Objectives/Goals: We hypothesized that adding cytomegalovirus (CMV) viral Fc gamma receptors (vFcγRs) to a glycoprotein B (gB) protein subunit vaccine would improve vaccine-elicited Fc mediated effector functions such as antibody dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC), over gB subunit alone. Methods/Study Population: We immunized rabbits (n = 4 per group) at Weeks 0, 4, and 8 with 20μg gB alone or with one vFcgR (gp34, gp68, or gp95) at 20μg or 40μg, adjuvanted with squalene emusion, Addavax. Plasma from immunized rabbits was analyzed for antigen-specific IgG binding via enzyme-linked immunosorbent assays (ELISAs). ADCP was measured by conjugating whole virions to a fluorescent marker (AF647), incubating the fluorescent virus with rabbit plasma, and measuring uptake of virus by THP-1 monocytes via flow cytometry. ADCC was measured by natural killer cell degranulation via flow cytometric detection of CD107a expression following co-incubation with CMV-infected fibroblasts and rabbit plasma. Results/Anticipated Results: Each vFcγR demonstrated immunogenicity, although average vFcγR-binding IgG titers were between 4- to 10-fold higher in animals receiving the 40μg dose of each vFcγR compared to the 20μg dose. We observed similar IgG binding responses against gB among all vaccine groups. Comparing groups at peak immunogenicity (Week 10), ADCP responses were improved over gB alone by approximately twofold in animals receiving 40ug of each vFcγR. This effect was maintained across several human CMV strains with variable vFcγR genes. ADCC responses were undetectable in all animals immunized with gB alone, yet those receiving 40μg gp34 or gp95 demonstrated detectable ADCC. Discussion/Significance of Impact: HCMV-specific ADCP and ADCC are associated with protection against vertical CMV transmission, so a vaccine including vFcγRs which can improve vaccine-elicited Fc-effector responses is promising toward reducing the immense global impact of congenital CMV and associated neurologic birth defects.

OBJECTIVES/GOALS: Patient-specific definition of extent of surgical excision is foundational to the safety offered by computer assisted interventions. Consequently, this study aims to develop a pipeline for automated segmentation of bone removed during cortical mastoidectomy, a technically complex otologic surgery. METHODS/STUDY POPULATION: A simulator, previously developed in our lab, allows fully immersive simulation of mastoidectomy using segmented temporal bones generated from CT data. Using the simulator, one attending surgeon will perform three trials of mastoidectomy on 20 different temporal bones. From the simulator we will obtain data on the volume of bone removed for a specific anatomy, averaged between trials. No new U-net (nnU-net), an open-source three-dimensional segmentation network, will then be trained to predict the volume of bone removed using segmented pre-operative CT imaging. Segmentation accuracy will be evaluated with the Dice coefficient, modified Hausdorff distance (mHD), sensitivity and specificity. RESULTS/ANTICIPATED RESULTS: We expect the mean pairwise Dice coefficient to be high indicating relative similarity of volume removed between trials. Moreover, we predict that following five-fold cross-validation the best model will result in a Dice coefficient, mHD, sensitivity, and specificity indicative of volume removed predictions consistent with surgeon-generated data. Finally, given that network training will penalize overlap of the predicted excised bone segment and previously segmented anatomic structures, we expect that no critical anatomical structures will be marked as tissue removed. DISCUSSION/SIGNIFICANCE: We hope to show that deep learning architectures can accurately predict bone removed during mastoidectomy. These predictions can be used for preoperative planning, as clinical endpoints in surgical simulators, or be used in conjunction with surgical robots, all ultimately improving patient safety.

