Adverse Outcome Pathways can drive non-animal approaches for safety assessment

PubMed Central

Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

2015-01-01

Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. This article explores how the development and application of Adverse Outcome Pathways (AOPs) could benefit the science and practice of chemical safety assessment, with a particular focus on how their use in practice could reduce reliance on traditional animal toxicity tests. This includes discussion of the key areas where current and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. PMID:25943792

Assuring consumer safety without animal testing: a feasibility case study for skin sensitisation.

PubMed

Maxwell, Gavin; Aleksic, Maja; Aptula, Aynur; Carmichael, Paul; Fentem, Julia; Gilmour, Nicola; Mackay, Cameron; Pease, Camilla; Pendlington, Ruth; Reynolds, Fiona; Scott, Daniel; Warner, Guy; Westmoreland, Carl

2008-11-01

Allergic Contact Dermatitis (ACD; chemical-induced skin sensitisation) represents a key consumer safety endpoint for the cosmetics industry. At present, animal tests (predominantly the mouse Local Lymph Node Assay) are used to generate skin sensitisation hazard data for use in consumer safety risk assessments. An animal testing ban on chemicals to be used in cosmetics will come into effect in the European Union (EU) from March 2009. This animal testing ban is also linked to an EU marketing ban on products containing any ingredients that have been subsequently tested in animals, from March 2009 or March 2013, depending on the toxicological endpoint of concern. Consequently, the testing of cosmetic ingredients in animals for their potential to induce skin sensitisation will be subject to an EU marketing ban, from March 2013 onwards. Our conceptual framework and strategy to deliver a non-animal approach to consumer safety risk assessment can be summarised as an evaluation of new technologies (e.g. 'omics', informatics), leading to the development of new non-animal (in silico and in vitro) predictive models for the generation and interpretation of new forms of hazard characterisation data, followed by the development of new risk assessment approaches to integrate these new forms of data and information in the context of human exposure. Following the principles of the conceptual framework, we have been investigating existing and developing new technologies, models and approaches, in order to explore the feasibility of delivering consumer safety risk assessment decisions in the absence of new animal data. We present here our progress in implementing this conceptual framework, with the skin sensitisation endpoint used as a case study. 2008 FRAME.

Occupational health and safety aspects of animal handling in dairy production.

PubMed

Lindahl, Cecilia; Lundqvist, Peter; Hagevoort, G Robert; Lunner Kolstrup, Christina; Douphrate, David I; Pinzke, Stefan; Grandin, Temple

2013-01-01

Livestock handling in dairy production is associated with a number of health and safety issues. A large number of fatal and nonfatal injuries still occur when handling livestock. The many animal handling tasks on a dairy farm include moving cattle between different locations, vaccination, administration of medication, hoof care, artificial insemination, ear tagging, milking, and loading onto trucks. There are particular problems with bulls, which continue to cause considerable numbers of injuries and fatalities in dairy production. In order to reduce the number of injuries during animal handling on dairy farms, it is important to understand the key factors in human-animal interactions. These include handler attitudes and behavior, animal behavior, and fear in cows. Care when in close proximity to the animal is the key for safe handling, including knowledge of the flight zone, and use of the right types of tools and suitable restraint equipment. Thus, in order to create safe working conditions during livestock handling, it is important to provide handlers with adequate training and to establish sound safety management procedures on the farm.

A Web-based Alternative Non-animal Method Database for Safety Cosmetic Evaluations.

PubMed

Kim, Seung Won; Kim, Bae-Hwan

2016-07-01

Animal testing was used traditionally in the cosmetics industry to confirm product safety, but has begun to be banned; alternative methods to replace animal experiments are either in development, or are being validated, worldwide. Research data related to test substances are critical for developing novel alternative tests. Moreover, safety information on cosmetic materials has neither been collected in a database nor shared among researchers. Therefore, it is imperative to build and share a database of safety information on toxicological mechanisms and pathways collected through in vivo, in vitro, and in silico methods. We developed the CAMSEC database (named after the research team; the Consortium of Alternative Methods for Safety Evaluation of Cosmetics) to fulfill this purpose. On the same website, our aim is to provide updates on current alternative research methods in Korea. The database will not be used directly to conduct safety evaluations, but researchers or regulatory individuals can use it to facilitate their work in formulating safety evaluations for cosmetic materials. We hope this database will help establish new alternative research methods to conduct efficient safety evaluations of cosmetic materials.

Do Performance-Safety Tradeoffs Cause Hypometric Metabolic Scaling in Animals?

PubMed

Harrison, Jon F

2017-09-01

Hypometric scaling of aerobic metabolism in animals has been widely attributed to constraints on oxygen (O 2 ) supply in larger animals, but recent findings demonstrate that O 2 supply balances with need regardless of size. Larger animals also do not exhibit evidence of compensation for O 2 supply limitation. Because declining metabolic rates (MRs) are tightly linked to fitness, this provides significant evidence against the hypothesis that constraints on supply drive hypometric scaling. As an alternative, ATP demand might decline in larger animals because of performance-safety tradeoffs. Larger animals, which typically reproduce later, exhibit risk-reducing strategies that lower MR. Conversely, smaller animals are more strongly selected for growth and costly neurolocomotory performance, elevating metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing Student Attitudes toward Animal Welfare, Resource Use, and Food Safety.

ERIC Educational Resources Information Center

Nordstrom, Patricia A.; Richards, Martha J.; Wilson, Lowell L.; Coe, Brenda L.; Fivek, Marianne L.; Brown, Michele B.

2000-01-01

Students participating in the Pennsylvania Governor's School for Agricultural Sciences (n=192) studied animal welfare, resource use, and food safety. They ranked food safety as a primary concern. Students with and without agricultural backgrounds showed positive changes in knowledge and perception of issues after the course. (SK)

Data-driven risk models could help target pipeline safety inspections

DOT National Transportation Integrated Search

2008-07-01

Federal safety agencies share a common problemthe : need to target resources effectively to reduce risk. One : way this targeting is commonly done is with a risk model : that uses safety data along with expert judgment to identify : and weight ris...

Assessment of the safety of aquatic animal commodities for international trade: the OIE Aquatic Animal Health code.

PubMed

Oidtmann, B; Johnston, C; Klotins, K; Mylrea, G; Van, P T; Cabot, S; Martin, P Rosado; Ababouch, L; Berthe, F

2013-02-01

Trading of aquatic animals and aquatic animal products has become increasingly globalized during the last couple of decades. This commodity trade has increased the risk for the spread of aquatic animal pathogens. The World Organisation for Animal Health (OIE) is recognized as the international standard-setting organization for measures relating to international trade in animals and animal products. In this role, OIE has developed the Aquatic Animal Health Code, which provides health measures to be used by competent authorities of importing and exporting countries to avoid the transfer of agents pathogenic for animals or humans, whilst avoiding unjustified sanitary barriers. An OIE ad hoc group developed criteria for assessing the safety of aquatic animals or aquatic animal products for any purpose from a country, zone or compartment not declared free from a given disease 'X'. The criteria were based on the absence of the pathogenic agent in the traded commodity or inactivation of the pathogenic agent by the commercial processing used to produce the commodity. The group also developed criteria to assess the safety of aquatic animals or aquatic animal products for retail trade for human consumption from potentially infected areas. Such commodities were assessed considering the form and presentation of the product, the expected volume of waste tissues generated by the consumer and the likely presence of viable pathogenic agent in the waste. The ad hoc group applied the criteria to commodities listed in the individual disease chapters of the Aquatic Animal Health Code (2008 edition). Revised lists of commodities for which no additional measures should be required by the importing countries regardless of the status for disease X of the exporting country were developed and adopted by the OIE World Assembly of Delegates in May 2011. The rationale of the criteria and their application will be explained and demonstrated using examples. © 2012 Crown Copyright. Reproduced

A Web-based Alternative Non-animal Method Database for Safety Cosmetic Evaluations

PubMed Central

Kim, Seung Won; Kim, Bae-Hwan

2016-01-01

Animal testing was used traditionally in the cosmetics industry to confirm product safety, but has begun to be banned; alternative methods to replace animal experiments are either in development, or are being validated, worldwide. Research data related to test substances are critical for developing novel alternative tests. Moreover, safety information on cosmetic materials has neither been collected in a database nor shared among researchers. Therefore, it is imperative to build and share a database of safety information on toxicological mechanisms and pathways collected through in vivo, in vitro, and in silico methods. We developed the CAMSEC database (named after the research team; the Consortium of Alternative Methods for Safety Evaluation of Cosmetics) to fulfill this purpose. On the same website, our aim is to provide updates on current alternative research methods in Korea. The database will not be used directly to conduct safety evaluations, but researchers or regulatory individuals can use it to facilitate their work in formulating safety evaluations for cosmetic materials. We hope this database will help establish new alternative research methods to conduct efficient safety evaluations of cosmetic materials. PMID:27437094

[Food safety and animal diseases. The French Food Safety Agency, from mad cow disease to bird flu].

PubMed

Keck, Frédéric

2008-01-01

Why has the French food safety agency been particularly mobilized on zoonoses like bovine spongiform encephalopathy ("mad cow disease") or highly pathogenic avian influenza ("bird flu") ? Because sanitary crisis make explicit an ambivalent relationship between humans and animals (animals being perceived alternatively as providers of goods and as bearers of threats), and to the circulation of life in general (the contaminated blood crises being due to the rapprochement of blood giving and blood receiving). The sociology of risks needs therefore to reintegrate the idea of an intention of the risk bearer (risk with enemy), and the sociology of alimentation needs to reintegrate the analysis of the conditions of production. Mad cow disease is the paradigmatic food safety crisis because it brings together the poles of production and consumption, of animals and humans. It therefore belongs to anthropology.

Process safety improvement--quality and target zero.

PubMed

Van Scyoc, Karl

2008-11-15

Process safety practitioners have adopted quality management principles in design of process safety management systems with positive effect, yet achieving safety objectives sometimes remain a distant target. Companies regularly apply tools and methods which have roots in quality and productivity improvement. The "plan, do, check, act" improvement loop, statistical analysis of incidents (non-conformities), and performance trending popularized by Dr. Deming are now commonly used in the context of process safety. Significant advancements in HSE performance are reported after applying methods viewed as fundamental for quality management. In pursuit of continual process safety improvement, the paper examines various quality improvement methods, and explores how methods intended for product quality can be additionally applied to continual improvement of process safety. Methods such as Kaizen, Poke yoke, and TRIZ, while long established for quality improvement, are quite unfamiliar in the process safety arena. These methods are discussed for application in improving both process safety leadership and field work team performance. Practical ways to advance process safety, based on the methods, are given.

Determining animal drug combinations based on efficacy and safety.

PubMed

Kratzer, D D; Geng, S

1986-08-01

A procedure for deriving drug combinations for animal health is used to derive an optimal combination of 200 mg of novobiocin and 650,000 IU of penicillin for nonlactating cow mastitis treatment. The procedure starts with an estimated second order polynomial response surface equation. That surface is translated into a probability surface with contours called isoprobs. The isoprobs show drug amounts that have equal probability to produce maximal efficacy. Safety factors are incorporated into the probability surface via a noncentrality parameter that causes the isoprobs to expand as safety decreases, resulting in lower amounts of drug being used.

Guiding principles for the implementation of non-animal safety assessment approaches for cosmetics: skin sensitisation.

PubMed

Goebel, Carsten; Aeby, Pierre; Ade, Nadège; Alépée, Nathalie; Aptula, Aynur; Araki, Daisuke; Dufour, Eric; Gilmour, Nicola; Hibatallah, Jalila; Keller, Detlef; Kern, Petra; Kirst, Annette; Marrec-Fairley, Monique; Maxwell, Gavin; Rowland, Joanna; Safford, Bob; Schellauf, Florian; Schepky, Andreas; Seaman, Chris; Teichert, Thomas; Tessier, Nicolas; Teissier, Silvia; Weltzien, Hans Ulrich; Winkler, Petra; Scheel, Julia

2012-06-01

Characterisation of skin sensitisation potential is a key endpoint for the safety assessment of cosmetic ingredients especially when significant dermal exposure to an ingredient is expected. At present the mouse local lymph node assay (LLNA) remains the 'gold standard' test method for this purpose however non-animal test methods are under development that aim to replace the need for new animal test data. COLIPA (the European Cosmetics Association) funds an extensive programme of skin sensitisation research, method development and method evaluation and helped coordinate the early evaluation of the three test methods currently undergoing pre-validation. In May 2010, a COLIPA scientific meeting was held to analyse to what extent skin sensitisation safety assessments for cosmetic ingredients can be made in the absence of animal data. In order to propose guiding principles for the application and further development of non-animal safety assessment strategies it was evaluated how and when non-animal test methods, predictions based on physico-chemical properties (including in silico tools), threshold concepts and weight-of-evidence based hazard characterisation could be used to enable safety decisions. Generation and assessment of potency information from alternative tools which at present is predominantly derived from the LLNA is considered the future key research area. Copyright © 2012 Elsevier Inc. All rights reserved.

International trade standards for commodities and products derived from animals: the need for a system that integrates food safety and animal disease risk management.

PubMed

Thomson, G R; Penrith, M-L; Atkinson, M W; Thalwitzer, S; Mancuso, A; Atkinson, S J; Osofsky, S A

2013-12-01

A case is made for greater emphasis to be placed on value chain management as an alternative to geographically based disease risk mitigation for trade in commodities and products derived from animals. The geographic approach is dependent upon achievement of freedom in countries or zones from infectious agents that cause so-called transboundary animal diseases, while value chain-based risk management depends upon mitigation of animal disease hazards potentially associated with specific commodities or products irrespective of the locality of production. This commodity-specific approach is founded on the same principles upon which international food safety standards are based, viz. hazard analysis critical control points (HACCP). Broader acceptance of a value chain approach enables animal disease risk management to be combined with food safety management by the integration of commodity-based trade and HACCP methodologies and thereby facilitates 'farm to fork' quality assurance. The latter is increasingly recognized as indispensable to food safety assurance and is therefore a pre-condition to safe trade. The biological principles upon which HACCP and commodity-based trade are based are essentially identical, potentially simplifying sanitary control in contrast to current separate international sanitary standards for food safety and animal disease risks that are difficult to reconcile. A value chain approach would not only enable more effective integration of food safety and animal disease risk management of foodstuffs derived from animals but would also ameliorate adverse environmental and associated socio-economic consequences of current sanitary standards based on the geographic distribution of animal infections. This is especially the case where vast veterinary cordon fencing systems are relied upon to separate livestock and wildlife as is the case in much of southern Africa. A value chain approach would thus be particularly beneficial to under-developed regions of

Crash Simulation and Animation: 'A New Approach for Traffic Safety Analysis'

DOT National Transportation Integrated Search

2001-02-01

This researchs objective is to present a methodology to supplement the conventional traffic safety analysis techniques. This methodology aims at using computer simulation to animate and visualize crash occurrence at high-risk locations. This methodol...

Developing a Comprehensive Animal Care Occupational Health and Safety Program at a Land-Grant Institution.

PubMed

Goodly, Lyndon J; Jarrell, Vickie L; Miller, Monica A; Banks, Maureen C; Anderson, Thomas J; Branson, Katherine A; Woodward, Robert T; Peper, Randall L; Myers, Sara J

2016-01-01

The Public Health Service Policy on the Humane Care and Use of Laboratory Animals and sound ethical practices require institutions to provide safe working environments for personnel working with animals; this mandate is achieved in part by establishing an effective animal care Occupational Health and Safety Program (OHSP). Land-grant institutions often face unique organizational challenges in fulfilling this requirement. For example, responsibilities for providing health and safety programs often have historically been dispersed among many different divisions scattered around the campus. Here we describe how our institutional management personnel overcame organizational structure and cultural obstacles during the formation of a comprehensive campus-wide animal care OHSP. Steps toward establishing the animal care OHSP included assigning overall responsibility, identifying all stakeholders, creating a leadership group, and hiring a fulltime Animal Care OHSP Specialist. A web-based portal was developed, implemented, and refined over the past 7 y and reflected the unique organizational structures of the university and the needs of our research community. Through this web-based portal, hazards are identified, risks are assessed, and training is provided. The animal care OHSP now provides easy mandatory enrollment, supports timely feedback regarding hazards, and affords enrollees the opportunity to participate in voluntary medical surveillance. The future direction and development of the animal care OHSP will be based on the research trends of campus, identification of emerging health and safety hazards, and ongoing evaluation and refinement of the program.

Developing a Comprehensive Animal Care Occupational Health and Safety Program at a Land-Grant Institution

PubMed Central

Goodly, Lyndon J; Jarrell, Vickie L; Miller, Monica A; Banks, Maureen C; Anderson, Thomas J; Branson, Katherine A; Woodward, Robert T; Peper, Randall L; Myers, Sara J

2016-01-01

The Public Health Service Policy on the Humane Care and Use of Laboratory Animals and sound ethical practices require institutions to provide safe working environments for personnel working with animals; this mandate is achieved in part by establishing an effective animal care Occupational Health and Safety Program (OHSP). Land-grant institutions often face unique organizational challenges in fulfilling this requirement. For example, responsibilities for providing health and safety programs often have historically been dispersed among many different divisions scattered around the campus. Here we describe how our institutional management personnel overcame organizational structure and cultural obstacles during the formation of a comprehensive campus-wide animal care OHSP. Steps toward establishing the animal care OHSP included assigning overall responsibility, identifying all stakeholders, creating a leadership group, and hiring a fulltime Animal Care OHSP Specialist. A web-based portal was developed, implemented, and refined over the past 7 y and reflected the unique organizational structures of the university and the needs of our research community. Through this web-based portal, hazards are identified, risks are assessed, and training is provided. The animal care OHSP now provides easy mandatory enrollment, supports timely feedback regarding hazards, and affords enrollees the opportunity to participate in voluntary medical surveillance. The future direction and development of the animal care OHSP will be based on the research trends of campus, identification of emerging health and safety hazards, and ongoing evaluation and refinement of the program. PMID:26817980

The SEURAT-1 approach towards animal free human safety assessment.

PubMed

Gocht, Tilman; Berggren, Elisabet; Ahr, Hans Jürgen; Cotgreave, Ian; Cronin, Mark T D; Daston, George; Hardy, Barry; Heinzle, Elmar; Hescheler, Jürgen; Knight, Derek J; Mahony, Catherine; Peschanski, Marc; Schwarz, Michael; Thomas, Russell S; Verfaillie, Catherine; White, Andrew; Whelan, Maurice

2015-01-01

SEURAT-1 is a European public-private research consortium that is working towards animal-free testing of chemical compounds and the highest level of consumer protection. A research strategy was formulated based on the guiding principle to adopt a toxicological mode-of-action framework to describe how any substance may adversely affect human health.The proof of the initiative will be in demonstrating the applicability of the concepts on which SEURAT-1 is built on three levels:(i) Theoretical prototypes for adverse outcome pathways are formulated based on knowledge already available in the scientific literature on investigating the toxicological mode-of-actions leading to adverse outcomes (addressing mainly liver toxicity);(ii)adverse outcome pathway descriptions are used as a guide for the formulation of case studies to further elucidate the theoretical model and to develop integrated testing strategies for the prediction of certain toxicological effects (i.e., those related to the adverse outcome pathway descriptions);(iii) further case studies target the application of knowledge gained within SEURAT-1 in the context of safety assessment. The ultimate goal would be to perform ab initio predictions based on a complete understanding of toxicological mechanisms. In the near-term, it is more realistic that data from innovative testing methods will support read-across arguments. Both scenarios are addressed with case studies for improved safety assessment. A conceptual framework for a rational integrated assessment strategy emerged from designing the case studies and is discussed in the context of international developments focusing on alternative approaches for evaluating chemicals using the new 21st century tools for toxicity testing.

The safety of 17a-Methyltestosterone medicated feed to tilapia

USDA-ARS?s Scientific Manuscript database

17a-Methyltestosterone (17MT) is used in U.S. aquaculture under an Investigational New Animal Drug exemption to produce male populations of tilapia. Efforts to gain FDA-approval include this Target Animal Safety study. A study was designed to determine its histological safety to tilapia when fed a...

Agroterrorism, Biological Crimes, and Biological Warfare Targeting Animal Agriculture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Terry M.; Logan-Henfrey, Linda; Weller, Richard E.

2000-04-12

There is a rising level of concern that agriculture might be targeted for economic sabotage by terrorists. Knowledge gathered about the Soviet Union biological weapons program and Iraq following the Gulf War, confirmed that animals and agricultural crops were targets of bioweapon development. These revelations are particularly disturbing in light of the fact that both countries are States Parties to the Biological and Toxin Weapons Convention that entered into force in 1975. The potential for misusing biotechnology to create more virulent pathogens and the lack of international means to detect unethical uses of new technologies to create destructive bioweapons ismore » of increasing concern. Disease outbreaks, whether naturally occurring or intentionally, involving agricultural pathogens that destroy livestock and crops would have a profound impact on a country's infrastructure, economy and export markets. This chapter deals with the history of agroterrorism, biological crimes and biological warfare directed toward animal agriculture, specifically, horses, cattle, swine, sheep, goats, and poultry.« less

Assuring safety without animal testing: Unilever's ongoing research programme to deliver novel ways to assure consumer safety.

PubMed

Westmoreland, Carl; Carmichael, Paul; Dent, Matt; Fentem, Julia; MacKay, Cameron; Maxwell, Gavin; Pease, Camilla; Reynolds, Fiona

2010-01-01

Assuring consumer safety without the generation of new animal data is currently a considerable challenge. However, through the application of new technologies and the further development of risk-based approaches for safety assessment, we remain confident it is ultimately achievable. For many complex, multi-organ consumer safety endpoints, the development, evaluation and application of new, non-animal approaches is hampered by a lack of biological understanding of the underlying mechanistic processes involved. The enormity of this scientific challenge should not be underestimated. To tackle this challenge a substantial research programme was initiated by Unilever in 2004 to critically evaluate the feasibility of a new conceptual approach based upon the following key components: 1.Developing new, exposure-driven risk assessment approaches. 2.Developing new biological (in vitro) and computer-based (in silico) predictive models. 3.Evaluating the applicability of new technologies for generating data (e.g. "omics", informatics) and for integrating new types of data (e.g. systems approaches) for risk-based safety assessment. Our research efforts are focussed in the priority areas of skin allergy, cancer and general toxicity (including inhaled toxicity). In all of these areas, a long-term investment is essential to increase the scientific understanding of the underlying biology and molecular mechanisms that we believe will ultimately form a sound basis for novel risk assessment approaches. Our research programme in these priority areas consists of in-house research as well as Unilever-sponsored academic research, involvement in EU-funded projects (e.g. Sens-it-iv, Carcinogenomics), participation in cross-industry collaborative research (e.g. Colipa, EPAA) and ongoing involvement with other scientific initiatives on non-animal approaches to risk assessment (e.g. UK NC3Rs, US "Human Toxicology Project" consortium).

A Template Analysis of Intimate Partner Violence Survivors' Experiences of Animal Maltreatment: Implications for Safety Planning and Intervention.

PubMed

Collins, Elizabeth A; Cody, Anna M; McDonald, Shelby Elaine; Nicotera, Nicole; Ascione, Frank R; Williams, James Herbert

2018-03-01

This study explores the intersection of intimate partner violence (IPV) and animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors recruited from community-based domestic violence programs. Template analysis revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective Safety Planning. Results demonstrate the potential impact of animal maltreatment exposure on women and child IPV survivors' health and safety.

Human Food Safety Implications of Variation in Food Animal Drug Metabolism

PubMed Central

Lin, Zhoumeng; Vahl, Christopher I.; Riviere, Jim E.

2016-01-01

Violative drug residues in animal-derived foods are a global food safety concern. The use of a fixed main metabolite to parent drug (M/D) ratio determined in healthy animals to establish drug tolerances and withdrawal times in diseased animals results in frequent residue violations in food-producing animals. We created a general physiologically based pharmacokinetic model for representative drugs (ceftiofur, enrofloxacin, flunixin, and sulfamethazine) in cattle and swine based on extensive published literature. Simulation results showed that the M/D ratio was not a fixed value, but a time-dependent range. Disease changed M/D ratios substantially and extended withdrawal times; these effects exhibited drug- and species-specificity. These results challenge the interpretation of violative residues based on the use of the M/D ratio to establish tolerances for metabolized drugs. PMID:27302389

Current Status of the Preharvest Application of Pro- and Prebiotics to Farm Animals to Enhance the Microbial Safety of Animal Products.

PubMed

Joerger, Rolf D; Ganguly, Arpeeta

2017-01-01

The selection of microorganisms that act as probiotics and feed additives that act as prebiotics is an ongoing research effort, but a sizable range of commercial pro-, pre- and synbiotic (combining pro- and prebiotics) products are already available and being used on farms. A survey of the composition of commercial products available in the United States revealed that Lactobacillus acidophilus, Enterococcus faecium, and Bacillus subtilis were the three most common species in probiotic products. Of the nearly 130 probiotic products (also called direct-fed microbials) for which information was available, about 50 also contained yeasts or molds. The focus on these particular bacteria and eukaryotes is due to long-standing ideas about the benefits of such strains, research data on effectiveness primarily in laboratory or research farm settings, and regulations that dictate which microorganisms or feed additives can be administered to farm animals. Of the direct-fed microbials, only six made a claim relating to food safety or competitive exclusion of pathogens. None of the approximately 50 prebiotic products mentioned food safety in their descriptions. The remainder emphasized enhancement of animal performance such as weight gain or overall animal health. The reason why so few products carry food safety-related claims is the difficulties in establishing unambiguous cause and effect relationships between the application of such products in varied and constantly changing farm environments and improved food safety of the end product.

Methods of targeting animal sources of fecal pollution in water

EPA Science Inventory

In this chapter, proposed chemical and biological MST indicators for the determination of animal fecal sources are discussed. The biological indicators are grouped based on the phylogenetic description of the proposed target (eukarya, bacteria, and virus). A comprehensive descrip...

Non-animal approaches for consumer safety risk assessments: Unilever's scientific research programme.

PubMed

Carmichael, Paul; Davies, Michael; Dent, Matt; Fentem, Julia; Fletcher, Samantha; Gilmour, Nicola; MacKay, Cameron; Maxwell, Gavin; Merolla, Leona; Pease, Camilla; Reynolds, Fiona; Westmoreland, Carl

2009-12-01

Non-animal based approaches to risk assessment are now routinely used for assuring consumer safety for some endpoints (such as skin irritation) following considerable investment in developing and applying new methods over the past 20 years. Unilever's research programme into non-animal approaches for safety assessment is currently focused on the application of new technologies to risk assessments in the areas of skin allergy, cancer and general toxicity (including inhalation toxicity). In all of these areas, a long-term investment is essential to increase the scientific understanding of the underlying biological and chemical processes that we believe will ultimately form a sound basis for novel risk assessment approaches. Our research programme in these priority areas consists of in-house research as well as Unilever-sponsored academic research, involvement with EU-funded projects (e.g. Sens-it-iv, carcinoGENOMICS), participation in cross-industry collaborative research (e.g. COLIPA, EPAA) and ongoing involvement with other scientific initiatives on non-animal approaches to risk assessment (e.g. UK NC3Rs, US 'Human Toxicology Project' consortium). 2009 FRAME.

A Template Analysis of Intimate Partner Violence Survivors’ Experiences of Animal Maltreatment: Implications for Safety Planning and Intervention

PubMed Central

Collins, Elizabeth A.; Cody, Anna M.; McDonald, Shelby Elaine; Nicotera, Nicole; Ascione, Frank R.; Williams, James Herbert

2018-01-01

This study explores the intersection of intimate partner violence (IPV) and animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors recruited from community-based domestic violence programs. Template analysis revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective Safety Planning. Results demonstrate the potential impact of animal maltreatment exposure on women and child IPV survivors’ health and safety. PMID:29332521

The likelihood of achieving quantified road safety targets: a binary logistic regression model for possible factors.

PubMed

Sze, N N; Wong, S C; Lee, C Y

2014-12-01

In past several decades, many countries have set quantified road safety targets to motivate transport authorities to develop systematic road safety strategies and measures and facilitate the achievement of continuous road safety improvement. Studies have been conducted to evaluate the association between the setting of quantified road safety targets and road fatality reduction, in both the short and long run, by comparing road fatalities before and after the implementation of a quantified road safety target. However, not much work has been done to evaluate whether the quantified road safety targets are actually achieved. In this study, we used a binary logistic regression model to examine the factors - including vehicle ownership, fatality rate, and national income, in addition to level of ambition and duration of target - that contribute to a target's success. We analyzed 55 quantified road safety targets set by 29 countries from 1981 to 2009, and the results indicate that targets that are in progress and with lower level of ambitions had a higher likelihood of eventually being achieved. Moreover, possible interaction effects on the association between level of ambition and the likelihood of success are also revealed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Regulatory Forum Opinion Piece*: Use and Utility of Animal Models of Disease for Nonclinical Safety Assessment: A Pharmaceutical Industry Survey.

PubMed

Morgan, Sherry J; Couch, Jessica; Guzzie-Peck, Peggy; Keller, Douglas A; Kemper, Ray; Otieno, Monicah A; Schulingkamp, Robert J; Jones, Thomas W

2017-04-01

An Innovation and Quality (IQ) Consortium focus group conducted a cross-company survey to evaluate current practices and perceptions around the use of animal models of disease (AMDs) in nonclinical safety assessment of molecules in clinical development. The IQ Consortium group is an organization of pharmaceutical and biotechnology companies with the mission of advancing science and technology. The survey queried the utilization of AMDs during drug discovery in which drug candidates are evaluated in efficacy models and limited short-duration non-Good Laboratory Practices (GLP) toxicology testing and during drug development in which drug candidates are evaluated in GLP toxicology studies. The survey determined that the majority of companies used AMDs during drug discovery primarily as a means for proactively assessing potential nonclinical safety issues prior to the conduct of toxicology studies, followed closely by the use of AMDs to better understand toxicities associated with exaggerated pharmacology in traditional toxicology models or to derisk issues when the target is only expressed in the disease state. In contrast, the survey results indicated that the use of AMDs in development is infrequent, being used primarily to investigate nonclinical safety issues associated with targets expressed only in disease states and/or in response to requests from global regulatory authorities.

DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS.

PubMed

Ahmari, Susanne E; Dougherty, Darin D

2015-08-01

Obsessive-compulsive disorder (OCD) is a chronic, severe mental illness with up to 2-3% prevalence worldwide. In fact, OCD has been classified as one of the world's 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms.([1]) Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology. However, this is now rapidly changing due to development of powerful technologies that can be used to dissect the neural circuits underlying pathologic behaviors. In this article, we describe recent technical advances that have allowed neuroscientists to start identifying the circuits underlying complex repetitive behaviors using animal model systems. In addition, we review current surgical and stimulation-based treatments for OCD that target circuit dysfunction. Finally, we discuss how findings from animal models may be applied in the clinical arena to help inform and refine targeted brain stimulation-based treatment approaches. © 2015 Wiley Periodicals, Inc.

The use of non-animal alternatives in the safety evaluations of cosmetics ingredients by the Scientific Committee on Consumer Safety (SCCS).

PubMed

Vinardell, M P

2015-03-01

In Europe, the safety evaluation of cosmetics is based on the safety evaluation of each individual ingredient. Article 3 of the Cosmetics Regulation specifies that a cosmetic product made available on the market is to be safe for human health when used normally or under reasonably foreseeable conditions. For substances that cause some concern with respect to human health (e.g., colourants, preservatives, UV-filters), safety is evaluated at the Commission level by a scientific committee, presently called the Scientific Committee on Consumer Safety (SCCS). According to the Cosmetics Regulations, in the EU, the marketing of cosmetics products and their ingredients that have been tested on animals for most of their human health effects, including acute toxicity, is prohibited. Nevertheless, any study dating from before this prohibition took effect is accepted for the safety assessment of cosmetics ingredients. The in vitro methods reported in the dossiers submitted to the SCCS are here evaluated from the published reports issued by the scientific committee of the Directorate General of Health and Consumers (DG SANCO); responsible for the safety of cosmetics ingredients. The number of studies submitted to the SCCS that do not involve animals is still low and in general the safety of cosmetics ingredients is based on in vivo studies performed before the prohibition. Copyright © 2014 Elsevier Inc. All rights reserved.

Foodservice employees benefit from interventions targeting barriers to food safety.

PubMed

York, Valerie K; Brannon, Laura A; Shanklin, Carol W; Roberts, Kevin R; Howells, Amber D; Barrett, Elizabeth B

2009-09-01

The number of foodborne illnesses traced to improper food handling in restaurants indicates a need for research to improve food safety in these establishments. Therefore, this 2-year longitudinal study investigated the effectiveness of traditional ServSafe (National Restaurant Association Educational Foundation, Chicago, IL) food-safety training and a Theory of Planned Behavior intervention program targeting employees' perceived barriers and attitudes toward important food-safety behaviors. The effectiveness of the training and intervention was measured by knowledge scores and observed behavioral compliance rates related to food-safety practices. Employees were observed for handwashing, thermometer usage, and proper handling of work surfaces at baseline, after receiving ServSafe training, and again after exposure to the intervention targeting barriers and negative attitudes about food-safety practices. Repeated-measures analyses of variance indicated training improved handwashing knowledge, but the intervention was necessary to improve overall behavioral compliance and handwashing compliance. Results suggest that registered dietitians; dietetic technicians, registered; and foodservice managers should implement a combination of training and intervention to improve knowledge and compliance with food-safety behaviors, rather than relying on training alone. Challenges encountered while conducting this research are discussed, and recommendations are provided for researchers interested in conducting this type of research in the future.

Online virtual isocenter based radiation field targeting for high performance small animal microirradiation

NASA Astrophysics Data System (ADS)

Stewart, James M. P.; Ansell, Steve; Lindsay, Patricia E.; Jaffray, David A.

2015-12-01

Advances in precision microirradiators for small animal radiation oncology studies have provided the framework for novel translational radiobiological studies. Such systems target radiation fields at the scale required for small animal investigations, typically through a combination of on-board computed tomography image guidance and fixed, interchangeable collimators. Robust targeting accuracy of these radiation fields remains challenging, particularly at the millimetre scale field sizes achievable by the majority of microirradiators. Consistent and reproducible targeting accuracy is further hindered as collimators are removed and inserted during a typical experimental workflow. This investigation quantified this targeting uncertainty and developed an online method based on a virtual treatment isocenter to actively ensure high performance targeting accuracy for all radiation field sizes. The results indicated that the two-dimensional field placement uncertainty was as high as 1.16 mm at isocenter, with simulations suggesting this error could be reduced to 0.20 mm using the online correction method. End-to-end targeting analysis of a ball bearing target on radiochromic film sections showed an improved targeting accuracy with the three-dimensional vector targeting error across six different collimators reduced from 0.56+/- 0.05 mm (mean  ±  SD) to 0.05+/- 0.05 mm for an isotropic imaging voxel size of 0.1 mm.

76 FR 13638 - Ensuring the Safety of Imported Foods and Animal Feed: Comparability of Food Safety Systems and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-14

... Practices of Foreign Countries; Public Hearing; Request for Comments AGENCY: Food and Drug Administration... regulators in other countries regarding the regulatory policies, practices, and programs they currently use to ensure the safety of foods and animal feed imported into their countries. In a separate notice...

Safe use of vaccines and vaccine compliance with food safety requirements.

PubMed

Grein, K; Papadopoulos, O; Tollis, M

2007-08-01

Advanced technologies and regulatory regimes have contributed to the availability of veterinary vaccines that have high quality and favourable safety profiles in terms of potential risks posed to the target animals, the persons who come into contact with the vaccine, the consumers of food derived from vaccinated animals and the environment. The authorisation process requires that a range of safety studies are provided to evaluate the products. The design and production of vaccines, and their safe use, are primarily assessed by using data gathered from extensive pre-marketing studies performed on target animals and specific quality tests. The current post-marketing safeguards include good manufacturing practices, batch safety testing, inspections and pharmacovigilance. In addition to hazard identification, a full benefit/risk evaluation needs to be undertaken. The outcome of that evaluation will determine options for risk management and affect regulatory decisions on the safety of the vaccine; options might, for example, include special warnings on package inserts and labels.

The role of veterinary services in animal health and food safety surveillance, and coordination with other services.

PubMed

Bellemain, V

2013-08-01

The control of animal health and food safety has undergone profound changes and is now seen in terms of a global approach, 'from the stable to the table'. The risks themselves have also evolved, principally due to changing practices, and this, coupled with increased knowledge and changes in consumer demands, has led to a more global conception of production chains. In terms of official controls, targeted control of the final food product has gradually been replaced by control of the production processes and an integrated approach to hazards throughout the production chain. This, in turn, has resulted in a new division of responsibilities among the producers (farmers), the manufacturers and the administration; namely, Veterinary Services. The areas in which veterinarians are involved have gradually been extended from animal production to all levels of the food production chain. Animal health interventions on farms are comparable to interventions in agri-food companies. Both are, or should be, included in veterinary training and education. To meet new challenges, the current trend is for Veterinary Services to be responsible for, or coordinate, sanitary interventions from the stable to the table. Coordination between Veterinary Services and other relevant authorities is a key component of good public governance, especially for effective action and optimal management of the resources available.

Applications and safety considerations of Lactobacillus salivarius as a probiotic in animal and human health.

PubMed

Chaves, B D; Brashears, M M; Nightingale, K K

2017-03-03

The goals of this review are to summarize the current knowledge on the application of Lactobacillus salivarius as a probiotic in animals and humans, and to address safety concerns with its use on live hosts. Overall, several strains of L. salivarius are well established probiotics with multiple applications in animal health, particularly to reduce colonization by gastrointestinal pathogens, and to a lesser extent, as a production and quality aid. In humans, L. salivarius has been used to prevent and treat a variety of chronic diseases, including asthma, cancer, atopic dermatitis and halitosis, and to a much limited extent, to prevent or treat infections. Based on the results from primary research evidence, it seems that L. salivarius does not pose a health risk to animals or humans in the doses currently used for a variety of applications; however, there is a systematic lack of studies assuring the safety of many of the strains intended for clinical use. This review provides researchers in the field with up-to-date information regarding applications and safety of L. salivarius. Furthermore, it helps researchers identify knowledge gaps and potential opportunities for microbiological and clinical research. © 2017 The Society for Applied Microbiology.

Steps towards the international regulatory acceptance of non-animal methodology in safety assessment.

PubMed

Sewell, Fiona; Doe, John; Gellatly, Nichola; Ragan, Ian; Burden, Natalie

2017-10-01

The current animal-based paradigm for safety assessment must change. In September 2016, the UK National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs) brought together scientists from regulatory authorities, academia and industry to review progress in bringing new methodology into regulatory use, and to identify ways to expedite progress. Progress has been slow. Science is advancing to make this possible but changes are necessary. The new paradigm should allow new methodology to be adopted once it is developed rather than being based on a fixed set of studies. Regulatory authorities can help by developing Performance-Based Standards. The most pressing need is in repeat dose toxicology, although setting standards will be more complex than in areas such as sensitization. Performance standards should be aimed directly at human safety, not at reproducing the results of animal studies. Regulatory authorities can also aid progress towards the acceptance of non-animal based methodology by promoting "safe-haven" trials where traditional and new methodology data can be submitted in parallel to build up experience in the new methods. Industry can play its part in the acceptance of new methodology, by contributing to the setting of performance standards and by actively contributing to "safe-haven" trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials.

PubMed

2008-03-01

In this report the various elements of the safety and nutritional assessment procedure for genetically modified (GM) plant derived food and feed are discussed, in particular the potential and limitations of animal feeding trials for the safety and nutritional testing of whole GM food and feed. The general principles for the risk assessment of GM plants and derived food and feed are followed, as described in the EFSA guidance document of the EFSA Scientific Panel on Genetically Modified Organisms. In Section 1 the mandate, scope and general principles for risk assessment of GM plant derived food and feed are discussed. Products under consideration are food and feed derived from GM plants, such as maize, soybeans, oilseed rape and cotton, modified through the introduction of one or more genes coding for agronomic input traits like herbicide tolerance and/or insect resistance. Furthermore GM plant derived food and feed, which have been obtained through extensive genetic modifications targeted at specific alterations of metabolic pathways leading to improved nutritional and/or health characteristics, such as rice containing beta-carotene, soybeans with enhanced oleic acid content, or tomato with increased concentration of flavonoids, are considered. The safety assessment of GM plants and derived food and feed follows a comparative approach, i.e. the food and feed are compared with their non-GM counterparts in order to identify intended and unintended (unexpected) differences which subsequently are assessed with respect to their potential impact on the environment, safety for humans and animals, and nutritional quality. Key elements of the assessment procedure are the molecular, compositional, phenotypic and agronomic analysis in order to identify similarities and differences between the GM plant and its near isogenic counterpart. The safety assessment is focussed on (i) the presence and characteristics of newly expressed proteins and other new constituents and possible

Engineering nucleases for gene targeting: safety and regulatory considerations.

