OBJECTIVES/SPECIFIC AIMS: Traditional clinical trials typically enroll a homogenous population to test the efficacy of an intervention. Pragmatic trials deliberately enroll a more diverse population to enhance generalizability, but doing so may increase heterogeneity of treatment effect among subpopulations. For example, the effect of a treatment on an outcome may vary based on patients’ sex, comorbidities, or baseline risk of experiencing the outcome. We hypothesized that heterogeneity of treatment effect by baseline risk for the outcome could be demonstrated in a large pragmatic clinical trial. METHODS/STUDY POPULATION: We performed a prespecified secondary analysis of a recent pragmatic trial comparing balanced crystalloids Versus 0.9% saline among critically ill adults. The primary endpoint of the trial was major adverse kidney events within 30 days of ICU admission, censored at hospital discharge (MAKE30). MAKE30 is a composite outcome of all-cause mortality, new renal replacement therapy, or persistent renal dysfunction. Using a previously published model with high predictive accuracy for MAKE30 (area under the curve=0.903), we calculated the baseline risk of MAKE30 for all trial participants. We then developed a logistic regression model for MAKE30 with independent covariates of fluid group assignment, baseline risk of MAKE30 as a nonlinear continuous variable, and the interaction between group assignment and MAKE30 baseline risk. RESULTS/ANTICIPATED RESULTS: Among 15,802 patients from 5 intensive care units enrolled in the original trial, 126 had missing variables for predicted risk of MAKE30. Mean predicted risk of MAKE30 among all patients was 15.4%; median was 4.4% (interquartile range 2.2%–17.1%). Predicted risk of MAKE30 did not significantly differ between groups (p=0.61 by Mann-Whitney U-test). The incidence of MAKE30 in the trial was 14.9%, and the prediction model was well-calibrated overall (AUC=0.891). In a logistic regression model examining the interaction between group assignment and predicted risk of MAKE30, group assignment significantly affected MAKE30 (odds ratio saline:balanced 1.13, 95% CI: 1.02–1.27, p=0.02), but we observed no interaction between the effect of group assignment on MAKE30 and patients’ predicted risk of MAKE30 at baseline (p=0.66 for interaction term). DISCUSSION/SIGNIFICANCE OF IMPACT: In a large pragmatic trial demonstrating a significant difference in the primary outcome of MAKE30 between balanced crystalloids and saline, a previously published model accurately predicted MAKE30 using baseline factors. However, contrary to our hypothesis, the baseline risk of MAKE30 did not modify the effect of fluid group on the observed incidence of MAKE30. Our analysis could not account for unmeasured confounders and may be underpowered to detect a significant interaction. Our findings suggest that the impact of balanced crystalloids versus normal saline on renal outcomes in critically patients is consistent across all levels of risk.

OBJECTIVES/GOALS: In preclinical Alzheimer disease (AD), biomarkers such as amyloid protein, decreased hippocampal volume, and weaker network connections are apparent in the brain, but memory symptoms assessed by paper and pencil tests have not yet appeared. Performance tests of complex daily tasks may be more sensitive and detect early functional impairment. METHODS/STUDY POPULATION: This is a cross-sectional analysis of an ongoing cohort study. Cognitively normal (CN) older adults completed 3 standardized complex daily tasks from the Performance Assessment of Self-Care Skills (PASS) in their home. Biomarkers of AD were assessed within 2-3 years of an individuals completion of the PASS and include: amyloid accumulation, hippocampal volume, and resting-state functional connectivity (rs-fc) signature. Associations between performance on PASS tasks and the biomarkers of AD were quantified by Pearson point-biserial correlations, as biomarker data was normally distributed and PASS scores fell between two categories (acceptable or optimal quality of performance). Correlations with a 95% confidence interval (CI) that did not include 0 were considered significant. RESULTS/ANTICIPATED RESULTS: 161 CN participants (mean age 74.3 years, 55% female) were included. Mean score on the 3 PASS tasks ranged from 2.67 [standard deviation (SD): .47] to 2.90 (SD: .16) out of 3. Mean amyloid PET on Centiloid scale was 23.8 (SD: 34.8); mean partial volume corrected hippocampal volume was 7448.5 (SD: 909.8); mean rs-fc signature was .805 (SD: .164). After controlling for age and gender, worse performance of complex daily activities was associated with smaller hippocampal volumes (Pearsons r: 0.302, p=.02, 95% CI: .179 to .416) and weaker rs-fc network connections (Pearsons r: 0.276, p=.03, 95% CI: .078 to .453), but not amyloid accumulation. DISCUSSION/SIGNIFICANCE: This study suggests that worse performance of complex daily tasks may be associated with markers of neurodegeneration. These findings could lead to a better understanding of functional changes that may occur during the preclinical stage of AD.