Objectives/Goals: There remains an urgent need for the development of safe and effective therapeutics for the long-term management of pain. We evaluated our novel analgesic in multiple pre-clinical models to assess its abuse liability, analgesic efficacy in models of chronic pain, and its mechanism of action in ex vivo spinal cord slices. Methods/Study Population: We evaluated SSA3’s abuse liability by utilizing an IV self-administration paradigm. In this experiment, rats are placed in a chamber and have the option to press two different levers. Abuse liability was determined based on extent of lever pressing on the drug-infusion lever. To evaluate chronic pain efficacy, mice underwent a spared nerve injury (SNI) which induces sustained hypersensitivity in their hind paw. Mice were then treated with SSA3, and their tactile hypersensitivity was assessed. Finally, the mechanism of action was investigated through patch clamp electrophysiology recordings taken from excised spinal cord slices in mice. We recorded currents from neurons involved in the pain signaling pathway before and after application of our compound to observe drug efficacy at the cellular level. Results/Anticipated Results: Our results demonstrated that in a pre-clinical IV self-administration paradigm, SSA3 exhibited no abuse liability, indicated by a lack of drug intake or escalation of drug intake. Results from our SNI model of chronic pain reveal that when SSA3 is administered directly onto the spinal cord via intrathecal injection, it is efficacious in reversing the pain hypersensitivity established by the model, suggesting a spinally mediated mechanism of action. Finally, we observed that SSA3 effectively reduced the amplitude of NMDA receptor-mediated excitatory postsynaptic currents in a concentration-dependent manner. This reduction in amplitude suggests that our compounds analgesic efficacy comes from the inhibition of spinally mediated NMDA receptor signaling. Discussion/Significance of Impact: This investigation into the therapeutic potential of substituted agmatine for the management of chronic pain revealed several key insights. Our drug is efficacious in models of chronic pain and, importantly, lacks the abuse liability commonly seen with analgesic drugs. Our drug’s mechanism of action involves inhibition of spinal NMDA receptors.

Objectives/Goals: Research supports the use of music to improve the care and well-being of adults living with dementia; however, the practice and implementation of music in elder care communities is not regulated. The goal of this qualitative study was to survey elder care communities in Northeast Kansas to determine the use of music with people living with dementia. Methods/Study Population: We interviewed staff (n = 10) at five elder care communities in the Kansas City Metro area and observed musical activities and artifacts in shared living spaces within each community. Interview questions included details of the frequency and purpose of using music, who determined which music to use, and any effects, positive or negative, the interviewee believed to be associated with the use of music. Musical events, visiting musicians or music therapists leading group sing-alongs were observed at two communities, and music-related activities led by staff were observed at two others. Results/Anticipated Results: Music was used in some way at each of the five communities. Each location had recorded music available to residents in the shared living spaces, and most had a piano in the main lounge area. During the sing-along and music-related activities, residents were observed singing along to songs from memory, engaging with one another and the group leader and smiling. Staff employed by each community varied in their level of musical training and experience, from none to a full-time music therapist in residence. Staff interviewed said they believed music was helpful to aid memory recall, reduce anxiety, and to engage interest. Interestingly, a music therapist at one site also described how music during mealtimes created too much of a distraction for residents and interfered with dietary care. Discussion/Significance of Impact: It is clear from both the staff interviews and direct observations of musical activities that music is important to consider for people living with dementia in care communities. Guidelines for implementation and minimum standards would be helpful to ensure all care community residents can experience benefits highlighted by staff in this study.

