In this report, we describe the implementation and short-term outcomes of a Special Populations Consultation Service within the University of California, Los Angeles (UCLA) Clinical and Translational Science Institute (CTSI). With the goal of increasing the quality and quantity of special population (SP) research, the UCLA CTSI Integrating Special Populations program designed a consultation service to support faculty and trainees conducting research involving one of three CTSI “special populations:” children, older adults, and/or minority; underserved; or health disparity populations. The Special Populations Consultation Service offers three types of activities: grant proposal studios, career consultations, and project reviews. UCLA CTSI faculty with appropriate content expertise serve as consultants. We evaluated this consultation model using satisfaction surveys and by quantifying funded grants and reported changes in career goals in SP research. Between 2016 and 2019, the Special Populations Consultation Service provided 59 consultations including 42 grant studios and was used by researchers at all levels from all four UCLA CTSI institutions. Recipients rated the consultations very highly. Funding success rates were 57% following K-level grant studios and 28% following R-level grant studios. Users of project and career consultations commonly attributed career accomplishments in part to their consultation experiences. The SP Consultation Service is feasible and acceptable and appears to enhance careers of investigators studying special populations.

Enterprise data warehouses for research (EDW4R) is a critical component of National Institutes of Health Clinical and Translational Science Award (CTSA) hubs. EDW4R operations have unique needs that require specialized skills and collaborations across multiple domains which limit the ability to apply existing models of information technology (IT) performance. Because of this uniqueness, we developed a new EDW4R maturity model based on prior qualitative study of operational practices for supporting EDW4Rs at CTSA hubs. In a pilot study, respondents from fifteen CTSA hubs completed the novel EDW4R maturity index survey by rating 33 maturity statements across 6 categories using a 5-point Likert scale. Of the six categories, respondents rated workforce as most mature (4.17 [3.67–4.42]) and relationship with enterprise IT as the least mature (3.00 [2.80–3.80]). Our pilot of a novel maturity index shows a baseline quantitative measure of EDW4R functions across fifteen CTSA hubs. The maturity index may be useful to faculty and staff currently leading an EDW4R by creating opportunities to explore the index in local context and comparison to other institutions.

Despite the availability of vaccinations, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to cause Coronavirus Disease 2019 (COVID-19) infection with a spectrum of disease in the acute setting. Transmission, infection, and severe disease remain common. There is a critical need to establish treatment regimens in the ambulatory setting that can reduce symptom burden and potentially prevent progression to severe disease and death. Many existing medicines previously approved for other uses may have benefit but remain unproven in informative clinical trials.

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 is a decentralized, placebo-controlled, double-blind, randomized, platform trial that has now enrolled more than 7500 participants and has reported on the effectiveness of ivermectin at two doses, fluticasone, and fluvoxamine for helping people with COVID-19. With additional repurposed therapies added to the platform, ACTIV-6 continues to enroll symptomatic outpatients aged ≥ 30 years with a confirmed positive PCR or antigen test for SARS-CoV-2. Potential participants are screened and enrolled online, through a call center, or facilitated by local study sites. Participants consent electronically and are randomized to placebo or to one of the open study drugs for which they are eligible at the time of enrollment. A shared, contemporary placebo approach is used. Participants receive study drug in the mail and remain on study for up to 180 days. While enrolled, electronic patient-reported outcome assessments are used to monitor symptoms, healthcare utilization, and mortality. The primary endpoint is time to recovery or a composite of hospitalization and mortality within 28 days. Symptoms, acute healthcare utilization, and the Patient-Reported Outcomes Measurement Information System-29 are collected for up to 180 days.

Using a decentralized trial approach allowed the ACTIV-6 platform to increase both reach and rate of enrollment. The decentralized approach did not simplify regulatory oversight, and we found unanticipated challenges in patient behavior and the study drug delivery process. Despite challenges, ACTIV-6 has enrolled thousands of participants from across the USA and continues to test the effectiveness of repurposed medicines for treating COVID-19. Our lessons learned contribute to the emerging understanding of how to optimize decentralized trials.

