Translational Framework Research Articles

Social Genomic Determinants of Health: Understanding the Molecular Pathways by Which Neighborhood Disadvantage Affects Cancer Outcomes.

Neighborhoods represent complex environments with unique social, cultural, physical, and economic attributes that have major impacts on disparities in health, disease, and survival. Neighborhood disadvantage is associated with shorter breast cancer recurrence-free survival (RFS) independent of individual-level (race, ethnicity, socioeconomic status, insurance, tumor characteristics) and health system-level determinants of health (receipt of guideline-concordant treatment). This persistent disparity in RFS suggests unaccounted mechanisms such as more aggressive tumor biology among women living in disadvantaged neighborhoods compared with advantaged neighborhoods. The objective of this article was to provide a clear framework and biological mechanistic explanation for how neighborhood disadvantage affects cancer survival. Development of a translational epidemiological framework that takes a translational disparities approach to study cancer outcome disparities through the lens of social genomics and social epigenomics. The social genomic determinants of health, defined as the physiological gene regulatory pathways (ie, neural/endocrine control of gene expression and epigenetic processes) through which contextual factors, particularly one's neighborhood, can affect activity of the cancer genome and the surrounding tumor microenvironment to alter disease progression and treatment outcomes. We propose a novel, multilevel determinants of health model that takes a translational epidemiological approach to evaluate the interplay between political, health system, social, psychosocial, individual, and social genomic determinants of health to understand social disparities in oncologic outcomes. In doing so, we provide a concrete biological pathway through which the effects of social processes and social epidemiology come to affect the basic biology of cancer and ultimately clinical outcomes and survival.

Nursing Education for Sustainable Development: A Concept Analysis.

Sustainability represents an increasingly vital yet inconsistently implemented topic in nursing education. Formal concept analysis can promote unified conceptualisation to inform sustainability integration in nursing curriculums. Analyse the concept of 'nursing education for sustainable development' using the Walker and Avant framework to clarify meaning and application in nursing programmes. The literature was systematically searched for attributes, antecedents and consequences used to formulate a concept definition, and compared to existing conceptualisations. Core concept attributes are interconnectedness of human/ecological health, sustainability-focused curriculums, competency cultivation and social justice orientations. Antecedents include recognising ecological determinants of health and committed nursing faculty. Consequences encompass the preparation of sustainability-competent nurses and elevated nursing contributions to sustainable health systems. The concept analysis provides an original synthesised perspective advancing coherence and applicability to guide sustainability education in nursing programmes through a translational framework for competency, curriculum design and content delivery approaches. We followed the guidelines outlined in the Walker and Avant framework in the conduct and reporting of this paper. No patient and public contribution.

The μ-opioid receptor differentiates two distinct human nociceptive populations relevant to clinical pain

The shortfall in new analgesic agents is a major impediment to reducing reliance on opioid medications for control of severe pain. In both animals and man, attenuating nociceptive transmission from primary afferent neurons with a μ-opioid receptor agonist yields highly effective analgesia. Consequently, deeper molecular characterization of human nociceptive afferents expressing OPRM1, the μ-opioid receptor gene, is a key component for advancing analgesic drug discovery and understanding clinical pain control. A co-expression matrix for the μ-opioid receptor and a variety of nociceptive channels as well as δ- and κ-opioid receptors is established by multiplex in situ hybridization. Our results indicate an OPRM1-positive population with strong molecular resemblance to rodent peptidergic C-nociceptors associated with tissue damage pain and an OPRM1-negative population sharing molecular characteristics of murine non-peptidergic C-nociceptors. The empirical identification of two distinct human nociceptive populations that differ profoundly in their presumed responsiveness to opioids provides an actionable translational framework for human pain control.

