Dynamic Modeling in the Health Sciences

1 Discoveries with a Computer: Dynamic behavior.- 1.1 A Small Discovery in a Remote Place.- 1.2 Discoveries with a Computer.- 1.3 From the Bench to the Mind and Back Again.- 1.4 The Chaos Game.- References.- 2 How to Create STELLA(R) Models to Solve Basic Equations.- 2.1 Using STELLA(R) for Computer-Assisted Simulation.- 2.2 Tools Used to Create and Run Models with STELLA(R).- 2.3 Lesson 1: Use STELLA(R) to Create a Calculator for Body Mass Index.- 2.4 Lesson 2: Create a Device to Calculate Total Energy Content in Meals.- 2.5 Modeling Projects Using STELLA(R).- 2.6 Record Keeping and Documentation.- References.- 3 How an Equation from Physiology Can Become a Model.- 3.1 Let STELLA(R) Solve the Nernst Equation.- References.- 4 Rates of Change.- 4.1 The Steady State.- 4.2 Temporal Behavior of the Single-Compartment Model.- 4.3 The Concept of Half-life and the Time Course of Change.- 4.4 The Concept of Fractional Elimination Rates.- 4.5 Half-lives and Half-Times.- 4.6 Symmetry and a Helpful Rule.- 4.7 STELLA(R) Can Make e Your Temporal Assistant.- 4.8 Use Powers of e to Simulate Time-Dependent Events.- 4.9 The General Function for Fractional Change.- 5 The Steady State: A Question of Balance.- 5.1 Setting Initial Conditions for STELLA(R) Compartmental Models.- 5.2 Calculating Initial and Final Values for STELLA(R) Models.- 6 Equations for Model Building: The Surface Law and Body Composition.- 6.1 Purposes for Modeling the Human Body.- 6.2 Sources for Equations Used in Model Building.- 6.3 Models of Human Body Composition: Reference Man and Reference Woman.- 6.4 The Surface Law: Calculating Surface Area in Adult Humans.- 6.5 Understanding Exponents for Body Surface and Mass.- 6.6 The Allometric Equation.- 6.7 Use STELLA(R) Models to Solve Equations with Exponential Terms.- 6.8 Heat and Energy Production Relative to Human Metabolic Needs.- 6.9 Estimating Daily Energy Expenditure.- References.- 7 A Primer on Biodynamics and Gene Expression.- 7.1 Simulation and Modeling Can Assist Analysis and Integration.- 7.2 Simulate to Think, but Model to Validate.- 7.3 Compartmental Models.- 7.4 A Compartmental Model of Gene Expression.- 7.5 Kinetic Behavior of a Single Compartment.- 7.6 Assumptions and Nomenclature Used in Modeling Systems.- 7.7 Transfer Rates Between Compartments Are Related to Half-Lives.- 7.8 Compartmental Models Help Predict Steady-State Relationships.- 7.9 Simulating Gene Expression Using a Single-Compartment Model.- 7.10 Writing Equations for the Steady-State Condition.- 7.11 Test How the Basic Kinetic Model Predicts Change Over Time.- 7.12 Viewing Results as Graphs and Tables.- 7.13 Advantage of the Tabular Form.- 7.14 Use STELLA(R) to Understand Rates of Change in More Complex Systems.- References.- 8 Chronological Time Versus Physiological Time.- 8.1 Metabolic Pools and Turnover Times.- 8.2 The Metabolic Rate in Mammals Is Related to the Rate of Heat Loss.- 8.3 Use STELLA(R) to Solve the Kleiber Equation for Basal Metabolic Rate.- 8.4 Specific Metabolic Rate and Physiological Time.- 8.5 Use STELLA(R) to Compare Scaling for Metabolic Time and Metabolic Rate.- 8.6 Effects of Body Size on Drug Dosing.- 8.7 Questions.- 8.8 A Natural Experiment.- 8.9 Conclusions.- References.- 9 Energy Needs for Work.- 9.1 Human Work Follows the Laws of Thermodynamics.- 9.2 Human Mechanical Work.- 9.3 The Osmotic Work of the Kidney.- 9.4 Conclusions.- References.- 10 The Human Thermostat.- 10.1 Heat Production and Body Temperature.- 10.2 Modeling the Human Thermostat.