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/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.

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.

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: Alcohol craving, particularly in response to stress and alcohol cues, can lead to relapse in alcohol-dependent individuals. Hypothalamus-pituitary-adrenal (HPA) axis markers such as the cortisol to corticotrophin (CORT:ACTH) ratio have been shown to be a significant predictor of alcohol relapse. Our objective was to evaluate the influence of HPA-axis measures on intravenous alcohol self-administration (IV-ASA) in binge and nonbinge drinkers. METHODS/STUDY POPULATION: Healthy, non-dependent binge drinkers (n=14) and nonbinge drinkers (n=11) participated in this study. They underwent 3 personalized imagery sessions, where they heard 5-minute personalized audio scripts designed to trigger stress, alcohol craving, and neutral-relaxation states. Immediately following these cues, participants were given access to alcohol using a novel IV-ASA paradigm for 120 minutes. Serial blood samples were collected for cortisol and ACTH levels. Subjective measures were collected serially using the Subjective Units of Distress Scale (SUDS), Drug Effects Questionnaire (DEQ), and Alcohol Urge Questionnaire (AUQ). Analyses were conducted using linear regression. RESULTS/ANTICIPATED RESULTS: Results showed that peak and average ACTH levels as well as the CORT:ACTH ratio during the early phase of the IV-ASA session following the stress and alcohol cues were significantly higher than the neutral script; this effect was seen primarily in binge drinkers. After script administration, a greater change from baseline for ACTH predicted time to peak BrAC during IV-ASA. Gender and binge group predicted AUQ MAX (peak alcohol craving over the entire study session) and WANT MAX (peak “want more alcohol” scores over the session). There was a significant correlation between IV-ASA and increased ACTH peak and average values in binge drinkers. The DEQ and AUQ measures were positively correlated with ACTH peak and ACTH change from baseline. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings, to our knowledge, are the first demonstration that exposure to both stress and alcohol cues lead to an increase in ACTH during cue-induced IV-ASA, particularly in binge drinkers. These results suggest that changes in HPA-axis reactivity following stress and alcohol may be important determinants of alcohol consumption in non-dependent binge drinkers.

OBJECTIVES/SPECIFIC AIMS: Clostridium difficile is the most common cause of infectious antibiotic associated diarrhea. It is often refractory to antimicrobial therapy and fecal microbiota transplantation (FMT) is emerging as a therapeutic option. The objective is to characterize the direct effects of FMT on the gut microbiota. METHODS/STUDY POPULATION: Fecal specimens were obtained from a cohort of 29 subjects with recurrent C. difficile infection who received FMTs from 1 of 4 healthy donors as part of a phase 2 trial (Rebiotix). Fecal specimens were collected from the subject before FMT and up to 6 months post FMT. 16S rRNA sequencing and whole-genome shotgun sequencing were used to assess microbial community composition as compared by weighted Unifrac. RESULTS/ANTICIPATED RESULTS: Before treatment, the microbial community of subjects with C. difficile infection was highly distinct from the composition of the healthy donors in terms of metabolic profile. Quantification of phylogenetic community distance from donor by weighted Unifrac distance showed a significant decrease within the 1st week (Wilcoxon rank sum, p<0.01). This metric was predictive of both treatment failures and antibiotic resistance gene count (LR=22.45, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that distance from donor is a useful metric to quantify FMT success and that FMTs are a promising treatment for otherwise untreatable carriage of antibiotic resistance genes and organisms.

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.

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: Understanding systematic review results help prioritise more valuable studies. However, evaluating whether a systematic review has conclusively answered a question is difficult, and it is unclear which tools are available for such assessments. Thus, we mapped the extent of methods for determining the conclusiveness of systematic review results. Methods/Study Population: We searched Medline (Ovid), EMBASE (Ovid), and Web of Science to find papers with methods to determine whether systematic review results were conclusive or should be updated. The characteristics of primary references for included methods are presented. We classified and summarized available methods. Results/Anticipated Results: A total of 58 unique methods were identified. Many have been published since 2010 and often did not include a worked example. We found 25 mathematical methods for the conclusiveness of meta-analyses, which included cumulative meta-analysis, fail-safe number, fragility index, prediction and machine learning model, simulation-based power, conditional power, and graphical approaches. There were 15 methods for the conclusiveness of cumulative meta-analyses, such as quality control approach, trial sequential analysis, sequential meta-analysis, and law of iterated logarithm. And, 18 methods assessed the conclusiveness of systematic reviews: GRADE framework, the strength of a body of evidence approach, methods for assessing the need to update a systematic review, and methods for specific clinical domains. Discussion/Significance of Impact: We found a wide range of methods that can be used to determine the conclusiveness of systematic review results. End-users of systematic reviews can review our results to find the most appropriate methods for their contexts and decisions.