Dose optimization of TBI-223 for enhanced therapeutic benefit compared to linezolid in antituberculosis regimen

TBI-223, a novel oxazolidinone for tuberculosis, is designed to provide improved efficacy and safety compared to linezolid in combination with bedaquiline and pretomanid (BPaL). We aim to optimize the dosing of TBI-223 within the BPaL regimen for enhanced therapeutic outcomes. TBI-223 is investigated in preclinical monotherapy, multidrug therapy, and lesion penetration experiments to describe its efficacy and safety versus linezolid. A translational platform incorporating linezolid and BPaL data from preclinical experiments and 4 clinical trials (NCT00396084, NCT02333799, NCT03086486, NCT00816426) is developed, enabling validation of the framework. TBI-223 preclinical and Phase 1 data (NCT03758612) are applied to the translational framework to predict clinical outcomes and optimize TBI-223 dosing in combination with bedaquiline and pretomanid. Results indicate that daily doses of 1200–2400 mg TBI-223 may achieve efficacy comparable to the BPaL regimen, with >90% of patients predicted to reach culture conversion by two months.

PFHpA alters lipid metabolism and increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in youth—a translational research framework

PFHpA alters lipid metabolism and increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in youth—a translational research framework

High-Risk Neuroblastoma Challenges and Opportunities for Antibody-Based Cellular Immunotherapy.

Immunotherapy has emerged as an attractive option for patients with relapsed or refractory high-risk neuroblastoma (HRNB). Neuroblastoma (NB), a sympathetic nervous system cancer arising from an embryonic neural crest cell, is heterogeneous clinically, with outcomes ranging from an isolated abdominal mass that spontaneously regresses to a widely metastatic disease with cure rates of about 50% despite intensive multimodal treatment. Risk group stratification and stage-adapted therapy to achieve cure with minimal toxicities have accomplished major milestones. Targeted immunotherapeutic approaches including monoclonal antibodies, vaccines, adoptive cellular therapies, their combinations, and their integration into standard of care are attractive therapeutic options, although curative challenges and toxicity concerns remain. In this review, we provide an overview of immune approaches to NB and the tumor microenvironment (TME) within the clinical translational framework. We propose a novel T cell-based therapeutic approach that leverages the unique properties of tumor surface antigens such as ganglioside GD2, incorporating specific monoclonal antibodies and recent advancements in adoptive cell therapy.

Predicting Tumor Volume Doubling Time and Progression-Free Survival in Untreated Patients from Patient-Derived-Xenograft (PDX) Models: A Translational Model-Based Approach

Tumor volume doubling time (TVDT) has been shown to be a potential surrogate marker of biological tumor activity. However, its availability in clinics is strongly limited due to ethical and practical reasons, as its assessment requires at least two subsequent tumor volume measurements in untreated patients. Here, a translational modeling framework to predict TVDT distributions in untreated cancer patient populations from tumor growth data in patient-derived xenograft (PDX) mice is proposed. Eleven solid cancer types were considered. For each of them, a set of tumor growth studies in PDX mice was selected and analyzed through a mathematical model to characterize the distribution of the exponential tumor growth rate in mice. Then, assuming an exponential growth of the tumor mass in humans, the growth rates were scaled from PDX mice to humans through an allometric scaling approach and used to predict TVDTs in untreated patients. A very good agreement was found between model predicted and clinically observed TVDTs, with 91% of the predicted TVDT medians fell within 1.5-fold of observations. Further, exploiting the intrinsic relationship between tumor growth dynamics and progression free survival (PFS), the exponential growth rates in humans were used to generate the expected PFS curves in absence of anticancer treatment. Predicted curves were extremely close to published PFS data from studies involving patient cohorts treated with supportive care or low effective therapies. The proposed approach shows promise as a potential tool to increase knowledge about TVDT in humans without the need of directly measuring tumor dimensions in untreated patients, and to predict PFS curves in untreated patients, that could fill the absence of placebo-controlled arms against which to compare treaded arms during clinical trials. However, further validation and refinement are needed to fully assess its effectiveness in this regard.