- 10.3 Modeling Heat Loss with STELLA(R).- 10.4 The Human Thermostat.- References.- 11 Dietary Polyunsaturated Fats and Your Cell Membranes.- 11.1 The Impact of the Food Supply on Proinflammatory Membrane Phospholipids.- 11.2 Competitive Model for the Effect of Diet on Membrane Phospholipids.- 11.3 Why Are Beef Fat and Pork Fat Protective Against Alcohol-Induced liver Disease?.- 11.4 Contradictory Guidelines for Dietary Fat.- 11.5 Biological Responses to Polyunsaturated Fatty Acids.- 11.6 PUFA as Sources for lipid Signaling Pathways.- 11.7 Basis for the Kinetic Model for Membrane Composition.- 11.8 Use STELLA(R) to Calculate Dietary Fatty Acid Content.- 11.9 Predict the Effects of Diet on Membrane Phospholipids.- 11.10 The Time Course of Change in Membrane Iipids.- 11.11 A Model of Phospholipid Kinetics.- 11.12 Points to Consider.- References.- 12 Responses to Nutrients.- 12.1 Models of Nutrient Response.- 12.2 The Saturation Kinetic Model.- 12.3 Use STELLA(R) Can Make e Your Temporal Assistant.- 4.8 Use Powers of e to Simulate Time-Dependent Events.- 4.9 The General Function for Fractional Change.- 5 The Steady State: A Question of Balance.- 5.1 Setting Initial Conditions for STELLA(R) Compartmental Models.- 5.2 Calculating Initial and Final Values for STELLA(R) Models.- 6 Equations for Model Building: The Surface Law and Body Composition.- 6.1 Purposes for Modeling the Human Body.- 6.2 Sources for Equations Used in Model Building.- 6.3 Models of Human Body Composition: Reference Man and Reference Woman.- 6.4 The Surface Law: Calculating Surface Area in Adult Humans.- 6.5 Understanding Exponents for Body Surface and Mass.- 6.6 The Allometric Equation.- 6.7 Use STELLA(R) Models to Solve Equations with Exponential Terms.- 6.8 Heat and Energy Production Relative to Human Metabolic Needs.- 6.9 Estimating Daily Energy Expenditure.- References.- 7 A Primer on Biodynamics and Gene Expression.- 7.1 Simulation and Modeling Can Assist Analysis and Integration.- 7.2 Simulate to Think, but Model to Validate.- 7.3 Compartmental Models.- 7.4 A Compartmental Model of Gene Expression.- 7.5 Kinetic Behavior of a Single Compartment.- 7.6 Assumptions and Nomenclature Used in Modeling Systems.- 7.7 Transfer Rates Between Compartments Are Related to Half-Lives.- 7.8 Compartmental Models Help Predict Steady-State Relationships.- 7.9 Simulating Gene Expression Using a Single-Compartment Model.- 7.10 Writing Equations for the Steady-State Condition.- 7.11 Test How the Basic Kinetic Model Predicts Change Over Time.- 7.12 Viewing Results as Graphs and Tables.- 7.13 Advantage of the Tabular Form.- 7.14 Use STELLA(R) to Understand Rates of Change in More Complex Systems.- References.- 8 Chronological Time Versus Physiological Time.- 8.1 Metabolic Pools and Turnover Times.- 8.2 The Metabolic Rate in Mammals Is Related to the Rate of Heat Loss.- 8.3 Use STELLA(R) to Solve the Kleiber Equation for Basal Metabolic Rate.- 8.4 Specific Metabolic Rate and Physiological Time.- 8.5 Use STELLA(R) to Compare Scaling for Metabolic Time and Metabolic Rate.- 8.6 Effects of Body Size on Drug Dosing.- 8.7 Questions.- 8.8 A Natural Experiment.- 8.9 Conclusions.- References.- 9 Energy Needs for Work.- 9.1 Human Work Follows the Laws of Thermodynamics.- 9.2 Human Mechanical Work.- 9.3 The Osmotic Work of the Kidney.- 9.4 Conclusions.- References.- 10 The Human Thermostat.- 10.1 Heat Production and Body Temperature.- 10.2 Modeling the Human Thermostat.- 10.3 Modeling Heat Loss with STELLA(R).