OBJECTIVES/GOALS: The grant writing process provides investigators with critical thinking, problem solving, and communication skills, crucial for personal and professional development. However, opportunities for junior faculty to learn these skills are highly variable. Thus, we developed a grant writing program to assist in the preparation of an NIH R proposal. METHODS/STUDY POPULATION: The R Club Grant Program was implemented in 2021 for junior faculty of the University of Cincinnati’s College of Medicine and Center for Clinical & Translational Science & Training (CCTST). The program consists of a series of workshops (e.g., How to Craft a Specific Aims Page, How to Construct a Competitive R01 Proposal) utilizing examples of successful proposals and grant review criteria to demonstrate how to translate a conceptual framework into a research proposal (level 1). All participants can receive constructive feedback on a Specific Aims page from an experienced grant writer (level 2), and for a select cohort, the program provides comprehensive scientific content edits and iterative feedback on a full research proposal, with a focus on grantsmanship, presentation, and overall competitiveness (level 3). RESULTS/ANTICIPATED RESULTS: Over three NIH grant cycles, the program to date has provided 38 early-career investigators with multi-level grant writing support. All participants attended the workshops and received supporting documents, 21 received feedback on a Specific Aims page, and 6 received one-on-one writing assistance on their full research proposal. Of the 6 investigators who received the greatest level of support, 3 have received NIH scientific review, with a 66.6% funding success rate for either an original (R01, n=1) or subsequent overlapping (R35, n=1) proposal. In a survey sent to workshop attendees, 100% of respondents (n=23) reported ( Strongly Agreed or Agreed ) that the training was a worthwhile investment in their professional development and 96% stated that they will be able to apply the knowledge and skills learned. DISCUSSION/SIGNIFICANCE: Initial evaluation measures suggest that grant writing support programs have great potential to enhance funding success rates. As the program evolves it will be crucial to evaluate both qualitative and quantitative feedback measures to ensure efforts are directed to the appropriate level(s) of service to maximize the funding success of our faculty.

OBJECTIVES/GOALS: The overarching objective is to assess the value of promoting team science practices across a diverse clinical translational science community through the development of learning modules. We aim to share lessons learned to help inform best practices for CTSA hubs interested in promoting team science. METHODS/STUDY POPULATION: We recently created a series of self-paced learning modules focused on the science of team science, which include a variety of text and multimedia content. A preliminary assessment was conducted to determine the perceived value of six video team science Learning Shots and to identify areas for improvement. Significant content revisions are underway based on respondent feedback. In early 2022, a follow up survey will solicit feedback from a larger sample of researchers to reassess the learning modules and to ensure that desired improvements were achieved. We will incorporate continuous improvement cycles to gather future feedback, track improvements, and identify potential future direction for new content. RESULTS/ANTICIPATED RESULTS: The preliminary assessment identified the most effective aspects of the modules to be the variety and knowledge of speakers, diversity of topics, organization of the content, and appropriateness of length. Least effective aspects included a desire for more information in some content areas and not enough focus on the challenges of team science for junior faculty. Suggested areas for improvement include a desire for supplemental descriptive text, links to tools that enable teams to be productive, and additional examples from researchers. The follow up study is expected to yield more detailed information on the impacts of the improvements and the overall effectiveness of the modules. DISCUSSION/SIGNIFICANCE: This project provides insights for CTSA Hubs interested in promoting team science and best practices when developing learning modules. Results contribute to what is known about researchers interest in learning about team science and the effectiveness of using online formats for delivery.

OBJECTIVES/GOALS: While the evolving treatment paradigm for Glioblastoma (GBM) leverages different modalities to improve outcomes, treatment access might be limited by cost and disparities. This study explores the influence of race and social determinants of health (SDoH) on healthcare access and outcomes of GBM patients in a large metropolitan area over a decade. METHODS/STUDY POPULATION: Our institution’s tumor registry (2009-2019) was queried to identify our GBM cohort. Data were supplemented by electronic health records to include demographics, outcome, NCI Comorbidity Index, and the Agency for Healthcare Research and Quality (AHRQ) socioeconomic status (SES) index. RESULTS/ANTICIPATED RESULTS: Of the 559 GBM records, 361 unique patients met the inclusion criteria, and 43% were Non-White. Non-White patients predominantly comprised the lowest AHRQ SES index quartile and had longer hospital stays (LOS; p<0.001). White patients accounted for 61% of privately insured patients (p<0.001). Private insurance (p= 0.02) and age < 65 years (p= 0.039) were associated with a higher rate of home discharge. Patients diagnosed with GBM in the emergency department were more likely to be discharged to acute rehab than home (p<0.001). At 2 years, privately insured patients had longer OS (HR= 1.46; p= 0.04). DISCUSSION/SIGNIFICANCE: In contrast to previous studies, the study demonstrates that GBM affected a higher proportion of Non-White patients. Our data show that SDoH influences multiple outcomes in GBM patients. Efforts to identify and correct these barriers are needed to improve the care of all GBM patients.