PubMed

Pauwels, Katia; Podevin, Nancy; Breyer, Didier; Carroll, Dana; Herman, Philippe

2014-01-25

Nuclease-based gene targeting (NBGT) represents a significant breakthrough in targeted genome editing since it is applicable from single-celled protozoa to human, including several species of economic importance. Along with the fast progress in NBGT and the increasing availability of customized nucleases, more data are available about off-target effects associated with the use of this approach. We discuss how NBGT may offer a new perspective for genetic modification, we address some aspects crucial for a safety improvement of the corresponding techniques and we also briefly relate the use of NBGT applications and products to the regulatory oversight. Copyright © 2013 Elsevier B.V. All rights reserved.

Microbiological Safety of Animal Wastes Processed by Physical Heat Treatment: An Alternative To Eliminate Human Pathogens in Biological Soil Amendments as Recommended by the Food Safety Modernization Act.

PubMed

Chen, Zhao; Jiang, Xiuping

2017-03-01

Animal wastes have high nutritional value as biological soil amendments of animal origin for plant cultivation in sustainable agriculture; however, they can be sources of some human pathogens. Although composting is an effective way to reduce pathogen levels in animal wastes, pathogens may still survive under certain conditions and persist in the composted products, which potentially could lead to fresh produce contamination. According to the U.S. Food and Drug Administration Food Safety Modernization Act, alternative treatments are recommended for reducing or eliminating human pathogens in raw animal manure. Physical heat treatments can be considered an effective method to inactivate pathogens in animal wastes. However, microbial inactivation in animal wastes can be affected by many factors, such as composition of animal wastes, type and physiological stage of the tested microorganism, and heat source. Following some current processing guidelines for physical heat treatments may not be adequate for completely eliminating pathogens from animal wastes. Therefore, this article primarily reviews the microbiological safety and economic value of physically heat-treated animal wastes as biological soil amendments.

Recent advances in the development of new transgenic animal technology.

PubMed

Miao, Xiangyang

2013-03-01

Transgenic animal technology is one of the fastest growing biotechnology areas. It is used to integrate exogenous genes into the animal genome by genetic engineering technology so that these genes can be inherited and expressed by offspring. The transgenic efficiency and precise control of gene expression are the key limiting factors in the production of transgenic animals. A variety of transgenic technologies are available. Each has its own advantages and disadvantages and needs further study because of unresolved technical and safety issues. Further studies will allow transgenic technology to explore gene function, animal genetic improvement, bioreactors, animal disease models, and organ transplantation. This article reviews the recently developed animal transgenic technologies, including the germ line stem cell-mediated method to improve efficiency, gene targeting to improve accuracy, RNA interference-mediated gene silencing technology, zinc-finger nuclease gene targeting technology and induced pluripotent stem cell technology. These new transgenic techniques can provide a better platform to develop transgenic animals for breeding new animal varieties and promote the development of medical sciences, livestock production, and other fields.

The Role of Veterinary Education in Safety Policies for Animal-Assisted Therapy and Activities in Hospitals and Nursing Homes.

PubMed

Linder, Deborah E; Mueller, Megan K; Gibbs, Debra M; Siebens, Hannah C; Freeman, Lisa M

Animal-assisted activities (AAA) and animal-assisted therapy (AAT) programs are increasing in popularity, but current programs vary in their safety and health policies. Veterinarians can have an important role in ensuring the safety of both the animals and humans involved, but it is unclear how best to educate veterinary students to serve effectively in this role. Therefore, the goal of this study was to assess the knowledge gaps and perceptions of first-year veterinary students on health and safety aspects of AAA/AAT programs by administering a survey. This information could then guide future educational training in veterinary schools to address the knowledge gaps in this area. Formal education during the veterinary curriculum had not yet been provided to these students on AAA/AAT before the survey. Of 98 first-year veterinary students, 91 completed the survey. When asked about policies on visiting animals, 58% of students responded that nursing homes are required to have a policy and 67% responded that hospitals are required to have one. Three quarters of students reported that veterinarians, animal handlers, and facilities should share the responsibility for ensuring safe human-animal interaction in AAA/AAT programs. Most (82%) of the students responded that all or most national and local therapy animal groups prohibit animals that consume raw meat diets from participating in AAA/AAT programs. The results of this survey will help veterinary schools better identify knowledge gaps that can be addressed in veterinary curricula so future veterinarians will be equipped to provide appropriate public health information regarding AAA/AAT programs.

Do whole-food animal feeding studies have any value in the safety assessment of GM crops?

PubMed

Herman, Rod A; Ekmay, Ricardo

2014-02-01

The use of whole-food (grain meal contained in feed) animal-feeding studies to support the safety assessment of genetically modified crops has been contentious. This may be, in part, a consequence of poorly agreed upon study objectives. Whole-food animal-feeding studies have been postulated to be useful in detecting both expected and unexpected effects on the composition of genetically modified crops. While the justification of animal feeding studies to detect unexpected effects may be inadequately supported, there may be better justification to conduct such studies in specific cases to investigate the consequences of expected compositional effects including expression of transgenic proteins. Such studies may be justified when (1) safety cannot reasonably be predicted from other evidence, (2) reasonable hypothesis for adverse effects are postulated, (3) the compositional component in question cannot be isolated or enriched in an active form for inclusion in animal feeding studies, and (4) reasonable multiples of exposure can be accomplished relative to human diets. The study design for whole-food animal-feeding studies should be hypotheses-driven, and the types of data collected should be consistent with adverse effects that are known to occur from dietary components of biological origin. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Testing Chemical Safety: What Is Needed to Ensure the Widespread Application of Non-animal Approaches?

PubMed Central

Burden, Natalie; Sewell, Fiona; Chapman, Kathryn

2015-01-01

Scientists face growing pressure to move away from using traditional animal toxicity tests to determine whether manufactured chemicals are safe. Numerous ethical, scientific, business, and legislative incentives will help to drive this shift. However, a number of hurdles must be overcome in the coming years before non-animal methods are adopted into widespread practice, particularly from regulatory, scientific, and global perspectives. Several initiatives are nevertheless underway that promise to increase the confidence in newer alternative methods, which will support the move towards a future in which less data from animal tests is required in the assessment of chemical safety. PMID:26018957

Deep Sequencing of Plant and Animal DNA Contained within Traditional Chinese Medicines Reveals Legality Issues and Health Safety Concerns

PubMed Central

Coghlan, Megan L.; Haile, James; Houston, Jayne; Murray, Dáithí C.; White, Nicole E.; Moolhuijzen, Paula; Bellgard, Matthew I.; Bunce, Michael

2012-01-01

Traditional Chinese medicine (TCM) has been practiced for thousands of years, but only within the last few decades has its use become more widespread outside of Asia. Concerns continue to be raised about the efficacy, legality, and safety of many popular complementary alternative medicines, including TCMs. Ingredients of some TCMs are known to include derivatives of endangered, trade-restricted species of plants and animals, and therefore contravene the Convention on International Trade in Endangered Species (CITES) legislation. Chromatographic studies have detected the presence of heavy metals and plant toxins within some TCMs, and there are numerous cases of adverse reactions. It is in the interests of both biodiversity conservation and public safety that techniques are developed to screen medicinals like TCMs. Targeting both the p-loop region of the plastid trnL gene and the mitochondrial 16S ribosomal RNA gene, over 49,000 amplicon sequence reads were generated from 15 TCM samples presented in the form of powders, tablets, capsules, bile flakes, and herbal teas. Here we show that second-generation, high-throughput sequencing (HTS) of DNA represents an effective means to genetically audit organic ingredients within complex TCMs. Comparison of DNA sequence data to reference databases revealed the presence of 68 different plant families and included genera, such as Ephedra and Asarum, that are potentially toxic. Similarly, animal families were identified that include genera that are classified as vulnerable, endangered, or critically endangered, including Asiatic black bear (Ursus thibetanus) and Saiga antelope (Saiga tatarica). Bovidae, Cervidae, and Bufonidae DNA were also detected in many of the TCM samples and were rarely declared on the product packaging. This study demonstrates that deep sequencing via HTS is an efficient and cost-effective way to audit highly processed TCM products and will assist in monitoring their legality and safety especially when

Comprehensive target populations for current active safety systems using national crash databases.

PubMed

Kusano, Kristofer D; Gabler, Hampton C

2014-01-01

The objective of active safety systems is to prevent or mitigate collisions. A critical component in the design of active safety systems is the identification of the target population for a proposed system. The target population for an active safety system is that set of crashes that a proposed system could prevent or mitigate. Target crashes have scenarios in which the sensors and algorithms would likely activate. For example, the rear-end crash scenario, where the front of one vehicle contacts another vehicle traveling in the same direction and in the same lane as the striking vehicle, is one scenario for which forward collision warning (FCW) would be most effective in mitigating or preventing. This article presents a novel set of precrash scenarios based on coded variables from NHTSA's nationally representative crash databases in the United States. Using 4 databases (National Automotive Sampling System-General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS], Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash Causation Survey [NMVCCS]) the scenarios developed in this study can be used to quantify the number of police-reported crashes, seriously injured occupants, and fatalities that are applicable to proposed active safety systems. In this article, we use the precrash scenarios to identify the target populations for FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash scenarios were derived using precrash variables (critical event, accident type, precrash movement) present in all 4 data sources. This study found that these active safety systems could potentially mitigate approximately 1 in 5 of all severity and serious injury crashes in the United States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In addition

New frontiers in gene targeting and cloning: success, application and challenges in domestic animals and human embryonic stem cells.

PubMed

Denning, Chris; Priddle, Helen

2003-07-01

Until recently, precise modification of the animal genome by gene targeting was restricted to the mouse because germline competent embryonic stem cells are not available in any other mammalian species. Nuclear transfer (NT) technology now provides an alternative route for cell-based transgenesis in domestic species, offering new opportunities in genetic modification. Livestock that produce human therapeutic proteins in their milk, have organs suitable for xenotransplantation, or that could provide resistance to diseases such as spongiform encephalopathies have been produced by NT from engineered, cultured somatic cells. However, improvements in the efficiency of somatic cell gene targeting and a greater understanding of the reprogramming events that occur during NT are required for the routine application of what is currently an inefficient process. The ability to reprogramme and genetically manipulate cells will also be crucial for full exploitation of human embryonic stem (hES) cells, which offer unparalleled opportunities in human health and biotechnology. Particularly pertinent are directed differentiation of hES lines to specific cell lineages, production of cells that evade the patient's immune system and ensuring the safety of ensuing transplants. This review will discuss some of the successes, applications and challenges facing gene targeting in livestock and hES cells.

COMPARATIVE DIVERSITY OF FECAL BACTERIA IN AGRICULTURALLY SIGNIFICANT ANIMALS TO IDENTIFY ALTERNATIVE TARGETS FOR MICROBIAL SOURCE TRACKING

EPA Science Inventory

Animals of agricultural significance contribute a large percentage of fecal pollution to waterways via runoff contamination. The premise of microbial source tracking is to utilize fecal bacteria to identify target populations which are directly correlated to specific animal feces...

Animal production food safety: priority pathogens for standard setting by the World Organisation for Animal Health.

PubMed

Knight-Jones, T J D; Mylrea, G E; Kahn, S

2010-12-01

In this short study, expert opinion and a literature review were used to identify the pathogens that should be prioritised by the World Organisation for Animal Health (OIE) for the development of future standards for animal production food safety. Prioritisation was based on a pathogen's impact on human health and amenability to control using on-farm measures. As the OIE mandate includes alleviation of global poverty, the study focused on developing countries and those with 'in-transition' economies. The regions considered were Eastern Europe, Asia, the Middle East, Africa and South America. Salmonella (from species other than poultry) and pathogenic Escherichia coli were considered to be top priorities. Brucella spp., Echinococcus granulosus and Staphylococcus aureus were also mentioned by experts. As Salmonella, and to a lesser extent pathogenic E. coli, can be controlled by on-farm measures, these pathogens should be considered for prioritisation in future standard setting. On-farm control measures for Brucella spp. will be addressed in 2010-2011 in a review of the OLE Terrestrial Animal/Health Code chapter on brucellosis. In Africa, E. granulosus, the causative agent of hydatidosis, was estimated to have the greatest impact of all pathogens that could potentially be transmitted by food (i.e. via contamination). It was also listed for the Middle East and thought to be of importance by both South American experts consulted. Taenia saginata was thought to be of importance in South America and Africa and by one expert in the Middle East.

High-throughput screening and small animal models, where are we?

PubMed Central

Giacomotto, Jean; Ségalat, Laurent

2010-01-01

Current high-throughput screening methods for drug discovery rely on the existence of targets. Moreover, most of the hits generated during screenings turn out to be invalid after further testing in animal models. To by-pass these limitations, efforts are now being made to screen chemical libraries on whole animals. One of the most commonly used animal model in biology is the murine model Mus musculus. However, its cost limit its use in large-scale therapeutic screening. In contrast, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the fish Danio rerio are gaining momentum as screening tools. These organisms combine genetic amenability, low cost and culture conditions that are compatible with large-scale screens. Their main advantage is to allow high-throughput screening in a whole-animal context. Moreover, their use is not dependent on the prior identification of a target and permits the selection of compounds with an improved safety profile. This review surveys the versatility of these animal models for drug discovery and discuss the options available at this day. PMID:20423335

An overview of animal models for assessing synthetic vitreous fibers (SVFs) safety.

PubMed

Johnson, N F

1994-12-01

Synthetic vitreous fibers (SVFs) are materials with many important commercial applications. The fibrous nature of the SVFs raises concerns about their potential human health hazards. However, sufficient epidemiological data do not exist to establish the hazardous nature of all SVFs. In addition, the cellular and molecular mechanisms underlying the induction of pulmonary lesions are only partially understood. Without sufficient evidence to associate fiber exposure and lung disease, animal bioassays have been used to identify specific hazardous fibers. These bioassays include inhalation exposures, intratracheal instillation, and intracavitary injection (intrapleural and intraperitoneal). Inhalation exposures of animals most closely represent the human experience, but these exposures are costly and time-consuming to conduct. Intratracheal and intracavitary administrations of fiber are alternatives to inhalation exposures; however, they do not represent human exposures and can give false positive results. The limitations of the noninhalation approaches must be considered when addressing the potential for a respirable fiber to induce human lung disease. In addition, when the results from inhalation exposures do not agree with the alternative animal assays, most weight should be given to the animal inhalation assays because of the limitations of the alternative approaches. To determine the safety of SVFs, both the inhalation and noninhalation approaches are suggested.

Biological preservation of plant derived animal feed with antifungal microorganisms: safety and formulation aspects.

PubMed

Melin, Petter; Sundh, Ingvar; Håkansson, Sebastian; Schnürer, Johan

2007-08-01

During storage of moist animal feed, growth of detrimental fungi causing spoilage, or being mycotoxigenic or pathogenic, is a severe problem. Addition of biopreservative yeasts or lactic acid bacteria can significantly reduce this problem. However, their use requires several careful considerations. One is the safety to the animal, humans and the environment, tightly connected to legal aspects and the need for pre-market authorisation when supplementing feed with microorganisms. Although both yeasts and lactic acid bacteria are considered comparatively safe organisms due to low production of toxic metabolites, it is of great importance to understand the mechanisms behind the biopreservative abilities. Another important issue concerns practical aspects, such as the economic production of large amounts of the organisms and the development of a suitable formulation giving the organisms a long shelf life. These aspects are discussed and a recommendation of this review is that both safety and formulation aspects of a specific microbe should be considered at an early stage in the selection of new organisms with biopreservation potential.

Critical Evaluation of Animal Alternative Tests for the Identification of Endocrine Active Substances

EPA Science Inventory

A significant amount of research is currently targeted to evaluate alternative test methods that may reduce, refine, or replace the use of animals, while ensuring human and environmental health and safety. It is important that the information gained from the alternative tests pr...

Technological Advances in Cardiovascular Safety Assessment Decrease Preclinical Animal Use and Improve Clinical Relevance.

PubMed

Berridge, Brian R; Schultze, A Eric; Heyen, Jon R; Searfoss, George H; Sarazan, R Dustan

2016-12-01

Cardiovascular (CV) safety liabilities are significant concerns for drug developers and preclinical animal studies are predominately where those liabilities are characterized before patient exposures. Steady progress in technology and laboratory capabilities is enabling a more refined and informative use of animals in those studies. The application of surgically implantable and telemetered instrumentation in the acute assessment of drug effects on CV function has significantly improved historical approaches that involved anesthetized or restrained animals. More chronically instrumented animals and application of common clinical imaging assessments like echocardiography and MRI extend functional and in-life structural assessments into the repeat-dose setting. A growing portfolio of circulating CV biomarkers is allowing longitudinal and repeated measures of cardiac and vascular injury and dysfunction better informing an understanding of temporal pathogenesis and allowing earlier detection of undesirable effects. In vitro modeling systems of the past were limited by their lack of biological relevance to the in vivo human condition. Advances in stem cell technology and more complex in vitro modeling platforms are quickly creating more opportunity to supplant animals in our earliest assessments for liabilities. Continuing improvement in our capabilities in both animal and nonanimal modeling should support a steady decrease in animal use for primary liability identification and optimize the translational relevance of the animal studies we continue to do. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[New advances in animal transgenic technology].

PubMed

Sun, Zhen-Hong; Miao, Xiang-Yang; Zhu, Rui-Liang

2010-06-01

Animal transgenic technology is one of the fastest growing biotechnology in the 21st century. It is used to integrate foreign genes into the animal genome by genetic engineering technology so that foreign genes can be expressed and inherited to the offspring. The transgenic efficiency and precise control of gene expression are the key limiting factors on preparation of transgenic animals. A variety of transgenic techniques are available, each of which has its own advantages and disadvantages and still needs further study because of unresolved technical and safety issues. With the in-depth research, the transgenic technology will have broad application prospects in the fields of exploration of gene function, animal genetic improvement, bioreactor, animal disease models, organ transplantation and so on. This article reviews the recently developed animal gene transfer techniques, including germline stem cell mediated method to improve the efficiency, gene targeting to improve the accuracy, RNA interference (RNAi)-mediated gene silencing technology, and the induced pluripotent stem cells (iPS) transgenic technology. The new transgenic techniques can provide a better platform for the study of trans-genic animals and promote the development of medical sciences, livestock production, and other fields.

Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

PubMed

Somogyi, A

1979-01-01

The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.

The Effect of Stress, Attitudes, and Behavior on Safety during Animal Handling in Swedish Dairy Farming.

PubMed

Lindahl, Cecilia; Pinzke, Stefan; Keeling, Linda J; Lundqvist, Peter

2015-01-01

Working with livestock is a hazardous activity, and animals have been found to be the most frequent injury source on dairy farms. Understanding the risk factors for injury and the causal relationships related to injuries and animal handling is important for developing prevention strategies and effective safety interventions. This study examined stress and handler attitude as possible risk factors for animal handling injuries in dairy farming, in particular when moving cows. Twelve dairy farms were visited on two occasions representing different stress levels: when cows were being moved to milking (low stress) and to hoof trimming (high stress). Behavioral observations of handlers and cows were performed, and questionnaires were completed on attitudes (risk acceptance, safety locus of control, and attitudes toward cows) and stress (perceived stress/energy level and job strain). The injury risks were found to be higher when moving cows to hoof trimming compared with moving cows to milking and gentle, moderately forceful, and forceful interactions were more frequently used. When moving cows to milking, observed risk situations were related only to the perceived energy level of the handler. When moving cows to hoof trimming, injury risks were correlated to job strain and time spent in the risk zone (defined as the area where the handler could be hit by the cow's head or hind legs). The time spent in the risk zone was positively correlated with job strain, age, and experience. Attitudes were not found to have significant impact on safety but were to some extent indirectly involved. These results suggest that the main focus in injury reduction work should be on reducing the time the handler spends in close proximity to animals during aversive procedures and on minimizing cow fear and stress by proper handling techniques and appropriate design of handling facilities.

Performance Measurement and Target-Setting in California's Safety Net Health Systems.

PubMed

Hemmat, Shirin; Schillinger, Dean; Lyles, Courtney; Ackerman, Sara; Gourley, Gato; Vittinghoff, Eric; Handley, Margaret; Sarkar, Urmimala

Health policies encourage implementing quality measurement with performance targets. The 2010-2015 California Medicaid waiver mandated quality measurement and reporting. In 2013, California safety net hospitals participating in the waiver set a voluntary performance target (the 90th percentile for Medicare preferred provider organization plans) for mammography screening and cholesterol control in diabetes. They did not reach the target, and the difference-in-differences analysis suggested that there was no difference for mammography ( P = .39) and low-density lipoprotein control ( P = .11) performance compared to measures for which no statewide quality improvement initiative existed. California's Medicaid waiver was associated with improved performance on a number of metrics, but this performance was not attributable to target setting on specific health conditions. Performance may have improved because of secular trends or systems improvements related to waiver funding. Relying on condition-specific targets to measure performance may underestimate improvements and disadvantage certain health systems. Achieving ambitious targets likely requires sustained fiscal, management, and workforce investments.

A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases.

PubMed

Verstockt, Bram; Deleenheer, Barbara; Van Assche, Gert; Vermeire, Séverine; Ferrante, Marc

2017-07-01

Many different compounds targeting the interleukin 23/17 axis have been developed and successfully studied in several autoimmune diseases, including inflammatory bowel diseases. Nevertheless, interfering with key immunological pathways raises potential safety concerns. This review focuses on the safety profile of these novel biological therapies. Areas covered: A literature search until March 2017 was performed to collect safety data on different compounds targeting this pathway, with emphasis on ustekinumab and secukinumab. Firstly, the authors discuss briefly how genetics can inform about potential safety issues. Secondly, they extensively describe safety issues (common adverse events, infections, malignancies…), immunogenicity, exposure to ustekinumab in specific populations and provide advice for vaccination. Finally, they address safety profiles of secukinumab and other biological targeting the IL-23/17 axis in IBD. Expert opinion: Current evidence suggests that ustekinumab therapy overweigh the potential drug-related risks. Additional safety data beyond randomized-controlled trials, derived from statistically powered, large prospective studies with long-term follow-up are urgently needed to assess the real-life ustekinumab-related risks and to establish the correct position of these novel class of biologicals in IBD treatment. Combining immunomodulators with ustekinumab seems to be safe, though prospective data specifically addressing this topic are currently missing. Similarly, the combination of different biological therapies still has to be studied.

Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

PubMed Central

Lin, Tai-Chi; Zhu, Danhong; Hinton, David R.; Clegg, Dennis O.; Humayun, Mark S.

2017-01-01

Dysfunction and death of retinal pigment epithelium (RPE) and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula). Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors) into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed. PMID:28928775

Animal Product Safety Information

MedlinePlus

... options Linkedin Pin it Email Print How to Report a Pet Food Complaint You can report complaints ... Food Complaint page for more information. How to report when your animal has a bad reaction to ...

The economic burden of patient safety targets in acute care: a systematic review

PubMed Central

Mittmann, Nicole; Koo, Marika; Daneman, Nick; McDonald, Andrew; Baker, Michael; Matlow, Anne; Krahn, Murray; Shojania, Kaveh G; Etchells, Edward

2012-01-01

Background Our objective was to determine the quality of literature in costing of the economic burden of patient safety. Methods We selected 15 types of patient safety targets for our systematic review. We searched the literature published between 2000 and 2010 using the following terms: “costs and cost analysis,” “cost-effectiveness,” “cost,” and “financial management, hospital.” We appraised the methodologic quality of potentially relevant studies using standard economic methods. We recorded results in the original currency, adjusted for inflation, and then converted to 2010 US dollars for comparative purposes (2010 US$1.00 = 2010 €0.76). The quality of each costing study per patient safety target was also evaluated. Results We screened 1948 abstracts, and identified 158 potentially eligible studies, of which only 61 (39%) reported any costing methodology. In these 61 studies, we found wide estimates of the attributable costs of patient safety events ranging from $2830 to $10,074. In general hospital populations, the cost per case of hospital-acquired infection ranged from $2132 to $15,018. Nosocomial bloodstream infection was associated with costs ranging from $2604 to $22,414. Conclusion There are wide variations in the estimates of economic burden due to differences in study methods and methodologic quality. Greater attention to methodologic standards for economic evaluations in patient safety is needed. PMID:23097615

Systematic evaluation of non-animal test methods for skin sensitisation safety assessment.

PubMed

Reisinger, Kerstin; Hoffmann, Sebastian; Alépée, Nathalie; Ashikaga, Takao; Barroso, Joao; Elcombe, Cliff; Gellatly, Nicola; Galbiati, Valentina; Gibbs, Susan; Groux, Hervé; Hibatallah, Jalila; Keller, Donald; Kern, Petra; Klaric, Martina; Kolle, Susanne; Kuehnl, Jochen; Lambrechts, Nathalie; Lindstedt, Malin; Millet, Marion; Martinozzi-Teissier, Silvia; Natsch, Andreas; Petersohn, Dirk; Pike, Ian; Sakaguchi, Hitoshi; Schepky, Andreas; Tailhardat, Magalie; Templier, Marie; van Vliet, Erwin; Maxwell, Gavin

2015-02-01

The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitization potency prediction. The results of the first phase – systematic evaluation of 16 test methods – are presented here. This evaluation involved generation of data on a common set of ten substances in all methods and systematic collation of information including the level of standardisation, existing test data,potential for throughput, transferability and accessibility in cooperation with the test method developers.A workshop was held with the test method developers to review the outcome of this evaluation and to discuss the results. The evaluation informed the prioritisation of test methods for the next phase of the non-animal testing strategy development framework. Ultimately, the testing strategy – combined with bioavailability and skin metabolism data and exposure consideration – is envisaged to allow establishment of a data integration approach for skin sensitisation safety assessment of cosmetic ingredients.

Can TTIP Improve Laboratory Animal Welfare in Safety Testing and 3Rs?

PubMed

Busquet, Francois; Zurlo, Joanne; Hartung, Thomas

2016-05-01

In the context of the current negotiations between the European Union (EU) and the United States under the Transatlantic Trade Investment Partnership (TTIP), there is the opportunity to look at both legislative frameworks to better pinpoint convergences, synergies, and gaps when it comes to use of laboratory animals for scientific purposes and bring together the best of both worlds. The objectives in this article are to indicate what are the current EU pieces of legislation that are relevant under TTIP regarding the uses of laboratory animals for scientific purposes under the regulations about cosmetics and chemicals, among others. The same approach will be taken to look at the relevant American legal frameworks, that is, the Food and Cosmetics Act and the Toxic Safety Control Act as well as its most recent reauthorization. In conclusion, the authors will identify future frameworks that can contribute to the harmonization of regulatory standards and further steps where TTIP negotiators should strengthen regulatory cooperation. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Performance and safety testing of lithium batteries for the Expendable, Mobile, ASW Training Target (EMATT)

NASA Astrophysics Data System (ADS)

Hallal, P. B.; Bis, R. F.

1986-08-01

The developmental EMATT (expendable, mobile, ASW training target) may use a high-energy (lithium/sulfuryl chloride) battery system. Safety problems with the original battery cell design were experienced during early performance and safety testing. After redesign of the battery cell, performance and safety tests were made under specified abuse conditions, as well as under simulated launch conditions. The test results showed that the power system now meets all safety requirements, and that the EMATT vehicle is safe to deploy for its engineering development phase.

Animal and human studies with the mitochondria-targeted antioxidant MitoQ.

PubMed

Smith, Robin A J; Murphy, Michael P

2010-07-01

As mitochondrial oxidative damage contributes to a wide range of human diseases, antioxidants designed to be accumulated by mitochondria in vivo have been developed. The most extensively studied of these mitochondria-targeted antioxidants is MitoQ, which contains the antioxidant quinone moiety covalently attached to a lipophilic triphenylphosphonium cation. MitoQ has now been used in a range of in vivo studies in rats and mice and in two phase II human trials. Here, we review what has been learned from these animal and human studies with MitoQ.

A study on current risk assessments and guidelines on the use of food animal products derived from cloned animals.

PubMed

Hur, Sun Jin

2017-10-01

The author widely surveyed and analyzed the food safety issues, ethical issues, permits, and approval of animal products from animals cloned by somatic cell nuclear transfer worldwide. As a result of a 2-year survey, the author found that there is no evidence that meat and milk derived from cloned animals or their progeny pose a risk to food safety in terms of genotoxicity, adverse reproductive effects, or allergic reactions. Most countries have not approved meat and milk derived from cloned animals, and their progeny are entering the food supply. To establish the guidelines, the author suggests four principles of safety assessment for meat and milk derived from cloned animals. The four main principles for safety assessment are similarities of chemical composition, adverse reproductive effects, genotoxicity, and allergic reactions under the influence of meat and milk from cloned animals and noncloned counterparts. This principle means that meat and milk derived from a cloned animal are safe if there are no differences in the four safety assessments of meat and milk between cloned animal's progeny and noncloned counterparts. Copyright © 2017 Elsevier Ltd. All rights reserved.

DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

PubMed Central

Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühlebach, Michael D

2013-01-01

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics. PMID:23380817

77 FR 75186 - Notice of Closure, Target Shooting Public Safety Closure on the Lake Mountains in Utah County, UT

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

... Closure, Target Shooting Public Safety Closure on the Lake Mountains in Utah County, UT AGENCY: Bureau of... Lake Mountains in Utah County, Utah, to recreational target shooting to protect public safety. This... shooting closure within the described area will remain in effect no longer than two years from December 19...

Animal-Assisted Interventions in Dutch Nursing Homes: A Survey.

PubMed

Schuurmans, Lonneke; Enders-Slegers, Marie-Jose; Verheggen, Theo; Schols, Jos

2016-07-01

Animal-assisted interventions (AAI) have become more and more popular in nursing homes in the past decade. Various initiatives for using animals in nursing homes have been developed over the years (eg, animal visiting programs, residential companion animals, petting zoos) and, on the whole, the number of nursing homes that refuse animals on their premises has declined. In this survey, we aimed to determine how many Dutch nursing homes offer AAIs, what type of interventions are used, and with what aim. We also focus on the use of underlying health, hygiene, and (animal) safety protocols. Using an online Dutch nursing home database, we invited all listed (457) nursing home organizations in the Netherlands (encompassing a total of 804 nursing home locations) to participate in our digital survey, powered by SurveyMonkey. The survey consisted of a total of 45 questions, divided into general questions about the use of animals in interventions; the targeted client population(s); and specific questions about goals, guidelines, and protocols. The results were analyzed with SPSS Statistics. In the end, 244 surveys, representing 165 organizations, were returned: 125 nursing homes used AAI in one way or another, 40 did not. Nursing homes that did not offer AAI cited allergy and hygiene concerns as the most important reasons. Most nursing homes offering AAI used visiting animals, mostly dogs (108) or rabbits (76). A smaller number of nursing homes had resident animals, either living on the ward or in a meadow outside. Almost all programs involved animal-assisted activities with a recreational purpose; none of the participating nursing homes provided animal assisted therapy with therapeutic goals. Psychogeriatric patients were most frequently invited to participate. A total of 88 nursing homes used alternatives when animals were not an option or not available. The most popular alternative was the use of stuffed animals (83) followed by FurReal Friends robotic toys (14). The

Electromagnetic Processing as a Way of Increasing Microbiological Safety of Animal Waste

NASA Astrophysics Data System (ADS)

Soboleva, O. M.; Kolosova, M. M.; Filipovich, L. A.; Aksenov, V. A.

2017-05-01

The article shows the possibility of using the electromagnetic field of ultrahigh frequency (EMF UHF) for drying and disinfecting of such animal waste as pig manure and poultry droppings. The studied modes included the following options: processing exposure of 60, 90, 120 sec, the capacity of 60 kW, the frequency of 915 MHz. The method of UHF processing of manure and poultry droppings is environmentally safe and effective in neutralizing the pathogenic microflora, as well as larvae and eggs of worms. The following processing mode of animal waste in the electromagnetic field of ultrahigh frequency was recognized as optimal: exposure of 90 seconds, the capacity of 60 kW, the frequency of 915 MHz. This option leads to the complete destruction of pathogenic and conditionally pathogenic microorganisms, as well as the eggs and larvae of worms. As a result of this processing, a high level of microbiological safety of pig manure and poultry droppings is achieved that allows using them as organic fertilizers. The peculiarities of some species of pathogenic fungi developing on the surface of the wheat grain are shown. Pre-processed animal waste (pig manure and and poultry droppings) were applied in experimental variants. Used organic fertilizers underwent electromagnetic processing of ultra-high frequency. The qualitative composition of the microflora on the surface of the grain depends on the type of animal waste (manure or droppings) and used dose. The safest part of the microflora of grain was marked with the application of the UHF-processed pig manure and poultry droppings in doses of 10 t/ha.

Animal Rights Groups Target High School Dissection.

ERIC Educational Resources Information Center

Trotter, Andrew

1992-01-01

Two groups leading the charge against dissection are People for the Ethical Treatment of Animals (PETA) and the Student Action Corps for Animals (SACA). Protests by student and community members remain the movement's strongest weapon. (MLF)

Effects of a Workplace Intervention Targeting Psychosocial Risk Factors on Safety and Health Outcomes

PubMed Central

Hammer, Leslie B.; Truxillo, Donald M.; Bodner, Todd; Rineer, Jennifer; Pytlovany, Amy C.; Richman, Amy

2015-01-01

The goal of this study was to test the effectiveness of a workplace intervention targeting work-life stress and safety-related psychosocial risk factors on health and safety outcomes. Data were collected over time using a randomized control trial design with 264 construction workers employed in an urban municipal department. The intervention involved family- and safety-supportive supervisor behavior training (computer-based), followed by two weeks of behavior tracking and a four-hour, facilitated team effectiveness session including supervisors and employees. A significant positive intervention effect was found for an objective measure of blood pressure at the 12-month follow-up. However, no significant intervention results were found for self-reported general health, safety participation, or safety compliance. These findings suggest that an intervention focused on supervisor support training and a team effectiveness process for planning and problem solving should be further refined and utilized in order to improve employee health with additional research on the beneficial effects on worker safety. PMID:26557703

Percutaneous irreversible electroporation for breast tissue and breast cancer: safety, feasibility, skin effects and radiologic-pathologic correlation in an animal study.

PubMed

Li, Sheng; Chen, Fei; Shen, Lujun; Zeng, Qi; Wu, Peihong

2016-08-05

To study the safety, feasibility and skin effects of irreversible electroporation (IRE) for breast tissue and breast cancer in animal models. Eight pigs were used in this study. IRE was performed on the left breasts of the pigs with different skin-electrode distances, and the right breasts were used as controls. The electrodes were placed 1-8 mm away from the skin, with an electrode spacing of 1.5-2 cm. Imaging and pathological examinations were performed at specific time points for follow-up evaluation. Vital signs, skin damage, breast tissue changes and ablation efficacy were also closely observed. Eight rabbit models with or without VX2 breast tumor implantations were used to further assess the damage caused by and the repair of thin skin after IRE treatment for breast cancer. Contrast-enhanced ultrasound and elastosonography were used to investigate ablation efficacy and safety. During IRE, the color of the pig breast skin reversibly changed. When the skin-electrode distance was 3 mm, the breast skin clearly changed, becoming white in the center and purple in the surrounding region during IRE. One small purulent skin lesion was detected several days after IRE. When the skin-electrode distance was 5-8 mm, the breast skin became red during IRE. However, the skin architecture was normal when evaluated using gross pathology and hematoxylin-eosin staining. When the skin-electrode distance was 1 mm, skin atrophy and yellow glabrescence occurred in the rabbit breasts after IRE. When the skin-electrode distance was ≥5 mm, there was no skin damage in the rabbit model regardless of breast cancer implantation. After IRE, complete ablation of the targeted breast tissue or cancer was confirmed, and apoptosis was detected in the target tissue and outermost epidermal layer. In the ablated breasts of the surviving animals, complete mammary regeneration with normal skin and hair was observed. Furthermore, no massive fibrosis or mass formation were detected on

The present and future of opioid analgesics in small animal practice.

PubMed

Simon, B T; Steagall, P V

2017-08-01

Opioids are the cornerstone for the treatment of acute pain in small animal patients. This is primarily because of their remarkable safety profile, high efficacy, and benefit of reversibility. There have been some significant advances in our knowledge on opioid pharmacology and clinical usage in companion animal medicine. This review discusses the progression of opioid use in small animal practice providing current misconceptions and controversies in light of routes of administration. Potential targets for research and drug development and novel therapies are discussed in addition to the concepts of glial cell modulators, individual variability, and opioid tolerance and hyperalgesia. The future brings an interesting perspective with the application of pharmacogenetics and individualized pain management in canine and feline practice. © 2016 John Wiley & Sons Ltd.

Radiation prevulcanized natural rubber latex: Cytotoxicity and safety evaluation on animal

NASA Astrophysics Data System (ADS)

Keong, C. C.; Zin, W. M. Wan; Ibrahim, P.; Ibrahim, S.

2010-05-01

Radiation prevulcanized natural rubber latex (RVNRL) was claimed to be more user friendly than natural rubber latex prevulcanized by sulphur curing system. The absence of Type IV allergy inducing chemicals in RVNRL make it a suitable material for manufacturing of many kinds of latex products, especially those come into direct contact with users. This paper reveals and discusses the findings of cytotoxicity test and safety evaluation on animal for RVNRL. The test was done on RVNRL films prepared by coagulant dipping method and RVNRL dipped products produced by latex dipped product manufacturers. Cytotocixity test was carried out on mammalian cell culture American Type Culture Collection CCL 81, Vero. Results indicated that no cytotoxic effect from RVNRL films and products was found on the cell culture. Two animal studies, namely dermal sensitization study and primary skin irritation study, were done on gloves made from RVNRL. Albino white guinea pigs were used as test subjects in dermal sensitization study and results showed no sensitization induced by the application of test material in the guinea pigs. Primary skin irritation study was done on New Zealand white rabbits and results showed that the product tested was not corrosive and was not a primary irritant

Safety comparison of four types of rabies vaccines in patients with WHO category II animal exposure

PubMed Central

Peng, Jun; Lu, Sha; Zhu, Zhenggang; Zhang, Man; Hu, Quan; Fang, Yuan

2016-01-01

Abstract To evaluate the safeties of 4 types of rabies vaccines for patients with WHO category II animal exposure, especially in different age groups. A total of 4000 patients with WHO category II animal exposure were randomly divided into 4 vaccine groups, and were respectively given with Vaccines A, B, C, and D. And subjects in each vaccine group were divided into 4 age groups (≤5, 5–18, 19–60, and ≥60-year-old groups). Then adverse events (including local and systemic ones) were recorded and compared. Consequently, except for Vaccine B, patients under the age of 5 in Groups A, C, and D suffered from more adverse reactions than those in other age groups. Furthermore, for the children aged less than 5 years, incidence of adverse events following administration of Vaccine B, with the dose of 0.5 mL and production of bioreactor systems, was significantly lower than Vaccines A and D. Our data showed that rabies vaccines with smaller doses and more advanced processing techniques are of relatively high safety for the patients, especially for the young children. PMID:27893654

Pesticides and Animal Health

Science.gov Websites

:00PM Pacific Time, Mon-Fri A B C D E F G H I J K L M N O P Q R S T U V W X Y Z A-Z Index Health & ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Home Page Pesticide Health and Safety Information Pesticides and Animal Health Related Topics

9 CFR 113.41 - Calf safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Calf safety test. 113.41 Section 113.41 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.41 Calf safety test. The calf safety test provided in this section shall be conducted when...

9 CFR 113.45 - Sheep safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Sheep safety test. 113.45 Section 113.45 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.45 Sheep safety test. The sheep safety test provided in this section shall be conducted when...

9 CFR 113.41 - Calf safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Calf safety test. 113.41 Section 113.41 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.41 Calf safety test. The calf safety test provided in this section shall be conducted when...

9 CFR 113.45 - Sheep safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Sheep safety test. 113.45 Section 113.45 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.45 Sheep safety test. The sheep safety test provided in this section shall be conducted when...

77 FR 38751 - Codification of Animal Testing Policy

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

... Animal Testing Policy AGENCY: Consumer Product Safety Commission. ACTION: Proposed Statement of Policy on Animal Testing SUMMARY: The Consumer Product Safety Commission (CPSC or Commission) proposes to codify its statement of policy on animal testing, as amended, which was previously published in the Federal...

