OBJECTIVES/SPECIFIC AIMS: The objective of this project is the application of complex fusion models, which combine observed and modeled data, to areas with sparse monitoring networks with multiple chemical components is under-developed. Such models could provide improved accuracy and coverage for air quality measurement predictions, an area greatly limited by the amount of missing data. METHODS/STUDY POPULATION: This project focuses on the development of methods for improved estimation of pollutant concentrations when only sparse monitor networks are found. Sparse monitoring networks are defined as areas where fewer than three criteria air pollutants (based on EPA standards) are monitored. Particularly, a multivariate air pollutant statistical model to predict spatio-temporally resolved concentration fields for multiple pollutants simultaneously is developed and evaluated. The multivariate predictions allow monitored pollutants to inform the prediction of nonmonitored pollutants in sparse networks. RESULTS/ANTICIPATED RESULTS: Daily, ZIP code level pollutant concentration estimates will be provided for 8 pollutants across South Carolina, and goodness of fit metrics for model variants and previously established methods will be compared. DISCUSSION/SIGNIFICANCE OF IMPACT: These methods utilize only widely available data resources, meaning that the improved predictive accuracy of sparsely monitored pollutant concentrations can benefit future studies in any US area by improving estimation of health effects and saving resources needed for supplemental air pollutant monitoring campaigns. Our method for estimation attempts to improve predictive accuracy and data availability for sparsely monitored pollutants and areas.

OBJECTIVES/GOALS: The objective of this research is to begin documenting barriers to regenerative care to proactively address issues of accessibility and determine and implement interventions in anticipation of equitable care. We will explore the accessibility of Platelet Rich Plasma (PRP) for the treatment of knee osteoarthritis (Knee OA) METHODS/STUDY POPULATION: This research has two components. First, retrospective chart analysis using electronic databases to gather factors such as sex, race, ethnicity, disease severity, price, insurance, and treatments. Second. Prospective survey to gather the information (income, employment, education level) that are not found in the chart. Patients with knee OA conditions who received standard care will be compared to knee OA patients who received the novel PRP treatment. Statistical prediction modeling will be employed to determine the probability of receiving novel regenerative PRP treatment based on gathered explanatory variables. Our sample size is about 1000 patients per group (PRP group vs standard care group). Patients are from the three Mayo sites (Rochester, Arizona, Florida) as well as Detroit Medical Center. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis shows that only a homogenous of patients (white) are receiving the novel PRP regenerative care to treat knee OA even though African Americans suffer from knee OA at a much greater rate. However, we still don’t know what is the main driver of this homogeneity. We anticipate that insurance coverage and out-of-pocket cost of care for PRP to be a huge barrier. Also, we are anticipating the lack of knowledge about PRP and its level 1 meta-analysis efficacy, as well as physician bias for not recommending PRP to certain underrepresented populations could play a role as well. We plan to order the level of influence of each barrier for each sex, race, and ethnicity, so intervention can be personalized and targeted for each population of interest. DISCUSSION/SIGNIFICANCE: Almost half of Americans live with at least one chronic medical condition and regenerative medicine holds tremendous promise to address many disease categories. To design any intervention to increase access requires knowledge about barriers in regenerative care, which is why this research is very critical now before the wide implementation of care.

Objectives/Goals: We aimed to discover treatment candidates for uterine fibroids, a common benign tumor with adverse impacts on quality of life. Repurposing already approved medications for fibroids can expedite treatment option expansion. Using genetic proxies, we identified novel fibroid drug candidates and estimated their effect on risk of fibroid diagnosis. Methods/Study Population: We performed a genetically predicted gene expression (GPGE) analysis using S-PrediXcan and GTEx tissue models with multi-ancestry genome-wide association study (GWAS) summary statistics of fibroids (cases  =  74,294, controls  =  465). There were 81 genes significantly associated with fibroid risk. Querying drug–gene interaction databases identified 56 approved medications that target these genes, including two antihypertensives, hydralazine, and spironolactone. Using independent multi-ancestry GWAS summary statistics (N  =  635,969) for systolic (SBP) and diastolic blood pressure (DBP), we conducted GPGE analyses. Blood pressure (exposure) and fibroids (outcome) GPGE summary statistics in the same tissues were used for two-sample Mendelian randomization (MR) analyses to proxy medication effects. Results/Anticipated Results: GPGE analyses identified hydralazine/tumor protein P53 (TP53) activity and spironolactone/thyroid hormone receptor beta (THRB) activity as drug-gene candidate pairs. Both drugs increase gene activity of their paired gene. Increased TP53 expression was associated with SBP in four tissues (exposure). The MR results indicated hydralazine use, proxied by increased TP53 expression, may reduce fibroid risk by 42% per standard deviation of gene expression (odds ratio [OR]  =  0.58, p  =  1.43E-12). Increased THRB expression was associated with DBP in eight tissues and were included in the MR (exposure). The MR results suggest spironolactone use, proxied by increased THRB expression, may reduce fibroid risk by 23% per standard deviation of gene expression (OR  =  0.77, p  = 5.94E-6). Discussion/Significance of Impact: We provide biologically plausible evidence for repurposing hydralazine and spironolactone for reducing risk of fibroid diagnosis. Repurposing these hypertension medications could provide novel preventative treatments for fibroids, particularly for individuals disproportionately affected by both conditions.