OBJECTIVES/GOALS: The modified Atkins diet (MAD) is used in the management of drug-resistant epilepsy in adults. Some patients on MAD show an increase in serum levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. We explored whether dietary fat composition predicts short-term elevations in serum lipid levels in diet-naïve adults who begin MAD. METHODS/STUDY POPULATION: Participants self-reported their diet intake with 3-day food records at baseline, 1 month and 2 months. Food records were analyzed using Nutrition Data System for Research software. Fasting serum levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides were also collected and LDL level calculated at baseline, 1 month, and 2 months. RESULTS/ANTICIPATED RESULTS: 38 patients submitted complete food records at each study visit (baseline, 1 month, and 2 month). Compared to baseline diet intake, there was a significant reduction in daily carbohydrate intake at 1 and 2 months months (p<0.001). There was also a significant increase in daily saturated fatty acid (SFA) intake at 1 and 2 months (p<0.001), daily mono-unsaturated fatty acid (MUFA) intake at 1 and 2 months (p<0.001), and daily cholesterol intake at 1 month (p<0.05) and 2 months (p<0.001), but no change in daily poly-unsaturated fatty acid (PUFA) intake over time. Compared to baseline, there was a significant increase in serum LDL at 1 month (p<0.001) and 2 months (p<0.01) and an increase in serum TC at 1 month (p<0.01) but not 2 months. DISCUSSION/SIGNIFICANCE OF IMPACT : Despite a significant increase in total fat, saturated fat and mono-unsaturated fat intake as well as an increase in total cholesterol and LDL levels following MAD initiation, dietary fat composition appears to minimally predict serum lipid values in the short term. CONFLICT OF INTEREST DESCRIPTION: Tanya McDonald has received speaking honoraria from Nutricia North America. Bobbie Henry-Barron receives grants from Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research, Nutricia and Vitaflo. Diane Vizthum receives grants from the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1 TR 001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Mackenzie C. Cervenka has received grant support from Nutricia North America, Vitaflo, Army Research Laboratory, The William and Ella Owens Medical Research Foundation and BrightFocus Foundation. She receives speaking honoraria from LivaNova, Epigenix, Nutricia North America and the Glut1 Deficiency Foundation and performs consulting with Nutricia North America and Sage Therapeutics and receives Royalties from Demos Health.

OBJECTIVES/GOALS: Many older sepsis survivors develop chronic critical illness (CCI) with poor outcomes. Sepsis is caused by a dysregulated immune response and biomarkers reflecting PICS. The purpose was to compare serial PICS biomarkers in a) older (versus young) adults and b) older CCI (versus older RAP) patients to gain insight into underlying pathobiology of CCI. METHODS/STUDY POPULATION: Prospective longitudinal study with young (≤ 45 years) and older (≥ 65 years) septic adults who were characterized by a) baseline predisposition, b) hospital outcomes, c) serial SOFA organ dysfunction scores over 14 days, d) Zubrod Performance status at three, six and 12-month follow-up and e) mortality over 12 months. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS. RESULTS/ANTICIPATED RESULTS: Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status and mortality over 12 months. Additionally, older (versus young) and older CCI (versus older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism and anti-angiogenesis over 14 days after sepsis. DISCUSSION/SIGNIFICANCE: Older (versus young) and older CCI (versus older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS. The population of older sepsis survivors is need of interventions to lower systemic inflammation and stimulate anabolism to prevent skeletal muscle wasting and disability.

OBJECTIVES/GOALS: Racial and ethnic minority populations have been historically underrepresented in clinical trials, which limits the external validity of study findings. We analyze data from the ACTIV-6 trial to assess whether inclusion efforts were effective in increasing participation from minority groups. METHODS/STUDY POPULATION: ACTIV-6 is a decentralized randomized placebo-controlled platform trial investigating repurposed drugs for the treatment of mild to moderate COVID-19. Study participants could either self-refer online or be recruited through a study site. Two inclusion efforts were introduced to increase participation from racial or ethnic minority populations: targeted advertising and outreach, and strategic selection of study sites that serve diverse populations. We assessed the effectiveness of these interventions by analyzing enrollment trends over time. We also assessed whether participants from racial or ethnic minority populations experienced higher loss to follow-up. RESULTS/ANTICIPATED RESULTS: At the start of the trial, enrollment of non-Hispanic White participants outpaced enrollment from racial or ethnic minority populations. At 4 months, only 108 participants (20.5%) were from racial or ethnic minority populations, but greatly increased by 28 months to 3,544 participants (46.4%), nearly half of all participants. This increase was predominantly due to recruitment through study sites rather than self-referral. In particular, certain sites recruited large numbers of minority participants. We also observed that participants from racial or ethnic minority populations were more likely to drop out of the study before receiving the study drug (3% vs 1%). DISCUSSION/SIGNIFICANCE: Our results suggest that strategic site selection is an effective strategy for recruiting a study population that represents racial and ethnic populations. The benefits of targeted advertising and outreach were less clear. Retention efforts remain important to reduce loss to follow-up.

OBJECTIVES/SPECIFIC AIMS: Depression is one of the leading causes of diseases and disability among women of all ages in the United States. Lack of resources to meet one’s daily needs, access to health care, job opportunities, and drug use significantly contribute to depression among women. This paper aimed to explore the determinants of depression among women from a large community-based sample. METHODS/STUDY POPULATION: HealthStreet is a community engagement research initiative at the University of Florida that utilizes the community health worker (CHW) model to assess health concerns and conditions of community members and link them to available social and medical services and health research. From October 2011 through December 2016, CHWs assessed 8469 community members from various locations in the community such as grocery stores, bus stops, health fairs, laundromats, and others. Among these 8469 participants contacted and assessed by the CHWs, 4952 (58.5%) were women. RESULTS/ANTICIPATED RESULTS: Of the total 8469 participants, 4952 were women and 1839 (37.1%) reported ever having depression. Mean age of women who reported depression was 44.1 years (SD±14.4). Women who were current users of 3 or more drugs were 10 times more likely (95% CI: 5.73, 18.40; OR 10.27) to report depression compared with those who did not currently use any drugs. Those who were food insecure in the past 12 months (95% CI: 1.970, 2.576; OR 2.253) were twice more likely to report depression, while never married (95% CI: 0.576, 0.771; OR 0.666), and currently unemployed (95% CI: 0.535, 0.715; OR 0.619) women were less likely to report depression. Chronic health conditions such as hypertension (41.6% vs. 33.7%), diabetes (14% vs. 10.5%), and cancer (12.1% vs. 8.3%), and comorbid psychiatric symptoms such as anxiety (54.2% vs. 10.8%) and bipolar disorder (23.8% vs. 2.8%) were significantly higher (p<0.001) among women with depression compared with their counterparts. Significantly more women without a history of depression had medical insurance (68.8% vs. 64.3%) as compared with women with depression. DISCUSSION/SIGNIFICANCE OF IMPACT: Depression was associated with food insecurity and drug use. The impact of drug use continues to be a major mental health concern among community-based women. Further, these findings emphasize the importance of community engagement programs such as HealthStreet, which utilizes the CHWs’ model to link community members to social and medical services within the community, in improving the mental health of women.

