C. Donald Combs, PhD, is Vice President and Dean of the School of Health Professions at Eastern Virginia Medical School and is also a senior faculty member in the Department of Modeling, Simulation, and Visualization Engineering at Old Dominion University.  John A. Sokolowski, PhD, is Associate Professor and Executive Director of the Virginia Modeling, Analysis, and Simulation Center at Old Dominion University.  Catherine M. Banks, PhD, is Research Associate Professor at the Virginia Modeling, Analysis, and Simulation Center at Old Dominion University.

• List of Contributors xiii Preface xviiPart 1 The Vision: The Digital Patient—Improving Research, Development, Education, and Healthcare Practice 11 The Digital Patient 3C. Donald CombsHealth, The Goal, 4Personalized Medicine, 4The Best Outcomes, 5The Emergence of the Digital Patient, 5The Human Physiome, 6Enabling the Digital Patient, 8P4 Medicine, 11Conclusion, 11References, 122 Reflecting on Discipulus and Remaining Challenges 15Vanessa Díaz]Zuccarini, Mona Alimohammadi, and César Pichardo]AlmarzaIntroduction, 15A Brief Contextual Background and a Call for Integration: Personalized Medicine is Holistic, 16The Many Versions of the Digital Patient: On the Road to Medical Avatars, 18Discipulus: The Digital Patient Technological Challenges and Main Conclusions, 19The Remaining Challenges and Big Data, 24Conclusion, 25References, 263 Advancing the Digital Patient 27Catherine M. BanksIntroduction, 27The Digital Patient: Its Early Start, 28Engaging the Digital Patient, 30Conclusion, 314 The Significance of Modeling and Visualization 33John A. Sokolowski and Hector M. GarciaIntroduction, 33Modeling a Complex System: Human Physiology, 34Medical Modeling, Simulation, and Visualization, 35Modes and Types of Visualization, 40Visualization for Patient]Specific Usefulness, 43Conclusion, 43References, 45Part 2 State of the Art: Systems Biology, the Physiome and Personalized Health 495 The Visible Human: A Graphical Interface for Holistic Modeling and Simulation 51Victor M. SpitzerIntroduction, 51Education, 53Modeling, 55Virtual Reality Trainers and Simulators, 56Conclusion, 58References, 596 The Quantifiable Self: Petabyte by Petabyte 63C. Donald Combs and Scarlett R. BarhamIntroduction, 63Smarr’s Quantified Self, 64Extending Smarr’s Research, 67The Quantified Self]Vision, Simplified, 69Criticism, 69Conclusion, 71References, 727 Systems Biology and Health Systems Complexity: Implications for the Digital Patient 73C. Donald Combs, Scarlett R. Barham, and Peter M. A. SlootIntroduction, 73Systems Biology, 75The Institute for Systems Biology, 76The Complexity Institute, 78The Potential of Systems Biology, 81Criticism, 82Conclusion, 83References, 838 Personalized Computational Modeling for the Treatment of Cardiac Arrhythmias 85Seth H. WeinbergIntroduction, 85Basics of Cardiac Electrophysiology, 86Cardiac Modeling Advancements, 89Regulation of Intracellular Calcium, 90From Cells to Cables to Sheets to Tissue to the Heart, 91Where Can we go from Here? What is the Cardiac Model in the Digital Patient? 95References, 969 The Physiome Project, openEHR Archetypes, and the Digital Patient 101David P. Nickerson, Koray Atalag, Bernard de Bono, and Peter J. HunterIntroduction, 101Multiscale Physiological Processes, 102Physiome Project Standards, Repositories, and Tools, 103Archetype Specialization, 112Archetype Definition Language, 113Linking Archetypes to External Knowledge Sources (Terminology and Biomedical Ontologies), 114Archetype Annotations, 114OpenEHR Model Repository and Governance, 115Fast Healthcare Interoperability Resources, 115A Disease Scenario, 116Summary and Conclusions, 121References, 12210 Physics]Based Modeling for the Physiome 127William A. Pruett and Robert