Safety testing of acellular pertussis vaccines: Use of animals and 3Rs alternatives

PubMed Central

Hoonakker, Marieke; Arciniega, Juan; Hendriksen, Coenraad

2017-01-01

ABSTRACT The current test of acellular Bordetella pertussis (aP) vaccines for residual pertussis toxin (PTx) is the Histamine Sensitization test (HIST), based on the empirical finding that PTx sensitizes mice to histamine. Although HIST has ensured the safety of aP vaccines for years, it is criticized for the limited understanding of how it works, its technical difficulty, and for animal welfare reasons. To estimate the number of mice used worldwide for HIST, we surveyed major aP manufacturers and organizations performing, requiring, or recommending the test. The survey revealed marked regional differences in regulatory guidelines, including the number of animals used for a single test. Based on information provided by the parties surveyed, we estimated the worldwide number of mice used for testing to be 65,000 per year: ∼48,000 by manufacturers and ∼17,000 by national control laboratories, although the latter number is more affected by uncertainty, due to confidentiality policies. These animals covered the release of approximately 850 final lots and 250 in-process lots of aP vaccines yearly. Although there are several approaches for HIST refinement and reduction, we discuss why the efforts needed for validation and implementation of these interim alternatives may not be worthwhile, when there are several in vitro alternatives in various stages of development, some already fairly advanced. Upon implementation, one or more of these replacement alternatives can substantially reduce the number of animals currently used for the HIST, although careful evaluation of each alternative's mechanism and its suitable validation will be necessary in the path to implementation. PMID:28857652

Safety testing of acellular pertussis vaccines: Use of animals and 3Rs alternatives.

PubMed

Hoonakker, Marieke; Arciniega, Juan; Hendriksen, Coenraad

2017-11-02

The current test of acellular Bordetella pertussis (aP) vaccines for residual pertussis toxin (PTx) is the Histamine Sensitization test (HIST), based on the empirical finding that PTx sensitizes mice to histamine. Although HIST has ensured the safety of aP vaccines for years, it is criticized for the limited understanding of how it works, its technical difficulty, and for animal welfare reasons. To estimate the number of mice used worldwide for HIST, we surveyed major aP manufacturers and organizations performing, requiring, or recommending the test. The survey revealed marked regional differences in regulatory guidelines, including the number of animals used for a single test. Based on information provided by the parties surveyed, we estimated the worldwide number of mice used for testing to be 65,000 per year: ∼48,000 by manufacturers and ∼17,000 by national control laboratories, although the latter number is more affected by uncertainty, due to confidentiality policies. These animals covered the release of approximately 850 final lots and 250 in-process lots of aP vaccines yearly. Although there are several approaches for HIST refinement and reduction, we discuss why the efforts needed for validation and implementation of these interim alternatives may not be worthwhile, when there are several in vitro alternatives in various stages of development, some already fairly advanced. Upon implementation, one or more of these replacement alternatives can substantially reduce the number of animals currently used for the HIST, although careful evaluation of each alternative's mechanism and its suitable validation will be necessary in the path to implementation.

Vascular targets for cannabinoids: animal and human studies

PubMed Central

Stanley, Christopher; O'Sullivan, Saoirse E

2014-01-01

Application of cannabinoids and endocannabinoids to perfused vascular beds or individual isolated arteries results in changes in vascular resistance. In most cases, the result is vasorelaxation, although vasoconstrictor responses are also observed. Cannabinoids also modulate the actions of vasoactive compounds including acetylcholine, methoxamine, angiotensin II and U46619 (thromboxane mimetic). Numerous mechanisms of action have been proposed including receptor activation, potassium channel activation, calcium channel inhibition and the production of vasoactive mediators such as calcitonin gene-related peptide, prostanoids, NO, endothelial-derived hyperpolarizing factor and hydrogen peroxide. The purpose of this review is to examine the evidence for the range of receptors now known to be activated by cannabinoids. Direct activation by cannabinoids of CB1, CBe, TRPV1 (and potentially other TRP channels) and PPARs in the vasculature has been observed. A potential role for CB2, GPR55 and 5-HT1A has also been identified in some studies. Indirectly, activation of prostanoid receptors (TP, IP, EP1 and EP4) and the CGRP receptor is involved in the vascular responses to cannabinoids. The majority of this evidence has been obtained through animal research, but recent work has confirmed some of these targets in human arteries. Vascular responses to cannabinoids are enhanced in hypertension and cirrhosis, but are reduced in obesity and diabetes, both due to changes in the target sites of action. Much further work is required to establish the extent of vascular actions of cannabinoids and the application of this research in physiological and pathophysiological situations. Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6 PMID:24329566

Assuring safety without animal testing: the case for the human testis in vitro.

PubMed

Chapin, Robert E; Boekelheide, Kim; Cortvrindt, Rita; van Duursen, Majorie B M; Gant, Tim; Jegou, Bernard; Marczylo, Emma; van Pelt, Ans M M; Post, Janine N; Roelofs, Maarke J E; Schlatt, Stefan; Teerds, Katja J; Toppari, Jorma; Piersma, Aldert H

2013-08-01

From 15 to 17 June 2011, a dedicated workshop was held on the subject of in vitro models for mammalian spermatogenesis and their applications in toxicological hazard and risk assessment. The workshop was sponsored by the Dutch ASAT initiative (Assuring Safety without Animal Testing), which aims at promoting innovative approaches toward toxicological hazard and risk assessment on the basis of human and in vitro data, and replacement of animal studies. Participants addressed the state of the art regarding human and animal evidence for compound mediated testicular toxicity, reviewed existing alternative assay models, and brainstormed about future approaches, specifically considering tissue engineering. The workshop recognized the specific complexity of testicular function exemplified by dedicated cell types with distinct functionalities, as well as different cell compartments in terms of microenvironment and extracellular matrix components. This complexity hampers quick results in the realm of alternative models. Nevertheless, progress has been achieved in recent years, and innovative approaches in tissue engineering may open new avenues for mimicking testicular function in vitro. Although feasible, significant investment is deemed essential to be able to bring new ideas into practice in the laboratory. For the advancement of in vitro testicular toxicity testing, one of the most sensitive end points in regulatory reproductive toxicity testing, such an investment is highly desirable. Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Role of Animal Models in Coronary Stenting.

PubMed

Iqbal, Javaid; Chamberlain, Janet; Francis, Sheila E; Gunn, Julian

2016-02-01

Coronary angioplasty initially employed balloon dilatation only. This technique revolutionized the treatment of coronary artery disease, although outcomes were compromised by acute vessel closure, late constrictive remodeling, and restenosis due to neointimal proliferation. These processes were studied in animal models, which contributed to understanding the biology of endovascular arterial injury. Coronary stents overcome acute recoil, with improvements in the design and metallurgy since then, leading to the development of drug-eluting stents and bioresorbable scaffolds. These devices now undergo computer modeling and benchtop and animal testing before evaluation in clinical trials. Animal models, including rabbit, sheep, dog and pig are available, all with individual benefits and limitations. In smaller mammals, such as mouse and rabbit, the target for stenting is generally the aorta; whereas in larger animals, such as the pig, it is generally the coronary artery. The pig coronary stenting model is a gold-standard for evaluating safety; but insights into biomechanical properties, the biology of stenting, and efficacy in controlling neointimal proliferation can also be gained. Intra-coronary imaging modalities such as intravascular ultrasound and optical coherence tomography allow precise serial evaluation in vivo, and recent developments in genetically modified animal models of atherosclerosis provide realistic test beds for future stents and scaffolds.

Measuring general animal health status: Development of an animal health barometer.

PubMed

Depoorter, Pieter; Van Huffel, Xavier; Diricks, Herman; Imberechts, Hein; Dewulf, Jeroen; Berkvens, Dirk; Uyttendaele, Mieke

2015-03-01

The development of an animal health barometer, an instrument to measure the general health of the Belgian livestock population on a yearly basis and to monitor its evolution over time, is described. The elaboration of a set of 13 animal health indicators (AHIs) as the basis for the animal health barometer is discussed. These indicators were weighted by experts - including scientists, policy makers and agro-industrial representatives - to determine their relative weight in the barometer. The result of the barometer is expressed as a comparison with a previous year. Based on the results of the 13 AHIs, it is concluded that general animal health in Belgium shows a positive evolution since 2008. The animal health barometer provides a composite view of the status of livestock health in Belgium and is a tool to communicate in an intelligible, comprehensible manner on aspects of animal health to consumers and professional stakeholders in the animal production and food chain. Together with the food safety barometer (Baert et al., 2011. Food Res. Int. 44, 940) and the plant health barometer (Wilmart et al., 2014. Eur. J. Plant Pathol. doi: 10.1007/s10658-014-0547-x), the animal health barometer is one of the three instruments to provide a holistic view on the overall status of the safety of the food chain in Belgium. Copyright © 2014 Elsevier B.V. All rights reserved.

Road safety risk evaluation and target setting using data envelopment analysis and its extensions.

PubMed

Shen, Yongjun; Hermans, Elke; Brijs, Tom; Wets, Geert; Vanhoof, Koen

2012-09-01

Currently, comparison between countries in terms of their road safety performance is widely conducted in order to better understand one's own safety situation and to learn from those best-performing countries by indicating practical targets and formulating action programmes. In this respect, crash data such as the number of road fatalities and casualties are mostly investigated. However, the absolute numbers are not directly comparable between countries. Therefore, the concept of risk, which is defined as the ratio of road safety outcomes and some measure of exposure (e.g., the population size, the number of registered vehicles, or distance travelled), is often used in the context of benchmarking. Nevertheless, these risk indicators are not consistent in most cases. In other words, countries may have different evaluation results or ranking positions using different exposure information. In this study, data envelopment analysis (DEA) as a performance measurement technique is investigated to provide an overall perspective on a country's road safety situation, and further assess whether the road safety outcomes registered in a country correspond to the numbers that can be expected based on the level of exposure. In doing so, three model extensions are considered, which are the DEA based road safety model (DEA-RS), the cross-efficiency method, and the categorical DEA model. Using the measures of exposure to risk as the model's input and the number of road fatalities as output, an overall road safety efficiency score is computed for the 27 European Union (EU) countries based on the DEA-RS model, and the ranking of countries in accordance with their cross-efficiency scores is evaluated. Furthermore, after applying clustering analysis to group countries with inherent similarity in their practices, the categorical DEA-RS model is adopted to identify best-performing and underperforming countries in each cluster, as well as the reference sets or benchmarks for those

Can we use genetic and genomic approaches to identify candidate animals for targeted selective treatment.

PubMed

Laurenson, Yan C S M; Kyriazakis, Ilias; Bishop, Stephen C

2013-10-18

Estimated breeding values (EBV) for faecal egg count (FEC) and genetic markers for host resistance to nematodes may be used to identify resistant animals for selective breeding programmes. Similarly, targeted selective treatment (TST) requires the ability to identify the animals that will benefit most from anthelmintic treatment. A mathematical model was used to combine the concepts and evaluate the potential of using genetic-based methods to identify animals for a TST regime. EBVs obtained by genomic prediction were predicted to be the best determinant criterion for TST in terms of the impact on average empty body weight and average FEC, whereas pedigree-based EBVs for FEC were predicted to be marginally worse than using phenotypic FEC as a determinant criterion. Whilst each method has financial implications, if the identification of host resistance is incorporated into a wider genomic selection indices or selective breeding programmes, then genetic or genomic information may be plausibly included in TST regimes. Copyright © 2013 Elsevier B.V. All rights reserved.

Investigation of nutriactive phytochemical - gamma-oryzanol in experimental animal models.

PubMed

Szcześniak, K A; Ostaszewski, P; Ciecierska, A; Sadkowski, T

2016-08-01

Gamma-oryzanol (GO) is an abundant dietary antioxidant that is considered to have beneficial effects in cardiovascular disease, cancer and diabetes. Other potential properties of GO include inhibition of gastric acid secretion and decreased post-exercise muscle fatigue. GO is a unique mixture of triterpene alcohol and sterol ferulates present in rice bran oil, a byproduct of rice processing. GO has been studied by many researchers over the last three decades. In particular, the utility of GO supplementation has been documented in numerous animal models. A large variety of species was examined, and various experimental methodologies and targets were applied. The aim of this study was to summarize the body of research on GO supplementation in animals and to examine possible mechanisms of GO action. Furthermore, while the safety of GO supplementation in animals has been well documented, studies demonstrating pharmacokinetics, pharmacodynamics and efficiency are less clear. The observed differences in these findings are also discussed. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

An overview of food safety and bacterial foodborne zoonoses in food production animals in the Caribbean region.

PubMed

Guerra, Maria Manuela Mendes; de Almeida, Andre M; Willingham, Arve Lee

2016-08-01

Foodborne diseases (FBDs) in the Caribbean have a high economic burden. Public health and tourism concerns rise along with the increasing number of cases and outbreaks registered over the last 20 years. Salmonella spp., Shigella spp., and Campylobacter spp. are the main bacteria associated with these incidents. In spite of undertaking limited surveillance on FBD in the region, records related to bacterial foodborne zoonoses in food-producing animals and their associated epidemiologic significance are poorly documented, giving rise to concerns about the importance of the livestock, food animal product sectors, and consumption patterns. In this review, we report the available published literature over the last 20 years on selected bacterial foodborne zoonoses in the Caribbean region and also address other food safety-related aspects (e.g., FBD food attribution, importance, surveillance), mainly aiming at recognizing data gaps and identifying possible research approaches in the animal health sector.

Trade and food safety aspects for animal influenza viruses

USDA-ARS?s Scientific Manuscript database

The World Organization for Animal Health provides sanitary standards for international trade and emphasizes science-based risk assessment for safe trade of animals and animal products. The goal is to prevent unacceptable risks to animal and human health while avoiding unjustified or politically mot...

Efficient Interruption of Infection Chains by Targeted Removal of Central Holdings in an Animal Trade Network

PubMed Central

Büttner, Kathrin; Krieter, Joachim; Traulsen, Arne; Traulsen, Imke

2013-01-01

Centrality parameters in animal trade networks typically have right-skewed distributions, implying that these networks are highly resistant against the random removal of holdings, but vulnerable to the targeted removal of the most central holdings. In the present study, we analysed the structural changes of an animal trade network topology based on the targeted removal of holdings using specific centrality parameters in comparison to the random removal of holdings. Three different time periods were analysed: the three-year network, the yearly and the monthly networks. The aim of this study was to identify appropriate measures for the targeted removal, which lead to a rapid fragmentation of the network. Furthermore, the optimal combination of the removal of three holdings regardless of their centrality was identified. The results showed that centrality parameters based on ingoing trade contacts, e.g. in-degree, ingoing infection chain and ingoing closeness, were not suitable for a rapid fragmentation in all three time periods. More efficient was the removal based on parameters considering the outgoing trade contacts. In all networks, a maximum percentage of 7.0% (on average 5.2%) of the holdings had to be removed to reduce the size of the largest component by more than 75%. The smallest difference from the optimal combination for all three time periods was obtained by the removal based on out-degree with on average 1.4% removed holdings, followed by outgoing infection chain and outgoing closeness. The targeted removal using the betweenness centrality differed the most from the optimal combination in comparison to the other parameters which consider the outgoing trade contacts. Due to the pyramidal structure and the directed nature of the pork supply chain the most efficient interruption of the infection chain for all three time periods was obtained by using the targeted removal based on out-degree. PMID:24069293

Target-Selectivity of Parvalbumin-Positive Interneurons in Layer II of Medial Entorhinal Cortex in Normal and Epileptic Animals

PubMed Central

Armstrong, Caren; Wang, Jessica; Lee, Soo Yeun; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

2015-01-01

The medial entorhinal cortex layer II (MEClayerII) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII. However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII. However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII. Taken together, these findings advance our

Target-selectivity of parvalbumin-positive interneurons in layer II of medial entorhinal cortex in normal and epileptic animals.

PubMed

Armstrong, Caren; Wang, Jessica; Yeun Lee, Soo; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

2016-06-01

The medial entorhinal cortex layer II (MEClayerII ) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII . However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII . However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII . Taken together, these findings advance

9 CFR 113.39 - Cat safety tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Cat safety tests. 113.39 Section 113.39 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Seed Virus is tested for safety. (1) The test animals shall be determined to be susceptible to the...

General Framework for Animal Food Safety Traceability Using GS1 and RFID

NASA Astrophysics Data System (ADS)

Cao, Weizhu; Zheng, Limin; Zhu, Hong; Wu, Ping

GS1 is global traceability standard, which is composed by the encoding system (EAN/UCC, EPC), the data carriers identified automatically (bar codes, RFID), electronic data interchange standards (EDI, XML). RFID is a non-contact, multi-objective automatic identification technique. Tracing of source food, standardization of RFID tags, sharing of dynamic data are problems to solve urgently for recent traceability systems. The paper designed general framework for animal food safety traceability using GS1 and RFID. This framework uses RFID tags encoding with EPCglobal tag data standards. Each information server has access tier, business tier and resource tier. These servers are heterogeneous and distributed, providing user access interfaces by SOAP or HTTP protocols. For sharing dynamic data, discovery service and object name service are used to locate dynamic distributed information servers.

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

9 CFR 314.8 - Dead animal carcasses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Dead animal carcasses. 314.8 Section 314.8 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Dead animal carcasses. (a) With the exception of dead livestock which have died en route and are...

Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

PubMed Central

Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

2016-01-01

Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

PVA gel as a potential adhesion barrier: a safety study in a large animal model of intestinal surgery.

PubMed

Renz, Bernhard W; Leitner, Kurt; Odermatt, Erich; Worthley, Daniel L; Angele, Martin K; Jauch, Karl-Walter; Lang, Reinhold A

2014-03-01

Intra-abdominal adhesions following surgery are a major source of morbidity and mortality including abdominal pain and small bowel obstruction. This study evaluated the safety of PVA gel (polyvinyl alcohol and carboxymethylated cellulose gel) on intestinal anastomoses and its potential effectiveness in preventing adhesions in a clinically relevant large animal model. Experiments were performed in a pig model with median laparotomy and intestinal anastomosis following small bowel resection. The primary endpoint was the safety of PVA on small intestinal anastomoses. We also measured the incidence of postoperative adhesions in PVA vs. control groups: group A (eight pigs): stapled anastomosis with PVA gel compared to group B (eight pigs), which had no PVA gel; group C (eight pigs): hand-sewn anastomosis with PVA gel compared to group B (eight pigs), which had no anti-adhesive barrier. Animals were sacrificed 14 days after surgery and analyzed. All anastomoses had a patent lumen without any stenosis. No anastomoses leaked at an intraluminal pressure of 40 cmH2O. Thus, anastomoses healed very well in both groups, regardless of whether PVA was administered. PVA-treated animals, however, had significantly fewer adhesions in the area of stapled anastomoses. The hand-sewn PVA group also had weaker adhesions and trended towards fewer adhesions to adjacent organs. These results suggest that PVA gel does not jeopardize the integrity of intestinal anastomoses. However, larger trials are needed to investigate the potential of PVA gel to prevent adhesions in gastrointestinal surgery.

The use of whole food animal studies in the safety assessment of genetically modified crops: limitations and recommendations.

PubMed

Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve; Walker, Kate

2013-11-01

There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable.

The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recommendations

PubMed Central

Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve

2013-01-01

There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable. PMID:24164514

Linking live animals and products: traceability.

PubMed

Britt, A G; Bell, C M; Evers, K; Paskin, R

2013-08-01

It is rarely possible to successfully contain an outbreak of an infectious animal disease, or to respond effectively to a chemical residue incident, without the use of a system for identifying and tracking animals. The linking of animals at the time they are slaughtered--through the use of identification devices or marks and accompanying movement documentation--with the meat produced from their carcasses, adds further value from the perspective of consumer safety. Over the past decade, animal identification technology has become more sophisticated and affordable. The development of the Internet and mobile communication tools, complemented bythe expanded capacity of computers and associated data management applications, has added a new dimension to the ability of Competent Authorities and industry to track animals and the food they produce for disease control, food safety and commercial purposes.

Efficacy and safety of damage control in experimental animal models of injury: protocol for a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Although abbreviated surgery with planned reoperation (damage control surgery) is now widely used to manage major trauma patients, the procedure and its component interventions have not been evaluated in randomized controlled trials (RCTs). While some have suggested the need for such trials, they are unlikely to be conducted because of patient safety concerns. As animal studies may overcome several of the limitations of existing observational damage control studies, the primary objective of this study is to evaluate the efficacy and safety of damage control versus definitive surgery in experimental animal models of injury. Methods/design We will search electronic databases (Medline, Embase, PubMed, Web of Science, Scopus, and the Cochrane Library), conference abstracts, personal files, and bibliographies of included articles. We will include RCTs and prospective cohort studies that utilized an animal model of injury and compared damage control surgery (or specific damage control interventions or adjuncts) to definitive surgery (or specific definitive surgical interventions). Two investigators will independently evaluate the internal and external/construct validity of individual studies. The primary outcome will be all-cause mortality. Secondary outcomes will include blood loss amounts; blood pressures and heart rates; urinary outputs; core body temperatures; arterial lactate, pH, and base deficit/excess values; prothrombin and partial thromboplastin times; international normalized ratios; and thromboelastography (TEG) results/activated clotting times. We will calculate summary relative risks (RRs) of mortality and mean differences (for continuous outcomes) using DerSimonian and Laird random effects models. Heterogeneity will be explored using subgroup meta-analysis and meta-regression. We will assess for publication bias using funnel plots and Begg’s and Egger’s tests. When evidence of publication bias exists, we will use the Duval and Tweedie trim

Dangerous animals capture and maintain attention in humans.

PubMed

Yorzinski, Jessica L; Penkunas, Michael J; Platt, Michael L; Coss, Richard G

2014-05-28

Predation is a major source of natural selection on primates and may have shaped attentional processes that allow primates to rapidly detect dangerous animals. Because ancestral humans were subjected to predation, a process that continues at very low frequencies, we examined the visual processes by which men and women detect dangerous animals (snakes and lions). We recorded the eye movements of participants as they detected images of a dangerous animal (target) among arrays of nondangerous animals (distractors) as well as detected images of a nondangerous animal (target) among arrays of dangerous animals (distractors). We found that participants were quicker to locate targets when the targets were dangerous animals compared with nondangerous animals, even when spatial frequency and luminance were controlled. The participants were slower to locate nondangerous targets because they spent more time looking at dangerous distractors, a process known as delayed disengagement, and looked at a larger number of dangerous distractors. These results indicate that dangerous animals capture and maintain attention in humans, suggesting that historical predation has shaped some facets of visual orienting and its underlying neural architecture in modern humans.

Animals in the Classroom

ERIC Educational Resources Information Center

Roy, Ken

2011-01-01

Use of animals in middle school science classrooms is a curriculum component worthy of consideration, providing proper investigation and planning are addressed. A responsible approach to this action, including safety, must be adopted for success. In this month's column, the author provides some suggestions on incorporating animals into the…

Risk assessment of coccidostatics during feed cross-contamination: animal and human health aspects.

PubMed

Dorne, J L C M; Fernández-Cruz, M L; Bertelsen, U; Renshaw, D W; Peltonen, K; Anadon, A; Feil, A; Sanders, P; Wester, P; Fink-Gremmels, J

2013-08-01

Coccidiosis, an intestinal plasmodium infection, is a major infectious disease in poultry and rabbits. Eleven different coccidiostats are licensed in the EU for the prevention of coccidiosis in these animal species. According to their chemical nature and main biological activity, these compounds can be grouped as ionophoric (monensin, lasalocid sodium, salinomycin, narasin, maduramicin and semduramicin) or non-ionophoric (robenidine, decoquinate, nicarbazin, diclazuril, and halofuginone) substances. Coccidiostats are used as feed additives, mixed upon request into the compounded feed. During the technical process of commercial feed production, cross-contamination of feed batches can result in the exposure of non-target animals and induce adverse health effects in these animals due to a specific sensitivity of mammalian species as compared to poultry. Residue formation in edible tissues of non-target species may result in unexpected human exposure through the consumption of animal products. This review presents recent risk assessments performed by the Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA). The health risk to non-target species that would result from the consumption of cross-contaminated feed with coccidostats at levels of 2, 5 or 10% was found to be negligible for most animal species with the exception of salinomycin and monensin in horses because of the particular sensitivity for which toxicity may occur when cross-contamination exceeds 2% and 5% respectively. Kinetic data and tissue analyses showed that residues of coccidiostats may occur in the liver and eggs in some cases. However, the level of residues of each coccidiostat in edible animal tissues remained sufficiently low that the aggregate exposure of consumers would not exceed the established acceptable daily intake (ADI) of each coccidiostat. It could be concluded that technical cross-contamination of animal feeds would not be expected to

Risk assessment of coccidostatics during feed cross-contamination: Animal and human health aspects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorne, J.L.C.M., E-mail: jean-lou.dorne@efsa.europa.eu; Fernández-Cruz, M.L.; Bertelsen, U.

Coccidiosis, an intestinal plasmodium infection, is a major infectious disease in poultry and rabbits. Eleven different coccidiostats are licensed in the EU for the prevention of coccidiosis in these animal species. According to their chemical nature and main biological activity, these compounds can be grouped as ionophoric (monensin, lasalocid sodium, salinomycin, narasin, maduramicin and semduramicin) or non-ionophoric (robenidine, decoquinate, nicarbazin, diclazuril, and halofuginone) substances. Coccidiostats are used as feed additives, mixed upon request into the compounded feed. During the technical process of commercial feed production, cross-contamination of feed batches can result in the exposure of non-target animals and induce adversemore » health effects in these animals due to a specific sensitivity of mammalian species as compared to poultry. Residue formation in edible tissues of non-target species may result in unexpected human exposure through the consumption of animal products. This review presents recent risk assessments performed by the Scientific Panel on Contaminants in the Food Chain (CONTAM) of the European Food Safety Authority (EFSA). The health risk to non-target species that would result from the consumption of cross-contaminated feed with coccidostats at levels of 2, 5 or 10% was found to be negligible for most animal species with the exception of salinomycin and monensin in horses because of the particular sensitivity for which toxicity may occur when cross-contamination exceeds 2% and 5% respectively. Kinetic data and tissue analyses showed that residues of coccidiostats may occur in the liver and eggs in some cases. However, the level of residues of each coccidiostat in edible animal tissues remained sufficiently low that the aggregate exposure of consumers would not exceed the established acceptable daily intake (ADI) of each coccidiostat. It could be concluded that technical cross-contamination of animal feeds would not be

Safety in Serbian animal source food industry and the impact of hazard analysis and critical control points: A review

NASA Astrophysics Data System (ADS)

Tomašević, I.; Đekić, I.

2017-09-01

There is a significant lack of HACCP-educated and/or HACCP-highly trained personnel within the Serbian animal source food workforces and veterinary inspectors, and this can present problems, particularly in hazard identification and assessment activities. However, despite obvious difficulties, HACCP benefits to the Serbian dairy industry are widespread and significant. Improving prerequisite programmes on the farms, mainly through infrastructural investments in milk collectors and transportation vehicles on one hand, and increasing hygiene awareness of farmers through training on the other hand has improved the safety of milk. The decline in bacterial numbers on meat contact surfaces, meat handlers’ hands and cooling facilities presents strong evidence of improved process hygiene and justifies the adoption of HACCP in Serbian meat establishments. Apart from the absence of national food poisoning statistics or national foodborne disease databases, the main obstacle to fully recognising the impact of HACCP on the safety of animal source food in Serbia is the lack of research regarding the occurrence of chemical and/or physical hazards interrelated with its production.

Balancing animal welfare and assisted reproduction: ethics of preclinical animal research for testing new reproductive technologies.

PubMed

Jans, Verna; Dondorp, Wybo; Goossens, Ellen; Mertes, Heidi; Pennings, Guido; de Wert, Guido

2018-02-07

In the field of medically assisted reproduction (MAR), there is a growing emphasis on the importance of introducing new assisted reproductive technologies (ARTs) only after thorough preclinical safety research, including the use of animal models. At the same time, there is international support for the three R's (replace, reduce, refine), and the European Union even aims at the full replacement of animals for research. The apparent tension between these two trends underlines the urgency of an explicit justification of the use of animals for the development and preclinical testing of new ARTs. Considering that the use of animals remains necessary for specific forms of ART research and taking account of different views on the moral importance of helping people to have a genetically related child, we argue that, in principle, the importance of safety research as part of responsible innovation outweighs the limited infringement of animal wellbeing involved in ART research.

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

9 CFR 311.29 - Unborn and stillborn animals.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Unborn and stillborn animals. 311.29 Section 311.29 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Unborn and stillborn animals. All unborn and stillborn animals shall be condemned and no hide or skin...

Application of Model Animals in the Study of Drug Toxicology

NASA Astrophysics Data System (ADS)

Song, Yagang; Miao, Mingsan

2018-01-01

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

Companion Animals. [Information Packet.

ERIC Educational Resources Information Center

National Anti-Vivisection Society, Chicago, IL.

This collection of articles reprinted from other National Anti-Vivisection Society (NAVS) publications was compiled to educate the public on issues of importance to NAVS concerning companion animals. Topics covered include spaying and neutering, animal safety, pet theft, and the use of cats and dogs in research. The article on spaying and…

Safety Precautions for Science.

ERIC Educational Resources Information Center

Folks, John; And Others

Safety information is discussed and outlined in this guide. Areas include: (1) general laboratory safety rules; (2) general rules and guidelines for animals in the elementary classroom; (3) general guidelines for the physical sciences; (4) general rules for using animals in investigations, with specifics on the care and handling of mammals,…

Characterization of the animal by-product meal industry in Costa Rica: Manufacturing practices through the production chain and food safety.

PubMed

Leiva, A; Granados-Chinchilla, F; Redondo-Solano, M; Arrieta-González, M; Pineda-Salazar, E; Molina, A

2018-06-01

Animal by-product rendering establishments are still relevant industries worldwide. Animal by-product meal safety is paramount to protect feed, animals, and the rest of the food chain from unwanted contamination. As microbiological contamination may arise from inadequate processing of slaughterhouse waste and deficiencies in good manufacturing practices within the rendering facilities, we conducted an overall establishment's inspection, including the product in several parts of the process.An evaluation of the Good Manufacturing Practices (GMP) was carried out, which included the location and access (i.e., admission) to the facilities, integrated pest management programs, physical condition of the facilities (e.g., infrastructure), equipments, vehicles and transportation, as well as critical control points (i.e., particle size and temperature set at 50 mm, 133°C at atmospheric pressure for 20 min, respectively) recommended by the OIE and the European Commission. The most sensitive points according to the evaluation are physical structure of the facilities (avg 42.2%), access to the facilities (avg 48.6%), and cleaning procedures (avg 51.4%).Also, indicator microorganisms (Salmonella spp., Clostridium spp., total coliforms, E. coli, E. coli O157:H7) were used to evaluate the safety in different parts of the animal meal production process. There was a prevalence of Salmonella spp. of 12.9, 14.3, and 33.3% in Meat and Bone Meal (MBM), poultry by-products, and fish meal, respectively. However, there were no significant differences (P = 0.73) in the prevalence between the different animal meals, according to the data collected.It was also observed that renderings associated with the poultry industry (i.e., 92.0%) obtained the best ratings overall, which reflects a satisfactory development of this sector and the integration of its production system as a whole.

Characterization of the animal by-product meal industry in Costa Rica: Manufacturing practices through the production chain and food safety

PubMed Central

Leiva, A; Granados-Chinchilla, F; Redondo-Solano, M; Arrieta-González, M; Pineda-Salazar, E; Molina, A

2018-01-01

ABSTRACT Animal by-product rendering establishments are still relevant industries worldwide. Animal by-product meal safety is paramount to protect feed, animals, and the rest of the food chain from unwanted contamination. As microbiological contamination may arise from inadequate processing of slaughterhouse waste and deficiencies in good manufacturing practices within the rendering facilities, we conducted an overall establishment's inspection, including the product in several parts of the process. An evaluation of the Good Manufacturing Practices (GMP) was carried out, which included the location and access (i.e., admission) to the facilities, integrated pest management programs, physical condition of the facilities (e.g., infrastructure), equipments, vehicles and transportation, as well as critical control points (i.e., particle size and temperature set at 50 mm, 133°C at atmospheric pressure for 20 min, respectively) recommended by the OIE and the European Commission. The most sensitive points according to the evaluation are physical structure of the facilities (avg 42.2%), access to the facilities (avg 48.6%), and cleaning procedures (avg 51.4%). Also, indicator microorganisms (Salmonella spp., Clostridium spp., total coliforms, E. coli, E. coli O157:H7) were used to evaluate the safety in different parts of the animal meal production process. There was a prevalence of Salmonella spp. of 12.9, 14.3, and 33.3% in Meat and Bone Meal (MBM), poultry by-products, and fish meal, respectively. However, there were no significant differences (P = 0.73) in the prevalence between the different animal meals, according to the data collected. It was also observed that renderings associated with the poultry industry (i.e., 92.0%) obtained the best ratings overall, which reflects a satisfactory development of this sector and the integration of its production system as a whole. PMID:29562297

Methylated glycans as conserved targets of animal and fungal innate defense

PubMed Central

Wohlschlager, Therese; Butschi, Alex; Grassi, Paola; Sutov, Grigorij; Gauss, Robert; Hauck, Dirk; Schmieder, Stefanie S.; Knobel, Martin; Titz, Alexander; Dell, Anne; Haslam, Stuart M.; Hengartner, Michael O.; Aebi, Markus; Künzler, Markus

2014-01-01

Effector proteins of innate immune systems recognize specific non-self epitopes. Tectonins are a family of β-propeller lectins conserved from bacteria to mammals that have been shown to bind bacterial lipopolysaccharide (LPS). We present experimental evidence that two Tectonins of fungal and animal origin have a specificity for O-methylated glycans. We show that Tectonin 2 of the mushroom Laccaria bicolor (Lb-Tec2) agglutinates Gram-negative bacteria and exerts toxicity toward the model nematode Caenorhabditis elegans, suggesting a role in fungal defense against bacteria and nematodes. Biochemical and genetic analysis of these interactions revealed that both bacterial agglutination and nematotoxicity of Lb-Tec2 depend on the recognition of methylated glycans, namely O-methylated mannose and fucose residues, as part of bacterial LPS and nematode cell-surface glycans. In addition, a C. elegans gene, termed samt-1, coding for a candidate membrane transport protein for the presumptive donor substrate of glycan methylation, S-adenosyl-methionine, from the cytoplasm to the Golgi was identified. Intriguingly, limulus lectin L6, a structurally related antibacterial protein of the Japanese horseshoe crab Tachypleus tridentatus, showed properties identical to the mushroom lectin. These results suggest that O-methylated glycans constitute a conserved target of the fungal and animal innate immune system. The broad phylogenetic distribution of O-methylated glycans increases the spectrum of potential antagonists recognized by Tectonins, rendering this conserved protein family a universal defense armor. PMID:24879441

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 113.38 - Guinea pig safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if...

9 CFR 318.20 - Use of animal drugs.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if...

The safety and physiologic effects of the anticoccidial drugs monensin and clazuril in sandhill cranes (Grus canadensis)

USGS Publications Warehouse

Carpenter, J.W.; Novilla, M.N.; Hatfield, J.S.

1992-01-01

Because crane chick mortality from disseminated visceral coccidiosis (DVC) at the Patuxent Wildlife Research Center increased in 1988, suggesting that the parasite may be developing a resistance to amprolium, a target animal safety study using coccidiostats, monensin and clazuril, was conducted on 27 subadult sandhill cranes.

9 CFR 113.39 - Cat safety tests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Cat safety tests. 113.39 Section 113... Procedures § 113.39 Cat safety tests. The safety tests provided in this section shall be conducted when... recommended for use in cats. (a) The cat safety test provided in this paragraph shall be used when the Master...

Animal models of asthma: innovative methods of lung research and new pharmacological targets.

PubMed

Braun, Armin; Tschernig, Thomas

2006-06-01

Allergic diseases like bronchial asthma are increasing in societies with western lifestyle. In the last years substantial progress was made in the understanding of the underlying mechanisms and explanations like the hygiene hypothesis were developed. However the exact mechanisms of the physiological and immunological events in the lung leading to bronchial asthma are still not fully understood. Therefore, animal models of asthma have been established and improved to study the complex cellular interactions in vivo. Since mice became the most frequently used animal species the methods for detecting lung physiology, e.g. lung function measurements were adapted to the small size of the murine lung. Laser-dissection and precision cut lung slices have become common techniques to get a view into distinct lung compartments and cells. In addition genomic and proteomic approaches are now used widely. On the other hand a major conclusion of the workshop stated that more than one species is necessary in research and for pharmacological screening in asthma and COPD. The resulting new understanding in the mechanisms of asthma pathogenesis has lead to a rapid identification of novel pharmaceutical targets for treatment of the disease.

Use of encapsulated bacteriophages to enhance farm to fork food safety.

PubMed

Hussain, Malik A; Liu, Huan; Wang, Qi; Zhong, Fang; Guo, Qian; Balamurugan, Sampathkumar

2017-09-02

Bacteriophages have been successfully applied to control the growth of pathogens in foods and to reduce the colonization and shedding of pathogens by food animals. They are set to play a dominant role in food safety in the future. However, many food-processing operations and the microenvironments in food animals' guts inactivate phages and reduce their infectivity. Encapsulation technologies have been used successfully to protect phages against extreme environments, and have been shown to preserve their activity and enable their release in targeted environments. A number of encapsulation technologies have shown potential for use with bacteriophages. This review discusses the current state of knowledge about the use of encapsulation technologies with bacteriophages to control pathogens in foods and food animals.

Children and Animals: Many Benefits--Some Concerns.

ERIC Educational Resources Information Center

Ross, Samuel B., Jr.

1989-01-01

Promotes value of using animals in therapeutic, vocational, and recreational education for children. Describes educational approaches, suggesting animals promote a sense of affection, understanding, self-worth, and responsibility among children. Discusses safety and hygienic considerations for having animals in both urban and rural environments.…

Safety of fenbendazole in common peafowl (Pavo cristatus).

PubMed

Umar, Sajid; Abbas, Seema; Khan, Muhammad Irfan; Nisa, Qamarun; Younus, Muhammad; Aqil, Kiran; Qayyum, Rizwan; Yaqoob, Muhammad; Ali, Asif; Yaseen, Muhammad Asif; Shah, Muhammad Ali

2018-01-01

The present study was undertaken to find out the safety levels of fenbendazole in common peafowl. This bird, raised on aviaries and zoos, can be severely parasitized with Ascaridia galli (enteric worms) and Syngamus trachea (gapeworm) along with other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic in animals. The objective of this work was to provide target animal safety data in young peafowl and to demonstrate reproductive safety in adult birds. During the experimental study, diets containing fenbendazole at 0, 100, 200 and 300 ppm were fed for 21 days (three times the normal treatment duration). Data for feed consumption, feed conversion rate, and body weights were recorded for each bird in each group. Drug concentrations in different tissues of birds were determined to correlate concentrations with clinical observations, clinical pathology, and histologic findings. There were no morbidities or mortalities after study day 21. Additionally, there were no statistically significant treatment-related differences among above mentioned parameters. Analysis of fenbendazole concentrations in kidney, liver, leg/thigh, and breast muscle and skin with associated fat revealed that, even at the highest dose level used and with no feed withdrawal, fenbendazole concentrations were relatively low in these tissues. These findings indicate that fenbendazole has a relatively wide margin of safety in young peafowl and that the proposed dose of 100 ppm in the feed for 7 consecutive days is well within the margin of safety. In the reproductive safety study, five breeder peafowl farms fed fendbendazole at 100ppm for 7 days and collected data on hatching percentage of peahen eggs before and after treatment. Reproductive performance in peahen was not adversely affected.

Frameless robotically targeted stereotactic brain biopsy: feasibility, diagnostic yield, and safety.

PubMed

Bekelis, Kimon; Radwan, Tarek A; Desai, Atman; Roberts, David W

2012-05-01

Frameless stereotactic brain biopsy has become an established procedure in many neurosurgical centers worldwide. Robotic modifications of image-guided frameless stereotaxy hold promise for making these procedures safer, more effective, and more efficient. The authors hypothesized that robotic brain biopsy is a safe, accurate procedure, with a high diagnostic yield and a safety profile comparable to other stereotactic biopsy methods. This retrospective study included 41 patients undergoing frameless stereotactic brain biopsy of lesions (mean size 2.9 cm) for diagnostic purposes. All patients underwent image-guided, robotic biopsy in which the SurgiScope system was used in conjunction with scalp fiducial markers and a preoperatively selected target and trajectory. Forty-five procedures, with 50 supratentorial targets selected, were performed. The mean operative time was 44.6 minutes for the robotic biopsy procedures. This decreased over the second half of the study by 37%, from 54.7 to 34.5 minutes (p < 0.025). The diagnostic yield was 97.8% per procedure, with a second procedure being diagnostic in the single nondiagnostic case. Complications included one transient worsening of a preexisting deficit (2%) and another deficit that was permanent (2%). There were no infections. Robotic biopsy involving a preselected target and trajectory is safe, accurate, efficient, and comparable to other procedures employing either frame-based stereotaxy or frameless, nonrobotic stereotaxy. It permits biopsy in all patients, including those with small target lesions. Robotic biopsy planning facilitates careful preoperative study and optimization of needle trajectory to avoid sulcal vessels, bridging veins, and ventricular penetration.

Evaluation of the microbial safety of child food of animal origin in Greece.

