Note: Front Cover -- Research in Medical and Biological Sciences -- Copyright Page -- Contents -- List of Contributors -- Preface -- 1 Philosophy of Science -- 1.1 Introduction -- 1.2 Philosophy of the Natural Sciences -- 1.3 What Is Science? Differentiating Science from Nonscience -- 1.4 Knowledge and Truth: What is Knowledge and What Constitutes a Scientific Fact? -- 1.5 The Glue That Holds the World Together: Causation -- 1.5.1 Necessary Conditions -- 1.5.2 Sufficient Conditions -- 1.5.3 Combination of Conditions that Together are Necessary and Sufficient -- 1.5.4 Combination of Conditions that Together are Sufficient -- 1.5.5 Probabilistic Causation -- 1.5.6 Counterfactual Conditions -- 1.6 Scientific Explanation -- 1.7 Modes of Inference -- 1.8 What Science Is About -- 1.9 Scientific Rationality -- 1.10 Hypothesis Testing -- 1.10.1 Hypothetical-Deductive Method -- 1.11 The Aim of Science: Reducing Uncertainty -- 1.12 The Empirical Turn in the Philosophy of Science: Science in Society -- 1.13 Philosophy of the Social Sciences -- 1.14 Interpretation, Understanding, and Explanation -- 1.14.1 Explanation and Understanding -- 1.14.2 Interpretation -- 1.15 The Hermeneutic Circle, Horizon of Understanding, and "Double Hermeneutics" -- 1.16 Power, Ideology, and Interests -- 1.17 Validity -- 1.18 Reductionism and Emergence -- 1.19 Generalization -- Questions to Discuss -- Acknowledgments -- References -- Further Reading -- 2 Ethics and Scientific Conduct -- 2.1 Why the Current Focus on Scientific Misconduct? -- 2.2 What Do We Know About Scientific Misconduct? -- 2.3 What Is Wrong with Scientific Misconduct? -- 2.3.1 Consequentialism -- 2.3.2 Deontological Ethics -- 2.3.3 Virtue Ethics -- 2.4 Scientific Conduct and Misconduct -- 2.4.1 Internal Norms -- 2.4.2 Linkage Norms and External Norms. , 2.5 Scientific Misconduct That Affects the Truth Claims of Scientific Findings -- 2.5.1 Wrong Observations and Wrong Analysis -- 2.5.2 Plagiarism -- 2.5.3 Fabrication -- 2.6 Authorship -- 2.6.1 Exclusion from Authorship -- 2.6.2 Gift Authorship -- 2.6.3 Authorship by Coercion -- 2.6.4 Unsolicited Authorship -- 2.6.5 Ghost Authorship -- 2.6.6 Refusal to Accept Responsibility -- 2.7 Salami, Imalas, and Duplicate Publication -- 2.8 The Investigation, Prevention, and Punishment of Scientific Misconduct -- Questions to Discuss -- Appendix 1 ICMJE Recommendations on the Role of Authors and Contributors -- Why Authorship Matters -- Who Is an Author? -- Nonauthor Contributors -- References -- Further Reading -- 3 Ethics in Human and Animal Studies -- 3.1 Basic Principles of Human Biomedical Research Ethics -- 3.2 International Regulation -- 3.2.1 Consent -- 3.2.2 Inability to Consent -- 3.2.3 Randomized Controlled Trials -- 3.2.4 Vulnerable Research Participants -- 3.2.5 Epidemiological Research, "Big Data," and Biobank Research -- 3.2.6 The Role of RECs -- 3.2.7 Data Protection, Good Clinical Practice, and Other Regulations Influencing Biomedical Research Ethics -- 3.3 The Ethics of Animal Research -- 3.3.1 Animal Research and Other Human Uses of Animals -- Questions to Discuss -- References -- Further Reading -- 4 Research Strategies, Planning, and Analysis -- 4.1 Introduction -- 4.2 Identifying Scientific Problems -- 4.3 The Experimental Design -- 4.4 Data Types -- 4.5 Methods and Experimental Techniques -- 4.6 Experimental Research Checklist -- 4.7 Repeatability, Reproducibility, and Reliability -- 4.8 Multifactorial Relationships and Observational Studies -- 4.9 Validity, Effect Estimate, and Choice of Statistical Test -- 4.10 Research Protocol -- 4.11 Experimental Routines -- Acknowledgments -- Questions to Discuss -- References -- Further Reading. , 5 Literature Searches and Reference Management -- 5.1 Information Literacy -- 5.2 Literature Searches -- 5.2.1 Bibliographic Databases -- 5.2.2 Sources of Information -- 5.2.2.1 Primary Sources of Information and Primary Studies -- 5.2.2.2 Secondary Sources of Information and Secondary Studies -- 5.2.3 The Evidence Pyramid -- 5.2.4 Search Strategy -- 5.3 Establishment of a Search Query -- 5.3.1 PICO: A Focused Approach -- 5.3.2 Boolean Operator -- 5.4 Selection of Relevant Sources of Information -- 5.5 Search Techniques -- 5.5.1 Thesaurus Mapping -- 5.5.2 Federated Search -- 5.5.3 Free-Text Search -- 5.5.4 Searching by Index Term Versus Publication Type -- 5.5.5 Methodology Filters -- 5.5.5.1 PubMed Filters-Clinical Queries -- 5.5.5.2 Searching for Qualitative Research -- 5.6 Critical Assessment -- 5.6.1 Abstracts -- 5.6.2 Errata and Retracted Publications -- 5.7 Bibliometric Measures -- 5.7.1 Impact Factors -- 5.7.2 The Highly-Cited Index -- 5.8 