Objectives/Goals: This systematic review aims to identify and synthesize evidence on the barriers and facilitators impacting the implementation of transcranial magnetic stimulation (TMS) in clinical practice, enhancing understanding for improved adoption and efficacy. Methods/Study Population: This systematic review follows PRISMA guidelines to identify relevant literature on barriers and facilitators to TMS in North America. We conducted a comprehensive search of databases including PubMed, Scopus, and PsycINFO, targeting studies published from 2000 onward. Eligible studies include qualitative and quantitative research focusing on adults aged 18 years and older in the USA and Canada. Two independent reviewers screened titles, abstracts, and full texts, extracting data on barriers and facilitators related to TMS implementation. Results/Anticipated Results: We anticipate identifying a diverse range of barriers and facilitators related to TMS implementation in North America. Expected barriers may include limited clinician knowledge, patient resistance, and logistical challenges in clinical settings. Facilitators could encompass supportive institutional policies, clinician training, and positive patient outcomes. The synthesis of findings will highlight key themes, guiding future research and practice. We aim to produce actionable recommendations for stakeholders, ultimately enhancing the effective integration of TMS in clinical care for adult populations. Discussion/Significance of Impact: This review will provide crucial insights into the barriers and facilitators of TMS implementation, informing clinicians, policymakers, and researchers. By highlighting actionable strategies, it aims to enhance TMS accessibility and efficacy, ultimately improving patient outcomes and advancing neurotherapeutic practices in North America.

OBJECTIVES/GOALS: In the crowded environment of the intestine, selected commensal bacteria and enteric viruses interact. The biological significance of this interaction, in either normal or pathological condition is not known. To study this interaction, we are developing a physiologically relevant model of an human intestinal epithelium. METHODS/STUDY POPULATION: Intestinal biopsies (ileum region) and fecal samples of 6 healthy and 6 active Crohn’s patients are being collected to derive human intestinal enteroid (HIE) lines. 2D-polarized HIE will be first characterized with studies of epithelial permeability, tight junctions and cell type composition, and co-cultured with matching fecal samples. The (co-)cultures will be then infected with human norovirus (HNoV), our model enteric virus, and infection will be quantified by RT-qPCR. In addition, the interaction of HNoV with bacteria derived from healthy or Crohn’s will be determined quantitatively by flow cytometry (viral tagging) and qualitatively by 16S sequencing of the total versus HNoV-bound bacterial species. RESULTS/ANTICIPATED RESULTS: Crohn’s patients are characterized by a microbiome dysbiosis and, in particular, by a high abundance of Enterobacteriacae. HNoV interacts with Enterobacter cloacae, and interestingly, HNoV infection is associated with exacerbation and reactivation of Crohn’s disease. By re-creating the intestinal milieu of healthy and Crohn’s patients, we expect that the kinetics of infection by HNoV will be higher in Crohn’s as compared to healthy volunteers. In addition, by studying the composition of the HNoV-bound bacterial component of Crohn’s versus heathy volunteers, we will be able to identify the contribution of selected bacteria to the expected increase of infection. DISCUSSION/SIGNIFICANCE OF IMPACT: With this study, we will fill the gap of knowledge on the importance of commensal bacteria and enteric virus interactions in healthy and diseased condition. This new knowledge will be paramount for the identification of novel strategies to combat highly prevalent virus infections.

