• What are the biological and behavioral dynamics of symptoms (e.g., dyspnea, fatigue, impaired sleep/insomnia, pain, depression) that can change the trajectory of chronic illnesses, and how can the dynamics be optimized and maintained to prevent symptom relapse?
  

• What innovative care delivery models (e.g. interdisciplinary, family-based), research methods (e.g. community engaged research, pragmatic trials) and technologies (e.g. eHealth) can be leveraged to improve symptom management and change the chronic illness trajectory especially among individuals who experience disparate health outcomes?

• How do lifestyle factors, environmental conditions, symptom clusters and symptom treatments impact quality of life and symptom management in different chronic conditions?

• How do symptom precursors (e.g. biomarkers or conditions such as obesity) contribute to the physiology of symptom risk, severity, duration and response to treatment?

• What are the 'omic', phenotypic and state dependent indicators related to the mechanism, assessment and management of high impact symptoms (e.g. pain, fatigue, dyspnea) and what is the added value of these indicators beyond clinical parameters in explaining physical and psychological symptoms in both patients and their informal caregivers?

• What are the common mechanistic pathways (e.g. stimulus to perception, perception to report) that can distinguish underlying symptom cluster trajectories that are amenable to intervention at various points along those pathways?

• What are the personalized markers (e.g. biomarkers and clinical factors) that can be used to stratify subgroups of patients with different patterns among symptoms to determine the symptom management strategies most effective in improving quality of life?

• What innovative methodologies (e.g. modeling) can be used to analyze symptom management algorithms?

• How can we create a standardized, feasible, valid, and relevant data and technology infrastructure to routinely collect and aggregate symptom data from patient health records but also from other types of assessments (biological, physiological, performance) to inform clinical care and research?

• What are the biological indicators that can help determine the presence and severity of subjective symptoms in individuals who cannot self-report (e.g. small children; individuals with cognitive decline) to help improve clinical assessment and management? Is there a role for fMRI?

• What state-of-the-art research designs/methods (e.g. mixed methods, SMART, MOST) should investigators use to test personalized symptom management strategies to include scalable interventions?

• What are the biologic, physiologic and/or omic mechanisms underlying symptoms and patient outcomes?
  
• For high risk patients who are at the end of life, how can genetic assessment and DNA banking be used to address familial risk?
• How should omic discoveries be used to create and test technologies (such as clinical tools) that can be used to diagnose clinical problems, predict the clinical course and promote optimal outcomes?
• In what ways can genomic information be used to promote adherence and improve self-management of chronic conditions?
• How does the social environment interact with gene expression to influence resilience in coping with life challenges?

All other aspects of this FOA remain unchanged.