Translational Research Projects Research Articles

Pharmacologic Therapy for Spinal Cord Injury.

Neuroprotective strategies aimed at preventing secondary neurologic injury following acute spinal cord injury remain an important area of clinical, translational, and basic science research. Despite recent advancement in the understanding of basic mechanisms of primary and secondary neurologic injury, few pharmacologic agents have shown consistent promise in improving neurologic outcomes following SCI in large randomized clinical trials. The authors review the existing literature and clinical guidelines for pharmacologic therapy investigated for managing acute SCI, including corticosteroids, GM-1 ganglioside (Sygen), Riluzole, opioid antagonists, Cethrin, minocycline, and vasopressors for mean arterial pressure augmentation. Therapies for managing secondary effects of SCI, such as bradycardia, are discussed. Current clinical trials for pharmacotherapy and cellular transplantation following acute SCI are also reviewed. Despite the paucity of current evidence for clinically beneficial post-SCI pharmacotherapy, future research efforts will hopefully elucidate promising therapeutic agents to improve neurologic function.

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing

Since the first novel gene discovery for a Mendelian condition was made via exome sequencing, the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare diseases. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene discovery research programs. Accordingly, clinical laboratories have both the opportunity, and some might argue a responsibility, to contribute to novel gene discovery, which should, in turn, increase the diagnostic yield for many conditions. However, clinical diagnostic laboratories must necessarily balance priorities for throughput, turnaround time, cost efficiency, clinician preferences, and regulatory constraints and often do not have the infrastructure or resources to effectively participate in either clinical translational or basic genome science research efforts. For these and other reasons, many laboratories have historically refrained from broadly sharing potentially pathogenic variants in novel genes via networks such as Matchmaker Exchange, much less reporting such results to ordering providers. Efforts to report such results are further complicated by a lack of guidelines for clinical reporting and interpretation of variants in novel candidate genes. Nevertheless, there are myriad benefits for many stakeholders, including patients/families, clinicians, and researchers, if clinical laboratories systematically and routinely identify, share, and report novel candidate genes. To facilitate this change in practice, we developed criteria for triaging, sharing, and reporting novel candidate genes that are most likely to be promptly validated as underlying a Mendelian condition and translated to use in clinical settings.

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.

Since the first novel gene discovery for a Mendelian condition was made via exome sequencing (ES), the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare disease. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene discovery research programs. Accordingly, clinical laboratories have both the opportunity, and some might argue a responsibility, to contribute to novel gene discovery which should in turn increase the diagnostic yield for many conditions. However, clinical diagnostic laboratories must necessarily balance priorities for throughput, turnaround time, cost efficiency, clinician preferences, and regulatory constraints, and often do not have the infrastructure or resources to effectively participate in either clinical translational or basic genome science research efforts. For these and other reasons, many laboratories have historically refrained from broadly sharing potentially pathogenic variants in novel genes via networks like Matchmaker Exchange, much less reporting such results to ordering providers. Efforts to report such results are further complicated by a lack of guidelines for clinical reporting and interpretation of variants in novel candidate genes. Nevertheless, there are myriad benefits for many stakeholders, including patients/families, clinicians, researchers, if clinical laboratories systematically and routinely identify, share, and report novel candidate genes. To facilitate this change in practice, we developed criteria for triaging, sharing, and reporting novel candidate genes that are most likely to be promptly validated as underlying a Mendelian condition and translated to use in clinical settings.

American College of Rheumatology White Paper: The Effects of Climate Change on Rheumatic Conditions-An Evolving Landscape and a Path Forward.

Increases in global temperatures and extreme weather events associated with climate change have complex yet poorly understood detrimental impacts on human health. We reviewed the current published literature on climate change-related effects and rheumatic conditions. To summarize our current understanding of the likely effects of climate change, including increased air pollution, on rheumatic disease, we searched the published, peer-reviewed English-language literature from January 2000 to December 2022. Articles were reviewed by a team of rheumatologists and clinical and translational science researchers. Systematic review articles were not included but informed additional literature searches. After extensive examination and adjudication, 88 articles met inclusion criteria and were selected for review. Much of the epidemiologic investigations assessed associations between air pollution and increased risk of development of rheumatoid arthritis, anti-citrullinated protein antibodies, flares of gout, and hospitalizations for systemic lupus erythematosus. Increased heat vulnerability was associated with higher odds of recurrent hospitalizations across rheumatic conditions. Mechanisms for observed associations are poorly understood but could include the effects of epigenetic changes, oxidative stress, and inflammatory cytokines. Studies had limitations, including restricted geography and populations studied without focus on historically marginalized communities at highest risk for adverse effects from pollution and climate change, the relative lack of mechanistic evaluations, and most with only indirect links to climate change. To date, the published literature lacks studies that directly examine effects of climate change on rheumatic diseases. Collaborative translational and epidemiologic research is needed to enhance our understanding and awareness in this area.