OBJECTIVES/SPECIFIC AIMS: Due to scope and breadth of research activity and infrastructure capacities at academic medical centers, the discipline of Biomedical Informatics is often deployed in a decentralized manner through geographically dispersed and unrelated organizational units. As a result, without a conscious strategy, an academic medical center risks redundant effort and gaps in resources, and perhaps poor coordination. A mechanism to bring together disparate organizational entities to identify, discuss, and negotiate Informatics-related concerns may produce a better institutional research environment. The University of Rochester (UR) has implemented such a strategy of Informatics governance, adapting tactics from team science, diplomacy, and deliberative engagement. METHODS/STUDY POPULATION: Based on current needs and institutional Informatics priorities, the UR’s Clinical and Translational Science Institute (CTSI) established 6 Informatics “clusters” in distinct but deliberately overlapping focal areas: (1) Data—capture, management, and analysis of all types of data for research. (2) Analytics—quantitative research across the spectrum of translational research. (3) Infrastructure—technical and computing infrastructure to support informatics. (4) Electronic health records (EHR)—(i) features within the EHR explicitly designed to address the needs of research; (ii) accessing and procuring EHR data for research. (5) Population health—Informatics design and systems expertise relevant to population health research (a key CTSI focus area). (6) Education—development, deployment, and assessment of Informatics learning opportunities for learners at all levels. Each cluster facilitates access to expertise and resources around the institution, promotes collaboration, identifies redundancy, and serves as a forum to strategize regarding institutional needs related to Biomedical Informatics. A CTSI faculty or staff member leads each cluster. To maximize effectiveness of the cluster, other members are decision-makers in the organizations they represent, or serve in a critical staff function. Clusters meet in person on a quarterly basis with more frequent electronic interaction. The clusters share documents via Box, a secure online file sharing app. The cluster coordinators meet as a group on a biweekly basis to monitor progress and make plans. RESULTS/ANTICIPATED RESULTS: There were 45 different people representing 46 distinct centers, departments or offices, and 2 outside agencies agreed to participate in the clusters. In total, 20 people represented a single organizational unit; 15 represented 2 units; 8 represented 3 units, and 2 represented 4 units. The richness and complexity of these organizational linkages illustrates the decentralized nature of Informatics at the institution and the promise of the cluster approach. DISCUSSION/SIGNIFICANCE OF IMPACT: Adapting to a decentralized Informatics environment, the CTSI established clusters that recognize and respect autonomy and capacity of a wide range of units throughout the university, creating a collaborative atmosphere for steering and implementing an overall Informatics vision. As Informatics capacity rapidly expands throughout growing biomedical research institutions without a centralized Informatics hub, this distributed, deliberative approach could offer an effective governance solution that promotes cooperation. In this model, the CTSI provides the leadership and staffing necessary to ensure progress at the institutional level around Informatics and creates a venue for communication and coordination on Informatics-related topics.

OBJECTIVES/SPECIFIC AIMS: Overall Research Aim: To develop an iNKT-cell engaging reagent (“CAb”)to induce neuroblastoma-directed cytotoxicity in vitro and in a mouse model of neuroblastoma. Objective 1: Explore the contribution of different GD2 affinities to the cytotoxicity against neuroblastoma cells in vitro. Objective 2: Deteremine whether use of different stimulatory glycolipids (alpha-GalCer vs. C34) alter the activation and cytotoxicity of iNKT cells against neuroblastoma in vitro. Objective 3: To analyze survival of an immunocompetent mouse model of neuroblastoma treated with C34-loaded vs alpha-GalCer-loaded CAb molecule, and to analyze the tumor microenvironment in each treatment condition. METHODS/STUDY POPULATION: CAb molecule will be generated by fusing a CD1d protein to an scFv domain for GD2 using cloning techniques. Previous work by our group has used a streptavidin-biotin system to link CD1d to an antibody against GD2, which is large and immunogenic. Protein expression of this novel fusion protein will occur in HEK293 cells. This new CAb molecule will then be loaded with alpha-GalCer or C34 for use in cytotoxicity and in vivo experiments. Cytotoxicity Assessment: Chromium assays will be used to assess the specific cytotoxicity generated by iNKT cells against neuroblastoma cells in vitro. iNKT cells will be activated by “CAb’s” with relatively high and low affinity for GD2, and also with Alpha-GalCer and C34 glycolipid antigen. flow cytometry will be used to assess for CD107a and Interferon Gamma. Mouse Model of Neuroblastoma: TH-MYCN +/+ mice will be used as an immunocompetent model of neuroblastoma. These mice have the MYCN gene under the control of a tyrosine hydroxylase promoter, and spontaneously develop neuroblastomas by 2 weeks of life which are uniformly fatal by 8 weeks of life. In vivo survival studies will be conducted by injecting CAb of relatively high and low affinity, loaded with glycolipid antigen intraperitonealy into TH-MYCN+/+ mice starting at 2 weeks of age, twice weekly. There will also be a matched negative control. Treatment groups are listed below: 1. alpha-GalCer loaded high-affinity Cab 2. alpha-GalCer loaded low-affinity Cab 3. C34-loaded high-affinity Cab 4. C34-loaded low-affinity Cab 5. Unloaded high-affinity Cab 6. Unloaded low-affinity Cab Enrollment will be 6 mice per group for the survival curves. Tumor Microenvironment analysis: 2 additional mice will be included in each group listed above to be sacrificed 2 weeks into treatment for tumor assessment with flow cytomtetry for iNKT cell, NK cell, T-Lymphocyte frequencies as well as interferon-Gamma expression. RESULTS/ANTICIPATED RESULTS: Objective 1: We expect to find that the highest affinity scFv domains for GD2 result in the greatest amount of cytotoxicity against neuroblastoma cells via iNKT cells. Objective 2: We expect that the C34 molecule will induce the greatest amounts of iNKT cell activation against neuroblastoma cells and higher cytotoxicity against neuroblastoma, which has not been shown previously. Objective 3: We expect to see prolonged survival of mice treated with the high affinity GD2 CAb loaded with C34 or alpha GalCer compared with the low affinity CAb loaded with C34 or alpha GalCer. We also expect that the C34 loaded CAb in both groups will have prolonged survival when compared with the alpha-GalCer loaded CAbs of either affinity. DISCUSSION/SIGNIFICANCE OF IMPACT: iNKT cells have been shown previously to confer an improved prognosis in neuroblastoma and other malignancies. Furthermore, high risk neuroblastomas tend to downregulate expression of a chemokine that attracts iNKT’s to the site of the neuroblastoma. Directing iNKT to the site of neuroblastoma holds promise as an effective immunotherapy option. Our preliminary data demonstrate that CAbs directed against GD2 are capable of exerting cytotoxicity of neuroblastoma in vitro. Furthermore a trend towards prolonged survival has been shown in TH-MYCN mice in early experiments. The development of a novel antibody that has reduced immunogenicity, incorporates a glycolipid antigen that does not induce iNKT cell anergy, and is specific for the GD2 tumor specific antigen has potential to result in increased iNKT-mediate neuroblastoma cytotoxicity and prolonged survival in TH-MYCN+/+ mice.

