Integrating guideline development and implementation: analysis of guideline development manual instructions for generating implementation advice

Directory of Open Access Journals (Sweden)

Gagliardi Anna R

2012-07-01

Full Text Available Abstract Background Guidelines are important tools that inform healthcare delivery based on best available research evidence. Guideline use is in part based on quality of the guidelines, which includes advice for implementation and has been shown to vary. Others hypothesized this is due to limited instructions in guideline development manuals. The purpose of this study was to examine manual instructions for implementation advice. Methods We used a directed and summative content analysis approach based on an established framework of guideline implementability. Six manuals identified by another research group were examined to enumerate implementability domains and elements. Results Manuals were similar in content but lacked sufficient detail in particular domains. Most frequently this was Accomodation, which includes information that would help guideline users anticipate and/or overcome organizational and system level barriers. In more than one manual, information was also lacking for Communicability, information that would educate patients or facilitate their involvement in shared decision making, and Applicability, or clinical parameters to help clinicians tailor recommendations for individual patients. Discussion Most manuals that direct guideline development lack complete information about incorporating implementation advice. These findings can be used by those who developed the manuals to consider expanding their content in these domains. It can also be used by guideline developers as they plan the content and implementation of their guidelines so that the two are integrated. New approaches for guideline development and implementation may need to be developed. Use of guidelines might be improved if they included implementation advice, but this must be evaluated through ongoing research.

Risk assessment of carcinogens in food

International Nuclear Information System (INIS)

Barlow, Susan; Schlatter, Josef

2010-01-01

Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a 'margin of exposure' approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

Risk assessment of carcinogens in food.

Science.gov (United States)

Barlow, Susan; Schlatter, Josef

2010-03-01

Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a "margin of exposure" approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

Guidelines for Guidelines: Are They Up to the Task? A Comparative Assessment of Clinical Practice Guideline Development Handbooks

Science.gov (United States)

Ansari, Shabnam; Rashidian, Arash

2012-01-01

Objectives We conducted a comparative review of clinical practice guideline development handbooks. We aimed to identify the main guideline development tasks, assign weights to the importance of each task using expert opinions and identify the handbooks that provided a comprehensive coverage of the tasks. Methods We systematically searched and included handbooks published (in English language) by national, international or professional bodies responsible for evidenced-based guideline development. We reviewed the handbooks to identify the main guideline development tasks and scored each handbook for each task from 0 (the handbook did not mention the task) to 2 (the task suitably addressed and explained), and calculated a weighted score for each handbook. The tasks included in over 75% of the handbooks were considered as ‘necessary’ tasks. Result Nineteen guideline development handbooks and twenty seven main tasks were identified. The guideline handbooks’ weighted scores ranged from 100 to 220. Four handbooks scored over 80% of the maximum possible score, developed by the National Institute for Health and Clinical Excellence, Swiss Centre for International Health, Scottish Intercollegiate Guidelines Network and World Health Organization. Necessary tasks were: selecting the guideline topic, determining the guideline scope, identifying relevant existing guidelines, involving the consumers, forming guideline development group,, developing clinical questions, systematic search for evidence, selecting relevant evidence, appraising identifies research evidence, making group decision, grading available evidence, creating recommendations, final stakeholder consultation, guideline implementation strategies, updating recommendations and correcting potential errors. Discussion Adequate details for evidence based development of guidelines were still lacking from many handbooks. The tasks relevant to ethical issues and piloting were missing in most handbooks. The findings

The development of oncology treatment guidelines: an analysis of the National Guidelines Clearinghouse.

Science.gov (United States)

Palta, Manisha; Lee, W Robert

2011-01-01

In the last 2 decades, guidelines have been developed to improve quality of patient care. A recent editorial of guideline development procedures suggested the process has significant limitations that affect their scientific validity.(1) This prompted us to review oncology treatment guidelines to determine if such limitations are widespread. We performed a review of oncology treatment guidelines registered at the National Guidelines Clearinghouse (www.guideline.gov). Each guideline was independently reviewed by 2 authors and the following criteria were assessed: coordinating organization, guideline panel composition, reporting conflict of interest, peer review, dissent, expiration date, PubMed citation, and evidence-based scoring and grading of recommendations. Disagreements were resolved by consensus in subsequent discussions. Sixty-four guidelines were reviewed (39 [61%] were developed by a medical specialty society and 25 [39%] were developed by government agencies). Fifty (78%) guideline panels were multidisciplinary and 44 (69%) included individuals with epidemiologic and health services research expertise. Potential conflicts of interest were disclosed in 43 (67%) guidelines. Sixty (94%) guidelines underwent peer review, with external review in 31 (48%). Seventeen (27%) guidelines are indexed by PubMed. Fifty-one (80%) guidelines included evidence-based methodologies and 46 (72%) used evidence-based scoring of recommendations. Significant differences were observed according to coordinating organization (eg, disclosure of conflict of interest in 46% of guidelines developed by medical specialty societies versus 100% authored by government agencies [P <.0001]). The majority of oncology-related treatment guidelines registered at the National Guidelines Clearinghouse satisfy most of the criteria for sound guideline development. Significant differences in these criteria were observed according to the coordinating organization that developed the guideline. Copyright

Development of cancer treatment guidelines

African Journals Online (AJOL)

Krystyna Kiel

2011-05-26

May 26, 2011 ... KEYWORDS. Cancer;. Therapy;. Guidelines. Contents. 1. Why develop guidelines? ... Widely available guideline resources in cancer care. ... The use of guidelines in medicine has a long history. Many .... She has a negative family history. ... The patient has 1 cm grade 3 infiltrating ductal carcinoma.

Report on carcinogens monograph on 1-bromopropane.

Science.gov (United States)

2013-09-01

The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in

Immunologic methods for monitoring carcinogen exposure

Science.gov (United States)

Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

1993-03-01

Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

Developing clinical practice guidelines: target audiences, identifying topics for guidelines, guideline group composition and functioning and conflicts of interest.

Science.gov (United States)

Eccles, Martin P; Grimshaw, Jeremy M; Shekelle, Paul; Schünemann, Holger J; Woolf, Steven

2012-07-04

Clinical practice guidelines are one of the foundations of efforts to improve health care. In 1999, we authored a paper about methods to develop guidelines. Since it was published, the methods of guideline development have progressed both in terms of methods and necessary procedures and the context for guideline development has changed with the emergence of guideline clearing houses and large scale guideline production organisations (such as the UK National Institute for Health and Clinical Excellence). It therefore seems timely to, in a series of three articles, update and extend our earlier paper. In this first paper we discuss: the target audience(s) for guidelines and their use of guidelines; identifying topics for guidelines; guideline group composition (including consumer involvement) and the processes by which guideline groups function and the important procedural issue of managing conflicts of interest in guideline development.

Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise

Science.gov (United States)

Schünemann, Holger J.; Wiercioch, Wojtek; Etxeandia, Itziar; Falavigna, Maicon; Santesso, Nancy; Mustafa, Reem; Ventresca, Matthew; Brignardello-Petersen, Romina; Laisaar, Kaja-Triin; Kowalski, Sérgio; Baldeh, Tejan; Zhang, Yuan; Raid, Ulla; Neumann, Ignacio; Norris, Susan L.; Thornton, Judith; Harbour, Robin; Treweek, Shaun; Guyatt, Gordon; Alonso-Coello, Pablo; Reinap, Marge; Brožek, Jan; Oxman, Andrew; Akl, Elie A.

2014-01-01

Background: Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline would address each item. Methods: We searched data sources, including manuals of international guideline developers, literature on guidelines for guidelines (with a focus on methodology reports from international and national agencies, and professional societies) and recent articles providing systematic guidance. We reviewed these sources in duplicate, extracted items for the checklist using a sensitive approach and developed overarching topics relevant to guidelines. In an iterative process, we reviewed items for duplication and omissions and involved experts in guideline development for revisions and suggestions for items to be added. Results: We developed a checklist with 18 topics and 146 items and a webpage to facilitate its use by guideline developers. The topics and included items cover all stages of the guideline enterprise, from the planning and formulation of guidelines, to their implementation and evaluation. The final checklist includes links to training materials as well as resources with suggested methodology for applying the items. Interpretation: The checklist will serve as a resource for guideline developers. Consideration of items on the checklist will support the development, implementation and evaluation of guidelines. We will use crowdsourcing to revise the checklist and keep it up to date. PMID:24344144

Predicting carcinogenicity of diverse chemicals using probabilistic neural network modeling approaches

Energy Technology Data Exchange (ETDEWEB)

Singh, Kunwar P., E-mail: kpsingh_52@yahoo.com [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Gupta, Shikha; Rai, Premanjali [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

2013-10-15

Robust global models capable of discriminating positive and non-positive carcinogens; and predicting carcinogenic potency of chemicals in rodents were developed. The dataset of 834 structurally diverse chemicals extracted from Carcinogenic Potency Database (CPDB) was used which contained 466 positive and 368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals and nonlinearity in the data were evaluated using Tanimoto similarity index and Brock–Dechert–Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) models were constructed for classification and function optimization problems using the carcinogenicity end point in rat. Validation of the models was performed using the internal and external procedures employing a wide series of statistical checks. PNN constructed using five descriptors rendered classification accuracy of 92.09% in complete rat data. The PNN model rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster and pesticide data, respectively. The GRNN constructed with nine descriptors yielded correlation coefficient of 0.896 between the measured and predicted carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data. The rat carcinogenicity model (GRNN) applied to the mouse and hamster data yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46, respectively. The results suggest for wide applicability of the inter-species models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN (inter-species) models constructed here can be useful tools in predicting the carcinogenicity of new chemicals for regulatory purposes. - Graphical abstract: Figure (a) shows classification accuracies (positive and non-positive carcinogens) in rat, mouse, hamster, and pesticide data yielded by optimal PNN model. Figure (b) shows generalization and predictive

An analysis of pharmaceutical experience with decades of rat carcinogenicity testing: support for a proposal to modify current regulatory guidelines.

Science.gov (United States)

Sistare, Frank D; Morton, Daniel; Alden, Carl; Christensen, Joel; Keller, Douglas; Jonghe, Sandra De; Storer, Richard D; Reddy, M Vijayaraj; Kraynak, Andrew; Trela, Bruce; Bienvenu, Jean-Guy; Bjurström, Sivert; Bosmans, Vanessa; Brewster, David; Colman, Karyn; Dominick, Mark; Evans, John; Hailey, James R; Kinter, Lewis; Liu, Matt; Mahrt, Charles; Marien, Dirk; Myer, James; Perry, Richard; Potenta, Daniel; Roth, Arthur; Sherratt, Philip; Singer, Thomas; Slim, Rabih; Soper, Keith; Fransson-Steen, Ronny; Stoltz, James; Turner, Oliver; Turnquist, Susan; van Heerden, Marjolein; Woicke, Jochen; DeGeorge, Joseph J

2011-06-01

Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.

Report on carcinogens monograph on cumene.

Science.gov (United States)

2013-09-01

The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

Guidelines for Developing Competency-Based Curriculum.

Science.gov (United States)

Goodson, Ludy

1979-01-01

Presents guidelines for the development of competency-based curriculum formulated as a result of an automotive mechanics curriculum workshop. Listed are specific guidelines for content development, writing style, and illustration. (LRA)

Blood proteins as carcinogen dosimeters

International Nuclear Information System (INIS)

Tannenbaum, S.R.; Skipper, P.L.

1986-01-01

The problem of quantifying exposure to genotoxins in a given individual represents a formidable challenge. In this paper methods which rely on the covalent binding of carcinogens and their metabolites to blood proteins are described. That carcinogens interact with proteins as well as with DNA has been established, although whether protein-carcinogen adducts can result in genetic damage has not been established. It has been shown, however, that the amount of a protein carcinogen adduct formed may be used as a quantitative measure of exposure to a carcinogen. Such a measure presumably is reflective of the absorption, metabolism, and excretion of the compound in an exposed individual. Protein adduction may reflect exposure in a time-frame of weeks to months. Thus, protein adduct measurement is a form of human chemical dosimetry. Hemoglobin and albumin are promising candidates for such dosimeters. Hemoglobin has a lifetime of about 120 days in humans; thus, circulating levels of carcinogen-modified hemoglobin will reflect the level of carcinogen exposure during a period of nearly four months. It also possesses some metabolic competence, particularly, the ability to oxidize aromatic hydroxylamines to nitroso compounds which react quite efficiently with sulfhydryl groups. Albumin has a half-life of 20 to 25 days in man. This protein does not possess metabolic capacity other than, perhaps, some esterase activity. In contrast to hemoglobin, though, it is not protected by the erythrocyte membrane and might be the target for a greater number of carcinogens. It is present and is synthesized in the same cells in which the reactive metabolic intermediates of carcinogens are mostly formed - the hepatocytes. Also, albumin has a number of high-affinity binding sites for a broad spectrum of xenobiotics and endobiotics. 25 refs., 1 tab

Biomarkers of carcinogen exposure and early effects.

OpenAIRE

2006-01-01

The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

Advanced control room design review guidelines: Integration of the NUREG-0700 guidelines and development of new human-system interface guidelines

Energy Technology Data Exchange (ETDEWEB)

Carter, R.J.

1997-07-01

This report documents the work conducted in four tasks of the Nuclear Regulatory Commission (NRC) project entitled Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation. The purpose of the first task was to integrate the applicable sections of NUREG-0700 into the advanced control room design review (ACRDR) guidelines to ensure that all applicable guidelines are together in one document and conveniently accessible to users. The primary objective of the second task was to formulate a strategy for the development of new ACRDR guidelines that have not otherwise been identified. The main focus of the third task was to modify the individual ACRDR guidelines generated to date to ensure that they are suitable for the intended nuclear power plant (NPP) control station system application. The goal of the fourth task was to develop human factors guidelines for two human-system interface categories that are missing from the current ACRDR guidelines document. During the first task those areas in NUREG-0700 that are not addressed by the ACRDR guidelines document were identified, the areas were subsequently reviewed against six recent industry human factors engineering review guidelines, and the NUREG-0700 guidelines were updated as necessary. In the second task 13 general categories of human-system interface guidelines that are either missing from or not adequately addressed by the ACRDR document were discovered. An approach was derived for the development of new ACRDR guidelines, a preliminary assessment of the available sources that may be useful in the creation of new guidelines and their applicability to the identified human-system interface categories was performed, and an estimate was made of the amount of time and level of effort required to complete the development of needed new ACRDR guidelines. During the third task those NPP control station systems to which the NUREG-0700 and ACRDR guidelines apply were identified, matrices of such

Advanced control room design review guidelines: Integration of the NUREG-0700 guidelines and development of new human-system interface guidelines

International Nuclear Information System (INIS)

Carter, R.J.

1997-07-01

This report documents the work conducted in four tasks of the Nuclear Regulatory Commission (NRC) project entitled Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation. The purpose of the first task was to integrate the applicable sections of NUREG-0700 into the advanced control room design review (ACRDR) guidelines to ensure that all applicable guidelines are together in one document and conveniently accessible to users. The primary objective of the second task was to formulate a strategy for the development of new ACRDR guidelines that have not otherwise been identified. The main focus of the third task was to modify the individual ACRDR guidelines generated to date to ensure that they are suitable for the intended nuclear power plant (NPP) control station system application. The goal of the fourth task was to develop human factors guidelines for two human-system interface categories that are missing from the current ACRDR guidelines document. During the first task those areas in NUREG-0700 that are not addressed by the ACRDR guidelines document were identified, the areas were subsequently reviewed against six recent industry human factors engineering review guidelines, and the NUREG-0700 guidelines were updated as necessary. In the second task 13 general categories of human-system interface guidelines that are either missing from or not adequately addressed by the ACRDR document were discovered. An approach was derived for the development of new ACRDR guidelines, a preliminary assessment of the available sources that may be useful in the creation of new guidelines and their applicability to the identified human-system interface categories was performed, and an estimate was made of the amount of time and level of effort required to complete the development of needed new ACRDR guidelines. During the third task those NPP control station systems to which the NUREG-0700 and ACRDR guidelines apply were identified, matrices of such

Development of human factors design review guidelines

International Nuclear Information System (INIS)

Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul

1997-10-01

The Objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, Human factors engineering program review model' and '26, Review criteria for human actors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides be ing performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we well update the guidelines by reviewing the literature related to alarm design published after 1994

Development of human factors design review guidelines

Energy Technology Data Exchange (ETDEWEB)

Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

1997-10-01

The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 12 refs., 5 figs., 2 tabs.

