Objectives/Goals: Clinical trial success requires recruiting and retaining diverse participants. The ER&R Certificate Program trains clinical research professionals (CRPs) in equity, diversity, and inclusion (EDI), addressing biases, and integrating regulatory knowledge with practical skills to foster inclusive research practices. Methods/Study Population: An interdisciplinary Steering Committee, supported by Duke CTSI and DOCR, developed and implemented an engagement, recruitment, and retention certificate program (ER&R) for CRPs. With expert-led instruction, including e-learning, group sessions, and hands-on activities, ER&R integrates EDI into participant engagement practices. Participants complete 7 core courses and at least 3 elective courses, reflecting their unique responsibilities. Program evaluation uses the Kirkpatrick model to assess participant learning, competency, and EDI integration into clinical research. Since launch, the program has expanded to include clinical research trainees from Durham Technical Community College. All elements of the program were designed to allow for sharing across academic medical institutions. Results/Anticipated Results: A total of 202 CRPs and trainees have participated since launch (2020), including 17 trainee participants from Durham Technical Community College (2022–2024). Post-program evaluations showed significant growth in recruitment and retention self-efficacy. An early evaluation of the first 2 cohorts (n = 59) included a self-assessment across defined competencies showing marked increases in comfort across all learning objectives, with notable gains in: Community and Stakeholder Engagement, Recruitment on a Shoestring Budget, Community-Engaged Research Initiatives, and Social Marketing. Participants valued the program’s focus on EDI and sought more practical strategies and peer collaboration. 50 additional institutions have engaged with our implementation consultations and program repository. Discussion/Significance of Impact: Barriers to equitable ER&R exist at the individual, study, and system levels. Addressing these requires more intentional engagement practices. The ER&R certificate program is an innovative model for integrating equity principles with practical and required knowledge and skills training for participant-facing research professionals.

Objectives/Goals: • To determine the impact of liraglutide on inflammation and organ injury during sepsis. • To investigate the protective effects of liraglutide on microvascular dysfunction in a clinically relevant model of sepsis. • To provide evidence for the potential therapeutic use of GLP-1 receptor agonists in endothelial dysfunction in sepsis. Methods/Study Population: Sepsis was induced in mice (N = 34) by intraperitoneal injection of cecal contents (1.8 mg/g body weight) and 24-hour hyperoxia (FiO2 90–95%). Mice received saline or liraglutide (0.1 mg/kg) at 6 and 18 hours post-injection and fluids and antibiotics at 12 hours. At 24 hours, mice were euthanized for plasma, bronchoalveolar lavage (BAL), and tissue collection. Plasma inflammatory markers, organ injury markers, and BAL components were measured. In vitro, primary human lung microvascular endothelial cells (HLMVECs) were treated with saline or liraglutide for 24 hours before exposure to saline or LPS (100 ng/mL). HLMVEC barrier dysfunction was evaluated using express permeability testing (XPerT) and electric cell-substrate impedance sensing (ECIS) to measure transendothelial electrical resistance (TER). Results/Anticipated Results: In murine sepsis, illness severity scores and lung injury were improved in mice pretreated with liraglutide (N = 10). Plasma blood urea nitrogen (BUN; P = 0.0036), alanine transaminase (ALT; P = 0.0311) and vascular inflammatory markers MCP-1 (P = 0.0172), ICAM-1 (P = 0.0356), and Pecam-1 (P = 0.0493) in plasma were reduced in mice treated with liraglutide. In HLMVECs, liraglutide (1.5 nM) significantly reduced LPS-induced barrier dysfunction measured by XPerT assay (P = 0.0030) and ECIS (P = 0.0075). Discussion/Significance of Impact: Liraglutide reduces illness severity, vascular inflammation, and organ injury in a two-hit model of sepsis. Liraglutide has direct effects in the microvascular endothelium, limiting LPS-mediated barrier dysfunction. These findings support a protective role for GLP-1 receptor agonism in sepsis, mediated through the microvasculature.