OBJECTIVES/GOALS: The goal of this study was to examine the attitudes of central Pennsylvania rural residents toward data sharing in the setting of the COVID-19 pandemic. We determined their willingness to provide cell phone data and personal information to public health staff investigating COVID-19 cases, as well as their concerns about sharing this information. METHODS/STUDY POPULATION: We used the electronic medical records of an academic healthcare institution in central Pennsylvania to obtain names and addresses of patients who had visited an outpatient clinic or been an inpatient within the prior three years, were 18 years or older, and who resided in a community defined as rural by the Commonwealth of Pennsylvania. The survey included four statements about contact tracing, three statements about intent to receive the COVID-19 vaccine, and validated scales for general trust and for distrust in healthcare organizations. All study variables were summarized to determine their distributions, and bivariate binomial logistic regression was conducted. A multivariable model including all of the independent variables was then fit for each outcome variable. RESULTS/ANTICIPATED RESULTS: The response rate was 19.5%. 95 % of respondents were white, 56% were female, and nearly two-thirds were older than 60 years. Binomial logistic regression showed that both distrust in healthcare organizations and political values influenced respondents willingness to share information with contact tracers as well as their concerns about sharing. In multivariate analysis, political values were a consistent predicator of willingness to share and concerns about sharing. Respondents who indicated that they wanted to get vaccinated as soon as possible were significantly more likely than those who did not want to be vaccinated to be willing to share their cell phone location data and personal data. Conversely, they were less likely to be concerned with these data being shared without their permission. DISCUSSION/SIGNIFICANCE: Understanding rural residents concerns about sharing personal information is critical if we are to develop successful strategies for lessening the impact of COVID-19 and managing future pandemics. This study is a first step in eliciting such concerns in the context of COVID-19and has implications for directing a successful pandemic response.

OBJECTIVES/SPECIFIC AIMS: (1) Obtain publically available citation data, funding data, and generate multiple networks topologies based on dynamic queries of individual faculty. (2) Determine successful pathways that lead to tenure, and career advancement, in addition to determining the effect of CTSA programs on faculty collaboration. (3) Develop publically available commercial interface for the study of faculty networks METHODS/STUDY POPULATION: For our study we included all available citation and funding data publically available on all CTSA programs (as of 2015) with historical data dating back to 2005. We then included the top 25 collegiate institutions who may not have had a CTSA program (eg, Princeton University). We then developed network topologies for each university network, and explore the evolution of individuals in these networks, and the effects of faculty development—as an example in the University of Rochester network, we singled out the directors of the CTSA program there to understand their level of centrality and overall impact on network development, with key observations being that early publications across varying domains lead to stronger network performance. Although individuals who did not benefit from such development, may have succeeded but if they did were likely to leave the institution for elsewhere. RESULTS/ANTICIPATED RESULTS: A secondary goal of this project is to evaluate the effectiveness of the Clinical & Translational Science Institute (CTSI) since its inception in 2006. The mission of CTSI is to advance the field of translational science and research, to link other departments at URMC and community stakeholders by research collaboration, publication, and goals to improve population health, and provide translational education and training to students, researchers, and physicians. To determine how the induction of CTSI affects collaboration within the URMC network, we examined the role of funding in the CTSI network. This was done around the second successful funding around 2013. In doing so we can see that not only did the funding request affect the network topology, but opened new collaborations which were not present prior to the request. DISCUSSION/SIGNIFICANCE OF IMPACT: We have developed an automated method, which is superior to manual methods necessary for citation generation and funding data analysis of faculty growth in citation networks. This technique is applicable to all institutions, not just those in a CTSA environment, but demonstrates the benefit of cross-collaborative efforts, in the case of the URMC network we can state the following. The key takeaway is for individuals to succeed in the URMC collaborative environment they should create their own network and expand it and eventually rise to prominence. There are 2 pathways to this you can take the Dewhurst approach which is to seek out collaborations among internal peers and scale up. Or you can take the Nedergaard approach which is develop the special network, and gain enough public recognition outside of the network that you are capable of leaving it (Fig. 2d). In either case, collaborations among communities and diverse out-degree networks allow faculty to succeed in their given field. Given the wealth of data which has been curated in this fashion, there are numerous explicit questions that can be asked of the data. One of the unique approaches of this data is that is highly reproducible, which allows various questions to be asked. Future work would try to determine what optimal pathways are in a given network to success, and who are ideal collaborators, and collaborations to avoid. Given this information, custom pathways to career success for individual faculty can be developed, moving beyond purely institutional level co-citation networks, which do little to advance faculty development at scale. In Figs 1c and d, the network increased by 75% in terms of graph density (0.007) and decreased by 18.8% (16) in terms of diameter. What this suggest in that the interconnectivity of the network grew dramatically, while the ability for new members to integrate into it increased. This also apparent when one examines the modularity of the network down by 3.6% (0.857), this suggest that the network has as many communities but these communities are less isolated that those in the previous funding year, meaning fields are becoming more transdisciplinary in their collaborations. This was the result of the presence of a CTSA program, thus demonstrating the effectiveness of such institutions, however, our analysis also lays the framework for applying this to other institutions which may be considering a CTSA. Or maintaining the success of a given CTSA program, and ultimately determining where faculty should place their efforts and choose which programs to pursue career advancement.