PubMed

Liandris, Emmanouil; Gazouli, Maria; Taka, Styliani; Andreadou, Margarita; Vaiopoulou, Anna; Tzimotoudis, Nikolaos; Kasampalidis, Ioannis; Mpaseas, Dionysis; Fyliousis, George; Poltronieri, Palmiro; Poltrionieri, Palmiro; Cook, Nigel; Ikonomopoulos, John

2014-03-01

Foodborne illness is a major cause of morbidity and mortality especially for children, even in the developed world. The aim of this study was to assess the microbial safety of food of animal origin intended for consumption by children in Greece. Sampling involved 8 categories of retail products and was completed with a collection of 850 samples. These were tested by PCR and/or culture for Listeria monocytogenes, Campylobacter spp., Escherichia coli O157, Salmonella spp., Cronobacter sakazakii, Brucella spp., and Mycobacterium avium subsp paratuberculosis (MAP). The number of positive results recorded collectively for the pathogens under investigation over the total number of samples tested was 3.52% and 0.12% by PCR and culture, respectively. The most frequently detected pathogen was enterohemorrhagic E. coli (1.29%) followed by Brucella (0.82%) and Listeria (0.82%). DNA belonging to MAP was detected in 0.35% of samples, which was also the percentage of positivity recorded for Campylobacter. The percentage for Salmonella was 0.12%. It can be concluded from the results that there is no indication of noncompliance for the tested food samples. However, detection of DNA belonging to pathogens that are transmissible to humans through food is indicative that constant vigilance regarding food safety is an absolute necessity. © 2014 Institute of Food Technologists®

Using an Animated Case Scenario Based on Constructivist 5E Model to Enhance Pre-Service Teachers' Awareness of Electrical Safety

ERIC Educational Resources Information Center

Hirca, Necati

2013-01-01

The objective of this study is to get pre-service teachers to develop an awareness of first aid knowledge and skills related to electrical shocking and safety within a scenario based animation based on a Constructivist 5E model. The sample of the study was composed of 78 (46 girls and 32 boys) pre-service classroom teachers from two faculties of…

Beta-agonists and animal welfare

USDA-ARS?s Scientific Manuscript database

The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

PubMed Central

Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

2014-01-01

It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment. PMID:24860564

Preclinical safety testing for cell-based products using animals.

PubMed

McBlane, James W

2015-09-01

The objectives of preclinical testing include to show why there might be therapeutic benefit in patients and to provide information on the product's toxicity. For cell-based products, given even once, there may be long term exposure and this could imply, unlike for conventional drugs, that all preclinical studies may be needed prior to first human use. The duration of exposure to cells should be studied in animals to guide toxicity assessments. Distribution of cells after administration by a route resembling that intended in humans should be studied to understand potential risks. Risk of tumour formation with the product may also need to be characterised. To the extent that this information can be generated by in vitro testing, studies in animals may not be needed and limitations on the capability of preclinical data to predict human toxicity are recognised: species-specificity make some cell products act only in humans and a human cell-product might be expected to be rejected by immunocompetent animals. Does this suggest testing in immunosuppressed animals or of development of an animal-cell product supposedly similar to the human cell product? No single answer seems to fit every situation. Copyright © 2015.

Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

DOE PAGES

Polyzos, Aris; Holt, Amy; Brown, Christopher; ...

2016-02-21

Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a grayingmore » phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.« less

Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polyzos, Aris; Holt, Amy; Brown, Christopher

Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a grayingmore » phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.« less

A randomised controlled study to evaluate the effectiveness of targeted occupational health and safety consultation or inspection in Ontario manufacturing workplaces.

PubMed

Hogg-Johnson, Sheilah; Robson, Lynda; Cole, Donald C; Amick, Benjamin C; Tompa, Emile; Smith, Peter M; van Eerd, Dwayne; Mustard, Cameron

2012-12-01

From 2004 to 2008, the prevention system in Ontario, Canada ran the High Risk Firm Initiative, an injury-experience based targeted consultation or inspection programme. Our objective was to establish whether prevention system targeting of firms was effective in improving injury outcomes. Randomised controlled parallel groups. Population included all manufacturing firms registered with the Ontario Workplace Safety & Insurance Board in 2005. Firms ranked between the 2nd and 10th percentile on a composite measure of occupational health and safety performance were randomised to three study arms in 2006: targeted for Health & Safety Association (HSA) consultation, targeted for Ministry of Labour (MOL) inspection, or services as usual. Data included firm characteristics (sector, size, years in business, region, branches), work injury claims 2002-2008 and measures of consulting and inspecting activity. Negative binomial generalised estimating equations modelled claim and disability day rates by study arm and year, controlling for firm characteristics. Among 2153 firms, firm characteristics and 2002-2005 rates of work injury claims and disability days were similar across arms. Firm outcomes were significantly different from year to year, but study arm by year interactions were insignificant indicating similar trends for all three study arms. 83% of HSA targeted firms were contacted and 63% engaged while 75% of MOL targeted firms were inspected with orders written in 56%. Consultation and enforcement programmes as implemented were not sufficient to reduce work injury outcomes over 21 month follow-up. Lack of benefit could be due to non-specific firm selection methods, limited firm participation in interventions, low intervention intensity or insensitivity of available outcomes.

A safety analysis of food waste-derived animal feeds from three typical conversion techniques in China.

PubMed

Chen, Ting; Jin, Yiying; Shen, Dongsheng

2015-11-01

This study was based on the food waste to animal feed demonstration projects in China. A safety analysis of animal feeds from three typical treatment processes (i.e., fermentation, heat treatment, and coupled hydrothermal treatment and fermentation) was presented. The following factors are considered in this study: nutritive values characterized by organoleptic properties and general nutritional indices; the presence of bovine- and sheep-derived materials; microbiological indices for Salmonella, total coliform (TC), total aerobic plate counts (TAC), molds and yeast (MY), Staphylococcus Aureus (SA), and Listeria; chemical contaminant indices for hazardous trace elements such as Cr, Cd, and As; and nitrite and organic contaminants such as aflatoxin B1 (AFB1) and hexachlorocyclohexane (HCH). The present study reveals that the feeds from all three conversion processes showed balanced nutritional content and retained a certain feed value. The microbiological indices and the chemical contaminant indices for HCH, dichlorodiphenyltrichloroethane (DDT), nitrite, and mercury all met pertinent feed standards; however, the presence of bovine- and sheep-derived materials and a few chemical contaminants such as Pb were close to or might exceed the legislation permitted values in animal feeding. From the view of treatment techniques, all feed retained part of the nutritional values of the food waste after the conversion processes. Controlled heat treatment can guarantee the inactivation of bacterial pathogens, but none of the three techniques can guarantee the absence of cattle- and sheep-derived materials and acceptable levels of certain contaminants. The results obtained in this research and the feedstuffs legislation related to animal feed indicated that food waste-derived feed could be considered an adequate alternative to be used in animal diets, while the feeding action should be changed with the different qualities of the products, such as restrictions on the application

Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: a critical overview.

PubMed

Navarro, Xavier

2016-02-01

Peripheral nerve injuries usually lead to severe loss of motor, sensory and autonomic functions in the patients. Due to the complex requirements for adequate axonal regeneration, functional recovery is often poorly achieved. Experimental models are useful to investigate the mechanisms related to axonal regeneration and tissue reinnervation, and to test new therapeutic strategies to improve functional recovery. Therefore, objective and reliable evaluation methods should be applied for the assessment of regeneration and function restitution after nerve injury in animal models. This review gives an overview of the most useful methods to assess nerve regeneration, target reinnervation and recovery of complex sensory and motor functions, their values and limitations. The selection of methods has to be adequate to the main objective of the research study, either enhancement of axonal regeneration, improving regeneration and reinnervation of target organs by different types of nerve fibres, or increasing recovery of complex sensory and motor functions. It is generally recommended to use more than one functional method for each purpose, and also to perform morphological studies of the injured nerve and the reinnervated targets. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach.

PubMed

Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

2010-02-19

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg(-1) day(-1) or 250 mg kg(-1) day(-1) for a period of 7 days (n=4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers. Copyright 2009 Elsevier B.V. All rights reserved.

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.33 - Mouse safety tests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Mouse safety tests. 113.33 Section 113... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be... or more ingredients makes the biological product lethal or toxic for mice but not lethal or toxic for...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.44 - Swine safety test.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Swine safety test. 113.44 Section 113... Procedures § 113.44 Swine safety test. The swine safety test provided in this section shall be conducted when.... (1) Inject each of two swine of the minimum age for which the product is recommended with the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

9 CFR 113.40 - Dog safety tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Dog safety tests. 113.40 Section 113... Procedures § 113.40 Dog safety tests. The safety tests provided in this section shall be conducted when... recommended for use in dogs. Serials which are not found to be satisfactory when tested pursuant to the...

Animal models for periodontal regeneration and peri-implant responses.

PubMed

Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E

2015-06-01

Translation of experimental data to the clinical setting requires the safety and efficacy of such data to be confirmed in animal systems before application in humans. In dental research, the animal species used is dependent largely on the research question or on the disease model. Periodontal disease and, by analogy, peri-implant disease, are complex infections that result in a tissue-degrading inflammatory response. It is impossible to explore the complex pathogenesis of periodontitis or peri-implantitis using only reductionist in-vitro methods. Both the disease process and healing of the periodontal and peri-implant tissues can be studied in animals. Regeneration (after periodontal surgery), in response to various biologic materials with potential for tissue engineering, is a continuous process involving various types of tissue, including epithelia, connective tissues and alveolar bone. The same principles apply to peri-implant healing. Given the complexity of the biology, animal models are necessary and serve as the standard for successful translation of regenerative materials and dental implants to the clinical setting. Smaller species of animal are more convenient for disease-associated research, whereas larger animals are more appropriate for studies that target tissue healing as the anatomy of larger animals more closely resembles human dento-alveolar architecture. This review focuses on the animal models available for the study of regeneration in periodontal research and implantology; the advantages and disadvantages of each animal model; the interpretation of data acquired; and future perspectives of animal research, with a discussion of possible nonanimal alternatives. Power calculations in such studies are crucial in order to use a sample size that is large enough to generate statistically useful data, whilst, at the same time, small enough to prevent the unnecessary use of animals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Examining the nexus between domestic violence and animal abuse in a national sample of service providers.

PubMed

Krienert, Jessie L; Walsh, Jeffrey A; Matthews, Kevin; McConkey, Kelly

2012-01-01

Companion animals play a complex role in families impacted by violence. An outlet of emotional support for victims, the family pet often becomes a target for physical abuse. Results from a comprehensive e-survey of domestic violence shelters nationwide (N = 767) highlight both improvements and existing gaps in service provision for domestic violence victims and their pets. Quantitative and qualitative data noted frequently encountered obstacles to successful shelter seeking by abuse victims with companion animals including a lack of availability, funding, space, and reliable programming. Although results indicate an overall improvement in organizational awareness, fewer than half of surveyed shelters include intake questions about animals. Continued awareness and an expansion of services is needed to create viable safety planning strategies and reliable alternatives for women with companion animals in order to improve the likelihood that abuse victims will seek escape and refuge for themselves, their children, and their pets.

Stochastic targeted (STAR) glycemic control: design, safety, and performance.

PubMed

Evans, Alicia; Le Compte, Aaron; Tan, Chia-Siong; Ward, Logan; Steel, James; Pretty, Christopher G; Penning, Sophie; Suhaimi, Fatanah; Shaw, Geoffrey M; Desaive, Thomas; Chase, J Geoffrey

2012-01-01

Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach that directly accounts for intra- and interpatient variability with a stochastically derived maximum 5% risk of blood glucose (BG) below 72 mg/dl. This research assesses the safety, efficacy, and clinical burden of a STAR TGC controller modulating both insulin and nutrition inputs in virtual and clinical pilot trials. Clinically validated virtual trials using data from 370 patients in the SPRINT (Specialized Relative Insulin and Nutrition Titration) study were used to design the STAR protocol and test its safety, performance, and required clinical effort prior to clinical pilot trials. Insulin and nutrition interventions were given every 1-3 h as chosen by the nurse to allow them to manage workload. Interventions were designed to maximize the overlap of the model-predicted (5-95(th) percentile) range of BG outcomes with the 72-117 mg/dl band and thus provide a maximum 5% risk of BG <72 mg/dl. Interventions were calculated using clinically validated computer models of human metabolism and its variability in critical illness. Carbohydrate intake (all sources) was selected to maximize intake up to 100% of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) goal (25 kg/kcal/h). Insulin doses were limited (8 U/h maximum), with limited increases based on current rate (0.5-2.0 U/h). Initial clinical pilot trials involved 3 patients covering ~450 h. Approval was granted by the Upper South A Regional Ethics Committee. Virtual trials indicate that STAR provides similar glycemic control performance to SPRINT with 2-3 h (maximum) measurement intervals. Time in the 72-126 mg/dl and 72-145 mg/dl bands was equivalent for all controllers, indicating that glycemic outcome differences between protocols were only shifted in this range. Safety from hypoglycemia was improved. Importantly

Immunogenicity and safety of a tetravalent E. coli O-antigen bioconjugate vaccine in animal models.

PubMed

van den Dobbelsteen, Germie P J M; Faé, Kellen C; Serroyen, Jan; van den Nieuwenhof, Ingrid M; Braun, Martin; Haeuptle, Micha A; Sirena, Dominique; Schneider, Joerg; Alaimo, Cristina; Lipowsky, Gerd; Gambillara-Fonck, Veronica; Wacker, Michael; Poolman, Jan T

2016-07-29

Extra-intestinal pathogenic Escherichia coli (ExPEC) are major human pathogens; however, no protective vaccine is currently available. We assessed in animal models the immunogenicity and safety of a 4-valent E. coli conjugate vaccine (ExPEC-4V, serotypes O1, O2, O6 and O25 conjugated to Exotoxin A from Pseudomonas aeruginosa (EPA)) produced using a novel in vivo bioconjugation method. Three doses of ExPEC-4V (with or without aluminum hydroxide) were administered to rabbits (2μg or 20μg per O-antigen, subcutaneously), mice (0.2μg or 2μg per O-antigen, subcutaneously) and rats (0.4μg or 4μg per O-antigen, intramuscularly). Antibody persistence and boostability were evaluated in rats using O6-EPA monovalent conjugate (0.4μg O-antigen/dose, intramuscularly). Toxicity was assessed in rats (16μg total polysaccharide, intramuscularly). Serum IgG and IgM antibodies were measured by ELISA. Robust antigen-specific IgG responses were observed in all animal models, with increased responses in rabbits when administered with adjuvant. O antigen-specific antibody responses persisted up to 168days post-priming. Booster immunization induced a rapid recall response. Toxicity of ExPEC-4V when administered to rats was considered to be at the no observed adverse effect level. ExPEC-4V conjugate vaccine showed good immunogenicity and tolerability in animal models supporting progression to clinical evaluation. Copyright © 2016 Elsevier Ltd. All rights reserved.

9 CFR 311.27 - Injured animals slaughtered at unusual hours.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Injured animals slaughtered at unusual hours. 311.27 Section 311.27 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT... AND VOLUNTARY INSPECTION AND CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND...

The influence of animal fear on attentional capture by fear-relevant animal stimuli in children.

PubMed

Waters, Allison M; Lipp, Ottmar V

2008-01-01

The present study demonstrated that pictures of fear-relevant animals, snakes and spiders, presented among backgrounds of other animal stimuli captured attention and interfered in the detection of a neutral target to the same extent in a large sample of unselected children (N=81). Moreover, detection of a neutral target animal was slowed more in the presence of a feared fear-relevant distracter, e.g., a snake for snake fearful children, than in the presence of a not feared fear-relevant distracter, e.g., a spider for snake fearful children. These results indicate attentional capture by phylogenetically fear-relevant animal stimuli in children and the selective enhancement of this effect by fear of these animals. These findings are consistent with current models of preferential processing of phylogenetically prepared threat stimuli and with cognitive models of anxiety that propose an enhancing effect of fear in the processing of fear-related stimuli.

Recent progress and future directions for reduction, refinement, and replacement of animal use in veterinary vaccine potency and safety testing: a report from the 2010 NICEATM-ICCVAM International Vaccine Workshop.

PubMed

Stokes, W S; Kulpa-Eddy, J; Brown, K; Srinivas, G; McFarland, R

2012-01-01

Veterinary vaccines contribute to improved animal and human health and welfare by preventing infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing, and to identify priority activities to advance new and improved methods that can further reduce, refine and replace animal use. Rabies, Clostridium sp., and Leptospira sp. vaccines were identified as the highest priorities, while tests requiring live viruses and bacteria hazardous to laboratory workers, livestock, pets, and wildlife were also considered high priorities. Priority research, development and validation activities to address critical knowledge and data gaps were identified, including opportunities to apply new science and technology. Enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers were recommended to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will benefit animal welfare and ensure continued and improved protection of human and animal health.

9 CFR 319.703 - Rendered animal fat or mixture thereof.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Rendered animal fat or mixture thereof. 319.703 Section 319.703 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Fats, Oils, Shortenings...

9 CFR 319.703 - Rendered animal fat or mixture thereof.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Rendered animal fat or mixture thereof. 319.703 Section 319.703 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Fats, Oils, Shortenings...

Divergent Isoprenoid Biosynthesis Pathways in Staphylococcus Species Constitute a Drug Target for Treating Infections in Companion Animals

PubMed Central

Cain, Christine L.; Morris, Daniel O.; Rankin, Shelley C.

2016-01-01

ABSTRACT Staphylococcus species are a leading cause of skin and soft tissue infections in humans and animals, and the antibiotics used to treat these infections are often the same. Methicillin- and multidrug-resistant staphylococcal infections are becoming more common in human and veterinary medicine. From a “One Health” perspective, this overlap in antibiotic use and resistance raises concerns over the potential spread of antibiotic resistance genes. Whole-genome sequencing and comparative genomics analysis revealed that Staphylococcus species use divergent pathways to synthesize isoprenoids. Species frequently associated with skin and soft tissue infections in companion animals, including S. schleiferi and S. pseudintermedius, use the nonmevalonate pathway. In contrast, S. aureus, S. epidermidis, and S. lugdunensis use the mevalonate pathway. The antibiotic fosmidomycin, an inhibitor of the nonmevalonate pathway, was effective in killing canine clinical staphylococcal isolates but had no effect on the growth or survival of S. aureus and S. epidermidis. These data identify an essential metabolic pathway in Staphylococcus that differs among members of this genus and suggest that drugs such as fosmidomycin, which targets enzymes in the nonmevalonate pathway, may be an effective treatment for certain staphylococcal infections. IMPORTANCE Drug-resistant Staphylococcus species are a major concern in human and veterinary medicine. There is a need for new antibiotics that exhibit a selective effect in treating infections in companion and livestock animals and that would not be used to treat human bacterial infections. We have identified fosmidomycin as an antibiotic that selectively targets certain Staphylococcus species that are often encountered in skin infections in cats and dogs. These findings expand our understanding of Staphylococcus evolution and may have direct implications for treating staphylococcal infections in veterinary medicine. PMID:27704053

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

42 CFR 86.33 - Human subjects; animal welfare.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Human subjects; animal welfare. 86.33 Section 86.33... Occupational Safety and Health Direct Traineeships § 86.33 Human subjects; animal welfare. Where the...) Chapter 1-43 of the Department Grants Administration Manual 2 068 concerning animal welfare. 2 See...

IN CASE YOU MISSED IT: EPA Releases New Chemical Safety Guidelines Aimed at Curbing Animal Testing, Tracking Mercury Imports, and Facilitating the Sharing of Confidential Business Information

EPA Pesticide Factsheets

EPA News Release: IN CASE YOU MISSED IT: EPA Releases New Chemical Safety Guidelines Aimed at Curbing Animal Testing, Tracking Mercury Imports, and Facilitating the Sharing of Confidential Business Information

Bear Spray Safety Program

USGS Publications Warehouse

Blome, C.D.; Kuzniar, R.L.

2009-01-01

A bear spray safety program for the U.S. Geological Survey (USGS) was officially initiated by the Firearms Safety Committee to address accident prevention and to promote personnel training in bear spray and its transportation, storage, and use for defense against wild animals. Used as part of a system including firearms, or used alone for those who choose not to carry a firearm, bear spray is recognized as an effective tool that can prevent injury in a wild animal attack.

Ending the use of animals in toxicity testing and risk evaluation.

PubMed

Rowan, Andrew N

2015-10-01

This article discusses the use of animals for the safety testing of chemicals, including pharmaceuticals, household products, pesticides, and industrial chemicals. It reviews changes in safety testing technology and what those changes mean from the perspective of industrial innovation, public policy and public health, economics, and ethics. It concludes that the continuing use of animals for chemical safety testing should end within the decade as cheaper, quicker, and more predictive technologies are developed and applied.

Pigs as laboratory animals

USDA-ARS?s Scientific Manuscript database

The pig is increasingly popular as a laboratory animal either as the target species in its own right or as a model for humans in biomedical science. As an intelligent, social animal it has a complex behavioral repertoire reminiscent of its ancestor, the wild boar. Within a laboratory setting, the pi...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

36 CFR 520.4 - Protection of zoo animals.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Protection of zoo animals... Protection of zoo animals. Except for official purposes, no person shall: (a) Kill, injure, or disturb any exhibit or research animal by any means except to secure personal safety; (b) Pet, attempt to pet, handle...

36 CFR 520.4 - Protection of zoo animals.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Protection of zoo animals... Protection of zoo animals. Except for official purposes, no person shall: (a) Kill, injure, or disturb any exhibit or research animal by any means except to secure personal safety; (b) Pet, attempt to pet, handle...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

36 CFR 520.4 - Protection of zoo animals.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Protection of zoo animals... Protection of zoo animals. Except for official purposes, no person shall: (a) Kill, injure, or disturb any exhibit or research animal by any means except to secure personal safety; (b) Pet, attempt to pet, handle...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

36 CFR 520.4 - Protection of zoo animals.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Protection of zoo animals... Protection of zoo animals. Except for official purposes, no person shall: (a) Kill, injure, or disturb any exhibit or research animal by any means except to secure personal safety; (b) Pet, attempt to pet, handle...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

42 CFR 86.19 - Human subjects; animal welfare.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Human subjects; animal welfare. 86.19 Section 86.19... Occupational Safety and Health Training Grants § 86.19 Human subjects; animal welfare. No grant award may be... concerning animal welfare. 2 The Department Grants Administration Manual is available for inspection at the...

A Framework for School Safety and Risk Management: Results from a Study of 18 Targeted School Shooters

ERIC Educational Resources Information Center

Lenhardt, Ann Marie C.; Graham, Lemuel W.; Farrell, Melissa L.

2018-01-01

Targeted violence continues to pose a threat to school safety. Reported here are the results of a study of 18 cases of school shooters from 1996 to 2012. Variables examined are individual factors and behaviors, family dynamics, and triggering events. Results indicate the need for expanded school-based mental health services, threat assessment, and…

ANIMAL ENTEROTOXIGENIC ESCHERICHIA COLI

PubMed Central

Dubreuil, J. Daniel; Isaacson, Richard E.; Schifferli, Dieter M.

2016-01-01

Enterotoxigenic Escherichia coli (ETEC) is the most common cause of E. coli diarrhea in farm animals. ETEC are characterized by the ability to produce two types of virulence factors; adhesins that promote binding to specific enterocyte receptors for intestinal colonization and enterotoxins responsible for fluid secretion. The best-characterized adhesins are expressed in the context of fimbriae, such as the F4 (also designated K88), F5 (K99), F6 (987P), F17 and F18 fimbriae. Once established in the animal small intestine, ETEC produces enterotoxin(s) that lead to diarrhea. The enterotoxins belong to two major classes; heat-labile toxin that consist of one active and five binding subunits (LT), and heat-stable toxins that are small polypeptides (STa, STb, and EAST1). This chapter describes the disease and pathogenesis of animal ETEC, the corresponding virulence genes and protein products of these bacteria, their regulation and targets in animal hosts, as well as mechanisms of action. Furthermore, vaccines, inhibitors, probiotics and the identification of potential new targets identified by genomics are presented in the context of animal ETEC. PMID:27735786

[Preclinical evaluation of the safety of biotechnology products: specific aspects].

PubMed

Descotes, Jacques; Ravel, Guillaume; Vial, Thierry

2003-01-01

Biotechnology-derived products represent a class of increasingly numerous drugs. One of their major characteristics is extreme diversity, which requires specific approaches for the preclinical evaluation of their safety. The selection of relevant animal species is not easy, as most of these products are human-specific. Thus, only one species will often be used, i.e. primates. As most of these products are large molecules, they can be directly immunogenic. When they are human-specific, no animal model is available to predict the risk. Many biotechnology-derived products have an expected influence on the immune system. This must be taken into account in the preclinical strategy of immunotoxicity evaluation that is now required for every new drug. As conventional toxicity testing is generally limited, safety pharmacology studies should include more than the core battery of assays required by current guidelines in order to complement missing data as much as possible. Because of these particularities, a comprehensive investigation of metabolism and pharmacokinetics is not usually needed. Some products can cross-react with cellular components not intended as therapeutic targets. It is, therefore, essential to rule out the risk of possible cross-reactions that can result in adverse effects. Finally, viral safety is a crucial component of the preclinical safety evaluation of these products. Overall, biotechnology-derived products raise specific issues because of their innovative and original characteristics, and it is difficult to address all these issues if not by using a case-by-case approach.

Parallel computation safety analysis irradiation targets fission product molybdenum in neutronic aspect using the successive over-relaxation algorithm

NASA Astrophysics Data System (ADS)

Susmikanti, Mike; Dewayatna, Winter; Sulistyo, Yos

2014-09-01

One of the research activities in support of commercial radioisotope production program is a safety research on target FPM (Fission Product Molybdenum) irradiation. FPM targets form a tube made of stainless steel which contains nuclear-grade high-enrichment uranium. The FPM irradiation tube is intended to obtain fission products. Fission materials such as Mo99 used widely the form of kits in the medical world. The neutronics problem is solved using first-order perturbation theory derived from the diffusion equation for four groups. In contrast, Mo isotopes have longer half-lives, about 3 days (66 hours), so the delivery of radioisotopes to consumer centers and storage is possible though still limited. The production of this isotope potentially gives significant economic value. The criticality and flux in multigroup diffusion model was calculated for various irradiation positions and uranium contents. This model involves complex computation, with large and sparse matrix system. Several parallel algorithms have been developed for the sparse and large matrix solution. In this paper, a successive over-relaxation (SOR) algorithm was implemented for the calculation of reactivity coefficients which can be done in parallel. Previous works performed reactivity calculations serially with Gauss-Seidel iteratives. The parallel method can be used to solve multigroup diffusion equation system and calculate the criticality and reactivity coefficients. In this research a computer code was developed to exploit parallel processing to perform reactivity calculations which were to be used in safety analysis. The parallel processing in the multicore computer system allows the calculation to be performed more quickly. This code was applied for the safety limits calculation of irradiated FPM targets containing highly enriched uranium. The results of calculations neutron show that for uranium contents of 1.7676 g and 6.1866 g (× 106 cm-1) in a tube, their delta reactivities are the still

Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses

PubMed Central

Ocana, Alberto; Ethier, Josee-Lyne; Díez-González, Laura; Corrales-Sánchez, Verónica; Srikanthan, Amirrtha; Gascón-Escribano, María J.; Templeton, Arnoud J.; Vera-Badillo, Francisco; Seruga, Bostjan; Niraula, Saroj; Pandiella, Atanasio; Amir, Eitan

2015-01-01

Background Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Methods and findings Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 versus 1.65, p < 0.001) and grade 3/4 AEs (OR = 1.09 versus 2.10, p < 0.001), but no difference in risk of toxic death (OR = 1.40 versus 1.27, p = 0.69). Differences between agents with and without companion diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p < 0.001), vomiting (OR = 0.86 vs. 1.44, p = 0.005), cutaneous toxicity (OR = 1.82 vs. 3.88, p < 0.001) and neuropathy (OR = 0.64 vs. 1.60, p < 0.001). Conclusions Targeted drugs with companion diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity. PMID:26446908

Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

PubMed

Ocana, Alberto; Ethier, Josee-Lyne; Díez-González, Laura; Corrales-Sánchez, Verónica; Srikanthan, Amirrtha; Gascón-Escribano, María J; Templeton, Arnoud J; Vera-Badillo, Francisco; Seruga, Bostjan; Niraula, Saroj; Pandiella, Atanasio; Amir, Eitan

2015-11-24

Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p < 0.001) and grade 3/4 AEs (OR = 1.09 vs. 2.10, p < 0.001), but no difference in risk of toxic death (OR = 1.40 vs. 1.27, p = 0.69). Differences between agents with and without companion diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p < 0.001), vomiting (OR = 0.86 vs. 1.44, p = 0.005), cutaneous toxicity (OR = 1.82 vs. 3.88, p < 0.001) and neuropathy (OR = 0.64 vs. 1.60, p < 0.001). Targeted drugs with companion diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.

Identifying specific beliefs to target to improve restaurant employees' intentions for performing three important food safety behaviors.

PubMed

Pilling, Valerie K; Brannon, Laura A; Shanklin, Carol W; Howells, Amber D; Roberts, Kevin R

2008-06-01

Current national food safety training programs appear ineffective at improving food safety practices in foodservice operations, given the substantial number of Americans affected by foodborne illnesses after eating in restaurants each year. The Theory of Planned Behavior (TpB) was used to identify important beliefs that may be targeted to improve foodservice employees' intentions for three food safety behaviors that have the most substantial affect on public health: hand washing, using thermometers, and proper handling of food contact surfaces. In a cross-sectional design, foodservice employees (n=190) across three midwestern states completed a survey assessing TpB components and knowledge for the three food safety behaviors. Multiple regression analyses were performed on the TpB components for each behavior. Independent-samples t tests identified TpB beliefs that discriminated between participants who absolutely intend to perform the behaviors and those with lower intention. Employees' attitudes were the one consistent predictor of intentions for performing all three behaviors. However, a unique combination of important predictors existed for each separate behavior. Interventions for improving employees' behavioral intentions for food safety should focus on TpB components that predict intentions for each behavior and should bring all employees' beliefs in line with those of the employees who already intend to perform the food safety behaviors. Registered dietitians; dietetic technicians, registered; and foodservice managers can use these results to enhance training sessions and motivational programs to improve employees' food safety behaviors. Results also assist these professionals in recognizing their responsibility for enforcing and providing adequate resources for proper food safety behaviors.

Non-targeted analyses of animal plasma: betaine and choline represent the nutritional and metabolic status.

PubMed

Katayama, K; Sato, T; Arai, T; Amao, H; Ohta, Y; Ozawa, T; Kenyon, P R; Hickson, R E; Tazaki, H

2013-02-01

Simple liquid chromatography-mass spectrometry (LC-MS) was applied to non-targeted metabolic analyses to discover new metabolic markers in animal plasma. Principle component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) were used to analyse LC-MS multivariate data. PCA clearly generated two separate clusters for artificially induced diabetic mice and healthy control mice. PLS-DA of time-course changes in plasma metabolites of chicks after feeding generated three clusters (pre- and immediately after feeding, 0.5-3 h after feeding and 4 h after feeding). Two separate clusters were also generated for plasma metabolites of pregnant Angus heifers with differing live-weight change profiles (gaining or losing). The accompanying PLS-DA loading plot detailed the metabolites that contribute the most to the cluster separation. In each case, the same highly hydrophilic metabolite was strongly correlated to the group separation. The metabolite was identified as betaine by LC-MS/MS. This result indicates that betaine and its metabolic precursor, choline, may be useful biomarkers to evaluate the nutritional and metabolic status of animals. © 2011 Blackwell Verlag GmbH.

Trends in greenhouse gas emissions from consumption and production of animal food products - implications for long-term climate targets.

PubMed

Cederberg, C; Hedenus, F; Wirsenius, S; Sonesson, U

2013-02-01

-increase target of 2° might imply a severe constraint on the long-term global consumption of animal food. Due to the relatively limited potential for reducing food-related emissions by higher productivity and technological means, structural changes in food consumption towards less emission-intensive food might be required for meeting the 2° target.

Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryan, Patricia C., E-mail: ryanp@medimmune.com; Sleeman, Matthew A.; Rebelatto, Marlon

Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters othermore » than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus

Human-animal interactions and safety during dairy cattle handling--Comparing moving cows to milking and hoof trimming.

PubMed

Lindahl, C; Pinzke, S; Herlin, A; Keeling, L J

2016-03-01

Cattle handling is a dangerous activity on dairy farms, and cows are a major cause of injuries to livestock handlers. Even if dairy cows are generally tranquil and docile, when situations occur that they perceive or remember as aversive, they may become agitated and hazardous to handle. This study aimed to compare human-animal interactions, cow behavior, and handler safety when moving cows to daily milking and moving cows to more rarely occurring and possibly aversive hoof trimming. These processes were observed on 12 Swedish commercial dairy farms. The study included behavioral observations of handler and cows and cow heart rate recordings, as well as recording frequencies of situations and incidents related to an increased injury risk to the handler. At milking, cows were quite easily moved using few interactions. As expected, the cows showed no behavioral signs of stress, fear, or resistance and their heart rate only rose slightly from the baseline (i.e., the average heart rate during an undisturbed period before handling). Moving cows to hoof trimming involved more forceful and gentle interactions compared with moving cows to milking. Furthermore, the cows showed much higher frequencies of behaviors indicative of aversion and fear (e.g., freezing, balking, and resistance), as well as a higher increase in heart rate. The risk of injury to which handlers were exposed also increased when moving cows to hoof trimming rather than to routine milking. Some interactions (such as forceful tactile interactions with an object and pulling a neck strap or halter) appeared to be related to potentially dangerous incidents where the handler was being kicked, head-butted, or run over by a cow. In conclusion, moving cows to hoof trimming resulted in higher frequencies of behaviors indicating fear, more forceful interactions, and increased injury risks to the handler than moving cows to milking. Improving potentially stressful handling procedures (e.g., by better animal handling

The role of the World Organisation for Animal Health (OIE) to facilitate the international trade in animals and animal products.

PubMed

Brückner, G K

2009-03-01

The international trade in animals and animal products has become a sensitive issue for both developed and developing countries by posing an important risk for the international spread of animal and human pathogens whilst at the same time being an essential activity to ensure world-wide food security and food safety. The OIE has since its founding in 1924, applied a democratic and transparent decision-making process to continuously develop and review international standards for animal health and zoonoses to facilitate trade in animals and animal products. The role of the OIE is also mandated by the World Trade Organization (WTO) as international reference point for standards related to animal health. In support of its overall objective of promoting animal health world-wide, the OIE has also launched several other initiatives such as the improvement of the governance of veterinary services within its member countries and territories and to enhance the availability of diagnostic and scientific expertise on a more even global geographical distribution. Several trade facilitating concepts such as country, zonal and compartment freedom from disease as well the trade in disease free commodities has been introduced to enhance the trade in animals and animal products for all its members including those from developing and transitional countries who are still in the process of enhancing to full compliance with international sanitary standards.

Exploring the Gaps in Practical Ethical Guidance for Animal Welfare Considerations of Field Interventions and Innovations Targeting Dogs and Cats.

PubMed

Tasker, Louisa; Getty, Susan F; Briggs, Joyce R; Benka, Valerie A W

2018-01-27

Domestic dogs ( Canis lupus familiaris ) and cats ( Felis silvestris catus ) are common species targeted by nongovernmental or intergovernmental organizations, veterinarians and government agencies worldwide, for field interventions (e.g., population management, rabies vaccination programs) or innovations (e.g., development of technologies or pharmaceuticals to improve animal welfare). We have a moral responsibility to ensure that the conduct of this work is humane for dogs or cats, and to consider the human communities in which the animals live. Ethical review is widely accepted as being integral to responsible practice, and it is fundamental to good science that underpins innovation. Despite the necessity of field interventions or innovations to advance the welfare of individuals or populations of animals, we found a lack of specific guidance and review processes to help navigate ethical dilemmas surrounding the conduct of such work. This can be detrimental to the wellbeing of animals and their human communities. Here we identify the gaps in existing ethical frameworks (specifically application of Reduction and Refinement principles, challenges of obtaining meaningful informed consent with variations in the quality of human-animal relationships, and limited resources regarding considerations of local stakeholders), and outline the need for additional tools to promote ethical conduct in the field.

Hazard identification and risk assessment for biologics targeting the immune system.

PubMed

Weir, Andrea B

2008-01-01

Biologic pharmaceuticals include a variety of products, such as monoclonal antibodies, fusion proteins and cytokines. Products in those classes include immunomodulatory biologics, which are intended to enhance or diminish the activity of the immune system. Immunomodulatory biologics have been approved by the U.S. FDA for a variety of indications, including cancer and inflammatory conditions. Prior to gaining approval for marketing, sponsoring companies for all types of products must demonstrate a product's safety in toxicology studies conducted in animals and show safety and efficacy in clinical trials conducted in patients. The overall goal of toxicology studies, which applies to immunomodulatory and other product types, is to identify the hazards that products pose to humans. Because biologics are generally highly selective for specific targets (receptors/epitopes), conducting toxicology studies in animal models with the target is essential. Such animals are referred to as pharmacologically relevant. Endpoints routinely included in toxicology studies, such as hematology, organ weight and histopathology, can be used to assess the effect of a product on the structure of the immune system. Additionally, specialized endpoints, such as immunophenotyping and immune function tests, can be used to define effects of immunomodulatory products on the immune system. Following hazard identification, risks posed to patients are assessed and managed. Risks can be managed through clinical trial design and risk communication, a practice that applies to immunomodulatory and other product types. Examples of risk management in clinical trial design include establishing a safe starting dose, defining the appropriate patient population and establishing appropriate patient monitoring. Risk communication starts during clinical trials and continues after product approval. A combination of hazard identification, risk assessment and risk management allows for drug development to proceed

48 CFR 1523.303-72 - Care of laboratory animals.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Care of laboratory animals... Material and Material Safety Data 1523.303-72 Care of laboratory animals. Contracting officers shall insert the clause at 1552.223-72, Care of Laboratory Animals, in all contracts involving the use of...

48 CFR 1523.303-72 - Care of laboratory animals.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Care of laboratory animals... Material and Material Safety Data 1523.303-72 Care of laboratory animals. Contracting officers shall insert the clause at 1552.223-72, Care of Laboratory Animals, in all contracts involving the use of...

48 CFR 1523.303-72 - Care of laboratory animals.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Care of laboratory animals... Material and Material Safety Data 1523.303-72 Care of laboratory animals. Contracting officers shall insert the clause at 1552.223-72, Care of Laboratory Animals, in all contracts involving the use of...

48 CFR 1523.303-72 - Care of laboratory animals.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Care of laboratory animals... Material and Material Safety Data 1523.303-72 Care of laboratory animals. Contracting officers shall insert the clause at 1552.223-72, Care of Laboratory Animals, in all contracts involving the use of...

Two-photon imaging of formaldehyde in live cells and animals utilizing a lysosome-targetable and acidic pH-activatable fluorescent probe.

PubMed

Xie, Xilei; Tang, Fuyan; Shangguan, Xiaoyan; Che, Shiyi; Niu, Jinye; Xiao, Yongsheng; Wang, Xu; Tang, Bo

2017-06-13

Lyso-TPFP presents lysosomal targetability and an acidic pH-activatable response toward formaldehyde. Thus, it exclusively visualizes lysosomal formaldehyde and is immune against it in neutral cytosol and other organelles. In addition, two-photon fluorescence imaging endows Lyso-TPFP with the capability of in situ tracking formaldehyde in live cells and animals.

SAFETY GUIDES FOR YOU--IN THE PRIMARY GRADES.

ERIC Educational Resources Information Center

WALKER, LUVERNE CRABTREE

THIS SAFETY INSTRUCTIONAL GUIDE FOR PRIMARY-GRADE TEACHERS PRESENTS NINE DIFFERENT SAFETY UNITS, INCLUDING TRAFFIC SAFETY, PLAYTIME SAFETY, SAFE EATING AND DRINKING HABITS, SAFE CLOTHING, HOME SAFETY, ANIMAL SAFETY, CIVIL DEFENSE SECURITY, AND TESTING SAFETY PRACTICES. EACH UNIT STRESSES THE REASONS FOR ACCENTING SAFETY, WHAT TO KNOW AND DO, AND…

Love, Safety, and Companionship: The Human-Animal Bond and Latino Families

ERIC Educational Resources Information Center

Faver, Catherine A.; Cavazos, Alonzo M., Jr.

