Note: Intro -- Contents -- 1. Introduction -- 2. Studies in the Logic of Explanation -- 3. Explanations, Predictions, and Laws -- 4. Statistical Explanation and Causality -- 5. A Deductive-Nomological Model of Probabilistic Explanation -- 6. The Pragmatic Theory of Explanation -- 7. Theoretical Explanation -- 8. Explanatory Unification -- 9. Explanation and Scientific Understanding -- 10. The Illocutionary Theory of Explanation.

Note: Cover -- Copyright -- Acknowledgments -- Abstract and Benefits -- Table of Contents -- List of Tables -- List of Figures -- List of Acronyms -- Executive Summary -- Chapter 1.0: Introduction -- Chapter 2.0: Getting Started -- 2.1 Running GELCAT -- 2.2 Main Menu Page -- 2.3 Quick Start Instructions -- Chapter 3.0: Entering Facility/Financial/Energy Information -- 3.1 Facility Information -- 3.2 Financial Parameters -- 3.3 Energy Cost Schedules -- 3.3.1 Electricity Costs -- 3.3.2 Fuel Costs -- Chapter 4.0: Phetovoltaic Systems -- 4.1 Review Photovoltaic Systems Technology -- 4.2 Photovoltaic System - Inputs -- 4.3 Photovoltaic System - Results -- Chapter 5.0: Wind Turbine Generators -- 5.1 Review Wind Turbine Generators Technology -- 5.2 Wind Turbine Generators - Inputs -- 5.3 Wind Turbine Generators - Results -- Chapter 6.0: Hydro-Turbine Generators -- 6.1 Review Hydro-Turbine Generators Technology -- 6.2 Hydro-Turbine Generators - Inputs -- 6.3 Hydro-Turbine Generators - Results.

Note: Intro -- CONTENTS -- List of Tables -- Acknowledgments -- INTRODUCTION -- Guiding Theoretic Perspectives -- Physics and Physicists -- Organization of the Book -- CHAPTER 1 Following the Scientists -- Foundations of the Follow-up Study -- Research Design and Sample -- The Ten-Year Career Interval -- The Fieldwork -- Analysis of Data -- Academic Worlds Then and Now -- CHAPTER 2 Early- to Mid-Career Passages -- Professional Profile -- Early Career Patterns -- Elites -- Pluralists -- Communitarians -- Summary -- CHAPTER 3 Mid- to Late-Career Passages -- Professional Profile -- Mid-Career Patterns -- Elites -- Pluralists -- Communitarians -- Summary -- CHAPTER 4 Late- to Post-Career Passages -- Professional Profile -- Late-Career Patterns -- Elites -- Pluralists -- Communitarians -- Summary -- CHAPTER 5 Lives of Learning -- Expectations and the Rhythm of Careers -- Anomie and Adaptation -- Reference Groups and Social Control -- Selection of Reference Groups -- Rejection of Reference Groups -- Social Control of the Life Course -- Careers in Other Academic Fields -- Future Cohorts of Scientists and Contexts of Science -- APPENDIX A Interview Protocol - Foundational Study, 1998 -- APPENDIX B Contact Letter to Scientists -- APPENDIX C Thank-You Letter to Scientists -- APPENDIX D Interview Protocol-Longitudinal Study, 2004 -- APPENDIX E Post-Interview Questionnnaire -- APPENDIX F Departmental Questionnaire -- APPENDIX G Propositions Generated by the Study -- Notes -- References -- Index.

