OBJECTIVES/SPECIFIC AIMS: To explore the racial differences in rotational thromboelastometry findings using whole blood and plasma samples from healthy volunteers. METHODS/STUDY POPULATION: We studied a cohort of patients at Tulane University Hospitals who came into the pre-op clinic to get blood drawn for labs. The cohort included a total of 44 patients who were otherwise healthy adult volunteers with no history of cardiovascular nor thromboembolic events, 30 African Americans and 14 Caucasians. Patients who required lab work for their upcoming surgery were asked to participate in the study by giving a sample of blood collecting in a light blue-top sodium citrate tube. We excluded patients who were currently on any anticoagulation or antiplatelet medications. We also excluded those with current or previous history of cancer, those with known bleeding disorder, and those who were on chronic transfusion protocol, or had received a blood transfusion within the last 21 days. Data collection was carried out after informed consent was obtained; we collected citrated whole-blood (WB) samples. WB samples were processed within 3 hours of phlebotomy. Platelet free plasma, obtained after centrifugation at 2500 cGy of whole blood for 20 minutes, was kept frozen at −70°C. Frozen plasma was thawed at 37°C for 5 minutes before testing. Samples were recalcified with star-tem reagent, and then the in-tem reagent was added. The latter contains an optimized concentration of ellagic acid and partial thromboplastin phospholipid from rabbit brain. Thromboelastometry (ROTEM) parameters including clotting time, clot formation time, alpha angle, maximum clot firmness, and Lysis Index after 30 and 45 minutes were determined. Data was then retrieved from the ROTEM database and put into an Excel sheet to be analyzed. RESULTS/ANTICIPATED RESULTS: Our results showed that the CFT was higher in both the plasma and the WB of Caucasians when compared with African Americans with a difference between means 137.5±233.7 (p=0.56) and 11±7.85 (p=0.168), respectively; while MCF was increased in the WB and plasma of AA with a difference between means of 1.719±1.974 (p=0.38) and 5.37±2.49 (p=0.037), respectively. In other words, the plasma of Caucasians did seem to take longer to reach the maximum firmness (however not statistically significant p>0.05), while the maximum clot firmness was significantly higher in plasma of AA. In summary and compatibly with the previously published data, our results showed significantly increased prothrombotic profile in the plasma of African Americans when compared with Caucasians. DISCUSSION/SIGNIFICANCE OF IMPACT: This reinforces the role of the whole vascular system and the interaction between its different components in the pathophysiology of thromboembolic events. In one case control study, African ethnicity was associated with increased risk of DVT in parallel with significantly increased peak thrombin on thrombin generation when compared with Caucasians. With our preliminary results, we confirm these data using another tool for the assessment of the plasma in addition to comparing WB samples too. More prospective studies, with higher number of subjects evaluating the value of the results in predicting the risk of development of thromboembolic events in different ethnicities, are needed for better understanding of this disease. In addition, thromboelastometry might require adjustment for ethnicity in studies evaluating ethnically diverse populations.

OBJECTIVES/SPECIFIC AIMS: To identify brain regions with the highest and least variable rate of multiple sclerosis (MS)-specific atrophy using an agnostic approach, and to perform simulation-based sample size calculations for Phase II s using these regions as primary endpoint. METHODS/STUDY POPULATION: In total, 601 subjects (2638 MRI scans) were analyzed; 520 subjects with relapsing forms of MS across the spectrum of disease severity and duration were followed in a single-center prospective cohort study at an academic MS Center between 2005 and 2010 with annual 3 T MRIs and clinical visits for 5 years, including standardized 1 mm3 3D T1-weighted images (3DT1s; 2483 MRIs). Separately, a convenience sample of 81 healthy controls (HC) was recruited from the same center and scanned longitudinally using the same MRI scanner and protocol (155 MRIs). 3DT1s were processed using FreeSurfer’s longitudinal pipeline (software version 5.3). Rates of change in all cortical and subcortical regions (n=119 brain regions) were estimated in MS patients and HC with linear mixed effects models. An effect size was calculated for each region as the difference in change over time between MS patients and HC divided by the standard error of the difference [d=β(MS×time)/SE β(MS×time)]. Regions were ranked according to absolute effect size, and the top regions were chosen for simulation-based sample size calculations to estimate the number of subjects needed to achieve 80% power to detect a slowing of MS atrophy down to normal aging, assuming significance levels of 5% and 10%. Ten percent was included because some have advocated for a more relaxed alpha in Phase II s. RESULTS/ANTICIPATED RESULTS: Four regions (putamen, subcortical grey matter, caudate, and thalamus) yielded the smallest sample sizes. At 80% power, ~50 subjects per arm would be needed with putamen or subcortical grey matter volume, or ~80–85 subjects per arm with caudate or thalamic volume as primary endpoint. For the remaining regions, >140 subjects per arm would be needed. A 20%–30% increase in sample size was observed when α=5% was used. DISCUSSION/SIGNIFICANCE OF IMPACT: Using an agnostic approach considering all brain regions and simulation-based sample size calculations specifically designed for longitudinal studies, putaminal, subcortical grey, caudate, and thalamic volumes are sensitive to change over time and yield feasible sample sizes for Phase II studies in MS. Because the effect size estimates incorporate normal aging, these regions represent the most sensitive outcomes for testing therapeutic interventions that target irreversible, MS-specific brain atrophy. The clinical relevance of these regions is our next focus to help inform which of these regions should be favored as primary endpoint.

