OBJECTIVES/SPECIFIC AIMS: (1) To assess the prevalence of mental health symptomatology (depressive symptoms, anxiety symptoms, PTSD symptoms, and problematic alcohol use) and psychosocial risk factors for mental health disorders (low social support, immigration stress, acculturation, and marital/partner discord), and their association with immigration status, health care access and contextual risk factors in Spanish-speaking parents of young children (ages 0–5) who attended a well-child visit. (2) To explore acceptability of screening for and discussing parental distress in the pediatric primary care setting, and parental acceptability of a group well-visit format to address both psychosocial risk factors and mental health symptoms in this population. METHODS/STUDY POPULATION: Latino immigrant parents (n=100) of children ages 0–5 attending well-child visits at Johns Hopkins Bayview Children’s Medical Practice were surveyed between October 2015 and February 2016. The verbally administered survey included the Woman Abuse Screening Tool (WAST), AUDIT-C, Primary Care Post-Traumatic Stress Disorder (PC-PTSD) Screener, California Health Interview Survey (CHIS), National Latino and Asian American Study (NLAAS), Appraisal Support Subscale from Interpersonal Support Evaluation List (ISEL), Personal Health Questionnaire Depression Scale (PHQ-8), and Generalized Anxiety Disorder Scale (GAD-2). These questionnaires have been used in large regional or national surveys and most have been validated with US Latino populations. Positive screens were defined as PHQ-8>5 (mild depression or greater), GAD-2>3, AUDIT-C>3 for women and >4 for men, and PC-PTSD>3. Descriptive information and comparisons were obtained by χ2 and Student t-test. Study protocol will allow review of childrens’ pediatric records (n=100). From this sample, parents were separately recruited to participate in in-depth interviews (n=11 of 20 planned have been completed) further exploring both sources of parental distress, acceptability of screening for parental mental health symptoms in the primary care pediatric setting, and acceptability of a potential group-based well-visit model in the pediatric setting. RESULTS/ANTICIPATED RESULTS: Survey participants were 93.0% women, and predominantly<35 years of age. The vast majority (94.0%) were undocumented, recently arrived (<15 years ago) and reported poor or very poor English proficiency (75.0%). Most (84.7%) reported living with a partner or spouse (84.7%), and 58% reported partner relationship strain. In all, 71% reported poor social support. The prevalence of “screen positive” mental health symptoms was highest for depression (55%) and PTSD (35%), followed by anxiety (29%) and alcohol risk use (25%). Having depression was significantly higher (68.4%) (p<0.02) in participants with less education (<6 grade). Partner relationship strain was associated with a higher prevalence of depressive symptoms (59.3%) (p<0.03). Immigration stress (feeling guilty for leaving family and friends) was also significantly associated with depressive symptoms (58.1%) and PTSD (43.5%) (p<0.03). More than half of the participants (60.0%) with depression were not covered by any health insurance and 56.3% of those with depression reported not having been seen by a health care provider in the past 12 months. A high prevalence of symptoms was found in those with poor appraised social support: alcohol risk use (76.0%), depression (69.1%), anxiety (69.0%), and PTSD (68.6%). Among participants, those aged<30 years old and those with more children reported poorer appraised social support. Data from child medical records (including BMI, presence of feeding problems, referrals for social work, or mental health services) has been extracted but not yet linked to parent survey or interview results. Preliminary review of In Depth Interviews suggests that the most common reported source of stress among participants was related to finances, followed by documentation/legal status difficulties, access to childcare, and limited English proficiency. Some mothers also mentioned interpersonal violence and lack of access to healthcare as stressors. All mothers expressed an interest in a pediatric primary care based parent focused the majority of which indicated that a group based intervention would be acceptable, some mothers indicated they preferred a one-to-one intervention if mental health were to be discussed. Mothers seem preferential to social worker-led interventions compared with pediatrician-led, but most mothers were indifferent. Finally, mothers expressed low support from the Latino community in Baltimore. DISCUSSION/SIGNIFICANCE OF IMPACT: Results from this study suggest that this population of parents is experiencing a relatively high rate of mental health symptoms, low perceived social support, and limited access to their own source of care. This suggests that an intervention delivered within a primary care pediatric setting would have the potential to reach parents who might not otherwise interact with their own providers, and that there are an array of problems that could be targeted. Intervening with parents of young children has the potential to affect multiple child outcomes. A group intervention may target poor social support, though this format is not universally preferred. Next steps for this project include assessing the acceptability of and preference for various content components (ie, depression, parenting stress, legal issues) and linking parent data with child data (including developmental screening results, weight, feeding problems, and behavior problems).