OBJECTIVES/GOALS: It is hypothesized that the global secular trend toward earlier puberty onset, with implications for many future health outcomes, is related to the obesity epidemic. This study aims to examine prospective associations between weight during specific developmental windows and timing of puberty onset. METHODS/STUDY POPULATION: This study includes 1,296 mother-infant dyads from the Boston Birth Cohort, a predominantly minority (>80% black/Hispanic), low-income, and urban prospective birth cohort recruited and followed between 1998 and 2019. Age at peak height velocity (APHV), a well-defined and standardized proxy for puberty onset, is derived by fitting height measurements recorded during clinical visits using a mixed effects growth curve model. Multiple linear regression is performed to examine the relationships between early childhood (ages 2-5y) and prepubertal (ages 6-9y) overweight and obesity, weight trajectories between these two periods, and APHV, while controlling for known contributors to early puberty. RESULTS/ANTICIPATED RESULTS: Compared to counterparts with normal BMIs, kids who were obese during ages 2-5y (boys: −0.21y, CI[−0.39, −0.04]; girls: −0.22y, CI[−0.39, −0.05]) or ages 6-9y (boys: −0.27y, CI[−0.43, −0.11]; girls: −0.37y, CI[−0.52, −0.23]) had an earlier APHV. Being overweight during ages 6-9y was also associated an earlier APHV (boys: −0.26y, CI[−0.46, −0.07]; girls: −0.26y, CI[−0.42, −0.10]). Looking at weight trajectories, kids who were persistently overweight or obese from ages 2-5y to ages 6-9y had an earlier APHV (boys: −0.28y, CI[−0.45, −0.12]; girls: −0.31y, CI[−0.46, −0.16]), as did girls with normal BMIs during ages 2-5y and who were overweight or obese during ages 6-9y (−0.45y CI[−0.64, −0.26]). DISCUSSION/SIGNIFICANCE OF IMPACT: The temporal and dose-response relationships seen in this historically understudied population suggests that childhood obesity is etiologically important in the development, and even programming, of early puberty. This has implications for prediction, prevention, and mitigation of health disparities.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to identify and categorize non-invasive measurement methods for autonomic nervous system (ANS) symptoms that develop in hypoglycemic episodes. METHODS/STUDY POPULATION: We first reviewed literature for hypoglycemia symptomology. We then performed a selective literature review of Google Scholar, PubMed and Scopus for an ANS symptom and/or synonyms and the words ‘sensor’ or ‘detection’, e.g. ‘sweat sensor’ and ‘tremor detection’, studies utilizing non-invasive measurements in DM, and datasets of non-invasive measurements in DM. Measurement methods were then organized based on the ANS symptoms and existing metadata models for harmonizing sensors and surveys. RESULTS/ANTICIPATED RESULTS: We identified several measurement methods to for ANS symptoms during hypoglycemic events: thermometer, accelerometer, electrocardiogram (ECG), galvanic skin response (GSR), image processing, infrared imaging, thermal actuator, and ecological momentary assessment (EMA). The stage of implementation varied across the measurement methods from under development, to use in research and clinical settings, and even commercially available consumer products. Measurement methods that could be worn as wrist-band wearables or as film-based epidermal sensors would be capable of automatically gathering data with little to no effort required of the person wearing the device. Image-based methods would require the individual to actively engage in generating a photograph for analysis. In the case of EMA’s, a message containing a question is sent to the individual, often via text message, soliciting short and immediate responses. It is anticipated that one sensor alone would not be sufficient to measure ANS responses to hypoglycemia, but rather several data points would be required. For example, if the GSR was the only signal, sweat in response to vigorous exercise or a warm environment would inject noise into the signal. Including the accelerometer data would allow for the identification of body movement which would indicate exercise, while an ECG signal could confirm the exercise. DISCUSSION/SIGNIFICANCE OF IMPACT: Impaired awareness of hypoglycemia (IAH) is a complication that develops in about 30% of type 1 DM and 10% type 2 DM populations. In individuals with intact awareness of hypoglycemia, the ANS leads to symptoms which includes: shaking, trembling, anxiety, nervousness, palpitation (i.e. change in heart rate and/or function), clamminess, sweating, dry mouth, hunger, pallor (i.e. drop in blood flow and/or skin-surface temperature), and pupil dilation. IAH is defined as the onset of hypoglycemia before the appearance of autonomic warning symptoms. IAH is caused by repeated exposures to low blood glucose levels, which reduces the body’s ability to sense hypoglycemia, and therefore it is difficult for patients to recognize and self-treat. Individuals with IAH are six times more likely to experience severe hypoglycemia, an emergent condition which can lead to unconsciousness, seizure, coma, and death. Clinical investigators are developing interventions that aim to improve awareness of hypoglycemia. Surveys, observations by clinicians, and laboratory tests, often carried out in highly controlled in-patient settings, are currently used to assess the severity of IAH and the ANS’s ability to respond to hypoglycemia. In other disease states, for example heart disease and Parkinson’s disease, electrocardiograms and accelerometers have been used to assess heart function and tremor, respectively. However, there is currently a barrier to examining the efficacy of IAH interventions in real world settings as there are no established objective and non-invasive means to measure ANS symptoms due to hypoglycemia. This work encompasses the first important step necessary to direct translational researchers interested in testing the efficacy of IAH interventions and developing diagnostic tools for IAH in real-world studies outside the clinic. Next steps include evaluating these sensors and specifying EMA surveys, designing studies, and integration and assimilation of these data streams to identify true events of IAH by leveraging informatics platform such as the Utah PRISMS Informatics Ecosystem. Investigators would then be able to conduct studies that aim to develop and validate models that take sensor and EMA data as the input to detect and assess the severity of IAH.