OBJECTIVES/GOALS: Rapid and accurate identification of primary malaria vector species from collected specimens is the most critical aspect of effective vector surveillance and control. This interdisciplinary team of engineers aims to automate identification using a deep learning computer vision algorithm. METHODS/STUDY POPULATION: The team spent August of 2019 observing and participating in control and surveillance activities in Zambia and Uganda. They conducted >65 interviews with key stakeholders across 9 malaria control and surveillance sites, ranging from field and community health workers, to malaria researchers and Ministry of Health employees. Stakeholder feedback validated the need for a more accurate and efficient method of vector identification in order to more effectively deploy targeted malaria interventions. The team set forth in designing and prototyping a portable, automated field tool that could speciate mosquito vectors to the complex level using artificial intelligence. RESULTS/ANTICIPATED RESULTS: The team’s research demonstrated that accuracy, cost effectiveness, and ease of use would be critical to the successful adoption of the tool. Results of initial prototyping, usability studies, and stakeholder surveys were used to determine the tool’s minimal user specifications: 1) the ability to distinguish between Anopheles Gambiae and Anopheles Funestus, the two principal malaria vectors in the countries visited, 2) achieving an identification accuracy of ≥90% to the complex level, and 3) accessibility to the speciation data 3-7 days following vector collection. Next steps include optimizing the tool to deploy a minimal viable product for testing in Kenya by the summer of 2020. DISCUSSION/SIGNIFICANCE OF IMPACT: The accurate, high-quality surveillance enabled by this device would allow malaria control programs to scale surveillance to remote regions where an entomologist may not be available, allowing malaria programs to deploy effective interventions, monitor results, and prevent disease.

OBJECTIVES/SPECIFIC AIMS: This study sought to determine the accessibility, utilization, and preference for mobile phone use among a marginalized population of teens enrolled in an adolescent substance abuse treatment program and their parents. Specific study aims were to: (1) characterize mobile phone use, (2) assess the accessibility and reliability of mobile phone usage, (3) determine specific barriers to mobile phone use, and (4) examine parent and teen perceptions of the utility of integrating communication technology in substance use treatment. METHODS/STUDY POPULATION: In total, 103 (78.6% female; 75.7% Hispanic) parents of teens participating in an outpatient substance abuse treatment program with an average age of 42.60 (SD=9.28) participated in our study. Upon enrollment in a substance abuse treatment program between October 2014 and July 2016, parents completed a technology use survey as part of program development and a chart review of clinic outbound calls to parent mobile phones was completed to evaluate reliability of parent mobile phone access throughout treatment. Survey collection among teens is ongoing. Study population information for teens will be presented at the conference. RESULTS/ANTICIPATED RESULTS: The vast majority of parents owned a cell phone and used it as their primary phone (97.1%); 83% of parents owned smart phones in particular, with the majority being Android phones (68.7%). Parents were more likely to have pay-as-you-go (41.4%) and yearly (32.3%) contracts, and only 15% of the sample endorsed changing their phone number more than once in the past year (64%=never; 21%=once). Parents reported using several of the phone features: text (97%), email (76%), pictures (93%), and accessing the internet (92%); 92% reported they did not have a texting limit; and the most popular use of the mobile phone was to send and receive text messages (58.6%), followed by accessing the internet (19.2%). During the course of a 10-week treatment program, the clinic made 2776 confirmation phone calls to parents who completed surveys. Report of accessibility matched the clinic’s ability to reach parents. Of the 2776 calls, 97.2% were made to the original number provided, which was in service. Only 2.7% were determined to be disconnected, with the median number of days for disconnected service being 2 days with no voice and no texting capabilities (range=14) and 2 days with no voice, but with texting capabilities (range=28). In terms of parent perceptions of the utility of integrating communication technology in substance use treatment, 91% of parents reported they would be receptive to receiving text messages with parenting tips as aftercare support. Preferred content areas included: strategies for monitoring teen substance use (56%), strategies for using consequences (62%), suggestions for encouraging positive activities (62%), and ways to improve parent-child communication (63%). Accessibility, utilization, and preference for mobile phone use in a treatment program among teen respondents will be presented at the conference. DISCUSSION/SIGNIFICANCE OF IMPACT: This study characterized both subjective and objective mobile phone accessibility and usability among teens participating in an adolescent substance abuse treatment program and their parents. This study also provides information on teen and parent perceptions of using mobile phones during the aftercare period and ratings of acceptable messages following treatment. This data will help researchers design mobile-based interventions both during and after treatment, which is the future direction of our research group.