OBJECTIVES/GOALS: To address investigator frustration and appropriate oversight for student interns performing clinical research activities, we created infrastructure to support matchmaking with clinical research teams and onboarding of student interns, thereby allowing for more meaningful internship experiences with access to clinical research systems. METHODS/STUDY POPULATION: Internship requests may be initiated by a student, an affiliated institution, or an investigator. Requests are triaged accordingly. Affiliation agreements define the parameters for these placements. Unaffiliated institutions may request an agreement by contacting CRISP; otherwise, unaffiliated interns will be classified as visiting scholars with restricted access. If a student is from an affiliated institution, the Clinical Research Internship Portal (CRISP) is used to collect and track information regarding the internship. CRISP provides: Matchmaking for student interns with placements Compilation of onboarding documentation Tools (e.g., learning agreements) for student intern supervisors Professional development workshop series for all student interns RESULTS/ANTICIPATED RESULTS: Launched in 2021, CRISP is a relative newcomer to the Duke research training landscape, but preliminary impact may be measured by the following metrics: Affiliated institutions: 8 agreements in place, 4 pending 25 student interns from 7 institutions placed across 11 departments/institutes 7-session professional development series garnering positive feedback from interns and supervisors Improved access to clinical and research systems aligned with clinical research activities Enhanced oversight and tracking of student interns across Duke enterprise Expansion of program to include internal and external student interns CRISP has engaged invested parties within and outside of Duke to ensure robust oversight of these valuable training opportunities and to create new pathways into our workforce. DISCUSSION/SIGNIFICANCE: Streamlining intern placements has lessened pain points related to including students in our research environment, both for investigators and institutional partners. Future plans include expanding the number of affiliation agreements, creating an interface to quickly triage intern requests, and scaling up the professional development series.

OBJECTIVES/SPECIFIC AIMS: The study aims to identify the short and long-term associations of HTPR and presence of CYP2C19 polymorphism in the occurrence of major adverse cardiovascular events (MACE). The primary outcome of the study will be the presence of MACE including stent thrombosis, need for revascularization, acute limb ischemia events, myocardial infarction and death in relation to the presence of HTPR and CYP2C19 polymorphism. Secondary outcomes will include the prevalence of HTPR and CYP2C19 polymorphism in patients with PAD, and association with other medications including aspirin and cilostazol. METHODS/STUDY POPULATION: Patients above 21 years of age with the diagnosis of PAD using clopidogrel therapy for at least for seven days will be recruited at the University of Puerto Rico District Hospital and Cardiovascular Hospital of Puerto Rico and the Caribbean. RESULTS/ANTICIPATED RESULTS: A total of 200 patients from Puertorrican, Dominican and Cuban ethnicity will be expected to be recruited. The most common comorbidities will include, coronary artery disease, hypertension, dyslipidemia, and diabetes mellitus type 2. No significant distr DISCUSSION/SIGNIFICANCE OF IMPACT: The status quo as it pertains to resistance to clopidogrel in PAD patients is to improve antiplatelet resistance using antiplatelet therapy guided by platelet assays in order to reduce MACE occurrence. Although HTPR and presence of CYP2C19 polymorphisms have been studied on the PAD population, currently there is no gold standard test for measuring antiplatelet resistance. In that regard, this study will expect to identify the contribution that HTPR and CYP2C19 polymorphism might have on MACE in patients with PAD. In this way, the results will allow identification of abnormality parameters in HTPR and CYP2C19 testing in relation to the impact on risk of having MACE. Once the association of these variables with MACE is established, testing for clopidogrel resistance could become a potential strategy to optimize antiplatelet therapy and reduce the impact that MACE have in this population.

