Monkey research in China: developing a natural resource.
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China's contribution to primate research is no longer limited to supplying monkeys to scientists abroad. With an abundance of wild rhesus macaques, low labor costs, and a nonhostile environment for animal research, scientists are finding that China is the place to be for research using macaques as models of human disease. (+info)
Refining animal models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use.
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BACKGROUND: In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation) in concert with the AO Research Institute (ARI), and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research. METHODS: The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: RESULTS & CONCLUSION: Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS) according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1) Intelligent study designs to receive appropriate answers; 2) Minimal complication rates (5 to max. 10%); 3) Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA) audit of protocols in GLP studies; 4) Sufficient details for materials and methods applied; 5) Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences); 6) Post-operative management with emphasis on analgesia and follow-up examinations; 7) Study protocols to satisfy criteria established for a "justified animal study"; 8) Surgical expertise to conduct surgery on animals; 9) Pilot studies as a critical part of model validation and powering of the definitive study design; 10) Criteria for funding agencies to include requirements related to animal experiments as part of the overall scientific proposal review protocols. Such agencies are also encouraged to seriously consider and adopt the recommendations described here when awarding funds for specific projects. Specific new requirements and mandates related both to improving the welfare and scientific rigour of animal-based research models are urgently needed as part of international harmonization of standards. (+info)
All is not well in the world of translational research.
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It is not unusual for novel treatment strategies to fail in clinical trials, despite highly encouraging results in preclinical proof-of-concept studies. Typically, such "failures of translation" are blamed on the poor predictiveness of animal models. Often, however, the poor predictiveness of today's preclinical proof-of-concept studies is related not to limitations of the models but to investigator bias and a lack of scientific rigor. The resulting false-positive results only serve to mislead the field and impede medical progress. With the resurgence of translational research, it is useful to examine some of the problems that plague these studies and consider their solutions. With thoughtful planning, execution, and analysis, it is possible to generate reliable and predictive data from preclinical proof-of-concept studies, results that should more rapidly advance medical progress. (+info)
Design and fabrication of multichannel cochlear implants for animal research.
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The effectiveness of multichannel cochlear implants depends on the activation of perceptually distinct regions of the auditory nerve. Increased information transfer is possible as the number of channels and dynamic range are increased and electrical and neural interaction among channels is reduced. Human and animal studies have demonstrated that specific design features of the intracochlear electrode directly affect these performance factors. These features include the geometry, size, and orientation of the stimulating sites, proximity of the device to spiral ganglion neurons, shape and position of the insulating carrier, and the stimulation mode (monopolar, bipolar, etc.). Animal studies to directly measure the effects of changes in electrode design are currently constrained by the lack of available electrodes that model contemporary clinical devices. This report presents methods to design and fabricate species-specific customizable electrode arrays. We have successfully implanted these arrays in guinea pigs and cats for periods of up to 14 months and have conducted acute electrophysiological experiments in these animals. Modifications enabling long-term intracochlear drug infusion are also described. Studies using these scale model arrays will improve our understanding of how these devices function in human subjects and how we can best optimize future cochlear implants. (+info)
The effectiveness of humane teaching methods in veterinary education.
