We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

s-Frames and i-frames do not represent two opposed types of intervention. Rather they are interpretive lenses for focusing on specific aspects of interventions, all of which include individual and structural dimensions. There is no sense to be made of prioritizing either system change or individual change, because each requires the other.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

OBJECTIVES/GOALS: The objective of this study was to use NIH RePORTER (Research Portfolio Online Reporting Tools) to analyze K99 funding trends and determine if R00 to R01 or R21 achievement time correlates with the future success of an early-stage NIH-funded investigator. METHODS/STUDY POPULATION: All award data were collected from NIH RePORTER. All K99 awards and funding data in this study were limited to All Clinical Departments (ACD). All researchers (n = 1,148) and awards (n = 2,022) were identified through a K99 search from FY 2007 to FY 2022 across ACD. Historic trends in K99 awards and funding from NIH Fiscal Year (FY) 2007 to FY 2022 were investigated. An R00 dataset was generated from NIH RePORTER. The K99 to R00 achievement statistics from FY 2007 to FY 2022 was investigated. NIH annual datafiles for FY 2007 to FY 2021 were aggregated to generate a master datafile of all R01 (n = 395,505) and R21 awards (n = 61,766). R01 and R21 award data were linked to the researcher previously identified through the K99 search. The connection between K99/R00 awardees and subsequent R01 or R21 awards was focused on. RESULTS/ANTICIPATED RESULTS: From FY 2008 to FY 2022, the number of K99 awards per year increased 123.4%, from 94 to 210. Over the same period, after correcting for inflation, the NIH K99 budget increased 127.0% while the NIH program level budget increased 17.3%. For researchers who achieved their first R01 or R21 0–3 years versus 3–6 years after the start of their R00, their average funding per year since the start of the R00 phase was $467,425 versus $290,604, respectively (p < 0.001). In summary, NIH investment in the K99 award pathway has substantially outpaced the NIH program level budget increase, and there is a strong relationship between average funding per year since the start of the R00 phase and time from R00 to R01 or R21. DISCUSSION/SIGNIFICANCE: Our study offers additional evidence of the Matthew effect in science, where previous success generates future success. This analysis may be useful to clinical departments as they evaluate selecting new and retaining current biomedical scientists for independent research positions.

Gaps in the implementation of effective interventions impact nearly all cancer prevention and control strategies in the US including Massachusetts. To close these implementation gaps, evidence-based interventions must be rapidly and equitably implemented in settings serving racially, ethnically, socioeconomically, and geographically diverse populations. This paper provides a brief overview of The Implementation Science Center for Cancer Control Equity (ISCCCE) and describes how we have operationalized our commitment to a robust community-engaged center that aims to close these gaps. We describe how ISCCCE is organized and how the principles of community-engaged research are embedded across the center. Principles of community engagement have been operationalized across all components of ISCCCE. We have intentionally integrated these principles throughout all structures and processes and have developed evaluation strategies to assess whether the quality of our partnerships reflects the principles. ISCCCE is a comprehensive community-engaged infrastructure for studying efficient, pragmatic, and equity-focused implementation and adaptation strategies for cancer prevention in historically and currently disadvantaged communities with built-in methods to evaluate the quality of community engagement. This engaged research center is designed to maximize the impact and relevance of implementation research on cancer control in community health centers.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is primarily associated with hospital-acquired infections and is an urgent public health threat due to its ability to contaminate the environment and cause severe disease. In 2019, Illinois began pilot surveillance for CRAB requiring select laboratories to submit specimens for molecular characterization. On July 17, 2020, the Chicago Department of Public Health (CDPH) was notified of an increase in CRAB infections in a 20-bed ICU at an acute-care hospital in Chicago (hospital A) during the initial COVID-19 surge. We summarize the outbreak investigation findings and infection control recommendations. Methods: Clinical cultures were collected from patients in hospital A, and CRAB-positive isolates were sent to the Wisconsin State Laboratory of Hygiene for mechanism of resistance and antibiotic susceptibility testing. On-site assessments and remote follow-ups were conducted by CDPH infection preventionists to evaluate infection control practices including environmental cleaning, hand hygiene compliance, and use of personal protective equipment (PPE). The Illinois Department of Public Health and CDPH summarized the testing results, facilitated a containment response, and provided recommendations for infection control. Results: From March 18, 2020, to September 30, 2021, 56 patients with CRAB infections were identified from hospital A, and 33 (59%) of these cases were pan-nonsusceptible. Most specimen sources were sputum (n = 30, 54%), followed by blood (n = 13, 23%), urine (n = 6, 11%) and other (n = 7, 13%). Among isolates with mechanism testing (n = 54), 45 (83%) were positive for OXA-24/40 and 9 (17%) were positive for OXA-23. Of the CRAB-positive patients, 28 (50%) were previously positive for SARS-CoV-2. To date, 25 of these patients (45%) have been discharged and 31 (55%) have died. Two onsite visits and 7 remote-assistance sessions were conducted as part of the investigation. In response to increased COVID-19 hospitalizations, hospital A moved to crisis-capacity PPE use and encountered staffing shortages, which led to compromised infection control measures. Cleaning agents (Quat disinfectant cleaner) were also found to be ineffective against CRAB and required long contact times. Conclusions: In response to the CRAB outbreak at hospital A, CDPH recommended that the hospital stop crisis-capacity protocols for PPE, conduct admission screening and point-prevalence testing for CRAB, implement a hand hygiene campaign, and use an EPA-registered List K product for environmental cleaning. These recommendations were implemented in May 2021, and no CRAB cases have been reported since July 2021. To reduce CRAB transmission during the pandemic, facility leadership must commit resources to educate staff on effective infection control practices including conventional use of PPE, appropriate cleaning agents, and improved hand hygiene.

Funding: None

Disclosures: None