METHODS/STUDY POPULATION: To serve as a baseline for disease correction, we characterized the severe VWM Eif2b5I98M murine model with clinically relevant readouts including motor function, gait mapping and myelin loss through magnetic resonance imaging (MRI). Molecular characterization through the identification of biomarkers was also investigated. To provide targeted disease correction, we designed four gene replacement constructs to drive the rapeutic EIF2B5 expression in astrocytes—a critical cell type for VWM pathology. We are currently evaluating our AAV vectors in two murine VWM models, Eif2b5R191H and Eif2b5I98M, and are monitoring disease progression using traditional and clinically relevant readouts. RESULTS/ANTICIPATED RESULTS: The I98M mice display significant mobility loss, ataxic gait, and demyelination. Molecular characterization also indicates that the integrated stress response is significantly dysregulated, supporting the classic VWM phenotype. Our previous biodistribution study confirmed our ability to efficiently target astrocytes using varying iterations—including one novel—of the glial fibrillary acidic protein (GFAP) promoter. Our data suggests that targeting astrocytes with gene addition delays disease onset, partially rescues motor function, and attenuates myelin loss. Survival of the AAV9-gfaABC(1)D-EIF2B5 treated I98M mice is also significantly increased (p<0.0001), currently with a 2-fold extension in life expectancy. DISCUSSION/SIGNIFICANCE: Overall, we anticipate emergence of a lead astrocyte-targeted gene therapy candidate in which the data will be strengthened through the evaluation of clinically relevant measures in two murine models of disease, allowing fortimely translation to the clinic.

ABSTRACT IMPACT: Building a patient cohort to support clinical-translational research in chronic hepatitis B OBJECTIVES/GOALS: The overall objective of my KL2 project is to delineate the effect of HIV coinfection, and CHB disease stage and hepatitis B (HBV) viremia on the ability of toll-like receptor 8 agonism to restore HBV-specific immune cell function. This abstract describes the characteristics of the cohort from which research blood samples for my KL2 are collected. METHODS/STUDY POPULATION: HOPE is a prospective cohort study enrolling people with CHB including HIV/CHB coinfection, and resolved CHB. Participants are enrolled at primary care clinics in Maryland, Washington D.C., and Virginia. Standard-of-care antiviral treatment with tenofovir alafenamide (TAF) is prescribed through the study if indicated. Patients receiving TAF from the study are either starting treatment, or switching to TAF from another antiviral medication. If receiving TAF, participants are seen every 3-6 months for medication refills, clinical and research blood draws, and adverse event evaluations. Liver fibrosis is measured by FibroScan and a minority undergo liver biopsy. RESULTS/ANTICIPATED RESULTS: So far, 204 people have been enrolled, 177 with CHB (23 HIV/CHB coinfection), and 22 with resolved HBV infection. To date, 45 patients who were viremic at baseline and initiated on TAF have been enrolled. CHB predominantly affects Asian and African immigrants in the U.S, and the majority (77%) of HOPE participants are immigrants from these countries. The majority are male (70%), mean age 51 years (SD ±14). So far, 86 people with CHB monoinfection have been prescribed TAF on-study. Thirty-five percent of these had significant (>F2) liver fibrosis at baseline and half had elevated ALT (mean 47.5, SD ±55 IU/ml). Forty-three percent switched to TAF from another oral antiviral. Most switched due to lack of coverage by health insurance. DISCUSSION/SIGNIFICANCE OF FINDINGS: HOPE is a CHB cohort dedicated to collecting research samples and providing antiviral treatment. It is the foundation for the CHB translational research program at the University of Maryland School of Medicine. The availability of paired viremic and virally suppressed, HIV/CHB, and resolved HBV research samples are strengths of HOPE.