A translational framework of genoproteomic studies for cardiovascular drug discovery

Cardiovascular drug development has faced significant challenges in recent decades. The emergence of population-scale genome- and proteome-wide data, alongside sophisticated genetic analytical tools like Mendelian randomization and pragmatic target trials, presents an unprecedented chance to identify and validate drug-targeting proteins for cardiovascular disease. However, how to translate these advances into clinical applications remains to be discovered. This study proposes and validates a translational framework that leverages emerging genoproteomic data and cutting-edge causal analysis techniques to address the intricate benefit-risk concerns associated with cardiovascular drug development. Specifically, the framework elucidates underlying biological mechanisms, identifies and validates potential drug-targeting proteins, and explores the unintended side effects, complementary with pragmatic target trials. Moreover, we illustrate the translational framework via a step-by-step example alongside practical implementation recommendations for cardiovascular drug discovery. We envision this translational framework as a starting point in advancing multi-omics studies, thereby accelerating cardiovascular drug development.

PFHpA alters lipid metabolism and increases the risk of metabolic dysfunction-associated steatotic liver disease in youth-a translational research framework.

To address the growing epidemic of liver disease, particularly in pediatric populations, it is crucial to identify modifiable risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals and have emerged as potential risk factors for liver damage. However, their impact on the etiology and severity of MASLD remains largely unexplored in humans. This study aims to bridge the gap between human and in vitro studies to understand how exposure to perfluoroheptanoic acid (PFHpA), one of the emerging PFAS replacements which accumulates in high concentrations in the liver, contributes to MASLD risk and progression. First, we showed that PFHpA plasma concentrations were significantly associated with increased risk of MASLD in obese adolescents. Further, we examined the impact of PFHpA on hepatic metabolism using 3D human liver spheroids and single-cell transcriptomics to identify major hepatic pathways affected by PFHpA. Next, we integrated the in vivo and in vitro multi-omics datasets with a novel statistical approach which identified signatures of proteins and metabolites associated with MASLD development triggered by PFHpA exposure. In addition to characterizing the contribution of PFHpA to MASLD progression, our study provides a novel strategy to identify individuals at high risk of PFHpA-induced MASLD and develop early intervention strategies. Notably, our analysis revealed that the proteomic signature exhibited a stronger correlation between both PFHpA exposure and MASLD risk compared to the metabolomic signature. While establishing a clear connection between PFHpA exposure and MASLD progression in humans, our study delved into the molecular mechanisms through which PFHpA disrupts liver metabolism. Our in vitro findings revealed that PFHpA primarily impacts lipid metabolism, leading to a notable increase of lipid accumulation in human hepatocytes after PFHpA exposure. Among the pathways involved in lipid metabolism in hepatocytes, regulation of lipid metabolism by PPAR-a showed a remarkable activation. Moreover, the translational research framework we developed by integrating human and in vitro data provided us biomarkers to identify individuals at a high risk of MASLD due to PFHpA exposure. Our framework can inform policies on PFAS-induced liver disease and identify potential targets for prevention and treatment strategies.

Tatia Lee: Neuropsychology and human neuroscience research insights inform the theoretical and translational framework for fostering brain and psychological health

Tatia Lee, PhD, is Chair Professor of Psychological Science and Clinical Psychology at The University of Hong Kong, a clinical psychologist, and a board-certified clinical neuropsychologist. Her research focuses on the neuroplastic basis of neurocognitive and affective processes underpinning normal and pathological neurocognitive and psychological functions. She is an elected Fellow of esteemed international societies, including the World Academy of Sciences, Academy of Social Sciences (UK), American College of Professional Neuropsychology, Association for Psychological Science, and American Psychological Association. She is the Founding Chair of the Clinical Neuropsychological Society under the Chinese Cognitive Science Society of China. She has received numerous awards and recognition, including The University of Alberta Alumni Horizon Award, the Fulbright Hong Kong Scholar, the State Scientific and Technological Progress Award, and the Humanities and Social Sciences Panel Prestigious Fellowship Award. Acknowledging her substantial contributions and academic achievements in advancing neuropsychological sciences, The University of Hong Kong bestowed her the “May Endowed Professorship in Neuropsychology.” Professor Lee is happy to provide our readers with reflections on her life and career.