OBJECTIVES/GOALS: 1) Investigate the network level interactions of attention and learning during an attention network task (ANT) and an implicit learning contextual cueing (CC) task. 2) Assess the effect attention rehabilitation strategies have on behavioral and neural responses pre/post-attentional intervention. METHODS/STUDY POPULATION: This study involves refractory epilepsy patients with implanted intracranial electrodes and moderate-to-severe traumatic brain injury (m/sTBI) survivors. In epileptic patients, we will identify connectivity of cortical regions via the ANT, which probes components of attention (alerting, orienting, and executive control) and a CC task that probes implicit learning. We hypothesize that modulation of attention and learning can be seen at the network level. In TBI we will assess improvement following two attention rehabilitation paradigms behaviorally; and use our results from epileptic patients to guide measurement of treatment-related neuroplastic change via scalp electroencephalography. RESULTS/ANTICIPATED RESULTS: When the proposed objectives are complete, we expect to determine how the implicit learning rate in m/sTBI changes as a result of both direct attention and metacognitive-strategy training, and discern the neuroanatomical networks associated with attention and implicit learning based on connectivity results. We expect to identify intracranial regions and networks that exhibit modulatory effects associated with attention and implicit learning. Additionally, we anticipate that deficits in attention will be mitigated following training and hypothesize that implicit learning rate will improve in TBI patients as a result of both attentional rehabilitation paradigms. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterizing intracranial activity in epilepsy patients will give electrophysiology data unattainable in TBI patients. This intracranial perspective will enable us to propose mechanisms of action that may result from our interventions and enable critique of current rehabilitation treatments.

OBJECTIVES/GOALS: Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Due to its relatively low incidence, prospective studies are limited. This makes administrative claims a promising data source to study VTE. We sought to examine the reproducibility of results using different VTE definitions from the published literature. METHODS/STUDY POPULATION: We conducted a retrospective analysis of a random 10% sample of the 2010-2022 IQVIA LifeLink PharMetrics Plus™ database, an administrative claims database representative of the commercially insured population of the United States. We selected cancer patients undergoing major gastrointestinal surgery, who have a higher risk for postoperative VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]). VTE was defined using ICD-9-CM and ICD-10-CM codes using definitions from 4 individual published studies. We compared the 4 definitions with respect to the incidence of VTE and factors associated with post-discharge VTE using standard univariate and multivariable logistic regression models. The same logistic regression models were used for each of the 4 definitions. RESULTS/ANTICIPATED RESULTS: There were substantial differences in VTE coding among the 4 definitions (range 107 to 225 ICD-9/10 codes for DVT and 12 to 24 codes for PE). The eligible population comprised 2,360 patients (49% female) with a median age of 49 years (interquartile range 47-52 years). During the index surgery hospitalization, a total of 58, 62, 63, and 83 patients developed VTE using the 4 definitions. In the 2,126 patients eligible for VTE prophylaxis, a total of 108, 68, 73, and 107 patients developed post-discharge VTE (range for DVT 35 to 81, range for PE 39 to 76). On multivariable analysis, factors independently associated with VTE included age using 1 of 4 definitions, esophageal surgery type using 3 of 4 definitions, and liver surgery type and Elixhauser score using all 4 definitions. DISCUSSION/SIGNIFICANCE: The incidence of VTE is directly affected by differences in ICD-9/10 codes used. Definitions for important clinical outcomes should be standardized when using administrative claims data in order to improve reproducibility of findings.