Introduction. Family health history (FHx) is an important factor in breast and ovarian cancer risk assessment. As such, multiple risk prediction models rely strongly on FHx data when identifying a patient’s risk. These models were developed using verified information and when translated into a clinical setting assume that a patient’s FHx is accurate and complete. However, FHx information collected in a typical clinical setting is known to be imprecise and it is not well understood how this uncertainty may affect predictions in clinical settings. Methods. Using Monte Carlo simulations and existing measurements of uncertainty of self-reported FHx, we show how uncertainty in FHx information can alter risk classification when used in typical clinical settings. Results. We found that various models ranged from 52% to 64% for correct tier-level classification of pedigrees under a set of contrived uncertain conditions, but that significant misclassification are not negligible. Conclusions. Our work implies that (i) uncertainty quantification needs to be considered when transferring tools from a controlled research environment to a more uncertain environment (i.e, a health clinic) and (ii) better FHx collection methods are needed to reduce uncertainty in breast cancer risk prediction in clinical settings.

OBJECTIVES/SPECIFIC AIMS: This project aimed to offer Citizen Scientists basic knowledge about clinical and translational research, as well as introductory information to the topics a Citizen Scientist may work with at the University of Florida (UF). As part of that goal, several objectives were identified: (1) create a curriculum to operationalize training for new Citizen Scientists, (2) utilize best practices in educational research for curriculum design and implementation, (3) create a resource that can be freely available to other groups, and (4) implement the finished curriculum with Citizen Scientists at UF. METHODS/STUDY POPULATION: Working with an expert in the field of instructional design, an overall design plan was created and implemented. This included first conducting interviews with Citizen Scientists to determine the most appropriate format for the content, creating 10-minute videos with subject matter experts, and crafting learning assessments for each didactic video. Topics for the curriculum were conceptualized by gathering input from CTSI leaders, Citizen Scientists, and staff members, and learning objectives were created to help guide the content creation. The ADDIE (Analysis, Design, Development, Implementation, Evaluation) instructional design model was utilized to help guide the creation process, and this included a formative evaluation of the content, where assessment questions or videos were edited in response to Citizen Scientist feedback. It was important to both CTSI leadership and the Citizen Scientists themselves that the curriculum be widely accessible, so the curriculum was made as an open educational resource, meaning that it is available online for use by anyone with content that can be customized to specific programs or organizations. To implement the curriculum with UF Citizen Scientists, the materials were ported into Canvas, a widely utilized learning management system at UF. Participants were split into two groups, one group with Citizen Scientists already in the program (n=6) and a group with new Citizen Scientists (n=2). IRB approval to conduct this pilot test and share the results was obtained, and implementation ran from July 2017- January 2018. RESULTS/ANTICIPATED RESULTS: Data were taken from participant scores on the curriculum’s 15 didactic learning assessments, and while the number of attempts on assessments was not limited, only first-attempt results were analyzed. Veteran Citizen Scientists scored higher than the new Citizen Scientists, with an overall score across all assessments of 84% vs 74%. The existing Citizen Scientists performed better on most topics, however the newer Citizen Scientists outscored the veterans on two modules: Cultural Competency (90% vs 77%) and Biomedical Informatics and Big Data (80% vs 73%). The newer members also had fewer retakes on these two modules, with the newer members having only one retake for these two modules, compared to seven total retakes across both modules for the established members. Participants were also asked basic questions about learning comprehension, video quality, and assessment item clarity, in addition to offering narrative feedback. Participants across both groups seemed largely pleased with the curriculum, as indicated by results of the course evaluation. Most (75%) Citizen Scientists felt it was easy to understand the information in the video tutorials, while 75% of Citizen Scientists felt that the assessment items were comprehensive, and 62.50% felt that the assessment items matched the learning objectives. The new Citizen Scientists were far more likely to respond favorably to the video and assessment evaluation questions, with 95% of all responses marked as “agree” or “strongly agree”, compared to 57% of the responses from the established Citizen Scientists. DISCUSSION/SIGNIFICANCE OF IMPACT: The performance of new vs veteran Citizen Scientists underscores the need for introductory information on clinical research topics for new community stakeholders, as well as the need for ongoing refresher training. Though the existing Citizen Scientists had been working with these topics already, and some had experienced the modules already through the formative evaluation, some topics remained a challenge for participants, a notion reflected in their assessment scores. Clinical research, particularly translational research, can be difficult to understand, and when a stakeholder understands the fundamentals underlying the research with which they are assisting, communication barriers are eliminated, feedback is well-reasoned and actionable, and there is greater buy-in from stakeholders. Understanding the clinical research process helps community stakeholders better understand their contribution to research and offer critical feedback to aid in implementation of research findings in health-related settings.