OBJECTIVES/GOALS: The purpose of the project was to create a Tableau dashboard to track metrics on requests for research data at Atrium Health Wake Forest Baptist. The objectives included: 1) define and identify request fulfillment metrics, 2) build a dashboard to capture metrics, and 3) integrate the dashboard into metrics tracking and reporting activities. METHODS/STUDY POPULATION: Project managers and team leaders in the Office of Informatics collaborated to determine which measures would be most relevant and impactful to report on. Metrics that were collected included: total count of tickets fulfilled over time, number of tickets currently open, sum of outstanding quoted hours, quoted hours vs. actual hours needed to fulfill ticket, and hours billed. Tableau's direct connection feature was used to extract the Trac ticket data from its Postgres database and the dashboard was published to Tableau Server. After the initial draft was created, several rounds of revisions were made as new data insights were discovered through further investigation of the data. RESULTS/ANTICIPATED RESULTS: Each morning, Tableau Server runs an automatic refresh of the data. On the dashboard homepage, users can see a quick view of all available metrics; to minimize noise, only the current statuses, active tickets, and stats for the most recent monitoring periods are displayed. Many of the charts give the user the option to link out to a page with related supplemental information (historic data, ticket status history, etc.). With the help of the dashboard, project managers and team leaders can now monitor how long tickets are in each status, increase quote accuracy using the hours quoted and hours billed charts, and examine ticket complexity over time. DISCUSSION/SIGNIFICANCE: Prior to dashboard creation, metrics were sparse and difficult to assemble. By providing information on the quantity, size, and complexity of data requests, the dashboard enables the Office of Informatics to monitor how the process is functioning overall, make informed decisions about resource allocation, and provide quick interventions.

OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.

OBJECTIVES/SPECIFIC AIMS: The purpose of the study was to describe patient characteristics associated with subsequent development of bowel ischemia. Primary outcomes were survival to discharge, 30-day and 1-year survival in patients with LVAD who subsequently develop bowel ischemia. Secondary outcomes included characteristics of patients who survive to discharge after bowel ischemia and those who do not. These included markers of patient condition prior to surgical/endoscopic intervention such as lactate levels, ICU admission, ventilator dependence, vasopressor and renal replacement requirements, as well as presence of sepsis. Of these, we predicted that lactate levels and white blood cell count would be significantly elevated pre- and post-operatively in patients who do not recover from bowel ischemic event. We used Mann-Whitney U Test to examine lactate levels between the two groups as our sample size was <30 and therefore necessitated the use of non-parametric testing. METHODS/STUDY POPULATION: In this single-center retrospective study, we analyzed all patients who underwent durable, CF-LVAD implantation at Duke University Medical Center (DUMC) between January 2008 and November 2018. Patients were screened using CPT codes for abdominal surgical exploration or ICD codes for intestinal vascular insufficiency. Final cohort was selected with confirmed diagnosis of intestinal ischemia based on surgical exploration or endoscopic intervention. Patient characteristics including pre-LVAD comorbidities, indication for LVAD implant, and clinical picture prior to bowel ischemic event were collected. Specific characteristics related to bowel ischemia were summarized, including diagnostic imaging, time from imaging study to operative intervention, and intraoperative details. Patient outcomes including survival to discharge, 30-day-, and 1-year survival were summarized. Patients were stratified based on survival to discharge status. Continuous variables were reported as median and interquartile range and compared using Mann-Whitney U test. Categorical variables were reported as proportions and compared using Fisher’s exact test as appropriate. RESULTS/ANTICIPATED RESULTS: A total of 754 patients underwent durable, CF-LVAD implant at DUMC, of which 21 subsequently developed intestinal ischemia (incidence 2.8%). The majority were male (81%) and treated as destination therapy (76.2%). Ten patients (50%) survived to discharge (one remains hospitalized). The proportions of patients receiving HeartMate II (60% vs. 50%, p=1.0), HeartMate III (20% vs. 10%, p=1.0), and HeartWare (20% vs. 40%, p=0.6) were not significantly different between patients who survived to discharge and patients who did not. Median time from LVAD implant to diagnosis of bowel ischemia did not vary significantly between the patient groups (11.5 days, IQR 34.75 vs. 16.5 days, IQR 173.8; p=0.40), nor did the median time from diagnosis to surgical intervention (264.5 minutes, IQR 497.8 vs. 323 minutes, IQR 440, p=0.82). In the 48 hours leading to diagnosis and intervention, renal replacement therapy (50% vs. 0%, p=0.033) was more prevalent in patients who did not survive to discharge. Differences in pre- and post-operative lactate levels were not significantly different in patient groups. A similar pattern of diagnostic study preference emerged from both groups, with CT being the most common (76.2%) followed by KUB (42.9%). Upper endoscopy/colonoscopy was performed in 7 patients (33.3%), of which 5 also had operative exploration. A total of 19 patients underwent abdominal exploration (90.5%). Nine had large bowel resection (42.9%) while 14 had small bowel resection (66.7% with average 75cm removed). Overall survival at 1-year was 33%. For those making it to discharge (n=10), one year survival was 60%. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first institutional study to our knowledge to describe intestinal ischemia in patients receiving CF-LVAD therapy. Intestinal ischemia in patients receiving CF-LVAD therapy is associated with high mortality and morbidity. Diagnosis of bowel ischemia should be considered in patients presenting with clinical symptoms of bowel ischemia in addition to requirement of renal replacement therapy. Imaging modalities used were dependent on the clinical situation and were not always necessary prior to intervention. Further investigation is warranted to identify predictors of this morbid complication.

