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Articles 811 - 840 of 1362
Full-Text Articles in Research Methods in Life Sciences
Possibilities For Refinement And Reduction: Future Improvements Within Regulatory Testing, Martin L. Stephens, Kathleen Conlee, Gina Alvino, Andrew N. Rowan
Possibilities For Refinement And Reduction: Future Improvements Within Regulatory Testing, Martin L. Stephens, Kathleen Conlee, Gina Alvino, Andrew N. Rowan
Andrew N. Rowan, DPhil
Approaches and challenges to refining and reducing animal use in regulatory testing are reviewed. Regulatory testing accounts for the majority of animals reported in the most painful and/or distressful categories in the United States and Canada. Refinements in testing, including the use of humane endpoints, are of increasing concern. Traditional approaches to reduction (e.g., improving experimental design) are being supplemented with complementary approaches, such as the use of tier testing to eliminate some chemicals prior to in vivo testing. Technological advances in telemetry and noninvasive techniques will help decrease either the demand for animals in testing or animal suffering. Further …
Estimates For Worldwide Laboratory Animal Use In 2005, Katy Taylor, Nicky Gordon, Gill Langley, Wendy Higgins
Estimates For Worldwide Laboratory Animal Use In 2005, Katy Taylor, Nicky Gordon, Gill Langley, Wendy Higgins
Gill Langley, PhD
Animal experimentation continues to generate public and political concern worldwide. Relatively few countries collate and publish animal use statistics, yet this is a first and essential step toward public accountability and an informed debate, as well as being important for effective policy-making and regulation. The implementation of the Three Rs (replacement, reduction and refinement of animal experiments) should be expected to result in a decline in animal use, but without regular, accurate statistics, this cannot be monitored. Recent estimates of worldwide annual laboratory animal use are imprecise and unsubstantiated, ranging from 28–100 million. We collated data for 37 countries that …
Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley
Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley
Gill Langley, PhD
Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …
The Validity Of Animal Experiments In Medical Research, Gill Langley
The Validity Of Animal Experiments In Medical Research, Gill Langley
Gill Langley, PhD
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.
Design Of Randomized Experiments In Networks, Dylan Walker, Lev Muchnik
Design Of Randomized Experiments In Networks, Dylan Walker, Lev Muchnik
Business Faculty Articles and Research
Over the last decade, the emergence of pervasive online and digitally enabled environments has created a rich source of detailed data on human behavior. Yet, the promise of big data has recently come under fire for its inability to separate correlation from causation-to derive actionable insights and yield effective policies. Fortunately, the same online platforms on which we interact on a day-to-day basis permit experimentation at large scales, ushering in a new movement toward big experiments. Randomized controlled trials are the heart of the scientific method and when designed correctly provide clean causal inferences that are robust and reproducible. However, …
Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey
Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey
Laboratory Experiments Collection
Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s …
Arkansas Animal Science Department Report 2014, David L. Kreider, Paul Beck
Arkansas Animal Science Department Report 2014, David L. Kreider, Paul Beck
Arkansas Agricultural Experiment Station Research Series
No abstract provided.
Annotated Bibliography: Attitudes Toward Animal Research (1998-2013), Erich Yahner
Annotated Bibliography: Attitudes Toward Animal Research (1998-2013), Erich Yahner
BIBLIOGRAPHIES
No abstract provided.
Evaluation Of Awarded Grant Applications Involving Animal Experimentation, Michael W. Fox, M. Andrea Ward, Andrew N. Rowan, Barbara Jaffe
Evaluation Of Awarded Grant Applications Involving Animal Experimentation, Michael W. Fox, M. Andrea Ward, Andrew N. Rowan, Barbara Jaffe
Andrew N. Rowan, DPhil
The potential benefits of animal research are accepted by most. However, painstaking care must be applied to the approach and design of the research to ensure the best possible chance of achieving the research objectives and to minimize both physical and psychological distress to the animals. Consideration should be given not only to transport and housing conditions, but also to practices used in the laboratory. Adequate reasons must also be given as to why the research is necessary.