L. HesterIntroduction, 127Modeling Schemes, 128Future Challenges, 142Conclusion, 142Acknowledgments, 143References, 14311 Modeling and Understanding the Human Body with SwarmScript 149Sebastian von Mammen, Stefan Schellmoser, Christian Jacob, and Jörg HähnerIntroduction, 149Related Work, 150Multiagent Organization, 152Designing Interactive Agents, 152Speaking SwarmScript, 153Answering Demand: The Design of SwarmScript, 153Graph]Based Rule Representation, 153The Source–Action–Target, 154SwarmScript INTO3D, 154A SwarmScript Dialogue, 155Discussion, 159Summary, 161References, 16212 Using Avatars and Agents to Promote Real]World Health Behavior Changes 167Sun Joo (Grace) AhnIntroduction, 167Avatars and Agents, 168Using Agents and Avatars to Promote Health Behavior Changes, 169Conclusion, 174References, 17413 Virtual Reality and Eating, Diabetes, and Obesity 179Jessica E. Cornick and Jim BlascovichIntroduction, 179Virtual Reality, 179Obesity and Weight Stigma, 184Virtual Reality as a Tool for Combatting Health Issues, 185Conclusion, 189References, 18914 Immersive Virtual Reality to Model Physical: Social Interaction and Self]Representation 197Eric B. BaumanIntroduction, 197Theory for Immersive Virtual Learning Spaces, 197Conclusion, 202References, 203Part 3 Challenges: Assimilating the Comprehensive Digital Patient 20515 A Roadmap for Building a Digital Patient System 207Saikou Y. Diallo and Christopher J. LynchIntroduction, 207Approach, 210Building the Digital Patient Through Interoperability, 211Conclusion, 221Acknowledgments, 221References, 22116 Multidisciplinary, Interdisciplinary, and Transdisciplinary Research: Contextualization and Reliability of the Composite 225Andreas TolkIntroduction, 225Interdisciplinarity and Interdisciplinary Research, 226Data Engineering to Support Interdisciplinarity and Interoperability, 228Base Object Models to Support Transdisciplinarity and Composability, 233Open Challenges on Reliability, 235Summary and Conclusion, 237References, 23917 Bayes Net Modeling: The Means to Craft the Digital Patient 241Joseph A. Tatman and Barry C. EzellIntroduction, 241Other Interesting Applications, 246Conclusion, 251References, 253Part 4 Potential Impact: Engaging The Digital Patient 25518 Virtual Reality Standardized Patients for Clinical Training 257Albert Rizzo and Thomas TalbotIntroduction, 257The Rationale for Virtual Standardized Patients, 258Conversational Virtual Human Agents, 259Usc Efforts to Create Virtual Standardized Patients, 260Conclusion, 269References, 27019 The Digital Patient: Changing the Paradigm of Healthcare and Impacting Medical Research and Education 273V. Andrea ParodiIntroduction, 273Overview Digital Medicine Projects, 275Personalized Patient Care Clinical Use, 279Recommended Education and Training for VPH Project Participation, 281From Flexner to the 2010 Carnegie Report, 284Summary Statements, 286References, 28720 The Digital Patient: A Vision for Revolutionizing the Electronic Medical Record and Future Healthcare 289Richard M. SatavaIntroduction, 289Applications of the Digital Patient as the EMR, 291Discussion, 296Conclusion, 297References, 29721 Realizing the Digital Patient 299C. Donald Combs and John A. SokolowskiIndex 305

C. Donald Combs, PhD, is Vice President and Dean of the School of Health Professions at Eastern Virginia Medical School and is also a senior faculty member in the Department of Modeling, Simulation, and Visualization Engineering at Old Dominion University.  John A. Sokolowski, PhD, is Associate Professor and Executive Director of the Virginia Modeling, Analysis, and Simulation Center at Old Dominion University.  Catherine M. Banks, PhD, is Research Associate Professor at the Virginia Modeling, Analysis, and Simulation Center at Old Dominion University.