OBJECTIVES/GOALS: To conceptualize, implement and evaluate a three-pronged social media plan with goals to: 1) disseminate information about the Southern California CTSI and its activities on multiple platforms; 2) educate the public about clinical research participation; 3) use storytelling methods to spread awareness about research careers. METHODS/STUDY POPULATION: We will start by creating a logic model to identify activities, outputs, short, medium and long-term outcomes of this social media innovation project, using CTSI and community stakeholder input (focus groups). This model will guide the creation of a comprehensive strategic social media plan that includes an editorial calendar for each platform, storyboarding and an operationalized narrative strategy, as well as KPIs relating to areas like reach, engagement, conversion, and sentiment. Collecting/analyzing these metrics will yield information about how the public feels about clinical research and will assist us in refining our content strategy. After completing formative research, we will create accounts on Instagram, TikTok, LinkedIn and Meta to complement our existing Twitter presence. RESULTS/ANTICIPATED RESULTS: We hope to identify which types of content lead to greater engagement and more positive sentiment on each platform, which will help us iteratively refine our content strategy. Examples of content type can include: imparting research-related information, debunking myths, providing career information, etc. Through this process we will also gain knowledge about what methods are more appealing to our users, such as narrative storytelling. Visually, we anticipate learning about what types of multimedia content works best as a mechanism to disseminate information about clinical research (e.g. video, photo, audio, or a combination). DISCUSSION/SIGNIFICANCE: In a post-pandemic world of dis- and misinformation, it is more important than ever to disseminate trusted, vetted information about clinical research in novel and engaging ways. Through this initiative we will gather information, metrics and key lessons learned to present back to CTSA hubs to inform their short and long-term social media strategies.

OBJECTIVES/SPECIFIC AIMS: Computed tomography (CT) enables 3-dimensional (3D) visualization of cortical bone structures with high spatial resolution, and thus has been the gold-standard method for evaluation and diagnosis of craniofacial skeletal pathologies. However, ionizing radiation and, in particular, repeated scanning for presurgery and postsurgery assessments, is of concern when applied to infants and young children. Recent advances in solid-state MRI allow the capture of the short-T2 signals in cortical bone while suppressing the signal from soft-tissue protons having T2 relaxation time 1–2 orders of magnitude longer (50–100 ms). One approach, a dual-radiofrequency (RF) pulse and ultrashort echo time (UTE) imaging based method, exploits different sensitivities of bone and soft tissue to different RF pulse widths and TEs. This study aims to demonstrate the feasibility of producing 3D renderings of the human skull and visualization of cranial sutures using the bone-selective MRI technique in comparison to CT. METHODS/STUDY POPULATION: Imaging technique: Two RF pulses differing in duration and amplitude are alternately applied in successive repetition time (TR) along the pulse train. Within each TR, 2 echoes are acquired. Acquisition of the first echo starts at the ramp-up of the encoding gradient (TE1), allowing for capture of signals with very short lifetimes (bone), while that of the second starts after a longer delay (TE2). In total, 4 echoes are obtained: ECHO11 (RF1TE1), ECHO12 (RF1TE2), ECHO21 (RF2TE1), and ECHO22 (RF2TE2). During reconstruction, ECHO11 is combined with ECHO21 and ECHO12 is combined with ECHO22, resulting in 2 images. The subtraction of these 2 images yields an enhanced bone contrast. Data acquisition/processing: The pulse sequence described above was applied for MR imaging of a human cadaveric skull and 2 adult human subjects in vivo, at 3T field strength (Siemens Prisma, Erlangen, Germany). Imaging parameters: TR/TE1/TE2=7/0.06/2.46 ms, RF1/RF2 durations=40/520 μs, flip angle=12°, matrix size=2563, field of view=2803 mm3, voxel size=1.1 mm isotropic, number of radial spokes=25,000, and scan time=6 minutes. Segmentation of bone voxels was performed using ITK-SNAP in a semi-automatic fashion, leading to 3D renderings of the skull. For comparison, a CT scan was also performed in the human cadaveric skull with 1 mm isotropic resolution. Validation: The biometric accuracy was assessed by measuring eight anatomic distances: (1) Maximum craniocaudal aperture of the right orbit. (2) Maximum craniocaudal aperture of the left orbit. (3) Maximum height of the mandible from chin point in the midline. (4) Maximum cranial length (5) Maximum cranial width. (6) Maximum height of piriform aperture. (7) Distance between lateral most aspect of mandibular condyles. (8) Distance between lateral most aspect of posterior hard palate in both CT- and MRI-based 3D renderings of the human cadaveric skull using Mimics software (Materialise®, Ghent, Belgium). These distances were compared with those directly measured on the cadaveric skull. RESULTS/ANTICIPATED RESULTS: Compares CT with the proposed MRI method on cadaveric human skull images, along with corresponding 3D renderings. Compared with CT, the 3D rendered images maintain most features over the entire head (e.g., zygomatic arch), except for appearance of some artifacts in the mandibular region. In vivo head images in 2 adult subjects: axial magnitude images and 3D rendering. In the axial images, bone voxels as well as the inner table of the cranium are clearly visualized, and cranial and spinal bone structures are well depicted in the 3D renderings. Some voxels were erroneously included or excluded in the renderings. The mean difference in measurements of the 8 anatomic distances was 6, 4, and 2 mm when comparing MRI Versus CT, MRI Versus in situ, and CT Versus in situ, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Bone proton magnetization exhibits a substantial level of signal decay during the relatively long duration of RF2 due to its very short T2 relaxation time. In contrast, soft-tissue retains nearly the same level of signal intensities over all echoes. Thus, subtraction of ECHO22 from ECHO11, when compared with the difference between ECHO11 and ECHO12, enhances bone contrast from soft tissue. The proposed, dual-RF dual-echo 3D UTE imaging technique produces isotropic high-resolution bone-specified images in the whole head within a clinically feasible imaging time (6 min), leading to clear visualization of craniofacial skeletal structures. These are key components necessary for translation to the clinical setting. Optimization of postprocessing for more realistic 3D renderings and thus accurate anatomic measurements is currently being implemented. The proposed method’s potential as a nonradiative alternative to CT will then be thoroughly evaluated in pediatric patients.