2008-01-01

A survey found that 69.2% of a sample of 208 Latino university students in south Texas owned companion animals. Dogs were the most commonly owned companion animals, and 92% of dog and cat guardians regarded their companion animals as family members. Over 80% of the dog and cat guardians specified companionship and unconditional love as benefits…

Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

PubMed Central

Bell, Richard L.; Sable, Helen J.K.; Colombo, Giancarlo; Hyytia, Petri; Rodd, Zachary A.; Lumeng, Lawrence

2012-01-01

The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models for assessing the efficacy of pharmaceuticals for the treatment of alcohol abuse and dependence in rodents, with particular emphasis on rats. Drugs that have been tested for their effectiveness in reducing alcohol/ethanol consumption and/or self-administration by these rat lines and their putative site of action are summarized. The paper also presents some current and future directions for developing pharmacological treatments targeting alcohol abuse and dependence. PMID:22841890

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2010 CFR

2010-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2012 CFR

2012-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2011 CFR

2011-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2014 CFR

2014-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

9 CFR 351.16 - Certificate required for shipments of technical animal fat.

Code of Federal Regulations, 2013 CFR

2013-01-01

... technical animal fat. 351.16 Section 351.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFICATION OF TECHNICAL ANIMAL FATS FOR EXPORT Transportation and Exportation of Certified Technical Animal Fat § 351.16 Certificate required for shipments of...

The role of the pharmaceutical animal health industry in post-marketing surveillance of resistance.

PubMed

Lens, S

1993-06-01

The pharmaceutical animal health industry must be committed to the total life cycle of products, i.e. during both the pre- and post-marketing period. Support of antibacterial agents during the postmarketing period is not restricted to maintaining a well-established distribution and promotion system. Care has to be taken continuously to maintain and/or improve the quality, safety (for user, target animal and environment) and clinical efficacy. The pharmaceutical industry contributes to this by: 1. Introducing antibacterials in different animal species for the most effective disease condition only and by ensuring the veterinary profession is informed about relevant findings on: a. the mechanism of action; b. pharmacodynamic properties; c. pharmacokinetic properties (plasma, target tissue); d. clinical efficacy data and in vitro sensitivity data; e. valid species-specific MIC breakpoints; f. precise dose and treatment regime. 2. Updating on a regular basis on: a. new findings on the mechanism of action (in vitro and in vivo); b. the optimal use program in the light of changes in animal husbandry, farm management and epidemiology on national and international level; c. adjustment of species-specific MIC breakpoints when necessary. 3. Providing continuous information in collaboration with animal health laboratories about: a. clinical field surveillance for efficacy (national, international); b. in vitro sensitivity/resistance surveillance (national, international); c. use of in vitro data to support prediction of in vivo efficacy. Surveillance of resistance, in vitro, is therefore part of a package of information needed on a routine basis by the pharmaceutical industry to allow the best possible use of antibacterials and to minimize induction of resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... (a) Any person desiring to process an exotic animal, exotic animal carcasses, exotic animal meat and... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Application by official exotic animal establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND...

Development of a Salmonella cross-protective vaccine for food animal production systems.

PubMed

Heithoff, Douglas M; House, John K; Thomson, Peter C; Mahan, Michael J

2015-01-01

Intensive livestock production is associated with increased Salmonella exposure, transmission, animal disease, and contamination of food and water supplies. Modified live Salmonella enterica vaccines that lack a functional DNA adenine methylase (Dam) confer cross-protection to a diversity of salmonellae in experimental models of murine, avian, ovine, and bovine models of salmonellosis. However, the commercial success of any vaccine is dependent upon the therapeutic index, the ratio of safety/efficacy. Herein, secondary virulence-attenuating mutations targeted to genes involved in intracellular and/or systemic survival were introduced into Salmonella dam vaccines to screen for vaccine candidates that were safe in the animal and the environment, while maintaining the capacity to confer cross-protective immunity to pathogenic salmonellae serotypes. Salmonella dam mgtC, dam sifA, and dam spvB vaccine strains exhibited significantly improved vaccine safety as evidenced by the failure to give rise to virulent revertants during the infective process, contrary to the parental Salmonella dam vaccine. Further, these vaccines exhibited a low grade persistence in host tissues that was associated with reduced vaccine shedding, reduced environmental persistence, and induction of cross-protective immunity to pathogenic serotypes derived from infected livestock. These data indicate that Salmonella dam double mutant vaccines are suitable for commercial applications against salmonellosis in livestock production systems. Reducing pre-harvest salmonellae load through vaccination will promote the health and productivity of livestock and reduce contamination of livestock-derived food products, while enhancing overall food safety. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Nuremberg Code subverts human health and safety by requiring animal modeling

PubMed Central

2012-01-01

Background The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. Discussion We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. Summary We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented. PMID:22769234

The Nuremberg Code subverts human health and safety by requiring animal modeling.

PubMed

Greek, Ray; Pippus, Annalea; Hansen, Lawrence A

2012-07-08

The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented.

Management of occupational health risks in small-animal veterinary practices.

PubMed

D'Souza, Eva; Barraclough, Richard; Fishwick, David; Curran, Andrew

2009-08-01

Small-animal work is a major element of veterinary practice in the UK and may be hazardous, with high levels of work-related injuries and ill-health reported in Australia and USA. There are no studies addressing the management of occupational health risks arising from small-animal work in the UK. To investigate the sources of health and safety information used and how health and safety and 12 specific occupational health risks are managed by practices. A cross-sectional postal survey of all small-animal veterinary practices in Hampshire. A response was mandatory as this was a Health & Safety Executive (HSE) inspection activity. A total of 118 (100%) practices responded of which 93 were eligible for inclusion. Of these, 99 and 86%, respectively, were aware of the Royal College of Veterinary Surgeons (RCVS) practice standards and had British Small Animal Veterinary Association (BSAVA) staff members, while only 51% had previous contact with HSE (publications, advice and visit). Ninety per cent had health and safety policies, but only 31% had trained responsible staff in health and safety. Specific health hazards such as occupational allergens and computer use were relatively overlooked both by practices and the RCVS/BSAVA guidance available in 2002. Failings in active health risk management systems could be due to a lack of training to ensure competence in those with responsibilities. Practices rely on guidance produced by their professional bodies. Current RCVS guidance, available since 2005, has remedied some previous omissions, but further improvements are recommended.

Improving animal research facility operations through the application of lean principles.

PubMed

Khan, Nabeel; Umrysh, Brian M

2008-06-01

Animal research is a vital component of US research and well-functioning animal research facilities are critical both to the research itself and to the housing and feeding of the animals. The Office of Animal Care (OAC) at Seattle Children's Hospital Research Institute realized it had to improve the efficiency and safety of its animal research facility (ARF) to prepare for expansion and to advance the Institute's mission. The main areas for improvement concerned excessive turnaround time to process animal housing and feeding equipment; the movement and flow of equipment and inventory; and personnel safety. To address these problems, management held two process improvement workshops to educate employees about lean principles. In this article we discuss the application of these principles and corresponding methods to advance Children's Research Institute's mission of preventing, treating, and eliminating childhood diseases.

Feasibility of Forecasting Highway Safety in Support of Safety Incentive and Safety Target Programs.

DOT National Transportation Integrated Search

2007-11-01

Using the frequency of fatal crashes from the current observation period (e.g. month, year, etc.) as the : prediction of expected future performance does not account for changes in safety that result from : increases in exposure (population, addition...

West Nile virus surveillance in Europe: moving towards an integrated animal-human-vector approach

PubMed Central

Gossner, Céline M; Marrama, Laurence; Carson, Marianne; Allerberger, Franz; Calistri, Paolo; Dilaveris, Dimitrios; Lecollinet, Sylvie; Morgan, Dilys; Nowotny, Norbert; Paty, Marie-Claire; Pervanidou, Danai; Rizzo, Caterina; Roberts, Helen; Schmoll, Friedrich; Van Bortel, Wim; Gervelmeyer, Andrea

2017-01-01

This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures. The creation of a formal interagency working group is identified as a crucial step towards integration. Blood safety is a key incentive for public health authorities to allocate sufficient resources for WNV surveillance, while the facts that an effective vaccine is available for horses and that most infected animals remain asymptomatic make the disease a lesser priority for animal health authorities. The examples described here can support other European countries wishing to strengthen their WNV surveillance or preparedness, and also serve as a model for surveillance and monitoring of other (vector-borne) zoonotic infections. PMID:28494844

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: skin irritation.

PubMed

Macfarlane, Martin; Jones, Penny; Goebel, Carsten; Dufour, Eric; Rowland, Joanna; Araki, Daisuke; Costabel-Farkas, Margit; Hewitt, Nicola J; Hibatallah, Jalila; Kirst, Annette; McNamee, Pauline; Schellauf, Florian; Scheel, Julia

2009-07-01

Evaluation of the skin irritancy and corrosivity potential of an ingredient is a necessity in the safety assessment of cosmetic ingredients. To date, there are two formally validated alternatives to the rabbit Draize test for skin corrosivity in place, namely the rat skin transcutaneous electrical resistance (TER) assay and the Human Skin Model Test using EpiSkin, EpiDerm and SkinEthic reconstructed human epidermal equivalents. For skin irritation, EpiSkin, EpiDerm and SkinEthic are validated as stand-alone test replacements for the rabbit Draize test. Data from these tests are rarely considered in isolation and are evaluated in combination with other factors to establish the overall irritating or corrosive potential of an ingredient. In light of the deadlines established in the Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. In conclusion, the safety assessments for skin irritation/corrosion of new chemicals for use in cosmetics can be confidently accomplished using exclusively alternative methods.

36 CFR § 520.4 - Protection of zoo animals.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Protection of zoo animals. Â... § 520.4 Protection of zoo animals. Except for official purposes, no person shall: (a) Kill, injure, or disturb any exhibit or research animal by any means except to secure personal safety; (b) Pet, attempt to...

Meat inspection of reindeer - a rich source of data for monitoring food safety and animal and environmental health in Sweden.

PubMed

Kautto, Arja Helena; Vågsholm, Ivar; Niskanen, Rauni

2017-01-01

Background : ​This study scrutinized carcass conditions recorded in post mortem inspections (PMI) of reindeer ( Rangifer tarandus tarandus , L.) during 2015-2016 because of the importance for monitoring food safety and animal and environmental health threats. Material and methods : PMI results were retrieved from the National Food Agency. A negative binomial regression model was applied. For actual parameters, incident risk rate (IRR) with confidence intervals was calculated. Results and discussion : The number of conditions found in PMI varied widely between years and batches. The most common conditions (43 and 57% of all reindeer slaughtered in 2015 and 2016, respectively) derived from non-zoonotic parasites as the most abundant one, Hypoderma tarandi. Setaria sp. as well as both inflammatory processes and trauma were found in low prevalences. Further investigation of interactions with slaughterhouse size and inspector experience is needed. The conditions found rarely indicated food safety hazards and no epizooties or zoonoses have been recorded in the past two decades. Visual PMI with complementary sampling for specific hazards in slaughterhouses could thus be a helpful tool for monitoring the health and welfare of the reindeer population, the food safety risks with reindeer meat, and the status of the environment. ​.

Estimation of concentration of radionuclides in skeletal muscle from blood, based on the data from abandoned animals in Fukushima.

PubMed

Fukuda, Tomokazu

2018-06-01

The damage caused by the earthquake on 11 March, 2011 resulted in a serious nuclear accident in Japan. Due to the damage to the Fukushima Daiichi Nuclear Power Plant (FNPP), large amounts of radioactive substances were released into the environment. In particular, one of the largest safety concerns is radioactive cesium ( 134 Cs and 137 Cs). Due to the FNPP nuclear accident, a 20 km area was restricted from human activity, and various types of domestic animals were left in the zone. We collected the organs and tissues from sacrificed animals to obtain scientific data to evaluate the internal deposition of radioactive compounds. At first, we found there is a strong correlation between blood 137 Cs and organ 137 Cs with data from 44 cattle, indicating that skeletal muscle is the target organ of deposition of radioactive cesium. Second, we analyzed the relationship between blood 137 Cs and muscle 137 Cs within relatively lower radioactive concentration, suggesting that estimation of concentration of 137 Cs is possible from blood concentration of 137 Cs. Finally, we developed computer software to estimate the muscle 137 Cs concentration from blood samples. Our study contributes to the food safety of livestock products. © 2018 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

Laboratory Animal Workers' Attitudes and Perceptions Concerning Occupational Risk and Injury.

PubMed

Steelman, Eric D; Alexander, Jeffrey L

2016-01-01

Little is known regarding the risk perceptions and attitudes of laboratory animal care workers toward biologic safety. The purpose of this descriptive study was to assess the attitudes and perceptions of laboratory animal workers toward occupational and injury risk. Subscribers to the CompMed and TechLink listservs (n = 4808) were surveyed electronically, and 5.3% responded; data from 215 respondents were included in the final analysis. Primary variables of interest included AALAS certifications status, level of education, and responses to Likert-scale questions related to attitudes and perceptions of occupational risk and injury. Nonparametric (χ(2)) testing and measures of central tendency and dispersion were used to analyze and describe the data. According to 88.6% of respondents, biologic safety training is provided with information about zoonotic diseases of laboratory animals. Level of education was significantly related to perception of importance regarding wearing personal protective equipment. Participants indicated that appropriate support from coworkers and management staff is received, especially when performance and perception are hindered due to stress and fatigue. Laboratory animal staff are susceptible to injury and exposure to dangerous organisms and toxic substances. For this reason, to maximize safety, yearly biologic safety training should be provided, the importance of protective equipment adherence strengthened, and the culture of safety made a priority within the institution.

Swedish dairy farmers' perceptions of animal-related injuries.

PubMed

Lindahl, Cecilia; Lundqvist, Peter; Norberg, Annika Lindahl

2012-01-01

Animal-related injuries are among the most common occupational injuries in agriculture. Despite the large number of documented animal-related injuries in dairy farming, the issue has received relatively limited attention in the scientific literature. The farmers' own perspectives and views on risks and safety during livestock handling and what they think are effective ways of preventing injuries are valuable for the future design of effective interventions. This paper presents results from a qualitative study with the aim to investigate Swedish dairy farmers' own experience of animal-related occupational injuries, as well as their perceptions of and attitudes towards them, including risk and safety issues, and prevention measures. A total of 12 dairy farmers with loose housing systems participated in the study. Data collection was conducted by means of semistructured in-depth interviews. Three main themes with an impact on risks and safety when handling cattle were identified: the handler, the cattle, and the facilities. They all interact with each other, influencing the potential risks of any work task. Most of the farmers believed that a majority of the injuries can be prevented, but there are always some incidents that are impossible to foresee. In conclusion, this study indicates that Swedish dairy farmers are aware of the dangers from working with cattle. However, even though safety is acknowledged by the farmers as an important and relevant issue, in the end safety is often forgotten or not prioritized. One concern is that farmers are willing to take calculated risks to save money or time. In situations where they work alone with high stress levels and under economic distress, safety issues are easily given low priority.

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

PubMed

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potential large animal models for gene therapy of human genetic diseases of immune and blood cell systems.

PubMed

Bauer, Thomas R; Adler, Rima L; Hickstein, Dennis D

2009-01-01

Genetic mutations involving the cellular components of the hematopoietic system--red blood cells, white blood cells, and platelets--manifest clinically as anemia, infection, and bleeding. Although gene targeting has recapitulated many of these diseases in mice, these murine homologues are limited as translational models by their small size and brief life span as well as the fact that mutations induced by gene targeting do not always faithfully reflect the clinical manifestations of such mutations in humans. Many of these limitations can be overcome by identifying large animals with genetic diseases of the hematopoietic system corresponding to their human disease counterparts. In this article, we describe human diseases of the cellular components of the hematopoietic system that have counterparts in large animal species, in most cases carrying mutations in the same gene (CD18 in leukocyte adhesion deficiency) or genes in interacting proteins (DNA cross-link repair 1C protein and protein kinase, DNA-activated catalytic polypeptide in radiation-sensitive severe combined immunodeficiency). Furthermore, we describe the potential of these animal models to serve as disease-specific preclinical models for testing the efficacy and safety of clinical interventions such as hematopoietic stem cell transplantation or gene therapy before their use in humans with the corresponding disease.

Ebola: Facing a New Transboundary Animal Disease?

PubMed Central

Feldmann, F.; Feldmann, H.

2016-01-01

Ebola viruses are zoonotic pathogens with the potential of causing severe viral hemorrhagic fever in humans and nonhuman primates. Bats have been identified as a reservoir for Ebola viruses but it remains unclear if transmission to an end host involves intermediate hosts. Recently, one of the Ebola species has been found in Philippine pigs raising concerns regarding animal health and food safety. Diagnostics have so far focused on human application, but enhanced pig surveillance and diagnostics, particularly in Asia, for Ebola virus infections seem to be needed to establish reasonable guidelines for public and animal health and food safety. Livestock vaccination against Ebola seems currently not justified but proper preparedness may include experimental vaccine approaches. PMID:23689898

USDA's Corner

USDA-ARS?s Scientific Manuscript database

SNARC has been working with the folks at AADAP on two studies: 1) a “near” GLP compliant Target Animal Safety study to evaluate the safety of Aquaflor® administered in feed to sunshine bass and 2) a GLP compliant Target Animal Safety study to evaluate the safety of 17a-methyltestosterone administere...

Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS) coronavirus.

PubMed

Vergara-Alert, Júlia; Vidal, Enric; Bensaid, Albert; Segalés, Joaquim

2017-06-01

Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013-2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV), which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV), associated with severe pneumonia, arose in the Kingdom of Saudi Arabia. Until December 2016, MERS has accounted for more than 1800 cases and 35% fatality rate. Finding an animal model of disease is key to develop vaccines or antivirals against such emerging pathogens and to understand its pathogenesis. Knowledge of the potential role of domestic livestock and other animal species in the transmission of pathogens is of importance to understand the epidemiology of the disease. Little is known about MERS-CoV animal host range. In this paper, experimental data on potential hosts for MERS-CoV is reviewed. Advantages and limitations of different animal models are evaluated in relation to viral pathogenesis and transmission studies. Finally, the relevance of potential new target species is discussed.

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2011 CFR

2011-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2013 CFR

2013-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2012 CFR

2012-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

9 CFR 352.3 - Application by official exotic animal establishment for inspection services.

Code of Federal Regulations, 2014 CFR

2014-01-01

... establishment for inspection services. 352.3 Section 352.3 Animals and Animal Products FOOD SAFETY AND... INSPECTION Exotic Animals § 352.3 Application by official exotic animal establishment for inspection services... meat food products in an establishment under exotic animal inspection service must receive approval of...

Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.

PubMed

Wallace, Lindsay M; Saad, Nizar Y; Pyne, Nettie K; Fowler, Allison M; Eidahl, Jocelyn O; Domire, Jacqueline S; Griffin, Danielle A; Herman, Adam C; Sahenk, Zarife; Rodino-Klapac, Louise R; Harper, Scott Q

2018-03-16

RNAi emerged as a prospective molecular therapy nearly 15 years ago. Since then, two major RNAi platforms have been under development: oligonucleotides and gene therapy. Oligonucleotide-based approaches have seen more advancement, with some promising therapies that may soon reach market. In contrast, vector-based approaches for RNAi therapy have remained largely in the pre-clinical realm, with limited clinical safety and efficacy data to date. We are developing a gene therapy approach to treat the autosomal-dominant disorder facioscapulohumeral muscular dystrophy. Our strategy involves silencing the myotoxic gene DUX4 using adeno-associated viral vectors to deliver targeted microRNA expression cassettes (miDUX4s). We previously demonstrated proof of concept for this approach in mice, and we are now taking additional steps here to assess safety issues related to miDUX4 overexpression and sequence-specific off-target silencing. In this study, we describe improvements in vector design and expansion of our miDUX4 sequence repertoire and report differential toxicity elicited by two miDUX4 sequences, of which one was toxic and the other was not. This study provides important data to help advance our goal of translating RNAi gene therapy for facioscapulohumeral muscular dystrophy.

Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

PubMed

Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

2014-03-25

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest

PubMed Central

2015-01-01

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

Prebiotics in food animals, a potential to reduce foodborne pathogens and disease

USDA-ARS?s Scientific Manuscript database

Animals can be seriously impacted by bacterial pathogens that affect their growth efficiency and overall health, as well as food safety of animal-derived products. Some pathogenic bacteria, such as Salmonella, can be a shared problem for both human and animal health and can be found in many animal ...

Prebiotics in food animals: A potential to reduce foodborne pathogens and disease

USDA-ARS?s Scientific Manuscript database

Animals can be seriously impacted by bacterial pathogens that affect their growth efficiency and overall health, as well as food safety of animal-derived products. Some pathogenic bacteria, such as Salmonella, can be a shared problem for both human and animal health and can be found in many animal ...

Cavitation-enhanced nonthermal ablation in deep brain targets: feasibility in a large animal model.

PubMed

Arvanitis, Costas D; Vykhodtseva, Natalia; Jolesz, Ferenc; Livingstone, Margaret; McDannold, Nathan

2016-05-01

OBJECT Transcranial MRI-guided focused ultrasound (TcMRgFUS) is an emerging noninvasive alternative to surgery and radiosurgery that is undergoing testing for tumor ablation and functional neurosurgery. The method is currently limited to central brain targets due to skull heating and other factors. An alternative ablative approach combines very low intensity ultrasound bursts and an intravenously administered microbubble agent to locally destroy the vasculature. The objective of this work was to investigate whether it is feasible to use this approach at deep brain targets near the skull base in nonhuman primates. METHODS In 4 rhesus macaques, targets near the skull base were ablated using a clinical TcMRgFUS system operating at 220 kHz. Low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes in conjunction with the ultrasound contrast agent Definity, which was administered as a bolus injection or continuous infusion. The acoustic power level was set to be near the inertial cavitation threshold, which was measured using passive monitoring of the acoustic emissions. The resulting tissue effects were investigated with MRI and with histological analysis performed 3 hours to 1 week after sonication. RESULTS Thirteen targets were sonicated in regions next to the optic tract in the 4 animals. Inertial cavitation, indicated by broadband acoustic emissions, occurred at acoustic pressure amplitudes ranging from 340 to 540 kPa. MRI analysis suggested that the lesions had a central region containing red blood cell extravasations that was surrounded by edema. Blood-brain barrier disruption was observed on contrast-enhanced MRI in the lesions and in a surrounding region corresponding to the prefocal area of the FUS system. In histology, lesions consisting of tissue undergoing ischemic necrosis were found in all regions that were sonicated above the inertial cavitation threshold. Tissue damage in prefocal areas was found in several cases, suggesting that in

Animal Science. Teacher Edition.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This curriculum package is designed to prepare students with highly technical information that will lead to success in the animal science field. It contains 19 units that highlight many of the specialist areas and teach students how to apply these skills. The units cover the following topics: safety, careers, private and government programs,…

[The prevention of distemper in zoo animals].

PubMed

Franke, V; Matern, B; Ackermann, O; Danner, K

1989-02-01

The distemper virus infection of different non-domestic carnivorous zoo animals is known since long. All species involved belonged to the suborder Fissipedia. In 1988 a distemper or morbillivirus-like infection occurred in harbour seals, a member of the suborder pinnipedia. For the prophylaxis of distemper in dogs attenuated live vaccines are commonly used. In zoo animals, however, these vaccines caused distemper several times. In contrast, an inactivated virus vaccine proved both its safety and efficacy in more than hundred zoo animals of various species.

Promoting a Culture of Safety as a Patient Safety Strategy

PubMed Central

Weaver, Sallie J.; Lubomksi, Lisa H.; Wilson, Renee F.; Pfoh, Elizabeth R.; Martinez, Kathryn A.; Dy, Sydney M.

2015-01-01

Developing a culture of safety is a core element of many efforts to improve patient safety and care quality. This systematic review identifies and assesses interventions used to promote safety culture or climate in acute care settings. The authors searched MEDLINE, CINAHL, PsycINFO, Cochrane, and EMBASE to identify relevant English-language studies published from January 2000 to October 2012. They selected studies that targeted health care workers practicing in inpatient settings and included data about change in patient safety culture or climate after a targeted intervention. Two raters independently screened 3679 abstracts (which yielded 33 eligible studies in 35 articles), extracted study data, and rated study quality and strength of evidence. Eight studies included executive walk rounds or interdisciplinary rounds; 8 evaluated multicomponent, unit-based interventions; and 20 included team training or communication initiatives. Twenty-nine studies reported some improvement in safety culture or patient outcomes, but measured outcomes were highly heterogeneous. Strength of evidence was low, and most studies were pre–post evaluations of low to moderate quality. Within these limits, evidence suggests that interventions can improve perceptions of safety culture and potentially reduce patient harm. PMID:23460092

Host-targeted approaches to managing animal health: old problems and new tools.

PubMed

Cook, M E; Bütz, D E; Yang, M; Sand, J M

2016-07-01

Our fellow medical and regulatory scientists question the animal producer's dependence on antibiotics and antimicrobial chemicals in the production of animal products. Retail distributors and consumers are putting even more pressure on the animal industry to find new ways to produce meat without antibiotics and chemicals. In addition, federal funding agencies are increasingly pressuring researchers to conduct science that has application. In the review that follows, we outline our approach to finding novel ways to improve animal performance and health. We use a strict set of guidelines in our applied research as follows: (1) Does the work have value to society? (2) Does our team have the skills to innovate in the field? (3) Is the product we produce commercially cost-effective? (4) Are there any reasons why the general consumer will reject the technology? (5) Is it safe for the animal, consumer, and the environment? Within this framework, we describe 4 areas of research that have produced useful products, areas that we hope other scientists will likewise explore and innovate such as (1) methods to detect infection in herds and flocks, (2) methods to control systemic and mucosal inflammation, (3) improvements to intestinal barrier function, and (4) methods to strategically potentiate immune defense. We recognize that others are working in these areas, using different strategies, but believe our examples will illustrate the vast opportunity for research and innovation in a world without antibiotics. Animal scientists have been given a new challenge that may help shape the future of both animal and human medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Veterinary Safety's Conflicts in the EAEU

ERIC Educational Resources Information Center

Kalymbek, Bakytzhan; Shulanbekova, Gulmira K.; Madiyarova, Ainur S.; Mirambaeva, Gulnaz Zh.

2016-01-01

This article is devoted to the problem of veterinary safety of the countries under the Eurasian Economic Union. Animal health's measures are provided in order to prevent the entry and spread of infectious animal diseases, including common to humans and animals, as well as goods not conforming to the common veterinary and sanitary requirements.…

Guide for Science Laboratory Safety.

ERIC Educational Resources Information Center

McDermott, John J.

General and specific safety procedures and recommendations for secondary school science laboratories are provided in this guide. Areas of concern include: (1) chemicals (storage, disposal, toxicity, unstable and incompatible chemicals); (2) microorganisms; (3) plants; (4) animals; (5) electricity; (6) lasers; (7) rockets; (8) eye safety and…

Setting quality and safety priorities in a target-rich environment: an academic medical center's challenge.

PubMed

Mort, Elizabeth A; Demehin, Akinluwa A; Marple, Keith B; McCullough, Kathryn Y; Meyer, Gregg S

2013-08-01

Hospitals are continually challenged to provide safer and higher-quality patient care despite resource constraints. With an ever-increasing range of quality and safety targets at the national, state, and local levels, prioritization is crucial in effective institutional quality goal setting and resource allocation.Organizational goal-setting theory is a performance improvement methodology with strong results across many industries. The authors describe a structured goal-setting process they have established at Massachusetts General Hospital for setting annual institutional quality and safety goals. Begun in 2008, this process has been conducted on an annual basis. Quality and safety data are gathered from many sources, both internal and external to the hospital. These data are collated and classified, and multiple approaches are used to identify the most pressing quality issues facing the institution. The conclusions are subject to stringent internal review, and then the top quality goals of the institution are chosen. Specific tactical initiatives and executive owners are assigned to each goal, and metrics are selected to track performance. A reporting tool based on these tactics and metrics is used to deliver progress updates to senior hospital leadership.The hospital has experienced excellent results and strong organizational buy-in using this effective, low-cost, and replicable goal-setting process. It has led to improvements in structural, process, and outcomes aspects of quality.

Germline modification of domestic animals

PubMed Central

Tang, L.; González, R.; Dobrinski, I.

2016-01-01

is introduced into the male germ line just before the onset of spermatogenesis, the time required for the production of genetically modified sperm is significantly shorter using germ cell transplantation compared to cloning or embryonic stem (ES) cell based technology. Moreover, the GSC-mediated germline modification circumvents problems associated with embryo manipulation and nuclear reprogramming. Currently, engineering targeted mutations in domestic animals using GSCs remains a challenge as GSCs from those animals are difficult to maintain in vitro for an extended period of time. Recent advances in genome editing techniques such as Zinc-Finger Nucleases (ZFNs), Transcription Activator-like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) greatly enhance the efficiency of engineering targeted genetic change in domestic animals as demonstrated by the generation of several gene knock-out pig and cattle models using those techniques. The potential of GSC-mediated germline modification in making targeted genetic modifications in domestic animal models will be maximized if those genome editing techniques can be applied in GSCs. PMID:27390591

Liquid Hydrogen Target Experience at SLAC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisend, J.G.; Boyce, R.; Candia, A.

2005-08-29

Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small ''beer can'' targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability. This paper surveys the evolutionmore » of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible.« less

Biosurveillance at the United States Meat Animal Research Center

USDA-ARS?s Scientific Manuscript database

The mission of the 50 scientists and 165 support staff at the U.S. Meat Animal Research Center (USMARC) is to develop new technologies to increase the efficiency of livestock production and improve meat safety, quality, and animal health to benefit consumers worldwide. The facilities include 35,000 ...

Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells?

PubMed

Hombach, Andreas A; Abken, Hinrich

2017-02-01

Adoptive therapy with chimeric antigen receptor (CAR) T cells redirected towards CD19 produces remissions of B cell malignancies, however, it also eradicates healthy B cells sharing the target antigen. Such 'on-target off-tumor' toxicity raises serious safety concerns when the target antigen is also expressed by tissue stem cells, with the risk of lasting tissue destruction. Areas covered: We discuss CAR T cell targeting of activation antigens versus lineage associated antigens on the basis of recent experimental and animal data and the literature in the field. Expert commentary: Targeting an activation associated antigen which is transiently expressed by stem cells seems to be safe, like CAR T cells targeting CD30 spare CD30 + hematopoietic stem and progenitor cells while eliminating CD30 + lymphoma cells, whereas targeting lineage associated antigens which increase in expression during cell maturation, like folate receptor-β and CD123, is of risk to destruct tissue stem cells.

Introduction: The provision of animal health services in a changing world.

PubMed

de Haan, C

2004-04-01

In the future, animal health services in developing countries will need to operate in a continuously changing policy, institutional and commercial environment. Firstly, the changing policies and priorities of national policy-makers regarding public and private sector roles, reinforced in Africa by the donors, have reduced funding and support for the large number of tasks that animal health services have traditionally performed, and there is continuing pressure from policy-makers to focus on what the public sector can do best. Secondly, poverty reduction has become one of the main criteria guiding the allocation of official development assistance, which has major implications for the main target clientele of veterinary services. Thirdly, population growth, increasing income and urbanisation are causing a marked increase in demand for livestock products in the developing world. As a result, the entire livestock commodity chain is undergoing major structural changes, which has significant implications for the definition and control of food safety standards. Fourthly, globalisation, and increasing trade and travel have greatly increased the risk of disease transmission between different countries and continents. Veterinary institutions in the developing world need to adapt to these challenges. They will have to be able to focus on the essential public sector roles. At the same time they must deliver those essential services to the poor, and provide the policy framework to ensure that the inevitable structural changes in the commodity chain take place in an equitable and sustainable fashion, with an acceptable level of health risk for the consumer. According to the weight given to these different objectives, changes in the institutional set-up need to be considered. This issue of the Scientific and Technical Review addresses these challenges. It begins by reviewing the basic economic characteristics underlying the provision of animal health services, and then examines

The new frontiers of the targeted interventions in the pulmonary vasculature: precision and safety (2017 Grover Conference Series).

PubMed

Brenner, Jacob S; Kiseleva, Raisa Yu; Glassman, Patrick M; Parhiz, Hamideh; Greineder, Colin F; Hood, Elizabeth D; Shuvaev, Vladimir V; Muzykantov, Vladimir R

2018-01-01

The pulmonary vasculature plays an important role in many lung pathologies, such as pulmonary arterial hypertension, primary graft dysfunction of lung transplant, and acute respiratory distress syndrome. Therapy for these diseases is quite limited, largely due to dose-limiting side effects of numerous drugs that have been trialed or approved. High doses of drugs targeting the pulmonary vasculature are needed due to the lack of specific affinity of therapeutic compounds to the vasculature. To overcome this problem, the field of targeted drug delivery aims to target drugs to the pulmonary endothelial cells, especially those in pathological regions. The field uses a variety of drug delivery systems (DDSs), ranging from nano-scale drug carriers, such as liposomes, to methods of conjugating drugs to affinity moieites, such as antibodies. These DDSs can deliver small molecule drugs, protein therapeutics, and imaging agents. Here we review targeted drug delivery to the pulmonary endothelium for the treatment of pulmonary diseases. Cautionary notes are made of the risk-benefit ratio and safety-parameters one should keep in mind when developing a translational therapeutic.

West Nile virus surveillance in Europe: moving towards an integrated animal-human-vector approach.

PubMed

Gossner, Céline M; Marrama, Laurence; Carson, Marianne; Allerberger, Franz; Calistri, Paolo; Dilaveris, Dimitrios; Lecollinet, Sylvie; Morgan, Dilys; Nowotny, Norbert; Paty, Marie-Claire; Pervanidou, Danai; Rizzo, Caterina; Roberts, Helen; Schmoll, Friedrich; Van Bortel, Wim; Gervelmeyer, Andrea

2017-05-04

This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures. The creation of a formal interagency working group is identified as a crucial step towards integration. Blood safety is a key incentive for public health authorities to allocate sufficient resources for WNV surveillance, while the facts that an effective vaccine is available for horses and that most infected animals remain asymptomatic make the disease a lesser priority for animal health authorities. The examples described here can support other European countries wishing to strengthen their WNV surveillance or preparedness, and also serve as a model for surveillance and monitoring of other (vector-borne) zoonotic infections. This article is copyright of The Authors, 2017.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).

PubMed

Winthrop, K L; Mariette, X; Silva, J T; Benamu, E; Calabrese, L H; Dumusc, A; Smolen, J S; Aguado, J M; Fernández-Ruiz, M

2018-06-01

The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection. Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab. Copyright © 2018 European Society of Clinical

Advanced Small Animal Conformal Radiation Therapy Device.

PubMed

Sharma, Sunil; Narayanasamy, Ganesh; Przybyla, Beata; Webber, Jessica; Boerma, Marjan; Clarkson, Richard; Moros, Eduardo G; Corry, Peter M; Griffin, Robert J

2017-02-01

We have developed a small animal conformal radiation therapy device that provides a degree of geometrical/anatomical targeting comparable to what is achievable in a commercial animal irradiator. small animal conformal radiation therapy device is capable of producing precise and accurate conformal delivery of radiation to target as well as for imaging small animals. The small animal conformal radiation therapy device uses an X-ray tube, a robotic animal position system, and a digital imager. The system is in a steel enclosure with adequate lead shielding following National Council on Radiation Protection and Measurements 49 guidelines and verified with Geiger-Mueller survey meter. The X-ray source is calibrated following AAPM TG-61 specifications and mounted at 101.6 cm from the floor, which is a primary barrier. The X-ray tube is mounted on a custom-made "gantry" and has a special collimating assembly system that allows field size between 0.5 mm and 20 cm at isocenter. Three-dimensional imaging can be performed to aid target localization using the same X-ray source at custom settings and an in-house reconstruction software. The small animal conformal radiation therapy device thus provides an excellent integrated system to promote translational research in radiation oncology in an academic laboratory. The purpose of this article is to review shielding and dosimetric measurement and highlight a few successful studies that have been performed to date with our system. In addition, an example of new data from an in vivo rat model of breast cancer is presented in which spatially fractionated radiation alone and in combination with thermal ablation was applied and the therapeutic benefit examined.

GMOs in animal agriculture: time to consider both costs and benefits in regulatory evaluations.

PubMed

Van Eenennaam, Alison L

2013-09-25

In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away

GMOs in animal agriculture: time to consider both costs and benefits in regulatory evaluations

PubMed Central

2013-01-01

In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away

Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques.

PubMed

McDannold, Nathan; Arvanitis, Costas D; Vykhodtseva, Natalia; Livingstone, Margaret S

2012-07-15

The blood-brain barrier (BBB) prevents entry of most drugs into the brain and is a major hurdle to the use of drugs for brain tumors and other central nervous system disorders. Work in small animals has shown that ultrasound combined with an intravenously circulating microbubble agent can temporarily permeabilize the BBB. Here, we evaluated whether this targeted drug delivery method can be applied safely, reliably, and in a controlled manner on rhesus macaques using a focused ultrasound system. We identified a clear safety window during which BBB disruption could be produced without evident tissue damage, and the acoustic pressure amplitude where the probability for BBB disruption was 50% and was found to be half of the value that would produce tissue damage. Acoustic emission measurements seem promising for predicting BBB disruption and damage. In addition, we conducted repeated BBB disruption to central visual field targets over several weeks in animals trained to conduct complex visual acuity tasks. All animals recovered from each session without behavioral deficits, visual deficits, or loss in visual acuity. Together, our findings show that BBB disruption can be reliably and repeatedly produced without evident histologic or functional damage in a clinically relevant animal model using a clinical device. These results therefore support clinical testing of this noninvasive-targeted drug delivery method.

Food Supply and Food Safety Issues in China

PubMed Central

Lam, Hon-Ming; Remais, Justin; Fung, Ming-Chiu; Xu, Liqing; Sun, Samuel Sai-Ming

2013-01-01

Food supply and food safety are major global public health issues, and are particularly important in heavily populated countries such as China. Rapid industrialisation and modernisation in China are having profound effects on food supply and food safety. In this Review, we identified important factors limiting agricultural production in China, including conversion of agricultural land to other uses, freshwater deficits, and soil quality issues. Additionally, increased demand for some agricultural products is examined, particularly those needed to satisfy the increased consumption of animal products in the Chinese diet, which threatens to drive production towards crops used as animal feed. Major sources of food poisoning in China include pathogenic microorganisms, toxic animals and plants entering the food supply, and chemical contamination. Meanwhile, two growing food safety issues are illegal additives and contamination of the food supply by toxic industrial waste. China’s connections to global agricultural markets are also having important effects on food supply and food safety within the country. Although the Chinese Government has shown determination to reform laws, establish monitoring systems, and strengthen food safety regulation, weak links in implementation remain. PMID:23746904

Unconventional oil and gas extraction and animal health.

PubMed

Bamberger, M; Oswald, R E

2014-08-01

The extraction of hydrocarbons from shale formations using horizontal drilling with high volume hydraulic fracturing (unconventional shale gas and tight oil extraction), while derived from methods that have been used for decades, is a relatively new innovation that was introduced first in the United States and has more recently spread worldwide. Although this has led to the availability of new sources of fossil fuels for domestic consumption and export, important issues have been raised concerning the safety of the process relative to public health, animal health, and our food supply. Because of the multiple toxicants used and generated, and because of the complexity of the drilling, hydraulic fracturing, and completion processes including associated infrastructure such as pipelines, compressor stations and processing plants, impacts on the health of humans and animals are difficult to assess definitively. We discuss here findings concerning the safety of unconventional oil and gas extraction from the perspectives of public health, veterinary medicine, and food safety.

Animal models of addiction

PubMed Central

Spanagel, Rainer

2017-01-01

In recent years, animal models in psychiatric research have been criticized for their limited translational value to the clinical situation. Failures in clinical trials have thus often been attributed to the lack of predictive power of preclinical animal models. Here, I argue that animal models of voluntary drug intake—under nonoperant and operant conditions—and addiction models based on the Diagnostic and Statistical Manual of Mental Disorders are crucial and informative tools for the identification of pathological mechanisms, target identification, and drug development. These models provide excellent face validity, and it is assumed that the neurochemical and neuroanatomical substrates involved in drug-intake behavior are similar in laboratory rodents and humans. Consequently, animal models of drug consumption and addiction provide predictive validity. This predictive power is best illustrated in alcohol research, in which three approved medications—acamprosate, naltrexone, and nalmefene—were developed by means of animal models and then successfully translated into the clinical situation. PMID:29302222

The Reversal of Direct Oral Anticoagulants in Animal Models

PubMed Central

Honickel, Markus; Akman, Necib; Grottke, Oliver

2017-01-01

ABSTRACT Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity). Though promising, most specific antidotes are still in development. Preclinical animal research is the key to establishing the efficacy and safety of potential reversal agents. Here, we summarize published preclinical animal studies on reversal of DOAC anticoagulation. These studies (n = 26) were identified via a PubMed search, and used rodent, rabbit, pig, and non-human primate models. The larger of these animals have the advantages of similar blood volume/hemodynamics to humans, and can be used to model polytrauma. We find that in addition to varied species being used, there is variability in the models and assays used between studies; we suggest that blood loss (bleeding volume) is the most clinically relevant measure of DOAC anticoagulation-related bleeding and its reversal. The studies covered indicate that both PCCs and specific reversal agents have the potential to be used as part of a clinical strategy for DOAC reversal. For the future, we advocate the development and use of standardized, clinically, and pharmacologically relevant animal models to study novel DOAC reversal strategies. PMID:28471371

Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

PubMed

Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

2016-07-01

Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Agricultural biotechnology safety assessment].