OBJECTIVES/SPECIFIC AIMS: Background: Renal transplantation (tx) is the optimal treatment for end-stage renal disease (ESRD) in children, but post-tx urinary tract infections (UTIs) may cause morbidity and reduce allograft survival. Objectives: To quantify the number and risk factors for UTIs in pediatric kidney tx recipients in preparation for an analysis of the morbidity and impact of UTIs on allograft survival. METHODS/STUDY POPULATION: Methods: We identified all patients who underwent kidney tx between 2001 and 2016 (n=390) at Children’s Healthcare of Atlanta (CHOA). Patients were included if they had >1 year of follow-up at CHOA. We conducted an IRB-approved, retrospective review of patient demographics, medical history, and tx outcomes in the 5 years following tx. RESULTS/ANTICIPATED RESULTS: Results: Of the 205 records reviewed to date, we identified 176 eligible patients (61.9% male). Mean age at tx was 11.7±5.5 years. In total, 58.5% had a deceased and 41.5% had a living kidney donor. Obstructive uropathy was the etiology of ESRD in 21.0%. Mean UTIs in all patients was 1.1/patient±2.7. On preliminary analysis, patients with a history of obstructive uropathy were more likely to develop a UTI than patients without (45.9% vs. 25.2%, p=0.014). There is a trend to more UTIs in patients with a history of obstructive uropathy compared with patients without (2.1±3.5 vs. 0.9±2.4, p=0.055). In males, there were more UTIs in patients with a history of obstructive uropathy compared to patients without (1.7±2.9 vs. 0.5±1.5, p=0.024). In all, 23.2% of all patients were on UTI prophylaxis post-tx; trimethoprim-sulfamethoxazole was the prophylactic antibiotic in 54.5%. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: UTIs are common post kidney tx in children, especially in those with a history of obstructive uropathy. The associated morbidity and impact on graft survival are unknown.

OBJECTIVES/GOALS: Assistive technology (AT) can improve older adults’ function in daily activities. However, Latinos are among the least likely to use AT. Given that primary health care physicians (PCPs) have low awareness about AT, this study aims to evaluate the usability and acceptability of an AT WebAPP among PCPs to increase older Latinos’ access to AT. METHODS/STUDY POPULATION: A team of an established researcher, a sub-graduate faculty and student, and a graduate student will recruit ten PCPs in Puerto Rico and will interview them to explore their current practice in addressing the functional needs of older Spanish-speaking Latinos. The researchers will then train PCPs in the use of a Spanish evidence-based AT WebAPP developed in one of our earlier studies. PCP participants will use the APP with their older patients for 30 days. At the end of the usage period, the analysis will include a mixed method design, consisting of the simultaneous collection of quantitative data using a validated scale followed by qualitative data through individual interviews. Quantitative data will be analyzed with descriptive statistics and qualitative data with thematic content analysis. RESULTS/ANTICIPATED RESULTS: We expect that the AT WebAPP will be rated as particularly useful and acceptable by the PCPs to increase older Latinos’ access to information about AT that could compensate for their physical function disabilities. We also expect that PCPs will offer recommendations for enhancing the design and usability of the AT WebAPP. DISCUSSION/SIGNIFICANCE: Studying the usability and acceptability of this AT WebAPP among PCPs will advance our understanding of its feasibility in enhancing PCPs AT knowledge and recommendations of AT devices for older adults with disabilities in Puerto Rico and in Latino communities in the continental United States.

OBJECTIVES/GOALS: The goal of this study was to perform a comparative, multi-reader, retrospective clinical evaluation of prostate multiparametric MRI (mpMRI) at 3 Tesla (3T) vs. 7 Tesla (7T) primarily in terms of prostate cancer localization. Subjective measures of image quality and artifacts were also evaluated. METHODS/STUDY POPULATION: Nineteen subjects were imaged at 3T and 7T between March 2016 and October 2018 under IRB-approved protocols. Four radiologists retrospectively and independently reviewed the data, and completed a two-part assessment for each dataset. First, readers assessed likelihood of cancer using Prostate Imaging Reporting & Data System (PI-RADS) guidelines. Accuracy of cancer detection was compared to findings from prostate biopsy. The numbers of correctly or incorrectly classified sextants were summed across all four readers, then used to summarize detection performance. Second, readers assigned a score on a five-point Likert scale to multiple image quality characteristics for the 3T and 7T datasets. RESULTS/ANTICIPATED RESULTS: Sensitivity and specificity of 3T and 7T datasets for sextant-wise cancer detection were compared by paired two-tailed t-tests. Readers identified more sextants harboring cancer with the 3T datasets while false-positive rates were similar, resulting in significantly higher sensitivity at 3T with no significant differences in specificity. Likert scores for image quality characteristics for 3T and 7T datasets were compared by applying paired two-tailed t-tests to mean scores of the four radiologists for each dataset. Readers generally preferred the 3T datasets, in particular for staging and assessment of extraprostatic extension as well as overall quality of the contrast-enhanced data. DISCUSSION/SIGNIFICANCE OF IMPACT: Readers agreed 7T prostate mpMRI produced images with more anatomic detail, though with equivocal clinical relevance and more pronounced artifacts. Reader unfamiliarity with 7T images is a major extenuating factor. Forthcoming technological developments are anticipated to improve upon the results.