Development and application of non-invasive biomarkers for carcinogen-DNA adduct analysis in occupationally exposed populations.

Science.gov (United States)

Talaska, G; Cudnik, J; Jaeger, M; Rothman, N; Hayes, R; Bhatnagar, V J; Kayshup, S J

1996-07-17

Biological monitoring of exposures to carcinogenic compounds in the workplace can be a valuable adjunct to environmental sampling and occupational medicine. Carcinogen-DNA adduct analysis has promise as a biomarker of effective dose if target organ samples can be obtained non-invasively. We have developed non-invasive techniques using exfoliated urothelial and bronchial cells collected in urine and sputum, respectively. First morning urine samples were collected from 33 workers exposed to benzidine or benzidine-based dyes and controls matched for age, education, and smoking status. Sufficient DNA for 32P-postlabelling analysis was obtained from every sample. Mean levels of a specific DNA adduct (which co-chromatographed with standard characterized by MS) were elevated significantly in the benzidine-exposed workers relative to controls. In addition, workers exposed to benzidine had higher adduct levels than those exposed to benzidine-based dyes. This study demonstrates the usefulness of these non-invasive techniques for exposure/effect assessment. To be useful in occupational studies, biomarkers must also be sensitive to exposure interventions. We have conducted topical application studies of used gasoline engine oils in mice and found that the levels of carcinogen-DNA adducts in skin and lung can be significantly lowered if skin cleaning is conducted in a timely manner. The combination of useful, non-invasive techniques to monitor exposure and effect and industrial hygiene interventions can be used to detect and prevent exposures to a wide range of carcinogens including those found in used gasoline engine oils and jet exhausts.

The effects of environmental chemical carcinogens on the microRNA machinery.

Science.gov (United States)

Izzotti, A; Pulliero, A

2014-07-01

The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens. Copyright © 2014 Elsevier GmbH. All rights reserved.

Methodological guidelines for developing accident modification functions

DEFF Research Database (Denmark)

Elvik, Rune

2015-01-01

This paper proposes methodological guidelines for developing accident modification functions. An accident modification function is a mathematical function describing systematic variation in the effects of road safety measures. The paper describes ten guidelines. An example is given of how to use...... limitations in developing accident modification functions are the small number of good evaluation studies and the often huge variation in estimates of effect. It is therefore still not possible to develop accident modification functions for very many road safety measures. © 2015 Elsevier Ltd. All rights...... the guidelines. The importance of exploratory analysis and an iterative approach in developing accident modification functions is stressed. The example shows that strict compliance with all the guidelines may be difficult, but represents a level of stringency that should be strived for. Currently the main...

Development application guidelines : Newfoundland offshore area

Energy Technology Data Exchange (ETDEWEB)

NONE

1988-12-01

The Canada-Newfoundland Offshore Petroleum Board has created a set of guidelines which describe the information needed by the Board to process a development application by a proponent of an offshore hydrocarbon development project. The guidelines also describe the review process that will be followed in considering a proponent`s application. Proponents must also refer to the Canada-Newfoundland Atlantic Accord Implementation Act and the Canada-Newfoundland Atlantic Accord Implementation (Newfoundland) Act. These guidelines also describe the requirements for the Canada-Newfoundland benefits plan, the environmental impact statement, the socio-economic impact statement, the safety plan, and the environmental protection plan.

Carcinogen susceptibility is regulated by genome architecture and predicts cancer mutagenesis.

Science.gov (United States)

García-Nieto, Pablo E; Schwartz, Erin K; King, Devin A; Paulsen, Jonas; Collas, Philippe; Herrera, Rafael E; Morrison, Ashby J

2017-10-02

The development of many sporadic cancers is directly initiated by carcinogen exposure. Carcinogens induce malignancies by creating DNA lesions (i.e., adducts) that can result in mutations if left unrepaired. Despite this knowledge, there has been remarkably little investigation into the regulation of susceptibility to acquire DNA lesions. In this study, we present the first quantitative human genome-wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer. Remarkably, the pattern of carcinogen susceptibility across the genome of primary cells significantly reflects mutation frequency in malignant melanoma. Surprisingly, DNase-accessible euchromatin is protected from UV, while lamina-associated heterochromatin at the nuclear periphery is vulnerable. Many cancer driver genes have an intrinsic increase in carcinogen susceptibility, including the BRAF oncogene that has the highest mutation frequency in melanoma. These findings provide a genome-wide snapshot of DNA injuries at the earliest stage of carcinogenesis. Furthermore, they identify carcinogen susceptibility as an origin of genome instability that is regulated by nuclear architecture and mirrors mutagenesis in cancer. © 2017 The Authors.

Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the ke test

International Nuclear Information System (INIS)

Mendelsohn, M.L.; Bakale, G.; McCreary, R.D.

1989-01-01

The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that ''carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or ''Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs

Addressing implementation challenges during guideline development - a case study of Swedish national guidelines for methods of preventing disease.

Science.gov (United States)

Richter-Sundberg, Linda; Kardakis, Therese; Weinehall, Lars; Garvare, Rickard; Nyström, Monica E

2015-01-22

Many of the world's life threatening diseases (e.g. cancer, heart disease, stroke) could be prevented by eliminating life-style habits such as tobacco use, unhealthy diet, physical inactivity and excessive alcohol use. Incorporating evidence-based research on methods to change unhealthy lifestyle habits in clinical practice would be equally valuable. However gaps between guideline development and implementation are well documented, with implications for health care quality, safety and effectiveness. The development phase of guidelines has been shown to be important both for the quality in guideline content and for the success of implementation. There are, however, indications that guidelines related to general disease prevention methods encounter specific barriers compared to guidelines that are diagnosis-specific. In 2011 the Swedish National board for Health and Welfare launched guidelines with a preventive scope. The aim of this study was to investigate how implementation challenges were addressed during the development process of these disease preventive guidelines. Seven semi-structured interviews were conducted with members of the guideline development management group. Archival data detailing the guideline development process were also collected and used in the analysis. Qualitative data were analysed using content analysis as the analytical framework. The study identified several strategies and approaches that were used to address implementation challenges during guideline development. Four themes emerged from the analysis: broad agreements and consensus about scope and purpose; a formalized and structured development procedure; systematic and active involvement of stakeholders; and openness and transparency in the specific guideline development procedure. Additional factors concerning the scope of prevention and the work environment of guideline developers were perceived to influence the possibilities to address implementation issues. This case study

The development of evidence-based guidelines in dentistry.

Science.gov (United States)

Faggion, C M

2013-02-01

Use of guidelines is an important means of reducing the gap between research and clinical practice. Sound and unbiased information should be available to enable dental professionals to provide better clinical treatment for their patients. The development of clinical guidelines in dentistry should follow standard and transparent methodology. The purpose of this article is to propose important steps for developing evidence-based clinical recommendations in dentistry. Initially, dental guidelines should be extensively sought and assessed to answer focused clinical questions. If there is a paucity of guidelines or if existing guidelines are not of good methodological quality, systematic reviews should be searched or conducted to serve as a basis for the development of evidence-based guidelines. When systematic reviews are produced, they should be rigorous in order to provide the best evidence possible. In the last phase of the process, the overall quality of evidence should be scrutinized and assessed, together with other factors (balance between treatment effects and side effects, patients' values, and cost-effectiveness of therapy) to determine the strength of recommendations. It is expected this approach will result in the development of sound clinical guidelines and consequent improvement of dental treatment.

Detection of carcinogen-DNA adducts by radioimmunoassay

International Nuclear Information System (INIS)

Poirier, M.C.; Yuspa, S.H.; Weinstein, I.B.; Blobstein, S.

1977-01-01

Covalent binding of carcinogen to nucleic acids is believed to be an essential component of the carcinogenic process, so it is desirable to have highly sensitive and specific methods for detecting such adducts in cells and tissues exposed to known and suspected carcinogens. A radioimmunoassay is here described capable of detecting nanogram amounts of DNA adducts resulting from the covalent binding of the carcinogen N-2-acetylaminofluorene and its activated N-acetoxy derivative. (author)

Oral carcinogenicity study with nickel sulfate hexahydrate in Fischer 344 rats

International Nuclear Information System (INIS)

Heim, Katherine E.; Bates, Hudson K.; Rush, Rusty E.; Oller, Adriana R.

2007-01-01

Until now, existing data on the oral carcinogenicity of nickel substances have been inconclusive. Yet, the assessment of oral carcinogenicity of nickel has serious scientific and regulatory implications. In the present study, nickel sulfate hexahydrate was administered daily to Fischer 344 rats by oral gavage for 2 years (104 weeks) at exposure levels of 10, 30 and 50 mg NiSO 4 ·6H 2 O/kg. This treatment produced a statistically significant reduction in body weight of male and female rats, compared to controls, in an exposure-related fashion at 30 and 50 mg/kg/day. An exposure-dependent increase in mortality was observed in female rats. However, the overall study survival rate (males and females) was at least 25 animals per group (compliant with OECD guidelines) in the treated animals. Daily oral administration of nickel sulfate hexahydrate did not produce an exposure-related increase in any common tumor type or an increase in any rare tumors. One tumor type was statistically increased in a nickel sulfate-treated group compared to the study controls (keratoacanthoma in the 10 mg NiSO 4 ·6H 2 O/kg/day males), but there was no exposure-response relationship for this common tumor type. This study achieved sufficient toxicity to reach the Maximum Tolerated Dose (MTD) while maintaining a sufficiently high survival rate to allow evaluation for carcinogenicity. The present study indicated that nickel sulfate hexahydrate does not have the potential to cause carcinogenicity by the oral route of exposure in the Fischer 344 rat. Data from this and other studies demonstrate that inhalation is the only route of exposure that might cause concern for cancer in association with nickel exposures

Development of human factors design review guidelines(II)

Energy Technology Data Exchange (ETDEWEB)

Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

1998-06-01

The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 11 refs., 2 figs., 2 tabs.

Management Guidelines for Database Developers' Teams in Software Development Projects

Science.gov (United States)

Rusu, Lazar; Lin, Yifeng; Hodosi, Georg

Worldwide job market for database developers (DBDs) is continually increasing in last several years. In some companies, DBDs are organized as a special team (DBDs team) to support other projects and roles. As a new role, the DBDs team is facing a major problem that there are not any management guidelines for them. The team manager does not know which kinds of tasks should be assigned to this team and what practices should be used during DBDs work. Therefore in this paper we have developed a set of management guidelines, which includes 8 fundamental tasks and 17 practices from software development process, by using two methodologies Capability Maturity Model (CMM) and agile software development in particular Scrum in order to improve the DBDs team work. Moreover the management guidelines developed here has been complemented with practices from authors' experience in this area and has been evaluated in the case of a software company. The management guidelines for DBD teams presented in this paper could be very usefully for other companies too that are using a DBDs team and could contribute towards an increase of the efficiency of these teams in their work on software development projects.

Identification and monitoring of non-radiological carcinogens

Energy Technology Data Exchange (ETDEWEB)

Chuaqui, C A; Petkau, A; Greenstock, C L; Brown, C P [Atomic Energy of Canada Ltd., Pinawa, MB (Canada). Whiteshell Labs.

1995-09-01

This study examines the feasibility of identifying and monitoring occupational exposures to non-radiological carcinogens in the workplace at Canadian nuclear establishments (Whiteshell Laboratories, Pickering Nuclear Generating Station, Cameco Limited and Canadian General Electric Company Limited). Recent epidemiological studies recommended that potential confounding factors of a non-radiological nature be identified and analyzed, particularly non-radiological carcinogens that may be present in the workplace at nuclear facilities. The feasibility of identifying and measuring occupational exposures to non-radiological carcinogens in Canadian nuclear facilities is examined. Also, the report describes the problem of chemical carcinogens and the mechanisms involved in chemical carcinogenesis; the epidemiology related to the problem, followed by a description of the analytical aspects of detection, monitoring and analysis of carcinogens, as well as a discussion on the regulatory aspects and the regulations in place; and the findings, recommendations and concluding remarks of this study. Several problem areas became apparent as the study proceeded. For example, the classification of a chemical as a human carcinogen is a difficult problem, as is its adequate monitoring and analysis. This situation reflects, in turn, the regulatory aspects in the workplace. A list of chemical carcinogens used industrially at the four Canadian nuclear facilities has been identified. The list includes arsenic, asbestos, benzene, cadmium, beryllium, nickel, polychlorinated biphenyls, lead and trichloroethylene. Several recommendations are made in relation to the need for practical and efficient monitoring methods for chemical carcinogens, the definition of radiation and chemical dose equivalencies, and the classification of human chemical carcinogens, as well as their disposal. (author). 122 refs., 8 tabs., 6 figs.

Identification and monitoring of non-radiological carcinogens

International Nuclear Information System (INIS)

Chuaqui, C.A.; Petkau, A.; Greenstock, C.L.; Brown, C.P.

1995-09-01

This study examines the feasibility of identifying and monitoring occupational exposures to non-radiological carcinogens in the workplace at Canadian nuclear establishments (Whiteshell Laboratories, Pickering Nuclear Generating Station, Cameco Limited and Canadian General Electric Company Limited). Recent epidemiological studies recommended that potential confounding factors of a non-radiological nature be identified and analyzed, particularly non-radiological carcinogens that may be present in the workplace at nuclear facilities. The feasibility of identifying and measuring occupational exposures to non-radiological carcinogens in Canadian nuclear facilities is examined. Also, the report describes the problem of chemical carcinogens and the mechanisms involved in chemical carcinogenesis; the epidemiology related to the problem, followed by a description of the analytical aspects of detection, monitoring and analysis of carcinogens, as well as a discussion on the regulatory aspects and the regulations in place; and the findings, recommendations and concluding remarks of this study. Several problem areas became apparent as the study proceeded. For example, the classification of a chemical as a human carcinogen is a difficult problem, as is its adequate monitoring and analysis. This situation reflects, in turn, the regulatory aspects in the workplace. A list of chemical carcinogens used industrially at the four Canadian nuclear facilities has been identified. The list includes arsenic, asbestos, benzene, cadmium, beryllium, nickel, polychlorinated biphenyls, lead and trichloroethylene. Several recommendations are made in relation to the need for practical and efficient monitoring methods for chemical carcinogens, the definition of radiation and chemical dose equivalencies, and the classification of human chemical carcinogens, as well as their disposal. (author). 122 refs., 8 tabs., 6 figs

Development of human factors design review guidelines(III)

Energy Technology Data Exchange (ETDEWEB)

Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1999-02-15

The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, human factors engineering program review model' and '26, review criteria for human factors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents NUREG--0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm system. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994.

Development of human factors design review guidelines(III)

International Nuclear Information System (INIS)

Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul

1999-02-01

The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, human factors engineering program review model' and '26, review criteria for human factors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents NUREG--0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm system. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994

Development of human factors design review guidelines(II)

International Nuclear Information System (INIS)

Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul

1998-06-01

The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, human factors engineering program review model' and '26, review criteria for human factors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents NUREG--0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm system. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994

Development of human factors design review guidelines(III)

Energy Technology Data Exchange (ETDEWEB)

Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1999-02-15

The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, human factors engineering program review model' and '26, review criteria for human factors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents NUREG--0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm system. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994.

METABOLISM, GENOTOXICITY, AND CARCINOGENICITY OF COMFREY

Science.gov (United States)

Mei, Nan; Guo, Lei; Fu, Peter P.; Fuscoe, James C.; Luan, Yang; Chen, Tao

2018-01-01

Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

Metabolism, genotoxicity, and carcinogenicity of comfrey.

Science.gov (United States)

Mei, Nan; Guo, Lei; Fu, Peter P; Fuscoe, James C; Luan, Yang; Chen, Tao

2010-10-01

Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction.

The CARE guidelines: consensus-based clinical case report guideline development.

Science.gov (United States)

Gagnier, Joel J; Kienle, Gunver; Altman, Douglas G; Moher, David; Sox, Harold; Riley, David

2014-01-01

A case report is a narrative that describes, for medical, scientific, or educational purposes, a medical problem experienced by one or more patients. Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design. Develop, disseminate, and implement systematic reporting guidelines for case reports. We used a three-phase consensus process consisting of (1) pre-meeting literature review and interviews to generate items for the reporting guidelines, (2) a face-to-face consensus meeting to draft the reporting guidelines, and (3) post-meeting feedback, review, and pilot testing, followed by finalization of the case report guidelines. This consensus process involved 27 participants and resulted in a 13-item checklist-a reporting guideline for case reports. The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes, discussion, patient perspective, and informed consent. We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery. Copyright © 2014 Reproduced with permission of Global Advances in Health and Medicine. Published by Elsevier Inc. All rights reserved.