OBJECTIVES/SPECIFIC AIMS: Prostate cancer is the second most common cancer in the world for men. For reasons still unclear, aggressive PCa disproportionately affects males of African ancestry (MoAA). Incidence and mortality rates are highest in MoAA as they have consistently shown a 2.3–3.0-fold higher risk of mortality compared with Caucasian men. This aggressiveness of PCa may be due to specific biological factors. Studies have established that microRNAs (miRNAs), essential in post-transcriptional gene regulation, are dysregulated in PCa. miR-1207-3p is encoded at the PVT1 gene locus, which is located downstream of MYC on the 8q24 PCa susceptibility locus. The chromosomal region 8q24 is associated with aggressive PCa. Yet miR-1207-3p in PCa in MoAA has never been investigated. Moreover, studies have shown that PVT1/MYC co-operation is a fundamental feature in all cancers with 8q24 amplification and 98% of the 8q24 amplicons contained concurrent amplification of the MYC and PVT1 loci. Moreover, MYC has been linked to PCa aggressiveness, and has been reported to be downstream of androgen receptor (AR) in some PCa. However, the mechanisms regulating c-MYC have never been studied in MoAA. We have recently demonstrated that miR-1207-3p has prognostic value in PCa, and directly binds to the 3′ UTR of Fibronectin type III domain containing 1 (FNDC1) to regulate a novel FNDC1/fibronectin (FN1)/AR pathway upregulated in metastatic PCa. However, the relevance of this novel and clinically significant miR-1207-3p molecular pathway in PCa in MoAA is unknown. Therefore, we hypothesized that miRNA 1207-3p, encoded at the 8q24 PCa susceptibility locus, is a PCa biomarker with clinical applications in MoAA. Our specific aim was to assess the clinical relevance of miR-1207-3p, FNDC1, FN1, AR, and MYC expression in aggressive PCa in a cohort of West African Black males. METHODS/STUDY POPULATION: Consequently, we aimed to determine the expression profile of miRNA-1207-3p, FNDC1, FN1, AR, and MYC in histologically confirmed normal prostate (n=24), benign prostate (n=44) and malignant prostate tissue (n=29) from prostatectomy or transrectal ultrasound-guided biopsies in patients recruited at the University College Hospital, Ibadan, Nigeria, a sub-Saharan Black African population. In total, 17 patients had tumor tissues with Gleason score ≥8. Tissues were collected in compliance with Institutional Ethics Board approved protocols. RNA extraction, cDNA synthesis, and quantitative-PCR were performed to analyze mRNA expression of miRNA-1207-3p, FNDC1, FN1, AR, and MYC. Statistical analysis were performed using SPSS software. All data were analyzed by the 1-way ANOVA test. Tukey post-hoc test was performed to determine the differences in mean expression between normal and tumor prostate tissues. p<0.05 were considered significant. RESULTS/ANTICIPATED RESULTS: We discovered that miR-1207-3p is significantly underexpressed in prostate tumor tissues [0.09±0.02, 95% CI (0.04, 0.136), p=0.000] in comparison with normal prostate tissue in MoAA [0.92±0.15, 95% CI (0.60, 1.244), p=0.000]. This is the first description of miR-1207-3p differential expression in human clinical PCa in MoAA. In contrast, FNDC1 was significantly overexpressed in prostate tumor tissues [21.93±8.21, 95% CI (4.97, 38.89), p=0.003] in comparison with normal prostate tissues in MoAA [1.57±0.45, 95% CI (0.625, 2.51), p=0.003]. The same positive correlation with advanced disease held true for FN1 [tumor: 13.66±3.53, 95% CI (6.38, 20.93), p=0.000; normal: 1.07±0.235, 95% CI (0.58, 1.56), p=0.000], AR [tumor: 20.49±6.74, 95% CI (6.50, 34.48), p=0.000; normal: 0.94±0.20, 95% CI (0.52, 1.36), p=0.000], and c-MYC [tumor: 33.93±8.43, 95% CI (16.53, 51.33), p=0.000; normal: 1.94±0.36, 95% CI (1.18, 2.70)]. The significantly increased mean expression for FNDC1, FN1, AR, and c-MYC in prostate tumor tissues in comparison with normal prostate tissues indicate that their overexpression is associated with increased risk of cancer progression in MoAA. DISCUSSION/SIGNIFICANCE OF IMPACT: These results show that the underexpression of miR-1207-3p and the overexpression of FNDC1, FN1, AR and MYC is associated with aggressive PCa in MoAA. miR-1207-3p, and it molecular target FNDC1, may be useful biomarkers for prognostication of PCa in MoAA.