Principal Scientific Bibliographic Databases -- 5.8.1 Medline -- 5.8.2 PubMed -- 5.8.3 EMBASE -- 5.8.4 Web of Science -- 5.8.5 BIOSIS Previews -- 5.8.6 PsycINFO -- 5.8.7 Cumulative Index to Nursing and Allied Health Literature -- 5.8.8 Cochrane Library -- 5.8.8.1 Cochrane Reviews -- 5.8.8.2 Other Reviews -- 5.8.8.3 Trials -- 5.8.8.4 Economic Evaluation -- 5.9 Staying Up to Date -- 5.9.1 Saving Search Strategies -- 5.9.2 Alert Services -- 5.9.3 Awareness Tools: Apps for Mobile Devices -- 5.9.3.1 BrowZine (for iOS and Android Devices) -- 5.9.3.2 Docphin (for iOS and Android Devices) -- 5.9.3.3 Read by QxMD (for iOS Devices, Coming on Android) -- 5.10 Medical and Scientific Internet Search Engines -- 5.10.1 Google Scholar -- 5.10.2 MacPLUS -- 5.10.3 SUMSearch2 -- 5.10.4 General Guidelines for Internet Searches -- 5.11 Finding Research Protocols and Ongoing Projects -- 5.12 Reference Management. , 5.12.1 Efficient Handling of References, Publications, and Manuscripts -- 5.12.2 EndNote -- 5.12.2.1 Settings for an EndNote Library -- 5.12.2.2 Journal Index -- 5.12.2.3 Entering References -- 5.12.2.4 Organizing References -- 5.12.2.5 Cite While You Write -- 5.12.2.6 Reference Lists-"Output Styles" -- 5.13 Open Access Publication, Copyright, and Self-Archiving -- 5.13.1 Open Access Publication -- 5.13.2 Retaining Copyright and Self-Archiving -- 5.13.3 Citing -- Questions to Discuss -- References -- Further Reading -- 6 Basic Medical Science -- 6.1 Introduction -- 6.2 Long-Term Goals and Specific Aims -- 6.3 Background and Significance -- 6.4 Experimental Strategies and Methods -- 6.5 Levels of Research-from Organisms to Cells -- 6.6 Research on Experimental Animals -- 6.7 The Three rs -- 6.8 Animal Models -- 6.9 Mouse Models for Studies of Mammalian Development and Disease -- 6.10 Legislation -- 6.11 Notes on the Use of Experimental Animals -- 6.12 Commonly Used Experimental Animals -- 6.13 Cell and Tissue Culture -- 6.14 An Overview of Selected Technical Developments -- 6.15 Applications of Cell Culture -- 6.16 Manipulation of Cultured Cells -- 6.17 Possibilities Provided by Molecular Biological Techniques -- Questions to Discuss -- References -- Further Reading -- 7 Translational Medical Research -- 7.1 Introduction -- 7.2 An Old Success Story-Aspirin -- 7.3 Research Provides a Path to Understanding Mechanisms and New Drugs -- 7.4 The Importance of Understanding Drug Metabolism-The Rise and Fall of Clopidogrel (Plavix) -- 7.5 The Need for More Translational Medical Research -- 7.6 Translational Medical Research and the Development of Orphan Drugs -- 7.7 From Rare Disorders to Common Disorders -- 7.8 Target-Based Drug Development-Aquaporins -- 7.9 Training of Investigators for Translational Medical Research. , 7.10 Collaboration Between Academia and the Pharmaceutical Industry -- Questions to Discuss -- References -- Further Reading -- 8 Clinical Research -- 8.1 Introduction -- 8.2 The Research Process-Important Steps -- 8.3 Controlled Clinical Trials -- 8.4 Drug Development -- 8.5 Clinical Trial Protocol -- 8.6 Trial Designs -- 8.7 Target Population -- 8.8 Historical Controls -- 8.9 Randomization -- 8.9.1 Stratification -- 8.9.2 Minimization -- 8.10 Blinding -- 8.11 Choice of Endpoints -- 8.12 Sample Size Estimation -- 8.12.1 Power -- 8.12.2 Sample Size Estimation for Categorical Outcomes -- 8.12.3 Sample Size Estimation for Continuous Outcomes -- 8.12.3.1 Pairs of Observations -- 8.12.3.2 Two Independent Samples (Parallel Group Trials) -- 8.12.3.3 Unequal Group Size -- 8.12.4 Sample Size Estimation Based on Precision of Estimates -- 8.12.4.1 Categorical Outcome -- 8.12.4.2 Continuous Outcome -- 8.13 Statistical Analysis -- 8.13.1 Analysis Sets -- 8.13.2 Handling of Missing Values -- 8.13.3 Analysis Strategies -- 8.13.3.1 Factorial Trials -- 8.13.3.2 Repeated Measurements -- 8.13.4 Multiple Endpoints -- 8.13.5 Interim Analyses -- 8.13.6 Subgroup Analyses -- 8.14 Personalized Medicine -- 8.15 Noninferiority Trials -- 8.16 Sources and Control of Bias -- 8.17 Generalization of Trial Results -- 8.18 Regulatory Issues -- Questions to Discuss -- Acknowledgments -- References -- 9 Epidemiology -- 9.1 Introduction -- 9.2 The Definition of Epidemiology -- 9.3 The Role of Epidemiology -- 9.3.1 Study Designs -- 9.4 Target Population, Source Population, and Study Sample -- 9.5 Disease Occurrence, Risk, Association, Importance, and Implication -- 9.5.1 Denominators, Numerators, and Time -- 9.5.2 Measures of Disease Occurrence and Risk (Incidence and Prevalence) -- 9.5.3 The Importance of Vital Statistics in an Epidemiological Setting -- 9.5.4 Mortality Rates. , 9.5.5 Cause of Death Statistics.