ABSTRACT IMPACT: A robust and collaborative network of expertise and services is essential for successful research commercialization, including timely and scalable educational support for CTSA institutions and individual faculty investigators with biomedical innovations. OBJECTIVES/GOALS: Leverage expertise at the University of Michigan (UM) by creating collaborative and scalable interactive online courses to instruct and prepare internal and external faculty to navigate critical stages of life science academic research commercialization. METHODS/STUDY POPULATION: UM’s Fast Forward Medical Innovation created two online courses with the UM Office of Technology Transfer and the Michigan Institute for Clinical & Health Research (MICHR). Collaborative planning committees, with content and educational experts, set course goals and learning objectives based on audience needs (e.g. preparation for consultations, commercialization concepts, etc.). Draft content was developed, peer reviewed, and revised before Articulate Storyline was used to convert didactic content to active learning content (e.g. interactive slides, scenarios, quizzes, and forms). Pilot testing was conducted prior to the launch to faculty investigators throughout the UM network. RESULTS/ANTICIPATED RESULTS: Intellectual Property in the Academic Setting launched via the FFMI website and newsletter in July 2020 and has had 66 learners to date. Medical Device Regulations launched in October 2020 and has 22 learners. OTT and MICHR have successfully integrated the courses into their consultation process by requesting review from faculty investigators. We suspect that this will lead to more in-depth and meaningful conversation. Additionally, these courses have been integrated into an FFMI commercialization course to instruct on critical concepts. Evaluation and refinement for both use cases will ensue, as well as inform future collaborative courses. DISCUSSION/SIGNIFICANCE OF FINDINGS: Early results suggest that the courses are advantageous and can serve as a model for future collaborations. The opportunity to disseminate the courses across the CTSA network, as well as collaborate with other institutions, to scale localized expertise to a broader network is promising.

ABSTRACT IMPACT: Implementation of digital and mobile applications in clinical research crisis response protocols can mitigate their impact on clinical research. OBJECTIVES/GOALS: Crisis management is fundamental to ensuring the protection of human subjects during a clinical trial. Mobile apps have the capacity to allow for quick access to crisis response plans and can serve to mitigate their impact on clinical research. Electronic data capture tools can be used to create digital applications for such a response. METHODS/STUDY POPULATION: The Clinical Research Center at Rutgers University transferred a paper-based crisis management response plan to a digital mobile application format using Vanderbuilt’s Research Electronic Data Capture Tool (REDCap). REDCap’s branching logic allowed for programming a decision support functionality to guide users through 3 specific crises. (1) threatening or aggressive study subject behavior; (2) clinical research center break in or theft; and (3) adverse event observed for ongoing or closed clinical research study. Applicable U.S. Code of Federal Regulations, IRB guidelines, institutional policies and procedures were also used as a component of the mobile development. RESULTS/ANTICIPATED RESULTS: The Crisis Management Decision-Support Portal within the Clinical Research Center has an interactive structure. The use of branching logic demonstrates the ability for users to answer each question and be guided to appropriate responses specific to selected criteria related to each event. The tool contains a self-correct function by providing a reset option after answering each section. The portal itself can be accessed using any computer or cellphone with an internet connection. It provides the users with appropriate criteria to determine to exact communication and management protocols for reporting for the crisis event they are witnessing. As users access the portal, usage data can be collected, tracked, and stored. DISCUSSION/SIGNIFICANCE OF FINDINGS: The REDCap platform offers the opportunity to digitize crisis management protocols that ensure professionals have easy access to appropriate responses to crises at the center. The use a digital application rather than paper allows for a CTSA sponsored hub to mitigate damage, simply build new protocols, modify existing protocols, and track usage.