Temporal challenges are not only contextual in nature but manifest internally in teams when members enter the team with different temporal orientations (e.g., time urgency and pacing style). Researchers have demonstrated that temporal diversity has important implications for key team outcomes (performance, timeliness, and team conflict) across a range of samples and countries. Unfortunately, the practical implications of this research have yet to be unpacked. We respond to this need by developing an approach to translate temporal diversity research studies into actionable, evidence-based team interventions. Because journal articles are often deficient on actionable steps, whereas practitioner-friendly outlets tend to be deficient on scientific rigor, incorporating both criteria necessitates merging these literatures. Specifically, we delineate four main steps: (1) identify significant moderators, (2) match the moderators to scientifically based interventions, (3) design intervention tools with specific, actionable procedures, and (4) evaluate the effectiveness of the intervention tools by designing research studies. We believe the process we outline to marry actionable and evidence-based benchmarks is applicable to other research domains in team science beyond temporal research. It is our hope that this research will be a catalyst for further exploration of interventions that can help team members navigate temporal differences.

The National Lung Cancer Screening Trial (NLST) demonstrated the use of low dose helical computed tomography (LDCT) scans for lung cancer screening. However, the NLST was implemented in urban hospitals and prior to the Lung CT Screening Reporting and Data System (Lung-RADS). In this retrospective cohort study, 774 eligible patients received LDCT screening using Lung-RADS criteria. Eighty-four patients (10.9%) had subsequent testing performed compared to 24.2% in the NLST study. Of those with subsequent testing, 21.4% were diagnosed with lung cancer compared to only 4.6% in the NLST study. Lung-RADS significantly reduced unnecessary testing while identifying higher rates of lung cancer compared to the NLST.

OBJECTIVES/SPECIFIC AIMS: Neurologic disorders are among the most significant health challenges facing society today. Although different neurologic disorders are often thought to be distinct from one another, evidence suggests similar processes may contribute to pathology in different diseases. Previous studies suggest that common disease mechanisms contribute to the development of epilepsy and tauopathy. The purpose of this study is to better characterize this relationship and explore potential therapeutic avenues to slow disease progress. METHODS/STUDY POPULATION: This study uses the pilocarpine-induced status epilepticus model of temporal lobe epilepsy to explore the effect of severe seizures on tau pathology. Brains were collected from mice at 6 or 24 hours after induced status epilepticus. Homogenates were analyzed via Western blot to look for changes in tau phosphorylation or activity of two major regulators of tau phosphorylation, GSK3β and PP2A. These data show that changes in tau phosphorylation dynamics occur at a much earlier time point after status epilepticus than has previously been described. RESULTS/ANTICIPATED RESULTS: GSK3β activity increased within 6 hours and remained elevated by 24 hours. PP2A activity initially decreased but returned to normal by 24 hours. These data show that changes in tau phosphorylation dynamics occur at a much earlier time point after status epilepticus than has previously been described. DISCUSSION/SIGNIFICANCE OF IMPACT: The current project supports previous observations that seizures promote tau phosphorylation in vivo, but suggests that changes begin much earlier than previously thought. Further work is needed to understand how post-seizure changes in tau phosphorylation develop over longer periods of time. Additionally, future work will characterize the effect of tauopathy on electrical activity in vivo and in vivo.