Surfing the best practice guidelines: national clinical guideline clearinghouse in development.

Science.gov (United States)

1997-08-01

The growth in development and usage of clinical guidelines during the last five years has been remarkable. Not only are health care practitioners reaching for what's deemed to be the best in protocols and practice, consumers, too, are looking toward standards and guidelines as they become more educated about the quality and quantity of health care services they should be receiving.

Comparison of international guideline programs to evaluate and update the Dutch program for clinical guideline development in physical therapy.

Science.gov (United States)

Van der Wees, Philip J; Hendriks, Erik J M; Custers, Jan W H; Burgers, Jako S; Dekker, Joost; de Bie, Rob A

2007-11-23

Clinical guidelines are considered important instruments to improve quality in health care. Since 1998 the Royal Dutch Society for Physical Therapy (KNGF) produced evidence-based clinical guidelines, based on a standardized program. New developments in the field of guideline research raised the need to evaluate and update the KNGF guideline program. Purpose of this study is to compare different guideline development programs and review the KNGF guideline program for physical therapy in the Netherlands, in order to update the program. Six international guideline development programs were selected, and the 23 criteria of the AGREE Instrument were used to evaluate the guideline programs. Information about the programs was retrieved from published handbooks of the organizations. Also, the Dutch program for guideline development in physical therapy was evaluated using the AGREE criteria. Further comparison the six guideline programs was carried out using the following elements of the guideline development processes: Structure and organization; Preparation and initiation; Development; Validation; Dissemination and implementation; Evaluation and update. Compliance with the AGREE criteria of the guideline programs was high. Four programs addressed 22 AGREE criteria, and two programs addressed 20 AGREE criteria. The previous Dutch program for guideline development in physical therapy lacked in compliance with the AGREE criteria, meeting only 13 criteria. Further comparison showed that all guideline programs perform systematic literature searches to identify the available evidence. Recommendations are formulated and graded, based on evidence and other relevant factors. It is not clear how decisions in the development process are made. In particular, the process of translating evidence into practice recommendations can be improved. As a result of international developments and consensus, the described processes for developing clinical practice guidelines have much in common

An estimation of the carcinogenic risk associated with the intake of multiple relevant carcinogens found in meat and charcuterie products.

Science.gov (United States)

Hernández, Ángel Rodríguez; Boada, Luis D; Almeida-González, Maira; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valeron, Pilar F; Camacho, María; Zumbado, Manuel; Henríquez-Hernández, Luis A; Luzardo, Octavio P

2015-05-01

Numerous epidemiological studies have demonstrated a link between excessive meat consumption and the incidence of various cancers, especially colorectal cancer, and it has been suggested that environmental carcinogens present in meat might be related to the increased risk of cancer associated with this food. However, there are no studies evaluating the carcinogenic potential of meat in relation to its content of carcinogens. Our purpose was to emphasize the relevance of environmental carcinogens existing in meat as a determinant of the association between cancer and meat consumption. Because within Europe, Spain shows high consumption of meat and charcuterie, we performed this study focusing on Spanish population. Based on the preferences of consumers we acquired 100 samples of meat and charcuterie that reflect the variety available in the European market. We quantified in these samples the concentration of 33 chemicals with calculated carcinogenic potential (PAHs, organochlorine pesticides, and dioxin-like PCBs). The carcinogenic risk of these contaminants was assessed for each food using a risk ratio based on the current consumption of meat and charcuterie and the maximum tolerable intake of these foods depending on the level of contamination by the carcinogens they contain. Our results indicate that the current consumption of beef, pork, lamb, chicken, and "chorizo", represents a relevant carcinogenic risk for consumers (carcinogenic risk quotient between 1.33 and 13.98). In order to reduce carcinogenic risk, the study population should halve the monthly consumption of these foods, and also not to surpass the number of 5 servings of beef/pork/chicken (considered together). Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitative structure activity relationship for the computational prediction of nitrocompounds carcinogenicity

International Nuclear Information System (INIS)

Morales, Aliuska Helguera; Perez, Miguel Angel Cabrera; Combes, Robert D.; Gonzalez, Maykel Perez

2006-01-01

Several nitrocompounds have been screened for carcinogenicity in rodents, but this is a lengthy and expensive process, taking two years and typically costing 2.5 million dollars, and uses large numbers of animals. There is, therefore, much impetus to develop suitable alternative methods. One possible way of predicting carcinogenicity is to use quantitative structure-activity relationships (QSARs). QSARs have been widely utilized for toxicity testing, thereby contributing to a reduction in the need for experimental animals. This paper describes the results of applying a TOPological substructural molecular design (TOPS-MODE) approach for predicting the rodent carcinogenicity of nitrocompounds. The model described 79.10% of the experimental variance, with a standard deviation of 0.424. The predictive power of the model was validated by leave-one-out validation, with a determination coefficient of 0.666. In addition, this approach enabled the contribution of different fragments to carcinogenic potency to be assessed, thereby making the relationships between structure and carcinogenicity to be transparent. It was found that the carcinogenic activity of the chemicals analysed was increased by the presence of a primary amine group bonded to the aromatic ring, a manner that was proportional to the ring aromaticity. The nitro group bonded to an aromatic carbon atom is a more important determinant of carcinogenicity than the nitro group bonded to an aliphatic carbon. Finally, the TOPS-MODE approach was compared with four other predictive models, but none of these could explain more than 66% of the variance in the carcinogenic potency with the same number of variables

Comparison of international guideline programs to evaluate and update the Dutch program for clinical guideline development in physical therapy

Directory of Open Access Journals (Sweden)

Burgers Jako S

2007-11-01

Full Text Available Abstract Background Clinical guidelines are considered important instruments to improve quality in health care. Since 1998 the Royal Dutch Society for Physical Therapy (KNGF produced evidence-based clinical guidelines, based on a standardized program. New developments in the field of guideline research raised the need to evaluate and update the KNGF guideline program. Purpose of this study is to compare different guideline development programs and review the KNGF guideline program for physical therapy in the Netherlands, in order to update the program. Method Six international guideline development programs were selected, and the 23 criteria of the AGREE Instrument were used to evaluate the guideline programs. Information about the programs was retrieved from published handbooks of the organizations. Also, the Dutch program for guideline development in physical therapy was evaluated using the AGREE criteria. Further comparison the six guideline programs was carried out using the following elements of the guideline development processes: Structure and organization; Preparation and initiation; Development; Validation; Dissemination and implementation; Evaluation and update. Results Compliance with the AGREE criteria of the guideline programs was high. Four programs addressed 22 AGREE criteria, and two programs addressed 20 AGREE criteria. The previous Dutch program for guideline development in physical therapy lacked in compliance with the AGREE criteria, meeting only 13 criteria. Further comparison showed that all guideline programs perform systematic literature searches to identify the available evidence. Recommendations are formulated and graded, based on evidence and other relevant factors. It is not clear how decisions in the development process are made. In particular, the process of translating evidence into practice recommendations can be improved. Conclusion As a result of international developments and consensus, the described processes

Acute otitis media guidelines in selected developed and developing countries: uniformity and diversity.

Science.gov (United States)

Ovnat Tamir, Sharon; Shemesh, Shay; Oron, Yahav; Marom, Tal

2017-05-01

Acute otitis media (AOM) is a common childhood disease, with an enormous economic and healthcare-related burden. Guidelines and consensus papers for AOM diagnosis and management were published in many countries. Our objective was to study the differences and similarities between these protocols in developing and developed countries. The keywords: 'acute otitis media' AND 'children' AND ['treatment' or 'management'] AND ['guideline' or 'consensus'] were used in various electronic databases between 1 January 1989 through 31 December 2015. Overall, 99 sources from 62 countries were retrieved: 53 from 22 developed countries, and 46 from 40 developing countries. Representative guidelines from America (the USA, Argentina), Europe (Italy, Moldova), Africa (South Africa, Tanzania, Ethiopia), Asia (Japan, Afghanistan, Sri Lanka),and Oceania (South Australia, Fiji) were compared. Paediatric societies publish guidelines in most developed countries; in developing countries, the Ministry of Health usually initiates guideline formulation. Most guidelines use the same diagnostic criteria and offer watchful waiting in mild-moderate scenarios. Amoxicillin is the suggested first-line antibiotic, whereas options for second-line and third-line therapies vary. Duration of therapy varies and is usually age dependent: 5-7 days for children 2 years in developed countries, while duration and age groups vary greatly in developing countries. Reduction of AOM risk factors is encouraged in developed countries, but rarely in developing countries. Guidelines for AOM from developing and developed countries are similar in many aspects, with variation in specific recommendations, due to local epidemiology and healthcare accessibility. Formulation of regional guidelines may help reduce AOM burden. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

World Health Organization guideline development: an evaluation.

Directory of Open Access Journals (Sweden)

David Sinclair

Full Text Available BACKGROUND: Research in 2007 showed that World Health Organization (WHO recommendations were largely based on expert opinion, rarely used systematic evidence-based methods, and did not follow the organization's own "Guidelines for Guidelines". In response, the WHO established a "Guidelines Review Committee" (GRC to implement and oversee internationally recognized standards. We examined the impact of these changes on WHO guideline documents and explored senior staff's perceptions of the new procedures. METHODS AND FINDINGS: We used the AGREE II guideline appraisal tool to appraise ten GRC-approved guidelines from nine WHO departments, and ten pre-GRC guidelines matched by department and topic. We interviewed 20 senior staff across 16 departments and analyzed the transcripts using the framework approach. Average AGREE II scores for GRC-approved guidelines were higher across all six AGREE domains compared with pre-GRC guidelines. The biggest changes were noted for "Rigour of Development" (up 37.6%, from 30.7% to 68.3% and "Editorial Independence" (up 52.7%, from 20.9% to 73.6%. Four main themes emerged from the interviews: (1 high standards were widely recognized as essential for WHO credibility, particularly with regard to conflicts of interest; (2 views were mixed on whether WHO needed a single quality assurance mechanism, with some departments purposefully bypassing the procedures; (3 staff expressed some uncertainties in applying the GRADE approach, with departmental staff concentrating on technicalities while the GRC remained concerned the underlying principles were not fully institutionalized; (4 the capacity to implement the new standards varied widely, with many departments looking to an overstretched GRC for technical support. CONCLUSIONS: Since 2007, WHO guideline development methods have become more systematic and transparent. However, some departments are bypassing the procedures, and as yet neither the GRC, nor the quality assurance

Indoor air-assessment: Indoor concentrations of environmental carcinogens

International Nuclear Information System (INIS)

Gold, K.W.; Naugle, D.F.; Berry, M.A.

1991-01-01

In the report, indoor concentration data are presented for the following general categories of air pollutants: radon-222, environmental tobacco smoke (ETS), asbestos, gas phase organic compounds, formaldehyde, polycyclic aromatic hydrocarbons (PAH), pesticides, and inorganic compounds. These pollutants are either known or suspect carcinogens (i.e., radon-222, asbestos) or more complex mixtures or classes of compounds which contain known or suspect carcinogens. Concentration data for individual carcinogenic compounds in complex mixtures are usually far from complete. The data presented for complex mixtures often include compounds which are not carcinogenic or for which data are insufficient to evaluate carcinogenicity. Their inclusion is justified, however, by the possibility that further work may show them to be carcinogens, cocarcinogens, initiators or promotors, or that they may be employed as markers (e.g., nicotine, acrolein) for the estimation of exposure to complex mixtures

[Risk assessment of carcinogenic and non-carcinogenic effects in the use of food].

Science.gov (United States)

Frolova, O A; Karpova, M V

2012-01-01

Application of methodology for assessing the risk of diseases associated with consumption of contaminated foods, is aimed at predicting possible changes in the future and helps to create a framework for the prevention of negative effects on public health. The purpose of the study is assessment of health risks formed under the influence of chemical contaminants that pollute the food. Exponential average daily dose of receipt of chemicals in the body, non-carcinogenic and carcinogenic risks were calculated.

Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

Science.gov (United States)

Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

2014-01-01

The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. © 2013.

Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the k sub e test

Energy Technology Data Exchange (ETDEWEB)

Mendelsohn, M.L. (ed.); Bakale, G.; McCreary, R.D.

1989-01-01

The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs.

Indoor air - assessment: Methods of analysis for environmental carcinogens

International Nuclear Information System (INIS)

Peterson, M.R.; Naugle, D.F.; Berry, M.A.

1990-06-01

The monograph describes, in a general way, published sampling procedures and analytical approaches for known and suspected carcinogens. The primary focus is upon carcinogens found in indoor air, although the methods described are applicable to other media or environments. In cases where there are no published methods for a particular pollutant in indoor air, methods developed for the workplace and for ambient air are included since they should be adaptable to indoor air. Known and suspected carcinogens have been grouped into six categories for the purposes of this and related work. The categories are radon, asbestos, organic compounds, inorganic species, particles, and non-ionizing radiation. Some methods of assessing exposure that are not specific to any particular pollutant category are covered in a separate section. The report is the fifth in a series of EPA/Environmental Criteria and Assessment Office Monographs

Development of environmental guidelines for electronic appliances

DEFF Research Database (Denmark)

Legarth, Jens Brøbech; Alting, Leo; Erichsen, Hanne K. Linnet

1994-01-01

This paper presents a general method for the development of environmental guidelines for complex products. The method is based on the life cycle concept. The application of life cycle assessment methods reveals the peak environmental impacts, and their source resulting in environmental guidelines...

Risk Assessment Approaches for Carcinogenic Food Contaminants

OpenAIRE

Gillespie, Zoe; Pulido, Olga; Vavasour, Elizabeth

2011-01-01

Health Canada has identified the need for a standardized department-wide approach for the risk assessment of carcinogens in foods (e.g., pesticides, food chemical contaminants, veterinary therapeutics). A standardized approach would better facilitate and inform risk management strategies for the control of human exposure to food sources of carcinogens. Within the post- market regulatory context, directly DNA-reactive carcinogens are of most concern because any exposure is theoretically assume...

Developing clinical guidelines: how much rigour is required?

Science.gov (United States)

Haroon, Munib; Ranmal, Rita; McElroy, Helen; Dudley, Jan

2015-04-01

Clinical guidelines that are rigorously developed play a fundamental role in improving healthcare and reducing unnecessary variations in practice. National guidelines are increasingly used by healthcare professionals, patients and commissioners; however, national bodies are unable to meet the demand for guidance on all topics. There are fewer resources available for guidance produced locally or by specialty groups, and it is necessary to achieve a balance between pragmatism and rigour while conforming to the widely accepted norms of what constitutes a good guideline. This paper introduces the key concepts around this topic with suggestions for those interested in developing their own guideline. An example of challenges encountered in generating high-quality clinical guidance is given in box 1. Box 1 Challenges in guideline development Professor Johnson runs a local developmental paediatrics service with eight other colleagues. All have different ways of managing children with PAVING syndrome. This was difficult for patients and staff and has led to disagreements on how certain patients should be managed. As a result, Professor Johnson developed a Guideline Development Group to look at the management of PAVING syndrome. The group identified 12 clinical questions (including diagnosis, exclusion of comorbidities, treatment modalities), searched the PubMed database and found some useful evidence that they used to formulate key recommendations. For one question about behavioural therapy, PubMed did not suggest any evidence so they informally arrived at a consensus among themselves and wrote up their guideline. On the back of this success, they applied for the guideline to be endorsed or supported by the Royal College of Paediatrics and Child Health (RCPCH). To their frustration, it was turned down on methodological grounds. Professor Johnson wrote to the RCPCH saying that he was "pretty peeved that the PAVING syndrome guideline had been rejected" for the College

Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

Energy Technology Data Exchange (ETDEWEB)

Lin, Chun-Hung [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China); Chou, Pei-Hsin [Department of Environmental Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China)

2014-07-30

Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

International Nuclear Information System (INIS)

Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

2014-01-01

Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

Evidence-based guidelines for the wise use of computers by children: physical development guidelines.