ABSTRACT IMPACT: Within three EDs in a regional health system in Connecticut, African American race, male gender, non-Hispanic ethnicity, lack of private insurance, and homelessness were associated with significant odds of being physically restrained during a visit. OBJECTIVES/GOALS: Agitated patient encounters in the Emergency Department (ED) are on the rise, and physical restraints are used to protect staff and prevent self-harm. However, these are associated with safety risks and potential stigmatization of vulnerable individuals. We aim to determine factors that are associated with odds of being restrained in the ED. METHODS/STUDY POPULATION: We conducted a retrospective cohort analysis of all patients (≥18 yo) placed in restraints during an ED visit to three hospitals within a large tertiary health system from Jan 2013-Aug 2018. We undertook descriptive analysis of the data and created a generalized linear mixed model with a binary logistic identity link to model restraint use and determine odds ratios for various clinically significant demographic factors. These include gender, race, ethnicity, insurance status, alcohol use, illicit drug use, and homelessness. Our model accounted for patients nested across the three EDs and also accounted for multiple patient visits. RESULTS/ANTICIPATED RESULTS: In 726,417 total ED visits, 7,090 (1%) had associated restraint orders. Restrained patients had an average age of 45, with 64% male, 54% Caucasian and 29% African American. 17% had private insurance, 36% endorsed illicit substances, 51.4% endorsed alcohol use and 2.3% were homeless. African Americans had statistically significant odds of being restrained compared to Caucasians with adjusted odds ratio (AOR) of 1.14 (1.08,1.21). Females (AOR 0.75 [0.71, 0.79] had lower odds of being restrained compared to males while patients with Medicaid (AOR 1.57 [1.46, 1.68]) and Medicare (AOR 1.70 [1.57, 1.85]) had increased odds compared to the privately insured. Illicit substance use (AOR 1.55 [1.46, 1.64]), alcohol use (AOR 1.13 [1.07, 1.20] and homelessness (AOR 1.35 [1.14, 1.16]) had increased odds of restraint use. DISCUSSION/SIGNIFICANCE OF FINDINGS: We showed statistically significant effects of patient demographics on odds of restraint use in the ED. The increased odds based on race, insurance status, and substance use highlight the potential effects of implicit bias on the decision to physically restrain patients and underscores the importance of objective assessments of these patients.

OBJECTIVES/GOALS: An evidence-based approach for childhood obesity is family-based treatment (FBT). Research supports that motivation and income level may impact treatment success; however, the relationship between the two is understudied. Therefore, the objective of this study was to examine whether motivation for beginning FBT is associated with income levels. METHODS/STUDY POPULATION: 459 parent and child dyads from the PLAN (Pediatric, Learning, Activity, Nutrition) with Families multisite study were included in this study. PLAN consists of FBT through personalized health coaching over the course of two years, focusing on nutrition, physical activity, and parenting skills. Parent and child also attend height and weight assessments every 6 months in the study. Outcomes of the study include weight change and mastery of behavioral skills. Motivation and income level were provided by self-report at the beginning of the study. Motivation was based on a scale from 1-10 (1 = no motivation, 10 = high motivation). Income levels were grouped into one of three broader categories- low income ($80,000/year). RESULTS/ANTICIPATED RESULTS: The mean level of motivation for the parent was 8.76 and for the child was 7.87. There was a significant difference in the mean level of motivation for the child and parent, t = 7.73, p = < .001. Post-hoc multiple comparisons using Tukey’s HSD test indicated that children in the high-income group had lower levels of motivation (M = 7.29, SD = 2.07) compared to children in the middle (M = 8.18) and low (M = 8.70) income groups. Level of motivation did not differ for children in the middle and low-income groups. Finally, parent motivation level did not differ significantly by income group. While there were significant differences between parent and child motivation levels, the motivation remained high for both groups. DISCUSSION/SIGNIFICANCE OF IMPACT: The data suggests a significant difference in mean child motivation and income level. Child’s high motivation may be from the idea of participating in something new, a rare opportunity for low-income children. To improve the implementation and efficacy of FBT, further study into the relationship between motivation and income level should be done.

