physiology and pathophysiology of stress and distress. Modeling this knowledge across species and strains would both enlarge our understanding of distress and enable translational approaches to human diseases as well as improvements in animal welfare. The absence of a consensus definition of distress affects the evaluation of distress and its impact on animal welfare in veterinary, scientific, and legislative contexts; integrative research approaches could be immensely helpful in this area.

  • The development of possible distress predictors could serve as the basis for a predictive scoring system for laboratory animals, similar to the system used for the severity of illness in human intensive care units (Knaus et al. 1985, 1991). The ability to perform standardized, quantitative, and comprehensive evaluations of animals in poor health or in distress would enable teams to make decisions about continued treatment versus euthanasia faster and with greater consensus. Such a system would further assist important decisions about the adoption and/or refinement of humane endpoints before the initiation of experiments, especially if the clinical assessment is validated through postmortem examinations. As shown in the Appendix, score sheets can be used to identify any number of abnormal signs, some of which will help diagnose the cause of the abnormality or will be relevant to individual research protocols. While some of the clinical observations and test results would be common among various experiments, the creation of a standardized predictive scoring system for distress is predicated upon a definition of distress and identification of the crucial parameters that accompany its clinical presentation.

  • New research could delineate the mechanisms of possible associations between stress/distress and disease behaviors or abnormal behaviors (e.g., stereotypies). Collaborative investigation is necessary to identify the neural processes, systems, and pathways that regulate active or passive coping in stressful situations, “permit” development of distress, or enable abnormal behaviors. Because stereotypies may adversely affect research outcomes and lead to invalidated studies and the need for repetitions, research is essential to determine, among other things, whether their presence could serve as a reliable indicator of animal welfare.

  • With the genetic manipulation of increasing numbers of animal species and the creation of new animal types (e.g., “humanized” mice) to better mimic human pathophysiology and disease, it is crucial to have a deeper and complete understanding of how the characteristics of an organism (such as gender or age) or its manipulated genotype can influence the development of distress (for an example



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