Note: Cover -- Title Page -- Copyright Page -- Table of Contents -- P -- Poly(Pkenylene Sulfide) and Copolymers -- Poly(P-Phenylene Sulfone) -- Poly(Phenylene Vinylene)s -- Poly(P-Phenylene Vinylene)s -- Polyphenylenes -- Polyphosphazene Block Copolymers -- Polyphosphazenes -- Polyphosphonates and Polyphosphates -- Polyphthalamides -- Polypropylene -- Polypropylene -- Peroxide-Promoted Degradation of Polypropylene -- Process Control for Polypropylene Degradation -- Polypropylene -- Polypropylene -- Polypropylene, Atactic -- Polypropylene Blends and Composites -- Poly(Propylene Carbonate) -- Polypropylene, Hemiisotactic -- Polypropylene, Isotactic -- Polypropylene, Isotactic -- Poly(Propylene Oxide) -- Poly(2,6-Pyridinediylvinylene) -- Polypyrrole -- Polypyrroles -- Polyradicals -- Polyrotaxanes -- Polysaccharide-Polysaccharide Interactions -- Polysaccharides, Synthetic -- Polysaccharides, Synthetic -- Polysilanes -- Polysilanes -- Polysilazanes -- Polysilylpropynes -- Polysoaps -- Polystyrene -- Poly(Styrene-Co-N-Alkylmaleimide)s -- Polystyrene and Derivatives, Photolysis -- Polystyrene, High Impact -- Polystyrene Manufacture -- Polystyrene, Rubber Toughened -- Polystyrene, Stereoregular -- Polystyrene, Syndiotactic -- Polystyrene, Syndiotactic -- Polysulfides -- Polysulfides -- Polysulfides -- Poly[N,N'-(Sulfo-P-Phenylene) Terephthalamide] -- Polysulfones -- Polyterpene Resins -- Polytetrafluoroethylene -- Polytetrafluoroethylene -- Poly(2,5-Thienylene Vinylene) and Derivatives -- Poly(Thioether Ketone and Sulfone)s -- Polythiophenes -- Polythiophenes -- Polythiophenes, Substituted -- Poly(1,2,4-Triazole)s -- Polyureas -- Polyurethane Catalysis -- Polyurethane Catalysts -- Polyurethane Elastomers, Segmented -- Polyurethane Ionomers -- Polyurethanes -- Polyurethanes, Blocked Copolymer -- Poly(Vinyl Alcohol) -- Poly(Vinyl Alcohol). , Poly(Vinyl Alcohol) Fiber -- Poly(Vinyl Alcohol) Fibers -- Poly (Vinyl Alcohol) Iodine Interactions -- Poly(Vinyl Alcohol)-Ion Complex Gels -- PVA-Borate Complexes -- PVA-Vanadate Gels -- Poly(Vinyl Chloride) -- Poly(Vinyl Chloride) -- Poly(Vinyl Chloride) -- Poly(Vinyl Chloride) -- Poly(Vinyl Chloride), Rigid -- Poly(Vinyl Chloride), Soft -- Poly(Vinyl Ketal)s -- Polyvinylamine -- Polyvinylamine -- PoLy(N-Vinylcarbazole) -- Poly(Vinylidene Fluoride) -- Poly(Vinylidene Fluoride) -- Poly(Vinylidene Fluoride) Phases and Morphology -- Poly(Vinylpyridinium Salt)s -- Poly(N-Vinyl-2-Pyrrolidone) Interactions -- Polyvinyltetrazoles -- Poly(P-Xylylene)s -- Poly(P-Xylylene)s, Coatings and Films -- Polyzwitterions -- Powder Coatings -- Preceramic Polymers -- Precipitation Polymerization -- Precipitation Polymerization -- Printing Inks -- [1.1.1] Propellanes -- Propylene Polymerization -- Protein-Based Polymeric Materials -- Protein-Based Polymer Synthesis -- Pseudo-Poly(Amino Acid)s (overview) -- Pyroelectricity.