OBJECTIVES/SPECIFIC AIMS: Research overview: Providing patient-centered care is increasingly a top priority in the U.S. healthcare system.1,2 Hospitals are required to publicly report patient-centered assessments, including results from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient satisfaction surveys.3 Furthermore, clinician and hospital reimbursements are partially determined by performance on patient satisfaction measures.3 Consequently, hospitals and clinicians may be incentivized to improve patient satisfaction scores over other important outcomes.4 Paradoxically then, the pursuit of patient-centered care may lead clinicians to fulfill patient requests for unnecessary and potentially harmful treatments.5 Opioid prescribing during hospitalizations may be particularly affected by clinicians’ seeking to optimize patient satisfaction scores.6,7 Satisfaction with pain care is an important predictor of overall patient satisfaction in the HCAHPS surveys,8,9 and clinicians report increased pressure to fulfill patient requests for immediate pain-relief.10,11 Therefore, clinicians may prescribe opioids to avoid receiving lower patient satisfaction scores.12,13 Furthermore, clinicians lack clear guidance on opioid prescribing for some populations, including non-surgical inpatients, who represent almost half of all hospitalizations.14 To reduce clinicians’ incentive to prescribe opioids as a means of achieving patient satisfaction, the Center for Medicare and Medicaid Services (CMS) temporarily removed questions related to patient satisfaction with pain care from the clinician and hospital reimbursement formulas beginning in 2018.15 Importantly, prior research16-20 has not rigorously tested the hypothesis implied by the CMS policy change: that certain opioid prescribing practices in inpatient pain care are associated with higher patient satisfaction. Objectives: The purpose of this study was to evaluate the association between the receipt/dose of opioids during non-surgical hospitalizations and patient satisfaction measured by the HCAHPS survey. METHODS/STUDY POPULATION: Methods/Study Population: We conducted a pooled cross-sectional study of adults (18 and older) with non-surgical hospitalizations within the 11-hospital healthcare system in a Midwestern state from 2011-2016. Data were extracted from electronic health records and linked to HCAHPS patient satisfaction surveys. We estimated the propensity score for receipt of any opioids during hospitalization and separately the receipt of high dose opioids (≥100 morphine milligram equivalent [MME]) based on patient, encounter, and facility characteristics for all hospitalizations with complete data. We used nearest neighbor matching to construct two matched samples to minimize selection bias and confounding by indication. We used a standardized difference threshold of < 0.1 as an indication of the balance between matched groups. Outcomes were compared with a test on the equality of proportions using large-sample statistics. All analysis was performed in STATA 14.0 analytical software. Main outcomes: We analyzed four dependent variables. Two pain-specific patient satisfaction variables were derived from the responses to the following survey questions: 1) “During this hospital stay, how often your pain was well controlled? (pain control)” and 2) “During this hospital stay, how often did the hospital staff do everything they could to help you with your pain? (pain help)”, with 4-point Likert scale responses ranging from “Never” to “Always.” We also used two global satisfaction measures derived from the responses to the following survey questions: 1) “Using any number from 0 to 10, where 0 is the worst hospital possible and 10 is the best hospital possible, what number would you use to rate this hospital during your stay (overall patient satisfaction)?” and 2) “Would you recommend this hospital to your friends and family (willingness to recommend a hospital)? (4-point scale of “Definitely Yes” to “Definitely No”). Because the responses are not normally distributed, and the response options are truncated, we dichotomized each of these questions following previously published approaches8 and CMS methodology3 (e.g. “always” vs. all other responses or “9 or 10 rating” vs. all others). RESULTS/ANTICIPATED RESULTS: Results: Among 17,691 patients who reported that they needed pain medications during hospitalization in their HCAHPS survey, 43.7% (n=7,735) received opioids. Among the matched sample (n=8,848), 55% were female, 90% were white, 9% were black, 74% were emergency admissions, 29% had a circulatory diagnosis, 92% were discharged home, and the average pain score ranged from 0.2 to 7.1 during the hospital stay. Compared to matched patients hospitalized but did not receiving opioids, those who received opioids did not significantly differ in their rating of pain help (75% of patients without opioids rated that they always received help for their pain versus 75% of patients with opioids; p=.78), pain control (55% of patients without opioids reported that their pain was well controlled versus 54% on opioids; p=.93), willingness to recommend the hospital (69% of patients without opioids reported that they would definitely recommend a hospital versus 71% with opioids; p=.16) and overall rating of their care (47% of patients without opioids rated their hospitalization as 10 versus 46% on opioids; p=.22). DISCUSSION/SIGNIFICANCE OF IMPACT: Discussion: We found no evidence that receipt of opioids is associated with patient satisfaction, including at doses. To our knowledge, this is the first study that used propensity score matching to examine the association between inpatient opioid prescribing practices and patient satisfaction. Furthermore, our sample is unique in the inclusion of patients hospitalized for non-surgical indicators over a five year period in the multi-hospital healthcare system in a Midwestern state. Our findings add to the existing literature which has shown contradictory associations between opioid prescribing and patient satisfaction.16-22 Specifically, few studies that looked at surgical inpatients showed a lack of association between patient satisfaction16,18 and opioid prescribing, whereas others showed that receipt of opioids was associated with lower patient satisfaction.17-20 Our findings may imply that satisfaction with pain care may be achieved without administering opioids to non-surgical inpatients. Alternatively, satisfaction with pain care may not be influenced by opioid prescribing for non-surgical inpatients. Future research should further examine the association between opioid prescribing and patient satisfaction among non-surgical inpatients on a national scale to get a better understanding of the relationship between certain pain care practices and patient satisfaction.