Objectives/Goals: We aim to develop and optimize extracellular vesicle (EV)-mediated delivery of Cas9/single-guide RNA (sgRNA) ribonucleoprotein (RNP) complex to target ACSL4, a key driver of dysregulated fatty acid metabolism in androgen receptor (AR)-independent prostate cancer, and to evaluate its therapeutic potential in vitro and in vivo. Methods/Study Population: We examined ACSL4 gene editing using lentiviral delivery and EV-mediated delivery of Cas9/sgRNA constructs. In HEK-293T cells, we optimized EV treatment frequency and concentration. In PC3 cells, we analyzed gene editing efficiency in detached cell population in comparison to attached cell population. Editing was determined by next generation sequencing. To examine EV-mediated gene editing in vivo, we employed a xenograft mouse model produced by subcutaneous injection of PC3 cells. EVs were administered by intratumoral injection three times a week for three weeks, and tumor growth, histology, and gene editing were assessed. Future studies will include patient-derived xenograft models to evaluate translational relevance. Results/Anticipated Results: Lentiviral delivery achieved up to 36% ACSL4 gene editing. EV-mediated delivery showed dose-dependent gene editing in HEK-293T cells, which contained up to 13% editing. Gene editing was enriched in detached PC3 cells, reaching a maximum editing efficiency of 47%, potentially contributing to cell death. Attached PC3 cells showed 1-2% editing and reduced proliferation after EV treatment. In the ongoing xenograft mouse model experiments, EV treatment is expected to decrease tumor growth, reduce proliferation, and induce apoptosis, confirmed by histology and sequencing. Further optimization of EV dosing and delivery aims to further enhance editing efficiency and therapeutic impact. Discussion/Significance of Impact: EV-mediated delivery of Cas9/sgRNA RNP to target ACSL4, a key metabolic driver of aggressive disease, represents a novel therapeutic strategy for treatment-resistant prostate cancer. Continued work on this nonviral platform will enable targeted, tumor-specific editing while minimizing safety concerns associated with viral delivery.

Objectives/Goals: We aimed to evaluate the representativeness of the patient population that is accessible through PCORnet®, both at the network level and within individual studies that enroll patients using the network, and to develop concrete recommendations regarding the design and evaluation of future studies. Methods/Study Population: We evaluated potential study participants that could be recruited through PCORnet, defined as patients with a healthcare encounter and any diagnosis recorded at a participating network site in 2023, relative to US population data from the American Community Survey (ACS) with respect to demographic, geographic, and socioeconomic summary data. Individual studies, conducted using the network, rarely involve all PCORnet patients, but rather those who meet clinical eligibility criteria and pass through a series of operational filters, such as site selection. We evaluated all patients at sites that have participated in at least 10 studies, as well as individual studies published in the COVID-19 clinical domain, compared to corresponding, eligible patients across the entire network. Results/Anticipated Results: PCORnet included data from over 47 million people across the USA with everyday healthcare encounters in 2023. This population of potential study participants was generally representative of the US population, though less likely to be from rural communities (11.7% vs. 18.4%) and low socioeconomic status (SES) (18.9% vs 25%). Patients from sites that frequently participate in PCORnet studies (10+) were representative of PCORnet overall, with an opportunity to improve inclusion of Hispanic populations. Among individual studies in the COVID-19 clinical domain, retrospective studies were largely representative, but prospective studies demonstrated large gaps in representation. Discussion/Significance of Impact: PCORnet provides access to a representative population of patients receiving healthcare. Differences in SES and rurality may be explained by differences in healthcare access. Population-level data, available through PCORnet, can be used to improve study design and evaluation, particularly for prospective studies.

OBJECTIVES/GOALS: Patients utilizing dialysis receive fewer primary care services, especially during the time of initiation of dialysis. This project aims to identify clinical or demographic factors that are associated with either initiation or continuity of PCP use after initiating home dialysis. METHODS/STUDY POPULATION: Using Medicare claims data from the United States Renal Data System (USRDS), we analyzed PCP use for patients aged 67 years or older. We included patients who initiated either peritoneal or home-hemodialysis between 2008-2014. Patients were followed for 2 years: 1 year before and after home dialysis initiation. We used a multivariable logistic model to control for various demographic and clinical factors believed to be confounders and to ascertain factors (i.e. age, race/ethnicity, area of residence, comorbidities, frailty scores) associated with initiation of PCP use or continuity of PCP use. RESULTS/ANTICIPATED RESULTS: Among the 9,854 patients analyzed, 68% of patients used PCP after dialysis initiation. 85% of patients who used PCP before dialysis continued PCP use after home dialysis initiation. Only 29% of patients who had not used PCP before dialysis initiated PCP use after. Employment (vs. unemployment) and use of home-hemodialysis (vs peritoneal) were associated with lower odds of PCP continuity of care. Diabetes and pre-dialysis nephrology care were associated with greater odds of PCP continuity of care. Black race (vs White) and high frailty scores were associated with lower odds of PCP initiation. Those with cardiovascular disease, residence in the South (vs the Northeast), and residence in more urban areas (vs low urban) were associated with greater odds of PCP initiation. DISCUSSION/SIGNIFICANCE: This study highlights the prevalence of PCP use, as well as the factors and subgroups that are associated with lower PCP use among patients receiving home dialysis. These findings will guide future research, interventions and policies in order to improve our understanding of the barriers to PCP use in that population.