The Common Metrics Initiative aims to develop and field metrics to improve research processes within the national Clinical and Translational Science Award (CTSA) Consortium. A Median Accrual Ratio (MAR) common metric was developed to assess the results of efforts to increase subject accrual into a set of clinical trials within the expected time period. A pilot test of the MAR was undertaken at Tufts Clinical and Translational Science Institute (CTSI) with eight CTSA Consortium hubs. Post-pilot interviews were conducted with 9 CTSA Principal Investigators (PIs) and 23 pilot team members. Over three-quarters (78%) of respondents reported that the MAR could be useful for performance improvement, but also described limitations or concerns. The most commonly cited barrier to MAR use for performance improvement was difficulty in interpreting the single value that is produced. Most respondents were interested in using the MAR to assess recruitment at an individual trial level. Majority of respondents (63%) had mixed opinions about aggregating metric results across the CTSA Consortium for comparison or benchmarking. Collecting data about additional contextual factors, and comparing accrual between subgroups, were cited as potentially helping address concerns about aggregation. Significant challenges remain in ensuring that the MAR can be sufficiently useful for collaborative process improvement. We offer recommendations to potentially improve metric usefulness.

OBJECTIVES/SPECIFIC AIMS: Women with GDM have a 7-fold higher risk of developing T2DM, and rates of GDM are higher among racial and ethnic minorities and women of lower socio-economic status. There are no data on postpartum diabetes screening after the first postpartum year or among women receiving care in FQHCs. We aim to address this gap in the literature by (1) defining the rates of follow-up screening for T2DM at 6–12 weeks and 1–3 years postpartum and (2) characterizing patient, provider, and healthcare system attributes that are associated with lack of follow-up screening for T2DM in a population of low-income women with GDM. METHODS/STUDY POPULATION: This is a retrospective cohort study of women with GDM during pregnancy receiving care in Missouri FQHCs from 2010 to 2015. Electronic health records (EHR) data from 26 FQHCs is housed in a central repository through the Missouri Primary Care Association (MPCA). This includes patient demographic, lab, and medication information as well as encounter level patient and provider data for the prenatal and postpartum period. EHR data does not include accurate delivery information, however. Pregnancies during the study time frame were identified using CPT and ICD9/10 codes. Deidentified data on individuals with a pregnancy was utilized to identify a subpopulation of “GDM candidates,” using a broad definition of glucose abnormalities as follows: ICD-9/ICD-10 codes for diabetes, medications and testing supplies used for diabetes, infant birth weight ≥4000 g or 8 lb or 13 oz, or abnormal glucose labs [defined as fasting glucose≥95, gestational glucose screen≥130, 1 h test≥130 (or ≥180 if 2 h test and 3 h test recorded on same day), 2 h test≥155, 3 h test≥140, A1C≥6, any glucose≥130, or any positive urine glucose]. This subpopulation was then linked to Medicaid administrative claims data [housed at the University of Missouri Office of Social and Economic Development Analysis (OSEDA)], providing detailed information on delivery, to further characterize patients with GDM in the time frame and provide all dates necessary to classify pregnancy and postpartum periods. RESULTS/ANTICIPATED RESULTS: From the de-identified pregnancy data set including 45,810 individuals, we identified 8008 “GDM candidates.” EHR data were linked to Medicaid claims data for these individuals from 2010 to 2015. Utilizing the enhanced data set, we are defining a pregnancy for each individual by the delivery date in the Medicaid record and an algorithm using lab and ultrasound record dates to define gestational age at delivery. This will result in a pregnancy level data set linked with individual encrypted identifiers with each record representing 1 pregnancy and postpartum period. GDM in pregnancy will be defined as having a baby with birth weight≥4000 g or 8 lb or 13 oz, ICD-9 or ICD-10 code for GDM during pregnancy or at delivery, or an oral glucose tolerance test (oGTT) 12–16 weeks before delivery with 2 or more abnormal results by Carpenter and Coustan criteria. We anticipate that our final GDM data set will include 2000–3000 individuals. We will then calculate the percentage of individuals receiving recommended screening tests at 6–12 weeks (fasting glucose or 2 h oGTT) and 1–3 years postpartum (fasting glucose, 2 h oGTT, HbA1C). We will use multivariable regression techniques to identify risk factors for lack of screening. We will be able to incorporate predictors not previously evaluated including distance from home to health center, access to public transport, specialty and training of the patient’s providers, pregnancy weight gain, postpartum appointment time of day, and number of various types of office visits. DISCUSSION/SIGNIFICANCE OF IMPACT: The creation of a linked data set of pregnancies complicated by GDM in women receiving care in FQHCs in Missouri is the first step toward better characterizing follow-up diabetes screening rates in this population and understanding patient, provider, and healthcare system variables that affect postpartum screening. The ultimate goal is to translate evidence-based patient-centered sustainable interventions into practice for low-income women with a history of GDM and improve population outcomes with the ability to track progress prospectively over time.