OBJECTIVES/GOALS: Diabetes is related to risk for heart disease, stroke, high blood pressure, and COVID-19. It is exacerbated by built/social environment issues, e.g., food insecurity, access to healthy foods and health care, and other poverty-related factors. Our goal is to assess the efficacy of an integrated care model for patients with poorly controlled diabetes. METHODS/STUDY POPULATION: We utilize an integrated, team-based approach to diabetes treatment. In a traditional care model, too little focus is on social determinants and their impacts on health and well-being. Our project involves enrollment of patients with diabetes in an intervention whereby their medical care is integrated with intensive diabetes education and provision of social and other health services, including diet and nutrition, exercise, provision of foods and nutritional supplements, and other support services as needed to achieve optimal health and to reduce morbidity and unnecessary hospitalization and emergency room visits. Subjects are underserved patients treated through our non-profit community clinic partners. We track metrics including individual outcomes, organizational outcomes, and collective impact. RESULTS/ANTICIPATED RESULTS: We anticipate that patients enrolled in this study will demonstrate significant improvements in diabetes control and management. Clinical improvements will include better glycemic control, improved hypertension and dyslipidemia management, reduced complications, and increased preventive measures including foot, eye and oral health exams and monitoring of microalbuminuria. Overall, we anticipate decreased frequency of hospitalizations and readmissions as well as decreased frequency of emergency care visits for treatment of diabetes-related issues. We expect patients to experience enhanced self-efficacy, increased physical activity, and improved quality of life. Their outcomes will be compared to controls receiving the standard medical regimen, matched on age, race, gender, and time of onset. DISCUSSION/SIGNIFICANCE: These activities will improve understanding of factors influencing diabetes outcomes at individual and upstream levels. It will inform food distribution and models of care for improved patient outcomes, including social determinants of health and will establish new protocols for community-based provision of health care to our most vulnerable.

OBJECTIVES/GOALS:

1. 1. Determine test characteristics of Neuro ICU nurse interpretation of real-time bedside qEEG for seizure detection

2. 2. Determine difference in time to detection of seizures between qEEG interpretation and raw cEEG reads

3. 3. Determine how seizure characteristics affect accuracy of qEEG reads

METHODS/STUDY POPULATION:

• Subjects: Nurses caring for patients admitted to the Neuro ICU at Duke University Hospital who are initiated on cEEG.

• Nurses evaluate qEEG display at the bedside on an hourly basis after undergoing a standardized qEEG training session. The standard practice of independent review of cEEG and treatment by the Neuro ICU team remains unchanged.

• Post-hoc review of cEEG data by two blinded, board-certified neurophysiologists will be performed for each patient. The raw cEEG data will be scored for the number of seizures present per hour, background, seizure duration, and seizure spatial extent.

• The time from first seizure occurrence to clinical recognition will be recorded.

RESULTS/ANTICIPATED RESULTS:

• Thus far, 91 patients with 583 1-hour blocks of nurse interpretations have been studied, with 6 patients experiencing seizures while on study. Enrollment will be completed on 1/17/20

• Preliminary data show a sensitivity of 95.8% (79.9%, 99.9%), specificity of 95.2 (93.1%, 96.8%), positive predictive value of 46.0% (36.9%, 55.4%), negative predictive value of 99.8% (98.7%, 99.9%), positive likelihood ratio of 19.8 (13.6, 28.9), negative likelihood ratio (0.04 (0.01, 0.3). All confidence intervals are 95%. False alarm rate is 0.05/hour.

• Further analyses are pending completion of enrollment in January 2020.

DISCUSSION/SIGNIFICANCE OF IMPACT: Nurse interpretation of real-time bedside qEEG for seizure detection is feasible in the Duke Neuro ICU. QEEG functions well as a screening tool with good specificity and low false alarm rate. Use of qEEG by nurses could lead to shorter time to seizure detection, which may improve patient outcomes. CONFLICT OF INTEREST DESCRIPTION: Safa Kaleem, BS: Research reported in this publication was supported by a Pfizer Foundation grant and the Duke Clinical Translational Science Institute (CTSI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Pfizer Foundation or the Duke CTSI. Jennifer H. Kang, MD: None to declare. Alok Sahgal, MD: None to declare. Christa B. Swisher, MD: Received speaker’s honorarium from EISAI and UCB.