OBJECTIVES/GOALS: Ecotin is a potent periplasmic serin protease inhibitor that was first described in Escherichia coli (E. coli). Ecotin is known to inhibit a broad range of serine proteases including NE. Therefore, we hypothesized that ecotin can inhibit the NE activity present in CF clinical sputum samples. METHODS/STUDY POPULATION: To investigate the function of ecotin on CF sputum, orthologues from Campylobacter rectus and Campylobacter showae were recombinantly expressed and purified from E. coli to generate C. rectus ecotin, C. showae ecotin, and E. coli ecotin. Ecotin was added to CF sputum supernatant samples at various concentrations and NE enzymatic activity was measured by a fluorometric assay kit. In addition, CF sputum and healthy sputum was added to PMNs isolated from healthy donors for 3.5 hours and NE was measured with immunofluorescence staining. The sputum was washed two times prior to measuring NE released and on the PMNs, and PBMCs was used as a control. RESULTS/ANTICIPATED RESULTS: Our results indicate a clear inhibition of NE activity in CF sputum supernatant. C. showae ecotin showed the greatest inhibitory effect on NE activity in CF sputum supernatant. We also saw that CF sputum supernatant causing healthy PMNs to release more NE suggesting that NE in the CF airway may trigger more NE release from newly incoming PMNs to the lung. Our next steps will be to determine if ecotin can inhibit NE on the PMN surface and released from PMNs. DISCUSSION/SIGNIFICANCE: Neutrophil elastases are produced by PMNs to kill microbial pathogens in the lung, however in CF, the pathogens are unable to be killed by NE and instead causes severe lung damage. PMNs and NE has been shown to be elevated in the sputum of CF patients and there is currently no NE therapeutic inhibitor that has been effective in these patients.

ABSTRACT IMPACT: Improved non-biased matching of clinical research professionals to PI needs will accelerate time to active project engagement for new hires. OBJECTIVES/GOALS: An ongoing challenge for HR recruiters when matching applicants to open job positions is the time-consuming screening effort, which relies on imprecise semantic searching. We propose building a precision-based matching tool using Natural Language Processing to automate the accurate and non-biased identification of suitable job candidates. METHODS/STUDY POPULATION: We conducted 30-45’ interviews with HR administration/recruitment specialists to delineate the recruitment and hiring process used to match CRC resumes to job descriptions (n=7). Next, CRC applicant resumes were evaluated by experts, first by independent review, followed by consensus and assignment of a final rating, 0= not qualified; 1= CRC1; 2= CRC2; 3= CRC3; 4= CRC4. Guidelines evolved after reviewing 6 batches of 50 unique resumes (300 total) and were based on applicant qualifications & experiences by job level, CRC 1-4. Using final guidelines an additional 3,145 resumes were rated. For uniform input into the NLP model, resume formats were converted and text contents extracted into multiple sections, i.e., education, professional experiences, etc. RESULTS/ANTICIPATED RESULTS: Guideline development: Rater agreement improved over time with poor agreement when no guidelines were present (.161- Kappa) to good agreement for final guidelines (.608- Kappa). Spearman’s rho correlation between guideline iterations and Kappa is large and positive (rho 0.886) indicating significant rater agreement. NLP Model: Resume to job description matching indicated a third of applications were qualified, a third overqualified, and a third underqualified, suggesting the majority of applicants were unable to identify their ‘best fit’ by job level. Our NLP model matched the candidate resume to CRC level with 73.3% accuracy; and achieved 79.2% accuracy when matching the applicant resume to the CRC job description. Refinement of the NLP Model is ongoing. DISCUSSION/SIGNIFICANCE OF FINDINGS: A precision-based NLP matching tool will improve applicant targeting for the hire of great, qualified candidates. Improved applicant to job matching offers several advantages, i.e., reduced bias with greater diversity and inclusion; reduced time-to-hire; ability to anticipate training needs; and a reduced time to active project engagement.

OBJECTIVES/GOALS: Errors in patient matching could result in serious adverse safety events. Unlike publicized mix-ups by healthcare providers these errors are insidious and with increased data sharing, this is a growing concern in healthcare. The following project will examine patient matching errors and quantify their association with safety. METHODS/STUDY POPULATION: EHR systems perform matching out-of-the-box with unknown quality. Using matching processes outside the EMR, the rate at which matching errors are present was quantified and the erroneous records were flagged providing both comparative measures and data necessary to evaluate patient safety. To understand the relationship between matching and safety we will establish a percent of voluntarily reported safety events in our institution where a matching error existed during an encounter. Any safety events occurring for a flagged patient will be reviewed to determine if matching errors contributed to the safety problem. Not all safety events are reported so we will perform full chart review of a filtered list of medical records that have a higher likelihood of safety events. RESULTS/ANTICIPATED RESULTS: We were able to quantify matching errors, and the preliminary matching error rate is approximately 1%, representing over 700 patients. The work is in progress and we are beginning to determine the association between safety events and incorrect matching. Together these results will provide an incentive to identify errors, make corrections, and develop methods to achieve these objectives. The number of matching errors impacts patient care as well as business operations and is likely to have a negative financial impact on institutions with high error rates regardless of its relationship to safety. DISCUSSION/SIGNIFICANCE OF IMPACT: Patient matching is bundled with EHR software and institutions have little control over error rates, yet bear the liability for resulting clinical error. Institutions need to be able to identify undetected matching errors and any associated safety events and this project will provide that solution.