Science.gov (United States)

Straker, L; Maslen, B; Burgess-Limerick, R; Johnson, P; Dennerlein, J

2010-04-01

Computer use by children is common and there is concern over the potential impact of this exposure on child physical development. Recently principles for child-specific evidence-based guidelines for wise use of computers have been published and these included one concerning the facilitation of appropriate physical development. This paper reviews the evidence and presents detailed guidelines for this principle. The guidelines include encouraging a mix of sedentary and whole body movement tasks, encouraging reasonable postures during computing tasks through workstation, chair, desk, display and input device selection and adjustment and special issues regarding notebook computer use and carriage, computing skills and responding to discomfort. The evidence limitations highlight opportunities for future research. The guidelines themselves can inform parents and teachers, equipment designers and suppliers and form the basis of content for teaching children the wise use of computers. STATEMENT OF RELEVANCE: Many children use computers and computer-use habits formed in childhood may track into adulthood. Therefore child-computer interaction needs to be carefully managed. These guidelines inform those responsible for children to assist in the wise use of computers.

Differences in gene expression profiles in the liver between carcinogenic and non-carcinogenic isomers of compounds given to rats in a 28-day repeat-dose toxicity study

International Nuclear Information System (INIS)

Nakayama, Koji; Kawano, Yukiko; Kawakami, Yuuki; Moriwaki, Norichika; Sekijima, Masaru; Otsuka, Masanori; Yakabe, Yoshikuni; Miyaura, Hideki; Saito, Koichi; Sumida, Kayo; Shirai, Tomoyuki

2006-01-01

Some compounds have structural isomers of which one is apparently carcinogenic, and the other not. Because of the similarity of their chemical structures, comparisons of their effects can allow gene expression elicited in response to the basic skeletons of the isomers to be disregarded. We compared the gene expression profiles of male Fischer 344 rats administered by daily oral gavage up to 28 days using an in-house oligo microarray. 2-Acetylaminofluorene (2-AAF), 2,4-diaminotoluene (2,4-DAT), 2-nitropropane (2-NP), and 2-nitro-p-phenylenediamine (2-NpP) are hepatocarcinogenic. However, their isomers, 4-acetylaminofluorene (4-AAF), 2,6-diaminotoluene (2,6-DAT), 1-nitropropane (1-NP), and 4-nitro-o-phenylenediamine (4-NoP), are non-hepatocarcinogenic. Because of the limited carcinogenicity of 2-NpP, we attempted to perform two-parametric comparison analyses with (1) a set of 4 isomers: 2-AAF, 2,4-DAT, 2-NP, and 2-NpP as 'carcinogenic', and 4-AAF, 2,6-DAT, 1-NP, and 4-NoP as 'non-carcinogenic'; and (2) a set of 3 isomers: 2-AAF, 2,4-DAT, and 2-NP, as 'carcinogenic', and 4-AAF, 2,6-DAT, and 1-NP as 'non-carcinogenic'. After ratio filtering and Welch's approximate t-test analysis, 54 and 28 genes were selected from comparisons between the sets of 3 and 4 isomers, respectively, for day 28 data. Using hierarchical clustering analysis with the 54 or 28 genes, 2-AAF, 2,4-DAT, and 2-NP clustered into a 'carcinogenic' branch. 2-NpP was in the same cluster as 4-NoP and 4-AAF. This clustering corresponded to the previous finding that 2-NpP is not carcinogenic in male Fischer 344 rats, which indicates that comparing the differences in gene expression elicited by different isomers is an effective method of developing a prediction system for carcinogenicity

Development of clinical practice guidelines.

Science.gov (United States)

Hollon, Steven D; Areán, Patricia A; Craske, Michelle G; Crawford, Kermit A; Kivlahan, Daniel R; Magnavita, Jeffrey J; Ollendick, Thomas H; Sexton, Thomas L; Spring, Bonnie; Bufka, Lynn F; Galper, Daniel I; Kurtzman, Howard

2014-01-01

Clinical practice guidelines (CPGs) are intended to improve mental, behavioral, and physical health by promoting clinical practices that are based on the best available evidence. The American Psychological Association (APA) is committed to generating patient-focused CPGs that are scientifically sound, clinically useful, and informative for psychologists, other health professionals, training programs, policy makers, and the public. The Institute of Medicine (IOM) 2011 standards for generating CPGs represent current best practices in the field. These standards involve multidisciplinary guideline development panels charged with generating recommendations based on comprehensive systematic reviews of the evidence. The IOM standards will guide the APA as it generates CPGs that can be used to inform the general public and the practice community regarding the benefits and harms of various treatment options. CPG recommendations are advisory rather than compulsory. When used appropriately, high-quality guidelines can facilitate shared decision making and identify gaps in knowledge.

An exploration of how guideline developer capacity and guideline implementability influence implementation and adoption: study protocol

Directory of Open Access Journals (Sweden)

Lemieux-Charles Louise

2009-07-01

Full Text Available Abstract Background Practice guidelines can improve health care delivery and outcomes but several issues challenge guideline adoption, including their intrinsic attributes, and whether and how they are implemented. It appears that guideline format may influence accessibility and ease of use, which may overcome attitudinal barriers of guideline adoption, and appear to be important to all stakeholders. Guideline content may facilitate various forms of decision making about guideline adoption relevant to different stakeholders. Knowledge and attitudes about, and incentives and capacity for implementation on the part of guideline sponsors may influence whether and how they develop guidelines containing these features, and undertake implementation. Examination of these issues may yield opportunities to improve guideline adoption. Methods The attributes hypothesized to facilitate adoption will be expanded by thematic analysis, and quantitative and qualitative summary of the content of international guidelines for two primary care (diabetes, hypertension and institutional care (chronic ulcer, chronic heart failure topics. Factors that influence whether and how guidelines are implemented will be explored by qualitative analysis of interviews with individuals affiliated with guideline sponsoring agencies. Discussion Previous research examined guideline implementation by measuring rates of compliance with recommendations or associated outcomes, but this produced little insight on how the products themselves, or their implementation, could be improved. This research will establish a theoretical basis upon which to conduct experimental studies to compare the cost-effectiveness of interventions that enhance guideline development and implementation capacity. Such studies could first examine short-term outcomes predictive of guideline utilization, such as recall, attitude toward, confidence in, and adoption intention. If successful, then long-term objective

In vitro transformation: interactions of chemical carcinogens and radiation

International Nuclear Information System (INIS)

DiPaolo, J.A.

1976-01-01

The development of reproducible quantitative in vitro procedures resulting in neoplastic transformation of mammalian cells has made possible the separation of events related to the process leading to transformation from secondary events that interfere with the early recognition of transformation. The use of chemical carcinogens on Syrian hamster cell strains results in a dose-response relation consistent with a Poisson distribution, indicating that the transformation phenomenon is inductive. In some circumstances, the joint action or interaction of chemical carcinogens with other agents results in an increased incidence of transformation. The pretreatment of Syrian hamster cells with ionizing radiation (250 R) or alkylating chemicals enhances the frequency of transformation on a cell or colony basis ordinarily obtained with known chemical carcinogens. Pretreatment with non-ionizing irradiation (uv, 254 nm) did not have a similar effect. The two types of irradiation and the alkylating agents reduced the cloning efficiency of the cells. X ray alone produced no transformation; the alkylating chemicals produced transformations infrequently, whereas uv produced a significant number of transformations. The number of transformations associated with uv is increased by pretreatment of the cells by x-irradiation. The enhancement of transformation by x-ray or x-ray-type agents appears to be independent of the type of second carcinogen used

Clinical practice guidelines within the Southern African development community: a descriptive study of the quality of guideline development and concordance with best evidence for five priority diseases

Science.gov (United States)

2012-01-01

Background Reducing the burden of disease relies on availability of evidence-based clinical practice guidelines (CPGs). There is limited data on availability, quality and content of guidelines within the Southern African Development Community (SADC). This evaluation aims to address this gap in knowledge and provide recommendations for regional guideline development. Methods We prioritised five diseases: HIV in adults, malaria in children and adults, pre-eclampsia, diarrhoea in children and hypertension in primary care. A comprehensive electronic search to locate guidelines was conducted between June and October 2010 and augmented with email contact with SADC Ministries of Health. Independent reviewers used the AGREE II tool to score six quality domains reporting the guideline development process. Alignment of the evidence-base of the guidelines was evaluated by comparing their content with key recommendations from accepted reference guidelines, identified with a content expert, and percentage scores were calculated. Findings We identified 30 guidelines from 13 countries, publication dates ranging from 2003-2010. Overall the 'scope and purpose' and 'clarity and presentation' domains of the AGREE II instrument scored highest, median 58%(range 19-92) and 83%(range 17-100) respectively. 'Stakeholder involvement' followed with median 39%(range 6-75). 'Applicability', 'rigour of development' and 'editorial independence' scored poorly, all below 25%. Alignment with evidence was variable across member states, the lowest scores occurring in older guidelines or where the guideline being evaluated was part of broader primary healthcare CPG rather than a disease-specific guideline. Conclusion This review identified quality gaps and variable alignment with best evidence in available guidelines within SADC for five priority diseases. Future guideline development processes within SADC should better adhere to global reporting norms requiring broader consultation of stakeholders

Protocol-developing meta-ethnography reporting guidelines (eMERGe).

Science.gov (United States)

France, E F; Ring, N; Noyes, J; Maxwell, M; Jepson, R; Duncan, E; Turley, R; Jones, D; Uny, I

2015-11-25

Designing and implementing high-quality health care services and interventions requires robustly synthesised evidence. Syntheses of qualitative research studies can provide evidence of patients' experiences of health conditions; intervention feasibility, appropriateness and acceptability to patients; and advance understanding of health care issues. The unique, interpretive, theory-based meta-ethnography synthesis approach is suited to conveying patients' views and developing theory to inform service design and delivery. However, meta-ethnography reporting is often poor quality, which discourages trust in, and use of, meta-ethnography findings. Users of evidence syntheses require reports that clearly articulate analytical processes and findings. Tailored research reporting guidelines can raise reporting standards but none exists for meta-ethnography. This study aims to create an evidence-based meta-ethnography reporting guideline articulating the methodological standards and depth of reporting required to improve reporting quality. The mixed-methods design of this National Institute of Health Research-funded study (http://www.stir.ac.uk/emerge/) follows good practice in research reporting guideline development comprising: (1) a methodological systematic review (PROSPERO registration: CRD42015024709) to identify recommendations and guidance in conducting/reporting meta-ethnography; (2) a review and audit of published meta-ethnographies to identify good practice principles and develop standards in conduct/reporting; (3) an online workshop and Delphi studies to agree guideline content with 45 international qualitative synthesis experts and 45 other stakeholders including patients; (4) development and wide dissemination of the guideline and its accompanying detailed explanatory document, a report template for National Institute of Health Research commissioned meta-ethnographies, and training materials on guideline use. Meta-ethnography, devised in the field of education

Pesticides and public health: an analysis of the regulatory approach to assessing the carcinogenicity of glyphosate in the European Union.

Science.gov (United States)

Clausing, Peter; Robinson, Claire; Burtscher-Schaden, Helmut

2018-03-13

The present paper scrutinises the European authorities' assessment of the carcinogenic hazard posed by glyphosate based on Regulation (EC) 1272/2008. We use the authorities' own criteria as a benchmark to analyse their weight of evidence (WoE) approach. Therefore, our analysis goes beyond the comparison of the assessments made by the European Food Safety Authority and the International Agency for Research on Cancer published by others. We show that not classifying glyphosate as a carcinogen by the European authorities, including the European Chemicals Agency, appears to be not consistent with, and in some instances, a direct violation of the applicable guidance and guideline documents. In particular, we criticise an arbitrary attenuation by the authorities of the power of statistical analyses; their disregard of existing dose-response relationships; their unjustified claim that the doses used in the mouse carcinogenicity studies were too high and their contention that the carcinogenic effects were not reproducible by focusing on quantitative and neglecting qualitative reproducibility. Further aspects incorrectly used were historical control data, multisite responses and progression of lesions to malignancy. Contrary to the authorities' evaluations, proper application of statistical methods and WoE criteria inevitably leads to the conclusion that glyphosate is 'probably carcinogenic' (corresponding to category 1B in the European Union). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Risk-based indicators of Canadians' exposures to environmental carcinogens.

Science.gov (United States)

Setton, Eleanor; Hystad, Perry; Poplawski, Karla; Cheasley, Roslyn; Cervantes-Larios, Alejandro; Keller, C Peter; Demers, Paul A

2013-02-12

Tools for estimating population exposures to environmental carcinogens are required to support evidence-based policies to reduce chronic exposures and associated cancers. Our objective was to develop indicators of population exposure to selected environmental carcinogens that can be easily updated over time, and allow comparisons and prioritization between different carcinogens and exposure pathways. We employed a risk assessment-based approach to produce screening-level estimates of lifetime excess cancer risk for selected substances listed as known carcinogens by the International Agency for Research on Cancer. Estimates of lifetime average daily intake were calculated using population characteristics combined with concentrations (circa 2006) in outdoor air, indoor air, dust, drinking water, and food and beverages from existing monitoring databases or comprehensive literature reviews. Intake estimates were then multiplied by cancer potency factors from Health Canada, the United States Environmental Protection Agency, and the California Office of Environmental Health Hazard Assessment to estimate lifetime excess cancer risks associated with each substance and exposure pathway. Lifetime excess cancer risks in excess of 1 per million people are identified as potential priorities for further attention. Based on data representing average conditions circa 2006, a total of 18 carcinogen-exposure pathways had potential lifetime excess cancer risks greater than 1 per million, based on varying data quality. Carcinogens with moderate to high data quality and lifetime excess cancer risk greater than 1 per million included benzene, 1,3-butadiene and radon in outdoor air; benzene and radon in indoor air; and arsenic and hexavalent chromium in drinking water. Important data gaps were identified for asbestos, hexavalent chromium and diesel exhaust in outdoor and indoor air, while little data were available to assess risk for substances in dust, food and beverages. The ability to

Chromium carcinogenicity: California strategies.

Science.gov (United States)

Alexeeff, G V; Satin, K; Painter, P; Zeise, L; Popejoy, C; Murchison, G

1989-10-01

Hexavalent chromium was identified by California as a toxic air contaminant (TAC) in January 1986. The California Department of Health Services (CDHS) concurred with the findings of the International Agency for Research on Cancer that there is sufficient evidence to demonstrate the carcinogenicity of chromium in both animals and humans. CDHS did not find any compelling evidence demonstrating the existence of a threshold with respect to chromium carcinogenesis. Experimental data was judged inadequate to assess potential human reproductive risks from ambient exposures. Other health effects were not expected to occur at ambient levels. The theoretically increased lifetime carcinogenic risk from a continuous lifetime exposure to hexavalent chromium fell within the range 12-146 cancer cases per nanogram hexavalent chromium per cubic meter of air per million people exposed, depending on the potency estimate used. The primary sources found to contribute significantly to the risk of exposure were chrome platers, chromic acid anodizing facilities and cooling towers utilizing hexavalent chromium as a corrosion inhibitor. Evaluation of genotoxicity data, animal studies and epidemiological studies indicates that further consideration should be given to the potential carcinogenicity of hexavalent chromium via the oral route.

Environmental exposure to carcinogens in northwestern Cameroon ...

African Journals Online (AJOL)

African Health Sciences ... Humans can prevent themselves from a number of workplace and environmental carcinogens. ... Methods: A structured questionnaire was used to collect information on carcinogen exposure in the workplace and environment through trained field staff from volunteers after gaining informed ...

Respiratory carcinogenicity assessment of soluble nickel compounds.

Science.gov (United States)

Oller, Adriana R

2002-10-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

The limits of two-year bioassay exposure regimens for identifying chemical carcinogens.

Science.gov (United States)

Huff, James; Jacobson, Michael F; Davis, Devra Lee

2008-11-01

Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. In this Commentary, we propose that the sensitivity of chemical carcinogenesis bio-assays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at up to about 3 years. Studies of three chemicals of different structures and uses-aspartame, cadmium, and toluene-suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives.

AREVA sustainable development indicators guidelines

International Nuclear Information System (INIS)

2003-12-01

These guidelines set out the procedures used to measure and report the sustainable development and continuous progress data and indicators used within the Areva Group. It defines the scope of the guide, the list of indicators, the measurement and calculation procedures, the internal and external audits. (A.L.B.)

Development of an ergonomics guideline for the furniture manufacturing industry.