OBJECTIVES/GOALS: Patient recruitment, enrollment, and retention continues to be one of the leading barriers to successful clinical trials, and results do not always reflect the diversity of the general population. This systematic review aims to assess the impact of decentralized methods on recruitment, retention, and diversity on recent clinical research. METHODS/STUDY POPULATION: A systematic search of the literature, using databases such as PubMed, Cochrane Library and EMBASE to find publications reporting on the aspect of recruitment in decentralized clinical trials was performed. The titles and abstracts of the publications were assessed, excluded those lacking sufficient or pertinent information regarding decentralization in clinical trials. The remaining publications were reviewed for those reporting sufficient data regarding the impact of decentralization on the aspect of recruitment in clinical trials to be included in the focused analysis. Studies reporting on participant retention and diversity in addition to recruitment were emphasized. RESULTS/ANTICIPATED RESULTS: This systematic search returned 13 studies highlighting the role of decentralized clinical trial methods impacting participant recruitment, retention, and diversity in clinical trials. Out of the 13 studies, 10 reported improved recruitment using virtual or decentralized methods, and 7 of these reported improvements when compared alongside with traditional methods. 7 studies reported a positive impact on participant retention, with 4 of these directly comparing decentralized methods with traditional methods. Lastly, of these studies, 5 were reported to have trended towards diversity in the demographics of the sample population, including race or geographic location. DISCUSSION/SIGNIFICANCE: Related reviews have stated a lack of published comparable data to determine if DCTs (Decentralized Clinical Trials) improved recruitment and retention. Results suggest this review addresses such a gap, by providing data on how decentralized methods can benefit recruitment and retention, potentially highlighting a new standard.

OBJECTIVES/SPECIFIC AIMS: The goal of this study was to determine if there are any sex differences in the pathophysiological effects of sFR. METHODS/STUDY POPULATION: Male Fischer rats (4-month-old) were maintained on a control (CT) (ad libitum regular chow; n=8) or sFR (60% reduction of daily food intake, n=8) diet for 2 weeks. On days 1, 2, 3 and 14, the rats were placed in metabolic cages for food and water intake and 24-hour urine collection. Body weight (BW) is measured daily. After 2 weeks, the animals are given free access to normal chow for 3 months. Short-term and long-term effects of sFR on blood pressure and heart rate will be measured. RESULTS/ANTICIPATED RESULTS: After 2 weeks, the male CT group gained 7% BW (p <0.05), while BW in the sFR males was reduced by 12% (p<0.05 vs. CT). In contrast, female controls did not gain BW while the sFR females lost 18% of their BW. Water intake was reduced by 35%, which was similar to the reduction in females (p=0.18). The hematocrit of sFR male rats was higher (51.1%) than the CT group (45.2%, p<0.05), which was most likely due to the 6% reduction in plasma volume. A similar effect on hematocrit was observed in sRF females. Similarly, also to female rats, sFR had no effect on Na+ and K+ plasma or urine concentrations by day 14 in the male rats. DISCUSSION/SIGNIFICANCE OF IMPACT: sFR has similar effects on electrolyte balance in males and females. Ongoing studies will determine if there is any sex difference in the effects of sFR on blood pressure, heart rate and susceptibility to hypertension and cardiac injury.

OBJECTIVES/GOALS: Implementation science evaluations are often too time-intensive to provide actionable feedback during implementation, suggesting the need for more agile methods. We present an evaluation of the World Health Organization’s Emergency Care Toolkit implementation in Zambia using rapid qualitative methods to provide timely feedback. METHODS/STUDY POPULATION: We evaluated the implementation of the Emergency Care Toolkit in eight general and referral hospitals in Zambia in 2023 using a rapid-cycle, qualitative template analysis approach grounded in the Consolidated Framework for Implementation Research (CFIR). We gathered qualitative data from operational field notes, focus groups, and key informant interviews of administrators, clinicians, nurses, and support staff in all eight hospitals in Zambia. We parsimoniously applied CFIR constructs and tool-specific codes, focused on barriers and facilitators, to allow for rapid but comprehensive cross-case analysis. The results were used to generate a matrix of stakeholder-relevant, plain-language barriers and facilitators for each tool. RESULTS/ANTICIPATED RESULTS: We completed eight site visits with focus groups and interviews following initial implementation in September 2023 to gather firsthand knowledge related to implementation of the Toolkit. The CFIR-focused coding accelerated analysis by centering on barriers and facilitators for each tool while maintaining a comprehensive evaluation framework. Summary tables of barriers and facilitators were easily interpreted by lay stakeholders. Visualization in tables allowed for identification of common themes across tools and hospitals, making comprehensive recommendations to the implementation and dissemination process quickly possible. We anticipate the study findings will empower implementing partners to make timely, actionable improvements. DISCUSSION/SIGNIFICANCE: Rapid-cycle qualitative implementation evaluations allow for rigorous yet timely feedback on the implementation process compared to traditional methods. This efficient strategy is particularly important in resource-constrained environments where inefficient implementation wastes limited resources and create delays that cost lives.

