Archaeological sites in Northwest Africa are rich in human fossils and artefacts providing proxies for behavioural and evolutionary studies. However, these records are difficult to underpin on a precise chronology, which can prevent robust assessments of the drivers of cultural/behavioural transitions. Past investigations have revealed that numerous volcanic ash (tephra) layers are interbedded within the Palaeolithic sequences and likely originate from large volcanic eruptions in the North Atlantic (e.g. the Azores, Canary Islands, Cape Verde). Critically, these ash layers offer a unique opportunity to provide new relative and absolute dating constraints (via tephrochronology) to synchronise key archaeological and palaeoenvironmental records in this region. Here, we provide an overview of the known eruptive histories of the potential source volcanoes capable of widespread ashfall in the region during the last ~300,000 years, and discuss the diagnostic glass compositions essential for robust tephra correlations. To investigate the eruption source parameters and weather patterns required for ash dispersal towards NW Africa, we simulate plausible ashfall distributions using the Ash3D model. This work constitutes the first step in developing a more robust tephrostratigraphic framework for distal ash layers in NW Africa and highlights how tephrochronology may be used to reliably synchronise and date key climatic and cultural transitions during the Palaeolithic.

Oceania is currently facing a substantial challenge: to provide sustainable and ethical food systems that support nutrition and health across land and water. The Nutrition Society of Australia and the Nutrition Society of New Zealand held a joint 2023 Annual Scientific Meeting on ‘Nutrition and Wellbeing in Oceania’ attended by 408 delegates. This was a timely conference focussing on nutrition challenges across the Pacific, emphasising the importance of nutrition across land and water, education settings, women’s health and gut health. Cutting-edge, multi-disciplinary and collaborative research was presented in a 4-day programme of keynote presentations, workshops, oral and poster sessions, breakfast and lunch symposiums and early career researcher sessions. The conference highlighted the importance of collaboration between nations to address the challenge facing nutrition and wellbeing across Oceania. A systems approach of collaboration among scientists, industry and government is vital for finding solutions to this challenge.

OBJECTIVES/GOALS: The inclusion of underrepresented racial and ethnic groups (URGs) in clinical research is critical for ethical and scientific reasons. This initiative aimed to assess the perspectives, barriers, needs, and recommendations encountered by research teams when enrolling and retaining URGs in clinical research. METHODS/STUDY POPULATION: An anonymous, web-based survey comprised of quantitative and qualitative questions was administered to individuals involved in clinical research at an academic medical center. The survey assessed three main domains: 1. Research teams' perceptions and experiences with enrolling URGs in clinical research, 2. Factors that discourage URGs from participating in clinical research, and 3. Research teams’ overall willingness to support URG enrollment. Demographics were also collected. The survey was reviewed by experts in clinical research, research ethics, and diversity, equity, inclusion, and accessibility (DEIA). The assessment was piloted among research professionals and edits were made accordingly prior to official dissemination. Data were analyzed using descriptive statistics. RESULTS/ANTICIPATED RESULTS: There was a total of 63 responses. A majority of respondents have more success enrolling patients whose primary language is the same as their own and that time arranging for an interpreter has negatively impacted enrollment efforts. Approximately half of the respondents believe that the race and/or ethnicity of the potential study participant influences enrollment success. Factors discouraging URGs from participating in clinical research include unavailability for follow-up visits due to transportation issues, distrust in doctors and/or researchers, fear of unknown side effects, and unavailability of medical interpreters. Respondents report that they are not discouraged from enrolling URGs and would utilize resources related to encouraging the inclusion of URGs DISCUSSION/SIGNIFICANCE: Language appears more influential than ethnicity or race when it comes to enrolling and retaining URGs. Additionally, it appears that enrolling is a bigger challenge than retaining. Major themes that emerge with respect to retaining enrolled participants include the inability to attend follow-up visits and the lack of incentives/compensation.

During their northward migration, Red Knots Calidris canutus rufa stop at the Lagoa do Peixe National Park in the extreme south of Brazil to build up fat reserves for their journey to their Canadian breeding grounds. We tracked five Red Knots with PinPoint Argos-75 GPS transmitters to investigate differences in migration strategies from this stopover. Tracked birds used two different routes: the Central Brazil route and the Brazilian Atlantic Coast route. One bird flew 8,300 km straight from Lagoa do Peixe to the Delaware Bay (USA). Another bird stopped in Maranhão (north-east Brazil) and a third one used a yet unknown environment for the species, the mouth of the Amazon River at Baía Santa Rosa, Brazil. These two birds made short flights, covering stretches of 1,600 km to 3,600 km between stop-overs, where they stayed from 4 to 18 days. Our study highlights the occurrence of intrapopulation variation in migratory strategies and reveals the connectivity of environments that are essential for the viability of rufa Red Knot populations.

