Research Methods in Life Sciences Commons^™

Assessing The Necessity Of Chimpanzee Experimentation, Andrew Knight

Experimentation Collection

No abstract provided.

A Guide To Defining And Implementing Protocols For The Welfare Assessment Of Laboratory Animals: Eleventh Report Of The Bvaawf/Frame/Rspca/Ufaw Joint Working Group On Refinement, P. Hawkins, D. B. Morton, O. Burman, N. Dennison, P. Honess, M. Jennings, S. Lane, V. Middleton, J. V. Roughan, S. Wells, K. Westwood

Research Methodology and Laboratory Animals Collection

The refinement of husbandry and procedures to reduce animal suffering and improve welfare is an essential component of humane science. Successful refinement depends upon the ability to assess animal welfare effectively, and detect any signs of pain or distress as rapidly as possible, so that any suffering can be alleviated. This document provides practical guidance on setting up and operating effective protocols for the welfare assessment of animals used in research and testing. It sets out general principles for more objective observation of animals, recognizing and assessing indicators of pain or distress and tailoring these to individual projects. Systems for …

Microct Study Of Critical-Sized Defects Restored With A New Rhbmp-2 Carrier, Joanne S. Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Regenerating bone in critical-sized maxillofacial osseous defects remains a challenge. The utilization of recombinant human bone morphogenetic protein-2 (rhBMP-2) to form new bone has been shown to be a promising alternative to autogenous bone grafts, and the development of a carrier matrix to effectively deliver the rhBMP-2 has been identified as the critical factor necessary for the successful clinical application of rhBMP-2. The objective of this study was to perform a microCT analysis to examine the density of reconstructed bone using different rhBMP-2 carriers in critical-sized defects.

Material and Methods: Critical-sized defects (approximately 2.5 cm) were created in the …

Can Animal Models Of Disease Reliably Inform Human Studies?, H. Bart Van Der Worp, David W. Howells, Emily Sena, Michelle J. Porritt, Sarah Rewell, Victoria O'Collins, Malcolm Macleod

Validation of Animal Experimentation Collection

• The value of animal experiments for predicting the effectiveness of treatment strategies in clinical trials has remained controversial, mainly because of a recurrent failure of interventions apparently promising in animal models to translate to the clinic.
• Translational failure may be explained in part by methodological flaws in animal studies, leading to systematic bias and thereby to inadequate data and incorrect conclusions about efficacy.
• Failures also result because of critical disparities, usually disease specific, between the animal models and the clinical trials testing the treatment strategy.
• Systematic review and meta-analysis of animal studies may aid in the selection of the most …

Publication Bias In Reports Of Animal Stroke Studies Leads To Major Overstatement Of Efficacy, Emily Sena, H. Bart Van Der Worp, Philip M.W. Bath, David W. Howells, Malcolm Macleod

Validation of Animal Experimentation Collection

The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst “experts” and in the public understanding. Where data are collected but remain unpublished, they cannot contribute to this distillation of knowledge. If these unpublished data differ substantially from published work, conclusions may not reflect adequately the underlying biological effects being described. The existence and any impact of such “publication bias” in the laboratory sciences have not been described. Using the CAMARADES (Collaborative Approach …

Noncompliance With Public Health Service (Phs) Policy On Humane Care And Use Of Laboratory Animals: An Exploratory Analysis, Leah M. Gomez, Kathleen Conlee, Martin Stephens

Laboratory Experiments Collection

The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS’s animal care and use standards must report these incidents to the NIH’s OLAW. This study is an exploratory analysis of all the significant deviations reported by animal-research facilities to OLAW during a 3-month period. The study identifies …

The Scher Report On Non-Human Primate Research — Biased And Deeply Flawed, Jarrod Bailey, Katy Taylor

Experimentation Collection

The European Commission’s Scientific Committee on Health and Environmental Risks (SCHER) recently issued an Opinion on the need for non-human primate (NHP) use in biomedical research, and the possibilities of replacing NHP use with alternatives, as part of the Directive 86/609/EEC revision process. Here, we summarise our recent complaint to the European Ombudsman about SCHER’s Opinion and the entire consultation process. It is our opinion that the Working Group almost entirely failed to address its remit, and that the Group was unbalanced and contained insufficient expertise. The Opinion presumed the validity of NHP research with inadequate supporting evidence, and ignored …

Are Animal Models Predictive For Humans?, Niall Shanks, Ray Greek, Jean Greek

Validation of Animal Experimentation Collection

It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is …

The Validity Of Animal Experiments In Medical Research, Gill Langley

Experimentation Collection

Other animals, such as mice, rats, rabbits, dogs and monkeys, are widely used as surrogates for humans in fundamental medical research. This involves creating disorders in animals by chemical, surgical or genetic means, with the aim of mimicking selected aspects of human illnesses.