Science.gov (United States)

Mirka, Gary A

2005-03-01

Industry-specific ergonomics guidelines are an important component in the four-pronged approach to workplace ergonomics currently pursued by the United States Occupational Safety and Health Administration. The American Furniture Manufacturers Association has taken the initiative of developing such a guideline for its members. The result of this effort is the "AFMA Voluntary Ergonomics Guideline for the Furniture Manufacturing Industry", a document that includes basic information about ergonomics program components as well as a compilation of work-proven, ergonomics best practices as submitted by members of the furniture manufacturing community. This guideline was developed through an industry-research-government partnership and made strategic use of the unique attributes that each sector brought to this effort. Outlined in this paper are some of the characteristics of this partnership including, the roles played by each, the different motivations for pursuing the guideline, the challenges faced during the development of the document, the successes experienced in this process, as well as a proposed outline for measuring the effectiveness of this effort. The hope is that this summary, and some of the lessons learned contained herein, would be helpful to others considering the prospect of developing such a guideline for their industry.

Identifying occupational carcinogens: an update from the IARC Monographs.

Science.gov (United States)

Loomis, Dana; Guha, Neela; Hall, Amy L; Straif, Kurt

2018-05-16

The recognition of occupational carcinogens is important for primary prevention, compensation and surveillance of exposed workers, as well as identifying causes of cancer in the general population. This study updates previously published lists of known occupational carcinogens while providing additional information on cancer type, exposure scenarios and routes, and discussing trends in the identification of carcinogens over time. Data were extracted from International Agency for Research on Cancer (IARC) Monographs covering the years 1971-2017, using specific criteria to ensure occupational relevance and provide high confidence in the causality of observed exposure-disease associations. Selected agents were substances, mixtures or types of radiation classified in IARC Group 1 with 'sufficient evidence of carcinogenicity' in humans from studies of exposed workers and evidence of occupational exposure documented in the pertinent monograph. The number of known occupational carcinogens has increased over time: 47 agents were identified as known occupational carcinogens in 2017 compared with 28 in 2004. These estimates are conservative and likely underestimate the number of carcinogenic agents present in workplaces. Exposure to these agents causes a wide range of cancers; cancers of the lung and other respiratory sites, followed by skin, account for the largest proportion. The dominant routes of exposure are inhalation and dermal contact. Important progress has been made in identifying occupational carcinogens; nevertheless, there is an ongoing need for research on the causes of work-related cancer. Most workplace exposures have not been evaluated for their carcinogenic potential due to inadequate epidemiologic evidence and a paucity of quantitative exposure data. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Infectious Diseases Society of America Lyme guidelines: a cautionary tale about the development of clinical practice guidelines

Directory of Open Access Journals (Sweden)

Johnson Lorraine

2010-06-01

Full Text Available Abstract Flawed clinical practice guidelines may compromise patient care. Commercial conflicts of interest on panels that write treatment guidelines are particularly problematic, because panelists may have conflicting agendas that influence guideline recommendations. Historically, there has been no legal remedy for conflicts of interest on guidelines panels. However, in May 2008, the Attorney General of Connecticut concluded a ground-breaking antitrust investigation into the development of Lyme disease treatment guidelines by one of the largest medical societies in the United States, the Infectious Diseases Society of America (IDSA. Although the investigation found significant flaws in the IDSA guidelines development process, the subsequent review of the guidelines mandated by the settlement was compromised by a lack of impartiality at various stages of the IDSA review process. This article will examine the interplay between the recent calls for guidelines reform, the ethical canons of medicine, and due process considerations under antitrust laws as they apply to the formulation of the IDSA Lyme disease treatment guidelines. The article will also discuss pitfalls in the implementation of the IDSA antitrust settlement that should be avoided in the future.

Methods for the guideline-based development of quality indicators--a systematic review

Science.gov (United States)

2012-01-01

Background Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development. Methods We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables. Results From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement. Conclusions Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork. PMID:22436067

Application of the key characteristics of carcinogens in cancer hazard identification

Science.gov (United States)

Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David C; Beland, Frederick A; Smith, Martyn T

2018-01-01

Abstract Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as ‘is genotoxic,’ ‘is immunosuppressive’ or ‘modulates receptor-mediated effects,’ and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification. PMID:29562322

Guidelines for guideline developers: a systematic review of grading systems for medical tests

NARCIS (Netherlands)

Gopalakrishna, Gowri; Langendam, Miranda W.; Scholten, Rob J. P. M.; Bossuyt, Patrick M. M.; Leeflang, Mariska M. G.

2013-01-01

A variety of systems have been developed to grade evidence and develop recommendations based on the available evidence. However, development of guidelines for medical tests is especially challenging given the typical indirectness of the evidence; direct evidence of the effects of testing on patient

Practical guidelines for development of web-based interventions.

Science.gov (United States)

Chee, Wonshik; Lee, Yaelim; Chee, Eunice; Im, Eun-Ok

2014-10-01

Despite a recent high funding priority on technological aspects of research and a high potential impact of Web-based interventions on health, few guidelines for the development of Web-based interventions are currently available. In this article, we propose practical guidelines for development of Web-based interventions based on an empirical study and an integrative literature review. The empirical study aimed at development of a Web-based physical activity promotion program that was specifically tailored to Korean American midlife women. The literature review included a total of 202 articles that were retrieved through multiple databases. On the basis of the findings of the study and the literature review, we propose directions for development of Web-based interventions in the following steps: (1) meaningfulness and effectiveness, (2) target population, (3) theoretical basis/program theory, (4) focus and objectives, (5) components, (6) technological aspects, and (7) logistics for users. The guidelines could help promote further development of Web-based interventions at this early stage of Web-based interventions in nursing.

Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water.

Science.gov (United States)

Kumasaka, Mayuko Y; Yamanoshita, Osamu; Shimizu, Shingo; Ohnuma, Shoko; Furuta, Akio; Yajima, Ichiro; Nizam, Saika; Khalequzzaman, Md; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

2013-03-01

Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 μM arsenic and 10 μM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.

Developing Guidelines for IRM: A Grassroots Process in a Decentralized Environment.

Science.gov (United States)

Balkan, Lore; Sheldon, Philip

1990-01-01

The offices of Information Resource Management and Institutional Research at Virginia Tech developed a set of guidelines for information management. This article describes the historical evolution, the forces that motivated the development of the guidelines, and the consensus-building activities that led to the acceptance of the guidelines.…

Mutagens and carcinogens in foods. Epidemiologic review.

OpenAIRE

Hislop, T. G.

1993-01-01

Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence.

Mutagens and carcinogens in foods. Epidemiologic review.

Science.gov (United States)

Hislop, T. G.

1993-01-01

Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence. PMID:8499796

Environmental carcinogenic agents and cancer prevention. Risk assessment and management

International Nuclear Information System (INIS)

Tsugane, Shoichiro

2013-01-01

Many agents in our environment have been established as being carcinogenic, and in most cases, the carcinogenic properties of these agents were identified because of high-dose occupational or accidental exposure. Risk characterization, taking into account the dose-response relationship, and exposure assessment are essential for risk assessment and subsequent cancer prevention. Based on scientific risk assessment, risk management should be conducted practically by considering the economic, social, political, and other technical issues and by balancing the risks and benefits. Asbestos and environmental tobacco smoke are typical examples of established carcinogenic agents in the general environment, contributing to low-dose exposure. Further epidemiological studies are required to investigate the carcinogenicity of low-dose exposure to known carcinogenic agents such as arsenic and cadmium through dietary intake, radiation via medical and natural exposure, and air pollution due to diesel exhaust. In contrast, occupational chemical exposure to 1,2-dichloropropane and/or dichloromethane, whose carcinogenicity had not been established, was suggested to cause cholangiocarcinoma among workers involved in offset color proof-printing only after a rare situation of high-dose exposure was unveiled. Continuous monitoring of unusual cancer occurrences in target populations such as workers in occupational and regional settings as well as exposure reduction to suspected carcinogenic agents to levels as low as reasonably achievable is essential for reducing the risk of cancer due to environmental carcinogens. (author)

Environmental exposure to carcinogens in northwestern Cameroon

African Journals Online (AJOL)

EB

2013-09-03

Sep 3, 2013 ... Twenty-nine (69.0%) [95% CI: 47.0 – 75.0] participants could smell the carcinogenic chemicals they use. Thirty. (71.4%) [95% CI: 65.0 – 77.0] participants had been instructed in the use of protective equipment against carcinogens. Participants used preventive devices like hand gloves, laboratory coats, ...

Modelling of carcinogenic effects resulting from the combined action of radon and smoking

Energy Technology Data Exchange (ETDEWEB)

Ryabova, S.V.; Petin, V.G. [Medical Radiological Research Centre, Obninsk (Russian Federation)

2002-03-01

A simple mathematical model designed for the description of cell survival [1] and later developed for the evaluation of mutagenic effects [2] was proposed for the optimisation of the determination and prognosis of levels of carcinogenic effects in organisms, resulting from the combined action of different agents. The model postulates that the occurrence of synergism is to be expected as a result of additional carcinogenic damage arising from the interaction of sublesions induced by the two agents under investigation. These molecular sublesions are suggested to be non-carcinogenic, if each agent is taken separately. The main conclusion pertaining to this model is the existence of the highest level of synergistic effect. The model predicts the input values and conditions under which this level is reached. The synergistic effect appeared to decline with any deviation from the optimal value for the ratio of carcinogenic effects produced by each agent alone. These conclusions were verified by comparison with experimental data published by other researchers. (orig.)

Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

Directory of Open Access Journals (Sweden)

Buonaguro Franco M

2009-06-01

Full Text Available Abstract Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV. Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC Monographs Working Group to re-assess the carcinogenicity of different HPV types.

EPA's evaluation of the carcinogenic potential of glyphosate

Science.gov (United States)

Recently, several international agencies have evaluated the carcinogenic potential of glyphosate. In March 2015, the International Agency for Research on Cancer (IARC), a subdivision of the World Health Organization (WHO), determined that glyphosate was a probable carcinogen (gro...

Legal issues in the development and use of clinical practice guidelines.

Science.gov (United States)

Gevers, S

2001-01-01

Over the last ten years, the development and dissemination of practice guidelines has increased at a rapid pace. From a legal point of view, it should always be made clear whether a guideline has been developed to improve the quality of care and is based on medical evidence and professional experience, or whether other concerns and considerations (organisational, financial) did prevail. Guidelines should not simply be imposed on health professionals; that would result in a standardisation of care that does no justice to individual patient needs and preferences. Patients have the right to be informed about reasonable and realistic treatment alternatives, even if they are not included in the guideline. Using cost effectiveness analysis in guideline development can help to reduce care of dubious effectiveness. But if cost considerations are used as a reason to limit effective medical care, the guidelines in question need political legitimation.

Carcinogenicity tests of certain environmental and industrial chemicals

International Nuclear Information System (INIS)

Weisburger, E.K.; Ulland, B.M.; Nam, J.; Gart, J.J.; Weisburger, J.H.

1981-01-01

Fourteen chemicals of varied uses were tested for carcinogenicity by oral administration in male and female Charles River CD rats. Under the conditions of the tests, propane sultone, propylene imine, and ethylenethiourea, in addition to the positive control N-2-fluorenylacetamide, were carcinogenic. Avadex, bis(2-chloroethyl) ether, the potassium salt of bis(2-hydroxyethyl) dithiocarbamic acid, ethylene carbonate, and semicarbazide hydrochloride were not carcinogenic under the test conditions. Dithiooxamide, glycerol alpha-monochlorohydrin, and thiosemicarbazide gave somewhat ambiguous results, though administered at high enough dose levels to be toxic. An inadequate number of animals survived treatments with sodium azide, sodium bisulfide, and vinylene carbonate, or the animals may not have received sufficiently high doses of the test chemicals to provide maximum test sensitivity. However, there were no indications that these three chemicals were carcinogenic under the test conditions

Cell-mediated mutagenesis and cell transformation of mammalian cells by chemical carcinogens

International Nuclear Information System (INIS)

Huberman, E.; Langenbach, R.

1977-01-01

We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro

The multitude and diversity of environmental carcinogens

International Nuclear Information System (INIS)

Belpomme, D.; Irigaray, P.; Hardell, L.; Clapp, R.; Montagnier, L.; Epstein, S.; Sasco, A.J.

2007-01-01

We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment

Environmental carcinogens in human target tissues in culture: Progress report

International Nuclear Information System (INIS)

Hsu, I.C.

1987-01-01

We have accumulated more experimental evidences that demonstrated the comparative approaches with human cells will allow us to predict human risk with good accuracy following exposure to toxic chemicals. We also synthesized several carcinogenic DNA adducts, i.e., the major benzo[a]pyrene DNA adduct, 0 6 -methyldeoxyguanosine, 7-methyl- deoxyguanosine and 2-methyl-deoxyguanosine to be used as standards for quantitating DNA adduct formation in carcinogen exposed cells. A simple synthetic method was developed for preparation of the major B[a]p DNA adduct with yields better than those reported. The main accomplishments related to the originally stated objectives are summarized. 8 refs., 2 figs., 1 tab

Carcinogenic and mutagenic properties of chemicals in drinking water

Energy Technology Data Exchange (ETDEWEB)

Bull, R J

1985-12-01

Isolated cases of careless handling of industrial and domestic waste has lead to a wide variety of dangerous chemicals being inadvertently introduced into drinking water. However, chemicals with established carcinogenic and mutagenic properties that occur with a high frequency and in multiple locations are limited in number. To date, the chief offenders have been chemicals of relatively low carcinogenic potency. Some of the more common chemicals are formed as by-products of disinfection. The latter process is generally regarded as essential to the production of a ''microbiologically safe'' drinking water. Consequently, any reductions in what may be a relatively small carcinogenic risk must be balanced against a potential for a higher frequency of waterborne infectious disease. The results of recent toxicological investigations will be reviewed to place the potential carcinogenic and mutagenic hazards frequently associated with drinking water into perspective. First, evidence for the carcinogenicity of certain volatile organic compounds such as trichloroethylene, tetrachloroethylene and carbon tetrachloride is considered. Second, the carcinogenic activity that can be ascribed to various by-products of chlorination is reviewed in some detail. Finally, recent evidence that other chemicals derived from the treatment and distribution of drinking water is highlighted as an area requiring move systematic attention. 72 references.

Is ionizing radiation regulated more stringently than chemical carcinogens

International Nuclear Information System (INIS)

Travis, C.C.; Pack, S.R.; Hattemer-Frey, H.A.

1989-01-01

It is widely believed that United States government agencies regulate exposure to ionizing radiation more stringently than exposure to chemical carcinogens. It is difficult to verify this perception, however, because chemical carcinogens and ionizing radiation are regulated using vastly different strategies. Chemical carcinogens are generally regulated individually. Regulators consider the risk of exposure to one chemical rather than the cumulative radiation exposure from all sources. Moreover, standards for chemical carcinogens are generally set in terms of quantities released or resultant environmental concentrations, while standards for ionizing radiation are set in terms of dose to the human body. Since chemicals and ionizing radiation cannot be compared on the basis of equal dose to the exposed individual, standards regulating chemicals and ionizing radiation cannot be compared directly. It is feasible, however, to compare the two sets of standards on the basis of equal risk to the exposed individual, assuming that standards for chemicals and ionizing radiation are equivalent if estimated risk levels are equitable. This paper compares risk levels associated with current standards for ionizing radiation and chemical carcinogens. The authors do not attempt to determine whether either type of risk is regulated too stringently or not stringently enough but endeavor only to ascertain if ionizing radiation is actually regulated more strictly than chemical carcinogens

Developing and implementing health and sustainability guidelines for institutional food service.

Science.gov (United States)

Kimmons, Joel; Jones, Sonya; McPeak, Holly H; Bowden, Brian

2012-05-01

Health and sustainability guidelines for institutional food service are directed at improving dietary intake and increasing the ecological benefits of the food system. The development and implementation of institutional food service guidelines, such as the Health and Human Services (HHS) and General Services Administration (GSA) Health and Sustainability Guidelines for Federal Concessions and Vending Operations (HHS/GSA Guidelines), have the potential to improve the health and sustainability of the food system. Institutional guidelines assist staff, managers, and vendors in aligning the food environment at food service venues with healthier and more sustainable choices and practices. Guideline specifics and their effective implementation depend on the size, culture, nature, and management structure of an institution and the individuals affected. They may be applied anywhere food is sold, served, or consumed. Changing institutional food service practice requires comprehensive analysis, engagement, and education of all relevant stakeholders including institutional management, members of the food supply chain, and customers. Current examples of food service guidelines presented here are the HHS and GSA Health and Sustainability Guidelines for Federal Concessions and Vending Operations, which translate evidence-based recommendations on health and sustainability into institutional food service practices and are currently being implemented at the federal level. Developing and implementing guidelines has the potential to improve long-term population health outcomes while simultaneously benefitting the food system. Nutritionists, public health practitioners, and researchers should consider working with institutions to develop, implement, and evaluate food service guidelines for health and sustainability.