• List of Contributors xiii Preface xviiPart 1 The Vision: The Digital Patient—Improving Research, Development, Education, and Healthcare Practice 11 The Digital Patient 3C. Donald CombsHealth, The Goal, 4Personalized Medicine, 4The Best Outcomes, 5The Emergence of the Digital Patient, 5The Human Physiome, 6Enabling the Digital Patient, 8P4 Medicine, 11Conclusion, 11References, 122 Reflecting on Discipulus and Remaining Challenges 15Vanessa Díaz]Zuccarini, Mona Alimohammadi, and César Pichardo]AlmarzaIntroduction, 15A Brief Contextual Background and a Call for Integration: Personalized Medicine is Holistic, 16The Many Versions of the Digital Patient: On the Road to Medical Avatars, 18Discipulus: The Digital Patient Technological Challenges and Main Conclusions, 19The Remaining Challenges and Big Data, 24Conclusion, 25References, 263 Advancing the Digital Patient 27Catherine M. BanksIntroduction, 27The Digital Patient: Its Early Start, 28Engaging the Digital Patient, 30Conclusion, 314 The Significance of Modeling and Visualization 33John A. Sokolowski and Hector M. GarciaIntroduction, 33Modeling a Complex System: Human Physiology, 34Medical Modeling, Simulation, and Visualization, 35Modes and Types of Visualization, 40Visualization for Patient]Specific Usefulness, 43Conclusion, 43References, 45Part 2 State of the Art: Systems Biology, the Physiome and Personalized Health 495 The Visible Human: A Graphical Interface for Holistic Modeling and Simulation 51Victor M. SpitzerIntroduction, 51Education, 53Modeling, 55Virtual Reality Trainers and Simulators, 56Conclusion, 58References, 596 The Quantifiable Self: Petabyte by Petabyte 63C. Donald Combs and Scarlett R. BarhamIntroduction, 63Smarr’s Quantified Self, 64Extending Smarr’s Research, 67The Quantified Self]Vision, Simplified, 69Criticism, 69Conclusion, 71References, 727 Systems Biology and Health Systems Complexity: Implications for the Digital Patient 73C. Donald Combs, Scarlett R. Barham, and Peter M. A. SlootIntroduction, 73Systems Biology, 75The Institute for Systems Biology, 76The Complexity Institute, 78The Potential of Systems Biology, 81Criticism, 82Conclusion, 83References, 838 Personalized Computational Modeling for the Treatment of Cardiac Arrhythmias 85Seth H. WeinbergIntroduction, 85Basics of Cardiac Electrophysiology, 86Cardiac Modeling Advancements, 89Regulation of Intracellular Calcium, 90From Cells to Cables to Sheets to Tissue to the Heart, 91Where Can we go from Here? What is the Cardiac Model in the Digital Patient? 95References, 969 The Physiome Project, openEHR Archetypes, and the Digital Patient 101David P. Nickerson, Koray Atalag, Bernard de Bono, and Peter J. HunterIntroduction, 101Multiscale Physiological Processes, 102Physiome Project Standards, Repositories, and Tools, 103Archetype Specialization, 112Archetype Definition Language, 113Linking Archetypes to External Knowledge Sources (Terminology and Biomedical Ontologies), 114Archetype Annotations, 114OpenEHR Model Repository and Governance, 115Fast Healthcare Interoperability Resources, 115A Disease Scenario, 116Summary and Conclusions, 121References, 12210 Physics]Based Modeling for the Physiome 127William A. Pruett and Robert L. HesterIntroduction, 127Modeling Schemes, 128Future Challenges, 142Conclusion, 142Acknowledgments, 143References, 14311 Modeling and Understanding the Human Body with SwarmScript 149Sebastian von Mammen, Stefan Schellmoser, Christian Jacob, and Jörg HähnerIntroduction, 149Related Work, 150Multiagent Organization, 152Designing Interactive Agents, 152Speaking SwarmScript, 153Answering Demand: The Design of SwarmScript, 153Graph]Based Rule Representation, 153The Source–Action–Target, 154SwarmScript INTO3D, 154A SwarmScript Dialogue, 155Discussion, 159Summary, 161References, 16212 Using Avatars and Agents to Promote Real]World Health Behavior Changes 167Sun Joo (Grace) AhnIntroduction, 167Avatars and Agents, 168Using Agents and Avatars to Promote Health Behavior Changes, 169Conclusion, 174References, 17413 Virtual Reality and Eating, Diabetes, and Obesity 179Jessica E. Cornick and Jim BlascovichIntroduction, 179Virtual Reality, 179Obesity and Weight Stigma, 184Virtual Reality as a Tool for Combatting Health Issues, 185Conclusion, 189References, 18914 Immersive Virtual Reality to Model Physical: Social Interaction and Self]Representation 197Eric B. BaumanIntroduction, 197Theory for Immersive Virtual Learning Spaces, 197Conclusion, 202References, 203Part 