Standardized Protocols for Clinical and Histopathological Characterization of Hidradenitis Suppurativa Tissue Specimens

Methods for describing and reporting the clinical and histological characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. Here we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from HS patients. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help consistently classify specimens in biobanks based on histological features and more accurately report and select samples used in translational research projects.

Informing future quarantine practices through the experiences of COVID‐19 quarantine facility staff

AbstractBackgroundThe COVID‐19 pandemic necessitated the rapid development of quarantine sites, prompting the need for new staff models and scopes of practice. This project surveyed health and non‐health staff at a large outdoor quarantine facility in regional Australia to gather insights for future quarantine facility guidelines based on their experiences and perceptions.MethodsThis translational research project implemented a mixed‐methods approach to analyse staff perceptions of working at a quarantine facility to inform the development of a policy and practice guide. An anonymous online survey utilising purposive sampling was distributed to 410 multidisciplinary survey participants over an 8‐week period. Survey questions focussed on site processes, challenges and recommendations for future implementation of quarantine services. Qualitative data was thematically analysed with the aid of Leximancer, and a descriptive statistical method was used for quantitative data analysis.ResultsThere were 92 survey respondents from health and non‐health roles; of these, 85% indicated they would work at the quarantine facility again, and 90% agreed residents were well cared for. There was a lack of anxiety of acquiring COVID‐19, with 95% feeling safe from COVID‐19 transmission onsite. Challenges staff identified highlighted future investment areas, including leadership communication models, information technology (IT) management systems specific for quarantine services and site processes to better accommodate weather elements.ConclusionOverall, staff validated the primary health model of quarantine care with key challenges highlighting the importance of leadership and investment in communication and IT. The results were aligned with site functions and operations and will inform the development of a pandemic quarantine facility guide.

Design and Construction of a Radiochemistry Laboratory and cGMP-Compliant Radiopharmacy Facility.

The establishment of a compliant radiopharmacy facility within a university setting is crucial for supporting fundamental and preclinical studies, as well as for the production of high-quality radiopharmaceuticals for clinical testing in human protocols as part of Investigational New Drug (IND) applications that are reviewed and approved by the U.S. Food and Drug Administration (FDA). This manuscript details the design and construction of a 550 ft2 facility, which included a radiopharmacy and a radiochemistry laboratory, to support radiopharmaceutical development research and facilitate translational research projects. The facility was designed to meet FDA guidelines for the production of aseptic radiopharmaceuticals in accordance with current good manufacturing practice (cGMP). A modular hard-panel cleanroom was constructed to meet manufacturing classifications set by the International Organization of Standardization (ISO), complete with a gowning room and an anteroom. Two lead-shielded hot cells and two dual-mini hot cells, connected via underground trenches containing shielded conduits, were installed to optimize radioactive material transfer while minimizing personnel radiation exposure. Concrete blocks and lead bricks provided sufficient and cost-effective radiation shielding for the trenches. Air quality was controlled using pre-filters and high-efficiency particulate air (HEPA) filters to meet cleanroom ISO7 (Class 10,000) standards. A laminar-flow biosafety cabinet was installed in the cleanroom for preparation of sterile dose vials. Noteworthy was a laminar-flow insert in the hot cell that provided a shielded laminar-flow sterile environment meeting ISO5 (class 100) standards. The design included the constant control and monitoring of differential air pressures across the cleanroom, anteroom, gowning room, and controlled research space, as well as maintenance of temperature and humidity. The facility was equipped with state-of-the-art equipment for quality control and release testing of radiopharmaceuticals. Administrative controls and standard operating procedures (SOPs) were established to ensure compliance with manufacturing standards and regulatory requirements. Overall, the design and construction of this radiopharmacy facility exemplified a commitment to advancing fundamental, translational, and clinical applications of radiopharmaceutical research within an academic environment.