Objectives/Goals: Urinary tract infections (UTIs) cause significant morbidity, and many patients require multiple courses of antibiotics increasing the risk of antibiotic resistance. We determined the prevalence of urinary antibiotic heteroresistance (HR), which has been associated with treatment failures in vivo, to three first-line antibiotics for UTIs. Methods/Study Population: Clinical urine Escherichia coli isolates from patients in metropolitan Atlanta, Georgia in August 2023 were collected as part of public health surveillance performed by the CDC-funded, Georgia Emerging Infections Program (EIP). Only the first E. coli isolate collected for each patient was included in this study. Antibiotic susceptibility was determined through medical record review. HR to nitrofurantoin, trimethoprim-sulfamethoxazole, and fosfomycin was determined by population analysis profiling (PAP), where broth dilutions of E. coli were plated on increasing concentrations of the antibiotic. HR was defined as survival of >1 in 106 cfu but fewer than 50% survival at 1X antibiotic breakpoint (bp), resistant as > 50% survival at 1X bp and susceptible as survival of Results/Anticipated Results: Among 355 patients, 21 (5.9%) were resistant or intermediate to nitrofurantoin and 92 (26%) were resistant to trimethoprim-sulfamethoxazole. Antibiotic susceptibility data were missing from 5(1.4%) and 11(3%) of isolates for nitrofurantoin and trimethoprim-sulfamethoxazole, respectively. Susceptibility testing was not routinely performed nor reported for fosfomycin, thus excluded. PAP revealed that of the total 355 isolates, 3(0.84%) were heteroresistant to nitrofurantoin, 17(4.8%) were heteroresistant to trimethoprim-sulfamethoxazole, and 27(7.6%) were heteroresistant to fosfomycin. Of the isolates found to be susceptible by standard testing, 1(0.3%) and 9(3.6%) were heteroresistant to nitrofurantoin and trimethoprim-sulfamethoxazole by PAP, respectively. Discussion/Significance of Impact: Despite low rates of HR to nitrofurantoin and trimethoprim-sulfamethoxazole (0.84%, 4.8%), HR to fosfomycin was more frequent (7.6%). Given that susceptibility is not generally performed for fosfomycin, this could have implications for including fosfomycin as a first-line treatment for E. coli UTIs.

OBJECTIVES/SPECIFIC AIMS: Patients are increasingly using online materials to learn about gynecologic cancer. Recent studies demonstrate that 85-96% of patients with a gynecologic malignancy utilize the Internet as a health resource. Providers can refer patients to educational materials produced by major medical associations available on their websites. However, patient educational materials (PEMs) published by professional organizations from other surgical specialties have been shown to be difficult to read for the average American. The NIH and AMA recommend that PEMs be written between a sixth and eighth grade reading level. In this study, we assess the readability of online PEMs on gynecologic cancer published by major medical associations. METHODS/STUDY POPULATION: Seven national medical association websites with PEMs on gynecologic malignancy were surveyed: American College of Obstetricians and Gynecologists, Center for Disease Control, Foundation for Women’s Cancer, National Cancer Institute, National Cervical Cancer Coalition, National Ovarian Cancer Coalition, and Society of Gynecologic Oncology. Online PEMs were identified and analyzed using five validated readability indices. One-way ANOVA and Tukey’s test were performed to detect differences in readability between publishers. RESULTS/ANTICIPATED RESULTS: Two hundred and thirty PEMs were included in this analysis. Mean readability grade levels with standard deviation were: 11.3 (2.8) for Coleman-Liau index; 11.8 (3.2) for Flesch-Kincaid; 11.1 (1.2) for FORCAST formula; 12.5 (2.7) for Gunning FOG formula; 12.1 (2.6) for New Dale-Chall formula; and 13.5 (2.5) for SMOG formula. Overall, PEMs were written at a mean 12th grade reading level. Only 4.3% of articles were written at an 8th grade reading level or below. ANOVA demonstrated a significant difference in readability between publishing associations (p<0.01). PEMs from the Center for Disease Control had a mean 10th grade reading level and were significantly lower than all other organizations. PEMs from The Foundation for Women’s Cancer had a mean 13th grade reading level and were significantly higher than most other organizations. DISCUSSION/SIGNIFICANCE OF IMPACT: Gynecologic oncology PEMs available from major medical association are written well above the recommended sixth to eight grade reading level. Simplifying PEMs may improve patient understanding of their disease and facilitate physician-patient communication.

OBJECTIVES/GOALS: Despite a steady rise of graduate degrees in biostatistics earned in the US, the percent from minorities remains low. This poster will describe the Collaborative Undergraduate Biostatistics Experience (CUBE), an 8-week program aimed to diversify and bring awareness to the field of collaborative biostatistics, from recruitment through evaluation. METHODS/STUDY POPULATION: The CUBE program is funded jointly by the NIH’s NIDA/NIAAA (award number: 1R25DA058482-01) and is designed to give underrepresented minority (URM) undergraduate students in STEM the opportunity to engage in a collaborative biostatistics and health data science experience, along with related professional development activities. The program is built on four pillars: 1) training in introductory biostatistics, 2) training in R programming, 3) professional development, and 4) a collaborative research project addressing research questions in various disciplines. The CUBE program was delivered in the summer of 2022 as a pilot to four URM students at Virginia Tech (VT) and the University of Virginia (UVA), with two at each site. In summer 2023, the program was offered to 5 students (3 VT, 2 UVA). RESULTS/ANTICIPATED RESULTS: This poster will provide strategies learned over two summers with respect to recruitment and enrollment, along with details on the program content, timeline, and short- and long-term program evaluation metrics (both quantitative and qualitative). The CUBE program was well-received by students participating in summers 2022 and 2023, where improved attitudes towards statistics were demonstrated, and 7 of the total 9 participants (78%) over the past two summers expressed interest in pursuing a graduate degree in biostatistics or a career in quantitative research. Of these 7 students, 1 is currently enrolled in a biostatistics graduate program in the United States. DISCUSSION/SIGNIFICANCE: Results can be used to offer recommendations to leaders in the field on how to establish similar programs seeking to provide a pipeline for equity and diversity in the practice of collaborative biostatistics and health data science.