OBJECTIVES/GOALS: Vaginal ring delivery of antiretroviral drugs may provide protection against acquisition of HIV-1 when used as pre-exposure prophylaxis. As part of a randomized placebo-controlled safety trial of a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR), we assessed product acceptability through surveys of 17 women after continuous ring use. METHODS/STUDY POPULATION: Sexually active, HIV negative women between the ages of 18 and 45 were enrolled to investigate the safety and pharmacokinetics of three months of continuous TDF IVR use. The study was designed to include 40 US participants randomly assigned (3:1) to a TDF or placebo IVR. Twelve were randomized to TDF and five were assigned to the placebo group before the study was electively discontinued due to development of vaginal ulcerations in eight women in the TDF group. Acceptability data regarding TDF and placebo ring use was gathered via self-administered, computer-based questionnaires at the one- and three-month study visits. Participants were asked about overall attitudes and feelings regarding the TDF and placebo IVR, vaginal changes associated with ring use, and their experiences with ring use during menses and with sex. RESULTS/ANTICIPATED RESULTS: The mean age of participants was 30 years (range 18 - 42). Sixteen of 17 (94%) participants completed all study questions at both visits. When asked about ring likeability at one-month, 12 of 16 (75%) women reported overall liking the ring, including 5 of 8 (63%) who developed ulcerations. Vaginal changes described during ring use included 8 participants who indicated that the “vagina was wetter” and 2 who reported that the “vagina was drier.” Additionally, 10 of 12 (83%) who had their period during the first month of the study were not bothered by ring use during menses, and 11 of 16 (69%) stated that the ring was not bothersome with use during sex. When asked at the three-month visit, most reported that they would prefer to wear the ring rather than use a condom during sex, however, condom use was low at baseline in this population. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite unanticipated ulcers, the IVRs were acceptable, especially when used with menses and during sex. Regardless of the group assigned or vaginal changes experienced, and even amongst those who developed ulcerations, the women had positive attitudes towards the ring, which is promising for future use of vaginal rings as a method for HIV prevention.

Objectives/Goals: Port-site metastasis (PSM), defined as the spread of malignancies to the abdominal wall at the site of surgical ports, poses a significant challenge in cancer management. The objective of this summary overview is to describe the prevalence of and risk factors associated with PSM in various gynecological cancers after laparoscopic surgery. Methods/Study Population: Study design: Systematic Review and Meta analysis Search strategy: All international databases, without language limitations, from January 1990 to December 2023. Inclusion/exclusion criteria: Cohort, case–control, or cross-sectional observational studies reporting the frequency of, or risk factors for PSM in young and middle-aged women will be included (using the PRISMA checklist). Data extraction: two reviewers independently extracting pertinent data (using the STROBE checklist). Quality assessment and risk of bias: The quality of each study will be assessed according to the Quality Assessment Tool for Observational Studies. Results/Anticipated Results: This meta-analysis of 36 studies evaluated the proportion of successes across various populations, with a pooled proportion of 0.02 (95% CI: 0.01–0.02) based on a random-effects model. Significant heterogeneity was identified (I²  =  88.12%), reflecting notable variability between studies. Despite this, the overall effect was statistically significant (p  =  0.00). A subgroup analysis will be conducted to explore potential sources of heterogeneity, considering factors such as cancer stage, diagnostic methods, surgical approach (conventional or robotic), and study type (retrospective/prospective). Discussion/Significance of Impact: By identifying the prevalence of, and the risk factors for, PSM, this study will better inform personalized treatment approaches, surveillance strategies, and surgical decision-making to improve patient-related outcomes and long-term survival in women with gynecological malignancies.

OBJECTIVES/SPECIFIC AIMS: Autism spectrum disorder (ASD) affects 1 in 68 people and includes restricted, repetitive behavior, and social communication deficits. Aspects of face processing (i.e., identity, emotion perception) are impaired in some with ASD. Neuroimaging studies have shown aberrant patterns of brain activation and connectivity of face processing regions. However, small sample sizes and inconsistent results have hindered clinical utility of these findings. The study aims to establish consistent patterns of brain responses to faces in ASD and provide directions for future research. METHODS/STUDY POPULATION: Neuroimaging studies were identified through a multi-database search according to PRISMA guidelines. In total, 23 studies were retained for a sample size of 383 healthy controls and 345 ASD. Peak coordinates were extracted for activation likelihood estimation (ALE) in GingerALE v2.3.6. Follow-up ALE analyses investigated directed Versus undirected gaze, static Versus dynamic, emotional Versus neutral, and familiar Versus unfamiliar faces. RESULTS/ANTICIPATED RESULTS: Faces produced bilateral activation of the fusiform gyrus (FG) in healthy controls (−42 −52 −20; 22 −74 −12, p<0.05, FDR) and left FG activation in ASD (−42 −54 −16, p<0.05, FDR). Activation in both groups was lateral to the mid-fusiform sulcus. Follow-up results pending. DISCUSSION/SIGNIFICANCE OF IMPACT: Reduced right FG activation to faces may inform biomarker or response to intervention studies. Mid-fusiform sulcus proved a reliable predictor of functional divides should be investigated on a subject-specific level.

