Report of the Working Group on Animal Distress in the Laboratory

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and often measures that alleviate one do not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining ‘distress,’ propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals

Survey of Canadian Animal-Based Researchers' Views on the Three Rs: Replacement, Reduction and Refinement

The ‘Three Rs’ tenet (replacement, reduction, refinement) is a widely accepted cornerstone of Canadian and international policies on animal-based science. The Canadian Council on Animal Care (CCAC) initiated this web-based survey to obtain greater understanding of ‘principal investigators’ and ‘other researchers’ (i.e. graduate students, post-doctoral researchers etc.) views on the Three Rs, and to identify obstacles and opportunities for continued implementation of the Three Rs in Canada. Responses from 414 participants indicate that researchers currently do not view the goal of replacement as achievable. Researchers prefer to use enough animals to ensure quality data is obtained rather than using the minimum and potentially waste those animals if a problem occurs during the study. Many feel that they already reduce animal numbers as much as possible and have concerns that further reduction may compromise research. Most participants were ambivalent about re-use, but expressed concern that the practice could compromise experimental outcomes. In considering refinement, many researchers feel there are situations where animals should not receive pain relieving drugs because it may compromise scientific outcomes, although there was strong support for the Three Rs strategy of conducting animal welfare-related pilot studies, which were viewed as useful for both animal welfare and experimental design. Participants were not opposed to being offered “assistance” to implement the Three Rs, so long as the input is provided in a collegial manner, and from individuals who are perceived as experts. It may be useful for animal use policymakers to consider what steps are needed to make replacement a more feasible goal. In addition, initiatives that offer researchers greater practical and logistical support with Three Rs implementation may be useful. Encouragement and financial support for Three Rs initiatives may result in valuable contributions to Three Rs knowledge and improve welfare for animals used in science

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review

<div><p>The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30–40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18–0.34, I² 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.</p></div

Pedagogical Merit Review of Animal Use for Education in Canada.

There are two components to the review of animal based protocols in Canada: review for the merit of the study itself, and review of the ethical acceptability of the work. Despite the perceived importance for the quality assurance these reviews provide; there are few studies of the peer-based merit review system for animal-based protocols for research and education. Institutional animal care committees (ACC)s generally rely on the external peer review of scientific merit for animal-based research. In contrast, peer review for animal based teaching/training is dependent on the review of pedagogical merit carried out by the ACC itself or another committee within the institution. The objective of this study was to evaluate the views of ACC members about current practices and policies as well as alternate policies for the review of animal based teaching/training. We conducted a national web-based survey of ACC members with both quantitative and qualitative response options. Responses from 167 ACC members indicated broad concerns about administrative burden despite strong support for both the current and alternate policies. Participants' comments focused mostly on the merit review process (54%) relative to the efficiency (21%), impact (13%), and other (12%) aspects of evaluation. Approximately half (49%) of the comments were classified into emergent themes that focused on some type of burden: burden from additional pedagogical merit review (16%), a limited need for the review (12%), and a lack of resources (expertise 11%; people/money 10%). Participants indicated that the current system for pedagogical merit review is effective (60%); but most also indicated that there was at least some challenge (86%) with the current peer review process. There was broad support for additional guidance on the justification, criteria, types of animal use, and objectives of pedagogical merit review. Participants also supported the ethical review and application of the Three Rs in the review process. A clear priority from participants in the survey was updating guidance to better facilitate the merit review process of animal-based protocols for education. Balancing the need for improved guidance with the reality of limited resources at local institutions will be essential to do this successfully; a familiar dilemma to both scientists and policy makers alike

Participant Experience (N = 167).

<p>Participant Experience (N = 167).</p

Participant Characteristics (N = 167).

<p>Participant Characteristics (N = 167).</p

Quantitative Responses for Questions 8–20

<p>Quantitative Responses for Questions 8–20</p