This study proposes a new practical approach for tracking institutional changes in research teamwork and productivity using commonly available institutional electronic databases such as eCV and grant management systems. We tested several definitions of interdisciplinary collaborations based on number of collaborations and their fields of discipline. We demonstrated that the extent of interdisciplinary collaboration varies significantly by academic unit, faculty appointment and seniority. Interdisciplinary grants constitute 24% of all grants but the trend has significantly increased over the last five years. Departments with more interdisciplinary grants receive more research funding. More research is needed to improve efficiency of interdisciplinary collaborations.

The commercialization of medical devices and biotechnology products is characterized by high failure rates and long development lead times particularly among start-up enterprises. To increase the success rate of these high-risk ventures, the University of Massachusetts Lowell (UML) and University of Massachusetts Medical School (UMMS) partnered to create key academic support centers with programs to accelerate entrepreneurship and innovation in this industry. In 2008, UML and UMMS founded the Massachusetts Medical Device Development Center (M2D2), which is a business and technology incubator that provides business planning, product prototyping, laboratory services, access to clinical testing, and ecosystem networking to medical device and biotech start-up firms. M2D2 has three physical locations that encompass approximately 40,000 square feet. Recently, M2D2 leveraged these resources to expand into new areas such as health security, point of care technologies for heart, lung, blood, and sleep disorders, and rapid diagnostics to detect SARS-CoV-2. Since its inception, M2D2 has vetted approximately 260 medical device and biotech start-up companies for inclusion in its programs and provided active support to more than 80 firms. This manuscript describes how two UMass campuses leveraged institutional, state, and Federal resources to create a thriving entrepreneurial environment for medical device and biotech companies.

Intervention development frameworks offer the behavioral sciences a systematic and rigorous empirical process to guide the translation of basic science into practice in pursuit of desirable public health and clinical outcomes. The multiple frameworks that have emerged share a goal of optimization during intervention development and can increase the likelihood of arriving at an effective and disseminable intervention. Yet, the process of optimizing an intervention differs functionally and conceptually across frameworks, creating confusion and conflicting guidance on when and how to optimize. This paper seeks to facilitate the use of translational intervention development frameworks by providing a blueprint for selecting and using a framework by considering the process of optimization as conceptualized by each. First, we operationalize optimization and contextualize its role in intervention development. Next, we provide brief overviews of three translational intervention development frameworks (ORBIT, MRC, and MOST), identifying areas of overlap and divergence thereby aligning core concepts across the frameworks to improve translation. We offer considerations and concrete use cases for investigators seeking to identify and use a framework in their intervention development research. We push forward an agenda of a norm to use and specify frameworks in behavioral science to support a more rapid translational pipeline.

OBJECTIVES/GOALS: Our aims are to 1) describe changes in thumb Carpometacarpal (CMC1) joint stability following an 8-week clinic-based dynamic stability exercise program using computerized tomography (CAT) and 2) to evaluate the agreement between ultrasound and CAT (reference standard) when quantifying thumb CMC stability. METHODS/STUDY POPULATION: Aim 1: We have enrolled 13/49 participants in a prospective pre-post interventional study of an 8-week clinic-based occupational therapy dynamic stability program. The primary outcome will be change in stability (thumb metacarpal subluxation in mm) when forcefully loading the thumb as per CAT from pre-treatment to post-treatment at 9 weeks. Aim 2: Same 49 participants are undergoing a one-time ultrasound during baseline assessment. Agreement of ultrasound and CAT measurements (thumb metacarpal subluxation in mm) will be assessed by the Bland-Altman method. RESULTS/ANTICIPATED RESULTS: Exercise is a first-line treatment of CMC1 OA yet there is insufficient evidence to support this. Progression of CMC1 OA is characterized by altered joint mechanics. Joint replacement surgery may reduce pain but often worsens thumb mechanics and overall hand function. This study is the first to test the sustained biomechanical effects of non-invasive thumb exercises. Should these benefits exist, this will further support exercise as a first-tier intervention. Should ultrasound be a suitable proxy for CAT, therapists/physicians could monitor thumb CMC mechanics in response to treatment without risk of radiation exposure. We anticipate 1) a statistically significant reduction in thumb CMC subluxation at 9 weeks follow up and 2) high agreement between sonographic and CAT measures of thumb stability. DISCUSSION/SIGNIFICANCE: This study will lay the foundation for future work and may offer critical support for the use of a non-pharmacological and non-surgical approach as first-line treatment of a highly disabling disease. Future study should include controlled trials where hand function, activity limitation, disease progression, and costs are the outcomes in interest.