OBJECTIVES/GOALS: To determine predictors of mortality in non-severe hemophilia A (NSHA) patients. METHODS/STUDY POPULATION: The ATHNdataset was used to identify NSHA patients who have authorized the sharing of their demographic and clinical information for research. Factors examined included race, ethnicity, hemophilia severity, Hepatitis B, Hepatitis C and HIV infections. A mortality rate was calculated for each factors examined. The relative risk of death between patients in different categories of the factors was assessed by using the ratio of these mortality rates. To adjust for the effects of all of the studied factors with mortality, a multivariate analysis was performed using logistic regression. All hypothesis testing was two-tailed, with a significance level of .05. RESULTS/ANTICIPATED RESULTS: A total of 6,606 NSHA patients were followed for an average of 8.5 years. During 56,064 person years of observation, 136 (2.1%) NSHA patients died; 20% of deaths were malignancy-related. Mortality rates were similar across racial group. Hispanic patients were 60% less likely to die than non-Hispanic patients (p = 0.006). Patients with Hepatitis C infection and HIV infection were 7 times as likely to die compared to those without infections (p<0.001). After adjusting for the effects of all examined factors in a multivariate analysis, patients with hepatitis C and HIV infection remain significantly associated with increased mortality at 6.1 times and 3.6 times the risk, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite significant improvement in the therapeutic approaches for infectious diseases, Hepatitis C and HIV infections remain strong predictors of mortality in this NSHA cohort. CONFLICT OF INTEREST DESCRIPTION: N/A.

ABSTRACT IMPACT: My work evaluates the impact of electronic data capture/eSource on several aspects of clinical trial efficiency and scale, aiming to demonstrate how eSource can be used to improve the way we run clinical trials. OBJECTIVES/GOALS: Using eSource may increase the efficiency of data collection in clinical trials. However, adoption of eSource has been slow. We reviewed over 100 large multinational clinical trials to analyze how eSource use correlated with trial size, sponsor collaborations, time to complete, and time to publication. METHODS/STUDY POPULATION: We searched ClinicalTrials.gov for completed, interventional, Stage II-IV clinical trials with posted results and an uploaded study protocol document. This produced 3,962 trials. We identified all studies with over 1,200 participants and sites in multiple countries (or at least 100 sites in one country). After eliminating ten studies with duplicate protocols, we had a database of 123 trials. From the ClinicalTrials.gov listing, the study protocol, and any published papers, we determined the start, end, and publication dates, data collection protocol, sponsors and collaborators, and any reasons given for delays for each trial. We performed statistical tests comparing trial delay, participant and country count, and collaboration status (yes or no) between the two groups (eSource users and non-eSource users). RESULTS/ANTICIPATED RESULTS: Of our 123 trials, 60 (48.7%) used eSource, 48 (39.1%) used paper source documentation, and 15 (12.2%) used some combination. We found no statistically significant difference between eSource and non-eSource trials in terms of trial delay (p=0.43), time to publish (p=0.33), collaboration status (p=0.54), number of participants (p=0.36), or number of countries (p=0.12). However, our analysis was limited by what data was publically available. To investigate the effects of eSource on site efficiency, data accuracy, and data security, which are three major factors behind the FDA’s 2013 eSource recommendation, we would need access to proprietary information from trial sponsors. DISCUSSION/SIGNIFICANCE OF FINDINGS: The use of eSource in large multinational clinical trials is not correlated with a change in time to completion or publication nor a higher number of participants or countries. We aim to acquire proprietary data to further analyze the impacts of eSource on trial efficiency, data accuracy, and data security.