Note: Front Cover -- Contents -- Preface for Instructors -- Preface for Students -- Authors -- Chapter 1: Surveying the Skies -- Chapter 2: Vectors -- Chapter 3: Using Vectors to Describe Motion -- Chapter 4: The First Conservation Law : Mass, Momentum, and Rocketry -- Chapter 5: Collisions and the Center of Mass -- Chapter 6: Acceleration, Force, and Newton's Laws -- Chapter 7: Circular Motion, Simple Harmonic Motion, and Time -- Chapter 8: Kepler's Laws and Newton's Discovery of Universal Gravitation -- Chapter 9: The Second Conservation Law : Energy -- Chapter 10: Gravitational Potential Energy and Orbital Motion -- Chapter 11: Rotations and the Third Conservation Law : Angular Momentum -- Chapter 12: Angular Momentum and Its Conservation -- Chapter 13: Torque, Angular Momentum, and the Earth-Moon System -- Chapter 14: Dark Matter, Dark Energy, and the Fate of the Universe -- EPILOGUE -- Appendix A: Physical Units -- Appendix B: Astrophysical Data -- Appendix C: Physical Constants -- Back Cover.

Note: MARKETS, PRICING, AND DEREGULATION OF UTILITIES -- Editor's page -- Copyright -- CONTENTS -- SPEAKERS AND DISCUSSANTS -- SPONSORS -- PREFACE AND ACKNOWLEDGEMENTS -- Chapter #1 Regulation Redux* -- Chapter #2 The Next Stage of Local Telephone Regulatory Reform* -- Chapter #3 The Long View of Demand-Side Management Programs -- Chapter #4 Determining the Competitiveness of Wholesale Electricity Markets -- Chapter #5 Metering in Electricity Markets -- Chapter #6 Regional Interactions in Electricity Prices in the Eastern United States -- Chapter #7 Auctions of Last Resort in Telecom and Energy Regulatory Restructuring* -- Chapter #8 Shakeout or Shakedown? -- Chapter #9 Public Safety as a Public Good -- Chapter #10 Universal Service*.

Note: Intro -- Preface -- Acknowledgments -- Panel of Reviewers -- Local Organizing Committee -- Scientific Committee -- Scientific Committee -- ISOTT Officers and Executive Committee -- Presidents -- Past Presidents -- President-Elect -- Secretary -- Treasurer -- Head of Publication Committee -- Chairman, Knisely Award Committee -- Executive Committee -- ISOTT Award Winners -- The Melvin H. Knisely Award -- Melvin H. Knisely Award Recipients -- The Dietrich W. Lübbers Award -- Dietrich W. Lübbers Award Recipients -- The Britton Chance Award -- Britton Chance Award Recipients -- The Duane F. Bruley Travel Awards -- The Duane F. Bruley Travel Award Recipients -- Kovach Lecture -- Kovach Lecture Recipients -- Contents -- Part I: Cell Metabolism, Tissue Oxygenation and Treatment -- Chapter 1: Oxygen Sensing by the Carotid Body: Past and Present -- 1 Introduction -- 2 Discovery of Carotid Bodies as an O2 Sensing Organ -- 3 Current Views on Carotid Body O2 Sensing -- 4 Physiological Implications of Carotid Body O2 Sensing by Gasotransmitters -- References -- Chapter 2: Predicted Decrease in Membrane Oxygen Permeability with Addition of Cholesterol -- 1 Introduction -- 2 Methods -- 3 Results and Discussion -- 4 Conclusion -- References -- Chapter 3: Chronic Diseases as Barriers to Oxygen Delivery: A Unifying Hypothesis of Tissue Reoxygenation Therapy -- 1 Chronic Disease and Inflammatory Hypoxia -- 2 Tuberculin Reaction: An In Vivo Human Model of Tissue Oxygen Demand, Diffusion and Deficit -- 3 Tissue Re-oxygenation Therapy (TROT): Chronic Disease, Compromised Tissues and the Potential of Hyperbaric Oxygen Therapy (HBOT) -- 4 Summary -- References -- Chapter 4: Dorsiflexor Muscle Oxygenation During Low, Moderate and Submaximal Sustained Isometric Contraction -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion -- 5 Conclusion -- References. , Chapter 5: Factors Determining