OBJECTIVES/GOALS: Obesity is associated with increased incidence of breast cancer (BC), yet is not included in many lifetime-risk calculators. Obesity may impact breast cancer screening sensitivity. Retrospective studies show that bariatric surgery is associated with a lower risk of BC, but the effects of surgical weight loss on breast tissue are poorly understood. METHODS/STUDY POPULATION: We proposed a mixed-methods before and after study design to investigate the effects of surgical weight loss on breast tissue via pre- and post-weight loss breast tissue biopsies and imaging. In addition, we aimed to better understand barriers to BC screening for patients with obesity by conducting qualitative interviews. With institutional review board approval, we have begun recruiting 14 cisgender women who plan to undergo Roux-en-Y gastric bypass or sleeve gastrectomy. Participants must be at least 40 years old, with no prior history of breast biopsies or breast cancer and will undergo comprehensive breast cancer screening including mammography with quantitative density assessment, breast MRI, as well as breast core biopsies. RESULTS/ANTICIPATED RESULTS: We hypothesize that obesity and its associated metabolic changes lead to altered breast stroma, including increased inflammation, and tissue stiffness, with subsequent risk of carcinogenesis. If true, we expect to find obese women will have measurably increased inflammatory markers in their breast tissue, which are reduced after bariatric surgery. We expect that change in mammographic density may correlate with fibroglandular volume change on MRI; there are little data on change in background parenchymal enhancement in the setting of obesity and weight change and quantifying this will provide preliminary data for future work. Last, we expect that undergoing BC screening will be easier for patients after weight loss due to constraints of imaging equipment and potential bias in the screening process. DISCUSSION/SIGNIFICANCE: Screening for BC is paramount to improving outcomes yet people with obesity are screened less with worse outcomes. Studying the effects of weight loss on the breast may improve interpretation of breast imaging in the setting of obesity and identify markers of risk. Understanding barriers to screening may help us develop strategies to improve screening.

OBJECTIVES/GOALS: Current long bone fracture standard of care uses inert metal intramedullary nails (IMN), 10x stiffer than femur cortex. Consequent “stress-shielding” bone loss sees >5% of patients needing revision surgery. To improve nonunion healing, we develop automated design optimization methods for biodegradable Mg alloy IMNs to control local reloading. METHODS/STUDY POPULATION: Finite element analysis (FEA) is performed on 3D bone-IMN representations to establish this study’s baseline strain states for existing inert IMN geometries within QCT-informed femoral models under simulated biomechanical loading. FEA with Mg alloy properties for same IMN designs simulate transient IMN material loss through discrete time-step models with experimental in vivo Mg corrosion rates and strain-based bone density evolution using remodeling algorithms from literature. Transient stability and strength metrics, fracture zone stress profiles under gradual reloading and manufacturing constraints are formulated through gradient-based sensitivity analysis into a topology optimization framework (TOF) incorporating a reaction-diffusion degradation model to generate IMN topologies. RESULTS/ANTICIPATED RESULTS: TOF designs for Mg alloy IMNs with transient allowable strength constraints, using safety factors to prevent IMN failure, demonstrate higher compliance than standard inert IMNs with mechanical properties closer to native cortical bone. The biodegradation model within the TOF, informed by corrosion behavior from bone-IMN FEA study, predicts how potential design evolutions affect transient strain states of the system. Thus, local fracture region stress states are controlled by the algorithm optimizing for desirable transient stiffness profiles based on a minimum variance objective of fracture zone stress compared to a target bone stress profile. Optimized IMNs with porous, high surface area features achieve 50% decrease in IMN stiffness over 6 months recovery time and complete in vivo degradation in 24 months. DISCUSSION/SIGNIFICANCE: Our TOF reduces “stress-shielding” effects via design for controlled IMN biodegradation to gradually increase fracture zone loading, stimulating remodeling and reducing current risk of post-operative fracture and surgical removal in ~15k cases/yr. in the U.S. In vitro mechanical and in vivo clinical testing is required to validate design results.