OBJECTIVES/SPECIFIC AIMS: This study applied a syndemic framework to 1) assess whether the concurrence of unhealthy alcohol use, smoking, and depressive symptoms is associated with increased risk for incident CVD among people living with and without HIV and 2) determine whether the association between this syndemic and incident CVD is differential by HIV status. METHODS/STUDY POPULATION: We evaluated 5731 participants (50.3% HIV+) without baseline CVD from the Veterans Aging Cohort Study, a prospective, observational cohort of PLWH and matched uninfected veterans enrolled in 2002 and followed through 2015. We assessed baseline number of conditions (syndemic score: 0-3; unhealthy alcohol use (>14 drinks per week for men [women] or 5 or more drinks in one occasion for men [women]), cigarette smoking (former/current), and depressive symptoms (Patient Health Questionnaire-9 score ≥ 10) and incident CVD through 14 years. Clinical ICD-9 codes identified incident cases of CVD (acute myocardial infarction, heart failure, revascularization, and stroke). We constructed age-adjusted survival curves and CVD rates. Multivariable Cox proportional hazards regressions estimated the hazard ratio (HR) and 95% confidence intervals (CI) of the syndemic score on incident CVD by HIV status, adjusting for baseline demographic, health status, and HIV-related factors. RESULTS/ANTICIPATED RESULTS: Under 10% of all veterans had zero conditions; 25.8% had one; 49.6% had two, and 14.3% had all three. Based on the prevalence of each individual condition in the cohort (unhealthy drinking: 41.5%, cigarette smoking: 75.0%, and depressive symptoms: 21.3%), the observed prevalence of all three conditions was more than double that expected by chance (6.6%). There were 835 cases of incident CVD (50.4% HIV+) during the median follow-up (10.6 years). Overall, age-adjusted incidence rates/1000 person-years increased with greater number of conditions (zero 10.1, one 12.5, two 15.8, three 19.6). Compared to uninfected people with zero conditions, the adjusted hazard ratios of incident CVD were similar by HIV status for each number of conditions. DISCUSSION/SIGNIFICANCE OF IMPACT: The syndemic of unhealthy drinking, cigarette smoking, and depressive symptoms is common and associated with high CVD risk. However, this risk was similar by HIV status. Our results underscore the need to screen for and treat these co-occurring conditions.

OBJECTIVES/GOALS: CTSI-RAP is a professional development program that provides undergraduate students with clinical research exposure and training. Students support UCLA research faculty by assisting with all aspects of the research process, including recruiting participants, data management, and presentations. METHODS/STUDY POPULATION: CTSI-RAP onboards a 15-20 volunteer student cohort annually in a competitive application and interview process with less than a 10% acceptance rate. Since the inaugural cohort in 2013, over 160 students have participated. The program engages hundreds of students each year through the recruitment process, campus clinical research events, and student-led conference opportunities. Evaluation surveys developed through REDCap in 2022 sought to assess the program’s impact on undergraduate experiences, professional development, and post-graduate careers. Surveys distributed to investigators and their study teams evaluated the student’s clinical research knowledge and engaged student involvement. RESULTS/ANTICIPATED RESULTS: Based on evaluation surveys, the CTSI-RAP program received excellent reviews from both students and their assigned study teams. 100% of students and faculty would recommend the program to a friend or colleague. 30% of students present or publish annually, indicating a wealth of meaningful contributions made by students. 90% of students go on to attend medical school, health-related graduate school, or other health-related employment. Several students continue working in clinical research through gap-year employment. As demonstrated by the high caliber of student and faculty experiences, CTSI-RAP has created an esteemed and valued symbiotic infrastructure to support clinical research endeavors at UCLA. DISCUSSION/SIGNIFICANCE: Through clinical research career exploration and professional skill-building in undergraduate careers, the CTSI-RAP program produces highly-trained future leaders in the field and benefits the capacity of UCLA research. CTSI-RAP provides a model for similar programs to be funded and implemented in other institutions.