Public concern over the use and care of laboratory animals in biomedical programs contributed to the passage of the Animal Welfare Act …
Sma-Causing Missense Mutations In Survival Motor Neuron (Smn) Display A Wide Range Of Phenotypes When Modeled In Drosophila, Kavita Praveen, Ying Wen, Kelsey M. Gray, John J. Noto, Akash R. Patlolla, Gregory D. Van Duyne, A. Gregory Matera
Sma-Causing Missense Mutations In Survival Motor Neuron (Smn) Display A Wide Range Of Phenotypes When Modeled In Drosophila, Kavita Praveen, Ying Wen, Kelsey M. Gray, John J. Noto, Akash R. Patlolla, Gregory D. Van Duyne, A. Gregory Matera
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of …
Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher
Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher
Pharmacy Faculty Articles and Research
PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the …
Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley
Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley
Experimentation Collection
Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …
Public Attitudes Toward Animal Research: A Review, Elisabeth H. Ormandy, Catherine A. Schuppli
Public Attitudes Toward Animal Research: A Review, Elisabeth H. Ormandy, Catherine A. Schuppli
Attitudes Toward Animal Research Collection
The exploration of public attitudes toward animal research is important given recent developments in animal research (e.g., increasing creation and use of genetically modified animals, and plans for progress in areas such as personalized medicine), and the shifting relationship between science and society (i.e., a move toward the democratization of science). As such, public engagement on issues related to animal research, including exploration of public attitudes, provides a means of achieving socially acceptable scientific practice and oversight through an understanding of societal values and concerns. Numerous studies have been conducted to explore public attitudes toward animal use, and more specifically …
Scientists And Animal Research: Dr. Jekyll Or Mr. Hyde?, Andrew N. Rowan
Scientists And Animal Research: Dr. Jekyll Or Mr. Hyde?, Andrew N. Rowan
Andrew N. Rowan, DPhil
Why is the public so sensitive about the use of a few tens of millions of animals in research when they do not object to killing hundreds of millions of pigs and cows and billions of chickens for our meat diet? Why is animal research considered so bad despite the public's high opinion of science (and scientists)? Perhaps it is the image of the scientist as an objective and cold individual who deliberately inflicts harm (pain, distress, or death) on his (the public image is usually male) innocent animal victims that arouses so much horror and concern. This paper does …
The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe
The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe
Jonathan Balcombe, Ph.D.
Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …
The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe
The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe
Jonathan Balcombe, PhD
Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …
Prolonged Pain Research In Mice: Trends In Reference To The 3rs, Jonathan Balcombe, Hope Ferdowsian, Lauren Briese
Prolonged Pain Research In Mice: Trends In Reference To The 3rs, Jonathan Balcombe, Hope Ferdowsian, Lauren Briese
Jonathan Balcombe, PhD
This literature review documents trends in the use of mice in prolonged pain research, defined herein as research that subjects mice to a source of pain for at least 14 days. The total amount of prolonged pain research on mice has increased dramatically in the past decade for the 3 pain categories examined: neuropathic, inflammatory, and chronic pain. There has also been a significant rise in the number of prolonged mouse pain studies as a proportion of all mouse studies and of all mouse pain studies. The use of transgenic mice has also risen significantly in prolonged pain research, though …
Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe
Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe
Jonathan Balcombe, PhD
The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.
The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p
An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls
An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls
Experimentation Collection
Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …
A Review Of The Institute Of Medicine’S Analysis Of Using Chimpanzees In Biomedical Research, Robert C. Jones, Ray Greek
A Review Of The Institute Of Medicine’S Analysis Of Using Chimpanzees In Biomedical Research, Robert C. Jones, Ray Greek
Biomedicine and Animal Models in Research Collection
We argue that the recommendations made by the Institute of Medicine’s 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity, are methodologically and ethically confused. We argue that a proper understanding of evolution and complexity theory in terms of the science and ethics of using chimpanzees in biomedical research would have had led the committee to recommend not merely limiting but eliminating the use of chimpanzees in biomedical research. Specifically, we argue that a proper understanding of the difference between the gross level of examination of species and examinations on finer levels can shed light on important methodological …
Laboratory Rodent Welfare: Thinking Outside The Cage, Jonathan P. Balcombe
Laboratory Rodent Welfare: Thinking Outside The Cage, Jonathan P. Balcombe
Jonathan Balcombe, PhD
This commentary presents the case against housing rats and mice in laboratory cages; the commentary bases its case on their sentience, natural history, and the varied detriments of laboratory conditions. The commentary gives 5 arguments to support this position: (a) rats and mice have a high degree of sentience and can suffer, (b) laboratory environments cause suffering, (c) rats and mice in the wild have discrete behavioral needs, (d) rats and mice bred for many generations in the laboratory retain these needs, and (e) these needs are not met in laboratory cages.
