Dynamic Modeling in the Health Sciences

This book and CD-ROM integrate the use of STELLA software into the teaching of health, nutrition and physiology. The book can be used on its own as a textbook, or can serve as a supplement in nutrition and physiology courses to introduce the role that simulation modeling can play. Dynamic Modeling in the Health Sciences discusses key subjects ranging from the theory of metabolic control to weight regulation to bone metabolism, and gives readers tools to simulate these processes.

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® Models to Solve Basic Equations.- 2.1 Using STELLA® for Computer-Assisted Simulation.- 2.2 Tools Used to Create and Run Models with STELLA®.- 2.3 Lesson 1: Use STELLA® 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®.- 2.6 Record Keeping and Documentation.- References.- 3 How an Equation from Physiology Can Become a Model.- 3.1 Let STELLA® 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® 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® Compartmental Models.- 5.2 Calculating Initial and Final Values for STELLA® 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® 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® 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® to Solve the Kleiber Equation for Basal Metabolic Rate.- 8.4 Specific Metabolic Rate and Physiological Time.- 8.5 Use STELLA® 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®.- 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® 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® 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® to Solve the Gompertz Equation.- 15.4 Risk for Coronary Artery Disease.- 15.5 STELLA® 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® Software Mechanics.