OBJECTIVES/SPECIFIC AIMS: The aim of this study was to assess the ultra-dose Na18F dPET protocol feasibility for skeleton imaging in a canine model with reduced radiation dose and preserved quantitative characteristics. We hypothesized that administering an ultra-low Na18F dose would provide suitable image quality while reducing subject’s exposure to radiation. METHODS/STUDY POPULATION: In total, 13 adult male beagles [weight (kg) mean±SD; 14.3±2.2] were scanned. The dogs were administered 3 different Na18F doses: 3 (standard dose/SD), 1 (low dose/LD), and 0.05 (ultra-low dose/ULD) mCi. Imaging started ≃45 minutes post injection for ≃ 33 minute total acquisition time. Covering the whole body, 11 bed positions, acquiring 120 (3 mCi) and 180 (1, 0.05 mCi) seconds per bed position. All imaging was performed on a digital photon counting system (Philips Vereos, pre-commercial release). PET list mode data were reconstructed using Time-of-flight with 4, 2, and 1 mm3 voxel volumes. Point spread function, and Gaussian filtering were applied. Two experienced blinded readers evaluated image sets overall quality, tissue characterization, and quality of background in the whole body skeleton. Three-dimensional (3D) regions of interest (ROI) were traced over the distal femur, first lumbar vertebra, and a portion of the liver, recording standard uptake values (SUVmax and SUVmean). RESULTS/ANTICIPATED RESULTS: All the scans and reconstructions were successfully completed in all subjects. Decreasing Na18F dose from the standard dose (3 mCi) to the ultra-low dose/ULDO (0.05 mCi), demonstrated acceptable image quality and quantification. Ultra-low dose Na18F SUVmean values for the 3D ROIs reported (mean±SD) 2.6±0.7, 2.5±1.1, 9±1.6, and 0.6±0.3 from the right and left distal femur, first lumbar vertebra, and a portion of the liver, respectively. When compared the SD with the LD and ULD, dPET demonstrated acceptable image quality and definition for qualitative overall assessment. This was also found for the overall quantitative ROI assessment of the healthy canine skeletons. DISCUSSION/SIGNIFICANCE OF IMPACT: Ultra-low dose Na18F at a level of 50 μCi for a 14 kg canine appears to be diagnostically feasible and a robust option to reduce (60-fold) radiotracer doses in a translational animal model using a dPET system. Furthermore, it allows us to move preclinical nuclear medicine imaging forward with substantial reduced exposure levels while preserving image quality. Both visual and quantitative results indicate that the standard-dose bone Na18F dPET can be decreased with a satisfactory diagnostic image quality. Ultra-low Na18F dose is indeed important for younger populations, control patients, and nononcological diseases/conditions. Favorable pharmacokinetics of Na18F (such as high bone uptake, minimal binding to serum proteins, rapid single-pass extraction, and fast clearance from the soft tissues) in addition to the technological capabilities of dPET/CT demonstrated feasibility enabling dose reduction strategies. Ultra-low dose has diagnostic reproducibility and lower radiation burden compared with higher fixed dose techniques in current available guidelines [Society of Nuclear Medicine and Molecular Imaging; SNMMI (5–10 mCi)]. Na18F dPET/CT provides higher sensitivity and diagnostic accuracy, which enables high-quality images with lower tracer activity in this translational animal model. Future research will apply the same methodology to other anatomical targets as well as to the use of different tracers. Preclinical nuclear medicine imaging using ultra-low tracer doses, demonstrated the potential to obtain reasonable quality images and diminishing radiation surveillance in accordance with as low as reasonably achievable tracer levels.