Acknowledgements: The authors thank Susan Wilson (MPCA), Jill Lucht, and Bhawani Mishra (OSEDA).

OBJECTIVES/SPECIFIC AIMS: Our objective is to create a Resistant Hypertension (RHTN) computable phenotype from electronic health record (EHR)-based data, and to determine the characteristics associated with RHTN within a large, diverse, EHR-based database. METHODS/STUDY POPULATION: The OneFlorida Clinical Research Consortium includes 10 unique health care systems providing care for approximately half of the state (48%, ~10 million). OneFlorida houses a Data Trust which contains longitudinal EHR data and claims data from these providers in a common format, the PCORnet common data model v3.0. For the current project, data from 5 health care systems were considered. All of the adult hypertension (HTN) patients with a HTN diagnosis from an outpatient encounter were extracted from the OneFlorida Data Trust. Additional data such as demographics, prescribing, and vitals information were also extracted. The RHTN computable phenotype was created by constructing a drug exposure variable that took into consideration the number of antihypertensive medications an individual was prescribed at any point in time over the course of the OneFlorida dataset. RHTN was defined as any blood pressure requiring four or more antihypertensive drugs, or uncontrolled blood pressure (≥140/90) on 3 antihypertensive drugs. RHTN cases had to meet the definition criteria twice during the data period, at least 30 days apart. All data extraction, computation phenotype coding, and statistical analyses were conducted using SQL or SAS. RESULTS/ANTICIPATED RESULTS: Our preliminary results show that there were n=342,026 adults with a HTN diagnosis from an outpatient visit in the data set. After the RHTN computable phenotype was constructed, n=11,670 RHTN cases were identified from the n=130,901 HTN individuals with all of the required variables in the data set (8.9% RHTN prevalence). In all, 55% of RHTN cases were Black or African American, compared with the total HTN population (25% Black/African American). RHTN cases also had more prescriptions for loop diuretics, centrally acting agents, α-blockers, and vasodilators compared with the total HTN population. Not surprisingly, the RHTN cases had 26% of the antihypertensive prescriptions in the data set, and the RHTN cases had fewer blood pressure readings that were in control (only 49.4% of readings <140/90). DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, our preliminary data shows that it is possible to create the very complicated computable phenotype of RHTN within the OneFlorida Data Trust. We found that the RHTN prevalence in OneFlorida is 8.9% which is consistent with previous studies from NHANES. Although promising, these results require further validation of the computable phenotype and replication in other similar data sets in order to ascertain their true meaning. Once validated, the experience gained from this computable phenotype can be applied to many other phenotypes.