- 10.4 The Human Thermostat.- References.- 11 Dietary Polyunsaturated Fats and Your Cell Membranes.- 11.1 The Impact of the Food Supply on Proinflammatory Membrane Phospholipids.- 11.2 Competitive Model for the Effect of Diet on Membrane Phospholipids.- 11.3 Why Are Beef Fat and Pork Fat Protective Against Alcohol-Induced liver Disease?.- 11.4 Contradictory Guidelines for Dietary Fat.- 11.5 Biological Responses to Polyunsaturated Fatty Acids.- 11.6 PUFA as Sources for lipid Signaling Pathways.- 11.7 Basis for the Kinetic Model for Membrane Composition.- 11.8 Use STELLA(R) to Calculate Dietary Fatty Acid Content.- 11.9 Predict the Effects of Diet on Membrane Phospholipids.- 11.10 The Time Course of Change in Membrane Iipids.- 11.11 A Model of Phospholipid Kinetics.- 11.12 Points to Consider.- References.- 12 Responses to Nutrients.- 12.1 Models of Nutrient Response.- 12.2 The Saturation Kinetic Model.- 12.3 Use STELLA(R) to Solve the Saturation Kinetic Equation.- 12.4 Running the Nutrient Response Model.- 12.5 Questions and Applications.- 12.6 Conclusions.- References.- 13 Symmetry of Human Growth and Aging.- 13.1 Simplifying Models of Growth.- 13.2 A General Model of Growth.- 13.3 A Model with a Declining Growth Rate.- 13.4 Specific Growth Rate.- 13.5 The Gompertz Growth Function.- 13.6 The Relationsip with Aging.- 137 The Symmetric Relationship Between Relative Growth and Physiologic Time.- 13.8 The Brody Model for Growth and Senescence.- 13.9 A Time Unit Based on Growth: The Chron.- 13.10 Time Standards for Growth and Aging.- 13.11 Summary and Applications.- References.- 14 A Stochastic Model of Senescence and Demise.- 14.1 Decline of Function with Aging.- 14.2 An Element of Randomness.- 14.3 Applications.- References.- 15 Mortality and Risk for Chronic Disease.- 15.1 Two Lovely Thoughts: Morbidity and Mortality.- 15.2 Ideas About Risk.- 15.3 Use STELLA(R) to Solve the Gompertz Equation.- 15.4 Risk for Coronary Artery Disease.- 15.5 STELLA(R) Can Make e Your Temporal Assistant.- 4.8 Use Powers of e to Simulate Time-Dependent Events.- 4.9 The General Function for Fractional Change.- 5 The Steady State: A Question of Balance.- 5.1 Setting Initial Conditions for STELLA(R) Compartmental Models.- 5.2 Calculating Initial and Final Values for STELLA(R) Models.- 6 Equations for Model Building: The Surface Law and Body Composition.- 6.1 Purposes for Modeling the Human Body.- 6.2 Sources for Equations Used in Model Building.- 6.3 Models of Human Body Composition: Reference Man and Reference Woman.- 6.4 The Surface Law: Calculating Surface Area in Adult Humans.- 6.5 Understanding Exponents for Body Surface and Mass.- 6.6 The Allometric Equation.- 6.7 Use STELLA(R) Models to Solve Equations with Exponential Terms.- 6.8 Heat and Energy Production Relative to Human Metabolic Needs.- 6.9 Estimating Daily Energy Expenditure.- References.- 7 A Primer on Biodynamics and Gene Expression.- 7.1 Simulation and Modeling Can Assist Analysis and Integration.- 7.2 Simulate to Think, but Model to Validate.- 7.3 Compartmental Models.- 7.4 A Compartmental Model of Gene Expression.- 7.5 Kinetic Behavior of a Single Compartment.- 7.6 Assumptions and Nomenclature Used in Modeling Systems.- 7.7 Transfer Rates Between Compartments Are Related to Half-Lives.- 7.8 Compartmental Models Help Predict Steady-State Relationships.- 7.9 Simulating Gene Expression Using a Single-Compartment Model.- 7.10 Writing Equations for the Steady-State Condition.- 7.11 Test How the Basic Kinetic Model Predicts Change Over Time.