OBJECTIVES/GOALS: This poster shares a case study on how a group at The Johns Hopkins University formed a translational lab missioned to reinvent currently existing treatments for acute spinal cord injuries, implanting in humans within a five-year window. The poster showcases how a project funded by the Defense Advanced Research Projects Agency has been implemented. METHODS/STUDY POPULATION: The translational team; Holistic Electrical; ultrasonic and Physiological Interventions Unburdening those with Spinal cord injury• (HEPIUS) Lab is composed of many parts as listed below: neurosurgeons; engineers; radiologists; public health specialists; statisticians; patient advocates; ethicists; sonographers; researchers; academic collaborators; and specialized industry partners. Sometimes physically separated; the team has videoconferencing carts across locations to stay connected at every step in the process. The lab facilities were organized with several key facets in mind: research and development (R&D); prototyping; fabrication; verification; and validation (V&V); animal model testing; cadaveric testing accessibility; mock operating room for simulations; and collaboration hubs. RESULTS/ANTICIPATED RESULTS: Due to communications with the US Food and Drug Administration (FDA), DARPA, patient advocates, ethicists, internal review boards, and other bodies, the team has a clear path towards clinical translation. The team has the following stages in progress or scheduled: manufacturing devices, benchtop testing, rat and pig models, biocompatibility testing, cadaveric testing, and clinical use. The lab space was designed to achieve these core functions. For rapid, in-house manufacturing, the lab has unique capabilities including 3D metal printing. For experiments, industry collaborations and equipment acquisitions enable the highest quality research. These technologies are assembled into diagnostic, therapeutic, testing, and manufacturing hubs to drive real change in the lives of many; the patient comes first. DISCUSSION/SIGNIFICANCE: This laboratory, team, and system of operation is aimed to enable novel practices for the clinical translation of spinal cord medical solutions. For researchers interested in launching their own translational work, this poster may serve as a reference, example, and inspiration for similar hopeful university-centered hubs.

OBJECTIVES/SPECIFIC AIMS: In an effort to elucidate the role of potentially cancer chemopreventive drugs, we leveraged the Mayo Clinic-Karolinska Institute collaboration to create a multidisciplinary team that included an epidemiologist, statisticians, and physicians. We performed a population-based cohort study to examine the association between low dose aspirin, non-aspirin NSAIDs, statins, metformin, other risk factors and the risk of biliary tract cancer (BTC), while assessing confounding by sex. METHODS/STUDY POPULATION: We conducted a nationwide Swedish population-based cohort study using the Swedish Prescribed Drug Registry, which virtually completely enumerates use of prescribed medications nationwide since 2005. BTC diagnosis (intrahepatic cholangiocarcinoma [iCCA], extrahepatic cholangiocarcinoma [eCCA] or gallbladder cancer [GBC]) was ascertained from the Swedish Cancer Registry. Age-scaled Cox models, with exposure as time-varying covariates, were used to calculate hazard ratios (HRs), separately for men and women. RESULTS/ANTICIPATED RESULTS: In the 5.7 million person cohort, the risk of iCCA was significantly lower in men using statins (HR 0.62,95%CI 0.39-1.00, p = 0.05), with a non-significant reduction in women. Statin use was associated with a significantly decreased risk of eCCA in both women (HR 0.60,0.38-0.94, p = 0.03) and men (HR 0.47,0.28-0.80, p = 0.01). Low dose aspirin (HR 0.76,0.60-0.97, p = 0.03) was associated with a lower risk of GBC only in women, while statins (HR 0.72,0.55-0.93, p = 0.01) showed a significantly decreased risk of GBC in women and a non-significant reduction in men. For all BTC subtypes, combined use of low dose aspirin and statins did not confer additional risk reductions beyond those achieved by statins alone. Male and female users of non-aspirin NSAIDs appeared to be at increased risk of BTC and its subtypes. Metformin did not significantly affect risk of BTC. DISCUSSION/SIGNIFICANCE OF IMPACT: Our collaborative efforts allowed us to develop the largest population-based cohort evaluating risk and protective factors for BTC. Our results provide strong evidence in favor of the chemopreventive roles of low dose aspirin and statins in a subtype- and sex-specific manner. Individual risk factors contribute to development of BTC subtypes in different magnitudes. The next steps to translate these findings into clinical practice require randomized clinical trials that validate our results and provide a more complete picture of the risk-benefit ratio.