The Water Resources Rebound Effect Threatening the Achievement of Sustainable Development Goal 6 (SDG 6)

Coaction of climate change and human activities exerts a significant impact on the fate of water resources, provoking the rebound effect in water resources and threatening the achievement of SDG (sustainable development goal) 6. However, the mechanisms of interactions between this effect and SDG 6 and how to decrease this effect towards the achievement of SDG 6 are less known. In this paper, a water resources rebound effect (WRRE) model is integrated into a river basin sustainable development decision support system to simulate and project the interactions between the WRRE and SDG 6 under multiple combination scenarios. The results show that multiple drivers, including precipitation, technological advances, and ecological water flow, coaffect the WRRE, not the silo technology factor. The transfer fate of the saved water is a major root cause leading to the WRRE and harming the achievement of SDG 6, and the WRRE is positively correlated to SDG 6 overall, which, nevertheless, can sometimes be reversed by technological advances. Our outcomes indicate that decoupling SDG 6 from the WRRE can promote the achievement of SDG 6 and decrease the rebound effect, relying on holistic integration that couples climatic, socioeconomic, and behavioral interaction between SDG 6 and the WRRE and translation of scientific research into available decision-making information for strict scientific-research-based policy actions.

535 Translational science vs. translational research in CTSA pilot projects: characteristics and perceptions

OBJECTIVES/GOALS: NCATS requires that CTSA-funded pilot projects focus on translational science (TS) and evaluate the translational process. However, a consistent understanding of TS remains elusive. This gap is being addressed by a consortium of 12 CTSA hubs aimed at identifying distinctive features of TS and translational research (TR) proposals. METHODS/STUDY POPULATION: CTSA External Review Exchange Consortium (CEREC) is a reciprocal review collaboration among CTSA hubs. Reviewers were CEREC members from hubs that submitted CTSA applications (PAR-21-293); read the Notice of Funding Opportunity (NOFO) Clinical and Translations Science Pilot Module; and discussed TS with their hubs “a fair amount” or “quite a bit” and then they independently categorized proposals. Proposals were labeled TS or TR if reviewers reached a consensus on category assignment; without consensus, proposals were labeled unclassified. In addition to category assignment, reviewers commented about their classifications. R was used to evaluate the comments and create word clouds with phrases/themes that distinguished between the categories of proposals. RESULTS/ANTICIPATED RESULTS: Twelve CEREC participating hubs submitted 26 proposals, which were funded prior to the new NCATS TS requirements. Eight reviewers from distinct CEREC hubs evaluated and classified each proposal as TS or TR. Consensus (at least 87% agreement) was reached for 12 proposals, 6 TS and 6 TR. Reviewers provided comments describing the rationale for their classifications for 70% of the proposals. Qualitative analysis of the reviewers’ comments and rationale by classification (TS, TR, or unclassified) revealed common themes within and differences between groups and shed light on what defines TS and TR. The most frequent themes that distinguished TS from TR were generalizability across multiple diseases and a focus on increasing research efficiency. DISCUSSION/SIGNIFICANCE: NIH is focused on research that meets the new definition of TS. Investigators seeking to address this funding priority should explicitly state the relevance of their research to multiple diseases and to the acceleration of future research. Programs seeking to attract TS projects should instruct applicants to include this information.