OBJECTIVES/GOALS: Our goal is to determine the structure of the CACHE domain of the Vibrio cholerae quorum sensing receptor CqsR as well as its autoinducer (AI). We are performing X-ray crystallography on the protein in its apo form, with the fractions containing the AI, and with known ligand ethanolamine (ETA). METHODS/STUDY POPULATION: We have transformed BL21(DE3) E. coli cells with a pTB146 vector to contain the gene for the CqsR CACHE domain. We grow these cells to high optical density and induce protein expression, at which point we harvest them and purify the protein. This entails lysing the cells, separating the protein with Ni-NTA resin, cleaving our protein tag, and column chromatography. With purified protein, high-throughput screens are set up to find crystallization conditions of apo CqsR, CqsR-ETA, and CqsR-AI. We then determine conditions that best lead to crystal formation and optimize them. Crystals are then diffracted with X-rays, process the data, and determine the structure of protein and AI. RESULTS/ANTICIPATED RESULTS: We anticipate finding the structure of the CqsR CACHE domain to a high resolution in addition to the identity of its autoinducer. Previous results found that the structure is homologous to another V. cholerae chemoreceptor, Mlp37, and we expect the results from this project to confirm this. In addition, we know that the autoinducer weighs approximately 62 daltons, the same as the known ligand, ethanolamine. Given that CACHE domains bind specifically to their ligands, we anticipate that the autoinducer will be structurally similar to ethanolamine. DISCUSSION/SIGNIFICANCE: The results will reveal the structure of the CqsR CACHE domain and its autoinducer. This knowledge will better allow researchers to treat cholera, as both autoinducer identity and receptor conformational changes will be uncovered, allowing for drug development to inhibit cell growth.

OBJECTIVES/SPECIFIC AIMS: Recent advances in microneedle technology have enabled practical, in vivo dermal interstitial fluid (ISF) sampling. These minimally-invasive techniques allow for collection of ISF without damage to adjacent tissues and do not rely on blister formation. Initial reports of extracellular vesicle (EV) isolation from dermal ISF and paired blood samples suggest that EVs may be more abundant in ISF. Analysis of ISF-derived EVs may allow for more detailed study of intercellular communication at the tissue level, particularly in acute inflammatory conditions. The objective of this study is to describe the isolation and initial characterization of interstitial fluid-derived exosomes. METHODS/STUDY POPULATION: We apply electron microscopy, nanoparticle tracking analysis (NTA), immuochemical, and sequencing methods to describe and distinguish the EV content of interstitial fluid. We include apparently healthy adult human subjects with no active skin disease. We also study immunocompetent, CD-hairless rats to demonstrate the generalizability of the methods. RESULTS/ANTICIPATED RESULTS: We successfully isolated EVs from human and rat interstitial fluid using commercially available precipitation methods. The EVs were initially characterized using UV/Vis spectroscopy, electron microscopy, and NTA. While the study is ongoing, initial results suggest that the concentration and size distribution of EVs differs significantly between blood fractions and ISF. Further immunochemical and sequencing characterization is ongoing. DISCUSSION/SIGNIFICANCE OF IMPACT: We present here the initial characterization of EVs isolated from dermal interstitial fluid. This appears to be the first report of EV characterization using ISF collection methods that do not perturb adjacent tissues (such as with blister or microdialysis methods). The present study lays a foundation for further examination of ISF-derived EVs in acute inflammatory disease such as cellulitis or infectious neuritis. This may enable minimally invasive diagnostics and new research tools to understand intercellular communication in living organisms with increased spatial and temporal resolution.

OBJECTIVES/GOALS: Coordinating research studies is multifaceted and requires a foundational level of research knowledge, skills and abilities in order to contribute to high-quality, ethical research projects that adhere to local and federal regulations as well as Good Clinical Practice. Oftentimes, coordinators who are new to research or new to an institution have trouble navigating the research landscape. Departments within the University of Minnesota have limited resources to devote to developing robust training programs above and beyond protocol or department-specific training. Therefore, UMN’s CTSI created a comprehensive training and support program for research professionals at the University of Minnesota. METHODS/STUDY POPULATION: CTSI employs several strategies to provide a comprehensive training program for the University of Minnesota Research Workforce. The offerings are based on the The Joint Task Force for Clinical Trial Competency (JTF). In addition to training programs, valuable resources, materials, and connections are provided to trainees.

