OBJECTIVES/SPECIFIC AIMS: Familial partial lipodystrophy (FPLD) is an inherited, rare syndrome characterized by selective absence of adipose tissue from extremities which is associated with severe insulin resistance, and metabolic dyslipidemia (with hypertriglyceridemia, and low HDL) Typically, 30%–50% of patients with FPLD demonstrate a pathogenic variant in Lamin A (LMNA) gene that is associated with inherited cardiomyopathy and arrhythmia syndromes. We inquired the prevalence of having abnormal ECGs and echocardiograms in FPLD and whether there is a difference in evaluated parameters with respect to genotype. METHODS/STUDY POPULATION: We conducted a retrospective review of an established a cohort of 58 patients (age range: 12–71, M/F 8/50) with FPLD. Demographic characteristics, genotype, fasting triglyceride, hemoglobin A1c, LDL, and HDL levels were collected; ECGs and echocardiograms were also interrogated. RESULTS/ANTICIPATED RESULTS: Out of 58 patients, 22 (38 %) displayed a pathogenic variant in the LMNA gene. In total, 71% of patients (41/58) had an abnormal ECG and echocardiogram; 40% (23/58) of the patients displayed an arrhythmia on the ECGs (13 in the patients with LMNA variants and 10 in the non-LMNA group). The likelihood of having an arrhythmia was significantly higher in the patients with LMNA variants versus those without (odds ratio of 3.4, CI: 1.1–10.6). DISCUSSION/SIGNIFICANCE OF IMPACT: The overall prevalence of abnormal ECHO and/or ECG is high at 45/58 (78 %) in FPLD. Patients with LMNA variants have a 3.4 times increased risk of developing cardiac arrhythmias compared to those without. We recommend vigilant, monitoring for cardiac disease in FPLD and for arrhythmias in patients with FPLD and LMNA variants.

OBJECTIVES/GOALS: Precisely, the goal of the device is to initiate a friction force between the delivery system and the arterial vessel wall to both assure immediate stent deployment and prevent axial advancement of the stent-anchoring wire. METHODS/STUDY POPULATION: A prototype was constructed and its effectiveness of applying a friction force to a vessel wall was tested ex vivo using an LRX Plus Materials Testing Machine. Afterwards, the experimental performance of the device was compared to that of a finite element simulated model. RESULTS/ANTICIPATED RESULTS: The device demonstrated the ability to apply a friction force to the vessel wall to meet its objective. However, experimental values were consistently greater than those gathered from the simulation. Since the force prescribed by the device is minimal, future work includes increasing the force capabilities of the device and defining force requirements. DISCUSSION/SIGNIFICANCE OF IMPACT: Upon further development and testing, this device can be implemented into endovascular neurosurgery to improve occlusion rates of intracranial aneurysms and reduce patient risk during these operations. CONFLICT OF INTEREST DESCRIPTION: I am pursuing intellectual property on this invention. I was careful not to describe the invention in too much detail in my abstract submission for this reason. This research is my thesis work, and I placed on one year embargo on it before it is published to give us time to sort out IP. I would like to be considered for inclusion in Translational Science 2020 if I am able to get IP on this work before publishing, which I expect will be the case. I have every intention of obtaining IP before the conference in April 2020.

The Clinical and Translational Science Award (CTSA) Program recognizes that advancing diversity, equity, inclusion, and accessibility (DEIA) requires moving beyond statements of commitment to transformative actions. In 2021, the CTSA Program created a Task Force (TF) to initiate work in support of structural and transformational initiatives that advance DEIA for the consortium and its individual hubs. We describe the process of forming the expertise-driven (DEIA) TF and our activities to date. We 1) developed and adopted the DEIA Learning Systems Framework to guide our approach; 2) defined a set of recommendations across four focus areas (Institutional; Programmatic; Community-Centered; and Social, Cultural, Environmental); and 3) designed and disseminated a survey to capture the CTSA Program’s baseline demographic, community, infrastructural, and leadership diversity. The CTSA Consortium also elevated the TF to a standing Committee to extend our understanding, development, and implementation of DEIA approaches to translational and clinical science. These initial steps provide a foundation for collectively fostering environment that support DEIA across the research continuum.

Access to local, population specific, and timely data is vital in understanding factors that impact population health. The impact of place (neighborhood, census tract, and city) is particularly important in understanding the Social Determinants of Health. The University of Rochester Medical Center’s Clinical and Translational Science Institute created the web-based tool RocHealthData.org to provide access to thousands of geographically displayed publicly available health-related datasets. The site has also hosted a variety of locally curated datasets (eg., COVID-19 vaccination rates and community-derived health indicators), helping set community priorities and impacting outcomes. Usage statistics (available through Google Analytics) show returning visitors with a lower bounce rate (leaving a site after a single page access) and spent longer at the site than new visitors. Of the currently registered 1033 users, 51.7% were from within our host university, 20.1% were from another educational institution, and 28.2% identified as community members. Our assessments indicate that these data are useful and valued across a variety of domains. Continuing site improvement depends on new sources of locally relevant data, as well as increased usage of data beyond our local region.

OBJECTIVES/GOALS: Physical therapy (PT) is key for treating functional decline that inpatients experience but is a constrained resource in hospital settings. The Activity Measure Post-Acute Care (AM-PAC) score is a mobility measurement tool that has been used to define misallocation of PT. We aim to optimize PT referrals using AM-PAC-based clinical decision support . METHODS/STUDY POPULATION: We conducted a prospective study of patients admitted to University of Chicago Medical Center. AM-PAC scores were assessed by nursing staff every 12 hours. Clinical decision support was designed using validated AM-PAC cutoffs (> 18, a predictor of discharge to home). The tool was embedded in hospital medicine note templates, requiring providers to indicate PT referral status based on current AM-PAC scores. The primary outcome, unskilled consult , was defined as PT referral for patients with AM-PAC > 18. Data were collected for one year prior to implementation and one year after implementation for intervention (hospital medicine) and control (general internal medicine) services. Difference in differences analysis was used to assess the association between the intervention and unskilled consults. RESULTS/ANTICIPATED RESULTS: Between October 2018 and March 2021, 18,241 admissions were eligible for the study. Compared to preintervention, there was a lower rate of referral to PT for patients with high AM-PAC mobility scores in the post-intervention period [18.5% vs 16.6%; X2(1) = 7.02; p < 0.01]. In the postintervention time period, the control group experienced a 2.6% increase in unskilled consults while the intervention group experienced a 2.3% decrease, a difference in differences of 4.9% (95% CI -0.07–-0.03 for difference in differences) controlling for age sex, race, LOS, and change in mobility. Compared to preintervention, there was no statistically significant difference in mean change in mobility score post-intervention for either group. DISCUSSION/SIGNIFICANCE: Our results suggest that clinical decision support can decrease unskilled PT consults. Many functionally independent patients can mobilize with nursing or other mobilization staff. Hospitals should consider mobility score-based decision support to prioritize PT for impaired and at-risk patients.

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: 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: 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: 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.

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: 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/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.

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.

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: 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.

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.