Pharmacological Analysis of NLRP3 Inflammasome Inhibitor Sodium [(1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl][(1-methyl-1H-pyrazol-4-yl)({[(2S)-oxolan-2-yl]methyl})sulfamoyl]azanide in Cellular and Mouse Models of Inflammation Provides a Translational Framework.

Interleukin (IL)-1β is an apex proinflammatory cytokine produced in response to tissue injury and infection. The output of IL-1β from monocytes and macrophages is regulated not only by transcription and translation but also post-translationally. Release of the active cytokine requires activation of inflammasomes, which couple IL-1β post-translational proteolysis with pyroptosis. Among inflammasome platforms, NOD-like receptor pyrin domain-containing protein 3 (NLRP3) is implicated in the pathogenesis of numerous human disorders in which disease-specific danger-associated molecular patterns (DAMPS) are positioned to drive its activation. As a promising therapeutic target, numerous candidate NLRP3-targeting therapeutics have been described and demonstrated to provide benefits in the context of animal disease models. While showing benefits, published preclinical studies have not explored dose-response relationships within the context of the models. Here, the preclinical pharmacology of a new chemical entity, [(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl][(1-methyl-1H-pyrazol-4-yl)({[(2S)-oxolan-2-yl]methyl})sulfamoyl]azanide (NT-0249), is detailed, establishing its potency and selectivity as an NLRP3 inhibitor. NT-0249 also is evaluated in two acute in vivo mouse challenge models where pharmacodynamic/pharmacokinetic relationships align well with in vitro blood potency assessments. The therapeutic utility of NT-0249 is established in a mouse model of cryopyrin-associated periodic syndrome (CAPS). In this model, mice express a human gain-of-function NLRP3 allele and develop chronic and progressive IL-1β-dependent autoinflammatory disease. NT-0249 dose-dependently reduced multiple inflammatory biomarkers in this model. Significantly, NT-0249 decreased mature IL-1β levels in tissue homogenates, confirming in vivo target engagement. Our findings highlight not only the pharmacological attributes of NT-0249 but also provide insight into the extent of target suppression that will be required to achieve clinical benefit.

494 Expert group decision making for pharmacogenomic testing in Ontario

OBJECTIVES/GOALS: There is a need to better understand how governments develop strategies to adopt, evaluate, and implement novel health technologies in a public healthcare system. The goal of this project is to understand this strategy development process for the translation of pharmacogenomic (PGx) testing in Ontario, Canada. METHODS/STUDY POPULATION: This observational case study of the Ontario Health PGx Working Group focused on developing recommendations for a PGx testing implementation strategy in the province. The group included 9 individuals affiliated with Ontario Health and 13 healthcare experts from multiple clinical fields. Ontario Health is the government agency that oversees provincial healthcare planning and service delivery. Guided by the Translational Thinking Framework and qualitative research methods, we observed the working group’s activities for eight months. We collected meeting recordings, slideshow decks, emails, and group characteristics. We used descriptive statistics and a nine-step inductive approach to analyze the data to create process maps, a case report, and key decision summaries. RESULTS/ANTICIPATED RESULTS: There were 19 meetings conducted remotely with videoconferencing technology. Throughout the working group’s activities, we identified 15 key decisions related to either administrative processes or PGx scientific content. We further stratified these two categories into four main themes relating to decisions about 1) membership involvement, 2) logistical management, 3) discussion and recommendation scope, and 4) information dissemination. These four decision themes represent tools by which Ontario Health guided the expert group activities and achieved their goal of generating a strategic roadmap for PGx testing implementation in Ontario. DISCUSSION/SIGNIFICANCE: The Ontario government makes decisions about how expert groups function by monitoring and controlling the group’s activities to ensure efficiency, standardization, and practicality. Describing expert group decision-making increases transparency and highlights the critical role they play in the translational pathway of health technologies.