the Oxygen Permeability of Biological Membranes: Oxygen Transport Across Eye Lens Fiber-Cell Plasma Membranes -- 1 Introduction -- 2 Methods -- 3 Results -- 3.1 Model Lipid Bilayer Membranes -- 3.1.1 Effect of Acyl Chains Unsaturation -- 3.1.2 Effect of Cholesterol Intercalation -- 3.1.3 Cholesterol-Induced Phases and Domains -- 3.1.4 Lens Lipid Membranes -- 3.2 Intact Fiber Cell Plasma Membranes of Eye Lenses -- 3.2.1 Lipid Domains -- 3.2.2 Oxygen Permeability across Domains in Intact Fiber Cell Membranes -- 4 Conclusions -- References -- Chapter 6: Multi-site Measurements of Muscle O2 Dynamics During Cycling Exercise in Early Post-myocardial Infarction -- 1 Introduction -- 2 Methods -- 2.1 Subjects -- 2.2 Experimental Design -- 2.3 Statistics -- 3 Results -- 4 Discussion -- References -- Chapter 7: Effects of 8 Weeks' Training on Systemic and Muscle Oxygen Dynamics in University Rugby Players -- 1 Introduction -- 2 Methods -- 2.1 Subjects -- 2.2 Experimental Design -- 2.3 Statistics -- 3 Results -- 4 Discussion -- References -- Chapter 8: Imaging Redox State in Mouse Muscles of Different Ages -- 1 Introduction -- 2 Materials and Methods -- 3 Results -- 4 Discussion -- References -- Chapter 9: Amino Acid Hydration Decreases Radiation-­Induced Nausea in Mice: A Pica Model -- 1 Introduction -- 2 Methods -- 3 Results -- 3.1 Radiation Altered Glucose and Amino Acid Absorption -- 3.2 Radiation Increased Cl− Secretion, and the Amino Acid Mixture Reduced Radiation-Related Secretion -- 3.3 Radiation Decreased Electrolyte Absorption -- 4 Conclusions -- References -- Chapter 10: Evaluation of Haemoglobin and Cytochrome Responses During Forearm Ischaemia Using Multi-wavelength Time Domain NIRS -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion -- References. , Chapter 11: Influence of Free Radicals on the Intrinsic MRI Relaxation Properties -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion -- References -- Chapter 12: Inter-individual Differences in Exercise-­Induced Spatial Working Memory Improvement: A Near-Infrared Spectroscopy Study -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion -- References -- Part II: Cancer Oxygenation and Metabolism -- Chapter 13: Tumor Oxygenation Status: Facts and Fallacies -- 1 Introduction -- 2 Facts and Fallacies -- 2.1 Can Typical Diffusion Distances Be Defined in Malignant Tumors? -- 2.2 Equivocal Conversion of In Vivo O2 Partial Pressures into O2 Concentrations -- 2.3 Oxygen Diffusivity in Normal Tissues Versus Malignant Tumors -- 2.4 O2 Depletion Merely Limits Proliferation Rather than Causing Tumor Necrosis -- 2.5 Switching the Warburg Dogma -- 2.6 Hypoxic Subvolumes Are Heterogeneously Distributed Over the Entire Tumor -- 2.7 Oxygen Diffusion Shunt: A Significant Factor in Hypoxia Development -- 2.8 Role of Hypoxia Markers as Surrogates Describing Tumor Oxygenation -- 3 Conclusion -- References -- Chapter 14: Multiparametric Analysis of the Tumor Microenvironment: Hypoxia Markers and Beyond -- 1 Introduction -- 2 Dimensions of Tumor Heterogeneity -- 3 Multiparametric Immunohistochemistry in Registered Serial Sections (MIRSS) -- 4 Multichannel Immunofluorescence Staining Combined with a Quantitative Single-Cell Based Analysis -- 5 Exploring a New Paradigm of Hypoxia-Mediated Treatment Resistance -- 6 Conclusion -- References -- Chapter 15: Computational Simulation of Tumor Hypoxia Based on In Vivo Microvasculature Assessed in a Dorsal Skin Window Chamber -- 1 Introduction -- 2 Methods -- 2.1 Animal Preparations -- 2.2 Fluorescence Imaging -- 2.3 Reaction-Diffusion PDE Model -- 3 Results and Discussion -- 4 Conclusions -- References. , Chapter 