Background: The Comprehensive Post-Acute Stroke Services (COMPASS) Study is one of the first large pragmatic randomized-controlled clinical trials using comparative effectiveness research methods, funded by the Patient-Centered Outcomes Research Institute. In the COMPASS Study, we compare the effectiveness of a patient-centered, transitional care intervention versus usual care for stroke patients discharged home from acute care. Outcomes include stroke patient post-discharge functional status and caregiver strain 90 days after discharge, and hospital readmissions. A central tenet of Patient-Centered Outcomes Research Institute-funded research is stakeholder engagement throughout the research process. However, evidence on how to successfully implement a pragmatic trial that changes systems of care in combination with robust stakeholder engagement is limited. This combination is not without challenges. Methods: We present our approach for broad-based stakeholder engagement in the context of a pragmatic trial with the participation of patients, caregivers, community stakeholders, including the North Carolina Stroke Care Collaborative hospital network, and policy makers. To maximize stakeholder engagement throughout the COMPASS Study, we employed a conceptual model with the following components: (1) Patient and Other Stakeholder Identification and Selection; (2) Patient and Other Stakeholder Involvement Across the Spectrum of Research Activities; (3) Dedicated Resources for Patient and Other Stakeholder Involvement; (4) Support for Patient and Other Stakeholder Engagement Through Organizational Processes; (5) Communication with Patients and Other Stakeholders; (6) Transparent Involvement Processes; (7) Tracking of Engagement; and (8) Evaluation of Engagement. Conclusion: In this paper, we describe how each component of the model is being implemented and how this approach addresses existing gaps in the literature on strategies for engaging stakeholders in meaningful and useful ways when conducting pragmatic trials.

Despite the adversity presented by COVID-19 pandemic, it also pushed for experimenting with innovative strategies for community engagement. The Community Research Advisory Council (C-RAC) at Johns Hopkins University (JHU), is an initiative to promote community engagement in research. COVID-19 rendered it impossible for C-RAC to conduct its meetings all of which have historically been in person. We describe the experience of advancing the work of the C-RAC during COVID-19 using digital and virtual strategies. Since March 2020, C-RAC transitioned from in person to virtual meetings. The needs assessment was conducted among C-RAC members, and individualized solutions provided for a successful virtual engagement. The usual working schedule was altered to respond to COVID-19 and promote community engaged research. Attendance to C-RAC meetings before and after the transition to virtual operation increased from 69% to 76% among C-RAC members from the community. In addition, the C-RAC launched new initiatives and in eighteen months since January 2020, it conducted 50 highly rated research reviews for 20 research teams. The experience of the C-RAC demonstrates that when community needs are assessed and addressed, and technical support is provided, digital strategies can lead to greater community collaborations.

Community engagement is essential to research. Community Advisory Boards (CABs) are frequently consulted to inform recruitment and engagement strategies. In our experience, a gap emerged between CAB recommendations and implementation, largely due to limitations in research infrastructure, funding, and team capacity. Researchers may underappreciate why providing contextual details about studies that relate to resources or constraints, can lead to tailored recommendations. In response, our institutional CAB now incorporates researcher input before and after consultations to clarify programmatic and institutional limitations. This ongoing, bidirectional dialogue supports more pragmatic, tailored recommendations that better align with research team capacity while advancing shared goals.