293 The MEND Initiative: Meaningfully Empowering the NeuroDiverse

OBJECTIVES/GOALS: This project’s objective is to empower verbally-communicating autistic adults to express their mental health needs to mental health professionals, regardless of their training or experience in autism. By enhancing empowerment in this area, we aim to enhance their self-awareness and confidence in navigating and accessing mental health support. METHODS/STUDY POPULATION: Following the Toronto Translational Framework (TTF), our approach involves co-designing and testing an intervention directly with the autistic population through three phases. Phase I will review published literature on autism, mental health, and patient empowerment, validate our identified need through informal meetings with stakeholders, and assemble an autistic advisory committee (AAC) of 5-8 members who are able to provide informed conset without assistant, are fluent in English, and 18 years of age or older. Phase II will involve participatory design sessions with our AAC to develop a low-fidelity prototype to address the identified need. Phase III will evaluate our prototype’s effectiveness through a separate series of focus groups, which will consist of members from our target population. RESULTS/ANTICIPATED RESULTS: We are anticipating that by the end of our research, we have successfully co-designed an intervention that effectievly empowers autistic adults in their mental health journey through increasing their self-awareness and confidence in navigating and receiving mental health support. At a larger scale, results may include the empowerment of autistic adults to seek and receive mental health care from mental health professionals, regardless of professionals’ prior autism expertise. DISCUSSION/SIGNIFICANCE: By enhancing self-awareness of their mental healthcare needs and boosting self-reported confidence in communicating with mental health professionals, we aim to take the first step in creating timely, patient-centered solutions, and bridging gaps in the evolving neuro-affirmative healthcare system.

Abstract 7440: Symptom network analysis and unsupervised clustering of a cohort of oncology patients identifies drivers of symptom burden and patient subgroups with distinct symptom patterns

Abstract Purpose: Inter-individual variability in oncology patients’ symptom experiences poses significant challenges in prioritizing symptoms for targeted intervention(s). In this study, computational approaches were used to unbiasedly characterize the heterogeneity of the symptom experience of oncology patients to elucidate their symptom patterns and drivers of symptom burden. Methods: Severity ratings for 32 symptoms on the Memorial Symptom Assessment Scale from 3088 oncology patients were analyzed. Gaussian Graphical Model symptom networks were constructed for the entire cohort and subgroups identified through unsupervised clustering of symptom co-severity patterns. Symptom network characteristics were analyzed and compared using permutation-based statistical tests. Demographic and clinical characteristic differences between subgroups were assessed using multinomial logistic regression. Results: Network analysis of the entire cohort revealed three core symptom clusters: constitutional, gastrointestinal-epithelial, and psychological. Lack of energy was identified as central to the network, suggesting that it plays a crucial role in driving overall symptom burden and may be the most salient to target clinically. Unsupervised clustering of patients based on shared symptom co-severity patterns identified six patient subgroups with distinct symptom patterns and demographic and clinical characteristics. The first subgroup represented a baseline cohort of patients who are most affected by common constitutional symptoms of cancer care. The second subgroup represented patients with severe overall symptom burden. The third subgroup represented patients primarily experiencing neuropathy. The fourth subgroup represented patients with advanced disease and treatment-related symptoms but relatively high quality of life. The fifth subgroup represented younger patients with pronounced psychological disease burden. The sixth subgroup represented patients with minimal symptom burden. Age, treatment status, and Karnofsky Performance Score were the strongest determinants of subgroup membership, but their interplay (in one case even with ethnicity) reaffirms the complex multi-factorial nature of the symptom experience. For each subgroup, symptoms with the highest network centralities that should be prioritized for management were identified. Conclusions: This study provides a translational research framework for clinicians to better understand and address the symptom care needs of oncology patients. The framework combines unbiased stratification of patients and in-depth modeling of symptom relationships to capture the heterogeneity in their experiences. When validated, the identified core symptoms and associated clinical determinants may inform precision-based symptom management. Citation Format: Brandon H. Bergsneider, Terri S. Armstrong, Yvette P. Conley, Bruce Cooper, Marilyn Hammer, Jon D. Levine, Steven Paul, Christine Miaskowski, Orieta Celiku. Symptom network analysis and unsupervised clustering of a cohort of oncology patients identifies drivers of symptom burden and patient subgroups with distinct symptom patterns [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7440.