It is a truism that any model or surrogate is not identical to the target being modelled. So, in medical research, experiments using animals or cell cultures or even healthy volunteers instead of patients (being the target population with the target illness) will inevitably have limitations, although these will be greater or lesser depending on the model.

The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Laboratory Experiments Collection

While the attention given to preventing, assessing, and alleviating pain in research animals has increased noticeably in recent decades, much remains to be done both in terms of implementing best practices and conducting studies to answer outstanding questions. In contrast, the attention to distress (particularly non-pain induced distress) has shown no comparable increase. There are many reasons for this discrepancy, including the conceptual untidiness of the distress concept, the paucity of pharmacological treatments for distress, and perceived lack of regulatory emphasis on distress. These are challenges that need to be addressed and overcome. This book is intended to help meet …

Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Experimentation Collection

While most people recognize that biomedical scientists are searching for knowledge that will improve the health of humans and animals, the image of someone deliberately causing harm to an animal in order to produce data that may lead to some future benefit has always prompted an uncomfortable reaction outside the laboratory. However, proponents of animal research have usually justified the practice by reference to greater benefits (new knowledge and medical treatments) over lesser costs (in animal suffering and death). Given that one of the costs of animal research is the suffering experienced by the animals, the goal of eliminating distress …

The Role Of Clinical Veterinary Medicine In The Assessment And Treatment Of Laboratory Animal Distress, V. Hampshire

Veterinary Science and Medicine Collection

It is doubtful that the scientific community will ever arrive at a consensus definition for distress as it may be attempted for the purposes of improving animal welfare in and across the myriad of research, testing and teaching facilities in the United States and throughout the minuet of protocols that exist for animals. The stakeholders in this attempt can however address most causes of physiologic distress by instituting time-honored veterinary and agrarian approaches to animal surveillance. In this manner, the majority of individuals who participate in responsible and humane animal care might be assuaged in that a condition of maximum …

An Assessment Of The Role Of Chimpanzees In Aids Vaccine Research, Jarrod Bailey

Laboratory Experiments Collection

Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the ‘model of choice’ in the 1990s, chimpanzees were widely used in AIDS vaccine research and testing. Faced with the continued failure to develop an effective human vaccine, some scientists are calling for a return to their widespread use. To assess the past and potential future contribution of chimpanzees to AIDS vaccine development, databases and published literature were systematically searched to compare the results of AIDS vaccine trials in chimpanzees with those of human clinical trials, and to determine whether the chimpanzee trials were predictive of the human response. Protective and/or therapeutic …

The Beginning Of The End For Chimpanzee Experiments?, Andrew Knight

Experimentation Collection

The advanced sensory, psychological and social abilities of chimpanzees confer upon them a profound ability to suffer when born into unnatural captive environments, or captured from the wild – as many older research chimpanzees once were – and when subsequently subjected to confinement, social disruption, and involuntary participation in potentially harmful biomedical research. Justifications for such research depend primarily on the important contributions advocates claim it has made toward medical advancements. However, a recent large-scale systematic review indicates that invasive chimpanzee experiments rarely provide benefits in excess of their profound animal welfare, bioethical and financial costs. The approval of large …

Systematic Reviews Of Animal Experiments Demonstrate Poor Contributions To Human Healthcare, Andrew Knight

Experimentation Collection

Widespread reliance on animal models during preclinical research and toxicity testing assumes their reasonable predictivity for human outcomes. However, of 20 published systematic reviews examining human clinical utility located during a comprehensive literature search, animal models demonstrated significant potential to contribute toward clinical interventions in only two cases, one of which was contentious. Included were experiments expected by ethics committees to lead to medical advances, highly-cited experiments published in major journals, and chimpanzee experiments—the species most generally predictive of human outcomes. Seven additional reviews failed to demonstrate utility in reliably predicting human toxicological outcomes such as carcinogenicity and teratogenicity. Results …

Medical Progress Depends On Animal Models - Doesn't It?, Robert A. J. Matthews

Validation of Animal Experimentation Collection

Animal models are widely recognized as being essential to the progress of medical science. In countering the critics’ arguments of the use of animals in medicine, one statement has acquired almost talismanic importance:

‘Virtually every medical achievement of the last century has depended directly or indirectly on research with animals.’

In this essay, the origins and justification of this oft-repeated statement are examined. Despite its endorsement by leading academic bodies, it is far from clear that the statement has been, or even could be, formally validated.