16: Hypoxia-Related Tumor Acidosis Affects MicroRNA Expression Pattern in Prostate and Breast Tumor Cells -- 1 Introduction -- 2 Methods -- 2.1 Cell Culture -- 2.2 Measurements -- 3 Results -- 4 Conclusion -- References -- Part III: Brain Oxygenation and Function -- Chapter 17: Cortical and Autonomic Stress Responses in Adults with High Versus Low Levels of Trait Anxiety: A Pilot Study -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion -- References -- Chapter 18: Relation Between EEG Activity and Brain Oxygenation in Preterm Neonates -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion and Conclusions -- References -- Chapter 19: Functional NIRS Measurement of Cytochrome-C-Oxidase Demonstrates a More Brain-Specific Marker of Frontal Lobe Activation Compared to the Haemoglobins -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion -- References -- Chapter 20: Brain Tissue PO2 Measurement During Normoxia and Hypoxia Using Two-Photon Phosphorescence Lifetime Microscopy -- 1 Introduction -- 2 Methods -- 2.1 Animal Preparation -- 2.2 Two-Photon Laser Scanning Microscopy -- 3 Results -- 4 Discussion -- References -- Chapter 21: Age-Related Changes in Physiological Reactivity to a Stress Task: A Near-Infrared Spectroscopy Study -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion -- References -- Chapter 22: Development and Validation of a Sensor Prototype for Near-Infrared Imaging of the Newborn Brain -- 1 Introduction -- 2 Methods -- 2.1 NIROT Sensor Overview -- 2.2 Development of NIROT Sensor -- 2.3 Validation with Phantoms -- 3 Results, Discussion and Conclusion -- References -- Chapter 23: Directional Migration of MDA-MB-231 Cells Under O2/pH Gradients -- 1 Introduction -- 2 Methods and Results -- 3 Discussion -- References. , Chapter 24: Environmental Enrichment Induces Increased Cerebral Capillary Density and Improved Cognitive Function in Mice -- 1 Introduction -- 2 Methods -- 2.1 Environmental Enrichment -- 2.2 Determination of Cerebral Capillary Density -- 2.3 Measurement of Cognitive Function -- 2.4 Statistical Analysis -- 3 Results -- 3.1 Effect of Environmental Enrichment on Cerebral Capillary Density -- 3.2 Effect of Environmental Enrichment on Cognitive Function in Aged Mice -- 4 Discussion -- References -- Chapter 25: Improving Retinal Image Quality Using Registration with an SIFT Algorithm in Quasi-­Confocal Line Scanning Ophthalmoscope -- 1 Introduction -- 2 Method -- 3 Result and Experiment -- 4 Conclusion -- Reference -- Chapter 26: A New Method Based on Graphics Processing Units for Fast Near-Infrared Optical Tomography -- 1 Introduction -- 2 Methods -- 2.1 MC Based fast Reconstruction Algorithm -- 2.2 Simulation Study on a Tissue Model Containing Air -- 2.3 Phantom Measurements -- 3 Results and Discussion -- 3.1 Simulation Results -- 3.2 Experimental Results -- 4 Conclusions -- References -- Chapter 27: PFC Blood Oxygenation Changes in Four Different Cognitive Tasks -- 1 Introduction -- 2 Methods -- 3 Results -- 4 Discussion -- References -- Chapter 28: Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse -- 1 Introduction -- 2 Methods -- 2.1 Animals -- 2.2 Middle Cerebral Artery Occlusion (MCAO) -- 2.3 Western Blot Analysis -- 2.4 Metabolic Panels: GCMS-Based Analysis -- 2.5 Statistical Analysis -- 3 Results -- 3.1 Diet-Induced Ketosis on Infarct Volume Following MCAO in Mice -- 3.2 Diet Induced Ketosis on HIF-1α Accumulation, AKT Activation, AMPK and Metabolites -- 4 Discussion -- References. , Chapter 29: Evaluation of Pleasure-Displeasure Induced by Use of Lipsticks with Near-Infrared Spectroscopy (NIRS): Usefulness of 2-Channel NIRS in Neuromarketing.