The eruption of Toba ca. 75 ka was the largest volcanic eruptive event during the Quaternary, and evidence for this eruption is widespread in terrestrial sediment sequences in South Asia as primary and reworked distal ash deposits. Youngest Toba Tuff horizons (YTT) have been widely employed as isochrons to understand and link regional sediment sequences and the evidence for environmental and cultural change in the archaeological records preserved within them. We identify the YTT deposits at Retlapalle, Andhra Pradesh, India, and present the optical ages of the K-feldspar grains recovered from sediments immediately underlying and overlying the tephra horizon. We combine these results with particle size and magnetic susceptibility analyses to establish the depositional conditions of YTT, which indicate that accumulation and reworking ceased by ca. 64 ka. We explore the role of YTT deposits as an isochron for examining the effect of the 75 ka Toba super-eruption, highlighting the need for an independent chronological assessment of YTT before using it as a Late Pleistocene chronological marker in reconstructing South Asian paleo-landscapes and hominin adaptations. Further, our findings support the regional continuity of human occupations within South Asia, spanning the eruption of Toba and the enduring utility of Middle Paleolithic tools.

OBJECTIVES/GOALS: Research ethics services are critical to the clinical, research, and educational missions of an academic health science center. Our ethics program aims to develop a culture where investigators are as intellectually engaged in ethical issues of scientific integrity as they are in study design, data collection, and implementation. METHODS/STUDY POPULATION: This descriptive analysis depicts the historical development, from 2010 to 2022, of our research ethics program as an exemplar of ethics integration into the research enterprise of an academic health science center that engages in translational research. In this culture, clinicians, translational researchers and their scientific peers, research participants, and community members become involved in ethics investigation, deliberation, and innovation. RESULTS/ANTICIPATED RESULTS: There are four pillars to our research ethics program: 1) research ethics consultation service, which fosters the development of ethical best practices and standards for the practice of translational research; 2) education, which provides customized training and educational opportunities in research ethics to diverse stakeholders; 3) leadership, through collaboration and partnerships; 4) scholarly engagement, in the pursuit of innovative ethics research and professional development. Through these initiatives we can engage a broad constituency of stakeholders, become an integral component of research oversight, engage as active participants in the research enterprise, and have a critical role in guiding institutional culture. DISCUSSION/SIGNIFICANCE: The integration of our ethics program mirrors the translational science continuum which promotes the multidirectional flow of ideas among ethics consultants, laboratory/clinical scientists, implementation researchers and the community.

OBJECTIVES/GOALS: The need for mechanisms of ethical discourse and guidance has increased as translational research collaborations become more complex. The goal of this project is to analyze the stakeholder engagement and ethical issues our research ethics consultation service (RECS) conducted over a two year period. METHODS/STUDY POPULATION: We conducted a retrospective review of our RECS database from 2020 to 2022. We examined the nature of the research and ethical issues of concern from consult requestors, including whether or not consults were preventative. In addition, we assessed the educational outreach conducted during that timeframe as a measure of service awareness. RESULTS/ANTICIPATED RESULTS: There was a total of 42 consults conducted over the previous year. There were a wide variety of issues related to informed IRB-related processes (31%), consent (24%), QA/QI determination (12%), authorship (10%), confidentiality (7%), diversity/inclusion (7%), grant preparation (7%). Many of the consults (n=28, 67%) included secondary issues. A few consults (n=4, 10%) were preventative, meaning that the consult was requested in anticipation or consideration of a potential ethical issue. Outreach efforts extended to a diverse array of institutional stakeholders and trainees. DISCUSSION/SIGNIFICANCE: The RECS serves numerous constituencies throughout our institution on ethical issues spanning nearly all aspects of research design, conduct, and analysis. These data highlight initiatives to increase study efficiency (in collaboration with institutional research oversight) and helps to direct educational efforts and outreach.

Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.