Systematic Reviews Of Animal Experiments Demonstrate Poor Human Clinical And Toxicological Utility, Andrew Knight

Experimentation Collection

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. In 20 reviews in which clinical utility was examined, the authors concluded that animal models were either significantly useful in contributing to the development of clinical interventions, or were substantially consistent with clinical outcomes, in only two cases, one …

Comparison Of Treatment Effects Between Animal Experiments And Clinical Trials: Systematic Review, Pablo Perel, Ian Roberts, Emily Sena, Philipa Wheble, Catherine Briscoe, Peter Sandercock, Malcolm Macleod, Luciano E. Mignini, Pradeep Jayaram, Khalid S. Khan

Validation of Animal Experimentation Collection

Objective To examine concordance between treatment effects in animal experiments and clinical trials.

Study design Systematic review.

Data sources Medline, Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS.

Study selection Animal studies for interventions with unambiguous evidence of a treatment effect (benefit or harm) in clinical trials: head injury, antifibrinolytics in haemorrhage, thrombolysis in acute ischaemic stroke, tirilazad in acute ischaemic stroke, antenatal corticosteroids to prevent neonatal respiratory distress syndrome, and bisphosphonates to treat osteoporosis.

Review methods Data were extracted on study design, allocation concealment, number of randomised animals, type of model, intervention, and outcome.

Results Corticosteroids did not show …

The Poor Contribution Of Chimpanzee Experiments To Biomedical Progress, Andrew Knight

Experimentation Collection

Biomedical research on captive chimpanzees incurs substantial nonhuman animal welfare, ethical, and financial costs that advocates claim result in substantial advancements in biomedical knowledge. However, demonstrating minimal contribution toward the advancement of biomedical knowledge generally, subsequent papers did not cite 49.5% (47/95), of 95 experiments randomly selected from a population of 749 published worldwide between 1995 and 2004. Only 14.7% (14/95) were cited by 27 papers that abstracts indicated described well-developed methods for combating human diseases. However, detailed examination of these medical papers revealed that in vitro studies, human clinical and epidemiological studies, molecular assays and methods, and genomic studies …

Overcoming Ideology: Why It Is Necessary To Create A Culture In Which The Ethical Review Of Protocols Can Flourish, Bernard E. Rollin

Experimentation Collection

My objective in this commentary is to describe and discuss a major threat to the continued thriving of science in our society, which is all the more insidious because it is largely unrecognized by those in the scientific community who are in a position to rectify the problem. Astute people in that community are well aware of many threats to science that include but are not limited to the following: appalling public scientific illiteracy; the unfortunate resurgence of “magic thinking”—reflected in turn in the reappearance of Creationism, which is hostile to evolution—and the billions of dollars spent on evidentially baseless …

In Vitro Antimicrobial Efficacy Of Calcium Hydroxides In Root Dentin, Josef W. Lubisich

Loma Linda University Electronic Theses, Dissertations & Projects

Enterococcus faecalis is the most commonly isolated bacteria in failed root canal treatment. Endodontic intracanal medicaments are commonly tested using standardized bovine cylinders infected with bacteria. The literature is not clear on whether calcium hydroxides are able to remove E. faecalis from the dentinal tubules. One reason for this is that there are several varying forms of calcium hydroxide commonly used. The purpose of the present experiment was to determine whether four commonly used calcium hydroxide products were able to reduce E. faecalis from four incremental samples of dentin and to determine if there was a statistically significant difference between …

Effects Of Diabetes Mellitus On The Healing Of The Dental Pulp, Stuart Evan Garber

Loma Linda University Electronic Theses, Dissertations & Projects

Diabetes Mellitus (DM) has been implicated as a factor affecting healing. The purpose of this study was to use the healing of experimentally exposed pulps subsequent to pulp capping as a model to determine the effect of DM on healing.

Twenty-two Sprague-Dawley rats were divided into two groups of eleven animals each. In one group, DM was induced by injection of 70 mg/KG of streptozotocin. In the other group, the animals were injected with sterile saline. Under anesthesia with Ketamine and Xylazine, the pulps of the maxillary first molars of all rats were exposed using a 1/16 round bur under …

The Effect Of Calcium Hydroxide Pastes On Root Dentin Fracture Resistance, Kurt W. Sturz

Loma Linda University Electronic Theses, Dissertations & Projects

Calcium hydroxide is a common intracanal medicament used in the treatment of immature teeth that have been subjected to trauma or decay prior to root canal therapy. The effect of calcium hydroxide on immature root dentin is important. One area of concern is the effect that calcium hydroxide has on the fracture resistance of an immature tooth. It is the aim of this study to compare the effect of four different commercially available calcium hydroxide pastes on the fracture resistance of bovine teeth. Seventy-five freshly extracted, intact bovine incisors were prepared according to a modified Haapasalo and Orstavik technique. Each …

The Effect Of Naocl, Ca(Oh)2, Mta And Mtad On Root Dentin Fracture Resistance, Sunil Ilapogu