Objectives/Goals: This scoping review examines common characteristics of Community Engagement Studios, defined as custom panels bringing together community partners with lived experience around a health issue to provide highly tailored feedback to a research team. The authors also identify health service fields that most commonly use community engagement studios. Methods/Study Population: This scoping review will follow procedures outlined in the Joanna Briggs Institute Manual for Evidence Synthesis. Inclusion criteria are limited to peer reviewed manuscripts published between 2010 and 2024. Key word searches for terms related to Community Engagement Studios will be conducted within Embase, MEDLINE, CINAHL, and Web of Science. Experimental, quasi-experimental, observational studies, process and conceptual manuscripts published in English or Spanish meet inclusion criteria. Two reviewers will reach consensus about article inclusion. Data analysis will include content analysis and descriptive statistics. Results/Anticipated Results: The results for studies that meet inclusion criteria will be summarized through descriptive tables of study characteristics, the number of studies excluded at the full-text review stage, and reasons for the exclusion of any studies that met the initial inclusion criteria. The results will also include a summary of common elements in the design of CE studios, the health disciplines for which CE Studios are most frequently conducted, and the aspect/phase of research design for which CE Studios are most frequently requested. Discussion/Significance of Impact: To date, no work exists examining key elements of Community Engagement Studios and the fields within health services using this valuable research tool. This scoping review is a critical first step to develop guidelines, standards, and best practices around consistent procedures and characteristics to include in the design and conduct of CE Studios.

OBJECTIVES/SPECIFIC AIMS: The central aim of the study is to examine the effect of a Dietary Approaches to Stop Hypertension (DASH) diet on hemodynamic, cardiometabolic, and inflammatory markers in advanced heart failure patients with implanted hemodynamic monitoring devices. METHODS/STUDY POPULATION: This pilot study will employ a clinical feeding trial using a 1-group pre-post test design with an anticipated sample size of n=36 (n=20 plus 44% expected attrition). Heart failure patients 18+ years of age with English language literacy, classified as NYHA functional stage III, regardless of ventricular ejection fraction, who have undergone CardioMEMS™ hemodynamic monitoring device (St. Jude Medical, Atlanta, GA, USA) implantation and have received optimized heart failure therapy for 3+ months will be recruited at Piedmont Athens Regional Hospital in Athens, GA. The study is divided in (a) a calibration (self-selected diet) and (b) a DASH feeding intervention phase (each 21 days in length). The DASH meals will strictly follow meal planning guidelines published by the National Heart, Lung, and Blood Institute of the National Institutes of Health, and be prepared under the supervision of a registered dietitian at the University Health Center in Athens, GA. The DASH diet is a heart-healthy eating pattern that is focused on adequate consumption of fruits, vegetables, whole grains, low-fat dairy, fish, poultry, beans, nuts, and vegetables oils while emphasizing limited intake of foods containing saturated fat, such as fatty red meats, full-fat dairy products, and tropical oils, such as coconut, palm kernel, and palm oils, as well as sugar-sweetened beverages and sweets. Participants will visit the University of Georgia Clinical and Translational Research Unit on 3 occasions at baseline, upon completion of the calibration phase, and following completion of the intervention phase for repeated collection of anthropometric (height, weight, waist and hip circumference, percent body fatness), cardiometabolic (blood pressure, blood glucose, HbA1C, lipid panel, basic metabolic panel, BNP, NT-proBNP, troponin 1, MR-proADM, sST2), functional status (6-min walk test), inflammatory (IL-1a, IL-1b, IL-6, TNF-a), and self-reported measures (demographic and economic characteristics, health, chronic diseases, perceived stress, heart failure-related quality of life, social support, sleep quality, food insecurity, tobacco smoking status, healthcare utilization, medication adherence). Hemodynamic marker (pulmonary artery pressure, heart rate) and pharmacotherapy information (medication count, type, strength, and dosing) will be obtained from through retrospective assessment of EHR data. Descriptive statistics [percentage, mean (SD), median (IQR), mode, range] will be used to describe sample characteristics at each of the study visits, as well as characteristics of participants’ self-selected diets during the calibration phase. To measure changes in hemodynamic, cardiometabolic, and inflammatory markers pre-post DASH diet intervention, we will use paired Student t-tests (normal distribution) or Wilcoxon rank-sum tests (non-normal distribution), as appropriate. Data collection will be carried out between February and November 2018. RESULTS/ANTICIPATED RESULTS: The study builds upon previous studies showing improvement of ventricular function, arterial stiffness, oxidative stress, and blood pressure after short-term consumption of a sodium-restricted DASH diet in heart failure patients with preserved ejection fraction, and will provide new information on the cumulative effect of short-term adherence with a DASH diet on indicators of heart failure complications, including hemodynamic, cardiometabolic, and inflammatory markers. In addition, it will give better insight on heart failure patients’ habitual dietary intake in the context of other sociodemographic, economic, health, and social factors. DISCUSSION/SIGNIFICANCE OF IMPACT: Findings from the proposed study will provide key knowledge of dietary influences on ventricular function in order to define evidence-based diet therapy needed for the early prevention of HF complications in advanced heart failure patients.

