Cover -- Title Page -- Copyright Page -- Contents -- List of contributors -- Foreword -- Chapter 1 Introduction -- PART 1 IMPLEMENTING THE THREE RS IN RESEARCH USING ANIMALS -- Chapter 2 The Three Rs -- Opening remarks -- Introduction -- Simple words, complex meanings -- The origin and evolution of the Three Rs -- A holistic approach to the Three Rs -- Replacement -- Replacement strategies -- Replacement methods -- The high-fidelity fallacy -- Reduction -- Experimental design -- Re-use of animals -- Optimising animal production -- Refinement -- Assessing animal well-being -- Severity scoring systems -- Observation schedules -- Contingent and direct harms -- Humane endpoints -- Responsibility for the Three Rs -- The individual -- The institution -- Funding bodies -- Scientific journals -- International and national efforts -- Concluding remarks -- References -- Chapter 3 The design of animal experiments -- Introduction -- The research strategy -- Choosing the animal and procedure -- Defining the purpose of the experiment -- The decision-making process -- Variation among the animals -- Steps in the design of an experiment -- Defining which dependent variables to measure -- Defining which effects to investigate -- Identifying the experimental unit -- Determining the sample size (replication of the experimental units) -- Assessing the measurement and procedural variability -- Choosing an experimental design -- Randomising the experiment -- Blinding the experiment -- Performing the statistical analysis -- Reporting the results of the experiment -- Types of experimental designs -- The completely randomised design -- The randomised block design -- The Latin square design -- The cross-over design -- The factorial design -- The repeated measures design -- Types of statistical analysis -- ANOVA and the t-test -- Analysis of covariance.

The chi-squared and Fisher's exact tests for discrete data (counts) -- The non-parametric tests -- Summary -- Concluding remarks -- Acknowledgements -- References -- Chapter 4 An introduction to laboratory animal genetics -- Introduction -- Molecular genetics -- DNA - the molecule of inheritance -- Protein-coding DNA -- Gene structure -- Chromosomes -- Genes and alleles -- Protein synthesis -- Regulatory DNA and cell-specificity -- Other non-coding DNA -- Mutations and variation -- Genetics and the laboratory animal -- Gene nomenclature -- Inbred strains -- Genetic drift -- Substrains -- Maintaining inbred strains -- Characteristics of an inbred line -- Selecting an appropriate inbred strain -- Inbred strains of other species -- Outbred strains -- GA laboratory animals -- Terminology -- Spontaneous mutations -- Inducing mutations in laboratory animals -- Gene editing - a revolution for the generation of GA animal models -- Concluding remarks -- Acknowledgements -- References -- Chapter 5 Phenotyping of genetically modified mice -- Introduction -- The welfare of GM animals -- Welfare assessment -- Phenotypic characterisation -- Systematic, broad-based phenotyping -- Early phenotyping protocols -- The Mouse Phenome Project -- Eumorphia -- From EUMODIC to IMPC -- Hypothesis-driven phenotyping -- Before phenotyping - search for information -- Testing for new traits - the hierarchical approach -- Phenotyping - how far do you take it? -- Issues with conventional phenotyping in mice -- Automated in-cage behavioural phenotyping -- Phenotyping challenges - the environment -- Phenotyping challenges - other issues -- Age and sex -- Genetics -- Controls -- Number of animals -- Scientific reporting -- Summary -- Concluding remarks -- Acknowledgement -- References -- Chapter 6 Brief introduction to welfare assessment: a 'toolbox' of techniques -- Introduction.