• An Onboarding process for new coordinators that includes a welcome email upon hire that provides resources as well an opportunity to meet face-to-face to get their questions answered about where to start with research training.

• Foundations for Research professionals, two week (20 hour) training program, provides a foundational level of knowledge to new coordinators via in-person and online training modules.

• Informed Consent 1 & 2 provides in-person training on the informed consent including the process, documentation, and ethical issues around consenting vulnerable populations.

• Over 40 on-line research training modules that coordinators can take at anytime.

• An active list serv that connects >600 research professionals with training updates and opportunities.

• Bi-weekly seminar series that provides a forum to share current regulations, best practices, resources, and guidelines pertaining to clinical research at the University.

• An online training “Roadmap” tool that customizes individual research training plans, and includes an inventory of training available.

RESULTS/ANTICIPATED RESULTS:

• 218 research professionals participated in our Foundations blended training program with 191 completing (88% completion rate) the entire training. A comprehensive assessment based on national competencies is completed by all participants at Baseline and Post training. Baseline scores average at 75% and Post scores average at 82% (7% increase). Satisfaction is measured and participants are overall satisfied with the training, 4 out of 5 on a Likert Scale.

• 353 research professionals have participated in our Informed Consent Session 1 & 2 in-person training. Satisfaction is measured and participants are overall satisfied with the training, 4.5 out of 5 on a Likert Scale.

• Over 190 research professionals have utilized our research on-line training modules.

• Training participants have been from 27 different departments across the University.

• The Clinical Research Professional Development Seminar Series has offered over 87 seminars with 4907 total attendees. These seminars are offered in-person and live stream.

DISCUSSION/SIGNIFICANCE OF IMPACT: Establishing a comprehensive training program at the University has streamlined the training that research professionals receive across departments. It also ensures that all coordinators have access to research training, a network of other research professionals, resources, and continuing education opportunities.

OBJECTIVES/GOALS: Severe malarial anemia due to Plasmodium falciparum is often accompanied by thrombocytopenia. Treatment includes transfusion of whole blood, which contains erythrocytes, platelets, and other blood components. The objective of the study was to assess the effect of whole blood transfusion on survival in children with severe falciparum malaria and to examine the potential interaction of thrombocytopenia with malaria mortality and transfusion response. METHODS/STUDY POPULATION: We analyzed a retrospective cohort of 842 hospitalized children in Zambia with severe malarial anemia (703 transfused, 139 not transfused due to stock-out or other reason). Severe malarial anemia was defined as a positive rapid diagnostic test or blood smear in combination with an admission hemoglobin concentration ≤5 g/dL. RESULTS/ANTICIPATED RESULTS: Mortality was 13% (94/703) in the transfused group and 24% (34/139) in the non-transfused group. Kaplan-Meier survival estimates stratified by transfusion status and thrombocytopenia (150,000/μL threshold) showed increased mortality in children with thrombocytopenia who did not undergo transfusion, with no differences in mortality among the other transfused and non-transfused groups (log-rank test P = 0.0001). Effect modification analysis by Cox proportional hazards regression adjusted for age, sex, hemoglobin concentration, blood group type, and eosinophilia showed a significant interaction between platelet count and transfusion status (P = 0.028). Children with thrombocytopenia who were transfused and died had little or no post-transfusion increase in platelets, in contrast to those who survived. Freshness of transfused whole blood, construed from expiration dates, correlated with greater platelet recovery and improved survival. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of platelets in malaria pathophysiology is complex and incompletely understood; prior studies describe preferential binding of platelets to parasitized erythrocytes and direct parasitocidal activity, whereas others detailed deleterious effects in malaria involving the central nervous system vasculature. These findings point to a potential clinical role for platelet-directed transfusion strategies to improve survival in children with severe falciparum malaria, which should be further assessed in randomized interventional studies.