Multisector stakeholders, including, community-based organizations, health systems, researchers, policymakers, and commerce, increasingly seek to address health inequities that persist due to structural racism. They require accessible tools to visualize and quantify the prevalence of social drivers of health (SDOH) and correlate them with health to facilitate dialog and action. We developed and deployed a web-based data visualization platform to make health and SDOH data available to the community. We conducted interviews and focus groups among end users of the platform to establish needs and desired platform functionality. The platform displays curated SDOH and de-identified and aggregated local electronic health record data. The resulting Social, Environmental, and Equity Drivers (SEED) Health Atlas integrates SDOH data across multiple constructs, including socioeconomic status, environmental pollution, and built environment. Aggregated health prevalence data on multiple conditions can be visualized in interactive maps. Data can be visualized and downloaded without coding knowledge. Visualizations facilitate an understanding of community health priorities and local health inequities. SEED could facilitate future discussions on improving community health and health equity. SEED provides a promising tool that members of the community and researchers may use in their efforts to improve health equity.

ABSTRACT IMPACT: Olfactory dysfunction is a defining symptom of COVID-19 infection. As the number of total, confirmed COVID-19 cases approaches 7 million in the United States, it is estimated that there will be up to 500,000 new cases of chronically diminished smell. We offer a promising treatment. OBJECTIVES/GOALS: The primary aim is to explore the main effects and interaction of bimodal visual-olfactory training and patient-preferred scents on olfactory training in patients with post-COVID-19 hyposmia or anosmia. METHODS/STUDY POPULATION: The study will utilize a 2x2 factorial design. The two effects we will explore are unimodal versus bimodal training and conventional versus patient-preferred odors. All 4 arms will undergo 12 weeks of olfactory training. Participants will be assessed pre and post-intervention. Measurements of olfactory function include the objective smell identification test and subjective measures including the Clinical Global Impression Scale and Olfactory Dysfunction Outcomes Rating. Individuals eligible for the study include men and women between 18 and 70 years of age with olfactory dysfunction of at least 3 months duration initially diagnosed within 2 weeks of a COVID-19 infection. Of note, we will enroll nationally. RESULTS/ANTICIPATED RESULTS: We anticipate that the bimodal, patient-preferred scents training group will have the greatest improvement in smell scores, number of responders, and patient-reported sense of smell and health-related quality of life due to an additive interaction between the bimodal visual-olfactory and patient-preferred interventions. DISCUSSION/SIGNIFICANCE OF FINDINGS: The pathophysiology of COVID-19 olfactory dysfunction is mediated through damage to the peripheral and central olfactory pathways. This suggests that interventions most likely to be efficacious target both pathways, as olfactory training does.

OBJECTIVES/GOALS: To increase public awareness and access to research opportunities at the University of Minnesota (UMN) utilizing StudyFinder, a public-facing website that features actively enrolling UMN research studies and directly connects website visitors with study teams. METHODS/STUDY POPULATION: Promote the University of Minnesota CTSI’s StudyFinder website to the public via social media ad campaigns and community outreach. Upon completion of the latest StudyFinder enhancement project in 2021, CTSI focused 2022 efforts on marketing and promotion of the site. CTSI created three StudyFinder social media ad campaigns in January, June, and October. CTSI also planned outreach events during the week of Clinical Trials Day, the Minnesota State Fair (1.8M attendees over 12 days), and the UMN’s Urban Research and Outreach-Engagement Center Community Day. RESULTS/ANTICIPATED RESULTS: Website traffic data from Google Analytics indicated a 72.76% increase in StudyFinder sessions from 2021 (Jan 1, 2021 to Nov 1, 2021) to 2022 (Jan 1, 2022 to Nov 1, 2022), with 16,262 sessions to 28,094 sessions, respectively. Direct emails from potential participants to study teams increased 89% in that same timeframe, from 3,082 emails to 5,819 emails. Targeted marketing campaigns and attending community events can improve the visibility of an institution’s research and connections of potential research participants to research teams. DISCUSSION/SIGNIFICANCE: Recruitment remains a main challenge in clinical and translational research. StudyFinder is an important patient-facing tool to connect individuals to specific studies. Future directions include expanding marketing efforts, events, and public feedback.