OBJECTIVES/GOALS: Infants of diabetic mothers (IDMs) may exhibit decreased oral intake, requiring nasogastric feedings and prolonged hospitalization. We hypothesize that increased insulin exposure and resulting overgrowth in utero disrupts hypothalamic regulation of food intake, correlates to body composition and impacts feeding in IDMs. METHODS/STUDY POPULATION: Infants born at ≥ 35 weeks gestation to mothers with gestational or type II diabetes (IDM cohort), and normoglycemic mothers (control cohort) were recruited. Infants born to mothers with Type I DM or preeclampsia and with a history of intrauterine growth restriction, opioid exposure, or major congenital anomalies were excluded. Salivary expression of known hunger signaling genes 5AMP-activated protein kinase (AMPK), Neuropeptide Y receptor Y2 (NPY2R), leptin (LEP), ghrelin (GHRL), proopiomelanocortin (POMC), and adiponectin (ADIPOQ) were quantified using RT-qPCR. Body composition was assessed via skinfold measurements and compared and correlated between cohorts. Feeding outcomes were recorded. RESULTS/ANTICIPATED RESULTS: 23 infants were recruited in each cohort. POMC and AMPK were expressed by 71% and 88% of infants respectively in both cohorts. NPY2R was expressed by 79% and 83% of the diabetic cohort and normoglycemia cohort respectively, while GHRL was expressed by 75% and 79% of the diabetic cohort and normoglycemia cohort, respectively. LEP and ADIPOQ were not reliably expressed in either cohort. Infants with a higher body fat percentage were less likely to express NPY2R (OR= 0.76). There was no significant association between body fat percentage and expression of AMPK, POMC, or GHRL. Only 3 IDMs were noted by providers to exhibit poor oral intake, limiting our ability to correlate gene expression and body composition with feeding outcomes. DISCUSSION/SIGNIFICANCE: Non-invasive assessment of hunger signaling gene expression is possible through salivary analysis of AMPK, POMC, NPY2R, and GHRL. Given the paucity of IDMs with poor feeding in our study, future studies should target IDMs requiring feeding support to understand mechanisms driving aberrant feeding behavior.

OBJECTIVES/GOALS: METHODS/STUDY POPULATION: The duration of the apprenticeship program is 2 years, with promotability to: -Research Program Coordinators -Senior Coordinators. CRCs learn essential clinical research foundations through courses and instructor led training, mentoring, and shadowing of other CRCs, such as: -Good Clinical Practices (GCP) -International Committee on Harmonization guidelines (ICH) -Institutional Review Board (IRB) -Office for Human Research Protections (OHRP) -Shipping Dangerous Goods (DOT/IATA) -REDCap data entry -Clinical Research Management System (CRMS) -Clinical Skills (i.e., vital signs, ECG, and phlebotomy) -CPR (etc.) -EPIC training RESULTS/ANTICIPATED RESULTS: -Over 100 CRCs have been trained since 2012 -Currently more than 40 active studies assigned between 16 CRCs -Over 10,000 hours of clinical trial activity in the past 15 months -The program is moving towards cost neutrality CRCs have gained access to begin DISCUSSION/SIGNIFICANCE:

OBJECTIVES/GOALS: Cognitive Processing Therapy (CPT) is a cognitive behavioral treatment for posttraumatic stress disorder (PTSD). CPT is effective in treating combat-related PTSD among Veterans and active duty service members. It is unknown whether improvement in PTSD is related to accommodation of patient preference of the modality of therapy, such as in-office, telehealth, and in-home settings. An equipoise-stratified randomization design allows for complete randomization of participants who are interested and eligible for all three treatment arms. It also allows participants to reject one treatment arm if they are not interested or eligible. Participants who elect to opt out of one arm are randomized to one of the two remaining treatment arms. The primary aim of this study was to evaluate differences in patient satisfaction, treatment stigma beliefs, and credibility beliefs based on patient treatment modality preference. The second aim of this study was to examine if baseline satisfaction, stigma beliefs, and credibility beliefs predicted PTSD treatment outcomes. METHODS/STUDY POPULATION: Active duty service members and veterans with PTSD (N = 123) were randomized to one of three arms using an equipoise stratified randomization. Participants underwent diagnostic interviews for PTSD at baseline and post-treatment and completed self-report measures of satisfaction, stigma, credibility and expectancies of therapy. RESULTS/ANTICIPATED RESULTS: A series of ANOVAs indicated that there were group differences on patient stigma beliefs regarding mental health, F = 5.61, p = .001, and therapist credibility, F = 5.11, p = .002. Post hoc analyses revealed that participants who did not opt of any treatment arm demonstrated lower levels of stigma beliefs compared to participants who opted-out of in-office, p = .001. Participants who opted out of in-home viewed the therapist as less credible compared to participants who did not opt of any arm, p = .004. Multiple regression analysis found that baseline patient satisfaction, stigma beliefs, and credibility beliefs were not predictive of PTSD treatment outcomes, p > .05. DISCUSSION/SIGNIFICANCE OF IMPACT: Combat PTSD patients may opt out of in-office therapy due to mental health stigma beliefs, and visibility in mental health clinics may be a concern. For patients who opted out of in-home therapy, lack of credibility may have decreased participants’ desire for therapists to enter their home. Despite concerns of mental health stigma and the credibility of the therapy in certain treatment arms, patients in each treatment arm significantly improved in PTSD symptomotology. Moreover, patient characteristics, including satisfaction, stigma, and credibility of the therapy, did not significantly predict treatment outcomes, which demonstrates the robustness of Cognitive Processing Therapy.