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Animal use resulting in harm or death has historically played an integral role in veterinary education, in disciplines such as surgery, physiology, biochemistry, anatomy, pharmacology, and parasitology. However, many non-harmful alternatives now exist, including computer simulations, high quality videos, ''ethically-sourced cadavers'' such as from animals euthanased for medical reasons, preserved specimens, models and surgical simulators, non-invasive self-experimentation, and supervised clinical experiences. Veterinary students seeking to use such methods often face strong opposition from faculty members, who usually cite concerns about their teaching efficacy. Consequently, studies of veterinary students were reviewed comparing learning outcomes generated by non-harmful teaching methods with those achieved by harmful animal use. Of eleven published from 1989 to 2006, nine assessed surgical training--historically the discipline involving greatest harmful animal use. 45.5% (5/11) demonstrated superior learning outcomes using more humane alternatives. Another 45.5% (5/11) demonstrated equivalent learning outcomes, and 9.1% (1/11) demonstrated inferior learning outcomes. Twenty one studies of non-veterinary students in related academic disciplines were also published from 1968 to 2004. 38.1% (8/21) demonstrated superior, 52.4% (11/21) demonstrated equivalent, and 9.5% (2/21) demonstrated inferior learning outcomes using humane alternatives. Twenty nine papers in which comparison with harmful animal use did not occur illustrated additional benefits of humane teaching methods in veterinary education, including: time and cost savings, enhanced potential for customisation and repeatability of the learning exercise, increased student confidence and satisfaction, increased compliance with animal use legislation, elimination of objections to the use of purpose-killed animals, and integration of clinical perspectives and ethics early in the curriculum. The evidence demonstrates that veterinary educators can best serve their students and animals, while minimising financial and time burdens, by introducing well-designed teaching methods not reliant on harmful animal use. (+info)
Non-human primates: the appropriate subjects of biomedical research?
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Following the publication of the Weatherall report on the use of non-human primates in research, this paper reflects on how to provide appropriate and ethical models for research beneficial to humankind. Two of the main justifications for the use of non-human primates in biomedical research are analysed. These are the "least-harm/greatest-good" argument and the "capacity" argument. This paper argues that these are equally applicable when considering whether humans are appropriate subjects of biomedical research. (+info)
Considerations that may influence the result of trials assessing tensile strength in experimental surgery.
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PURPOSE: To provide information gathered upon the execution of trials assessing tensile strength in experimental surgeries. METHODS: Descriptive study considering details on the execution of trials assessing tensile strength in experimental surgery. RESULTS: The analysis of the rupture force in a mechanical test machine is an adequate technique since it provides precise and quick results. It can, undoubtedly, be developed in this context of the eminently mechanical analysis of trials on experimental surgery. CONCLUSION: The utilization of a mechanical test machine is a useful tool in the assessment of materials' strength, providing accurate results. Nevertheless the trials must be well structured analyzing the multiple variables so as to attain a pattern of constant reproducibility and to provide the necessary reliability. (+info)
Animal experiments scrutinised: systematic reviews demonstrate poor human clinical and toxicological utility.
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The assumption that animal models are reasonably predictive of human outcomes provides the basis for their widespread use in toxicity testing and in biomedical research aimed at developing cures for human diseases. To investigate the validity of this assumption, the comprehensive "Scopus" biomedical bibliographic databases were searched for published systematic reviews of the human clinical or toxicological utility of animal experiments. Of 20 reviews examining clinical utility, authors concluded that the animal models were substantially consistent with or useful in advancing clinical outcomes in only two cases, and the conclusion in one case was contentious. Included were reviews of the clinical utility of experiments expected by ethics committees to lead to medical advances, of highly-cited experiments published in major journals, and of chimpanzee experiments - the species most likely to be predictive of human outcomes. Seven additional reviews failed to clearly demonstrate utility in predicting human toxicological outcomes such as carcinogenicity and teratogenicity. Consequently, animal data may not generally be assumed to be substantially useful for these purposes. Possible causes include interspecies differences, the distortion of experimental outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments evident in at least 11 reviews. No reviews existed in which a majority of animal experiments were of good quality. While the latter problems might be minimised with concerted effort, given their widespread nature, the interspecies limitations are likely to be technically and theoretically impossible to overcome. Yet, unlike non-animal models, animal models are not normally subjected to formal scientific validation. Instead of simply assuming they are predictive of human outcomes, the consistent application of formal validation studies to all test models is clearly warranted, regardless of their animal, non-animal, historical, contemporary or possible future status. Expected benefits would include greater selection of models truly predictive of human outcomes, increased safety of people exposed to chemicals that have passed toxicity tests, increased efficiency during the development of human pharmaceuticals, and decreased wastage of animal, personnel and financial resources. The poor human clinical and toxicological utility of most animal models for which data exists, in conjunction with their generally substantial animal welfare and economic costs, justify a ban on animal models lacking scientific data clearly establishing their human predictivity or utility. (+info)