ABSTRACT IMPACT: Improved radiation treatment will yield higher doses at the tumor site, while reducing damage to healthy tissue, which will improve clinical outcomes. OBJECTIVES/GOALS: Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized and the mechanism uncovered. The efficacy of these particles will be tested in a murine system. METHODS/STUDY POPULATION: Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol then covalently conjugated to chlorin e6, a known, FDA approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species following X-irradiation was measured. Enhanced cell killing was measured clonogenically and in vivo efficacy and tumor pathology was assessed in a murine system. Further studies will determine the optimum combination of particle shape, photosensitizer structure, and ratio of components, as well as the optimal dosing schedule. RESULTS/ANTICIPATED RESULTS: Conjugation of the particle to the photosensitizer was successfully achieved, and the molecule was detectable by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates significantly increased cell killing during radiation treatment, while neither the particle alone or the photosensitizer significantly affected clonogenic survival at the same concentrations. Pathology of breast tumors grown in immunocompetent mice showed a significant increase in necrotic tissue following a single 20 gy treatment when the conjugate was present. DISCUSSION/SIGNIFICANCE OF FINDINGS: Radiation therapy is widely used clinically and it is a highly localized form of treatment. However, the total dose of radiation is limited largely to prevent injury to adjacent normal tissue. This conjugate has the potential to increase the effective dose in the tumor thereby reducing damage to healthy tissue and providing a more effective therapy.

OBJECTIVES/SPECIFIC AIMS: Translating conventional and regenerative medicine strategies from the research laboratory into the clinic is a complex process that can delay bringing novel therapies to the patient. Navigating the increasingly complex regulation surrounding cell-based and combination product technologies is a major challenge for the translational biomedical scientist. To this end, Mayo Clinic created a new position, the “Translational Integrator,” as part of the cGMP Biomaterials Facility in the Center for Regenerative Medicine. METHODS/STUDY POPULATION: The Translational Integrator educates investigators about FDA standards and regulatory pathways; determines where the product is on the translational spectrum; works to understand the science behind the product; determines what additional studies may be needed; supports investigators in preparing for FDA communications and submissions; and educates researchers about institutional resources and funding mechanisms needed to move their product into manufacturing and trials. A primary objective is to meet investigators at an early stage in product development to avoid conducting potentially redundant work to meet regulatory requirements. RESULTS/ANTICIPATED RESULTS: Robust training in clinical and translational research methodology enables the integrator to facilitate the collaboration necessary between investigators, clinicians, institutional resources, regulators and funders to move products towards FDA IND/IDE approval and first-in-human trials. It is an iterative process using technology/translational readiness criteria, project management and review by subject matter experts that is highly interactive and customized to each project. Current projects include topics in orthopedic surgery and ENT. In creating and refining this position, several key lessons have been learned. DISCUSSION/SIGNIFICANCE OF IMPACT: First, the Translational Integrator must undergo constant reflection and assessment of investigator needs, which requires flexibility and understanding that their role may change in the context of each product. Second, the support that the Translational Integrator provides can shift the mindset of the investigator from being averse to engaging in the translational process to eager to move their product forward. Finally, for the investigator who does not personally want to move their work into first-in-human trials, establishing connections to intellectual property generation and licensing may support movement of their findings into patients.

OBJECTIVES/SPECIFIC AIMS: Compare the short- and long-term effects of 2 treatments, MST and SF, on limitations in function, pain, and movement characteristics. The movement characteristics included the amount of early excursion (1st half of decent) of the knee, hip, and lumbar spine during a functional activity test of picking up an object. METHODS/STUDY POPULATION: 154 participants were randomized to 6, 1-hour treatment sessions (once/week for 6 weeks) of MST or SF. The MST group received individualized training to modify pain-provoking altered movement patterns during functional activities. The SF group received exercises for trunk strength and trunk and limb flexibility. At baseline, post-treatment and 6-month follow-up participants completed the modified Oswestry Disability Questionnaire (MODQ, a functional limitation measure; 0-100%), the Numeric Pain Rating Scale (NRS, average pain prior 7 days; 0-10) and a standardized pick up an object test, where sagittal plane knee, hip and lumbar spine excursion were calculated using 3D motion capture. A mixed model repeated measures ANOVA was used to examine the following effects: Treatment group (Tx), Time and Tx X Time for each self-report and movement variable. When the ANOVA was significant (p < 0.05), a priori planned contrasts were examined. RESULTS/ANTICIPATED RESULTS: There was a significant Tx X Time interaction (p < 0.01) for each outcome. Baseline: MST and SF were similar in MODQ scores [Δ 0.4% (−3.4− 2.9)], NRS [Δ 0.0 (−0.6− 0.6)], knee [Δ 2.2° (−6.7− 2.5)], hip [Δ 0.4° (−2.9− 2.5)], and lumbar spine [Δ 0.1° (−1.4− 1.2)] early excursion. Post-Treatment: Both group’s MODQ and NRS scores decreased (p < 0.01), but MST had a greater reduction in MODQ scores [Δ −7.6% (−3.9− −11.0)] and lower average NRS scores [Δ −0.8 (−0.1− −1.4)] compared to SF. MST changed knee [Δ +18.6° (14.6− 22.1)], hip [Δ +10.8° (8.5− 13.1)], and lumbar spine [Δ −2.0° (−3.0− −1.0)] early excursion, while SF did not change early joint excursion (all p > 0.72). 6-Month Follow-up: The differences between MST and SF were maintained for all outcomes (p > 0.26). DISCUSSION/SIGNIFICANCE OF IMPACT: MST was more effective at reducing functional limitations and pain and improving movement patterns during a functional activity compared to SF. For all variables, the differences identified during treatment between MST and SF were maintained at 6-month follow-up. Therefore compared to SF, MST that targets performance of altered movement patterns during functional activities appears to be superior for attaining and maintaining changes in functional limitations, pain, and movement characteristics in people with CLBP.