Laboratory Routines Cause Animal Stress, Jonathan P. Balcombe, Neal D. Barnard, Chad Sandusky
Laboratory Routines Cause Animal Stress, Jonathan P. Balcombe, Neal D. Barnard, Chad Sandusky
Jonathan Balcombe, PhD
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 …
A Longitudinal View Of Primate Life In Two American Laboratories, Jonathan Balcombe
A Longitudinal View Of Primate Life In Two American Laboratories, Jonathan Balcombe
Experimentation Collection
If representative of other facilities, our findings uncover serious welfare concerns for the wellbeing of primates kept in American research facilities. These animals face regular or chronic sources of pain and distress including noxious experimental and non‐experimental events and illness and injury; and severe and prolonged social disruptions. Pain relief is meager by comparison to that normally provided to humans, despite legislative requirements to minimize pain and distress and assume similarity to humans in terms of ability to experience pain and distress. Living environments are usually confinement indoors to a metal cage, often alone, and often with a minimum of …
Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe
Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe
Jonathan Balcombe, PhD
The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …
Medical Training Using Simulation: Toward Fewer Animals And Safer Patients, Jonathan Balcombe
Medical Training Using Simulation: Toward Fewer Animals And Safer Patients, Jonathan Balcombe
Jonathan Balcombe, PhD
This paper presents the current status of computer-based simulation in medicine. Recent technological advances have enabled this field to emerge from esoteric explorations in academic laboratories to commercially available simulators designed to train users to perform medical procedures from start to finish. Today, more than a dozen companies are producing virtual reality simulators and interactive manikins for training in endoscopy, laparoscopy, anaesthesia, trauma management, angiography, and needle insertion. For many of these procedures, thousands of animals are still being used in training. Yet simulation has many advantages that can transcend scientific, ethical, economic and logistical problems that arise when using …
Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe
Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe
Jonathan Balcombe, PhD
The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …
A Multivariate Model Of Stakeholder Preference For Lethal Cat Management, Dara M. Wald, Susan K. Jacobson
A Multivariate Model Of Stakeholder Preference For Lethal Cat Management, Dara M. Wald, Susan K. Jacobson
Dara Wald
State-Of-The-Art Of 3d Cultures (Organs-On-A-Chip) In Safety Testing And Pathophysiology, Natalie Alépée, Anthony Bahinski, Mardas Daneshian, Bart De Wever, Alan Goldberg, Jan Hansmann, Thomas Hartung, John Haycock, Helena T. Hogberg, Lisa Hoelting, Jens M. Kelm, Suzanne Kadereit, Emily Mcvey, Robert Landsiedel, Marcel Leist, Marc Lübberstedt, Fozia Noor, Christian Pellevoisin, Dirk Petersohn, Uwe Pfannenbecker, Kerstin Reisinger, Tzutzuy Ramirez, Barbara Rothen-Rutishauser, Monika Schäfer-Korting, Katrin Zeilinger, Marie-Gabriele Zurich
State-Of-The-Art Of 3d Cultures (Organs-On-A-Chip) In Safety Testing And Pathophysiology, Natalie Alépée, Anthony Bahinski, Mardas Daneshian, Bart De Wever, Alan Goldberg, Jan Hansmann, Thomas Hartung, John Haycock, Helena T. Hogberg, Lisa Hoelting, Jens M. Kelm, Suzanne Kadereit, Emily Mcvey, Robert Landsiedel, Marcel Leist, Marc Lübberstedt, Fozia Noor, Christian Pellevoisin, Dirk Petersohn, Uwe Pfannenbecker, Kerstin Reisinger, Tzutzuy Ramirez, Barbara Rothen-Rutishauser, Monika Schäfer-Korting, Katrin Zeilinger, Marie-Gabriele Zurich
in Vitro Research Models Collection
Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This …
Rethinking The Ethics Of Research Involving Nonhuman Animals: Introduction, Tom L. Beauchamp, Hope Ferdowsian, John P. Gluck
Rethinking The Ethics Of Research Involving Nonhuman Animals: Introduction, Tom L. Beauchamp, Hope Ferdowsian, John P. Gluck
Experimentation Collection
No abstract provided.
Moving Beyond The Welfare Standard Of Psychological Well-Being For Nonhuman Primates: The Case Of Chimpanzees, John P. Gluck
Moving Beyond The Welfare Standard Of Psychological Well-Being For Nonhuman Primates: The Case Of Chimpanzees, John P. Gluck
Experimentation Collection
Since 1985, the US Animal Welfare Act and Public Health Service policy have required that researchers using nonhuman primates in biomedical and behavioral research develop a plan ‘‘for a physical environment adequate to promote the psychological well-being of primates.’’ In pursuing this charge, housing attributes such as social companionship, opportunities to express species-typical behavior, suitable space for expanded locomotor activity, and nonstressful relationships with laboratory personnel are dimensions that have dominated the discussion. Regulators were careful not to direct a specific set of prescriptions (i.e., engineering standards) for the attainment of these goals, but to leave the design of the …