Enrollment into a prospective cohort study of mother–preterm infant dyads during the COVID-19 pandemic progressed slower than anticipated. Enrollment occurred during the first week after preterm birth, while infants were still hospitalized. We hypothesized that slower enrollment was attributable to mothers testing positive for COVID-19 as hospital policies restricted them from entering the neonatal intensive care unit, thus reducing interactions with research staff. However, only 4.5% of 245 screened mothers tested COVID-19 positive. Only 24.9% of those screened, far fewer than anticipated, were eligible for enrollment. Assumptions about pandemic-related enrollment barriers were not substantiated in this pediatric cohort.

The authors report on ancient DNA data from two human skeletons buried within the chancel of the 1608–1616 church at the North American colonial settlement of Jamestown, Virginia. Available archaeological, osteological and documentary evidence suggest that these individuals are Sir Ferdinando Wenman and Captain William West, kinsmen of the colony's first Governor, Thomas West, Third Baron De La Warr. Genomic analyses of the skeletons identify unexpected maternal relatedness as both carried the mitochondrial haplogroup H10e. In this unusual case, aDNA prompted further historical research that led to the discovery of illegitimacy in the West family, an aspect of identity omitted, likely intentionally, from genealogical records.

Recent theories suggest that for youth highly sensitive to incentives, perceiving more social threat may contribute to social anxiety (SA) symptoms. In 129 girls (ages 11–13) oversampled for shy/fearful temperament, we thus examined how interactions between neural responses to social reward (vs. neutral) cues (measured during anticipation of peer feedback) and perceived social threat in daily peer interactions (measured using ecological momentary assessment) predict SA symptoms two years later. No significant interactions emerged when neural reward function was modeled as a latent factor. Secondary analyses showed that higher perceived social threat was associated with more severe SA symptoms two years later only for girls with higher basolateral amygdala (BLA) activation to social reward cues at baseline. Interaction effects were specific to BLA activation to social reward (not threat) cues, though a main effect of BLA activation to social threat (vs. neutral) cues on SA emerged. Unexpectedly, interactions between social threat and BLA activation to social reward cues also predicted generalized anxiety and depression symptoms two years later, suggesting possible transdiagnostic risk pathways. Perceiving high social threat may be particularly detrimental for youth highly sensitive to reward incentives, potentially due to mediating reward learning processes, though this remains to be tested.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.

Icebergs in proglacial fjords serve as pupping, resting and molting habitat for some of the largest seasonal aggregations of harbor seals (Phoca vitulina richardii) in Alaska. One of the largest aggregations in Southeast Alaska occurs in Johns Hopkins Inlet, Glacier Bay National Park, where up to 2000 seals use icebergs produced by Johns Hopkins Glacier. Like other advancing tidewater glaciers, the advance of Johns Hopkins Glacier over the past century has been facilitated by the growth and continual redistribution of a submarine end moraine, which has limited mass losses from iceberg calving and submarine melting and enabled glacier thickening by providing flow resistance. A 15-year record of aerial surveys reveals (i) a decline in iceberg concentrations concurrent with moraine growth and (ii) that the iceberg size distributions can be approximated as power law distributions, with relatively little variability and no clear trends in the power law exponent despite large changes in ice fluxes over seasonal and interannual timescales. Together, these observations suggest that sustained tidewater glacier advance should typically be associated with reductions in the number of large, habitable icebergs, which may have implications for harbor seals relying on iceberg habitat for critical life-history events.

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.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Despite becoming increasingly represented in academic departments, women scholars face a critical lack of support as they navigate demands pertaining to pregnancy, motherhood, and child caregiving. In addition, cultural norms surrounding how faculty and academic leaders discuss and talk about tenure, promotion, and career success have created pressure for women who wish to grow their family and care for their children, leading to questions about whether it is possible for these women to have a family and an academic career. This paper is a call to action for academia to build structures that support professors who are women as they navigate the complexities of pregnancy, the postpartum period, and the caregiving demands of their children. We specifically call on those of us in I-O psychology, management, and related departments to lead the way. In making this call, we first present the realistic, moral, and financial cases for why this issue needs to be at the forefront of discussions surrounding success in the academy. We then discuss how, in the U.S. and elsewhere, an absence of policies supporting women places two groups of academics—department heads (as the leaders of departments who have discretion outside of formal policies to make work better for women) and other faculty members (as potential allies both in the department and within our professional organizations)—in a critical position to enact support and change. We conclude with our boldest call—to make a cultural shift that shatters the assumption that having a family is not compatible with academic success. Combined, we seek to launch a discussion that leads directly to necessary and overdue changes in how women scholars are supported in academia.