Advanced human-system interface design review guideline. General evaluation model, technical development, and guideline description

International Nuclear Information System (INIS)

O'Hara, J.M.

1994-07-01

Advanced control rooms will use advanced human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the operator's overall role in the system, the method of information presentation, and the ways in which operators interact with the system. The U.S. Nuclear Regulatory Commission (NRC) reviews the HSI aspects of control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported to protect public health and safety. The principal guidance available to the NRC, however, was developed more than ten years ago, well before these technological changes. Accordingly, the human factors guidance needs to be updated to serve as the basis for NRC review of these advanced designs. The purpose of this project was to develop a general approach to advanced HSI review and the human factors guidelines to support NRC safety reviews of advanced systems. This two-volume report provides the results of the project. Volume I describes the development of the Advanced HSI Design Review Guideline (DRG) including (1) its theoretical and technical foundation, (2) a general model for the review of advanced HSIs, (3) guideline development in both hard-copy and computer-based versions, and (4) the tests and evaluations performed to develop and validate the DRG. Volume I also includes a discussion of the gaps in available guidance and a methodology for addressing them. Volume 2 provides the guidelines to be used for advanced HSI review and the procedures for their use

Advanced human-system interface design review guideline. General evaluation model, technical development, and guideline description

Energy Technology Data Exchange (ETDEWEB)

O`Hara, J.M.

1994-07-01

Advanced control rooms will use advanced human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the operator`s overall role in the system, the method of information presentation, and the ways in which operators interact with the system. The U.S. Nuclear Regulatory Commission (NRC) reviews the HSI aspects of control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported to protect public health and safety. The principal guidance available to the NRC, however, was developed more than ten years ago, well before these technological changes. Accordingly, the human factors guidance needs to be updated to serve as the basis for NRC review of these advanced designs. The purpose of this project was to develop a general approach to advanced HSI review and the human factors guidelines to support NRC safety reviews of advanced systems. This two-volume report provides the results of the project. Volume I describes the development of the Advanced HSI Design Review Guideline (DRG) including (1) its theoretical and technical foundation, (2) a general model for the review of advanced HSIs, (3) guideline development in both hard-copy and computer-based versions, and (4) the tests and evaluations performed to develop and validate the DRG. Volume I also includes a discussion of the gaps in available guidance and a methodology for addressing them. Volume 2 provides the guidelines to be used for advanced HSI review and the procedures for their use.

Carcinogenic and antitumor effects of aminotriazole on acatalasemic and normal catalase mice

International Nuclear Information System (INIS)

Feinstein, R.N.; Fry, R.J.M.; Staffeidt, E.F.

1978-01-01

Dietary 3-amino-1H-1,2,4-triazole (AT), although carcinogenic when administered alone, was an antitumor agent when combined with certain other carcinogenic stimuli. The carcinogenic effect was prominent in the livers of C3H mice; thyroid tumors were less common because they required a longer period of development, and the life-span of the animal was shortened by the AT diet. The antitumor effects of AT included: delay in appearance of mammary tumors, striking reduction in γ-radiation-induced lymphomas, and sharp reduction in neutron radiation-induced harderian gland and ovarian tumors. On an AT diet, the inbred C3H acatalasemic mouse substrain developed more liver tumors, starting earlier, than did the C3H normal catalase substrain. We suggest that our findings pointed to a possible relevance of catalase and H 2 O 2 in carcinogenesis. The most probable mechanism for the increased incidence of liver tumors in AT-treated acatalasemic mice was the diminished rate of degradation of endogenous H 2 O 2

Development of the International Guidelines for Home Health Nursing.

Science.gov (United States)

Narayan, Mary; Farris, Cindy; Harris, Marilyn D; Hiong, Fong Yoke

2017-10-01

Throughout the world, healthcare is increasingly being provided in home and community-based settings. There is a growing awareness that the most effective, least costly, patient-preferred setting is patients' home. Thus, home healthcare nursing is a growing nursing specialty, requiring a unique set of nursing knowledge and skills. Unlike many other nursing specialties, home healthcare nursing has few professional organizations to develop or support its practice. This article describes how an international network of home healthcare nurses developed international guidelines for home healthcare nurses throughout the world. It outlines how the guidelines for home healthcare nursing practice were developed, how an international panel of reviewers was recruited, and the process they used for reaching a consensus. It also describes the plan for nurses to contribute to future updates to the guidelines.

The development of a multidisciplinary, evidence-based guideline for "HIV and employment".

Science.gov (United States)

Wagener, Marlies N; Roelofs, Pepijin; Miedema, Harold S; Brandjes, Dees P M; Dahmen, Rutger; van Gorp, Eric C M

2015-01-01

The objective of this study was to develop a multidisciplinary guideline that supports the care and vocational rehabilitation of HIV-infected people with employment-related problems. The guideline was developed according to the "evidence-based guideline development" method developed by the Dutch Institute for Health Care Improvement. This method consists of the following steps: forming a multidisciplinary core group and an expert panel, formulating key questions, searching and appraising the available literature, formulating considerations and recommendations, peer reviewing the draft guideline, and authorizing the final guideline. All relevant professional associations were represented in the core group that was assembled to develop the guideline, i.e., HIV doctors, HIV nurses, general practitioners, occupational health physicians, psychologists, social workers, occupational health nurses, vocational experts, and insurance physicians. Five key questions for the guideline were formulated with the following themes: determinants of employment, disclosure and stigma, self-management, interventions, and the organization of care. In the literature review on these topics, 45 studies met the inclusion criteria. The methodological quality of the included articles was poor. Factors such as patient preferences and medical/ethical issues were considered. The recommendations in the guideline are a weighting of the scientific evidence and the considerations of the core group. The guideline, as well as its summary for daily practice, clarifies the most important barriers and facilitators to people with HIV either staying at work or returning to work, and it constitutes a clinical, easy-to-use guideline for health-care providers and how they can support people with HIV who want to work.

Nuclear DNA synthesis rate and labelling index: effects of carcinogenic and non-carcinogenic chemicals on its behaviour in the organism of growing CBA mice

International Nuclear Information System (INIS)

Amlacher, E.; Rudolph, C.

1978-01-01

Well known bioassays have been compared with the author's thymidine incorporation-screening system and other assays based on biochemical quantification of DNA synthesis as a possibility of identification of carcinogens. The partial inhibition of the whole DNA synthesis in a proliferating cell population after treatment with toxic and carcinogenic chemicals is an early common response especially in hepatectomized animal, livers caused by the effects of those substances. However, by quantitative evaluation of the nuclear DNA synthesis rate as a basic parameter, using autoradiographs of kidney and liver of juvenile growing CBA mice, it is possible to differentiate carcinogenic from non-carcinogenic chemicals by means of silver grain counting after 3 H-TdR incorporation. On the contrary, the whole DNA synthesis, expressed by the 3 H-labelling index (in per cent) of kidney and liver, did not permit such a differentiation in the experimental arrangement used. It could be demonstrated that carcinogenic compounds of different chemical classes partially inhibit the nuclear DNA synthesis rate significantly over a period of more than 24 hours. The tested non-carcinogenic compounds did not show this suppressive effect on the nuclear DNA synthesis rate. (author)

Carcinogenicity of methyl-tertiary butyl ether in gasoline.

Science.gov (United States)

Mehlman, Myron A

2002-12-01

Methyl tertiary butyl ether (MTBE) was added to gasoline on a nationwide scale in 1992 without prior testing of adverse, toxic, or carcinogenic effects. Since that time, numerous reports have appeared describing adverse health effects of individuals exposed to MTBE, both from inhalation of fumes in the workplace and while pumping gasoline. Leakage of MTBE, a highly water-soluble compound, from underground storage tanks has led to contamination of the water supply in many areas of the United States. Legislation has been passed by many states to prohibit the addition of MTBE to gasoline. The addition of MTBE to gasoline has not accomplished its stated goal of decreasing air pollution, and it has posed serious health risks to a large portion of the population, particularly the elderly and those with respiratory problems, asthma, and skin sensitivity. Reports of animal studies of carcinogenicity of MTBE began to appear in the 1990s, prior to the widespread introduction of MTBE into gasoline. These reports were largely ignored. In ensuing years, further studies have shown that MTBE causes various types of malignant tumors in mice and rats. The National Toxicology Program (NTP) Board of Scientific Counselors' Report on Carcinogens Subcommittee met in December 1998 to consider listing MTBE as "reasonably anticipated to be a human carcinogen." In spite of recommendations from Dr. Bailer, the primary reviewer, and other scientists on the committee, the motion to list MTBE in the report was defeated by a six to five vote, with one abstention. On the basis of animal studies, it is widely accepted that if a chemical is carcinogenic in appropriate laboratory animal test systems, it must be treated as though it were carcinogenic in humans. In the face of compelling evidence, NTP Committee members who voted not to list MTBE as "reasonably anticipated to be a human carcinogen" did a disservice to the general public; this action may cause needless exposure of many to health risks

Carcinogenicity assessments of biotechnology-derived pharmaceuticals: a review of approved molecules and best practice recommendations.

Science.gov (United States)

Vahle, John L; Finch, Gregory L; Heidel, Shawn M; Hovland, David N; Ivens, Inge; Parker, Suezanne; Ponce, Rafael A; Sachs, Clifford; Steigerwalt, Ronald; Short, Brian; Todd, Marque D

2010-06-01

An important safety consideration for developing new therapeutics is assessing the potential that the therapy will increase the risk of cancer. For biotherapeutics, traditional two-year rodent bioassays are often not scientifically applicable or feasible. This paper is a collaborative effort of industry toxicologists to review past and current practice regarding carcinogenicity assessments of biotherapeutics and to provide recommendations. Publicly available information on eighty marketed protein biotherapeutics was reviewed. In this review, no assessments related to carcinogenicity or tumor growth promotion were identified for fifty-one of the eighty molecules. For the twenty-nine biotherapeutics in which assessments related to carcinogenicity were identified, various experimental approaches were employed. This review also discusses several key principles to aid in the assessment of carcinogenic potential, including (1) careful consideration of mechanism of action to identify theoretical risks, (2) careful investigation of existing data for indications of proliferative or immunosuppressive potential, and (3) characterization of any proliferative or immunosuppressive signals detected. Traditional two-year carcinogenicity assays should not be considered as the default method for assessing the carcinogenicity potential of biotherapeutics. If experimentation is considered warranted, it should be hypothesis driven and may include a variety of experimental models. Ultimately, it is important that preclinical data provide useful guidance in product labeling.

Using Qualitative Research to Inform Development of Professional Guidelines: A Case Study of the Society of Critical Care Medicine Family-Centered Care Guidelines.

Science.gov (United States)

Coombs, Maureen A; Davidson, Judy E; Nunnally, Mark E; Wickline, Mary A; Curtis, J Randall

2017-08-01

To explore the importance, challenges, and opportunities using qualitative research to enhance development of clinical practice guidelines, using recent guidelines for family-centered care in the ICU as an example. In developing the Society of Critical Care Medicine guidelines for family-centered care in the neonatal ICU, PICU, and adult ICU, we developed an innovative adaptation of the Grading of Recommendations, Assessments, Development and Evaluations approach to explicitly incorporate qualitative research. Using Grading of Recommendations, Assessments, Development and Evaluations and the Council of Medical Specialty Societies principles, we conducted a systematic review of qualitative research to establish family-centered domains and outcomes. Thematic analyses were undertaken on study findings and used to support Population, Intervention, Comparison, Outcome question development. We identified and employed three approaches using qualitative research in these guidelines. First, previously published qualitative research was used to identify important domains for the Population, Intervention, Comparison, Outcome questions. Second, this qualitative research was used to identify and prioritize key outcomes to be evaluated. Finally, we used qualitative methods, member checking with patients and families, to validate the process and outcome of the guideline development. In this, a novel report, we provide direction for standardizing the use of qualitative evidence in future guidelines. Recommendations are made to incorporate qualitative literature review and appraisal, include qualitative methodologists in guideline taskforce teams, and develop training for evaluation of qualitative research into guideline development procedures. Effective methods of involving patients and families as members of guideline development represent opportunities for future work.

Developing the Botswana Primary Care Guideline: an integrated, symptom-based primary care guideline for the adult patient in a resource-limited setting

Directory of Open Access Journals (Sweden)

Tsima BM

2016-08-01

Full Text Available Billy M Tsima,1 Vincent Setlhare,1 Oathokwa Nkomazana2 1Department of Family Medicine and Public Health, 2Department of Surgery, Faculty of Medicine, University of Botswana, Gaborone, Botswana Background: Botswana’s health care system is based on a primary care model. Various national guidelines exist for specific diseases. However, most of the guidelines address management at a tertiary level and often appear nonapplicable for the limited resources in primary care facilities. An integrated symptom-based guideline was developed so as to translate the Botswana national guidelines to those applicable in primary care. The Botswana Primary Care Guideline (BPCG integrates the care of communicable diseases, including HIV/AIDS and noncommunicable diseases, by frontline primary health care workers.Methods: The Department of Family Medicine, Faculty of Medicine, University of Botswana, together with guideline developers from the Knowledge Translation Unit (University of Cape Town collaborated with the Ministry of Health to develop the guideline. Stakeholder groups were set up to review specific content of the guideline to ensure compliance with Botswana government policy and the essential drug list.Results: Participants included clinicians, academics, patient advocacy groups, and policymakers from different disciplines, both private and public. Drug-related issues were identified as necessary for implementing recommendations of the guideline. There was consensus by working groups for updating the essential drug list for primary care and expansion of prescribing rights of trained nurse prescribers in primary care within their scope of practice. An integrated guideline incorporating common symptoms of diseases seen in the Botswana primary care setting was developed.Conclusion: The development of the BPCG took a broad consultative approach with buy in from relevant stakeholders. It is anticipated that implementation of the BPCG will translate into better

Risk assessment of DNA-reactive carcinogens in food.

Science.gov (United States)

Jeffrey, A M; Williams, G M

2005-09-01

Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B(1) (AFB(1)), a limit of 20 ppb or approximately 30 microg/day has been set and is considered a tolerable daily intake (TDI). Since AFB(1) is considered a potent carcinogen, doses of carcinogens is made.

Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

Science.gov (United States)

Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

1987-05-01

carcinogenicity and the four in vitro STTs to attempt to confirm the current findings. The standard against which the performance of STTs is measured has changed dramatically in the past decade. The high levels of concordance published in the early 1970s were accurate at the time. Nearly all known carcinogens tested were genotoxic, and there was little experimental evidence on which to base a judgment of noncarcinogenicity which, taken together, restricted assessment of test performances with noncarcinogens. With the increasing availability of results from NCI and NTP 2-year carcinogenicity studies in rodents, higher frequencies of nongenotoxic carcinogens and genotoxic noncarcinogens have been observed; this has resulted in the reduced concordance of the STT results with carcinogenicity results. It is clear that even with a battery of assays, not all rodent carcinogens are in vitro mutagens nor are all in vitro mutagens rodent carcinogens. If current in vitro STTs are expected to replace long-term rodent studies for the identification of chemical carcinogens, then that expectation should be abandoned. STTs do, however, continue to offer an economical, rapid, and dependable means to detect genotoxic chemicals. There is a range of applications in which STTs have been used successfully, from the identification of mutagenic fractions in complex mixtures such as cooked meat (32, 33) or air pollutants (34) to the early identification of genetic toxicity in the development of new chemical products (35). Requirements for the use of STT have not been consistent in both the national and international regulatory agencies. This is evident in the variety of testing requirements (8) and the different impacts that positive test results have on the registration or further testing requirements of chemicals. Consensus on these matters is not likely to occur in the near future, but agreement should be possible in certain areas. For instance, any time a new test or strategy is proposed, it is

The carcinogenicity of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU).