Cardiac arrhythmogenesis: roles of ion channels and their functional modification.

Cardiac arrhythmias cause significant morbidity and mortality and pose a major public health problem. They arise from disruptions in the normally orderly propagation of cardiac electrophysiological activation and recovery through successive cardiomyocytes in the heart. They reflect abnormalities in automaticity, initiation, conduction, or recovery in cardiomyocyte excitation. The latter properties are dependent on surface membrane electrophysiological mechanisms underlying the cardiac action potential. Their disruption results from spatial or temporal instabilities and heterogeneities in the generation and propagation of cellular excitation. These arise from abnormal function in their underlying surface membrane, ion channels, and transporters, as well as the interactions between them. The latter, in turn, form common regulatory targets for the hierarchical network of diverse signaling mechanisms reviewed here. In addition to direct molecular-level pharmacological or physiological actions on these surface membrane biomolecules, accessory, adhesion, signal transduction, and cytoskeletal anchoring proteins modify both their properties and localization. At the cellular level of excitation-contraction coupling processes, Ca2+ homeostatic and phosphorylation processes affect channel activity and membrane excitability directly or through intermediate signaling. Systems-level autonomic cellular signaling exerts both acute channel and longer-term actions on channel expression. Further upstream intermediaries from metabolic changes modulate the channels both themselves and through modifying Ca2+ homeostasis. Finally, longer-term organ-level inflammatory and structural changes, such as fibrotic and hypertrophic remodeling, similarly can influence all these physiological processes with potential pro-arrhythmic consequences. These normal physiological processes may target either individual or groups of ionic channel species and alter with particular pathological conditions. They are also potentially alterable by direct pharmacological action, or effects on longer-term targets modifying protein or cofactor structure, expression, or localization. Their participating specific biomolecules, often clarified in experimental genetically modified models, thus constitute potential therapeutic targets. The insights clarified by the physiological and pharmacological framework outlined here provide a basis for a recent modernized drug classification. Together, they offer a translational framework for current drug understanding. This would facilitate future mechanistically directed therapeutic advances, for which a number of examples are considered here. The latter are potentially useful for treating cardiac, in particular arrhythmic, disease.

The explore/exploit trade-off: An ecologically valid and translational framework that can advance mechanistic understanding of eating disorders.