ABSTRACT IMPACT: This work seeks to improve the diagnostic accuracy of urinary tract infection among hospitalized older adults and mitigate antibiotic overuse in this population. OBJECTIVES/GOALS: Primary objective: To determine the diagnostic accuracy of serum procalcitonin (PCT) for the diagnosis of symptomatic urinary tract infection (UTI) in hospitalized older adults. Secondary objectives: (1) To develop a predictive model for the diagnosis of UTI; (2) To determine the ability of PCT in discriminating between lower and upper UTI. METHODS/STUDY POPULATION: We performed a prospective observational cohort study of 228 participants from a single institution. The study population included older adults (age 65 or older) who were hospitalized on the general medicine wards with a possible or suspected urinary tract infection (UTI). Upon obtaining informed consent, serum procalcitonin (PCT) was processed on remnant blood samples collected from the emergency department. We performed additional data collection through the electronic health record to obtain demographic information, clinical characteristics, and other laboratory and imaging results. Clinicians were surveyed for the diagnosis of UTI and charts were adjudicated by independent reviews of the medical record by infectious diseases experts to determine the primary endpoint of symptomatic UTI. RESULTS/ANTICIPATED RESULTS: We anticipate that serum procalcitonin predicts the presence of symptomatic urinary tract infection (UTI) by demonstrating an area under the receiver operating characteristic curve of at least 0.85. A predictive model developed in our cohort for the diagnosis of symptomatic UTI will be improved by the addition of serum PCT to the prediction model. Finally, we anticipate the serum PCT will accurately discriminate between upper and lower UTI. DISCUSSION/SIGNIFICANCE OF FINDINGS: Diagnosis of symptomatic UTI in hospitalized older adults is challenging and may lead to overuse of antibiotics and the development of antibiotic resistance in this vulnerable patient population. Serum procalcitonin offers a novel diagnostic strategy in the diagnosis of symptomatic UTI to enable more appropriate antibiotic therapy.

OBJECTIVES/SPECIFIC AIMS: (1) To delineate the function of the heavy-chain receptor binding domain (HCR), a portion of botulinum neurotoxin type A (BoNT/A) and synaptic vesicle 2 (SV2) signaling pathway, which provide a novel multipurpose biologic with potential clinical applications in tumor detection/imaging, inhibition of tumor progression, and reduction of bioactive hormone secretion in metastatic neuroendocrine (NE) cancers. (2) To evaluate the expression pattern of SV2 receptors in NE cancer patient-derived tissues for prediction of patient response for recombinant HCR (rHCR) treatment. (3) To assess the in vivo efficacy and toxicity of rHCR in a NE cancer liver metastasis mouse models and in the NE patient-derived 3D MicroTumor system. (4) To collect preclinical data to design and conduct a clinical trial with NE cancer patients, a major goal toward translating our discoveries into much needed therapies. METHODS/STUDY POPULATION: Recombinant botulinum heavy chain (rHCR) was produced using an IPTG-inducible expression vector in E. coli BL21. The rHCR was His-Tag purified and stored in PBS buffer before usage. Cytotoxicity: H727, TT, and MZ cells were plated at a density of 5000 cells/well in 96-well plates and incubated under standard conditions overnight. The next day, cells were treated with 10, 100, or 500 nmol/L of rHCR and incubated for 72 hours. Following incubation, cell viability was assessed by ATP quantification using the CellTiter-Glo (Promega) assay. Fresh NE tumors were dissociated and injected into polydimethylsiloxane bioreactors in a matrigel and collagen suspension for 3D culture experiments. The viability of 3D cultures incubated with various doses of rHCR was assessed by measuring the uptake of the near-infrared dye IR-783 using an IVIS imaging system. Western blot: H727, TT, and MZ cells were seeded in 6-well plates at a density of 3×105 cells/well for 24 hours followed by treatment with 100 nmol/L for 72 hours. Total cellular proteins were isolated and analyzed to assess the level of SV2A expression and the effect of rHCR on the expression levels of NET marker proteins. Immunohistochemistry: Deparaffinized tissue culture slides were incubated with SV2A primary antibody in 1% BSA and incubated overnight at 4°C. Slides were rinsed twice with TBS containing 0.025% Triton, followed by 0.3% H2O2 for 15 minutes. Slides were then incubated with HRP-conjugated secondary antibody for 1 hour at room temperature. Detection of protein-protein interaction: Precleared cell lysate was incubated with glutathione-agarose beads in the presence of 10 μg of GST-tagged rHCR for 2 h at 4°C with end-over end mixing. Samples were then centrifuged at 10,000 g for 2 minutes and the supernatant was analyzed by SDS-PAGE. Preclinical models: To allow rHCR testing on NET patient derived cells in a very novel 3D surrogates, sterile collected fresh NET tissues will be obtained from the UAB Tissue Procurement, dissociated into a single cell suspension and injected into a polydimethylsiloxane bioreactors containing extracellular matrix composed of bovine collagen and matrigel. Such 3D cell culture will be maintained in bioreactors with constant supply of media through the microchannels and treated with rHCR at concentrations ranging from 10 nM to 1 mM. Following histologic confirmation of growth and morphology of NET patient-derived 3D surrogates we will test the anticancer activity of rHCR in this system using the standard cytotoxicity assays as well as we will validate the NET hormone expression using immunohistochemistry assay. To create an animal model of NE cancer progression, we will perform intrasplenic injection of NET cell lines. In approximately 4 weeks, the animals should develop NE liver metastases based upon our previous experience. rHCR-iFPs accumulation in the tumor mass: rHCR-iFPs will be injected to the tumor bearing mice after 4 weeks of cells implantation in 1 week interval for total of 4 treatments at the concentrations of 0.125, 1.25, and 12.5 mg/kg. RESULTS/ANTICIPATED RESULTS: Based on the preliminary data, we expect to detect rHCR-iFPs in NE cancer xenografts and in patient derived 3D explants. Our preliminary data revealed that treating NETcells with rHCR significantly reduced NE peptide expression in 3 days. Thus, we expect to see the decrease of NE tumor markers even if the fluorescent detection method is not sensitive enough to monitor the signal. The reduction of the NET markers can be used as an indicator of the rHCR-iFPs uptake by the tumor mass. If HCR exhibit high binding affinity to SV2 receptors in NET models but moderate anticancer efficacy, we plan to use rHCR peptide to conjugate with the nanocarrier for targeted drug delivery. In this case rHCR peptide can be used as a ligand that specifically binds to NE cancer cells and delivers anticancer drug. In 3D NET patient derived explants we expect significant reduction of NET markers and hormones (serotonin and calcitonin) in NE cancer cells upon long-term rHCR-iFPs treatment. In addition, we will perform multiplex protein quantification assay using Luminex to assess the various hormones, cytokines, and growth factors to be repurposed into a diagnostic and detection reagent, or a drug delivery ligand for targeted therapies. DISCUSSION/SIGNIFICANCE OF IMPACT: NE cancers are highly metastatic: NE cancers such as carcinoid, islet cell tumors, and medullary thyroid cancer frequently metastasize to the liver. They are the second most prevalent GI malignancy. Ninety percent of patients with pancreatic carcinoid tumors and 50% of patients with islet cell tumors develop isolated hepatic metastases. Patients with untreated, isolated NE liver metastases have <30% 5-year survival. Thus, there is a critical need for new therapies for NE cancers. Surgery is the only curative therapy available for patients with NE cancers but most cannot be cured: surgical removal is the most effective treatment for NE cancers; however, a very high percentage of patients present with metastatic disease. While surgical resection can be potentially curative, many patients are not candidates for operative intervention due to widespread metastases or the degree of hepatic involvement by the NE cancers. Moreover, other forms of therapy including chemoembolization, radioembolization, cryoablation, and chemotherapy have had limited efficacy. We hope that our in vitro data on rHCR toxicity and specificity to NET, validated in the pre-clinical models will allow the first in-human application of this technology in clinical studies.