278 Accelerating the Practice of Human-Centered Design in Translational Research

OBJECTIVES/GOALS: Human-centered design (HCD) provides a practical, collaborative approach to integrating diverse perspectives throughout the translational research process. We highlight two CTSAs with established HCD teams who are utilizing varied approaches to accelerate the use of HCD in health intervention design and community engagement. METHODS/STUDY POPULATION: The CTSAs at the University of Michigan (MICHR) and the University of Pittsburgh (Pitt CTSI) have dedicated teams of human-centered designers that assist investigators with the application of HCD in their studies. MICHR’s service approach utilizes facilitated Design Sprints with study teams, guiding them from early conception of a research question through the co-design of interventions and innovations with end-users. Pitt CTSI’s training and consultation approach employs a two-day intensive training with group coaching sessions that provide investigators and research staff with skills and knowledge needed to implement HCD within translational research projects. Both hubs offer consultations on methodology for investigators interested in pursuing funding for studies utilizing HCD. RESULTS/ANTICIPATED RESULTS: Research teams at both hubs are pursuing HCD to co-design health research interventions and mHealth technologies with end-users locally and internationally, to facilitate meaningful engagement within advisory boards and collaboratives, and to enhance team science. To date, MICHR has conducted 13 research study-focused Design Sprints with 73 participants, as well as providing consultations to 26 research teams. Pitt CTSI has trained 164 investigators and staff and provided 146 consultations with research teams. Requests for HCD training have increased at MICHR while requests for HCD service provision have increased at Pitt CTSI. Both hubs are now building capacity to enact a more holistic approach to HCD that combines service delivery and training approaches to better meet the needs of investigators. DISCUSSION/SIGNIFICANCE: Increasing CTSA hub capacity to support the use of HCD in translational research by offering service and training opportunities can position investigators to conduct high impact health research that elevates the voices of those most likely to benefit from interventions, treatments, and innovations.

374 Operationalization of a Translational Ethics Program

OBJECTIVES/GOALS: Within our CTSA hub, greater emphasis is on understanding innovation and human health impact of translational science writ large rather than focus on translational research projects. Our program is restructured to reflect distinguishing ethical features of translational science which are complimentary to traditional research ethics issues. METHODS/STUDY POPULATION: This descriptive analysis depicts the development of our ethics program as an exemplar of how to integrate into the research enterprise of an academic health science center that engages in translational research. Our relational approach is predicated on the embodiment of ethical values by all who are involved in research committed to proactive dialog, team building, and collaboration. This translational research culture is facilitated by a multidisciplinary ethics team who are embedded throughout the translational research enterprise. RESULTS/ANTICIPATED RESULTS: Our program is integrated into a translational science enterprise within a CTSA hub in four areas: relational structure (from leadership team to community engagement), education (from trainees to the research community to the public), support (through ethics consultation with multiple touchpoints in the translational science pathway), and team science (from team on-boarding and communication to D&I research of team science interventions). We have developed a research agenda examining research ethics topics that increase quality, applicability and downstream social impact of research; understanding translational science through historical and science & technologies studies lenses, and ethnographic and mixed-method approaches to understanding team science and the science of team science. DISCUSSION/SIGNIFICANCE: The integration of a translational ethics program provides attention to traditional research ethics issues regarding study conduct and integrity but also transcends those concerns to focus on the translational science enterprise itself through relationships, cultivating trust, team science, DEIA, and social responsibility.

220 The Unheard Voices of Clinical Trials: Fostering Inclusivity for People Experiencing Homelessness in Clinical Trials

OBJECTIVES/GOALS: Investigate the perspectives of people experiencing homelessness (PEH) on clinical trials to uncover knowledge gaps and attitudes. This study aims to offer insights for clinical researchers to enhance engagement with this marginalized group, ushering in a more inclusive clinical trial process. METHODS/STUDY POPULATION: A 14-question survey was developed in collaboration with the Street Medicine Team at the University of Southern California and other stakeholders of PEH research. Initial questions assess knowledge of clinical trials, followed by questions gauging sentiments on clinical trial participation, and final questions on the significance, benefits, and risks of clinical trials. Upon approval by the local Institutional Review Board, the survey will be administered in an interview format. Study participants will be from locations within the area of operations of the USC Street Medicine team–in and around Hollywood, South Los Angeles, and/or the Los Angeles Council District 1. RESULTS/ANTICIPATED RESULTS: We anticipate that the results of this study will offer valuable insights into the perspectives of PEH regarding clinical trials. Results will also provide varying levels of knowledge and understanding among PEH about clinical trials, along with their past experiences in clinical trial participation, and willingness for future involvement in such trials. Further, the results will reveal whether respondents feel they are being properly represented in clinical research projects that could impact themselves and their community. This project can also enhance our understanding of the expectations and concerns of PEH regarding their potential participation in clinical trials. DISCUSSION/SIGNIFICANCE: The outcomes of this research project have the potential to lay the groundwork for enhancing the involvement of PEH in translational science research, encompassing aspects from study design to participation. This improvement could benefit not only participants but also various stakeholders involved.