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: CTSA Program hubs provide a wide range of research support services (funding, training, consultations, etc.) to individuals and teams. The CTSA Program hub at Columbia University seeks to identify best practices across CTSA hubs in how they facilitate researchers to identify, navigate, and access services at complex academic medical centers. METHODS/STUDY POPULATION: o A landscape analysis across CTSA Program hub websites was conducted during December 2021-February 2022, with the goal of assessing the availability of research navigation services and the ease of accessing and requesting research support services at each hub. Websites of 66 CTSA hubs were accessed and browsed for the following: 1) if a research navigation or concierge service was available; 2) how to request and apply to use common services such as pilot funding, biostatistics, clinical research services; 3) if there was a contact form and/or email address for general inquiries. Binary coding (1=Yes, 2=No) was used to track and summarize if these features were available, and then further classification and observations were noted into the full data set. RESULTS/ANTICIPATED RESULTS: The landscape analysis determined that 68% of CTSA hubs offer a form of research navigation including consultative models (personalized guidance, studios) and web-based models (self-service web portals, graphics, toolkits). Consultative models could be classified into three levels of support ranging from general information sharing to providing scientific expertise to convening more intensive studio sessions. 92% of CTSA hubs have at least 1 system in place for researchers to request services with a majority of hubs using a mix of tools and systems. In addition, 36% of hubs have additional general contact forms and 75% have general email addresses to assist researchers in obtaining more information. DISCUSSION/SIGNIFICANCE: There is a relative lack of data and information on the effectiveness of different research navigation models across the CTSA network, and barriers for researchers to identify services remain (Elworth et al). Our team is planning additional evaluations including interviews with leaders at other CTSA hubs and researchers and trainees at Columbia.

OBJECTIVES/GOALS: The goal of the CTSA consortium is to move scientific discoveries to clinical application. Translational science (TS) focuses on the process by which this happens, and NCATS supports pilot projects that propose TS questions. We are developing a rubric to guide program managers’ability to discriminate between TS and translational research (TR). METHODS/STUDY POPULATION: The CTSA External Review Exchange Consortium (CEREC) and CEREC II are reciprocal review collaborations between CTSA hubs that identify reviewers for each other’s pilot grant applications. CEREC and CEREC II partners developed a 31-item rubric, based on NIH’s Translational Science Principles, for discriminating pilot TS grant applications from those proposing TR. The hubs contributed proposals pre-selected as either TS or TR projects. Then, experienced reviewers and/or program administrators from the hubs used the rubric to score each of the proposals. Reliability of the rubric will be assessed using inter-rater reliability (% agreement and kappa). To identify which of the items in the rubric best discriminate between TS and TR, Item Response Theory analysis will be employed. RESULTS/ANTICIPATED RESULTS: Ten CEREC participating hubs submitted 30 applications: 20 TS proposals and 10 TR proposals. Twenty-two reviewers from 12 CEREC hubs evaluated the applications by using the scoring rubric; at least two reviewers evaluated each proposal. The results of the analyses will describe the reliability of the rubric and identify which of the seven TS Principles are most useful for distinguishing between TS and TR pilot grant proposals. Ultimately, this work will yield a scoring rubric that will be disseminated throughout the CTSA network to facilitate the screening of TS applications. DISCUSSION/SIGNIFICANCE: Optimizing research processes is critical to ensure that scientific discoveries are integrated into clinical practice and public health policy as rapidly, efficiently, and equitably as possible. By appropriately identifying and funding TS projects, CTSA hubs can accelerate the impact of clinical and translational research.