Note: Intro -- Preface -- Contents -- List of Contributors -- Reviewers of the Subgroup Book -- Part I Subgroups in Clinical Trial Design and Analysis -- 1 Issues Related to Subgroup Analyses and Use of Intensive Stratification -- 1.1 Introduction -- 1.2 Issues in Interpreting Subgroup Data -- 1.2.1 Confounding Due to Sampling Error -- 1.2.2 Confounding Due to Repeated Hypothesis Testing -- 1.2.3 Confounding Due to Lack of Statistical Power -- 1.2.4 Confounding Due to Baseline Incomparability -- 1.3 Intensive Stratification in Subgroup Analysis -- 1.4 Statistical Simulations -- 1.4.1 Setting -- 1.4.2 Results -- 1.5 Conclusion -- References -- 2 Biomarker-Targeted Confirmatory Trials -- 2.1 Introduction -- 2.2 Inference Errors in an All-Comer Design -- 2.3 Multiple-Step Inferences for the Overall Population and Marker Subgroups -- 2.4 Simultaneous Inferences for the Overall Population and Marker-Positive Subgroup -- 2.5 Extension to Sequential Analysis -- 2.6 Discussion -- References -- 3 Data-Driven and Confirmatory Subgroup Analysisin Clinical Trials -- 3.1 Introduction -- 3.2 Overview of Regulatory Guidance for Subgroup Analysis -- 3.2.1 International Framework: ICH Guidelines -- 3.2.2 Multi-Regional Clinical Trials: Case Study -- 3.2.3 FDA Regulations -- 3.2.4 EMA Regulations -- 3.2.5 China National Medical Product Administration (NMPA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) Regulations -- 3.3 Data-Driven Subgroup Analysis -- 3.3.1 Key Principles of Data-Driven Subgroup Analysis -- 3.3.2 Types of Data-Driven Subgroup Analyses -- 3.3.3 ``Guideline Driven'' Versus Data-Driven Subgroup Analysis -- 3.3.4 Case Study -- 3.3.5 Typology of Data-Driven Subgroup Analysis Methods -- 3.3.5.1 Global Outcome Modeling -- 3.3.5.2 Global Treatment Effect Modeling -- 3.3.5.3 Modeling Individual Treatment Regimes. , 3.3.5.4 Local Modeling (Direct Subgroup Search) -- 3.3.5.5 Summary of Key Features of Data-Driven Methods -- 3.4 Confirmatory Subgroup Analysis -- 3.4.1 Multi-Population Trials -- 3.4.2 Multiplicity Issues in Multi-Population Trials -- 3.4.2.1 Traditional Multiplicity Problems -- 3.4.2.2 Advanced Multiplicity Problems -- 3.4.2.3 Clinical Scenario Evaluation Approach -- 3.4.3 Decision-Making Framework in Multi-Population Trials -- 3.4.4 Adaptive Designs in Multi-Population Trials -- 3.4.4.1 Adaptive Trials with Pre-planned Subpopulations -- 3.4.4.2 Adaptive Trials with Data-Driven Subpopulations -- 3.5 Discussion -- References -- 4 Considerations on Subgroup Analysis in Design and Analysis of Multi-Regional Clinical Trials -- 4.1 Introduction -- 4.2 Trial Design Considerations -- 4.2.1 Region Definition -- 4.2.2 Regional Requirements -- 4.2.3 Randomization -- 4.3 Models and the Overall Sample Sizes -- 4.4 Considerations for Regional Subgroup Analysis -- 4.5 Trial Conduct -- 4.6 Interpretation of Results -- 4.7 The Regular Subgroup Analyses -- 4.8 Discussion -- References -- Part II Subgroup Identification and Personalized Medicine -- 5 Practical Subgroup Identification Strategies in Late-Stage Clinical Trials -- 5.1 