OBJECTIVES/SPECIFIC AIMS: Cardiac complications are common after hospital admission for sepsis, and elevated troponin has been associated with increased all-cause mortality. However, little is known about clinical or imaging factors that predict these cardiac events. Coronary artery calcification (CAC) is an easily identifiable imaging finding, even on nongated CT scans. The goal of this study is to identify if CAC predicts all cause mortality and acute myocardial infarction. METHODS/STUDY POPULATION: This is a single center, nonconcurrent cohort study including 899 patients who were admitted for sepsis and had a detectable TnI level from January 2013 to December 2013. Patients with a CT scan of the chest or abdomen done for other clinical indications within 6 months of this admission were reviewed for the presence or absence of CAC. Medical records were individually reviewed for mortality and type I acute myocardial infarctions at 1 year. RESULTS/ANTICIPATED RESULTS: In total, 144 patients (mean age 57±14.8 years, 48% female) were included in the analysis. CAC was seen in 59% of these scans. Compared to those without detectable CAC, the CAC group had similar APACHE score (18 vs. 16.6, p=0.259), peak TnI (3.64 vs. 2.11 mg/dL, p=0.363), aspirin (63% vs. 51%, p=0.144), and β blocker use (90% vs. 85%, p=0.357) and had higher statin use (48% vs. 27%, p=0.013). CAC was associated with increased all-cause mortality (59.5% vs. 38.9%, p=0.016) and type I myocardial infarctions (10.6% vs. 1.7%, p=0.039) compared with those without CAC. DISCUSSION/SIGNIFICANCE OF IMPACT: Coronary artery calcification is often seen when patients present with a noncardiac acute illness, such as sepsis, often making a new diagnosis for these patients. Mortality and acute MI after sepsis can be predicted by coronary calcification, and identify patients who should be targeted for therapy and close follow-up.

People experiencing incarceration are often invisible to the public due to the restricted settings in which they reside and receive services. Limited access to criminal justice settings leaves policymakers and healthcare professionals with sparse information to understand the unique needs of this population. The unmet needs of justice-involved individuals are more likely observed by professionals who provide services in correctional settings. We provide three distinct examples of projects conducted within correctional settings and how they formed pathways to interdisciplinary research and community partnerships to address the unique health and social needs of incarcerated individuals. Our partnerships in a variety of correctional settings led to exploratory research of women and men’s prepregnancy health needs, participatory workplace health interventions, and process evaluation of reentry programming. The limitations and challenges to research in correctional settings are considered along with the clinical and policy implications of these projects.

Despite federal regulations mandating the inclusion of underrepresented groups in research, recruiting diverse participants remains challenging. Identifying and implementing solutions to recruitment barriers in real time might increase the participation of underrepresented groups. Hence, the present study created a comprehensive dashboard of barriers to research participation. Barriers to participation were recorded in real time for prospective participants. Overall, 230 prospective participants expressed interest in the study but were unable to join due to one or more barriers. Awareness of the most common obstacles to research in real time will give researchers valuable data to meaningfully modify recruitment methods.