272 Engaging Michigan’s Rural, Upper Peninsula Community in Translational Science to Advance Community Engagement Among Nonprofits

OBJECTIVES/GOALS: The Michigan Institute for Clinical & Health Research (MICHR) Community Engagement (CE) Program fosters translational science and community-engaged research (CenR) through education, connecting, supporting, and funding efforts and opportunities. METHODS/STUDY POPULATION: In Michigan’s Upper Peninsula, CE partnered with the Michigan Health Endowment Fund to develop a 3-hour workshop that consisted of a panel discussion on best practices of community engagement and a presentation on community engaged nonprofit management. The workshop was designed from mapping 60 participants’ pre-workshop survey findings and reviewing themes from a planning meeting transcript with six community partners. Key themes that emerged included participatory budgeting, collaborative governance, communications, and community planning. RESULTS/ANTICIPATED RESULTS: A mix methods post-workshop evaluation feedback survey was completed. The 9-item survey assessed workshop content, satisfaction, and knowledge gained using a Likert scale as well as opened questions about key takeaway and value added. Quantitative results to be analyzed. Qualitatively, some participants described the workshop as helpful and thoughtful about how to strengthen community engagement within their organizations. Others expressed a desire for more time. Regarding impact, CE received an uptake in consultations and inquiries into statewide pilot grants. The workshop facilitated new collaborations with philanthropic and community organizations serving the Upper Peninsula. DISCUSSION/SIGNIFICANCE: Lessons learned highlight trust, understanding community culture, and moving slowly in a newly formed collaboration. The approach utilized in the Upper Peninsula can inform translational methods for additional partnerships underway across the state of Michigan.

158 Building a National Network for Collaborative Quantitative Staff

OBJECTIVES/GOALS: Quantitative Staff are an essential workforce for biomedical research. While faculty can engage with peers locally and through national organizations, similar opportunities are limited for staff and often do not meet their unique needs and interests. Creating a professional community is valuable for supporting and developing this workforce. METHODS/STUDY POPULATION: We established the Quantitative Scientific Staff National Network (QS2N2) with the mission to provide professional development and networking opportunities, and to serve as an information resource and advocate through the fostering of community among staff quantitative analysts at any career stage. The initial membership outreach was to all Biostatistics, Epidemiology, and Research Design (BERD) programs through members of ACTS BERD Special Interest Group (SIG). We created a Leadership Team and an Advisory Board consisting of staff and faculty biostatisticians with experience working as or managing staff to govern the network. A Core Planning Committee consisting of 15 members guides planning, implementation, and execution of network activities as operationalized through subcommittees. RESULTS/ANTICIPATED RESULTS: The network currently has 131 members from over 30 health science institutions. Subcommittees focused on Education and Training, Membership, Communication and Web Development, and Mentoring were created and are developing events, programs and infrastructure to further the network’s mission. Network events such as webinars will be offered quarterly; with our first event planned for Nov 3rd. Expansion and maturation of QS2N2 will be done through regular remote meetings where members can connect with peers at other institutions, engage in career development activities, and attend technical seminars. Additional membership outreach will seek to connect with staff in government and private sectors. DISCUSSION/SIGNIFICANCE: Knowledgeable, highly skilled collaborative analysts (e.g., biostatisticians, data scientists) are an essential workforce in clinical and translational science and health research centers.The QS2N2 will support professional development, engagement and growth of this critical workforce which is necessary to advance quality research.