Science.gov (United States)

Warzok, R; Martin, J; Mendel, J; Thust, R; Schwarz, H

1983-01-01

In long-term experiments with Hooded rats the carcinogenic potential of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU) could be demonstrated for the first time. Br-MPNU is formed also endogenously after combined administration of 1-methyl-3(p-bromophenyl)-urea (Br-MPU) and sodium nitrite. After repeated intragastric administration of 0.33 mmol Br-MPU and 0.73 mmol NaNO2 per kg b.w. papillomas and carcinomas of the forestomach developed in 83%. After repeated administration of 0.28 mmol Br-MPNU per kg b.w. these neoplasms were observed in 88%. The comparison of results obtained in similar experiments with 1-methyl-3-phenyl-1-nitrosourea shows that bromine substitution led to a reduction of the carcinogenic activity. The present paper is part of a complex program studying the interrelationships between structure, physico-chemical properties, mutagenicity and carcinogenicity of nitrosoureas.

Standing operating procedures for developing acute exposure guideline levels for hazardous chemicals

National Research Council Canada - National Science Library

National Research Council (U.S.). Subcommittee on Acute Exposure Guideline Levels

2001-01-01

Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals contains a detailed and comprehensive methodology for developing acute exposure guideline levels (AEGLs...

The Role of Health Services Research in Developing Practice Policy: Development of Practice Guidelines.

Science.gov (United States)

Crall, James J.

1990-01-01

The paper offers guidance for the incorporation of treatment effectiveness research into clinical dental practice guidelines. Recommended is inclusion of patients' preferences for different outcomes as well as of clinical outcomes in development of valid practice guidelines. (DB)

Developing a Clinician Friendly Tool to Identify Useful Clinical Practice Guidelines: G-TRUST.

Science.gov (United States)

Shaughnessy, Allen F; Vaswani, Akansha; Andrews, Bonnie K; Erlich, Deborah R; D'Amico, Frank; Lexchin, Joel; Cosgrove, Lisa

2017-09-01

Clinicians are faced with a plethora of guidelines. To rate guidelines, they can select from a number of evaluation tools, most of which are long and difficult to apply. The goal of this project was to develop a simple, easy-to-use checklist for clinicians to use to identify trustworthy, relevant, and useful practice guidelines, the Guideline Trustworthiness, Relevance, and Utility Scoring Tool (G-TRUST). A modified Delphi process was used to obtain consensus of experts and guideline developers regarding a checklist of items and their relative impact on guideline quality. We conducted 4 rounds of sampling to refine wording, add and subtract items, and develop a scoring system. Multiple attribute utility analysis was used to develop a weighted utility score for each item to determine scoring. Twenty-two experts in evidence-based medicine, 17 developers of high-quality guidelines, and 1 consumer representative participated. In rounds 1 and 2, items were rewritten or dropped, and 2 items were added. In round 3, weighted scores were calculated from rankings and relative weights assigned by the expert panel. In the last round, more than 75% of experts indicated 3 of the 8 checklist items to be major indicators of guideline usefulness and, using the AGREE tool as a reference standard, a scoring system was developed to identify guidelines as useful, may not be useful, and not useful. The 8-item G-TRUST is potentially helpful as a tool for clinicians to identify useful guidelines. Further research will focus on its reliability when used by clinicians. © 2017 Annals of Family Medicine, Inc.

Mycotoxins as human carcinogens-the IARC Monographs classification.

Science.gov (United States)

Ostry, Vladimir; Malir, Frantisek; Toman, Jakub; Grosse, Yann

2017-02-01

Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)-through its IARC Monographs programme-has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B 1 , B 2 , G 1 , G 2 and M 1 ), fumonisins (fumonisin B 1 and B 2 ) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis-should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans-could lead to the reclassification of OTA.

Guideline group composition and group processes: article 3 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.

Science.gov (United States)

Kunz, Regina; Fretheim, Atle; Cluzeau, Françoise; Wilt, Timothy J; Qaseem, Amir; Lelgemann, Monika; Kelson, Marcia; Guyatt, Gordon; Schünemann, Holger J

2012-12-01

Professional societies, like many other organizations around the world, have recognized the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the third of a series of 14 articles that were prepared to advise guideline developers in respiratory and other diseases on considerations for group compositions and group processes in guideline development, and how this can be effectively integrated in the context of respiratory disease guidelines on a national and international level. We updated a review of the literature addressing group composition and group process, focusing on the following questions: 1. How to compose a functioning and representative guideline group; Who should be included in a guideline panel?; How to select organizations, groups, and individuals; What expertise is needed?; Consultation with non-included groups. 2. How to assure a functioning group process; How to make the process constructive; Balancing participation and finding agreement; Administrative support; What constitutes sufficient resources? Our conclusions are based on available evidence from published literature, experience from guideline developers, and workshop discussions. Formal studies addressing optimal processes in developing guidelines are limited, and experience from guideline organizations supplement the formal studies. When resources are available, guideline development groups should aim for multidisciplinary groups, including patients. Prerequisites for a multidisciplinary group include: a strong chair experienced in group facilitation with broad acceptance in the group, training the group in guideline methodology, and professional technical support. Formal consensus developing methods have proved effective in reaching agreement on the final recommendations.

Final report of advisory subcommittee on development of JENDL. Guideline for developing next JENDL

International Nuclear Information System (INIS)

Chiba, Go; Iwamoto, Osamu

2015-01-01

Advisory Subcommittee on Development of JENDL was established under JENDL Committee on fiscal year 2013 to discuss the subject concerning on development of next JENDL. Members of the subcommittee were selected from developers and users of JENDL and researchers on nuclear data measurements. They discussed guidelines on next JENDL with exchanging ideas on problems of JENDL and its solution from each view point. This report describes the results of the discussions on the problems and guideline with the present status on the JENDL development. (author)

Why consider patients' preferences? A discourse analysis of clinical practice guideline developers.

Science.gov (United States)

Boivin, Antoine; Green, Judith; van der Meulen, Jan; Légaré, France; Nolte, Ellen

2009-08-01

Several organizations are advocating for patients' preferences to be considered in clinical practice guideline development and implementation. However, lack of agreement on the goal and meaning of this policy curtails evaluation and development of patient involvement programs. To describe guideline developers' discourses on the goal of considering patients' preferences. Qualitative study using discourse analysis. 18 participants (patients, health professionals, and public health experts) from 2 groups of British guideline developers. Template analysis of semi-structured individual interviews was strengthened by active search for deviant cases, team debriefing, and member checking. All respondents supported the idea of taking account of patients' preferences in guidelines. Divergences with the goal and meaning of considering preferences were structured in 4 discourses: (1) The Governance discourse constructs guideline development as a rational process of synthesizing population data-including evidence on patients' preferences-to maximize public health within the constraints of available resources; (2) the Informed Decision discourse aims at fostering patients' choice by providing tailored information on the risks and benefits of interventions; (3) the Professional Care discourse insists on basing professionals' recommendations on the individual characteristics of patients; (4) The Consumer Advocacy discourse argues for greater political power and influence over guideline development and clinical decision making. The identified discourses provide a set of hypothesis on how patient involvement programs are expected to work, which could help clarify the goals pursued by guideline organizations and anchor further evaluation efforts.

RADON AND CARCINOGENIC RISK IN MOSCOW

Directory of Open Access Journals (Sweden)

S. M. Golovanev

2015-01-01

Full Text Available Objective: comparative evaluation of carcinogenic risk inMoscowfrom radon in indoor and atmospheric pollutants.Materials and methods: the lung cancer incidence in Moscow; radiation-hygienic passport of the territory; .U.S. EPA estimated average age at all and radon induced deaths, years of life lost; Report of UNSCEAR 2006 and WHO handbook on indoor radon, 2009. Trend analysis of incidence; evaluation of the excess relative risk; assessment of ratio radon-induced population risk and published values оf total population carcinogenic risk from chemical carcinogens.Results: it is shown that the 304 cases of lung cancer per year (1. 85 10-3 on average from 2006 to 2011 (21280diseases for 70 years in addition to background level induced by radon; the differences in average trends of all lungcancer incidence in the districts can exceed 25%.Conclusion. The potential of risk reduction by measures of mitigation radon concentration exceeds 5 times the cost efficiency to reduce emissions from vehicles and can reduce cancer incidence, on average 236 cases per year; population risk 16520 cases over 70 years or save not less than 2832 person-years of life per year. The annual effect of reducing losses from not-survival of 12 years as a result of radon-induced lung cancer deaths exceeds 14160000 dollars. The evaluating of the carcinogenic risk from radon in accordance with the definition of population risk increases the predictive evaluation of the effectiveness of preventive measures more than twice.

Dietary Carcinogens and Anticarcinogens.

Science.gov (United States)

Ames, Bruce N.

1983-01-01

Describes 16 mutagens/carcinogens found in plant food and coffee as well as several anticarcinogens also found in such food. Speculates on relevant biochemical mechanisms, particularly the role of oxygen radicals and their inhibitors in the fat/cancer relationship, promotion, anticarcinogenesis, and aging. (JN)

Consumer involvement in dietary guideline development: opinions from European stakeholders.

Science.gov (United States)

Brown, Kerry A; Hermoso, Maria; Timotijevic, Lada; Barnett, Julie; Lillegaard, Inger Therese L; Řehůřková, Irena; Larrañaga, Ainhoa; Lončarević-Srmić, Azra; Andersen, Lene Frost; Ruprich, Jiří; Fernández-Celemín, Laura; Raats, Monique M

2013-05-01

The involvement of consumers in the development of dietary guidelines has been promoted by national and international bodies. Yet, few best practice guidelines have been established to assist with such involvement. Qualitative semi-structured interviews explored stakeholders' beliefs about consumer involvement in dietary guideline development. Interviews were conducted in six European countries: the Czech Republic, Germany, Norway, Serbia, Spain and the UK. Seventy-seven stakeholders were interviewed. Stakeholders were grouped as government, scientific advisory body, professional and academic, industry or non-government organisations. Response rate ranged from 45 % to 95 %. Thematic analysis was conducted with the assistance of NVivo qualitative software. Analysis identified two main themes: (i) type of consumer involvement and (ii) pros and cons of consumer involvement. Direct consumer involvement (e.g. consumer organisations) in the decision-making process was discussed as a facilitator to guideline communication towards the end of the process. Indirect consumer involvement (e.g. consumer research data) was considered at both the beginning and the end of the process. Cons to consumer involvement included the effect of vested interests on objectivity; consumer disinterest; and complications in terms of time, finance and technical understanding. Pros related to increased credibility and trust in the process. Stakeholders acknowledged benefits to consumer involvement during the development of dietary guidelines, but remained unclear on the advantage of direct contributions to the scientific content of guidelines. In the absence of established best practice, clarity on the type and reasons for consumer involvement would benefit all actors.

Developing and Implementing Health and Sustainability Guidelines for Institutional Food Service123

Science.gov (United States)

Kimmons, Joel; Jones, Sonya; McPeak, Holly H.; Bowden, Brian

2012-01-01

Health and sustainability guidelines for institutional food service are directed at improving dietary intake and increasing the ecological benefits of the food system. The development and implementation of institutional food service guidelines, such as the Health and Human Services (HHS) and General Services Administration (GSA) Health and Sustainability Guidelines for Federal Concessions and Vending Operations (HHS/GSA Guidelines), have the potential to improve the health and sustainability of the food system. Institutional guidelines assist staff, managers, and vendors in aligning the food environment at food service venues with healthier and more sustainable choices and practices. Guideline specifics and their effective implementation depend on the size, culture, nature, and management structure of an institution and the individuals affected. They may be applied anywhere food is sold, served, or consumed. Changing institutional food service practice requires comprehensive analysis, engagement, and education of all relevant stakeholders including institutional management, members of the food supply chain, and customers. Current examples of food service guidelines presented here are the HHS and GSA Health and Sustainability Guidelines for Federal Concessions and Vending Operations, which translate evidence-based recommendations on health and sustainability into institutional food service practices and are currently being implemented at the federal level. Developing and implementing guidelines has the potential to improve long-term population health outcomes while simultaneously benefitting the food system. Nutritionists, public health practitioners, and researchers should consider working with institutions to develop, implement, and evaluate food service guidelines for health and sustainability. PMID:22585909

Identification of Radiation Effects on Carcinogenic Food Estimated by Ames Test

International Nuclear Information System (INIS)

Afifi, M.; Eid, I.; El - Nagdy, M.; Zaher, R.; Abd El-Karem, H.; Abd EL Karim, A.

2016-01-01

A major concern in studies related to carcinogenesis is the exposure to the exogenous carcinogens that may occur in food in both natural and polluted human environments. The purpose of the present study is to examine some of food products by Ames test to find out if food products carcinogenic then expose food to gamma radiation to find out the effect of radiation on it as a treatment. In this study, the food samples were examined by Ames test (Salmonella typhimurium mutagenicity test) to find out that a food product could be carcinogenic or highly mutated. Testing of chemicals for mutagenicity is based on the knowledge that a substance which is mutagenic in the bacterium is more likely than not to be a carcinogen in laboratory animals, and thus , by extension, present a risk of cancer to humans. After that food products that showed mutagenicity exposed to gamma radiation at different doses to examine the effect of gamma radiation on food products. This study represent γ radiation effect on carcinogenic food by using Ames test in the following steps: Detect food by Ames test using Salmonella typhimurium strains in which the colony count /plate for each food sample will show if food is slightly mutated or highly mutated or carcinogenic. If food is highly mutated or carcinogenic with high number of colonies /plate, then the carcinogenic food or highly mutated food exposed to different doses of radiation The applied doses in this study were 0, 2.5, 5, and 10 (KGy). Detect the radiation effect on food samples by Ames test after irradiation. The study shows that mutated and carcinogenic food products estimated by Ames test could be treated by irradiation

Understanding arsenic carcinogenicity by the use of animal models

International Nuclear Information System (INIS)

Wanibuchi, Hideki; Salim, Elsayed I.; Kinoshita, Anna; Shen Jun; Wei Min; Morimura, Keiichirou; Yoshida, Kaoru; Kuroda, Koichi; Endo, Ginji; Fukushima, Shoji

2004-01-01

Although numerous epidemiological studies have indicated that human arsenic exposure is associated with increased incidences of bladder, liver, skin, and lung cancers, limited attempts have been made to understand mechanisms of carcinogenicity using animal models. Dimethylarsinic acid (DMA), an organic arsenic compound, is a major metabolite of ingested inorganic arsenics in mammals. Recent in vitro studies have proven DMA to be a potent clastogenic agent, capable of inducing DNA damage including double strand breaks and cross-link formation. In our attempts to clarify DMA carcinogenicity, we have recently shown carcinogenic effects of DMA and its related metabolites using various experimental protocols in rats and mice: (1) a multi-organ promotion bioassay in rats; (2) a two-stage promotion bioassay by DMA of rat urinary bladder and liver carcinogenesis; (3) a 2-year carcinogenicity test of DMA in rats; (4) studies on the effects of DMA on lung carcinogenesis in rats; (5) promotion of skin carcinogenesis by DMA in keratin (K6)/ornithine decarboxylase (ODC) transgenic mice; (6) carcinogenicity of DMA in p53(+/-) knockout and Mmh/8-OXOG-DNA glycolase (OGG1) mutant mice; (7) promoting effects of DMA and related organic arsenicals in rat liver; (8) promoting effects of DMA and related organic arsenicals in a rat multi-organ carcinogenesis test; and (9) 2-year carcinogenicity tests of monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) in rats. The results revealed that the adverse effects of arsenic occurred either by promoting and initiating carcinogenesis. These data, as covered in the present review, suggest that several mechanisms may be involved in arsenic carcinogenesis

Carcinogenicity assessment of water-soluble nickel compounds.

Science.gov (United States)

Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

2009-01-01

IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

Carcinogenic compounds in alcoholic beverages: an update.

Science.gov (United States)

Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

2016-10-01

The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

A study of tobacco carcinogenesis XLVIII. Carcinogenicity of N'-nitrosonornicotine in mink (Mustela vison).