OBJECTIVES/SPECIFIC AIMS: Our goal is to assess age-related changes in osteogenic stem cell populations of bone tissue. We hypothesize that aging mice have reduced osteogenic capacity in response to physical stimulation due to aging-associated decline in osteoprogenitor cell number and their proliferative capacity. METHODS/STUDY POPULATION: Mechanical loading: The NYU School of Medicine Institutional Animal Care and Use Committee approved all procedures. The response of tibial periosteal cells to physical stimulation or mechanical loading was assessed in 16-week-old adult (n=6) and aged 78-week-old female (n=4) mice subjected to 4 consecutive days of strain-matched axial compressive loading (1400 μm, 120 cycles, 2 Hz). Whole Mount Staining: Baseline periosteal cell numbers and nuclear morphology were assessed by whole bone DAPI staining of the antero-medial region of the tibiae in adult and aged mice (n=6). Immunohistochemistry: Tibiae were fixed in 4% PFA, decalcified in 19% EDTA, OCT-embedded, and thickly sectioned (150 μm) at midshaft. Sca1+, Prrx1+, and Ki67+cell numbers were quantified by simultaneous fluorescent immunohistochemical staining from loaded and nonloaded contralateral tibiae. Nonimmune species specific serum served as negative controls. Imaging: 3D image datasets of the periosteum at the antero-medial region of the tibial midshaft were acquired by multi-photon and confocal microscopy. Quantification of Sca1+, Prrx1+, and Ki67+ cells was carried out using Particle Analysis software (ImageJ) and Imaris 7.4.2 Surface Rendering Statistics functions. Cell number was normalized to periosteal area (~0.04 mm2). A Student t-test determined significance at p<0.05. RESULTS/ANTICIPATED RESULTS: At baseline, aged periosteal cell nuclei (DAPI+) area (14% decrease, p<0.0001), nuclei number, and Prrx1+ cell number (22% decrease) was significantly lower compared with adult mice. In loaded adult mice, Prrx1+but not Sca1+cell number increased significantly (35%, p=0.0115). Proliferating Sca1+(top panel) and Prrx1+(top panel) cells also increased with loading, 62%, p=0.0253 and 115%, p=0.0004, respectively, in adult but not aged mice. The percentage of Prrx1+ cells undergoing proliferation (co-expressing Ki67+) in the total Prrx1+ cell population increased significantly with loading (bottom panel). Aged mice did not exhibit significant differences in loaded versus nonloaded controls for all other outcomes. Our data suggest fundamental changes in periosteal cell morphology, number and response to mechanical loading with aging. The significant increase in total Prrx1+ cell number and the number of Prrx1+ cells undergoing proliferation with loading in adult mice, suggest that the Prrx1+ cell population expands through proliferation. In fact, loading resulted in a 2-fold increase in the percentage of Prrx1+ preosteogenic cells undergoing proliferation. Accordingly, the significant age-related decrease in Prrx1+ cells may explain, in part, the attenuation of load-induced bone formation in aged mice. Loading resulted in greater numbers of proliferating Sca1+ cells (the more primitive cell) in adult mice, though this represented only a small percentage (<10%) of the total Sca1+ population. Mechanical loading expands the Prrx1+ pre-osteogenic cell population, but not the more primitive Sca1+ population. However, this load-induced osteogenic effect in the periosteum is not observed in aged mice, which may explain age-related diminishment of load-induced bone formation. DISCUSSION/SIGNIFICANCE OF IMPACT: Mechanical loading presents an inexpensive treatment for increasing bone mass and bone strength, but may be insufficient to prevent or reverse age-related bone loss due to reduced numbers of osteogenic progenitors in the periosteum. Therapeutic approaches targeting the osteogenic capacity of periosteal cells will be required to address declining mechanoresponsiveness with age.

OBJECTIVES/GOALS: Clinical Issue/ Practice Problem: A high turnover rate for research nurses was identified between 2017-2022 in the clinical research center at an urban Midwest academic health center. Inexperienced staff and high turnover are barriers to maintaining high-quality research integrity, efficacy, and safety for research projects and participants. METHODS/STUDY POPULATION: Project Implementation: A formal mentorship program was developed based on a curriculum from the International Association of Clinical Research Nursing Scope and Standards of Practice. The six-week project was implemented for research nurses with less than 2 years of experience. Mentees were paired with senior research nurses and met one-on-one weekly. Mentees completed the Anticipated Turnover Scale (ATS) survey in week 1 and week 6. All program participants completed a final evaluation survey. RESULTS/ANTICIPATED RESULTS: Outcomes: There was a one-point average reduction in pre- and post-ATS survey scores. This result supports the theory that mentees were less likely to leave their research role after a formal mentorship program. Qualitative results from the final evaluation survey demonstrate the program had a positive impact and benefits for both the mentees and the mentors. DISCUSSION/SIGNIFICANCE: Clinical Implications: By decreasing turnover rates, a highly competent and knowledgeable research nursing staff is attained to ensure appropriate nursing action and safety profiles for novel therapies.