PubMed

McClain, Scott; Jones, Wendelyn; He, Xiaoyun; Ladics, Gregory; Bartholomaeus, Andrew; Raybould, Alan; Lutter, Petra; Xu, Haibin; Wang, Xue

2015-01-01

Genetically modified (GM) crops were first introduced to farmers in 1995 with the intent to provide better crop yield and meet the increasing demand for food and feed. GM crops have evolved to include a thorough safety evaluation for their use in human food and animal feed. Safety considerations begin at the level of DNA whereby the inserted GM DNA is evaluated for its content, position and stability once placed into the crop genome. The safety of the proteins coded by the inserted DNA and potential effects on the crop are considered, and the purpose is to ensure that the transgenic novel proteins are safe from a toxicity, allergy, and environmental perspective. In addition, the grain that provides the processed food or animal feed is also tested to evaluate its nutritional content and identify unintended effects to the plant composition when warranted. To provide a platform for the safety assessment, the GM crop is compared to non-GM comparators in what is typically referred to as composition equivalence testing. New technologies, such as mass spectrometry and well-designed antibody-based methods, allow better analytical measurements of crop composition, including endogenous allergens. Many of the analytical methods and their intended uses are based on regulatory guidance documents, some of which are outlined in globally recognized documents such as Codex Alimentarius. In certain cases, animal models are recommended by some regulatory agencies in specific countries, but there is typically no hypothesis or justification of their use in testing the safety of GM crops. The quality and standardization of testing methods can be supported, in some cases, by employing good laboratory practices (GLP) and is recognized in China as important to ensure quality data. Although the number of recommended, in some cases, required methods for safety testing are increasing in some regulatory agencies, it should be noted that GM crops registered to date have been shown to be

In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease

PubMed Central

Lau, Cia-Hin; Suh, Yousin

2017-01-01

Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics. PMID:29333255

Meat inspection of reindeer – a rich source of data for monitoring food safety and animal and environmental health in Sweden

PubMed Central

Kautto, Arja Helena; Vågsholm, Ivar; Niskanen, Rauni

2017-01-01

ABSTRACT Background: ​This study scrutinized carcass conditions recorded in post mortem inspections (PMI) of reindeer (Rangifer tarandus tarandus, L.) during 2015–2016 because of the importance for monitoring food safety and animal and environmental health threats. Material and methods: PMI results were retrieved from the National Food Agency. A negative binomial regression model was applied. For actual parameters, incident risk rate (IRR) with confidence intervals was calculated. Results and discussion: The number of conditions found in PMI varied widely between years and batches. The most common conditions (43 and 57% of all reindeer slaughtered in 2015 and 2016, respectively) derived from non-zoonotic parasites as the most abundant one, Hypoderma tarandi. Setaria sp. as well as both inflammatory processes and trauma were found in low prevalences. Further investigation of interactions with slaughterhouse size and inspector experience is needed. The conditions found rarely indicated food safety hazards and no epizooties or zoonoses have been recorded in the past two decades. Visual PMI with complementary sampling for specific hazards in slaughterhouses could thus be a helpful tool for monitoring the health and welfare of the reindeer population, the food safety risks with reindeer meat, and the status of the environment. ​ PMID:28811870

SEURAT: Safety Evaluation Ultimately Replacing Animal Testing--recommendations for future research in the field of predictive toxicology.

PubMed

Daston, George; Knight, Derek J; Schwarz, Michael; Gocht, Tilman; Thomas, Russell S; Mahony, Catherine; Whelan, Maurice

2015-01-01

The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December 2015. Drawing on the experience gained in SEURAT-1 and appreciating international advancement in both basic and regulatory science, we reflect here on how SEURAT should evolve and propose that further research and development should be directed along two complementary and interconnecting work streams. The first work stream would focus on developing new 'paradigm' approaches for regulatory science. The goal here is the identification of 'critical biological targets' relevant for toxicity and to test their suitability to be used as anchors for predicting toxicity. The second work stream would focus on integration and application of new approach methods for hazard (and risk) assessment within the current regulatory 'paradigm', aiming for acceptance of animal-free testing strategies by regulatory authorities (i.e. translating scientific achievements into regulation). Components for both work streams are discussed and may provide a structure for a future research programme in the field of predictive toxicology.

Assessment of safety and efficiency of nitrogen organic fertilizers from animal-based protein hydrolysates--a laboratory multidisciplinary approach.

PubMed

Corte, Laura; Dell'abate, Maria Teresa; Magini, Alessandro; Migliore, Melania; Felici, Barbara; Roscini, Luca; Sardella, Roccaldo; Tancini, Brunella; Emiliani, Carla; Cardinali, Gianluigi; Benedetti, Anna

2014-01-30

Protein hydrolysates or hydrolysed proteins (HPs) are high-N organic fertilizers allowing the recovery of by-products (leather meal and fluid hydrolysed proteins) otherwise disposed of as polluting wastes, thus enhancing matter and energy conservation in agricultural systems while decreasing potential pollution. Chemical and biological characteristics of HPs of animal origin were analysed in this work to assess their safety, environmental sustainability and agricultural efficacy as fertilizers. Different HPs obtained by thermal, chemical and enzymatic hydrolytic processes were characterized by Fourier transform infrared spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis, and their safety and efficacy were assessed through bioassays, ecotoxicological tests and soil biochemistry analyses. HPs can be discriminated according to their origin and hydrolysis system by proteomic and metabolomic methods. Three experimental systems, soil microbiota, yeast and plants, were employed to detect possible negative effects exerted by HPs. The results showed that these compounds do not significantly interfere with metabolomic activity or the reproductive system. The absence of toxic and genotoxic effects of the hydrolysates prepared by the three hydrolytic processes suggests that they do not negatively affect eukaryotic cells and soil ecosystems and that they can be used in conventional and organic farming as an important nitrogen source derived from otherwise highly polluting by-products. © 2013 Society of Chemical Industry.

The Anime Revelation: How I Learned to Love Japanese Animation and Changed Our Teen Video Collection Forever

ERIC Educational Resources Information Center

Halsall, Jane

2004-01-01

What is the appeal of anime? For one thing, the graphic storytelling is uniquely compelling and spans multiple genres. It tends to be targeted to different audiences: young children and families, males or females aged 10-18, or strictly adults for the mature genre called hentai. In America, almost all animation is produced for and watched by…

Determination of sulfonamides in animal tissues by modified QuEChERS and liquid chromatography tandem mass spectrometry.

PubMed

Wen, Ching-Hsuan; Lin, Shu-Ling; Fuh, Ming-Ren

2017-03-01

In this study, the salting-out solvent extraction and dispersive solid-phase extraction (dSPE) clean-up steps in QuEChERS (quick, easy, cheap, effective, rugged, and safe) method were optimized to reduce matrix effect and efficiently extract target sulfonamides from a variety of edible animal tissues. The extracted sulfonamides were then analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Good extraction recoveries (74.0-100.3% in five different sources of animal tissues; n=3) with acceptable matrix effect (<10%, except for liver samples) were obtained using the proposed method. For the first time, a commercial ND-lipids cartridge was used to remove hydrophobic matrix components from fat-rich animal tissues in the clean-up step of QuEChERS. In addition, good linearity (0.125-12.5ngg -1 ) was observed using matrix-matched calibration (in beef). Limits of detection (LODs) were estimated at 0.01-0.03ngg -1 in beef, pork, and chicken samples. For beef tripe and pig liver samples, the LODs were in the range of 0.02-0.04ngg -1 . Good intra-day/inter-day precision (1.0-10.5%/0.4-8.0%) and accuracy (95.2-107.2%/97.8-102.1%) were also achieved using the modified QuEChERS for sample pretreatment. The applicability of the modified QuEChERS-LC-MS/MS method was demonstrated by determining the occurrence of target sulfonamides in various edible animal tissues for potential food safety analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

An Overview on Recent Progress in Electrochemical Biosensors for Antimicrobial Drug Residues in Animal-Derived Food

PubMed Central

Majdinasab, Marjan; Yaqub, Mustansara; Rahim, Abdur; Catanante, Gaelle; Hayat, Akhtar; Marty, Jean Louis

2017-01-01

Anti-microbial drugs are widely employed for the treatment and cure of diseases in animals, promotion of animal growth, and feed efficiency. However, the scientific literature has indicated the possible presence of antimicrobial drug residues in animal-derived food, making it one of the key public concerns for food safety. Therefore, it is highly desirable to design fast and accurate methodologies to monitor antimicrobial drug residues in animal-derived food. Legislation is in place in many countries to ensure antimicrobial drug residue quantities are less than the maximum residue limits (MRL) defined on the basis of food safety. In this context, the recent years have witnessed a special interest in the field of electrochemical biosensors for food safety, based on their unique analytical features. This review article is focused on the recent progress in the domain of electrochemical biosensors to monitor antimicrobial drug residues in animal-derived food. PMID:28837093

Safety and toxicological evaluation of a novel anti-obesity formulation LI85008F in animals.

PubMed

Krishnaraju, A V; Sundararaju, D; Srinivas, P; Rao, C V; Sengupta, K; Trimurtulu, G

2010-02-01

LI85008F is a novel synergistic composition of Moringa oleifera, Murraya koenigi, and Curcuma longa. These herbs are well recognized and widely used in ayurvedic system of medicine for treating a variety of diseases and are also have been used for culinary purposes for thousands of years. LI85008F inhibits preadipocyte differentiation and potentiates lipid breakdown in mature adipocytes. In diet-induced obese rats, LI85008F significantly reduced weight gain and improved serum adiponectin levels. These findings motivated the authors to determine the broad-spectrum safety of LI85008F. Acute oral toxicity, acute dermal toxicity, primary skin irritation, primary eye irritation, and dose-dependent 28-day sub-acute toxicity studies were conducted. The acute oral LD50 of LI85008F was greater than 5000 mg/kg in female SD rats and no changes in body weight or adverse effects were observed following necropsy. Acute dermal LD50 of LI85008F was greater than 2000 mg/kg. LI85008F was classified as non-irritating to skin in a primary dermal irritation study conducted using New Zealand Albino rabbits. LI85008F caused minimal irritation to eyes in a primary eye irritation test conducted on New Zealand Albino rabbits. A dose-dependent 28-day sub-acute toxicity study demonstrated no significant changes in selected organ weights. Evaluations on hematology, clinical chemistry, and histopathology did not show any significant adverse changes. The NOAEL of LI85008F was found to be greater than 2500 mg/kg body weight. These results demonstrate the broad spectrum safety of LI85008F in animal models.

Safety testing of GM-rice expressing PHA-E lectin using a new animal test design.

PubMed

Poulsen, Morten; Schrøder, Malene; Wilcks, Andrea; Kroghsbo, Stine; Lindecrona, Rikke Hvid; Miller, Andreas; Frenzel, Thomas; Danier, Jürgen; Rychlik, Michael; Shu, Qingyao; Emami, Kaveh; Taylor, Mark; Gatehouse, Angharad; Engel, Karl-Heinz; Knudsen, Ib

2007-03-01

The 90-day animal study is the core study for the safety assessment of genetically modified foods in the SAFOTEST project. The model compound tested in the 90-day study was a rice variety expressing the kidney bean Phaseolus vulgaris lectin agglutinin E-form (PHA-E lectin). Female Wistar rats were given a nutritionally balanced purified diet with 60% parental rice, 60% PHA-E rice or 60% PHA-E rice spiked with 0.1% recombinant PHA-E lectin for 90 days. This corresponded to a mean daily PHA-E lectin intake of approximately 0, 30 and 100mg/kg body weight for each group, respectively. The spiking was used to increase the specificity and to demonstrate the sensitivity of the study. A range of biological, biochemical, microbiological and pathological parameters were examined and significant differences in weight of small intestine, stomach and pancreas and plasma biochemistry were seen between groups. Included in this paper are also data from the molecular characterisation and chemical analysis of the PHA-E rice, from the construction and production of the PHA-E lectin, and from the preceding 28-day in vivo study where the toxicity of the pure PHA-E lectin was determined. In conclusion, the combined use of information from the compositional analysis, the 28-day study and the characterisation of the PHA-E rice and the PHA-E lectin has improved the design of the 90-day study. The spiking procedure has facilitated the interpretation of the results of the study and transferred it into a valuable tool for the future safety testing of genetically modified foods.

Safety Precautions. Child Health and Safety Series (Module I).

ERIC Educational Resources Information Center

Iscoe, Louise; And Others

This manual for parents and child care personnel in day care homes and centers provides guidelines and information on indoor and outdoor safety precautions, emergency preparation and first aid. Contents focus on monitoring arrivals and departures, prevention of suffocation and strangulation, control of pets and other animals, preventing and…

Realistic facial animation generation based on facial expression mapping

NASA Astrophysics Data System (ADS)

Yu, Hui; Garrod, Oliver; Jack, Rachael; Schyns, Philippe

2014-01-01

Facial expressions reflect internal emotional states of a character or in response to social communications. Though much effort has been taken to generate realistic facial expressions, it still remains a challenging topic due to human being's sensitivity to subtle facial movements. In this paper, we present a method for facial animation generation, which reflects true facial muscle movements with high fidelity. An intermediate model space is introduced to transfer captured static AU peak frames based on FACS to the conformed target face. And then dynamic parameters derived using a psychophysics method is integrated to generate facial animation, which is assumed to represent natural correlation of multiple AUs. Finally, the animation sequence in the intermediate model space is mapped to the target face to produce final animation.

Cueing Animations: Dynamic Signaling Aids Information Extraction and Comprehension

ERIC Educational Resources Information Center

Boucheix, Jean-Michel; Lowe, Richard K.; Putri, Dian K.; Groff, Jonathan

2013-01-01

The effectiveness of animations containing two novel forms of animation cueing that target relations between event units rather than individual entities was compared with that of animations containing conventional entity-based cueing or no cues. These relational event unit cues ("progressive path" and "local coordinated" cues) were specifically…

Preharvest food safety.

PubMed

Childers, A B; Walsh, B

1996-07-23

Preharvest food safety is essential for the protection of our food supply. The production and transport of livestock and poultry play an integral part in the safety of these food products. The goals of this safety assurance include freedom from pathogenic microorganisms, disease, and parasites, and from potentially harmful residues and physical hazards. Its functions should be based on hazard analysis and critical control points from producer to slaughter plant with emphasis on prevention of identifiable hazards rather than on removal of contaminated products. The production goal is to minimize infection and insure freedom from potentially harmful residues and physical hazards. The marketing goal is control of exposure to pathogens and stress. Both groups should have functional hazard analysis and critical control points management programs which include personnel training and certification of producers. These programs must cover production procedures, chemical usage, feeding, treatment practices, drug usage, assembly and transportation, and animal identification. Plans must use risk assessment principles, and the procedures must be defined. Other elements would include preslaughter certification, environmental protection, control of chemical hazards, live-animal drug-testing procedures, and identification of physical hazards.

Optimal chemotaxis in intermittent migration of animal cells

NASA Astrophysics Data System (ADS)

Romanczuk, P.; Salbreux, G.

2015-04-01

Animal cells can sense chemical gradients without moving and are faced with the challenge of migrating towards a target despite noisy information on the target position. Here we discuss optimal search strategies for a chaser that moves by switching between two phases of motion ("run" and "tumble"), reorienting itself towards the target during tumble phases, and performing persistent migration during run phases. We show that the chaser average run time can be adjusted to minimize the target catching time or the spatial dispersion of the chasers. We obtain analytical results for the catching time and for the spatial dispersion in the limits of small and large ratios of run time to tumble time and scaling laws for the optimal run times. Our findings have implications for optimal chemotactic strategies in animal cell migration.

Multiple Targets of Salicylic Acid and Its Derivatives in Plants and Animals

PubMed Central

Klessig, Daniel F.; Tian, Miaoying; Choi, Hyong Woo

2016-01-01

Salicylic acid (SA) is a critical plant hormone that is involved in many processes, including seed germination, root initiation, stomatal closure, floral induction, thermogenesis, and response to abiotic and biotic stresses. Its central role in plant immunity, although extensively studied, is still only partially understood. Classical biochemical approaches and, more recently, genome-wide high-throughput screens have identified more than two dozen plant SA-binding proteins (SABPs), as well as multiple candidates that have yet to be characterized. Some of these proteins bind SA with high affinity, while the affinity of others exhibit is low. Given that SA levels vary greatly even within a particular plant species depending on subcellular location, tissue type, developmental stage, and with respect to both time and location after an environmental stimulus such as infection, the presence of SABPs exhibiting a wide range of affinities for SA may provide great flexibility and multiple mechanisms through which SA can act. SA and its derivatives, both natural and synthetic, also have multiple targets in animals/humans. Interestingly, many of these proteins, like their plant counterparts, are associated with immunity or disease development. Two recently identified SABPs, high mobility group box protein and glyceraldehyde 3-phosphate dehydrogenase, are critical proteins that not only serve key structural or metabolic functions but also play prominent roles in disease responses in both kingdoms. PMID:27303403

Challenges of Sanitary Compliance Related to Trade in Products of Animal Origin in Southern Africa.

PubMed

Magwedere, Kudakwashe; Songabe, Tembile; Dziva, Francis

2015-06-30

Irrespective of the existence of potentially pathogenic organisms carried by animals, foods of animal origin remain the prime nutrition of humans world-wide. As such, food safety continues to be a global concern primarily to safeguard public health and to promote international trade. Application of integrated risk-based quality assurance procedures on-farm and at slaughterhouses plays a crucial role in controlling hazards associated with foods of animal origin. In the present paper we examine safety assurance systems and associated value chains for foods of animal origin based on historical audit results of some Southern African countries with thriving export trade in animal products, mainly to identify areas for improvement. Among the key deficiencies identified were: i) failure to keep pace with scientific advances related to the ever-changing food supply chain; ii) lack of effective national and regional intervention strategies to curtail pathogen transmission and evolution, notably the zoonotic Shiga toxin-producing Escherichia coli ; and iii) a lack of effective methods to reduce contamination of foods of wildlife origin. The introduction of foods of wildlife origin for domestic consumption and export markets seriously compounds already existing conflicts in legislation governing food supply and safety. This analysis identifies gaps required to improve the safety of foods of wildlife origin.

Challenges of Sanitary Compliance Related to Trade in Products of Animal Origin in Southern Africa

PubMed Central

Magwedere, Kudakwashe; Songabe, Tembile

2015-01-01

Irrespective of the existence of potentially pathogenic organisms carried by animals, foods of animal origin remain the prime nutrition of humans world-wide. As such, food safety continues to be a global concern primarily to safeguard public health and to promote international trade. Application of integrated risk-based quality assurance procedures on-farm and at slaughterhouses plays a crucial role in controlling hazards associated with foods of animal origin. In the present paper we examine safety assurance systems and associated value chains for foods of animal origin based on historical audit results of some Southern African countries with thriving export trade in animal products, mainly to identify areas for improvement. Among the key deficiencies identified were: i) failure to keep pace with scientific advances related to the ever-changing food supply chain; ii) lack of effective national and regional intervention strategies to curtail pathogen transmission and evolution, notably the zoonotic Shiga toxin-producing Escherichia coli; and iii) a lack of effective methods to reduce contamination of foods of wildlife origin. The introduction of foods of wildlife origin for domestic consumption and export markets seriously compounds already existing conflicts in legislation governing food supply and safety. This analysis identifies gaps required to improve the safety of foods of wildlife origin. PMID:27800409

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Marking of mule meat and animal food mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... CARNIVORA; INSPECTION, CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Mule...

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Marking of mule meat and animal food mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... CARNIVORA; INSPECTION, CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Mule...

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Marking of mule meat and animal food mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... CARNIVORA; INSPECTION, CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Mule...

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Marking of mule meat and animal food mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... CARNIVORA; INSPECTION, CERTIFICATION, AND IDENTIFICATION AS TO CLASS, QUALITY, QUANTITY, AND CONDITION Mule...

Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model.

PubMed

Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Hayward, Andrew; Marshall, Kay M; Neill, Joanna C

2015-04-01

Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

The flaws and human harms of animal experimentation.

PubMed

Akhtar, Aysha

2015-10-01

Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

Safety of targeting ROR1 in primates with chimeric antigen receptor-modified T cells

PubMed Central

Berger, Carolina; Sommermeyer, Daniel; Hudecek, Michael; Berger, Michael; Balakrishnan, Ashwini; Paszkiewicz, Paulina J.; Kosasih, Paula L.; Rader, Christoph; Riddell, Stanley R.

2014-01-01

Genetic engineering of T cells for adoptive transfer by introducing a tumor-targeting chimeric antigen receptor (CAR) is a new approach to cancer immunotherapy. A challenge for the field is to define cell surface molecules that are both preferentially expressed on tumor cells and can be safely targeted with T cells. The orphan tyrosine kinase receptor ROR1 is a candidate target for T-cell therapy with CAR-modified T cells (CAR-T cells) since it is expressed on the surface of many lymphatic and epithelial malignancies and has a putative role in tumor cell survival. The cell surface isoform of ROR1 is expressed in embryogenesis but absent in adult tissues except for B-cell precursors, and low levels of transcripts in adipocytes, pancreas, and lung. ROR1 is highly conserved between humans and macaques and has a similar pattern of tissue expression. To determine if low-level ROR1-expression on normal cells would result in toxicity or adversely affect CAR-T cell survival and/or function, we adoptively transferred autologous ROR1 CAR-T cells into nonhuman primates. ROR1 CAR-T cells did not cause overt toxicity to normal organs and accumulated in bone marrow and lymph node sites where ROR1-positive B cells were present. The findings support the clinical evaluation of ROR1 CAR-T cells for ROR1+ malignancies and demonstrate the utility of nonhuman primates for evaluating the safety of immunotherapy with engineered T cells specific for tumor-associated molecules that are homologous between humans and nonhuman primates. PMID:25355068

Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

PubMed

Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

2011-04-01

Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

Recommendations from a global cross-company data sharing initiative on the incorporation of recovery phase animals in safety assessment studies to support first-in-human clinical trials.

PubMed

Sewell, Fiona; Chapman, Kathryn; Baldrick, Paul; Brewster, David; Broadmeadow, Alan; Brown, Paul; Burns-Naas, Leigh Ann; Clarke, Janet; Constan, Alex; Couch, Jessica; Czupalla, Oliver; Danks, Andy; DeGeorge, Joseph; de Haan, Lolke; Hettinger, Klaudia; Hill, Marilyn; Festag, Matthias; Jacobs, Abby; Jacobson-Kram, David; Kopytek, Stephan; Lorenz, Helga; Moesgaard, Sophia Gry; Moore, Emma; Pasanen, Markku; Perry, Rick; Ragan, Ian; Robinson, Sally; Schmitt, Petra M; Short, Brian; Lima, Beatriz Silva; Smith, Diane; Sparrow, Sue; van Bekkum, Yvette; Jones, David

2014-10-01

An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in the assessment of pharmaceutical safety for early development. These data have been used as an evidence-base to make recommendations on the inclusion of recovery animals in toxicology studies to achieve scientific objectives, while reducing animal use. Recovery animals are used in pharmaceutical development to provide information on the potential for a toxic effect to translate into long-term human risk. They are included on toxicology studies to assess whether effects observed during dosing persist or reverse once treatment ends. The group devised a questionnaire to collect information on the use of recovery animals in general regulatory toxicology studies to support first-in-human studies. Questions focused on study design, the rationale behind inclusion or exclusion and the impact this had on internal and regulatory decisions. Data on 137 compounds (including 53 biologicals and 78 small molecules) from 259 studies showed wide variation in where, when and why recovery animals were included. An analysis of individual study and programme design shows that there are opportunities to reduce the use of recovery animals without impacting drug development. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Transgenic maize event TC1507: Global status of food, feed, and environmental safety

PubMed Central

Baktavachalam, Gajendra B; Delaney, Bryan; Fisher, Tracey L; Ladics, Gregory S; Layton, Raymond J; Locke, Mary EH; Schmidt, Jean; Anderson, Jennifer A; Weber, Natalie N; Herman, Rod A; Evans, Steven L

2015-01-01

Maize (Zea mays) is a widely cultivated cereal that has been safely consumed by humans and animals for centuries. Transgenic or genetically engineered insect-resistant and herbicide-tolerant maize, are commercially grown on a broad scale. Event TC1507 (OECD unique identifier: DAS-Ø15Ø7–1) or the Herculex®# I trait, an insect-resistant and herbicide-tolerant maize expressing Cry1F and PAT proteins, has been registered for commercial cultivation in the US since 2001. A science-based safety assessment was conducted on TC1507 prior to commercialization. The safety assessment addressed allergenicity; acute oral toxicity; subchronic toxicity; substantial equivalence with conventional comparators, as well as environmental impact. Results from biochemical, physicochemical, and in silico investigations supported the conclusion that Cry1F and PAT proteins are unlikely to be either allergenic or toxic to humans. Also, findings from toxicological and animal feeding studies supported that maize with TC1507 is as safe and nutritious as conventional maize. Maize with TC1507 is not expected to behave differently than conventional maize in terms of its potential for invasiveness, gene flow to wild and weedy relatives, or impact on non-target organisms. These safety conclusions regarding TC1507 were acknowledged by over 20 regulatory agencies including United States Environment Protection Agency (US EPA), US Department of Agriculture (USDA), Canadian Food Inspection Agency (CFIA), and European Food Safety Authority (EFSA) before authorizing cultivation and/or food and feed uses. A comprehensive review of the safety studies on TC1507, as well as some benefits, are presented here to serve as a reference for regulatory agencies and decision makers in other countries where authorization of TC1507 is or will be pursued. PMID:26018138

Transgenic maize event TC1507: Global status of food, feed, and environmental safety.

PubMed

Baktavachalam, Gajendra B; Delaney, Bryan; Fisher, Tracey L; Ladics, Gregory S; Layton, Raymond J; Locke, Mary Eh; Schmidt, Jean; Anderson, Jennifer A; Weber, Natalie N; Herman, Rod A; Evans, Steven L

2015-01-01

Maize (Zea mays) is a widely cultivated cereal that has been safely consumed by humans and animals for centuries. Transgenic or genetically engineered insect-resistant and herbicide-tolerant maize, are commercially grown on a broad scale. Event TC1507 (OECD unique identifier: DAS-Ø15Ø7-1) or the Herculex®(#) I trait, an insect-resistant and herbicide-tolerant maize expressing Cry1F and PAT proteins, has been registered for commercial cultivation in the US since 2001. A science-based safety assessment was conducted on TC1507 prior to commercialization. The safety assessment addressed allergenicity; acute oral toxicity; subchronic toxicity; substantial equivalence with conventional comparators, as well as environmental impact. Results from biochemical, physicochemical, and in silico investigations supported the conclusion that Cry1F and PAT proteins are unlikely to be either allergenic or toxic to humans. Also, findings from toxicological and animal feeding studies supported that maize with TC1507 is as safe and nutritious as conventional maize. Maize with TC1507 is not expected to behave differently than conventional maize in terms of its potential for invasiveness, gene flow to wild and weedy relatives, or impact on non-target organisms. These safety conclusions regarding TC1507 were acknowledged by over 20 regulatory agencies including United States Environment Protection Agency (US EPA), US Department of Agriculture (USDA), Canadian Food Inspection Agency (CFIA), and European Food Safety Authority (EFSA) before authorizing cultivation and/or food and feed uses. A comprehensive review of the safety studies on TC1507, as well as some benefits, are presented here to serve as a reference for regulatory agencies and decision makers in other countries where authorization of TC1507 is or will be pursued.

Structural basis for microRNA targeting

DOE PAGES

Schirle, Nicole T.; Sheu-Gruttadauria, Jessica; MacRae, Ian J.

2014-10-31

MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. In this paper, we determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions withmore » the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, whereas an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. Finally, these results explain the conserved nucleotide-pairing patterns in animal miRNA target sites first observed over two decades ago.« less

Contemporary Animal Models For Human Gene Therapy Applications.

PubMed

Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

2015-01-01

Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

Winter Weather: Outdoor Safety

MedlinePlus

... Hot Weather Tips Warning Signs and Symptoms FAQs Social Media How to Stay Cool Missouri Cooling Centers Extreme ... PSAs for Disasters Resources for Emergency Health Professionals Social Media Health and Safety Concerns for All Disasters Animals ...

Animal use for science in Europe.

PubMed

Daneshian, Mardas; Busquet, Francois; Hartung, Thomas; Leist, Marcel

2015-01-01

To investigate long-term trends of animal use, the EU animal use statistics from the 15 countries that have been in the EU since 1995 plus respective data from Switzerland were analyzed. The overall number of animals used for scientific purposes in these countries, i.e., about 11 million/year, remained relatively constant between 1995 and 2011, with net increases in Germany and the UK and net decreases in Belgium, Denmark, Italy, Finland, the Netherlands and Sweden. The relatively low and constant numbers of experimental animals used for safety assessment (toxicology, 8%) may be due to the particularly intensive research on alternative methods in this area. The many efficiently working NGOs, multiple initiatives of the European Parliament, and coordinated activities of industry and the European Commission may have contributed to keeping the animal numbers in this field in check. Basic biological science, and research and development for medicine, veterinary and dentistry together currently make up 65% of animal use in science. Although the total numbers have remained relatively constant, consumption of transgenic animals has increased drastically; in Germany transgenic animals accounted for 30% of total animal use in 2011. Therefore, more focus on alternatives to the use of animals in biomedical research, in particular on transgenic animals, will be important in the future. One initiative designed to provide inter-sector information exchange for future actions is the "MEP - 3Rs scientists pairing scheme" initiated in 2015 by CAAT-Europe and MEP Pietikäinen.

The what as well as the why of animal fun.

PubMed

Byrne, Richard W

2015-01-05

Fun is functional: play is evolution's way of making sure animals acquire and perfect valuable skills in circumstances of relative safety. Yet precisely what animals find fun has seldom been examined for what it can potentially reveal about how they represent and think about the world. Copyright © 2015 Elsevier Ltd. All rights reserved.

9 CFR 355.42 - Marking of mule meat and animal food mule meat by-product.

Code of Federal Regulations, 2010 CFR

2010-01-01

... mule meat by-product. 355.42 Section 355.42 Animals and Animal Products FOOD SAFETY AND INSPECTION... Meat and Animal Food, Mule Meat By-Product § 355.42 Marking of mule meat and animal food mule meat by-product. All mule meat and animal food mule meat by-product inspected under this part shall be marked and...

Neuroprotective and cognitive enhancing effects of a multi-targeted food intervention in an animal model of neurodegeneration and depression.

PubMed

Borre, Yuliya E; Panagaki, Theodora; Koelink, Pim J; Morgan, Mary E; Hendriksen, Hendrikus; Garssen, Johan; Kraneveld, Aletta D; Olivier, Berend; Oosting, Ronald S

2014-04-01

Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This diet was tested on the olfactory bulbectomized rat (OBX), an established animal model of depression and cognitive decline. The ingredients of the diet have been individually shown to attenuate glutamate excitoxicity, exert potent anti-oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that all have been implicated in neurodegenerative diseases and in the cognitive deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced cognitive and behavioral deficits, except long-term spatial memory. Ameliorating effects of the diet extended to the control animals. Furthermore, the experimental diet reduced hippocampal atrophy and decreased the peripheral immune activation in the OBX rats. The ameliorating effects of the diet on the OBX-induced changes were comparable to those of the NMDA receptor antagonist, memantine, a drug used for the management of Alzheimer's disease. This proof-of-concept study suggests that a diet, which simultaneously targets multiple disease etiologies, can prevent/impede the development of a neurodegenerative and depressive disorders and the concomitant cognitive deficits. Copyright © 2014. Published by Elsevier Ltd.

LIQUID TARGET

DOEpatents

Martin, M.D.; Salsig, W.W. Jr.

1959-01-13

A liquid handling apparatus is presented for a liquid material which is to be irradiated. The apparatus consists essentially of a reservoir for the liquid, a target element, a drain tank and a drain lock chamber. The target is in the form of a looped tube, the upper end of which is adapted to be disposed in a beam of atomic particles. The lower end of the target tube is in communication with the liquid in the reservoir and a means is provided to continuously circulate the liquid material to be irradiated through the target tube. Means to heat the reservoir tank is provided in the event that a metal is to be used as the target material. The apparatus is provided with suitable valves and shielding to provide maximum safety in operation.

Food Safety

Science.gov Websites

veggies? Federal Pesticide Regulation Pesticides and Human Health Regulating Organic Food Production fruit and veggies? Federal Pesticide Regulation Pesticides and Human Health Regulating Organic Food ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife

Handedness helps homing in swimming and flying animals.

PubMed

Bandyopadhyay, Promode R; Leinhos, Henry A; Hellum, Aren M

2013-01-01

Swimming and flying animals rely on their ability to home on mobile targets. In some fish, physiological handedness and homing correlate, and dolphins exhibit handedness in their listening response. Here, we explore theoretically whether the actuators, sensors, and controllers in these animals follow similar laws of self-regulation, and how handedness affects homing. We find that the acoustic sensor (combined hydrophone-accelerometer) response maps are similar to fin force maps-modeled by Stuart-Landau oscillators-allowing localization by transitional vortex-propelled animals. The planar trajectories of bats in a room filled with obstacles are approximately reproduced by the states of a pair of strong and weak olivo-cerebellar oscillators. The stereoscopy of handedness reduces ambiguity near a mobile target, resulting in accelerated homing compared to even-handedness. Our results demonstrate how vortex-propelled animals may be localizing each other and circumventing obstacles in changing environments. Handedness could be useful in time-critical robot-assisted rescues in hazardous environments.

Handedness helps homing in swimming and flying animals

PubMed Central

Bandyopadhyay, Promode R.; Leinhos, Henry A.; Hellum, Aren M.

2013-01-01

Swimming and flying animals rely on their ability to home on mobile targets. In some fish, physiological handedness and homing correlate, and dolphins exhibit handedness in their listening response. Here, we explore theoretically whether the actuators, sensors, and controllers in these animals follow similar laws of self-regulation, and how handedness affects homing. We find that the acoustic sensor (combined hydrophone-accelerometer) response maps are similar to fin force maps—modeled by Stuart-Landau oscillators—allowing localization by transitional vortex-propelled animals. The planar trajectories of bats in a room filled with obstacles are approximately reproduced by the states of a pair of strong and weak olivo-cerebellar oscillators. The stereoscopy of handedness reduces ambiguity near a mobile target, resulting in accelerated homing compared to even-handedness. Our results demonstrate how vortex-propelled animals may be localizing each other and circumventing obstacles in changing environments. Handedness could be useful in time-critical robot-assisted rescues in hazardous environments. PMID:23350035

Opportunities to Apply the 3Rs in Safety Assessment Programs

PubMed Central

Sewell, Fiona; Edwards, Joanna; Prior, Helen; Robinson, Sally

2016-01-01

Abstract Before a potential new medicine can be administered to humans it is essential that its safety is adequately assessed. Safety assessment in animals forms an integral part of this process, from early drug discovery and initial candidate selection to the program of recommended regulatory tests in animals. The 3Rs (replacement, reduction, and refinement of animals in research) are integrated in the current regulatory requirements and expectations and, in the EU, provide a legal and ethical framework for in vivo research to ensure the scientific objectives are met whilst minimizing animal use and maintaining high animal welfare standards. Though the regulations are designed to uncover potential risks, they are intended to be flexible, so that the most appropriate approach can be taken for an individual product. This article outlines current and future opportunities to apply the 3Rs in safety assessment programs for pharmaceuticals, and the potential (scientific, financial, and ethical) benefits to the industry, across the drug discovery and development process. For example, improvements to, or the development of, novel, early screens (e.g., in vitro, in silico, or nonmammalian screens) designed to identify compounds with undesirable characteristics earlier in development have the potential to reduce late-stage attrition by improving the selection of compounds that require regulatory testing in animals. Opportunities also exist within the current regulatory framework to simultaneously reduce and/or refine animal use and improve scientific outcomes through improvements to technical procedures and/or adjustments to study designs. It is important that approaches to safety assessment are continuously reviewed and challenged to ensure they are science-driven and predictive of relevant effects in humans. PMID:28053076

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: eye irritation.

PubMed

McNamee, Pauline; Hibatallah, Jalila; Costabel-Farkas, Margit; Goebel, Carsten; Araki, Daisuke; Dufour, Eric; Hewitt, Nicola J; Jones, Penny; Kirst, Annette; Le Varlet, Béatrice; Macfarlane, Martin; Marrec-Fairley, Monique; Rowland, Joanna; Schellauf, Florian; Scheel, Julia

2009-07-01

The need for alternative approaches to replace the in vivo rabbit Draize eye test for evaluation of eye irritation of cosmetic ingredients has been recognised by the cosmetics industry for many years. Extensive research has lead to the development of several assays, some of which have undergone formal validation. Even though, to date, no single in vitro assay has been validated as a full replacement for the rabbit Draize eye test, organotypic assays are accepted for specific and limited regulatory purposes. Although not formally validated, several other in vitro models have been used for over a decade by the cosmetics industry as valuable tools in a weight of evidence approach for the safety assessment of ingredients and finished products. In light of the deadlines established in the EU Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision-tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. Furthermore, recommendations are given on how remaining data gaps and research needs can be addressed.

2011 Annual Meeting of the Safety Pharmacology Society: an overview.

PubMed

Cavero, Icilio

2012-03-01

The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization

Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients.

PubMed

Vinken, Mathieu; Pauwels, Marleen; Ates, Gamze; Vivier, Manon; Vanhaecke, Tamara; Rogiers, Vera

2012-03-01

Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients.

Animal health: foundation of a safe, secure, and abundant food supply.

PubMed

DeHaven, W Ron; Goldberg, Ruth

2006-01-01

During the past century, reductions in animal diseases have resulted in a safer, more uniform, and more economical food supply. In the United States, the passage of the 1906 Federal Meat Inspection Act mandated better sanitary conditions for slaughter and processing, as well as inspection of live animals and their processed products. Following World War II, Congress passed the Poultry Products Inspection Act. Both acts are regulated by the Food Safety and Inspection Service (FSIS) of the US Department of Agriculture (USDA). The USDA's Animal and Plant Health Inspection Service (APHIS) is responsible for regulations governing the health of live animals prior to slaughter. This article is a brief overview of the ways in which the current predominance of zoonotics among emerging diseases underscores the importance of veterinary health professionals and the need for continued coordination between animal-health and public-health officials. Examples of intersections between animal- and public-health concerns include bovine spongiform encephalopathy (BSE) and Johne's disease, as well as extending beyond food safety to diseases such as avian influenza (AI). In the United States, we have in place an extensive public and private infrastructure to address animal-health issues, including the necessary expertise and resources to address animal-health emergencies. However, many challenges remain, including a critical shortage of food-animal veterinarians. These challenges can be met by recruiting and training a cadre of additional food-supply veterinarians, pursuing new technologies, collaborating with public-health officials to create solutions, and sending a clear and consistent message to the public about important animal-health issues.

Differential Impact of Plasma Proteins on the Adhesion Efficiency of Vascular-Targeted Carriers (VTCs) in Blood of Common Laboratory Animals.

PubMed

Namdee, Katawut; Sobczynski, Daniel J; Onyskiw, Peter J; Eniola-Adefeso, Omolola

2015-12-16

Vascular-targeted carrier (VTC) interaction with human plasma is known to reduce targeted adhesion efficiency in vitro. However, the role of plasma proteins on the adhesion efficiency of VTCs in laboratory animals remains unknown. Here, in vitro blood flow assays are used to explore the effects of plasma from mouse, rabbit, and porcine on VTC adhesion. Porcine blood exhibited a strong negative plasma effect on VTC adhesion while no significant plasma effect was found with rabbit and mouse blood. A brush density poly(ethylene glycol) (PEG) on VTCs was effective at improving adhesion of microsized, but not nanosized, VTCs in porcine blood. Overall, the results suggest that porcine models, as opposed to mouse, can serve as better models in preclinical research for predicting the in vivo functionality of VTCs for use in humans. These considerations hold great importance for the design of various pharmaceutical products and development of reliable drug delivery systems.

Animal production systems in the industrialised world.

PubMed

Sørensen, J T; Edwards, S; Noordhuizen, J; Gunnarsson, S

2006-08-01

The production of food from animal origin is relatively stable in the industrialised world. However, animal production systems are changing dramatically with respect to location, herd size and specialisation. Increased pressure from a critical public is moving animal-based production towards systems such as organic production and loose-housing systems which allow the animals to better express normal behaviour. The focus on food safety promotes systems with a high degree of biosecurity, often associated with an increase in herd size and self-containment. The globalisation of agricultural trade and increased competition also favours an increase in herd size and specialisation. These trends also lead to regions with livestock-dense areas, giving rise to environmental concerns. Therefore, good farming practice regulations and systems to provide a higher level of transparency, such as quality risk management programmes, are being developed.