3 Challenges: Assimilating the Comprehensive Digital Patient 20515 A Roadmap for Building a Digital Patient System 207Saikou Y. Diallo and Christopher J. LynchIntroduction, 207Approach, 210Building the Digital Patient Through Interoperability, 211Conclusion, 221Acknowledgments, 221References, 22116 Multidisciplinary, Interdisciplinary, and Transdisciplinary Research: Contextualization and Reliability of the Composite 225Andreas TolkIntroduction, 225Interdisciplinarity and Interdisciplinary Research, 226Data Engineering to Support Interdisciplinarity and Interoperability, 228Base Object Models to Support Transdisciplinarity and Composability, 233Open Challenges on Reliability, 235Summary and Conclusion, 237References, 23917 Bayes Net Modeling: The Means to Craft the Digital Patient 241Joseph A. Tatman and Barry C. EzellIntroduction, 241Other Interesting Applications, 246Conclusion, 251References, 253Part 4 Potential Impact: Engaging The Digital Patient 25518 Virtual Reality Standardized Patients for Clinical Training 257Albert Rizzo and Thomas TalbotIntroduction, 257The Rationale for Virtual Standardized Patients, 258Conversational Virtual Human Agents, 259Usc Efforts to Create Virtual Standardized Patients, 260Conclusion, 269References, 27019 The Digital Patient: Changing the Paradigm of Healthcare and Impacting Medical Research and Education 273V. Andrea ParodiIntroduction, 273Overview Digital Medicine Projects, 275Personalized Patient Care Clinical Use, 279Recommended Education and Training for VPH Project Participation, 281From Flexner to the 2010 Carnegie Report, 284Summary Statements, 286References, 28720 The Digital Patient: A Vision for Revolutionizing the Electronic Medical Record and Future Healthcare 289Richard M. SatavaIntroduction, 289Applications of the Digital Patient as the EMR, 291Discussion, 296Conclusion, 297References, 29721 Realizing the Digital Patient 299C. Donald Combs and John A. SokolowskiIndex 305

C. Donald Combs, PhD, is Vice President and Dean of the School of Health Professions at Eastern Virginia Medical School and is also a senior faculty member in the Department of Modeling, Simulation, and Visualization Engineering at Old Dominion University.  John A. Sokolowski, PhD, is Associate Professor and Executive Director of the Virginia Modeling, Analysis, and Simulation Center at Old Dominion University.  Catherine M. Banks, PhD, is Research Associate Professor at the Virginia Modeling, Analysis, and Simulation Center at Old Dominion University.

• List of Contributors xiii Preface xviiPart 1 The Vision: The Digital Patient—Improving Research, Development, Education, and Healthcare Practice 11 The Digital Patient 3C. Donald CombsHealth, The Goal, 4Personalized Medicine, 4The Best Outcomes, 5The Emergence of the Digital Patient, 5The Human Physiome, 6Enabling the Digital Patient, 8P4 Medicine, 11Conclusion, 11References, 122 Reflecting on Discipulus and Remaining Challenges 15Vanessa Díaz]Zuccarini, Mona Alimohammadi, and César Pichardo]AlmarzaIntroduction, 15A Brief Contextual Background and a Call for Integration: Personalized Medicine is Holistic, 16The Many Versions of the Digital Patient: On the Road to Medical Avatars, 18Discipulus: The Digital Patient Technological Challenges and Main Conclusions, 19The Remaining Challenges and Big Data, 24Conclusion, 25References, 263 Advancing the Digital Patient 27Catherine M. BanksIntroduction, 27The Digital Patient: Its Early Start, 28Engaging the Digital Patient, 30Conclusion, 314 The Significance of Modeling and Visualization 33John A. Sokolowski and Hector M. GarciaIntroduction, 33Modeling a Complex System: Human Physiology, 34Medical Modeling, Simulation, and Visualization, 35Modes and Types of Visualization, 40Visualization for Patient]Specific Usefulness, 43Conclusion, 43References, 45Part 2 State of the Art: Systems Biology, the Physiome and Personalized Health 495 The Visible Human: A Graphical Interface for Holistic Modeling and Simulation 51Victor M. SpitzerIntroduction, 51Education, 53Modeling, 55Virtual Reality Trainers and Simulators, 56Conclusion, 58References, 596 The Quantifiable Self: Petabyte by Petabyte 63C. Donald Combs and Scarlett R. BarhamIntroduction, 63Smarr’s Quantified Self, 64Extending Smarr’s Research, 67The Quantified Self]Vision, Simplified, 69Criticism, 69Conclusion, 71References, 727 Systems Biology and Health Systems Complexity: Implications for the Digital Patient 73C. Donald Combs, Scarlett R. Barham, and Peter M. A. SlootIntroduction, 73Systems Biology, 75The Institute for Systems Biology, 76The Complexity Institute, 78The Potential of Systems Biology, 81Criticism, 82Conclusion, 83References, 838 Personalized Computational Modeling for the Treatment of Cardiac Arrhythmias 85Seth H. WeinbergIntroduction, 85Basics of Cardiac Electrophysiology, 86Cardiac Modeling Advancements, 89Regulation of Intracellular Calcium, 90From Cells to Cables to Sheets to Tissue to the Heart, 91Where Can we go from Here? What is the Cardiac Model in the Digital Patient? 