110 Answering the Call for Greater LGBTQ+ Research Inclusivity by Co-Developing A Workshop for Researchers

OBJECTIVES/GOALS: The objectives of this workshop were to: (1) provide learners with a space to become aware of and discuss the history of the LGBTQ+ community in medical and public health research; (2) apply frameworks for LGBTQ+ inclusivity in research, inspired by lived experience and multimedia; and (3) assess LGBTQ+ research inclusivity best practices. METHODS/STUDY POPULATION: The CTSC provided the LGBT Community Center of Greater Cleveland (Center) with access to academic resources via an affiliate account and insights on the clinical and translational science research process. Members of the CTSC Research Equity, Accessibility, Diversity, and Inclusion team met regularly with the education and programming team at the Center to review research findings for workshop segments, ideate and provide feedback on activities, and strategize to ensure a psychologically safe virtual environment for learners. Zoom registration was used for workshop registration. An evaluation survey, created by the LGBT Community Center of Greater Cleveland (Center), was deployed by the CTSC to learners after the workshop. Respondents reported that the LGBTQ+ terminology focus was most valuable. RESULTS/ANTICIPATED RESULTS: To maximize investment in and scale theLGBTQ+ Inclusivity For Researchers workshop, the LGBT Community Center of Greater Cleveland offered a shortened version to their Youth Participatory Action Research group and will continue to offer the workshop in their suite of program/educational offerings. The CTSC plans to offer opportunities to co-host the workshop at its hospital system partner institutions, with room to tailor content based on internal LGBT resources (e.g., gender care offered at the institution). We hope to see a remarkable increase in LGBTQ+ identifying researchers, LGBTQ+ participation in research studies and clinical trials, and LGBTQ+ research topics/ideas/questions in response to CTSC pilots, local, national, and global funding opportunities. DISCUSSION/SIGNIFICANCE: LGBTQ+ people are less likely to have a regular health care provider—impeding screening, diagnosis, and treatment. This is reflected in health research where clinical research participation may follow a diagnosis. By providing tools for LGBTQ+ research inclusion, we will catalyze more research with LGBTQ+ people—as researchers and participants.

515 Implementation of a Translational Science Research Center in a high education level institution in Colombia - Latin America: Unisabana Center for Translational Science (UCTS)

OBJECTIVES/GOALS: To establish and develop a high-level, dynamic, and self-sustainable Translational Science – research center in Colombia that promotes and articulates collaborative participation among different disciplines at Universidad de La Sabana to generate impactful solutions in health to transfer the knowledge to the local community. METHODS/STUDY POPULATION: With the support of core units of the University, internal funding was given for the establishment of the Research Center. An internal call was performed for recruiting researchers for multiple disciplines interested in joining the UCTS. After the researchers were selected, training of the research community in translational science and funding acquisition was performed towards the objective of interdisciplinary projects with impact in the local community. Project management strategies have been used for the follow-up of the advancements of the implementation of the UCTS. Operational structure and business plan for future self-sustainability are being designed. UCTS is proposed as an articulating party among different actors in clinics, research, and industry, for science and funding management. RESULTS/ANTICIPATED RESULTS: As an starting point, 8 research groups of different disciplines of the University have been integrated with the UCTS, increasing the research capacity in translational science. Internal administrative processes have been articulated within the institution and unified processes for international grants applications have been established in order to optimize the funding acquisition and management. Training programs for the research community, and community engagement activities have been offered as well. Networking relationships have been strengthened among the researchers enhancing international collaborations. Novel research projects are being designed towards real solutions in health for the local community, promoting the transference of knowledge from the benchside to the community. DISCUSSION/SIGNIFICANCE: The implementation of the UCTS led to the integration of disciplines within the University, towards new research projects with common interests for the local community. It has been an enriched experience using the project management approach, fulfilling a huge milestone for the University, aligned with the internal strategic priorities

Methodology for small animals targeted irradiations at conventional and ultra-high dose rates 65 MeV proton beam

As part of translational research projects, mice may be irradiated on radiobiology platforms such as the one at the ARRONAX cyclotron. Generally, these platforms do not feature an integrated imaging system. Moreover, in the context of ultra-high dose-rate radiotherapy (FLASH-RT), treatment planning should consider potential changes in the beam characteristics and internal movements in the animal.A patient-like set-up and methodology has been implemented to ensure target coverage during conformal irradiations of the brain, lungs and intestines. In addition, respiratory cycle amplitudes were quantified by fluoroscopic acquisitions on a mouse, to ensure organ coverage and to assess the impact of respiration during FLASH-RT using the 4D digital phantom MOBY. Furthermore, beam incidence direction was studied from mice µCBCT and Monte Carlo simulations. Finally,in vivodosimetry with dose-rate independent radiochromic films (OC-1) and their LET dependency were investigated.The immobilization system ensures that the animal is held in a safe and suitable position. The geometrical evaluation of organ coverage, after the addition of the margins around the organs, was satisfactory. Moreover, no measured differences were found between CONV and FLASH beams enabling a single model of the beamline for all planning studies. Finally, the LET-dependency of the OC-1 film was determined and experimentally verified with phantoms, as well as the feasibility of using these filmsin vivoto validate the targeting.The methodology developed ensures accurate and reproducible preclinical irradiations in CONV and FLASH-RT without in-room image guidance in terms of positioning, dose calculation andin vivodosimetry.