Basic principles of welfare assessment -- Considerations when assessing welfare -- The 'welfare assessment toolbox' -- Routine welfare monitoring -- Assessing welfare and changes in welfare: physiological measures -- Assessing welfare and changes in welfare: behavioural measures -- Assessing welfare and changes in welfare: brain measures -- Assessing animals' preferences and motivation for resources -- Consumer demand -- Assessing pain -- Concluding remarks -- Acknowledgements -- References -- Chapter 7 Welfare and 'best practice' in field studies of wildlife -- Introduction -- Reasons for wildlife research -- Welfare impacts of wildlife studies -- Effects of stress -- Injuries -- Other welfare effects -- The three Rs and welfare -- Replacement -- Reduction -- Refinement -- Capture, handling, release -- General welfare issues -- Capture -- Handling -- Anaesthesia -- Sampling -- Marking -- Release -- To treat or not to treat? -- Legislation appropriate to wildlife studies -- Legislation relating to the use of animals in research -- Wildlife and Countryside Acts -- Other wildlife legislation -- Licences -- International legislation -- Best practice' guidelines -- UK -- Worldwide -- Summary -- References -- Chapter 8 Legislation and oversight of the conduct of research using animals: a global overview -- Introduction -- History -- Principles -- The Three Rs -- International Guiding Principles for Biomedical Research Involving Animals -- The World Organisation for Animal Health (OIE) -- Engineering versus performance standards -- Adequate veterinary care -- Training and competence -- Institutional and governmental review, oversight and authorisation of animal activities -- Inspection and compliance -- International accreditation of animal care and use programmes -- Regional and international harmonisation of guidelines -- Europe.

Harmonisation in the region -- From ETS 123 to Directive 2010/63/EU -- Levels of authorisation to work with animals -- Other important aspects of the European framework -- North America -- Canada -- The United States -- Asia -- Japan -- Republic of Korea -- People's Republic of China -- Taiwan, ROC -- India -- Singapore -- Australia and New Zealand -- Australia -- New Zealand -- Examples of oversight elsewhere in the world -- Latin America -- Russian Federation -- Israel -- South Africa -- References -- Chapter 9 Planning, design and construction of the modern animal facility -- Introduction -- Overriding requirements for all research animal facilities -- Project brief -- Types of animal research facility -- Facility accommodation factors -- Legislation -- Procurement models -- Project procurement strategy -- Contractor procurement models -- The client team -- The role of user advisors -- Documentation of the User Requirement Specification (URS) -- Cost consultants -- Budget -- Value engineering (VE) -- The design process -- Project stages as defined by RIBA -- The project team -- Project manager (PM) -- Design team -- Architect -- Services engineer (mechanical, electrical and plumbing services - MEP) -- Fire protection engineer (FP) -- Structural engineer (SE) -- Construction team -- Main contractor -- The sub-contractors -- The suppliers -- Heating, ventilation and air conditioning (HVAC) -- Building management system (BMS) -- Specifications -- Prescriptive specifications -- Performance specifications -- Commissioning -- Pre-handover demonstration of facility reliability -- Verification, validation, stability, reliability -- FRT process -- System/Equipment failure -- Special requirements for research animal facilities -- Environment -- Barrier integrity -- Acceptance of FRT data -- Soft Landings -- Conclusions -- Acknowledgement -- References.

Chapter 10 Environmental enrichment: animal welfare and scientific validity -- Introduction -- Terminology -- Approaches to enrichment -- Why is enrichment needed? -- Animal behaviour and enrichment in captive environments -- Behaviour in captivity associated with poor welfare -- Behaviour in captivity associated with good welfare -- Effect of environmental enrichment on behaviour and welfare -- Effects of enrichment on experimental outcomes -- Bias and internal validity -- Precision and test sensitivity -- External validity and replicability -- Conclusions -- Factors to consider when choosing enrichment -- What are the benefits of the proposed enrichment? -- Enrichment and animal safety -- Enrichment and human safety -- Enrichment and the experiment -- Validating new enrichment -- Managing an enrichment programme -- Acknowledgement -- References -- Chapter 11 Special housing arrangements -- Introduction -- Types of containment -- Protective clothing -- The animal room -- Flexible film isolators -- Rigid isolators -- Individually ventilated cages -- Filter-top cages -- Ventilated cabinets -- Laminar flow booths or cubicles -- Bespoke systems -- Species -- Mice -- Rats -- Hamsters -- Guinea pigs -- Rabbits -- Ferrets -- Nonhuman primates -- Welfare considerations with the use of containment systems for nonhuman primates -- Pigs -- Ruminants -- Birds -- Checklist for containment -- Legislative requirements -- The future -- References -- Chapter 12 Transportation of laboratory animals -- Introduction -- General principles and requirements -- The health and welfare of animals -- Health and infectious status -- Considerations for Animal Models with Special Needs -- Animal provisions during shipment -- Transport container design and construction -- Transport container stocking density -- Stressors during animal transport -- Journey planning.