- 7.12 Viewing Results as Graphs and Tables.- 7.13 Advantage of the Tabular Form.- 7.14 Use STELLA(R) to Understand Rates of Change in More Complex Systems.- References.- 8 Chronological Time Versus Physiological Time.- 8.1 Metabolic Pools and Turnover Times.- 8.2 The Metabolic Rate in Mammals Is Related to the Rate of Heat Loss.- 8.3 Use STELLA(R) to Solve the Kleiber Equation for Basal Metabolic Rate.- 8.4 Specific Metabolic Rate and Physiological Time.- 8.5 Use STELLA(R) to Compare Scaling for Metabolic Time and Metabolic Rate.- 8.6 Effects of Body Size on Drug Dosing.- 8.7 Questions.- 8.8 A Natural Experiment.- 8.9 Conclusions.- References.- 9 Energy Needs for Work.- 9.1 Human Work Follows the Laws of Thermodynamics.- 9.2 Human Mechanical Work.- 9.3 The Osmotic Work of the Kidney.- 9.4 Conclusions.- References.- 10 The Human Thermostat.- 10.1 Heat Production and Body Temperature.- 10.2 Modeling the Human Thermostat.- 10.3 Modeling Heat Loss with STELLA(R).- 10.4 The Human Thermostat.- References.- 11 Dietary Polyunsaturated Fats and Your Cell Membranes.- 11.1 The Impact of the Food Supply on Proinflammatory Membrane Phospholipids.- 11.2 Competitive Model for the Effect of Diet on Membrane Phospholipids.- 11.3 Why Are Beef Fat and Pork Fat Protective Against Alcohol-Induced liver Disease?.- 11.4 Contradictory Guidelines for Dietary Fat.- 11.5 Biological Responses to Polyunsaturated Fatty Acids.- 11.6 PUFA as Sources for lipid Signaling Pathways.- 11.7 Basis for the Kinetic Model for Membrane Composition.- 11.8 Use STELLA(R) to Calculate Dietary Fatty Acid Content.- 11.9 Predict the Effects of Diet on Membrane Phospholipids.- 11.10 The Time Course of Change in Membrane Iipids.- 11.11 A Model of Phospholipid Kinetics.- 11.12 Points to Consider.- References.- 12 Responses to Nutrients.- 12.1 Models of Nutrient Response.- 12.2 The Saturation Kinetic Model.- 12.3 Use STELLA(R) to Solve the Saturation Kinetic Equation.- 12.4 Running the Nutrient Response Model.- 12.5 Questions and Applications.- 12.6 Conclusions.- References.- 13 Symmetry of Human Growth and Aging.- 13.1 Simplifying Models of Growth.- 13.2 A General Model of Growth.- 13.3 A Model with a Declining Growth Rate.- 13.4 Specific Growth Rate.- 13.5 The Gompertz Growth Function.- 13.6 The Relationsip with Aging.- 137 The Symmetric Relationship Between Relative Growth and Physiologic Time.- 13.8 The Brody Model for Growth and Senescence.- 13.9 A Time Unit Based on Growth: The Chron.- 13.10 Time Standards for Growth and Aging.- 13.11 Summary and Applications.- References.- 14 A Stochastic Model of Senescence and Demise.- 14.1 Decline of Function with Aging.- 14.2 An Element of Randomness.- 14.3 Applications.- References.- 15 Mortality and Risk for Chronic Disease.- 15.1 Two Lovely Thoughts: Morbidity and Mortality.- 15.2 Ideas About Risk.- 15.3 Use STELLA(R) to Solve the Gompertz Equation.- 15.4 Risk for Coronary Artery Disease.- 15.5 STELLA(R) Model for CAD Risk.- 15.6 Simulation Results.- 15.7 Discussion of the Model.- References.- 16 Kinetic Genetics: Compartmental Models of Gene Expression.- 16.1 Using the Idea of Approximation to Simulate Gene Expression.- 16.2 Solving a Model of Gene Expression with a Simulation Program.- 16.3 The Necessary Balance of Synthesis and Degradation.- 16.4 Transcriptional Controls Are Most Efficient.- 16.5 Rapidly Inducible Proteins Are Encoded by Labile mRNAs.- 16.6 Do Exons Coordinate mRNA and Protein Stability?.- 16.7 Conclusion.- References.- 17 From Genotype to Phenotype.