Cohort Profile Update: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12-18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.

Improving Palliative and End of Life Care on the Central Coast, Australia: Results from Two Clinically-Led Mixed-Methods Research Projects

In 2019, New South Wales Regional Health Partners commissioned the Central Coast Local Health District to undertake clinician-driven research that would lead to the implementation of new service models designed to improve palliative and end-of-life care to the Central Coast community.
 During 2020, a series of five stakeholder workshops with clinicians, healthcare managers, consumers and other local stakeholders involved in palliative and end of life care led to the development of two translational research projects: palliative and end of life care for people with advanced dementia; and the experiences of people who access emergency care towards the end of life. The subsequent clinically-led research programs were undertaken between January 2021 and September 2022. In this presentation, we discuss the results of these two mixed-methods research projects.
 To understand the patient journey, both projects undertook audits. For people who died with dementia, a retrospective case notes audit of 705 people who died between January 2015 and December 2019 found half died in public hospitals, and the other half in other settings. Less than one in five patients dying in public hospitals had an advanced care directive recorded, and fewer than one in 13 had an advanced care plan. The second audit of 1730 Central Coast residents who died between August 2020 and July 2021 found nearly half had 1 (45%) emergency department presentation in the 90 days before their death, and more than one in four had 2 presentations. There was a significant difference in the number of emergency department presentations and hospital admissions when comparing patient age and place of death.
 Across both projects, a total of 303 bereaved carers completed a postal survey. Respondents reported high levels of satisfaction with end of life care across settings. Most people receiving care were always treated with respect and dignity. Pain was managed best in hospital, compared to residential aged care and home settings. Less than half of carers said the person cared for had enough choice about where they died, but on balance, more than four in five said the person died in the right place. 
 Thematic analysis of 19 in-depth interviews with bereaved carers found three themes were common across projects: 1) There is a lack of acknowledgement of end of life, and discussions about death usually happen in the final days; 2) Services and supports are complex and fragmented, knowledge is needed to navigate them and experiences vary; and 3) End of life caring is challenging and there is limited support for carers to care.
 Drawing on previous evidence that was presented during ICIC22, we examine the lessons learned from these research projects on the importance of clinically-led research and how this is translating into the implementation of an integrated model of end of life care on the Central Coast. Key lessons for international colleagues from this research are considered.

Distinguishing between translational science and translational research in CTSA pilot studies: A collaborative project across 12 CTSA hubs.

The institutions (i.e., hubs) making up the National Institutes of Health (NIH)-funded network of Clinical and Translational Science Awards (CTSAs) share a mission to turn observations into interventions to improve public health. Recently, the focus of the CTSAs has turned increasingly from translational research (TR) to translational science (TS). The current NIH Funding Opportunity Announcement (PAR-21-293) for CTSAs stipulates that pilot studies funded through the CTSAs must be "focused on understanding a scientific or operational principle underlying a step of the translational process with the goal of developing generalizable solutions to accelerate translational research." This new directive places Pilot Program administrators in the position of arbiters with the task of distinguishing between TR and TS projects. The purpose of this study was to explore the utility of a set of TS principles set forth by NCATS for distinguishing between TR and TS. Twelve CTSA hubs collaborated to generate a list of Translational Science Principles questions. Twenty-nine Pilot Program administrators used these questions to evaluate 26 CTSA-funded pilot studies. Factor analysis yielded three factors: Generalizability/Efficiency, Disruptive Innovation, and Team Science. The Generalizability/Efficiency factor explained the largest amount of variance in the questions and was significantly able to distinguish between projects that were verified as TS or TR (t = 6.92, p < .001) by an expert panel. The seven questions in this factor may be useful for informing deliberations regarding whether a study addresses a question that aligns with NCATS' vision of TS.