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research into underlying mechanisms of disease and injury, including the sequence and timing of events after insult and injury. In addition, the development of cost-effective, rapid, and accurate diagnostic strategies to be used in the setting of potentially serious but nonspecific patient presentations (e.g., fever in infants, shock, altered mental status, abdominal pain, chest pain, respiratory distress) will improve health care in two distinct ways: • Patients with serious illness will be more quickly and unambiguously identified, leading to more rapid initiation of effective treatment. • Patients without serious illness will be more rapidly identified, minimize the need for additional testing, reduce unnecessary and potentially harmful empiric treatment, reduce lengths of stay in the ED, and decrease unnecessary hospitalization. These latter effects will reduce ED and hospital crowding, that currently impact the quality of and access to emergency care. Beyond patient characterization, there is an imperative to develop effective initial therapeutic strategies for broad classes of patients with emergency conditions (e.g., those with shock, altered mental status, and respiratory distress). Furthermore, the process of therapeutic decision making in the emergency setting of diagnostic uncertainty needs to be studied. Equally important is the development of early therapeutic strategies for patients with specific time-sensitive illnesses and injuries (e.g., closed head injury; myocardial, cerebral, or mesenteric ischemia; hemorrhagic shock; cardiopulmonary arrest). The development of novel diagnostic and therapeutic strategies will require new and substantive research into underlying mechanisms of disease and injury. In order to optimize value in the development of emergency therapeutic strategies, mechanistic investigations must pay particular attention to the sequence and timing of pathophysiological events. Furthermore, the effective translation of therapies developed in preclinical models of timesensitive disease states to the clinical research setting will require the enrollment of research subjects early in their clinical course when such therapies are most likely to be effective. RESEARCH AGENDAS FOR EMERGENCY CARE Emergency care research has been the subject of two important research agenda setting efforts. The Macy Foundation reports suggested these specific recommendations for the further evolution of emergency medicine research (1): • Enhance support for basic, clinical, and health services research pertinent to emergency medicine practice. • Promote collaborative and interdisciplinary research within and across traditional institutional boundaries. • Develop new systems to manage clinical information. • Develop new methods to assess the outcomes of emergency care. • Seek and develop increased funding sources for emergency medicine research. CHAPTER 1 — WHAT IS ACUTE AND EMERGENCY CARE RESEARCH? 5 More recently, the Institute of Medicine Committee on the Future of Emergency Care in the United States Health System convened and identified a crisis in emergency care in the United States, including a need to enhance the research base for emergency care (7). As a result, the National Institutes of Health (NIH) formed an NIH Task Force on Research in Emergency Medicine to enhance NIH support for emergency care research. Members of the NIH Task Force and academic leaders in emergency care participated in three Roundtable discussions to prioritize current opportunities for enhancing and conducting emergency care research (2, 8, 9). The Roundtables were focused on: (a) neurological and psychiatric emergencies; (b) medical and surgical emergencies; and (c) emergency trauma. The objectives of these NIH Roundtables were to identify key research questions essential to advancing the scientific underpinnings of emergency care and to discuss the barriers and best means to advance research by exploring the role of research networks and collaboration between NIH and the emergency care community. The key themes of each of the three Roundtable reports are highlighted in Table 1-2. Overarching themes of the NIH Roundtable reports included (2, 8, 9): • Emergency care research is characterized by focus on the timing, sequence, and time sensitivity of disease processes and treatment effects. • Rapidly identifying the phenotype of patients manifesting a specific disease process, and the mechanistic reasons for heterogeneity in outcome are important challenges in emergency care research. • Need to elucidate the timing, sequence, and duration of causal molecular and cellular events involved in time-critical illnesses and injuries, and the development of treatments capable of halting or reversing them. • Need for novel experimental models of emergency conditions. • Understand regional differences in outcome for the same emergency disease processes. In addition, a number of important barriers to emergency care research were identified in the NIH Roundtable reports (2, 8, 9), including: • Limited number of trained investigators and experienced mentors in emergency care research. • Limited emergency care research infrastructure and support, and regulatory hurdles. The NIH Roundtables recommended that the science of emergency care may be advanced by facilitating the following: (a) 

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