The explore/exploit trade-off is a decision-making process that is conserved across species and balances exploring unfamiliar choices of unknown value with choosing familiar options of known value to maximize reward. This framework is rooted in behavioral ecology and has traditionally been used to study maladaptive versus adaptive non-human animal foraging behavior. Researchers have begun to recognize the potential utility of understanding human decision-making and psychopathology through the explore/exploit trade-off. In this article, we propose that explore/exploit trade-off holds promise for advancing our mechanistic understanding of decision-making processes that confer vulnerability for and maintain eating pathology due to its neurodevelopmental bases, conservation across species, and ability to be mathematically modeled. We present a model for how suboptimal explore/exploit decision-making can promote disordered eating and present recommendations for future research applying this framework to eating pathology. Taken together, the explore/exploit trade-off provides a translational framework for expanding etiologic and maintenance models of eating pathology, given developmental changes in explore/exploit decision-making that coincide in time with the emergence of eating pathology and evidence of biased explore/exploit decision-making in psychopathology. Additionally, understanding explore/exploit decision-making in eating disorders may improve knowledge of their underlying pathophysiology, informing targeted clinical interventions such as neuromodulation and pharmacotherapy. PUBLIC SIGNIFICANCE STATEMENT: The explore/exploit trade-off is a cross-species decision-making process whereby organisms choose between a known option with a known reward or sampling unfamiliar options. We hypothesize that imbalanced explore/exploit decision-making can promote disordered eating and present preliminary data. We propose that explore/exploit trade-off has significant potential to advance understanding of the neurocognitive and neurodevelopmental mechanisms of eating pathology, which could ultimately guide revisions of etiologic models and inform novel interventions.

A transdiagnostic and translational framework for delineating the neuronal mechanisms of compulsive exercise in anorexia nervosa.

The development of novel treatments for anorexia nervosa (AN) requires a detailed understanding of the biological underpinnings of specific, commonly occurring symptoms, including compulsive exercise. There is considerable bio-behavioral overlap between AN and obsessive-compulsive disorder (OCD), therefore it is plausible that similar mechanisms underlie compulsive behavior in both populations. While the association between these conditions is widely acknowledged, defining the shared mechanisms for compulsive behavior in AN and OCD requires a novel approach. We present an argument that a better understanding of the neurobiological mechanisms that underpin compulsive exercise in AN can be achieved in two critical ways. First, by applying a framework of the neuronal control of OCD to exercise behavior in AN, and second, by taking better advantage of the activity-based anorexia (ABA) rodent model to directly test this framework in the context of feeding pathology. A cross-disciplinary approach that spans preclinical, neuroimaging, and clinical research as well as compulsive neurocircuitry and behavior can advance our understanding of when, why, and howcompulsive exercise develops in the context of AN and provide targets for novel treatment strategies. In this article, we (i) link the expression of compulsive behavior in AN and OCD via a transition between goal-directed and habitual behavior, (ii) present disrupted cortico-striatal circuitry as a key substrate for the development of compulsive behavior in both conditions, and (iii) highlight the utility of the ABA rodent model to better understand the mechanisms of compulsive behavior relevant to AN. Individuals with AN who exercise compulsively are at risk of worse health outcomes and have poorer responses to standard treatments. However, when, why, and how compulsive exercise develops in AN remains inadequately understood. Identifying whether the neural circuitry underlying compulsive behavior in OCD also controls hyperactivity in the activity-based anorexia model will aid in the development of novel eating disorder treatment strategies for this high-risk population.

THE PAID AND FAMILY DEMENTIA WORKFORCE IN THE COVID-19 PANDEMIC ERA

Abstract The COVID-19 pandemic has had a disproportionate impact on persons living with dementia and their carers. The early period of the pandemic led to drastic changes in dementia care at home, in healthcare services, community programs, and institutional care settings, with lasting effects (Capstick et al., 2022; Giebel et al., 2022). This symposium describes the impact of the COVID-19 pandemic on a variety of individuals providing care for persons living with dementia through different stages of the pandemic. Our work will be presented within a translational framework and include a discussion of ways of leveraging findings to improve resources for individuals and caregivers living with dementia in the COVID-19 era. Karen Donelan will provide an overview of the dementia workforce and describe study procedures. Michael Vetter will describe findings from a survey study of self-efficacy of dementia caregiving for family caregivers of individuals in community and assisted living facilities (ALF). Inga Antonsdottir will describe survey data on family caregivers in community and ALF – focus on newer experiential members; how lives changed, how COVID impacted them. Esteban Barreto will present findings describing the impact of the COVID-19 pandemic on frontline staff. Finally, Sarah Bannon will present findings from a qualitative study identifying family caregivers’ impressions of their psychosocial stressors and enacted coping strategies in the post-vaccine era of the COVID-19 pandemic.