- 17.1 Toward a Comprehensive Model of Gene Expression.- 17.2 Creating a Computer Program to Simulate Gene Expression.- 17.3 Translational Control.- 17.4 The Activation of Transcription.- 17.5 Kinetics of Transcriptional Activation.- 17.6 Rates of Association Between Iigands and Their Receptors.- 17.7 Delays and the Idea of Relaxation Time.- 17.8 The Law of Diminishing Returns.- 17.9 Conclusions.- References.- 18 The Plateau Principle: A Key to Biological System Dynamics.- 18.1 Origins of the Plateau Principle.- 18.2 The Plateau Principle Is Widely Applicable.- 18.3 Outcomes Depend on Input Timing and Output Rates.- 18.4 Elimination Rate, Daily Needs, and the Potential for Toxicity.- 18.5 Simulate Effects of Changing the Intake of Vitamin C and Vitamin A.- References.- 19 Compartmental Models in Metabolic Studies: Vitamin C.- 19.1 Compartmental Analysis.- 19.2 A Note About Linearity.- 193 Compartmental Analysis of Nutrient Metabolism.- 194 A Multicompartment Model of Ascorbic Acid Metabolism.- 19.5 Volume of Distribution.- 19.6 Clearance.- 19.7 Routes of Elimination.- 19.8 Predictions Based on the Model of Vitamin C Metabolism.- 19.9 Challenge to the Student.- References.- 20 Orcadian Rhythms.- 20.1 The Van der Pol Oscillator.- 20.2 A Generic Oscillator.- 20.3 Circadian Rhythms in Synthesis of Specific Proteins.- References.- 21 Diet Composition and Fat Balance.- 21.1 Introduction.- 21.2 Purpose.- 21.3 Health-Related Goals Concerning Obesity.- 21.4 Assumptions and Sources of Equations.- 21.5 How to Use the Program.- 21.6 Tests to Perform Using the Fat Balance Program.- 21.7 A Source of Error in the Original Program.- 21.8 Notes on Model Development.- 21.9 Diet Composition and Conditions for Energy Balance and Fat Balance.- 21.10 Effects of Activity and Resistance Training.- 21.11 How Much Fat Do We Oxidize in a Day?.- 21.12 Effect of Energy Balance on Fat Oxidation.- 21.13 Efficiency of Fat Deposition.- 21.14 Effect of Physical Activity on Fat Oxidation.- 21.15 Effect of Body Composition on Rate of Weight Change.- 21.16 Evidence that the Simplest Model of Fat Balance Was Wrong.- 21.17 Modifying the Model.- 21.18 Different Ways to Use the Fat Balance Model.- 21.19 Major Conclusions.- References.- 22 Human Cholesterol Dynamics.- 22.1 Effects of Dietary Cholesterol and Fat on Serum Cholesterol.- 22.2 Minimal Model of Cholesterol Metabolism.- 22.3 The Complex Model of Cholesterol Dynamics.- References.- 23 Stochastic Model of Bone Remodeling and Osteoporosis.- 23.1 Computer Simulation of Bone Remodeling and Osteoporosis as a Tool for Medical Education.- 23.2 The Three Levels of the Stochastic Model.- 233 Compare the Loss of Trabeculae in Young and Old Individuals.- 23.4 Examine the Effects of Menopause on Loss of Bone Trabeculae.- 23.5 The Effects of Drug Treatment on Bone Remodeling.- 23.6 Outcomes.- References.- 24 Positive and Negative Feedback: Insulin and the Use of Fatty Acids and Glucose for Energy.- 24.1 The Effect of Insulin on Fuel Use.- 24.2 A Model of Glucose and Fat Regulation.- References.- 25 A Multistage Model for Tumor Progression.- 25.1 Molecular Biology and Staging of Colorectal Cancer.- 25.2 A Multistage Model for Colon Cancer.- 25.3 Using the Model of Tumor Growth.- 25.4 Modifications in the Model.- References.- 26 The Biokinetic Database.- 26.1 Epilogue.- 26.2 Software for Modeling and Simulation.- 26.3 Using Published Models.- 26.4 Hypothesis Testing and Publication.- 26.5 Divergent Origins of Modeling and System Dynamics.- Appendix: Quick Help Guide to STELLA(R) Software Mechanics.