95References, 969 The Physiome Project, openEHR Archetypes, and the Digital Patient 101David P. Nickerson, Koray Atalag, Bernard de Bono, and Peter J. HunterIntroduction, 101Multiscale Physiological Processes, 102Physiome Project Standards, Repositories, and Tools, 103Archetype Specialization, 112Archetype Definition Language, 113Linking Archetypes to External Knowledge Sources (Terminology and Biomedical Ontologies), 114Archetype Annotations, 114OpenEHR Model Repository and Governance, 115Fast Healthcare Interoperability Resources, 115A Disease Scenario, 116Summary and Conclusions, 121References, 12210 Physics]Based Modeling for the Physiome 127William A. Pruett and Robert L. HesterIntroduction, 127Modeling Schemes, 128Future Challenges, 142Conclusion, 142Acknowledgments, 143References, 14311 Modeling and Understanding the Human Body with SwarmScript 149Sebastian von Mammen, Stefan Schellmoser, Christian Jacob, and Jörg HähnerIntroduction, 149Related Work, 150Multiagent Organization, 152Designing Interactive Agents, 152Speaking SwarmScript, 153Answering Demand: The Design of SwarmScript, 153Graph]Based Rule Representation, 153The Source–Action–Target, 154SwarmScript INTO3D, 154A SwarmScript Dialogue, 155Discussion, 159Summary, 161References, 16212 Using Avatars and Agents to Promote Real]World Health Behavior Changes 167Sun Joo (Grace) AhnIntroduction, 167Avatars and Agents, 168Using Agents and Avatars to Promote Health Behavior Changes, 169Conclusion, 174References, 17413 Virtual Reality and Eating, Diabetes, and Obesity 179Jessica E. Cornick and Jim BlascovichIntroduction, 179Virtual Reality, 179Obesity and Weight Stigma, 184Virtual Reality as a Tool for Combatting Health Issues, 185Conclusion, 189References, 18914 Immersive Virtual Reality to Model Physical: Social Interaction and Self]Representation 197Eric B. BaumanIntroduction, 197Theory for Immersive Virtual Learning Spaces, 197Conclusion, 202References, 203Part 3 Challenges: Assimilating the Comprehensive Digital Patient 20515 A Roadmap for Building a Digital Patient System 207Saikou Y. Diallo and Christopher J. LynchIntroduction, 207Approach, 210Building the Digital Patient Through Interoperability, 211Conclusion, 221Acknowledgments, 221References, 22116 Multidisciplinary, Interdisciplinary, and Transdisciplinary Research: Contextualization and Reliability of the Composite 225Andreas TolkIntroduction, 225Interdisciplinarity and Interdisciplinary Research, 226Data Engineering to Support Interdisciplinarity and Interoperability, 228Base Object Models to Support Transdisciplinarity and Composability, 233Open Challenges on Reliability, 235Summary and Conclusion, 237References, 23917 Bayes Net Modeling: The Means to Craft the Digital Patient 241Joseph A. Tatman and Barry C. EzellIntroduction, 241Other Interesting Applications, 246Conclusion, 251References, 253Part 4 Potential Impact: Engaging The Digital Patient 25518 Virtual Reality Standardized Patients for Clinical Training 257Albert Rizzo and Thomas TalbotIntroduction, 257The Rationale for Virtual Standardized Patients, 258Conversational Virtual Human Agents, 259Usc Efforts to Create Virtual Standardized Patients, 260Conclusion, 269References, 27019 The Digital Patient: Changing the Paradigm of Healthcare and Impacting Medical Research and Education 273V. Andrea ParodiIntroduction, 273Overview Digital Medicine Projects, 275Personalized Patient Care Clinical Use, 279Recommended Education and Training for VPH Project Participation, 281From Flexner to the 2010 Carnegie Report, 284Summary Statements, 286References, 28720 The Digital Patient: A Vision for Revolutionizing the Electronic Medical Record and Future Healthcare 289Richard M. SatavaIntroduction, 289Applications of the Digital Patient as the EMR, 291Discussion, 296Conclusion, 297References, 29721 Realizing the Digital Patient 299C. Donald Combs and John A. SokolowskiIndex 305