A Historical View and Vision into the Future of the Field of Safety Pharmacology.

PubMed

Bass, Alan S; Hombo, Toshiyasu; Kasai, Chieko; Kinter, Lewis B; Valentin, Jean-Pierre

2015-01-01

Professor Gerhard Zbinden recognized in the 1970s that the standards of the day for testing new candidate drugs in preclinical toxicity studies failed to identify acute pharmacodynamic adverse events that had the potential to harm participants in clinical trials. From his vision emerged the field of safety pharmacology, formally defined in the International Conference on Harmonization (ICH) S7A guidelines as "those studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above." Initially, evaluations of small-molecule pharmacodynamic safety utilized efficacy models and were an ancillary responsibility of discovery scientists. However, over time, the relationship of these studies to overall safety was reflected by the regulatory agencies who, in directing the practice of safety pharmacology through guidance documents, prompted transition of responsibility to drug safety departments (e.g., toxicology). Events that have further shaped the field over the past 15 years include the ICH S7B guidance, evolution of molecular technologies leading to identification of new therapeutic targets with uncertain toxicities, introduction of data collection using more sophisticated and refined technologies, and utilization of transgenic animal models probing critical scientific questions regarding novel targets of toxicity. The collapse of the worldwide economy in the latter half of the first decade of the twenty-first century, continuing high rates of compound attrition during clinical development and post-approval and sharply increasing costs of drug development have led to significant strategy changes, contraction of the size of pharmaceutical organizations, and refocusing of therapeutic areas of investigation. With these changes has come movement away from dedicated internal safety pharmacology capability to utilization of capabilities within external contract

Cardiac AAV9-S100A1 gene therapy rescues postischemic heart failure in a preclinical large animal model

PubMed Central

Pleger, Sven T.; Shan, Changguang; Ksienzyk, Jan; Bekeredjian, Raffi; Boekstegers, Peter; Hinkel, Rabea; Schinkel, Stefanie; Leuchs, Barbara; Ludwig, Jochen; Qiu, Gang; Weber, Christophe; Kleinschmidt, Jürgen A.; Raake, Philip; Koch, Walter J.; Katus, Hugo A.; Müller, Oliver J.; Most, Patrick

2014-01-01

As a prerequisite to clinical application, we determined the long-term therapeutic effectiveness and safety of adeno-associated viral (AAV) S100A1 gene therapy in a preclinical, large animal model of heart failure. S100A1, a positive inotropic regulator of myocardial contractility, becomes depleted in failing cardiomyocytes in humans and various animal models, and myocardial-targeted S100A1 gene transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium Ca2+ handling in acutely and chronically failing hearts in small animal models. We induced heart failure in domestic pigs by balloon-occlusion of the left circumflex coronary artery, resulting in myocardial infarction. After 2 weeks, when the pigs displayed significant left ventricular contractile dysfunction, we administered through retrograde coronary venous delivery, AAV9-S100A1 to the left ventricular non-infarcted myocardium. AAV9-luciferase and saline treatment served as control. At 14 weeks, both control groups showed significantly decreased myocardial S100A1 protein expression along with progressive deterioration of cardiac performance and left ventricular remodeling. AAV9-S100A1 treatment prevented and reversed this phenotype by restoring cardiac S100A1 protein levels. S100A1 treatment normalized cardiomyocyte Ca2+ cycling, sarcoplasmic reticulum calcium handling and energy homeostasis. Transgene expression was restricted to cardiac tissue and extra-cardiac organ function was uncompromised indicating a favorable safety profile. This translational study shows the pre-clinical feasibility, long-term therapeutic effectiveness and a favorable safety profile of cardiac AAV9-S100A1 gene therapy in a preclinical model of heart failure. Our study presents a strong rational for a clinical trial of S100A1 gene therapy for human heart failure that could potentially complement current strategies to treat end-stage heart failure. PMID:21775667

Safety and health concerns in forestry operations

Treesearch

Robert B. Rummer

1997-01-01

The author discusses several safety models, including the "Three E?s": engineering, education, and enforcement; the Heinrich-Lateiner model; the organizational model; and the behavioral safety model. Rummer encourages approaching safety from a broader perspective, enabling the industry to track changes in all aspects and to keep leading the safety target....

Biodistribution and Pharmacokinetic Analysis of Combination Lonidamine and Paclitaxel Delivery in an Orthotopic Animal Model of Multi-drug Resistant Breast Cancer Using EGFR-Targeted Polymeric Nanoparticles

PubMed Central

Milane, Lara; Duan, Zhen-feng; Amiji, Mansoor

2011-01-01

The aim of this study was to assess the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer blend nanoparticles loaded with the anticancer drugs lonidamine and paclitaxel. Plasma, tumor, and tissue distribution profiles were quantified in an orthotopic animal model of multi-drug resistant (MDR) breast cancer and were compared to treatment with non-targeted nanoparticles and to treatment with drug solution. Poly(D,L-lactide-co-glycolide)/poly(ethylene glycol)/EGFR targeting peptide (PLGA/PEG/EFGR peptide) construct was synthesized for incorporation in poly(ε-caprolactone) (PCL) particles to achieve active EGFR targeting. An isocratic HPLC method was developed to quantify lonidamine and paclitaxel in mice plasma, tumors, and vital organs. The targeted nanoparticles demonstrated superior pharmacokinetic profile relative to drug solution and non-targeted nanoparticles, particularly for lonidamine delivery. The first target site of accumulation is the liver, followed by the kidneys, and then the tumor mass; maximal tumor accumulation occurs at 3 hours post-administration. Lonidamine/paclitaxel combination therapy administered via EGFR-targeted polymer blend nanocarriers may become a viable platform for the future treatment of MDR cancer. PMID:21220050

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com; Nolte, Marc W.; Solomon, Cristina

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii)more » the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well

Neuropsychiatric SLE: from animal model to human.

PubMed

Pikman, R; Kivity, S; Levy, Y; Arango, M-T; Chapman, J; Yonath, H; Shoenfeld, Y; Gofrit, S G

2017-04-01

Animal models are a key element in disease research and treatment. In the field of neuropsychiatric lupus research, inbred, transgenic and disease-induced mice provide an opportunity to study the pathogenic routes of this multifactorial illness. In addition to achieving a better understanding of the immune mechanisms underlying the disease onset, supplementary metabolic and endocrine influences have been discovered and investigated. The ever-expanding knowledge about the pathologic events that occur at disease inception enables us to explore new drugs and therapeutic approaches further and to test them using the same animal models. Discovery of the molecular targets that constitute the pathogenic basis of the disease along with scientific advancements allow us to target these molecules with monoclonal antibodies and other specific approaches directly. This novel therapy, termed "targeted biological medication" is a promising endeavor towards producing drugs that are more effective and less toxic. Further work to discover additional molecular targets in lupus' pathogenic mechanism and to produce drugs that neutralize their activity is needed to provide patients with safe and efficient methods of controlling and treating the disease.

Animal health pharmaceutical industry.

PubMed

Carnevale, Richard A; Shryock, Thomas R

2006-02-24

The animal health pharmaceutical industry has proactively reported on the volumes of member company antimicrobial active ingredients sold in the U.S. At the individual company level, reporting of finished product distribution data to the FDA is a regulatory requirement, with applications to surveillance and pharmacovigilance. An accounting of product manufactured is done for purposes of good business practices, as well as marketing analyses. Additional applications of antimicrobial usage data might include use in risk assessments, such as for the FDA's Center for Veterinary Medicine Guidance for Industry #152 for the evaluation of the microbiological safety of antimicrobials intended for use in food animals. Compilation of national usage data will be a complex undertaking, hindered by issues such as confidentiality, auditing, field use practice variations, population dynamics (e.g. disease incidence, market conditions for poultry and livestock production), and generic usage. The amounts or volumes in pounds should be considered relative to the large number of animals under husbandry in the United States. Large volumes might seem impressive unless put into proper context. Until such time as a clearly defined application of national usage data is agreed, it is recommended that local usage programs will provide more useful information to perpetuate prudent antimicrobial use in animals.

Pet Food Safety A Shared Concern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchanan, Robert L; Baker, Robert C; Charlton, Adrian J

2011-01-01

The safety of the food supply is a subject of intense interest to consumers, particularly as a result of large scale outbreaks that involve hundreds and sometimes thousands of consumers. During the last decade this concern about food safety has expanded to include the diets of companion animals as a result of several incidences of chemical toxicities and infectious disease transmission. This has led to increased research into the causes and controls for these hazards for both companion animals and their owners. The following summary provides an introduction to the issues, challenges, and new tools being developed to ensure thatmore » commercial pet foods are both nutritious and safe.« less

Rodent Control Pesticide Safety Review

EPA Pesticide Factsheets

EPA completed a safety review in 2008 of rat and mouse poison products. Many companies' products have our safety measures that reduce risks to humans, pets, and non-target wildlife. Products must be sold with bait stations that securely contain the poison.

Occupational health and safety in small animal veterinary practice: Part I--nonparasitic zoonotic diseases.

PubMed

Weese, J S; Peregrine, A S; Armstrong, J

2002-08-01

Zoonotic diseases are an ever-present concern in small animal veterinary practice and are often overlooked. A variety of nonparasitic zoonotic diseases may be encountered in small animal practice, including cat scratch disease (bartonellosis), cat bite abscesses, rabies, leptospirosis, methicillin-resistant Staphylococcus aureus, Clostridium difficile-associated diarrhea, salmonellosis, avian chlamydiosis, campylobacteriosis, dermatophytosis, and blastomycosis. These may cause human disease ranging from mild and self-limiting to fatal. The risk of development of a zoonotic disease can be lessened by early recognition of infected animals, proper animal handling, basic biosecurity precautions, and, most importantly, personal hygiene.

Genetic modification of hematopoietic cells using retroviral and lentiviral vectors: safety considerations for vector design and delivery into target cells.

PubMed

Dropulic, Boro

2005-07-01

The recent development of leukemia in three patients following retroviral vector gene transfer in hematopoietic stem cells, resulting in the death of one patient, has raised safety concerns for the use of integrating gene transfer vectors for human gene therapy. This review discusses these serious adverse events from the perspective of whether restrictions on vector design and vector-modified target cells are warranted at this time. A case is made against presently establishing specific restrictions for vector design and transduced cells; rather, their safety should be ascertained by empiric evaluation in appropriate preclinical models on a case-by-case basis. Such preclinical data, coupled with proper informed patient consent and a risk-benefit ratio analysis, provide the best available prospective evaluation of gene transfer vectors prior to their translation into the clinic.

Biological safety concepts of genetically modified live bacterial vaccines.

PubMed

Frey, Joachim

2007-07-26

Live vaccines possess the advantage of having access to induce cell-mediated and antibody-mediated immunity; thus in certain cases they are able to prevent infection, and not only disease. Furthermore, live vaccines, particularly bacterial live vaccines, are relatively cheap to produce and easy to apply. Hence they are suitable to immunize large communities or herds. The induction of both cell-mediated immunity as well as antibody-mediated immunity, which is particularly beneficial in inducing mucosal immune responses, is obtained by the vaccine-strain's ability to colonize and multiply in the host without causing disease. For this reason, live vaccines require attenuation of virulence of the bacterium to which immunity must be induced. Traditionally attenuation was achieved simply by multiple passages of the microorganism on growth medium, in animals, eggs or cell cultures or by chemical or physical mutagenesis, which resulted in random mutations that lead to attenuation. In contrast, novel molecular methods enable the development of genetically modified organisms (GMOs) targeted to specific genes that are particularly suited to induce attenuation or to reduce undesirable effects in the tissue in which the vaccine strains can multiply and survive. Since live vaccine strains (attenuated by natural selection or genetic engineering) are potentially released into the environment by the vaccinees, safety issues concerning the medical as well as environmental aspects must be considered. These involve (i) changes in cell, tissue and host tropism, (ii) virulence of the carrier through the incorporation of foreign genes, (iii) reversion to virulence by acquisition of complementation genes, (iv) exchange of genetic information with other vaccine or wild-type strains of the carrier organism and (v) spread of undesired genes such as antibiotic resistance genes. Before live vaccines are applied, the safety issues must be thoroughly evaluated case-by-case. Safety assessment

Safety and Immunological Efficacy of a DNA Vaccine Encoding the Androgen Receptor Ligand-Binding Domain (AR-LBD).

PubMed

Olson, Brian M; Bradley, Eric S; Sawicki, Thomas; Zhong, Weixiong; Ranheim, Erik A; Bloom, Jordan E; Colluru, Viswa T; Johnson, Laura E; Rekoske, Brian T; Eickhoff, Jens C; McNeel, Douglas G

2017-05-01

The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR. Groups of male mice (n = 6-10 per group) were evaluated after four or seven immunizations, using different schedules and inclusion of GM-CSF as a vaccine adjuvant. Animals were assessed for toxicity using gross observations, pathological analysis, and analysis of serum chemistries. Animals were analyzed for evidence of vaccine-augmented immunity by tetramer analysis. Survival studies using different immunization schedules and inclusion of GM-CSF were conducted in an autochthonous genetically engineered mouse model. No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries, although there was a trend to lower serum glucose in animals treated with the vaccine. There was specifically no evidence of toxicity in other tissues that express AR, including liver, muscle, hematopoietic, and brain. Vaccination was found to elicit AR LBD-specific CD8+ T cells. In a subsequent study of tumor-bearing animals, animals treated with vaccine had prolonged survival compared with control-immunized mice. These studies demonstrate that, in immunocompetent mice expressing the target antigen, immunization with the pTVG-AR vaccine was both safe and effective in eliciting AR-specific cellular immune responses, and prolonged the survival of prostate tumor-bearing mice. These findings support the clinical evaluation of pTVG-AR in patients with recurrent prostate

Seismic signature analysis for discrimination of people from animals

NASA Astrophysics Data System (ADS)

Damarla, Thyagaraju; Mehmood, Asif; Sabatier, James M.

2013-05-01

Cadence analysis has been the main focus for discriminating between the seismic signatures of people and animals. However, cadence analysis fails when multiple targets are generating the signatures. We analyze the mechanism of human walking and the signature generated by a human walker, and compare it with the signature generated by a quadruped. We develop Fourier-based analysis to differentiate the human signatures from the animal signatures. We extract a set of basis vectors to represent the human and animal signatures using non-negative matrix factorization, and use them to separate and classify both the targets. Grazing animals such as deer, cows, etc., often produce sporadic signals as they move around from patch to patch of grass and one must characterize them so as to differentiate their signatures from signatures generated by a horse steadily walking along a path. These differences in the signatures are used in developing a robust algorithm to distinguish the signatures of animals from humans. The algorithm is tested on real data collected in a remote area.

Understanding drug targets: no such thing as bad news.

PubMed

Roberts, Ruth A

2018-05-24

How can small-to-medium pharma and biotech companies enhance the chances of running a successful drug project and maximise the return on a limited number of assets? Having a full appreciation of the safety risks associated with proposed drug targets is a crucial element in understanding the unwanted side-effects that might stop a project in its tracks. Having this information is necessary to complement knowledge about the probable efficacy of a future drug. However, the lack of data-rich insight into drug-target safety is one of the major causes of drug-project failure today. Conducting comprehensive target-safety reviews early in the drug discovery process enables project teams to make the right decisions about which drug targets to take forward. Copyright © 2018 Elsevier Ltd. All rights reserved.

Robotically Driven CT-guided Needle Insertion: Preliminary Results in Phantom and Animal Experiments.

PubMed

Hiraki, Takao; Kamegawa, Tetsushi; Matsuno, Takayuki; Sakurai, Jun; Kirita, Yasuzo; Matsuura, Ryutaro; Yamaguchi, Takuya; Sasaki, Takanori; Mitsuhashi, Toshiharu; Komaki, Toshiyuki; Masaoka, Yoshihisa; Matsui, Yusuke; Fujiwara, Hiroyasu; Iguchi, Toshihiro; Gobara, Hideo; Kanazawa, Susumu

2017-11-01

Purpose To evaluate the accuracy of the remote-controlled robotic computed tomography (CT)-guided needle insertion in phantom and animal experiments. Materials and Methods In a phantom experiment, 18 robotic and manual insertions each were performed with 19-gauge needles by using CT fluoroscopic guidance for the evaluation of the equivalence of accuracy of insertion between the two groups with a 1.0-mm margin. Needle insertion time, CT fluoroscopy time, and radiation exposure were compared by using the Student t test. The animal experiments were approved by the institutional animal care and use committee. In the animal experiment, five robotic insertions each were attempted toward targets in the liver, kidneys, lungs, and hip muscle of three swine by using 19-gauge or 17-gauge needles and by using conventional CT guidance. The feasibility, safety, and accuracy of robotic insertion were evaluated. Results The mean accuracies of robotic and manual insertion in phantoms were 1.6 and 1.4 mm, respectively. The 95% confidence interval of the mean difference was -0.3 to 0.6 mm. There were no significant differences in needle insertion time, CT fluoroscopy time, or radiation exposure to the phantom between the two methods. Effective dose to the physician during robotic insertion was always 0 μSv, while that during manual insertion was 5.7 μSv on average (P < .001). Robotic insertion was feasible in the animals, with an overall mean accuracy of 3.2 mm and three minor procedure-related complications. Conclusion Robotic insertion exhibited equivalent accuracy as manual insertion in phantoms, without radiation exposure to the physician. It was also found to be accurate in an in vivo procedure in animals. © RSNA, 2017 Online supplemental material is available for this article.

The SEURAT-1 Approach towards Animal Free Human Safety Assessment

EPA Science Inventory

SEURAT-1 is a European public-private research consortium that is working towards animal-free testing of chemical compounds and the highest level of consumer protection. A research strategy was formulated based on the guiding principle to adopt a toxicological mode-of-action fram...

Safety of Microbubbles and Transcranial Ultrasound in Rabbits

NASA Astrophysics Data System (ADS)

Culp, William C.; Brown, Aliza T.; Hennings, Leah; Lowery, John; Culp, Benjamin C.; Erdem, Eren; Roberson, Paula; Matsunaga, Terry O.

2007-05-01

The object of this study was to evaluate the safety of large doses of microbubbles and ultrasound administered to the head of rabbits as if they were receiving acute stroke therapy of a similar nature. Materials and Methods: Female New Zealand White rabbits were used, N=24, in three groups 1] n=4 control (no treatment), 2] n=10 bubble control (ultrasound plus aspirin), and 3] n=10 target group (ultrasound plus aspirin plus MRX-815 microbubbles). Group 3 was infused with IV bubbles over 1 hour at 0.16cc/kg. Ultrasound was delivered to the dehaired side of the head during bubble infusion and for 1 additional hour at 0.8 W/cm2 20% pulsed wave. Rabbits survived for 22 to 24 hours, were imaged with computerized tomography and 3 Tesla magnetic resonance imaging including contrast studies, and sacrificed. Tetrazolium (TTC) and Hematoxylin and Eosin (H&E) sections were made for pathological examination. Results: All 24 animals showed absence of bleeding, endothelial damage, EKG abnormalities, stroke, blood-brain-barrier breakdown, or other acute abnormalities. CT and MRI showed no bleeding or signs of stroke, but two animals had mild hydrocephalus. The EKGs showed normal variation in QTc. Rabbit behavior was normal in all. Minimal chronic inflammation unrelated to the study was seen in 5. Two animals were excluded because of protocol violations and replaced during the study. Conclusion: The administered dose of microbubbles and ultrasound demonstrated no detrimental effects on the healthy rabbit animal model.

21 CFR 500.86 - Marker residue and target tissue.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Regulation of Carcinogenic Compounds Used in Food-Producing Animals § 500.86 Marker residue and target tissue. (a) For each edible tissue, the sponsor shall... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Marker residue and target tissue. 500.86 Section...

21 CFR 500.86 - Marker residue and target tissue.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Regulation of Carcinogenic Compounds Used in Food-Producing Animals § 500.86 Marker residue and target tissue. (a) For each edible tissue, the sponsor shall... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Marker residue and target tissue. 500.86 Section...

21 CFR 500.86 - Marker residue and target tissue.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS GENERAL Regulation of Carcinogenic Compounds Used in Food-Producing Animals § 500.86 Marker residue and target tissue. (a) For each edible tissue, the sponsor shall... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Marker residue and target tissue. 500.86 Section...

Crisis planning to manage risks posed by animal rights extremists.

PubMed

Bailey, Matthew R; Rich, Barbara A; Bennett, B Taylor

2010-01-01

Among the multitude of crises that US research institutions may face are those caused by animal rights activists. While most activists opposed to animal research use peaceful and lawful means of expressing their opinions, some extremists resort to illegal methods. Arson, break-ins, and theft with significant property damage at US animal research facilities began in the 1980s. The most troubling trend to develop in the past decade is the targeting of individuals associated with animal research, whether directly or indirectly, and the use of violent scare tactics to intimidate researchers and their families. The National Association for Biomedical Research has a 30-year history of monitoring the animal rights movement and assisting member institutions with crisis situations. In this article we discuss attacks on researchers at their homes, cyber crimes, exploitation of new media formats, infiltration of research facilities, and the targeting of external research stakeholders and business partners. We describe the need for a well-conceived crisis management plan and strong leadership to mitigate crisis situations. Institutions with well-informed leaders and crisis management teams ready to take timely action are best equipped to protect staff, laboratory animals, and research programs. They act on early warnings, provide support for targeted staff, seek legal remedies, thoughtfully control access to research facilities, and identify and enlist new research supporters. We underscore the importance of up-to-date crisis planning so that institutions are not only aware of ongoing risks posed by animal rights extremists but also better prepared to take preemptive action and able to manage those risks successfully.

[Professional driving and safety, a target for occupational medicine].

PubMed

Rosso, G L; Zanelli, R; Bruno, Santina; Feola, M; Bobbio, M

2007-01-01

Road traffic injuries constitute one of the main causes of death and disability in Italy and in the European Union. Occupational medicine should pay special attention to the field of road transport because every year a large number of road accidents occur with fatal outcomes. Via health surveillance the occupational physician can play an important role in the prevention of such events. The aim of the article is to summarize the results of the most recent studies on the main risk factors for road transport safety and discuss possible strategies of health surveillance, according to the recent indications of the European Agency for Safety and Health at Work, Bilbao. A review of the literature was made. The scientific literature provides a large amount of interesting information on the most important risk factors for road accidents, such as drinking and drug abuse, sleepiness and other medical conditions, or excessive speed. The presence of numerous and varied hazards for road transport safety requires, as suggested by the Bilbao Agency, the adoption of occupational health measures, including risk assessment, health education, technical and environmental prevention, health surveillance and clinical interventions (diagnosis and rehabilitation of occupational accidents). Moreover, the paper stresses the need to strengthen collaboration between occupational health physicians and other medical specialists.

Animal models for microbicide studies.

PubMed

Veazey, Ronald S; Shattock, Robin J; Klasse, Per Johan; Moore, John P

2012-01-01

There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the use of anti-retroviral drugs. However, much work remains to be accomplished before a microbicide becomes a standard element of prevention science strategies. Animal models should continue to play an important role in pre-clinical testing, with emphasis on safety, pharmacokinetic and efficacy testing.

Construction safety research in the United States: targeting the Hispanic workforce

PubMed Central

Brunette, M

2004-01-01

While it is known that Hispanics have a continuous growing participation in the construction workforce and that their fatal and non-fatal occupational injuries are higher than any other ethnic group, very little construction safety and health research has been conducted in the United States. Research that focuses on safety and health of Hispanic workers employed in the construction industry might prove beneficial in reducing injuries and promoting safe and decent workplaces for all. The purpose of this article was twofold. First, to propose a research agenda where topics such as surveillance, intervention research on high risk occupations, intervention effectiveness evaluation, design and development of effective and appropriate safety training and educational materials, and the socioeconomic impact of injuries and illnesses, are investigated among the Hispanic construction workforce. Second, to present relevant aspects inherent to this particular population that need to be incorporated into the design and development stages of any safety and health research initiative. They include the occupational, social, economic, and cultural background of Hispanic workers; use of a participatory approach, proper selection and use of translation methods; and conducting collaborative research. Certain limitations and challenges related to the availability of resources for conducting safety and health research on Hispanic workers are further discussed. PMID:15314054

Construction safety research in the United States: targeting the Hispanic workforce.

PubMed

Brunette, M J

2004-08-01

While it is known that Hispanics have a continuous growing participation in the construction workforce and that their fatal and non-fatal occupational injuries are higher than any other ethnic group, very little construction safety and health research has been conducted in the United States. Research that focuses on safety and health of Hispanic workers employed in the construction industry might prove beneficial in reducing injuries and promoting safe and decent workplaces for all. The purpose of this article was twofold. First, to propose a research agenda where topics such as surveillance, intervention research on high risk occupations, intervention effectiveness evaluation, design and development of effective and appropriate safety training and educational materials, and the socioeconomic impact of injuries and illnesses, are investigated among the Hispanic construction workforce. Second, to present relevant aspects inherent to this particular population that need to be incorporated into the design and development stages of any safety and health research initiative. They include the occupational, social, economic, and cultural background of Hispanic workers; use of a participatory approach, proper selection and use of translation methods; and conducting collaborative research. Certain limitations and challenges related to the availability of resources for conducting safety and health research on Hispanic workers are further discussed.

Safety profile of a replication-deficient human adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle.

PubMed

Barrera, J; Brake, D A; Kamicker, B J; Purcell, C; Kaptur, R; Schieber, T; Lechtenberg, K; Miller, T D; Ettyreddy, D; Brough, D E; Butman, B T; Colby, M; Neilan, J G

2018-04-01

The safety of a replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was evaluated in five independent safety studies. The target animal safety studies were designed in compliance with United States (U.S.) regulatory requirements (Title 9, U.S. Code of Federal Regulation [9CFR]) and international standard guidelines (VICH Topic GL-44) for veterinary live vaccines. The first three studies were conducted in a total of 22 vaccinees and demonstrated that the AdtA24 master seed virus (MSV) was safe, did not revert to virulence and was not shed or spread from vaccinees to susceptible cattle or pigs. The fourth safety study conducted in 10 lactating cows using an AdtA24 vaccine serial showed that the vaccine was completely absent from milk. The fifth safety study was conducted under typical U.S. production field conditions in 500 healthy beef and dairy cattle using two AdtA24 vaccine serials. These results demonstrated that the vaccine was safe when used per the product label recommendations. Additional data collected during these five studies confirmed that AdtA24 vaccinees developed FMDV A24 and the HAd5 vaccine vector serum neutralization antibodies that test negative in a FMDV non-structural protein antibody test, confirming AdtA24 vaccine's capability to differentiate infected from vaccinated animals (DIVA). In conclusion, results from this comprehensive set of cattle studies demonstrated the safety of the replication-deficient AdtA24 vaccine and fulfilled safety-related requirements for U.S. regulatory requirements. © 2017 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders.

PubMed

Ivachtchenko, Alexandre V; Lavrovsky, Yan; Okun, Ilya

2016-05-25

Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2-2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41-3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer's disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis.

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders

PubMed Central

Ivachtchenko, Alexandre V.; Lavrovsky, Yan; Okun, Ilya

2016-01-01

Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2–2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41–3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer’s disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis. PMID:27232215

Animal Models of Substance Abuse and Addiction: Implications for Science, Animal Welfare, and Society

PubMed Central

Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

2010-01-01

Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models. PMID:20579432

Animal models of substance abuse and addiction: implications for science, animal welfare, and society.

PubMed

Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

2010-06-01

Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.

The spread of zoonoses and other infectious diseases through the international trade of animals and animal products.

PubMed

Seimenis, Aristarhos M

2008-01-01

For trade purposes, ever increasing quantities of food animals and animal products that are transported more rapidly than ever before are contributing to the spread of zoonoses and are creating threats on a permanent basis. Most countries in south-eastern Europe, the Mediterranean and the Middle East are increasing imports of food animals and meat and products of animal origin. They can become potential sources of zoonotic and other infectious diseases if controls are not performed under the most effective conditions. Developing countries with their organisational weakness are particularly vulnerable to fraudulent international trade practices of animals and animal products. To prevent such risks, the World Trade Organization, the World Organisation for Animal Health and their member countries support the measures stipulated in the Sanitary and Phytosanitary Agreement which targets the liberalisation of trade in animals and animal products under specific conditions while protecting public health and national economies. Vigilance must be exercised and appropriate inspection made at points of entry by veterinary and other authorities to ensure the strict implementation of international and national regulations. National legislation, appropriate infrastructures and the respect of international regulations can become barriers to avoid animal trade, contributing to the spread of zoonotic and other infectious diseases.

Therapeutic Gene Editing Safety and Specificity.

PubMed

Lux, Christopher T; Scharenberg, Andrew M

2017-10-01

Therapeutic gene editing is significant for medical advancement. Safety is intricately linked to the specificity of the editing tools used to cut at precise genomic targets. Improvements can be achieved by thoughtful design of nucleases and repair templates, analysis of off-target editing, and careful utilization of viral vectors. Advancements in DNA repair mechanisms and development of new generations of tools improve targeting of specific sequences while minimizing risks. It is important to plot a safe course for future clinical trials. This article reviews safety and specificity for therapeutic gene editing to spur dialogue and advancement. Copyright © 2017 Elsevier Inc. All rights reserved.

A toolkit of measures for reducing animal-vehicle collisions.

DOT National Transportation Integrated Search

2006-01-01

Animal-vehicle collisions are a growing concern in terms of human safety; costs related to injury, property damage, and disposal; and the viability of wildlife populations. These collisions are rapidly increasing throughout the United States, and Vir...

Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review.

PubMed

Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F; Huo, Li-Jun

2017-01-01

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations.

Effect of target animacy on hand preference in Sichuan snub-nosed monkeys (Rhinopithecus roxellana).

PubMed

Zhao, Dapeng; Tian, Xiangling; Liu, Xinchen; Chen, Zhuoyue; Li, Baoguo

2016-09-01

Twenty-eight captive Sichuan snub-nosed monkeys (Rhinopithecus roxellana) were involved in the current study. Many individuals showed handedness, with a modest tendency toward left-hand use especially for animate targets, although no group-level handedness was found. There was no significant gender difference in the direction and strength of hand preference for both targets. Females showed a significantly higher overall rate of actions toward animate targets than inanimate targets for both hands, whereas males displayed almost the reversed pattern. There were no significant interactions between lateral hand use and target animacy for either males or females. Most individuals showed rightward or leftward laterality shift trends between inanimate and animate targets. These findings to some extent support the existence of a potential trend concerning a categorical neural distinction between targets demanding functional manipulation (inanimate objects) and those demanding social manipulation (animate objects), even though specialized hand preference based on target animacy has not been fully established in this arboreal Old World monkey species.

The necessity of animal models in pain research.

PubMed

Mogil, Jeffrey S; Davis, Karen D; Derbyshire, Stuart W

2010-10-01

There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Animal models for microbicide studies

PubMed Central

Veazey, Ronald S.; Shattock, Robin J; Klasse, Per Johan; Moore, John P.

2013-01-01

There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the use of anti-retroviral drugs. However, much work remains to be accomplished before a microbicide becomes a standard element of prevention science strategies. Animal models should continue to play an important role in pre-clinical testing, with emphasis on safety, pharmacokinetic and efficacy testing. PMID:22264049

Measuring Health Information Dissemination and Identifying Target Interest Communities on Twitter: Methods Development and Case Study of the @SafetyMD Network.

PubMed

Kandadai, Venk; Yang, Haodong; Jiang, Ling; Yang, Christopher C; Fleisher, Linda; Winston, Flaura Koplin

2016-05-05

Little is known about the ability of individual stakeholder groups to achieve health information dissemination goals through Twitter. This study aimed to develop and apply methods for the systematic evaluation and optimization of health information dissemination by stakeholders through Twitter. Tweet content from 1790 followers of @SafetyMD (July-November 2012) was examined. User emphasis, a new indicator of Twitter information dissemination, was defined and applied to retweets across two levels of retweeters originating from @SafetyMD. User interest clusters were identified based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) of a random sample of 170 followers. User emphasis of keywords remained across levels but decreased by 9.5 percentage points. PCA and HCA identified 12 statistically unique clusters of followers within the @SafetyMD Twitter network. This study is one of the first to develop methods for use by stakeholders to evaluate and optimize their use of Twitter to disseminate health information. Our new methods provide preliminary evidence that individual stakeholders can evaluate the effectiveness of health information dissemination and create content-specific clusters for more specific targeted messaging.

Investigative safety science as a competitive advantage for Pharma.

PubMed

Moggs, Jonathan; Moulin, Pierre; Pognan, Francois; Brees, Dominique; Leonard, Michele; Busch, Steve; Cordier, Andre; Heard, David J; Kammüller, Michael; Merz, Michael; Bouchard, Page; Chibout, Salah-Dine

2012-09-01

Following a US National Academy of Sciences report in 2007 entitled "Toxicity Testing of the 21st Century: a Vision and a Strategy," significant advances within translational drug safety sciences promise to revolutionize drug discovery and development. The purpose of this review is to outline why investigative safety science is a competitive advantage for the pharmaceutical industry. The article discusses the essential goals for modern investigative toxicologists including: cross-species target biology; molecular pathways of toxicity; and development of predictive tools, models and biomarkers that allow discovery researchers and clinicians to anticipate safety problems and plan ways to address them, earlier than ever before. Furthermore, the article emphasizes the importance of investigating unanticipated clinical safety signals through a combination of mechanistic preclinical studies and/or molecular characterization of clinical samples from affected organs. The traditional boundaries between pharma industry teams focusing on safety/efficacy and preclinical/clinical development are rapidly disappearing in favor of translational safety science-centric organizations with a vision of bringing more effective medicines forward safely and quickly. Comparative biology and mechanistic toxicology approaches facilitate: i) identifying translational safety biomarkers; ii) identifying new drug targets/indications; and iii) mitigating off-target toxicities. These value-adding safety science contributions will change traditional toxicologists from side-effect identifiers to drug development enablers.

Animal research as a basis for clinical trials.

PubMed

Faggion, Clovis M

2015-04-01

Animal experiments are critical for the development of new human therapeutics because they provide mechanistic information, as well as important information on efficacy and safety. Some evidence suggests that authors of animal research in dentistry do not observe important methodological issues when planning animal experiments, for example sample-size calculation. Low-quality animal research directly interferes with development of the research process in which multiple levels of research are interconnected. For example, high-quality animal experiments generate sound information for the further planning and development of randomized controlled trials in humans. These randomized controlled trials are the main source for the development of systematic reviews and meta-analyses, which will generate the best evidence for the development of clinical guidelines. Therefore, adequate planning of animal research is a sine qua non condition for increasing efficacy and efficiency in research. Ethical concerns arise when animal research is not performed with high standards. This Focus article presents the latest information on the standards of animal research in dentistry, more precisely in the field of implant dentistry. Issues on precision and risk of bias are discussed, and strategies to reduce risk of bias in animal research are reported. © 2015 Eur J Oral Sci.

Political incentives towards replacing animal testing in nanotechnology?

PubMed

Sauer, Ursula G

2009-01-01

The Treaty of Lisbon requests the European Union and the Member States to pay full regard to animal welfare issues when implementing new policies. The present article discusses how these provisions are met in the emerging area of nanotechnology. Political action plans in Europe take into account animal welfare issues to some extent. Funding programmes promote the development of non-animal test methods, however only in the area of nanotoxicology and also here not sufficiently to "pay full regard" to preventing animal testing, let alone to bring about a paradigm change in toxicology or in biomedical research as such. Ethical deliberations on nanotechnology, which influence future policies, so far do not address animal welfare at all. Considering that risk assessment of nanoproducts is conceived as a key element to protect human dignity, ethical deliberations should address the choice of the underlying testing methods and call for basing nanomaterial safety testing upon the latest scientific--and ethically acceptable--technologies. Finally, public involvement in the debate on nanotechnology should take into account information on resulting animal experiments.

GPR Imaging of Prehistoric Animal Bone-beds

NASA Astrophysics Data System (ADS)

Schneider, Blair Benson

This research investigates the detection capabilities of Ground-penetrating radar for imaging prehistoric animal bone-beds. The first step of this investigation was to determine the dielectric properties of modern animal bone as a proxy for applying non-invasive ground-penetrating radar (GPR) for detecting prehistoric animal remains. Over 90 thin section samples were cut from four different modern faunal skeleton remains: bison, cow, deer, and elk. One sample of prehistoric mammoth core was also analyzed. Sample dielectric properties (relative permittivity, loss factor, and loss-tangent values) were measured with an impedance analyzer over frequencies ranging from 10 MHz to 1 GHz. The results reveal statistically significant dielectric-property differences among different animal fauna, as well as variation as a function of frequency. The measured sample permittivity values were then compared to modeled sample permittivity values using common dielectric-mixing models. The dielectric mixing models were used to report out new reported values of dry bone mineral of 3-5 in the frequency range of 10 MHz to 1 GHz. The second half of this research collected controlled GPR experiments over a sandbox containing buried bison bone elements to evaluate GPR detection capabilities of buried animal bone. The results of the controlled GPR sandbox tests were then compared to numerical models in order to predict the ability of GPR to detect buried animal bone given a variety of different depositional factors, the size and orientation of the bone target and the degree of bone weathering. The radar profiles show that GPR is an effective method for imaging the horizontal and vertical extent of buried animal bone. However, increased bone weathering and increased bone dip were both found to affect GPR reflection signal strength. Finally, the controlled sandbox experiments were also utilized to investigate the impact of survey design for imaging buried animal bone. In particular, the

Occupational zoonoses in animal husbandry and related activities.

PubMed

Battelli, Giorgio; Baldelli, Raffaella; Ghinzelli, Massimo; Mantovani, Adriano

2006-01-01

The fact that people working with animals or their products may contract some infections has been known for centuries, before the introduction of the concept of zoonoses. Only recently, at least in Italy, was the prevention of occupational risks taken into account by legislation in spite of the fact that some zoonoses of livestock are of noticeable socio-economic importance. Nowadays some factors such as new production technologies, trade globalization, movements of people, changes in working conditions, are generating new zoonotic and occupational risks, some of which are considered re-emerging. The prevention of occupational zoonoses must be implemented jointly by both veterinary and medical services through prevention and epidemiological surveillance of human and animal health, risk evaluation, diagnosis of infections and working safety. Hopefully, we expect that in the future there will be better interdisciplinary collaboration and that legislation be timely tailored to the need to safeguard working health and safety.

The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology.

PubMed

O'Callaghan, T F; Ross, R P; Stanton, C; Clarke, G

2016-07-01

The gut microbiome exerts a marked influence on host physiology, and manipulation of its composition has repeatedly been shown to influence host metabolism and body composition. This virtual endocrine organ also has a role in the regulation of the plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Control over the hypothalamic-pituitary-adrenal axis also appears to be under the influence of the gut microbiota. This is clear from studies in microbiota-deficient germ-free animals with exaggerated responses to psychological stress that can be normalized by monocolonization with certain bacterial species including Bifidobacterium infantis. Therapeutic targeting of the gut microbiota may thus be useful in treating or preventing stress-related microbiome-gut-brain axis disorders and metabolic diseases, much the same way as redirections of metabolopathies can be achieved through more traditional endocrine hormone-based interventions. Moreover, the implications of these findings need to be considered in the context of farm and domestic animal physiology, behavior, and food safety. Copyright © 2016 Elsevier Inc. All rights reserved.

D Animation Reconstruction from Multi-Camera Coordinates Transformation

NASA Astrophysics Data System (ADS)

Jhan, J. P.; Rau, J. Y.; Chou, C. M.

2016-06-01

Reservoir dredging issues are important to extend the life of reservoir. The most effective and cost reduction way is to construct a tunnel to desilt the bottom sediment. Conventional technique is to construct a cofferdam to separate the water, construct the intake of tunnel inside and remove the cofferdam afterwards. In Taiwan, the ZengWen reservoir dredging project will install an Elephant-trunk Steel Pipe (ETSP) in the water to connect the desilting tunnel without building the cofferdam. Since the installation is critical to the whole project, a 1:20 model was built to simulate the installation steps in a towing tank, i.e. launching, dragging, water injection, and sinking. To increase the construction safety, photogrammetry technic is adopted to record images during the simulation, compute its transformation parameters for dynamic analysis and reconstruct the 4D animations. In this study, several Australiscoded targets are fixed on the surface of ETSP for auto-recognition and measurement. The cameras orientations are computed by space resection where the 3D coordinates of coded targets are measured. Two approaches for motion parameters computation are proposed, i.e. performing 3D conformal transformation from the coordinates of cameras and relative orientation computation by the orientation of single camera. Experimental results show the 3D conformal transformation can achieve sub-mm simulation results, and relative orientation computation shows the flexibility for dynamic motion analysis which is easier and more efficiency.

Expert opinions on the acceptance of alternative methods in food safety evaluations: Formulating recommendations to increase acceptance of non-animal methods for kinetics.