Objectives/Goals: The objective of this project is to develop a tool for evaluating clinical trial (CT) eligibility criteria for demonstrated “gender literacy,” defined as the recognition that biologically assigned “sex” is distinct from personally defined “gender identity,” as a way to quantify the inclusion of gender minority populations. Methods/Study Population: The study is validating an assessment scale that evaluates gender literacy based on CT eligibility criteria (EC). Two health professionals will serve as “coders,” tasked with grading 15 CTs. EC for all CTs will be exported from clinicaltrials.gov. Once trained with using the scale, each coder will give a score for each trial. After this first scoring period, coders will share their scores and experiences using the scale. Coders will be tasked again with grading 15 new CTs. This second scoring period will yield final scores to calculate the inter-rater reliability (IRR), or the extent to which qualitative measurements are consistent and not due to random chance. IRR will be quantified by Cohen’s kappa to validate the scale. Results/Anticipated Results: Cohen’s kappa is on a continuous interval from 0 to 1, where 0 means no agreement and 1 means perfect agreement. It is expected that the Cohen’s kappa for this assessment scale will exceed 0.80. Such validation is necessary to ensure the scale is robust and dynamic for multiple use-cases and consistent across any coder. By having a discussion after the initial scoring period, we can identify confusions or challenges with the scale early on and correct them before the secondary scoring period. In comparing these two coders’ performance, it is expected that the second scores will be more similar, thus a kappa closer to 1. However, if the kappa is low, this may be because gender literacy is a learned skill, through the internalized recognition that gender is truly different from sex. Discussion/Significance of Impact: Systemic barriers and exclusionary language have excluded gender minorities from CT spaces for too long. Tools such as these, paired with standardized language for sex and gender eligibility criteria, will greatly bolster the representation of this population and spark change for a more inclusive future.

OBJECTIVES/GOALS: To comprehensively understand the training needs of clinical research professionals (CRPs) employed across various roles in team science. The purpose is to identify areas for competency development and determine the modality of training desired to enhance their skills further. METHODS/STUDY POPULATION: This study targets Clinical Research Professionals (CRPs) across various roles in Academic Health Centers via an online survey. From novices to experts, participants are often trained on the job covering some clinical research competencies, but team science aspects like communication and leadership are usually overlooked. The survey will assess current skills, identify training gaps, and explore preferred learning methods and topics. Participants will be recruited through the CTSA hub research network. Additionally, they'll share experiences of team cohesion, dynamics, conflict, and their contributions to the team through participation in focus group sessions.The focus groups will be held via Zoom with volunteer participants from the survey (6 per session, 3 sessions, N=18). RESULTS/ANTICIPATED RESULTS: The recently developed leveled CRP team science competencies based on Lotrechianno (2022) will be the basis of the survey items. Demographic characteristics of the participants by role will be presented. Moreover, perceptions of team science applications, learning needs and training preferences will be described. Results will be compared across CRP roles. Finally, three recorded and transcribed focus groups (n=18) will contribute to knowledge gained through this research allowing for a deeper understanding of training needs. Qualitative analyzes of recorded focus-group discussions will present key themes. Qualitative data will be coded by more than two people for interrater reliability. DISCUSSION/SIGNIFICANCE: This study offers the first needs assessment on academic medical center CRP team science learning requirements, utilizing newly established CRP individual and team competencies. Findings will guide the creation of tailored training and research initiatives.