OBJECTIVES/GOALS: The New Jersey Alliance for Clinical & Translational Science conducted an observational study of current clinical research training to establish a comprehensive infrastructure. The goal was to develop a cross training catalogue of available resources for trainees to fill gaps in their Clinical Research training. METHODS/STUDY POPULATION: The focus of this observational study is the evaluation of (1) available clinical research training programs, (2) training areas aligned with the Joint Task Force competency domains, (3) specific target audiences who utilize trainings offered nationally, and (4) availability of resource toolboxes. This assessment was extracted by clicking on each of the hubs Education & Training and Resources tabs. The determination of the training areas and competency skills that aligned with the JTFs eight domains was confirmed by reviewing the course description on each website. RESULTS/ANTICIPATED RESULTS: CTSA hub website analysis of each hub revealed that each CTSA hub region has their own regional focus on training areas targeted for specific audiences. The validation of the NJ ACTS Education and Offering Inventory study allowed authors to categorize available training programs which significantly showed that Basic Training Programs targeted 22% of Undergraduate Students, Community Engagement Training Programs targeted 15% of Early Career Faculty, Experiential Training targeted 20% of Early Career Faculty and Undergraduate Students, Scholarly & Certificate Training targeted 20.5% of Graduate Students, and Graduate/Post Graduate Programs targeted 22.5% of Graduate Students and KL2 scholars. DISCUSSION/SIGNIFICANCE: This information helps build the infrastructure of a National Cross-Training Resource Platform in aid to encourage trainees to take advantage of available trainings across the CTSA Consortium.

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/SPECIFIC AIMS: Our aim is to test whether osteocyte-specific CXCL12 expression is critical to exercise-driven bone formation. METHODS/STUDY POPULATION: All procedures were approved by the NEW YORK UNIVERSITY Institutional Animal Care and Use Committee. We generated male and female mice in which CXCL12 was deleted from OCYs (CXCL12ΔOCY) by crossing CXCL12 floxed mice and 10kb DMP1-Cre transgenic mice (gifts from Drs. Geoffrey Gurtner and Lynda Bonewald, respectively). The 10kb DMP1-Cre has been shown to be robustly expressed in odontoblasts and OCYs, with little to no activity in cells from non-mineralized tissues (Lu+ J Dent Res 2007). Growing male and female mice (n=3-8/group) were given fluorochrome labels every two weeks between 4-16 weeks of age, to monitor the role of CXCL12 during development. A second group, of adult 16-week-old mice (n=5/group), were subjected to tibial axial cyclic loading (1200µɛ, 2Hz, 120cycles, 3days/wk for 2 wks) (Liu+ Bone 2018). Basal and load-induced periosteal (Ps) and endosteal (Es) mineralizing surface (MS/BS, %), mineral apposition (MAR, µm/day) and bone formation rates (BFR/BS, µm3/µm2/year) were calculated (Dempster+ JBMR.2013) at mid-length. RESULTS/ANTICIPATED RESULTS: No significant differences were detected in basal bone formation during development. However, relative load-induced Ps MAR (rMAR) was reduced by 50% in female (p=0.02) and 75% in male (p=0.002) CXCL12ΔOCY mice; and similarly, Ps rBFR/BS was reduced by 50% in female (p=0.01) and 70% in male (p=0.001) CXCL12ΔOCY mice (Figure 1). Es bone formation was not affected by CXCL12 deletion. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, osteocyte-specific CXCL12 expression plays a critical role in exercise-driven periosteal new bone formation, suggesting that CXCL12 signaling may positively regulate osteogenic differentiation and/or mature osteoblast function. Further underlying mechanisms are currently being explored. Thus, osteocyte-specific CXCL12 signaling may be a promising target to enhance load-induced bone formation in patients with compromised ability to form new bone.