OBJECTIVES/GOALS: Computational pathology is an emerging discipline that resides at the intersection of engineering, computer science, and pathology. There is a growing need to develop innovative pedagogical approaches to train future computational pathologists who have diverse educational backgrounds. METHODS/STUDY POPULATION: Our work proposes an iterative approach toward teaching master’s and Ph.D. students from various backgrounds, such as electrical engineering, biomedical engineering, and cell biology the basics of cell-type identification. This approach is grounded in the active learning framework to allow for observation, reflection, and independent application. The learners are trained by a team of an electrical engineer and pathologist and provided with eight images containing a glomerulus. They must then classify nuclei in each of the glomeruli as either a podocyte (blue), endothelial cell (green), or mesangial cell (red). RESULTS/ANTICIPATED RESULTS: A simple web application was built to calculate agreement, measured using Cohen’s kappa, between annotators for both individual glomeruli and across all eight images. Automating the process of providing feedback from an expert renal pathologist to the learner allows for learners to quickly determine where they can improve. After initial training, agreement scores for cells scored by both the learner and the expert were high (0.75), however, when including cells not scored by both the agreement was relatively low (0.45). This indicates that learners needed more instruction on identifying unique cells within each image. This low-stakes approach encourages exploratory and generative learning. DISCUSSION/SIGNIFICANCE: Computation medical sciences require interdisciplinary training methods. We report on a robust approach for team-based mentoring and skill development. Future implementations will include undergraduate learners and provide opportunities for graduate students to engage in near-peer mentoring.

Over the past 40 years, positive ageing discourses that speak to an expectation of continued productivity have gained prominence within research and policy. Such discourses have been critiqued as placing disproportionate value on the extension of older adults' working lives, while obscuring other valuable forms of work performed by older adults. Despite the emergence of theoretical conversations about the expansion of conceptions of work, few studies have adopted an explicit focus on the work performed by older adults within their neighbourhoods. Informed by conceptions of work positioned at the intersection of critical gerontology and critical feminism, we drew upon qualitative data from a larger ethnographic study, generated from 17 participants aged 65 and older, to examine: (a) the various forms and contributions of unpaid work that older adults carry out at the neighbourhood level, and (b) the ways in which older adults' representations of this work relate to dominant notions of productivity. Specifically, each participant engaged in three types of qualitative interviews, including additional spatial and visual data generation: (a) completing a narrative interview; (b) carrying a small Global Positioning System (GPS) device to automatically log locations, completing an activity diary and a follow-up interview; and (c) participating in a go-along interview or a photo elicitation interview. Our findings highlight a range of unpaid work performed by participants in their neighbourhood, including formal volunteering, informal caring and informal civic participation. Although these forms of work were, at times, discussed by participants as enabling social inclusion, significant tensions arose from the general lack of discursive and social value assigned to them. In particular, participants described being subject to overwhelming expectations placed on older adults, and women in particular, to carry out this work, with little recognition or acknowledgement of their contributions to the neighbourhood. Taken together, our findings suggest the need not only to diversify understandings of the forms of work perceived as aligning with productive contributions to society in older age, but also to attend to the invisible work performed by older adults within their neighbourhoods. Additionally, we propose a variety of ways organisations and communities that benefit from older adults' unpaid labour may enhance accessibility, thereby reducing the work done by older adults to negotiate tensions between ableist expectations for productivity and their ageing bodies.

How does civil society affect support for the political system during times of political crises? Some argue that civil society strengthens support for political systems by increasing trust and participation. Yet recent scholarship demonstrates that civil society can also facilitate mobilization and dissent, which may undermine support for the political system, especially in times of crisis. We test these competing claims using individual-level data from a country in the midst of a major political crisis: Bolivia in 2004. We find that membership in civil society organizations leads to higher levels of diffuse support for the political system even during a crisis—and even among those who have recently participated in protest. Civil society, however, is not associated with higher support for government during the crisis. Despite extremely high levels of mobilization, extreme dissatisfaction with government, and evidence that membership in associations actively facilitates political protest, civil society continues to be positively associated with support for the political system.