OBJECTIVES/GOALS: Micronutrient deficiencies contribute to poor health and childhood development outcomes. The objective of this study was to examine the independent and combined effects of responsive parenting and multiple micronutrient supplementation interventions on preschooler hemoglobin and ferritin concentrations in southwestern Guatemala. METHODS/STUDY POPULATION: We enrolled 387 preschoolers (36-52 months) at nutritional risk (height-for-age z-score < -1) (51% male; 17% indigenous ethnicity) in a double blind, 2 x 2, cluster randomized controlled trial. Participants in the parenting intervention received culturally tailored responsive parenting or nutrition education (control) curriculum, delivered over 6 home visits. Participants in the nutrition supplementation group received daily supplementation with a maize-soy product fortified with 21 micronutrients for 6 months or a control product fortified with vitamin B2 only. Linear mixed models were used to estimate changes in hemoglobin and ferritin from baseline (2015) to endline (2017) in a subsample with blood specimens (n = 218). RESULTS/ANTICIPATED RESULTS: At baseline, 14% of preschoolers were iron deficient and 11% were anemic. Preschooler ferritin significantly increased over time in most arms, with the largest increase in the combined responsive parenting + multiple micronutrient supplementation arm (ferritin = 95.6 (95% CI 46.4, 144.74); rates of change did not differ between study arms (p = 0.16). Preschooler hemoglobin did not change over time. Further analysis will examine the moderation of intervention effects by pre-specified child and household factors. DISCUSSION/SIGNIFICANCE: Increases in preschooler ferritin did not differ between intervention and control arms. There was no effect of the intervention on hemoglobin. Future analyses will examine intervention effects on pre-specified subgroups including baseline micronutrient deficiencies.

OBJECTIVES/GOALS: The purpose of this study was to assess if the Mentoring Competency Assessment (MCA) could be used to capture mentee gains in mentorship skills and how the mentorship competencies may vary structurally for mentees compared to mentors, while the original MCA was shown to be a validated measure to assess mentor skills. METHODS/STUDY POPULATION: The mentee training survey data were collected nationally from 2015 to 2022. The survey data set included 401 respondents who consented to participate after 59 mentee training events hosted by 34 institutions/organizations who participated in face-to-face and online training as well as completed the Mentoring Competency Assessment (MCA) in their surveys. We conducted principal component analysis (PCA) with varimax rotation to investigate the internal structure of the MCA and Hatcher’s criteria were applied. After a team of mentoring experts independently interpreted the PCA results and reached a consensus on the interpretations of the components, factor analysis and internal consistency reliability analysis were applied to assess the construct validity and the reliability. RESULTS/ANTICIPATED RESULTS: There were significant component loadings of the eight components with varimax rotation and 22 of the total 26 items were loaded into components. Four items, (5) pursuing strategies to improve communication, (6) coordinating with other mentors, (11) developing strategies to meet goals, and (23) setting career goals, were excluded from the factor analysis and Cronbach’s alpha analysis since these items were not significantly loaded into any components. The eight-component structure was validated (χ2=313.209, p<.001, RMSEA=.083, CFI=.907, TLI=.881, SRMR=.073) and the hypothesized model of the eight components resulted in an acceptable fit to the data with standardized factor loadings ranging from 0.58 to 0.93. The alpha coefficient is from 0.58 to 0.90, suggesting the items have high internal consistency. DISCUSSION/SIGNIFICANCE: Based upon the findings we recommend that the full revised MCA for mentees is used to capture mentees’ mentorship skill gains even if not all of the competency modules are used in the training. The development and validation of measures such as the MCA are important as we move toward the use of common measures across programs such as the CTSAs.

ABSTRACT IMPACT: The purpose of the T1-T4 in 3 Minutes program is to improve trainees’ capacity for communication of complex to a non-scientific audience as well as to ensure that our community stakeholders have access to, and understanding of, ongoing clinical and translation research OBJECTIVES/GOALS: The T1-T4 in 3 Program: ο Increases knowledge of research across institution; ο Increases capacity of trainees to convey complex science to lay audiences, funders, colleagues, and the media; ο Increases health and scientific literacy; ο Bridges gaps between trainees and potential entrepreneurial mentors METHODS/STUDY POPULATION: T1-T4 in 3 (Minutes) is an adaptation of the University of Queensland’s Three Minute Thesis competition in which PhD students present their thesis in 3 minutes or less to a lay audience. The competition enables them to cogently communicate their ideas and research findings to a non-specialist audience. Our adapted version, T1-T4 in 3, requires a presentation in three minutes or less to a lay audience, but rather than a thesis, the topics are on trainees’ research, and in this particular case, an idea for a commercial venture. The competition provides awards for the first- and second-best projects as determined by a panel of judges, and a ‘people’s choice’ award determined by a lay audience. RESULTS/ANTICIPATED RESULTS: This exercise is anticipated to improve trainees’ capacity for communications as well as ensure that community stakeholders and research and business community partners have access to, and understanding of, ongoing clinical and translation research with potential commercial applications. Further, the increased ability of our faculty and trainees to effectively communicate complex science to the public and other audiences’‘ including potential funders’‘ supports additional stakeholder dissemination mechanisms by increasing their confidence in their abilities to converse with non-specialists about their research, thus increasing the likelihood of participation in other community-based activities. DISCUSSION/SIGNIFICANCE OF FINDINGS: To increase ITS commercialization efforts, we envision involving numerous external partners to educate, fund, and support new ventures. T1-T4 in 3 judges will include commercialization scholars from regional and national institutions as well as pharmaceutical entities and regional angel investors.