OBJECTIVES/GOALS: The purpose of this 4-phase exploratory study is to create a human-centered protocol for a new program, CAPABLE-FAMILY, to address older adults with physical disability and dementia and their caregivers. METHODS/STUDY POPULATION: The Szanton-Gill Resilience Model, Verbrugge & Jett Disablement, and Life Span Theory of Control are theoretical frameworks guiding this study. Phase 1. Using qualitative research (n = 10 dyads) methods (ex. Photovoice) we seek to understand the context for older adults with dementia regarding disability. Phase 2. Using synthesis/ideation (n = 10 dyads) tools (ex. Journey Maps) we will synthesize the qualitative research during group ideation sessions with stakeholders. Phase 3. Using prototype testing (n = 3 dyads) methods (ex. Semantic Differentials, Storyboards), we will build the most promising prototypes. Phase 4. Using an open-label pilot (n = 3 dyads), we will test the interventions. RESULTS/ANTICIPATED RESULTS: We will assess disability (ADL, IADL), environmental changes pain, depression, polypharmacy, provider communication needs, and caregiver burden. We will interview the dyads and multiple CAPABLE Registered Nurses (RN), Occupational Therapists (OT), and Handymen (HM) about their prior experiences and perceptions of the pilot. CFQ, MocA, pain (BPI), and ZBI will be measured pre/post RN, OT, HM visit. While there are evidence-based programs to separately address cognitive impairment and physical disability, we anticipate this is the first study to develop a community-based goal-directed, human-centered approach for the maintenance of physical function for persons with dementia in the home. DISCUSSION/SIGNIFICANCE OF IMPACT: Persons with more cognitive impairment did not improve as much as those with less cognitive impairment in the original CAPABLE study, an evidenced based program which reduced disability. This suggests the need to adapt CAPABLE to reduce the burden of disability in persons with Alzheimer’s dementia. CONFLICT OF INTEREST DESCRIPTION: None

Objectives/Goals: Cholangiocarcinoma is an aggressive cancer with a poor prognosis. Fibroblast Growth Factor Receptor 2 fusions are therapeutic targets in ~20% of cholangiocarcinoma, which restricts their benefit to only a subset of patients. We investigate reverse phase protein array, as a novel assay for biomarker identification in cholangiocarcinoma. Methods/Study Population: Tumor samples were obtained via our registry (OSU-13053, NCT02090530). RPPA analysis was performed on tumor samples from 24 cholangiocarcinoma patients. Of these, 12 had FGFR2 fusions, 4 had FGFR2 SNVs, and 8 were FGFR wildtype. Tumor content was enriched using laser capture microdissection prior to analysis by reverse phase protein array. RPPA signal was measured by antibody binding to the phosphorylated tyrosine residue at location Y653.654 of FGFR2. Additional analysis was done for the following proteins: CD3, RSK, SGK1, STAT3, VEGFR2, 4EBP1, AKT, EGFR, eIF4G, ERK, FSR2, HLA, mTOR, p38 MAPK, p70S6K, p90RSK, PD-L1, PDGFR, RET, SHC, STAT, and ZAP70. Results/Anticipated Results: There was not a significant difference between FGFR2-phosphorylation in tumors with FGFR2 genomic alterations and tumors with wildtype FGFR. On the other hand, CD3 protein abundance was significantly lower in FGFR-altered tumors compared to wildtype, potentially indicating a cold tumor immune microenvironment in these patients. We plan to perform RPPA analysis on 61 more cases (17 FGFR-altered and 44 FGFR-wildtype) to generate a more robust sample size for subsequent analysis. Furthermore, we have access to 580 additional archival cholangiocarcinoma tumors for RPPA analysis (IRB approved protocol OSU-15030). We plan to sequence these tumors to determine FGFR status. We predict approximately 116 (20%) of these cases to be FGFR-altered. Discussion/Significance of Impact: Our results suggest that FGFR wildtype tumor may have increased FGFR pathway activation and could respond to FGFR inhibitors. Additionally, the cold tumor microenvironment in FGFR-altered tumors provide rationale for combination of FGFR inhibitors and immunotherapy. These results will be confirmed by RPPA analysis on additional cases.