OBJECTIVES/GOALS: Disparities in pediatric kidney transplantation (KT) result in reduced access and worse outcomes for minority children. We aimed to assess the impact of recent systemic changes on these disparities. METHODS/STUDY POPULATION: Retrospective cohort study of pediatric patients utilizing data from the United States Renal Data System (USRDS) and Scientific Registry of Transplant Recipients (SRTR). We compared access to transplantation, time to deceased donor kidney transplant (DDKT), and allograft failure (ACGF) using Cox proportional hazards in the 4 years preceding KAS to the 4 years post-KAS implementation. RESULTS/ANTICIPATED RESULTS: Compared to the pre-KAS era, patients post-KAS were more likely to be pre-emptively listed (26.8% vs 38.1%, p<0.001) and pre-emptively transplanted (23.8% vs 28.0%, p<0.001), however these benefits were not uniform across racial groups. Only 12.7% and 15.7% of Black and Hispanic children received a pre-emptive transplant compared to 29.6%, 49.8% and 54.4% of White, Asian and Other race children respectively. Compared to White children, Black and Hispanic children had a lower likelihood of transplant listing within 2 years of first dialysis service aHR 0.67 (0.59-0.76) and 0.82 (0.73-0.92), in the post-KAS era. Time to DDKT after listing was comparable across all racial groups in both eras. Black children have disproportionally worse 5-yr ACGF, aHR 1.50 (1.08-2.09), p=0.02. DISCUSSION/SIGNIFICANCE: After KAS implementation there remains equity in time to DDKT, however disparities persist in transplant listing and ACGF among Black children. Further studies are needed to identify granular SES factors impacting delayed referral and systemic barriers to transplant, as well as risk factors for poor allograft outcomes among minority children.

OBJECTIVES/GOALS: The aim of this study was to design and implement the Pharos application to map the cellular network support structure around Lake Victoria in Western Kenya. Additionally, the Pharos app was used to collect images of disease-relevant vector and plant life surrounding the study sites to train a computer vision algorithm to map disease-relevant areas. METHODS/STUDY POPULATION: Pharos was provided to a 4-person team of healthcare workers. The app was pre-loaded on both iOS and Android devices to be used during the course of normal field activity. Pharos ambiently collects network data and the team was asked to capture images of landmarks relevant to their work in schistosomiasis control. The field team traveled to 4 counties of differing schistosomiasis risk surrounding Kisumu, Kenya in autumn 2022 and will return to these areas in early spring 2023. Cell signal indicators (upload and download speed) were collected and asynchronously uploaded to a database for further analysis. Additionally, all landmark images (cell network towers, landmarks (e.g. schools, churches, public centers), plant life, vectors, and water bodies) were recorded and tagged with GPS coordinates and time stamps. RESULTS/ANTICIPATED RESULTS: Iterative development powered by small, informal, user-centered focus group discussions with the field team led to several key adaptations to the Pharos software. On the first deployment, 1,297 unique upload and download events were recorded across 3 Kenyan cell providers and 1 American provider. 1,197 data points were collected in Kenya using both Android and iOS devices using several versions of the Pharos application. 154 unique landmarks were photographed, but a distinct difference in landmark recording was observed between devices, prompting a transition to iOS-only data collection. Of the landmarks recorded, the majority (120, 77.9%) were landmarks or cell network towers, while 22.1% were water bodies, plant life, or schistosomiasis vectors. DISCUSSION/SIGNIFICANCE: For the first time, high-detail maps of cellular signal and critical schistosomiasis-related landmarks were generated. Future work on this project is focused on training computer vision algorithms using the captured images of environmental and ecological factors to isolate possible areas of human disease transmission.

OBJECTIVES/SPECIFIC AIMS: This research project envisions the integration of Homeless Management Information System (HMIS) and UI Health Cerner electronic medical record (EMR) system with the following goals: (1) enable sharing of data about the status of the housing insecure and homeless. (2) Identify and match patient record accurately. (3) Record housing insecurity or homelessness information with structured data elements in the EMR. METHODS/STUDY POPULATION: We created a Master Person Index (MPI) of the homeless individuals from HMSI using OpenEMPI software package, which is an open source implementation of an Enterprise Master Patient Index (EMPI). An entity model was generated based on the selective data elements from HMIS database, which were relevant for the patient identity management and healthcare service management. An automated script was implemented to extract data from HMIS and load it into OpenEMPI to build the MPI. Once the MPI is setup, the Emergency Department users were able to perform patient identity matching and confirm housing insecure or homeless status of their patients by querying the index using the web-based tool. We developed structured data elements to record homelessness information, which will allow us to measure the prevalence of this risk among patients. We are also exploring the possibility to integrate the systems the using the IHE PIX/PDQ profile, which provides ways for healthcare applications to query a patient information server for a patient based on user-defined search criteria, and retrieve a patient’s information directly into the application. RESULTS/ANTICIPATED RESULTS: We implemented a MPI of homeless individuals, which would allow the emergency department users to perform patient identity matching of housing insecure or homeless patients, without undue privacy intrusions. We are confident that IHE PIX/PDQ profile is able to support the integration of healthcare and housing and homeless services systems and enable the data sharing in an efficient way. DISCUSSION/SIGNIFICANCE OF IMPACT: The project addressed the gap in the sharing of data about housing insecure or homeless persons between healthcare and housing and social services that will result in improvements in coordination of care, reduce the cycle time from recognition of risk to the referral to housing and services and improve health outcomes and residential stability. Successful completion of this integration project will give us a model that we can scale to many other communities.