PubMed

Punt, Ans; Bouwmeester, Hans; Schiffelers, Marie-Jeanne W A; Peijnenburg, Ad A C M

2018-02-01

Inclusion of alternative methods that replace, reduce, or refine (3R) animal testing within regulatory safety evaluations of chemicals generally faces many hurdles. The goal of the current work is to i) collect responses from key stakeholders involved in food safety evaluations on what they consider the most relevant factors that influence the acceptance and use of 3R methods and to ii) use these responses to formulate activities needed to increase the acceptance and use of 3R methods, particularly for kinetics. The stakeholders were contacted by e-mail for their opinions, asking the respondents to write down three barriers and/or drivers and scoring these by distributing 5 points over the three factors. The main barriers that obtained the highest aggregated scores were i) uncertain predictability 3R methods/lack of validation, ii) insufficient guidance regulators/industry and iii) insufficient harmonization of legislation. The major driver identified was the possibility of 3R methods to provide more mechanistic information. Based on the results, recommendations are given to enhance the acceptance and application of 3R toxicokinetic methods in food safety evaluations. These include steering of regulatory data requirements as well as creating (funding) opportunities for development and validation of alternative methods for kinetics and development of guidances. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Frequency of target crashes for IntelliDrive safety systems

DOT National Transportation Integrated Search

2010-10-01

This report estimates the frequency of different crash types that would potentially be addressed by various categories of Intelligent Transportation Systems as part of the IntelliDriveSM safety systems program. Crash types include light-vehicle crash...

Utility and importance of animal data in drug product labels.

PubMed

Baldrick, Paul

2014-08-01

Information on the use and safety of medicines to assist prescription by healthcare professionals occurs in drug labels (Summary of Product Characteristics in Europe and Package Insert in the USA). Animal data (notably genotoxicity, reproduction toxicity and carcinogenicity and/or repeat dose toxicity testing) comprise an important component of the information (having a vital role in giving assurance that an extensive safety assessment for the medicinal product has occurred) and regulatory guidance is available to help inform on its input into drug labels. However, an evaluation of animal data for the 27 new drugs approved in the USA in 2013 (and the same drugs if available in Europe) shows great variability in detail and level of information presented within and across regions and/or the possibility of confusion on interpretation of some of the presented animal study findings. It is concluded that it may be time to revisit what animal data are presented in drug product labels (although bearing in mind current regional regulatory guidance requirements), not only to allow within and across region consistency on information given but to present it in a way that fully assists healthcare professions when prescribing a medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

Diabetic aggravation of stroke and animal models

PubMed Central

Rehni, Ashish K.; Liu, Allen; Perez-Pinzon, Miguel A.; Dave, Kunjan R.

2017-01-01

Cerebral ischemia in diabetics results in severe brain damage. Different animal models of cerebral ischemia have been used to study the aggravation of ischemic brain damage in the diabetic condition. Since different disease conditions such as diabetes differently affect outcome following cerebral ischemia, the Stroke Therapy Academic Industry Roundtable (STAIR) guidelines recommends use of diseased animals for evaluating neuroprotective therapies targeted to reduce cerebral ischemic damage. The goal of this review is to discuss the technicalities and pros/cons of various animal models of cerebral ischemia currently being employed to study diabetes-related ischemic brain damage. The rational use of such animal systems in studying the disease condition may better help evaluate novel therapeutic approaches for diabetes related exacerbation of ischemic brain damage. PMID:28274862

ASAS Centennial Paper: Developments and future outlook for preharvest food safety.

PubMed

Oliver, S P; Patel, D A; Callaway, T R; Torrence, M E

2009-01-01

The last century of food animal agriculture is a remarkable triumph of scientific research. Knowledge derived through research has resulted in the development and use of new technologies that have increased the efficiency of food production and created a huge animal production and food manufacturing industry capable of feeding the US population while also providing significant quantities of high-quality food for export to other countries. Although the US food supply is among the safest in the world, the US Center for Disease Prevention and Control estimates that 76 million people get sick, more than 300,000 are hospitalized, and 5,000 die each year from foodborne illness. Consequently, preventing foodborne illness and death remains a major public health concern. Challenges to providing a safe, abundant, and nutritious food supply are complex because all aspects of food production, from farm to fork, must be considered. Given the national and international demand and expectations for food safety as well as the formidable challenges of producing and maintaining a safe food supply, food safety research and educational programs have taken on a new urgency. Remarkable progress has been made during the last century. Wisdom from a century of animal agriculture research now includes the realization that on-farm pathogens are intricately associated with animal health and well-being, the production of high-quality food, and profitability. In this review, some of the developments that have occurred over the last few decades are summarized, including types, sources, and concentrations of disease-causing pathogens encountered in food-producing animal environments and their association with food safety; current and future methods to control or reduce foodborne pathogens on the farm; and present and future preharvest food safety research directions. Future scientific breakthroughs will no doubt have a profound impact on animal agriculture and the production of high-quality food

Altered egos: antibiotic effects on food animal microbiomes

USDA-ARS?s Scientific Manuscript database

The human food chain begins with upwards of 1000 species of bacteria that inhabit the intestinal tracts of poultry and livestock. These intestinal denizens are responsible for the health and safety of a major protein source for humans. The use of antibiotics to treat animal diseases was followed b...

A FRAME response to the Draft Report on Alternative (Non-animal) Methods for Cosmetics Testing: Current Status and Future Prospects--2010.

PubMed

Balls, Michael; Clothier, Richard

2010-10-01

This response on behalf of FRAME to the European Commission's consultation on the five chapters of the Draft Report on Alternative (Non-animal) Methods for Cosmetics Testing: Current Status and Future Prospects--2010, is via a Comment in ATLA, rather than via the template supplied by the Commission. This is principally so that a number of general points about cosmetic ingredient testing can be made. It is concluded that the five draft chapters do not provide a credible basis for the Commission's forthcoming report to the European Parliament and the European Council on the five cosmetic ingredient safety issues for which the 7th Amendment to the Cosmetic Directive's ban on animal testing was postponed until 2013. This is mainly because there is insufficient focus in the draft chapters on the specific nature of cosmetic ingredients, their uses, their local effects and metabolism at their sites of application, and, in particular, on whether their possible absorption into the body would be likely to lead to their accumulation in target sites at levels approaching Thresholds of Toxicological Concern. Meanwhile, there continues to be uncertainty about how the provisions of the Cosmetics Directive should be applied, given the requirements of the REACH system and directives concerned with the safety of other chemicals and products. © 2010 FRAME.

Improvement of the performance of animal crossing warning signs.

PubMed

Khalilikhah, Majid; Heaslip, Kevin

2017-09-01

Animal-vehicle collisions (AVCs) can result in serious injury and death to drivers, animals' death, and significant economic costs. However, the cost effectiveness of the majority of AVC mitigation measures is a significant issue. A mobile-based data collection effort was deployed to measure signs under the Utah Department of Transportation's (UDOT) jurisdiction. The crash data were obtained from the UDOT risk management database. ArcGIS was employed to link these two data sets and extract animal-related crashes and signs. An algorithm was developed to process the data and identify AVCs that occurred within sign recognition distance. Kernel density estimation (KDE) technique was applied to identify potential crash hotspots. Only 2% of AVCs occurred within the recognition distance of animal crossing signs. Almost 58% of animal-related crashes took place on the Interstate and U.S. highways, wherein only 30% of animal crossing signs were installed. State routes with a higher average number of signs experienced a lower number of AVCs per mile. The differences between AVCs that occurred within versus outside of sign recognition distance were not statistically significant regarding crash severity, time of crash, weather condition, driver age, vehicle speed, and type of animal. It is more likely that drivers become accustomed to deer crossing signs than cow signs. Based on the historical crash data and landscape structure, with attention given to the low cost safety improvement methods, a combination of different types of AVC mitigation measures can be developed to reduce the number of animal-related crashes. After an in-depth analysis of AVC data, warning traffic signs, coupled with other low cost mitigation countermeasures can be successfully placed in areas with higher priority or in critical areas. Practical applications: The findings of this study assist transportation agencies in developing more efficient mitigation measures against AVCs. Copyright © 2017 National

IIKmTA: Inter and Intra Kingdom miRNA-Target Analyzer.

PubMed

Mal, Chittabrata; Aftabuddin, Md; Kundu, Sudip

2018-03-16

Growing evidences suggest that microRNAs (miRNAs) can efficiently regulate gene expression at intracellular and extracellular levels. It has been previously reported that plant/food-derived miRNAs are highly enriched in human serum or serum from phytophagous animals, and they are responsible for regulating mammalian gene expression. Thus, miRNAs could function as active signaling molecules, which carry information across distinct species or even kingdoms. However, the mode of miRNA shuttling among various organisms is still a mystery to unravel. The intra and inter kingdom miRNA transfer has boosted up the hypothesis about the potential impact of plant or animal miRNAs on each other. To our knowledge, the software for analyzing cross-kingdom miRNA-targets is lacking. We have developed a web-tool "IIKmTA: Inter and Intra Kingdom miRNA-Target Analyzer" utilizing a database; the data of which have been collected from another web server. Here, user can analyze the targeting potential of (i) plant miRNAs on animal UTRs (Untranslated regions), and vice versa (i.e., inter kingdom), (ii) plant miRNAs on plant UTRs and animal miRNAs on animal UTRs (i.e., intra kingdom). Further, user can analyze (i) miRNAs to targets, (ii) targets to miRNAs, and (iii) miRNA sets targeting sets of targets. For a wide variety of animal and plant species, IIKmTA can identify the miRNA binding sites in the probable target UTRs. Moreover, GC% and AU% of miRNAs will be calculated. All the results can be saved as .csv file. Recent researches identified miRNAs in plants and human secretions and their role in regulating the human genes. Such findings indicate the therapeutic role of secretory miRNAs of such plants which exhibits medicinal value and in near future many diseases may be treated by consumption of these plant miRNAs through food. Using our newly developed database and analyzing tool, one can easily determine the different relationships between miRNAs and their targets across kingdoms

Use of animals in the development and control of viral vaccines.

PubMed

Minor, P D

1996-01-01

Animal models were central to the development of poliovaccines and remain essential in some form in the routine quality control of both live and killed vaccines. The necessity of an animal model is illustrated by the examples of mumps and measles vaccines where the existing materials, while satisfactory, have a number of drawbacks and where changes in current practice raise concerns for safety and efficacy.

Animal and non-animal experiments in nanotechnology - the results of a critical literature survey.

PubMed

Sauer, Ursula G

2009-01-01

A literature survey funded by the Foundation Animalfree Research was performed to obtain an overview on animal experiments in nanotechnology. Scientific articles from Germany, France, the United Kingdom, Italy, the Netherlands and Switzerland published between 2004 and 2007 were collected. A total of 164 articles was retrieved covering in vivo nanotechnological research. The majority of animal experiments were conducted in "nanomedicine", i.e. nanotechnology in the health care area, to study targeted drug, vaccine or gene delivery. Further areas of research relate to nanotechnology-based imaging technologies, the toxicity of nanomaterials, tissue engineering for regenerative treatments, and magnetic tumour thermotherapy. Many experiments were classified as moderately and even severely distressful to the animals. Due to the significance of the scientific topics pursued, the possible scientific benefit of the research depicted in the articles is also assigned to be moderate to high. Nevertheless, it has to be asked whether such animal experiments are truly the only means to answer the scientific questions addressed in nanotechnology. An overview on non-animal test methods used in nanotechnological research revealed a broad spectrum of methodologies applied in a broad spectrum of scientific areas, including those for which animal experiments are being performed. Explicit incentives to avoid animal experiments in nanotechnology currently can only be found in the area of nanotoxicology, but not in the area of nanomedicine. From the point of view of animal welfare, not least because of the new technologies that arise due to nanotechnology, it is time for a paradigm change both in fundamental and applied biomedical research to found research strategies on non-animal test methods.

Food safety and organic meats.

PubMed

Van Loo, Ellen J; Alali, Walid; Ricke, Steven C

2012-01-01

The organic meat industry in the United States has grown substantially in the past decade in response to consumer demand for nonconventionally produced products. Consumers are often not aware that the United States Department of Agriculture (USDA) organic standards are based only on the methods used for production and processing of the product and not on the product's safety. Food safety hazards associated with organic meats remain unclear because of the limited research conducted to determine the safety of organic meat from farm-to-fork. The objective of this review is to provide an overview of the published results on the microbiological safety of organic meats. In addition, antimicrobial resistance of microbes in organic food animal production is addressed. Determining the food safety risks associated with organic meat production requires systematic longitudinal studies that quantify the risks of microbial and nonmicrobial hazards from farm-to-fork.

Why the Eurocontrol Safety Regulation Commission Policy on Safety Nets and Risk Assessment is Wrong

NASA Astrophysics Data System (ADS)

Brooker, Peter

2004-05-01

Current Eurocontrol Safety Regulation Commission (SRC) policy says that the Air Traffic Management (ATM) system (including safety minima) must be demonstrated through risk assessments to meet the Target Level of Safety (TLS) without needing to take safety nets (such as Short Term Conflict Alert) into account. This policy is wrong. The policy is invalid because it does not build rationally and consistently from ATM's firm foundations of TLS and hazard analysis. The policy is bad because it would tend to retard safety improvements. Safety net policy must rest on a clear and rational treatment of integrated ATM system safety defences. A new safety net policy, appropriate to safe ATM system improvements, is needed, which recognizes that safety nets are an integrated part of ATM system defences. The effects of safety nets in reducing deaths from mid-air collisions should be fully included in hazard analysis and safety audits in the context of the TLS for total system design.

'Next-Generation' Surveillance: An Epidemiologists' Perspective on the Use of Molecular Information in Food Safety and Animal Health Decision-Making.

PubMed

Muellner, P; Stärk, K D C; Dufour, S; Zadoks, R N

2016-08-01

Advances in the availability and affordability of molecular and genomic data are transforming human health care. Surveillance aimed at supporting and improving food safety and animal health is likely to undergo a similar transformation. We propose a definition of 'molecular surveillance' in this context and argue that molecular data are an adjunct to rather than a substitute for sound epidemiological study and surveillance design. Specific considerations with regard to sample collection are raised, as is the importance of the relation between the molecular clock speed of genetic markers and the spatiotemporal scale of the surveillance activity, which can be control- or strategy-focused. Development of standards for study design and assessment of molecular surveillance system attributes is needed, together with development of an interdisciplinary skills base covering both molecular and epidemiological principles. © 2015 Blackwell Verlag GmbH.

Animal models of sarcoidosis.

PubMed

Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

2017-03-01

Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

Alternatives to antibiotics: a symposium on the challenges and solutions for animal production.

PubMed

Seal, Bruce S; Lillehoj, Hyun S; Donovan, David M; Gay, Cyril G

2013-06-01

Antibiotics are one of the most important medical discoveries of the 20th century and will remain an essential tool for treating animal and human diseases in the 21st century. However, antibiotic resistance among bacterial pathogens and concerns over their extensive use in food animals has garnered global interest in limiting antibiotic use in animal agriculture. Yet, limiting the availability of medical interventions to prevent and control animal diseases on the farm will directly impact global food security and safety as well as animal and human health. Insufficient attention has been given to the scientific breakthroughs and novel technologies that provide alternatives to antibiotics. The objectives of the symposium 'Alternatives to Antibiotics' were to highlight promising research results and novel technologies that could potentially lead to alternatives to conventional antibiotics, and assess challenges associated with their commercialization, and provide actionable strategies to support development of alternative antimicrobials. The symposium focused on the latest scientific breakthroughs and technologies that could provide new options and alternative strategies for preventing and treating diseases of animals. Some of these new technologies have direct applications as medical interventions for human health, but the focus of the symposium was animal production, animal health and food safety during food-animal production. Five subject areas were explored in detail through scientific presentations and expert panel discussions, including: (1) alternatives to antibiotics, lessons from nature; (2) immune modulation approaches to enhance disease resistance and to treat animal diseases; (3) gut microbiome and immune development, health and diseases; (4) alternatives to antibiotics for animal production; and (5) regulatory pathways to enable the licensure of alternatives to antibiotics.

[Reduction of animal experiments in experimental drug testing].

PubMed

Behrensdorf-Nicol, H; Krämer, B

2014-10-01

In order to ensure the quality of biomedical products, an experimental test for every single manufactured batch is required for many products. Especially in vaccine testing, animal experiments are traditionally used for this purpose. For example, efficacy is often determined via challenge experiments in laboratory animals. Safety tests of vaccine batches are also mostly performed using laboratory animals. However, many animal experiments have clear inherent disadvantages (low accuracy, questionable transferability to humans, unclear significance). Furthermore, for ethical reasons and animal welfare aspects animal experiments are also seen very critical by the public. Therefore, there is a strong trend towards replacing animal experiments with methods in which no animals are used ("replacement"). If a replacement is not possible, the required animal experiments should be improved in order to minimize the number of animals necessary ("reduction") and to reduce pain and suffering caused by the experiment to a minimum ("refinement"). This "3R concept" is meanwhile firmly established in legislature. In recent years many mandatory animal experiments have been replaced by alternative in vitro methods or improved according to the 3R principles; numerous alternative methods are currently under development. Nevertheless, the process from the development of a new method to its legal implementation takes a long time. Therefore, supplementary regulatory measures to facilitate validation and acceptance of new alternative methods could contribute to a faster and more consequent implementation of the 3R concept in the testing of biomedical products.

Teaching with Toys: Using Stuffed Animals as Teaching Tools in Head Start Classrooms.

ERIC Educational Resources Information Center

LeMasurier, Beth

1998-01-01

Stuffed animals provide comfort and security to children, and many Head Start teachers are putting this knowledge to work in the classroom. This article shows how to incorporate stuffed animals and puppets into the Head Start curriculum to help children deal with conflict resolution, separation anxiety, grief and loss, safety, and cultural…

Targeting therapeutics to the glomerulus with nanoparticles.

PubMed

Zuckerman, Jonathan E; Davis, Mark E

2013-11-01

Nanoparticles are an enabling technology for the creation of tissue-/cell-specific therapeutics that have been investigated extensively as targeted therapeutics for cancer. The kidney, specifically the glomerulus, is another accessible site for nanoparticle delivery that has been relatively overlooked as a target organ. Given the medical need for the development of more potent, kidney-targeted therapies, the use of nanoparticle-based therapeutics may be one such solution to this problem. Here, we review the literature on nanoparticle targeting of the glomerulus. Specifically, we provide a broad overview of nanoparticle-based therapeutics and how the unique structural characteristics of the glomerulus allow for selective, nanoparticle targeting of this area of the kidney. We then summarize literature examples of nanoparticle delivery to the glomerulus and elaborate on the appropriate nanoparticle design criteria for glomerular targeting. Finally, we discuss the behavior of nanoparticles in animal models of diseased glomeruli and review examples of nanoparticle therapeutic approaches that have shown promise in animal models of glomerulonephritic disease. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity.

PubMed

Amacher, David E

2010-05-15

Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in

Integration of optical imaging with a small animal irradiator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weersink, Robert A., E-mail: robert.weersink@rmp.uhn.on.ca; Ansell, Steve; Wang, An

Purpose: The authors describe the integration of optical imaging with a targeted small animal irradiator device, focusing on design, instrumentation, 2D to 3D image registration, 2D targeting, and the accuracy of recovering and mapping the optical signal to a 3D surface generated from the cone-beam computed tomography (CBCT) imaging. The integration of optical imaging will improve targeting of the radiation treatment and offer longitudinal tracking of tumor response of small animal models treated using the system. Methods: The existing image-guided small animal irradiator consists of a variable kilovolt (peak) x-ray tube mounted opposite an aSi flat panel detector, both mountedmore » on a c-arm gantry. The tube is used for both CBCT imaging and targeted irradiation. The optical component employs a CCD camera perpendicular to the x-ray treatment/imaging axis with a computer controlled filter for spectral decomposition. Multiple optical images can be acquired at any angle as the gantry rotates. The optical to CBCT registration, which uses a standard pinhole camera model, was modeled and tested using phantoms with markers visible in both optical and CBCT images. Optically guided 2D targeting in the anterior/posterior direction was tested on an anthropomorphic mouse phantom with embedded light sources. The accuracy of the mapping of optical signal to the CBCT surface was tested using the same mouse phantom. A surface mesh of the phantom was generated based on the CBCT image and optical intensities projected onto the surface. The measured surface intensity was compared to calculated surface for a point source at the actual source position. The point-source position was also optimized to provide the closest match between measured and calculated intensities, and the distance between the optimized and actual source positions was then calculated. This process was repeated for multiple wavelengths and sources. Results: The optical to CBCT registration error was 0.8 mm. Two

Testing of Safety-Critical Software Embedded in an Artificial Heart

NASA Astrophysics Data System (ADS)

Cha, Sungdeok; Jeong, Sehun; Yoo, Junbeom; Kim, Young-Gab

Software is being used more frequently to control medical devices such as artificial heart or robotic surgery system. While much of software safety issues in such systems are similar to other safety-critical systems (e.g., nuclear power plants), domain-specific properties may warrant development of customized techniques to demonstrate fitness of the system on patients. In this paper, we report results of a preliminary analysis done on software controlling a Hybrid Ventricular Assist Device (H-VAD) developed by Korea Artificial Organ Centre (KAOC). It is a state-of-the-art artificial heart which completed animal testing phase. We performed software testing in in-vitro experiments and animal experiments. An abnormal behaviour, never detected during extensive in-vitro analysis and animal testing, was found.

Development of an algorithm for assessing the risk to food safety posed by a new animal disease.

PubMed

Parker, E M; Jenson, I; Jordan, D; Ward, M P

2012-05-01

An algorithm was developed as a tool to rapidly assess the potential for a new or emerging disease of livestock to adversely affect humans via consumption or handling of meat product, so that the risks and uncertainties can be understood and appropriate risk management and communication implemented. An algorithm describing the sequence of events from occurrence of the disease in livestock, release of the causative agent from an infected animal, contamination of fresh meat and then possible adverse effects in humans following meat handling and consumption was created. A list of questions complements the algorithm to help the assessors address the issues of concern at each step of the decision pathway. The algorithm was refined and validated through consultation with a panel of experts and a review group of animal health and food safety policy advisors via five case studies of potential emerging diseases of cattle. Tasks for model validation included describing the path taken in the algorithm and stating an outcome. Twenty-nine per cent of the 62 experts commented on the model, and one-third of those responding also completed the tasks required for model validation. The feedback from the panel of experts and the review group was used to further develop the tool and remove redundancies and ambiguities. There was agreement in the pathways and assessments for diseases in which the causative agent was well understood (for example, bovine pneumonia due to Mycoplasma bovis). The stated pathways and assessments of other diseases (for example, bovine Johne's disease) were not as consistent. The framework helps to promote objectivity by requiring questions to be answered sequentially and providing the opportunity to record consensus or differences of opinion. Areas for discussion and future investigation are highlighted by the points of diversion on the pathway taken by different assessors. © 2011 Blackwell Verlag GmbH.

Stochastic modelling of animal movement.

PubMed

Smouse, Peter E; Focardi, Stefano; Moorcroft, Paul R; Kie, John G; Forester, James D; Morales, Juan M

2010-07-27

Modern animal movement modelling derives from two traditions. Lagrangian models, based on random walk behaviour, are useful for multi-step trajectories of single animals. Continuous Eulerian models describe expected behaviour, averaged over stochastic realizations, and are usefully applied to ensembles of individuals. We illustrate three modern research arenas. (i) Models of home-range formation describe the process of an animal 'settling down', accomplished by including one or more focal points that attract the animal's movements. (ii) Memory-based models are used to predict how accumulated experience translates into biased movement choices, employing reinforced random walk behaviour, with previous visitation increasing or decreasing the probability of repetition. (iii) Lévy movement involves a step-length distribution that is over-dispersed, relative to standard probability distributions, and adaptive in exploring new environments or searching for rare targets. Each of these modelling arenas implies more detail in the movement pattern than general models of movement can accommodate, but realistic empiric evaluation of their predictions requires dense locational data, both in time and space, only available with modern GPS telemetry.

Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology.

PubMed

Roberts, Stanley A; Andrews, Paul A; Blanset, Diann; Flagella, Kelly M; Gorovits, Boris; Lynch, Carmel M; Martin, Pauline L; Kramer-Stickland, Kimberly; Thibault, Stephane; Warner, Garvin

2013-12-01

Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities to enable first-in-human (FIH) studies. Specific discussions are also included that provide details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. Copyright © 2013 Elsevier Inc. All rights reserved.

Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env protein

PubMed Central

Curtin, François; Perron, Hervé; Kromminga, Arno; Porchet, Hervé; Lang, Alois B

2015-01-01

Monoclonal antibodies (mAbs) play an increasing important role in the therapeutic armamentarium against multiple sclerosis (MS), an inflammatory and degenerative disorder of the central nervous system. Most of the mAbs currently developed for MS are immunomodulators blocking the inflammatory immune process. In contrast with mAbs targeting immune function, GNbAC1, a humanized IgG4 mAb, targets the multiple sclerosis associated retrovirus envelope (MSRV-Env) protein, an upstream factor in the pathophysiology of MS. MSRV-Env protein is of endogenous retroviral origin, expressed in MS brain lesions, and it is pro-inflammatory and toxic to the remyelination process, by preventing the differentiation of oligodendrocyte precursor cells. We present the preclinical and early clinical development results of GNbAC1. The specificity of GNbAC1 for its endogenous retroviral target is described. Efficacy of different mAb versions of GNbAC1 were assessed in MSRV-Env induced experimental allergic encephalitis (EAE), an animal model of MS. Because the target MSRV-Env is not expressed in animals, no relevant animal model exists for a proper in vivo toxicological program. An off-target 2-week toxicity study in mice was thus performed, and it showed an absence of safety risk. Additional in vitro analyses showed an absence of complement or antibody-dependent cytotoxicity as well as a low level of cross-reactivity to human tissues. The first-in-man clinical study in 33 healthy subjects and a long-term clinical study in 10 MS patients showed that GNbAC1 is well tolerated in humans without induction of immunogenicity and that it induces a pharmacodynamic response on MSRV biomarkers. These initial results suggest that the mAb GNbAC1 could be a safe long-term treatment for patients with MS with a unique therapeutic mechanism of action. PMID:25427053

Development and dosimetry of a small animal lung irradiation platform

PubMed Central

McGurk, Ross; Hadley, Caroline; Jackson, Isabel L.; Vujaskovic, Zeljko

2015-01-01

Advances in large scale screening of medical counter measures for radiation-induced normal tissue toxicity are currently hampered by animal irradiation paradigms that are both inefficient and highly variable among institutions. Here, we introduce a novel high-throughput small animal irradiation platform for use in orthovoltage small animal irradiators. We used radiochromic film and metal oxide semiconductor field effect transistor detectors to examine several parameters, including 2D field uniformity, dose rate consistency, and shielding transmission. We posit that this setup will improve efficiency of drug screens by allowing for simultaneous, targeted irradiation of multiple animals, improving efficiency within a single institution. Additionally, we suggest that measurement of the described parameters in all centers conducting counter measure studies will improve the translatability of findings among institutions. We also investigated the use of tissue equivalent phantoms in performing dosimetry measurements for small animal irradiation experiments. Though these phantoms are commonly used in dosimetry, we recorded a significant difference in both the entrance and target tissue dose rates between euthanized rats and mice with implanted detectors and the corresponding phantom measurement. This suggests that measurements using these phantoms may not provide accurate dosimetry for in vivo experiments. Based on these measurements, we propose that this small animal irradiation platform can increase the capacity of animal studies by allowing for more efficient animal irradiation. We also suggest that researchers fully characterize the parameters of whatever radiation setup is in use in order to facilitate better comparison among institutions. PMID:23091878

Animal welfare towards sustainability in pork meat production.

PubMed

Velarde, Antonio; Fàbrega, Emma; Blanco-Penedo, Isabel; Dalmau, Antoni

2015-11-01

Animal welfare is an important pillar of sustainability in meat production and is associated with other aspects of this concept, such as animal health, productivity, food safety, food quality and efficiency from a cost of production perspective. These interactions are present at all stages of the production cycle, from the beginning of the animals' farm life until their slaughter. On farm, some of the main welfare issues are related to neonatal mortality and low level of sensory input, which are likely to engender stereotypes and injurious behaviours, such as tail-biting. Pre-slaughter handling refers to the interaction between humans and animals prior to and during transport and at slaughter. Strategies to reduce pre-slaughter stress will benefit carcass and meat quality, being the training of stockpeople one of the most cost-effective policies to improve animal welfare. These strategies include also the implementation of standard monitoring procedures to detect signs of consciousness after stunning, before sticking and during bleeding until death occurs. Copyright © 2015 Elsevier Ltd. All rights reserved.

The use of pre- and probiotics to improve food safety in the live animal

USDA-ARS?s Scientific Manuscript database

Too many foodborne illnesses happen around the world and are linked to the consumption of meat or contact with animals or their feces. Strategies to reduce these pathogen levels in food animals include the use of probiotics, prebiotics, and competitive exclusion cultures. These products all utiliz...

Colorado animal-based plague surveillance systems: relationships between targeted animal species and prediction efficacy of areas at risk for humans.

PubMed

Lowell, Jennifer L; Eisen, Rebecca J; Schotthoefer, Anna M; Xiaocheng, Liang; Montenieri, John A; Tanda, Dale; Pape, John; Schriefer, Martin E; Antolin, Michael F; Gage, Kenneth L

2009-06-01

Human plague risks (Yersinia pestis infection) are greatest when epizootics cause high mortality among this bacterium's natural rodent hosts. Therefore, health departments in plague-endemic areas commonly establish animal-based surveillance programs to monitor Y. pestis infection among plague hosts and vectors. The primary objectives of our study were to determine whether passive animal-based plague surveillance samples collected in Colorado from 1991 to 2005 were sampled from high human plague risk areas and whether these samples provided information useful for predicting human plague case locations. By comparing locations of plague-positive animal samples with a previously constructed GIS-based plague risk model, we determined that the majority of plague-positive Gunnison's prairie dogs (100%) and non-prairie dog sciurids (85.82%), and moderately high percentages of sigmodontine rodents (71.4%), domestic cats (69.3%), coyotes (62.9%), and domestic dogs (62.5%) were recovered within 1 km of the nearest area posing high peridomestic risk to humans. In contrast, the majority of white-tailed prairie dog (66.7%), leporid (cottontailed and jack rabbits) (71.4%), and black-tailed prairie dog (93.0%) samples originated more than 1 km from the nearest human risk habitat. Plague-positive animals or their fleas were rarely (one of 19 cases) collected within 2 km of a case exposure site during the 24 months preceding the dates of illness onset for these cases. Low spatial accuracy for identifying epizootic activity prior to human plague cases suggested that other mammalian species or their fleas are likely more important sources of human infection in high plague risk areas. To address this issue, epidemiological observations and multi-locus variable number tandem repeat analyses (MLVA) were used to preliminarily identify chipmunks as an under-sampled, but potentially important, species for human plague risk in Colorado.

The Impact of an Integrated Program of Return-to-Field and Targeted Trap-Neuter-Return on Feline Intake and Euthanasia at a Municipal Animal Shelter

PubMed Central

Spehar, Daniel D.; Wolf, Peter J.

2018-01-01

Simple Summary Dramatic declines in the number of cats admitted to and euthanized at U.S. shelters have taken place in recent decades. Still, millions of cats, many of them free-roaming, enter shelters each year. At some facilities, as many as 70% of feline admissions are euthanized, and it is estimated that, nationally, up to one million or more cats are euthanized each year. New approaches, including return-to-field (RTF) and targeted trap-neuter-return (TNR) appear to have transformative potential. The present study examines changes in feline intake and euthanasia, as well as impacts on associated metrics, at a municipal animal shelter in Albuquerque, New Mexico, after formal RTF and targeted TNR protocols, collectively referred to as a community cat program (CCP), were added to ongoing community-based TNR efforts and a pilot RTF initiative. As part of the three-year CCP, 11,746 cats were trapped, sterilized, vaccinated and returned or adopted. Feline euthanasia at the Albuquerque Animal Welfare Department (AAWD) declined by 84.1% and feline intake dropped by 37.6%; the live release rate (LRR) increased by 47.7% due primarily to these reductions in both intake and euthanasia. Modest increases in the percentage of cats returned to owner (RTO) and the adoption rate were also observed, although both metrics decreased on an absolute basis, while the number of calls to the city about dead cats declined. Abstract Available evidence indicates that overall levels of feline intake and euthanasia at U.S. shelters have significantly declined in recent decades. Nevertheless, millions of cats, many of them free-roaming, continue to be admitted to shelters each year. In some locations, as many as 70% of cats, perhaps up to one million or more per year nationally, are euthanized. New approaches, including return-to-field (RTF) and targeted trap-neuter-return (TNR) appear to have transformative potential. The purpose of the present study was to examine changes in feline intake

Revisiting the safety of aspartame.

PubMed

Choudhary, Arbind Kumar; Pretorius, Etheresia

2017-09-01

Aspartame is a synthetic dipeptide artificial sweetener, frequently used in foods, medications, and beverages, notably carbonated and powdered soft drinks. Since 1981, when aspartame was first approved by the US Food and Drug Administration, researchers have debated both its recommended safe dosage (40 mg/kg/d) and its general safety to organ systems. This review examines papers published between 2000 and 2016 on both the safe dosage and higher-than-recommended dosages and presents a concise synthesis of current trends. Data on the safe aspartame dosage are controversial, and the literature suggests there are potential side effects associated with aspartame consumption. Since aspartame consumption is on the rise, the safety of this sweetener should be revisited. Most of the literature available on the safety of aspartame is included in this review. Safety studies are based primarily on animal models, as data from human studies are limited. The existing animal studies and the limited human studies suggest that aspartame and its metabolites, whether consumed in quantities significantly higher than the recommended safe dosage or within recommended safe levels, may disrupt the oxidant/antioxidant balance, induce oxidative stress, and damage cell membrane integrity, potentially affecting a variety of cells and tissues and causing a deregulation of cellular function, ultimately leading to systemic inflammation. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hyperspectral small animal fluorescence imaging: spectral selection imaging

NASA Astrophysics Data System (ADS)

Leavesley, Silas; Jiang, Yanan; Patsekin, Valery; Hall, Heidi; Vizard, Douglas; Robinson, J. Paul

2008-02-01

Molecular imaging is a rapidly growing area of research, fueled by needs in pharmaceutical drug-development for methods for high-throughput screening, pre-clinical and clinical screening for visualizing tumor growth and drug targeting, and a growing number of applications in the molecular biology fields. Small animal fluorescence imaging employs fluorescent probes to target molecular events in vivo, with a large number of molecular targeting probes readily available. The ease at which new targeting compounds can be developed, the short acquisition times, and the low cost (compared to microCT, MRI, or PET) makes fluorescence imaging attractive. However, small animal fluorescence imaging suffers from high optical scattering, absorption, and autofluorescence. Much of these problems can be overcome through multispectral imaging techniques, which collect images at different fluorescence emission wavelengths, followed by analysis, classification, and spectral deconvolution methods to isolate signals from fluorescence emission. We present an alternative to the current method, using hyperspectral excitation scanning (spectral selection imaging), a technique that allows excitation at any wavelength in the visible and near-infrared wavelength range. In many cases, excitation imaging may be more effective at identifying specific fluorescence signals because of the higher complexity of the fluorophore excitation spectrum. Because the excitation is filtered and not the emission, the resolution limit and image shift imposed by acousto-optic tunable filters have no effect on imager performance. We will discuss design of the imager, optimizing the imager for use in small animal fluorescence imaging, and application of spectral analysis and classification methods for identifying specific fluorescence signals.

Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo.

PubMed

Altenburg, Arwen F; van de Sandt, Carolien E; Li, Bobby W S; MacLoughlin, Ronan J; Fouchier, Ron A M; van Amerongen, Geert; Volz, Asisa; Hendriks, Rudi W; de Swart, Rik L; Sutter, Gerd; Rimmelzwaan, Guus F; de Vries, Rory D

2017-08-17

Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies.

Toxicity of Nanoparticles on the Reproductive System in Animal Models: A Review

PubMed Central

Brohi, Rahim Dad; Wang, Li; Talpur, Hira Sajjad; Wu, Di; Khan, Farhan Anwar; Bhattarai, Dinesh; Rehman, Zia-Ur; Farmanullah, F.; Huo, Li-Jun

2017-01-01

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, fetal development, and the female reproductive system. These impacts are associated with nanoparticle modification, composition, concentration, route of administration, and the species of the animal. Therefore, understanding the impacts of nanoparticles on animal growth and reproduction is essential. Many studies have examined the effects of nanoparticles on primary and secondary target organs, with a concentration on the in vivo and in vitro effects of nanoparticles on the male and female reproductive systems at the clinical, cellular, and molecular levels. This review provides important information regarding organism safety and the potential hazards of nanoparticle use and supports the application of nanotechnologies by minimizing the adverse effects of nanoparticles in vulnerable populations. PMID:28928662

Animal-Assisted Interventions in the Classroom-A Systematic Review.

PubMed

Brelsford, Victoria L; Meints, Kerstin; Gee, Nancy R; Pfeffer, Karen

2017-06-22

The inclusion of animals in educational practice is becoming increasingly popular, but it is unclear how solid the evidence for this type of intervention is. The aim of this systematic review is to scrutinise the empirical research literature relating to animal-assisted interventions conducted in educational settings. The review included 25 papers; 21 from peer-reviewed journals and 4 obtained using grey literature databases. Most studies reported significant benefits of animal-assisted interventions in the school setting. Despite this, studies vary greatly in methods and design, in intervention types, measures, and sample sizes, and in the length of time exposed to an animal. Furthermore, a worrying lack of reference to risk assessment and animal welfare must be highlighted. Taken together, the results of this review show promising findings and emerging evidence suggestive of potential benefits related to animals in school settings. The review also indicates the need for a larger and more robust evidence base driven by thorough and strict protocols. The review further emphasises the need for safeguarding for all involved-welfare and safety are paramount.

Animal Models of Tick-Borne Hemorrhagic Fever Viruses

PubMed Central

Zivcec, Marko; Safronetz, David; Feldmann, Heinz

2013-01-01

Tick-borne hemorrhagic fever viruses (TBHFV) are detected throughout the African and Eurasian continents and are an emerging or re-emerging threat to many nations. Due to the largely sporadic incidences of these severe diseases, information on human cases and research activities in general have been limited. In the past decade, however, novel TBHFVs have emerged and areas of endemicity have expanded. Therefore, the development of countermeasures is of utmost importance in combating TBHFV as elimination of vectors and interrupting enzootic cycles is all but impossible and ecologically questionable. As in vivo models are the only way to test efficacy and safety of countermeasures, understanding of the available animal models and the development and refinement of animal models is critical in negating the detrimental impact of TBHFVs on public and animal health. PMID:25437041

Zoonoses of occupational health importance in contemporary laboratory animal research.

PubMed

Hankenson, F Claire; Johnston, Nancy A; Weigler, Benjamin J; Di Giacomo, Ronald F

2003-12-01

In contemporary laboratory animal facilities, workplace exposure to zoonotic pathogens, agents transmitted to humans from vertebrate animals or their tissues, is an occupational hazard. The primary (e.g., macaques, pigs, dogs, rabbits, mice, and rats) and secondary species (e.g., sheep, goats, cats, ferrets, and pigeons) of animals commonly used in biomedical research, as classified by the American College of Laboratory Animal Medicine, are established or potential hosts for a large number of zoonotic agents. Diseases included in this review are principally those wherein a risk to biomedical facility personnel has been documented by published reports of human cases in laboratory animal research settings, or under reasonably similar circumstances. Diseases are listed alphabetically, and each section includes information about clinical disease, transmission, occurrence, and prevention in animal reservoir species and humans. Our goal is to provide a resource for veterinarians, health-care professionals, technical staff, and administrators that will assist in the design and on-going evaluation of institutional occupational health and safety programs.

History of the Animal Care Program at Johnson Space Center

NASA Technical Reports Server (NTRS)

Khan-Mayberry, Noreen; Bassett, Stephanie

2010-01-01

NASA has a rich history of scientific research that has been conducted throughout our numerous manned spaceflight programs. This scientific research has included animal test subjects participating in various spaceflight missions, including most recently, Space Shuttle mission STS-131. The Animal Care Program at Johnson Space Center (JSC) in Houston, Texas is multi-faceted and unique in scope compared to other centers within the agency. The animal care program at JSC has evolved from strictly research to include a Longhorn facility and the Houston Zoo's Attwater Prairie Chicken refuge, which is used to help repopulate this endangered species. JSC is home to more than 300 species of animals including home of hundreds of white-tailed deer that roam freely throughout the center which pose unique issues in regards to population control and safety of NASA workers, visitors and tourists. We will give a broad overview of our day to day operations, animal research, community outreach and protection of animals at NASA Johnson Space Center.

ANIMAL BEHAVIOR AND WELL-BEING SYMPOSIUM: The Common Swine Industry Audit: Future steps to assure positive on-farm animal welfare utilizing validated, repeatable and feasible animal-based measures.