Introduction -- 5.2 Case Study -- 5.3 SIDES-Based Subgroup Identification Methods -- 5.3.1 Subgroup Generation Algorithm -- 5.3.2 Subgroup and Biomarker Selection Tools -- 5.3.3 Subgroup Interpretation Tools -- 5.4 Practical Considerations in Subgroup Identification -- 5.4.1 Candidate Biomarkers -- 5.4.2 Primary Analysis Model -- 5.5 Subgroup Search Strategies in the BPH Trial -- 5.5.1 Less Formal Subgroup Search Strategy -- 5.5.2 More Formal Subgroup Search Strategy -- 5.6 Simulation Study -- 5.7 Discussion -- References -- 6 The GUIDE Approach to Subgroup Identification -- 6.1 Introduction -- 6.2 Univariate Uncensored Response. , 6.2.1 Node Models -- 6.2.2 Split Variable Selection -- 6.2.3 Split Set Selection -- 6.2.3.1 Ordinal Variable -- 6.2.3.2 Categorical Variable -- 6.3 Bootstrap Confidence Intervals -- 6.4 Multivariate Uncensored Responses -- 6.5 Time-to-Event Response -- 6.6 Concluding Remarks -- References -- 7 A Novel Method of Subgroup Identification by Combining Virtual Twins with GUIDE (VG) for Development of Precision Medicines -- 7.1 Introduction -- 7.2 Methods -- 7.2.1 Step I -- 7.2.2 Step II -- 7.3 Simulations -- 7.3.1 Set-up -- 7.3.2 Results -- 7.4 Case Study -- 7.4.1 Type I Error Control -- 7.4.2 Bootstrap -- 7.4.3 Application -- 7.5 Discussion -- References -- 8 Subgroup Identification for Tailored Therapies: Methods and Consistent Evaluation -- 8.1 Background -- 8.2 A Resampling-Based Ensemble Tree Method to Identify Patient Subgroups with Enhanced Treatment Effect -- 8.3 Consistent Assessment of Biomarker and Subgroup Identification Methods -- 8.3.1 Data Generation -- 8.3.2 Performance Measurement -- 8.4 Simulation Study -- 8.5 Concluding Remarks -- References -- 9 A New Paradigm for Subset Analysis in RandomizedClinical Trials -- 9.1 Introduction -- 9.2 Methods -- 9.2.1 Predictive Classifiers -- 9.2.2 De-biasing the Re-substitution Estimates -- 9.2.3 Pre-validated Estimates of Treatment Effect -- 9.2.4 Testing Treatment Effects in Subsets S2 , S1 and S0 -- 9.2.5 PPV and NPV of the Predictive Classifier -- 9.2.6 Calibration of Pre-Validated Treatment Effects -- 9.3 Discussion -- References -- 10 Logical Inference on Treatment Efficacy When Subgroups Exist -- 10.1 Introduction -- 10.2 Fundamental Statistical Considerations When Subgroups Exist -- 10.2.1 Treatment Efficacy Measures -- 10.2.1.1 Which Group(s) Need to Be Assessed? -- 10.2.1.2 Logic-Respecting Efficacy Measures -- 10.2.1.3 Prognostic or Predictive?. , 10.2.2 Inference on Mixture Populations -- 10.2.2.1 Marginal Means -- 10.2.2.2 LSmeans -- 10.3 Subgroup Mixable Inference Procedure -- 10.3.1 The General SME Principle -- 10.3.2 Simultaneous Confidence Intervals -- 10.3.3 Application of SME on Binary Outcomes -- 10.3.3.1 Theoretical Derivations -- 10.3.3.2 A Real Example -- 10.3.4 Application of SME on Time-to-Event Outcomes -- 10.3.4.1 Theoretical Derivations -- 10.3.4.2 A Real Example -- 10.4 Discussion -- 10.4.1 Additional Issues or Challenges -- 10.4.2 Moving Forward -- References -- 11 Subgroup Analysis with Partial Linear Regression Model -- 11.1 Introduction -- 11.2 The Method -- 11.2.1 The Semiparametric Model Specification -- 11.2.2 Estimation of Model Parameters -- 11.2.2.1 Computation of g(r+1) -- 11.2.3 Asymptotic Results of the Estimates -- 11.3 Testing the Null Hypothesis and the Classification Rules -- 11.3.1 Test the Null Hypothesis -- 11.3.2 The Classification Rule -- 11.4 Simulation Study and Application -- 11.4.1 Simulation Study -- 11.4.2 Application to Real Data Problem -- 11.5 Conclusion -- References -- 12 Exploratory Subgroup Identification for Biopharmaceutical Development -- 12.1 Introduction -- 12.2 Single Biomarker Signature -- 12.2.1 Prognostic Biomarker Signature Analysis -- 12.2.2 Predictive Biomarker Signature Analysis -- 12.2.3 A Framework for Robust Cutoff Derivation -- 12.3 Complex Biomarker Signature -- 12.3.1 Scoring-Based Methods -- 12.3.2 Rule-Based Methods -- 12.3.2.1 Sequential BATTing -- 12.3.2.2 AIM-Rule -- 12.4 Model Evaluation: Nested Cross-Validation -- 12.5 Optimizing Long-Term Treatment Strategy: An Example of Subgroup Identification Leading to Label Inclusion -- 12.5.1 Motivation and Background -- 12.5.2 Method -- 12.5.3 Result -- 12.6 Discussion -- References. , 13 Statistical Learning Methods for Optimizing Dynamic Treatment Regimes in Subgroup Identification -- 13.1 Introduction -- 13.2 Conceptual Framework -- 13.2.1 Q-learning -- 13.2.2 Outcome-Weighted Learning -- 13.2.2.1 Outcome-Weighted Learning Without Augmentation -- 13.2.2.2 Augmented Outcome-Weighted Learning (AOL) -- 13.2.2.3 Surrogate Loss Functions in Outcome-Weighted Learning -- 13.2.3 Evaluation of DTRs -- 13.3 Estimation and Algorithm -- 13.3.1 Q-learning -- 13.3.2 Outcome-Weighted Learning -- 13.3.2.1 Under SVM Hinge Loss -- 13.3.2.2 Under SVM Ramp Loss -- 13.3.2.3 Under Binomial Deviance Loss -- 13.3.2.4 Under L2 Loss -- 13.3.2.5 Tuning Parameters -- 13.3.3 Handling Observational Study Data -- 13.3.4 DTR Evaluation and Future Use -- 13.3.4.1 Empirical Value Function and Benefit Function -- 13.3.4.2 Apply the Learned DTR to an Independent Sample -- 13.4 Software and Illustrations -- 13.4.1 DTR Estimation -- 13.4.1.1 Q-learning -- 13.4.1.2 Outcome-Weighted Learning -- 13.4.2 Apply the Estimated DTR to an Independent Sample -- 13.4.3 Other Details -- 13.5 Simulations and Real Data Implementation -- 13.5.1 Simulations -- 13.5.2 Illustration of the Real Data Implementation -- 13.6 Summary -- References -- Part III General Issues About Subgroup Analysis, Including Regulatory Considerations -- 14 Subgroups in Design and Analysis of Clinical Trials, General Considerations -- 14.1 General Issues in Subgroup Analysis as Part of the Overall Evaluation of a Clinical Trial -- 14.1.1 Successful Trial for the Overall Study Population -- 14.1.2 Failed Trial for the Intended Overall Patient Population -- 14.2 Trial Design Considerations to Establish Treatment Efficacy in Specific Subgroup of Patients -- 14.3 Bayesian Subgroup Analysis -- 14.4 Summary -- References -- 15 Subgroup Analysis: A View from Industry -- 15.1 Introduction. , 15.2 Defining a Subgroup Effect.