OBJECTIVES/SPECIFIC AIMS: To compare the accuracy and precision for estimating the diagnostic accuracies (sensitivities and specificities) between differential verification (DV) and partial verification (PV) methods. Comparisons were made under scenarios with different values of design parameters including disease prevalence, proportion of verification for positive results, proportion of verification for negative result, sensitivity and specificity of the brass standard (BS) test in DV method. Through comparing 2 different verification methods under different scenarios, we give suggestions that which verification method is optimal under different design settings. METHODS/STUDY POPULATION: For both PV and DV methods, simulation studies were performed using statistical package R, version 3.1.3. We were primarily interested in studying how the unbiasedness and precision for estimation of diagnostic accuracies (sensitivity and specificity) of an index test change with the following design parameters: disease prevalence, proportion of verification for positive test results, the proportion of verification for negative test results, and the sensitivity and specificity of a BS test. We chose different values for each of the above parameters. For each estimation, we allowed values in only 1 parameter to change by fixing the other 2 parameters, so that the effect of each design parameter on the unbiasedness and precision of both sensitivity and specificity can be determined. For the DV method, we also developed an analytical method to estimate the sensitivity and specificity of an index test using a quadratic equation with a unique solution of the specificity and sensitivity. RESULTS/ANTICIPATED RESULTS: For rare disease with prevalence less than 1%, the PV method resulted in a less biased and more precise estimate of sensitivities and specificities of the index test. If the disease prevalence was between 1% and 10%, the DV method using a BS test with moderate or high sensitivity and specificity (sensitivity and specificity >90%) resulted in a less biased and more precise estimate of diagnostic accuracies of the index test. When the disease prevalence was greater than 10%, the PV method was superior when the BS test had sensitivity and specificity <80%, and the DV method was superior when the BS test had both sensitivity and specificity >90%. When the proportion of verification of positive test results was <30% or >70%, the DV method yielded smaller bias for the estimated specificity than the PV method. However, the PV method generated a much smaller mean square error (MSE) for specificity than the DV method when the proportion of verification for positive test results was >50%. Although the disease prevalence was >10% and the proportion of verification of positive test results was <30%, the DV method resulted in a smaller MSE for specificity. DISCUSSION/SIGNIFICANCE OF IMPACT: Disease prevalence and proportions of verification for patients with positive and negative test results influence the accuracy of a new diagnostic test. If a new index test for a very rare disease is evaluated, the PV method should be used for assessing the performance of the index test. When a disease prevalence is >1%, the DV method will result in a less biased and more precise estimate of diagnostic accuracy of an index test, if the BS test itself used in the DV method has large specificity and specificity. One concern of using BS test for the DV method is the clinical cost. Depending on the disease type, the BS tests usually are imperfect, but may be less aggressive and/or less expensive than the gold standard test. Moreover, as all clinical examinations require professional personnel to perform, verification of the index test for relative large proportion of a large cohort of patients could become a burden on human resources. Thus, the future research of the optimal design method for a diagnostic accuracy study should be based on the comprehensive cost-effectiveness analysis.

The National Center for Advancing Translational Sciences has called for more comprehensive research with priority populations to reduce disparities and for the development of additional resources to assist researchers in implementing these recommendations. Here we report the development and initial evaluation of five Priority Populations Toolkits, which are resources developed by the University of Illinois Center for Clinical and Translational Science to meet these goals. Three aims guide the content: increasing knowledge, facilitating communication, and improving research design. Materials were curated from scientific literature reviews and Internet searches and revised iteratively. Analytics and user surveys provide information about usage. In 22 months, 387 unique users accessed the toolkits. The top reason for usage was to improve research recruitment. Comprehensive toolkits for working with priority populations show promising potential for increasing knowledge and readiness to work with underrepresented populations. Further toolkit development and evaluation of effectiveness are warranted.