Loma Linda University Electronic Theses, Dissertations & Projects

Various materials are used for the treatment of immature teeth that have been subjected to trauma or decay. It is not well established what effect these materials may have on the immature root dentin. A concern would be the resistance to fracture of the remaining root dentin. The purpose of this study was to compare the resistance of fracture of bovine teeth treated with sodium hypochlorite, calcium hydroxide, gray MTA and gray MTA in conjunction with MTAD after certain periods of time. One hundred and ninety five freshly extracted, intact bovine incisors were prepared using a modified Haapasalo and Orstavik …

Laboratory Routines Cause Animal Stress, Jonathan P. Balcombe, Neal D. Barnard, Chad Sandusky

Laboratory Experiments Collection

Eighty published studies were appraised to document the potential stress associated with three routine laboratory procedures commonly performed on animals: handling, blood collection, and orogastric gavage. We defined handling as any non-invasive manipulation occurring as part of routine husbandry, including lifting an animal and cleaning or moving an animal's cage. Significant changes in physiologic parameters correlated with stress (e.g., serum or plasma concentrations of corticosterone, glucose, growth hormone or prolactin, heart rate, blood pressure, and behavior) were associated with all three procedures in multiple species in the studies we examined. The results of these studies demonstrated that animals responded with …

Condylar Remodeling After Distraction Osteogenesis And Bilateral Sagittal Split Osteotomy, Robert Barker Hoffman

Loma Linda University Electronic Theses, Dissertations & Projects

The present pilot study is a histological evaluation of mandibular condyles taken from minipigs that underwent either traditional mandibular advancement (bilateral sagittal split osteotomy), or a distraction osteogenesis procedure to advance the mandible. One pig received a bilateral sagittal split osteotomy with an immediate mandibular advancement of 14 mm, while another pig underwent distraction osteogenesis consisting of a gradual advancement of 2 mm per day to advance the mandible the same distance. The control animal received no surgery.

In the present study, the mandibular condyles of the three pigs (2 control, 2 bilateral sagittal split osteotomy, and 2 distraction osteogenesis) …

Animal Model Research: The Apples And Oranges Quandary, Kenneth J. Shapiro

Experimentation Collection

In this paper, I explore the premises underlying the problem of the evaluation of animal models. I argue that the presence of similarities and differences between the model and the modelled, although historically and currently a dominant antinomy framing evaluation, is not a bottom-line consideration. What is critical is 1) whether we learn and 2) whether we improve treatment through the animal model research. Similarity between model and modelled and the closely related concept of validity are not coterminus with these critical evaluative measures. In fact, differences between the model and modelled also can provide impetus to new understanding and …

Comparison Of Bracket Bond Strength By Total, Self-Etch And Laser Treatment, Kyo Sung Shawn Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Laser etching of enamel surfaces alters the physical and chemical characteristics of the enamel. These changes in characteristics enhance the bonding to enamel. The purpose of this study was to compare the shear and tensile bond strength of Er,Cr:YSGG hydrokinetic laser system (Biolase) with 37% phosphoric acid and self etching primer 30 minutes and 72 hours after bonding. Four different laser power output setting was observed: 1.5W, 2.0W, 2.5W, and 3.0W. Two hundred forty bovine teeth free of defect, caries, and dentin exposure were mounted in acrylic resin and divided into 24 groups of 10 teeth. Sixteen groups of 10 …

A Bond Strength Comparison Of Led And Halogen Light Curing Units, John Richard Kavanagh

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this research was to compare the tensile bond strength of orthodontic flat based buttons bonded to bovine teeth with four commercial light-emitting diode (LED) curing lights and one conventional quartz tungsten halogen (QTH) curing light.

The dental market has recently been introduced to a number of commercially available light-emitting diode (LED) curing lights. Tensile bond strength was evaluated for LED curing lights (Rembrandt® Allegro^TM, Den-Mat Corp, Santa Maria, CA), (LEDemetron, Kerr/Demetron Corp, Danbury, Conn), (Ortholux LED, 3M^TMESPE^TM, St. Paul, MN),and (FLASH-lite 1001, Discus Dental, Culver City, CA) are compared with one …

Behavioral Evaluation Of The Psychological Welfare And Environmental Requirements Of Agricultural Research Animals: Theory, Measurement, Ethics, And Practical Implications, Lesley A. King

Experimentation Collection

The welfare of agricultural research animals relies not only on measures of good health but also on the presence of positive emotional states and the absence of aversive or unpleasant subjective states such as fear, frustration, or association with pain. Although subjective states are not inherently observable, their interaction with motivational states can be measured through assessment of motivated behavior, which indicates the priority animals place on obtaining or avoiding specific environmental stimuli and thus allows conclusions regarding the impact of housing, husbandry, and experimental procedures on animal welfare. Preference tests and consumer demand models demonstrate that animal choices are …