PRESIDENTIAL SYMPOSIUM: HIGHLIGHTING EMERGING PROFESSIONALS WHO BUILD BRIDGES, CATALYZE RESEARCH, AND EMPOWER ALL AGES

Abstract There are many ways to carve a path forward in aging research, policy, and practice. Sometimes the career possibilities are overwhelming, leaving us unsure of how best to proceed. As aging professionals, we know that there is much to learn from those who have gone before us. Therefore, in the ESPO Presidential Symposium we highlight four emerging professionals who are trailblazing diverse and fulfilling career paths in aging by building bridges, catalyzing research, and empowering all ages. Speakers include Drs. Cal Halvorsen, Lindsay Kobayashi, Jamie Justice, and Glenna Brewster Glasgow. Dr. Jacqui Smith will serve as the discussant, synthesizing main findings, emphasizing positive outcomes, and exploring challenges. Starting with identifying the “So What?” of his career, Dr. Cal Halvorsen will explore how his practice roots in policy and advocacy led to his current approach of merging scholarly pursuits and public communication to make an impact beyond the walls of academia. Next, moving to cross-national aging research, Dr. Lindsay Kobayashi will discuss the opportunities and challenges of combining diverse cross-national cohorts to identify policy-relevant and context-specific modifiers of health risks for older adults. Next, Dr. Jamie Justice will focus on her career in translational geroscience and share a translational framework for aging outcomes trials. Finally, from an interdisciplinary approach to conducting research with families living with cognitive impairment in the US and the Caribbean, Dr. Glenna Brewster Glasgow will reflect on practical strategies to develop and maintain collaborative relationships with researchers and stakeholders locally, nationally, and internationally.

Exploring the Social Connection of Young Caregivers of People Living with Dementia in Ontario

AbstractBackgroundCaregiving at a young age can have negative effects on relationships, mental health, and emotional regulation. Notably, dementia caregivers are at higher risk of experiencing social isolation due to their caregiving responsibilities (1‐3). However, there is a lack of knowledge of the experiences of young caregivers of people living with dementia (YCPLWD). Our project is the first to recognize YCPLWD as a unique population and seeks to improve their social connection, which is how individuals connect with each other, and it is comprised of multiple aspects (4) (Figure 1). Our project goals are to:1. Describe the experiences of social connection among YCPLWD.2. Identify barriers and facilitators to social connection.MethodOur project applies the Toronto Translational Framework (5) (Figure 2), a patient‐centric approach to identify person‐centered needs in healthcare and co‐create innovative solutions. Qualitative data will be collected through 2‐4 focus groups, each with 6‐8 YCPLWD. Participant criteria include English‐speaking post‐secondary students (aged 18‐24 years) who have provided care to a person(s) living with dementia in the past 12 months and are currently living in the Greater Toronto and Hamilton area. Participants will be recruited using both convenience and snowball sampling. Focus groups will be audio‐recorded, transcribed verbatim, then analyzed using Braun & Clarke’s thematic analysis (6) to identify significant themes.ResultFocus group discussions will focus on (1) experiences with and the impact of social connection, and (2) facilitators and barriers to social connection. These sessions will enable YCPLWD to co‐create knowledge with their peers and share unique insights about the social experience of caregiving. Moreover, focus group findings will be mapped onto Liougas et al.’s framework (4) to verify how YCPLWD experience and articulate different aspects of social connection, including resources, activities, and subjective feelings.ConclusionThis project will recognize YCPLWD as a vulnerable population with unique and specific needs. Given the heterogeneity of dementia caregiving experiences, YCPLWD may face various challenges that can be further understood. Moreover, by exploring barriers and facilitators to social connection, this project will inform the development of novel resources to educate and support YCPLWD.