ABSTRACT IMPACT: This study highlights the importance of creatine in developmental myelination and remyelination to investigate whether creatine provides a therapeutic value during a central nervous system (CNS) demyelinating insult with a potential value in patients with Multiple Sclerosis. OBJECTIVES/GOALS: Creatine is vital for ATP buffering in the brain. Interestingly, the cells that generate myelin express the main enzyme for creatine synthesis, Gamt. Patients with Gamt mutations display intellectual delays and impaired myelination. Therefore, we hypothesize that creatine is essential for developmental myelination and improves remyelination. METHODS/STUDY POPULATION: To investigate these hypotheses, we developed a new transgenic mouse model with LoxP sites flanking exons 2-6 of the guanidinoacetate methyltransferase (Gamt) gene where excision leads to expression of a green fluorescent tag allowing us to track the cells normally expressing Gamt. We used immunohistochemistry techniques to look at the corpus callosum, the main white matter tract in the brain, and evaluate the number of oligodendrocytes (OL), glial cells responsible for generating myelin. We also used the cuprizone model of toxic demyelination to investigate whether dietary creatine and cyclocreatine, a planar analog of creatine that more efficiently crosses the blood-brain barrier, can enhance remyelination. RESULTS/ANTICIPATED RESULTS: In this mouse model, we show a 95% (+/-0.47%, n=3) co-localization of Gamt within mature OL during postnatal (P) day P14 with no co-localization in neurons or other glial cells. This suggests that mature OL are the main cells making creatine in the CNS. Next, we show that knocking out Gamt leads to a significant reduction in OL in the developing corpus callosum, at P14 and P21 (P14: 0.007, n=3; P21: 0.04, n=3). We also show that creatine supplementation causes a trending increase in mature OL density in the corpus callosum following cuprizone demyelination (2% creatine; p=0.052; n=4). Interestingly, cyclocreatine supplementation significantly increased mature OL density in the corpus callosum following cuprizone demyelination (0.1% cyclocreatine; p=0.034; n=4). DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies highlight the important role creatine plays in developmental myelination and remyelination to investigate whether creatine and cyclocreatine provide a therapeutic value during a CNS demyelinating insult. This work investigates a potential therapeutic value of creatine to patients with Multiple Sclerosis.

Over the last year, COVID-19 has emerged as a highly transmissible and lethal infection. As we address this global pandemic, its disproportionate impact on Black, Indigenous, and Latinx communities has served to further magnify the health inequities in access and treatment that persist in our communities. These sobering realities should serve as the impetus for reexamination of the root causes of inequities in our health system. An increased commitment to strategic partnerships between academic and nonacademic health systems, industry, local communities, and policy-makers may serve as the foundation. Here, we examine the impact of the recent COVID-19 pandemic on health care inequities and propose a strategic roadmap for integration of clinical and translational research into our understanding of health inequities.

Engaging communities can increase the speed of translating health and health equity research into practice. Effective engagement requires a shared understanding of the health of a community. This can be challenging without timely and accurate local health data, or ways to provide that data, that are directly applicable to improving community health outcomes. The University of Wisconsin Institute for Clinical and Translational Research formed the Neighborhood Health Partnerships Program (NHP) to overcome this challenge, making sub-county health data available to researchers and community stakeholders while incorporating community voice into data delivery processes. The NHP team used a human-centered design approach to facilitate community engagement. Through co-design, the team created NHP reports and data-to-action tools to maximize accessibility and utility for a diverse set of community stakeholders. Early indicators show that the final co-designed NHP reports and data-to-action tools will be immediately useful in promoting community–academic partnerships and in planning, implementing, and evaluating research and other initiatives in communities. The NHP program demonstrates that an effective co-design strategy can lead to increased usability and adoption of Clinical and Translational Science Award resources, enabling a shared understanding of community health and ultimately leading to the successful translation of research into practice.

OBJECTIVES/GOALS: Oligodendrocytes (OL) are glial cells of the central nervous system (CNS) responsible for the energy demanding task of generating myelin sheaths during development and remyelination after demyelinating injury. One metabolite shown to significantly increase ATP production in OL is the nitrogenous organic acid, creatine. Creatine plays an essential role in ATP buffering within tissues with highly fluctuating energy demands such as brain and muscle. Interestingly, mature OL, which are the cells capable of myelin production, are the main cells in the CNS expressing the rate-limiting enzyme for creatine synthesis, guanidinoacetate methyltransferase (Gamt). Patients with mutations in Gamt display intellectual disabilities, impaired myelination and seizures. Therefore, we hypothesize that creatine may be essential for developmental myelination and improve remyelination. METHODS/STUDY POPULATION: To investigate these hypotheses, we developed a new transgenic mouse model with LoxP sites flanking exons 2-6 of the Gamt gene where excision leads to expression of a green fluorescent tag allowing us to track the cells normally expressing Gamt. RESULTS/ANTICIPATED RESULTS: In this mouse model, we show a 95% (±0.47%, n = 3) co-localization of Gamt within mature OL during postnatal (P) day P14. Next, we show that knocking out Gamt leads to a significant reduction in OL in the major CNS white matter tract, the corpus callosum, at P14 and P21 (P14: 0.007, n = 3; P21: 0.04, n = 3). Here, we also investigate whether dietary creatine can enhance remyelination in the cuprizone model of toxic demyelination. DISCUSSION/SIGNIFICANCE OF IMPACT: These studies highlight the important role creatine plays in developmental myelination and investigate whether creatine can provide a therapeutic value during a CNS demyelinating insult.