Science.gov (United States)

Koppang, N; Rivenson, A; Reith, A; Dahle, H K; Evensen, O; Hoffmann, D

1992-11-01

During tobacco processing and smoking, nicotine and nornicotine give rise to N'-nitrosonornicotine (NNN), a highly abundant, strong carcinogen. NNN is known to exert carcinogenic activity in mice, rats and hamsters. Major target organs for NNN carcinogenicity in the rat are the esophagus and the nasal mucosa, and in the Syrian golden hamster trachea and nasal mucosa. In comparison with the rat, the mink (Mustela vison) has a markedly expanded nasal mucosa. Therefore, we explored in this study whether the mink could serve as a non-rodent model for nasal carcinogenesis using NNN as the carcinogen. Twenty random-bred mink, beginning at the age of 3 weeks, received twice weekly s.c. injections of NNN, a total dose of 11.9 mM per animal over a 38 week period. All of the 19 mink at risk developed malignant tumors of both the respiratory and the olfactory region of the nose within 3.5 years. In most animals the malignant tumors, primarily esthesioneuroepithelioma, invaded the brain. Remarkably, NNN induced no other tumors in the mink. None of the control animals developed nasal tumors nor tumors at other sites during the 3.5 years of the assay. The historical data from the farm did not reveal any spontaneous occurrence of nasal tumors in mink at any age. This study supports the concept that NNN is a proven carcinogen for multiple species of mammals and that the mink can serve as a non-rodent, non-inbred animal model for nasal carcinogenesis, especially since NNN induces only tumors in the nasal cavity in this species and not at other sites, as it does in mice, rats and hamsters.

Mutagenic and carcinogenic properties of drinking water

International Nuclear Information System (INIS)

Kool, H.J.; van Kreijl, C.F.; Hrubec, J.

1985-01-01

In this chapter results of oxidation treatments with chlorine, ozone, chlorine dioxide, and ultraviolet (UV), with respect to their effects on activity (Ames test) in drinking water supplies are reviewed. In addition, the authors present the preliminary results of a pilot plant study on the effects of chlorine and chlorine dioxide on mutagenicity. Furthermore, results of several carcinogenicity studies performed with organic drinking water concentrates are discussed in relation to the results of a Dutch carcinogenicity study with mutagenic drinking water concentrates

Theoretical Guidelines for a Psychology of Rural Development

NARCIS (Netherlands)

Landini, F.; Long, N.; Leeuwis, C.; Murtagh, S.

2014-01-01

Many processes related to rural development have a strong psychosocial component. Yet, there exists no specific psychosocial theoretical framework for addressing them. In this paper, then, we present a set of theoretical guidelines for analysing rural development processes and interventions from the

Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens.

Science.gov (United States)

Enzmann, H; Brunnemann, K; Iatropoulos, M; Shpyleva, S; Lukyanova, N; Todor, I; Moore, M; Spicher, K; Chekhun, V; Tsuda, H; Williams, G

2013-09-01

In three independent laboratories carcinogens (diethylnitrosamine, DEN, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) and non-carcinogens (N-nitrosoproline, nicotine) were evaluated in turkey eggs for in ovo carcinogenicity assessment (IOCA). Compounds were injected into aseptic fertilized eggs. After incubation for 24 days, foci of altered hepatocytes (FAH), some with a pseudoglandular structure and/or signs of compression of the surrounding tissue were observed in the fetal liver. All laboratories were able to distinguish unequivocally the hepatocarcinogen-exposed groups from those exposed to non-carcinogens or the vehicle controls, based on the pre-specified evaluation parameters: tumor-like lesions, pseudoglandular areas and FAH. In addition to focal changes, only the carcinogens induced hepatocellular karyomegaly. Lower doses of the carcinogens, which did not induce FAH, were sufficient to induce hepatocellular karyomegaly. After exposure to 4 mg DEN, gall bladder agenesis was observed in all fetuses. The IOCA may be a valuable tool for early investigative studies on carcinogenicity and since it does not use rodents may complement chronic rat or mouse bioassays. Test substances that are positive in both rodents and fertilized turkey eggs are most probably trans-species carcinogens with particular significance for humans. The good concordance observed among the three laboratories demonstrates that the IOCA is a reliable and robust method. Copyright © 2012 Elsevier GmbH. All rights reserved.

Development of evidence-based clinical practice guidelines (CPGs: comparing approaches

Directory of Open Access Journals (Sweden)

Harris Claire

2008-10-01

Full Text Available Abstract Background While the potential of clinical practice guidelines (CPGs to support implementation of evidence has been demonstrated, it is not currently being achieved. CPGs are both poorly developed and ineffectively implemented. To improve clinical practice and health outcomes, both well-developed CPGs and effective methods of CPG implementation are needed. We sought to establish whether there is agreement on the fundamental characteristics of an evidence-based CPG development process and to explore whether the level of guidance provided in CPG development handbooks is sufficient for people using these handbooks to be able to apply it. Methods CPG development handbooks were identified through a broad search of published and grey literature. Documents published in English produced by national or international organisations purporting to support development of evidence-based CPGs were included. A list of 14 key elements of a CPG development process was developed. Two authors read each handbook. For each handbook a judgement was made as to how it addressed each element; assigned as: 'mentioned and clear guidance provided', 'mentioned but limited practical detail provided ', or 'not mentioned'. Results Six CPG development handbooks were included. These were produced by the Council of Europe, the National Health and Medical Research Council of Australia, the National Institute for Health and Clinical Excellence in the UK, the New Zealand Guidelines Group, the Scottish Intercollegiate Guideline Network, and the World Health Organization (WHO. There was strong concordance between the handbooks on the key elements of an evidence-based CPG development process. All six of the handbooks require and provide guidance on establishment of a multidisciplinary guideline development group, involvement of consumers, identification of clinical questions or problems, systematic searches for and appraisal of research evidence, a process for drafting

Risk assessment of DNA-reactive carcinogens in food

International Nuclear Information System (INIS)

Jeffrey, A.M.; Williams, G.M.

2005-01-01

Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B 1 (AFB 1 ), a limit of 20 ppb or ∼30 μg/day has been set and is considered a tolerable daily intake (TDI). Since AFB 1 is considered a potent carcinogen, doses of 32 P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the results. A discussion of approaches to estimating possible threshold effects for DNA-reactive carcinogens is made

Effect of DNA type on response of DNA biosensor for carcinogens

Science.gov (United States)

Sani, Nor Diyana bt. Md.; Heng, Lee Yook; Surif, Salmijah; Lazim, Azwani Mat

2013-11-01

Carcinogens are cancer causing chemicals that can bind to DNA and cause damage to the DNA. These chemicals are available everywhere including in water, air, soil and food. Therefore, a sensor that can detect the presence of these chemicals will be a very useful tool. Since carcinogens bind to DNA, DNA can be used as the biological element in a biosensor. This study has utilized different types of DNA in a biosensor for carcinogen detection. The DNAs include double stranded calf thymus DNA, single stranded calf thymus DNA and guanine rich single stranded DNA. The modified SPE was exposed to a carcinogen followed by interaction with methylene blue which acts as the electroactive indicator. The SPE was then analysed using differential pulse voltammetry (DPV). Optimization studies were conducted for MB concentration and accumulation time, DNA concentration, as well as effect of buffer concentration, buffer pH and ionic strength. The performance of the biosensor was tested on a group 1 carcinogen, formaldehyde. The results indicated that the usage of guanine rich single stranded DNA also gives higher response as carcinogens prefer to bind with guanine compared to other bases.

Development of Safe Food Handling Guidelines for Korean Consumers.

Science.gov (United States)

Kang, Hee-Jin; Lee, Min-Woo; Hwang, In-Kyeong; Kim, Jeong-Weon

2015-08-01

The purpose of this study was to develop guidelines for Korean consumers with regard to safe food handling practices at home by identifying current food handling issues. Korean consumers' behaviors regarding their safe food handling were identified via survey questionnaires that included items on individual hygiene practices, prepreparation steps when cooking, the cooking process, and the storage of leftover foods. The subjects were 417 Korean parents with elementary school children living in Seoul and Gyeonggi Province in the central area of Korea. The survey results revealed gaps between the knowledge or practices of Korean consumers and scientific evidence pertaining to safe food handling practices. Based on these findings, a leaflet on safe food handling guidelines was developed in accordance with Korean food culture. These guidelines suggest personal hygiene practices as well as fundamental principles and procedures for safe food handling from the stage of food purchase to that of keeping leftover dishes. A pilot application study with 50 consumers revealed that the guidelines effectively improved Korean consumers' safe food handling practices, suggesting that they can serve as practical educational material suitable for Korean consumers.

The First Meeting of the WHO Guideline Development Group for the Revision of the WHO 1999 Guidelines for Iodine Thyroid Blocking

International Nuclear Information System (INIS)

Reiners, Christoph; Schneider, Rita; Akashi, Makoshi; Akl, Eli A.; Jourdain, Jean-Rene; Li, Chunsheng; Murith, Christoph; Van Bladel, Lodewijk; Yamashita, Shunichi; Zeeb, Hajo; Vitti, Paolo; Carr, Zhanat

2016-01-01

The meeting held in May 2014 in Wuerzburg, Germany, discussed the scope of the revision of the 1999 WHO guidelines for iodine thyroid blocking (ITB) by following the WHO handbook for guideline development. This article describes the process and methods of developing the revised, evidence-based WHO guidelines for ITB following nuclear and radiological accidents, the results of the kick-off meeting as well as further steps taken to complete the revision. (authors)

Conflict of Interest Policies and Industry Relationships of Guideline Development Group Members: A Cross-Sectional Study of Clinical Practice Guidelines for Depression.

Science.gov (United States)

Cosgrove, Lisa; Krimsky, Sheldon; Wheeler, Emily E; Peters, Shannon M; Brodt, Madeline; Shaughnessy, Allen F

2017-01-01

Because of increased attention to the issue of trustworthiness of clinical practice guidelines, it may be that both transparency and management of industry associations of guideline development groups (GDGs) have improved. The purpose of the present study was to assess a) the disclosure requirements of GDGs in a cross-section of guidelines for major depression; and, b) the extent and type of conflicts of panel members. Treatment guidelines for major depression were identified and searched for conflict of interest policies and disclosure statements. Multi-modal screens for undeclared conflicts were also conducted. Fourteen guidelines with a total of 172 panel members were included in the analysis. Eleven of the 14 guidelines (78%) had a stated conflict of interest policy or disclosure statement, although the policies varied widely. Most (57%) of the guidelines were developed by panels that had members with industry financial ties to drug companies that manufacture antidepressant medication. However, only a minority of total panel members (18%) had such conflicts of interest. Drug company speakers bureau participation was the most common type of conflict. Although some progress has been made, organizations that develop guidelines should continue to work toward greater transparency and minimization of financial conflicts of interest.

Development of international guidelines for RAM shipment security

Energy Technology Data Exchange (ETDEWEB)

Luna, R.E.

2004-07-01

In October of 2003 a weeklong IAEA Technical Meeting developed a set of guidelines for providing security to consignments of radioactive materials in transport. These guidelines will be published shortly in an IAEA TECDOC. The guidelines produced reflect consideration of many influences and concerns that currently revolve around the potential for terrorist use of radioactive material for malevolent ends. The influences discussed here include: public perception of hazard and concern that new requirements will further limit global shipping capability, international efforts to control sealed sources, national efforts to increment protection on selected materials, the basis for exemption of materials, concern for cost impacts of overly broad requirements, questions on how to adjust requirements for a national threat assessment, and issues relating to consistency within the international community on security needs.

Development of international guidelines for RAM shipment security

International Nuclear Information System (INIS)

Luna, R.E.

2004-01-01

In October of 2003 a weeklong IAEA Technical Meeting developed a set of guidelines for providing security to consignments of radioactive materials in transport. These guidelines will be published shortly in an IAEA TECDOC. The guidelines produced reflect consideration of many influences and concerns that currently revolve around the potential for terrorist use of radioactive material for malevolent ends. The influences discussed here include: public perception of hazard and concern that new requirements will further limit global shipping capability, international efforts to control sealed sources, national efforts to increment protection on selected materials, the basis for exemption of materials, concern for cost impacts of overly broad requirements, questions on how to adjust requirements for a national threat assessment, and issues relating to consistency within the international community on security needs

Introducing guidelines for eco-dynamic development and design

NARCIS (Netherlands)

Van Koningsveld, M.; Van Raalte, G.H.

2011-01-01

One of the key activities within the Building with Nature innovation programme is the development of a guideline for Eco-dynamic Development and Design. This guidance will be focussed on implementation of the Building with Nature principles throughout all of the stages of hydraulic engineering

Best Practice No 177: Best practice guideline: writing a business case for service development in pathology.

Science.gov (United States)

Galloway, M J

2004-04-01

This guideline reviews the introduction and development of business planning in the National Health Service. A guideline for writing a business case for service development that would form part of a pathology business plan has been developed. This guideline outlines six steps that are required in the preparation of a business case. The format of the guideline has been developed largely from other national guidelines that have been published for the development of capital projects. In view of the publication of these guidelines, the scope of this guideline excludes business cases for information, management, and technology projects and large capital projects.

Polyamines modulate carcinogen-induced mutagenesis in vivo.

Science.gov (United States)

Wallon, U Margaretha; O'Brien, Thomas G

2005-01-01

Elevated polyamine levels as a consequence of targeted overexpression of ornithine decarboxylase (ODC) to murine skin enhance susceptibility to tumorigenesis in this tissue. A possible mechanism for the enhanced susceptibility phenotype is an increased sensitivity of tissues with elevated polyamine levels to the mutagenic action of carcinogens. To test this hypothesis, a transgenic mouse model containing the Big Blue transgene and also expressing a K6/ODC transgene was developed. Incorporation of the K6/ODC transgene into the Big Blue model did not affect the spontaneous lacI mutant frequency in either skin or epidermis of the double-transgenic mice. After skin treatment with single doses of either 7,12-dimethylbenz[a]anthracene or N-methyl-N'-nitro-N-nitrosoguanidine, however, the mutant frequency was significantly increased in the skin of double-transgenic Big Blue;K6/ODC mice compared to Big Blue controls. The increases in mutant frequency were clearly due to ODC transgene activity, since treatment of mice with the ODC inhibitor, alpha-difluoromethylornithine, completely abolished the difference in mutant frequencies between double-transgenic and Big Blue mice. These results demonstrate that intracellular polyamine levels modulate mutation induction following carcinogen exposure. 2004 Wiley-Liss, Inc.

Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

Energy Technology Data Exchange (ETDEWEB)

Brink, Willem van den; Emerenciana, Annette [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Medicines Evaluation Board, Utrecht (Netherlands); Bellanti, Francesco [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Della Pasqua, Oscar [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Stockley Park, Uxbridge (United Kingdom); Clinical Pharmacology & Therapeutics, UCL, School of Life and Medical Sciences, London (United Kingdom); Laan, Jan Willem van der, E-mail: jw.vd.laan@cbg-meb.nl [Division of Toxicology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Medicines Evaluation Board, Utrecht (Netherlands)

2017-04-01

Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to

Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

International Nuclear Information System (INIS)

Brink, Willem van den; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; Laan, Jan Willem van der

2017-01-01

Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to

Use of the modified Ames test as an indicator of the carcinogenicity of residual aromatic extracts

Energy Technology Data Exchange (ETDEWEB)

Boogaard, P.; Hedelin, A.; Riley, A.; Rushton, E.; Vaissiere, M.; Minsavage, G.; Rohde, A.; Dalbey, W.

2013-01-15

Existing data demonstrate that residual aromatic extracts (RAEs) can be either carcinogenic or non-carcinogenic. CONCAWE had previously concluded that 'Although limited data available indicate that some RAEs are weakly carcinogenic, it is not possible to provide a general recommendation. Classify on a case-by-case basis' (CONCAWE 2005). Therefore CONCAWE's Health/Toxicology Subgroup (H/TSG) has developed a proposal for the use of the modified Ames test as a short-term predictive screening tool for decisions on the classification of RAEs for carcinogenicity. The relationship between RAE chemistry and carcinogenic potential is not as well understood as it is for some other categories of substances, e.g. Other Lubricant Base Oils (OLBO). However, a correlation has been found between the results of the skin carcinogenicity bioassay and the mutagenicity index (MI) obtained from the modified Ames test. Data supporting this correlation are summarised in this report. The H/TSG confirmed that the modified Ames test can be used as a predictive screening tool and that a cut-off value can be established to make a distinction between carcinogenic and non-carcinogenic products. RAEs with a MI > 0.4 demonstrated carcinogenic potential upon dermal application to mouse skin with chronic exposure. RAEs with a MI > 0.4 did not demonstrate a carcinogenic potential. To justify the use of the modified Ames test with RAEs, additional analysis of the repeatability of the test with RAEs was required. With this objective, CONCAWE sponsored a round robin study with different samples of RAEs from member companies, at three different laboratories. The repeatability demonstrated in the round robin study with RAEs support the proposed use of the modified Ames test. As part of the tools available for use by member companies, the H/TSG proposed a standard operating procedure (SOP) (included as an Appendix to this report) on the conduct of the modified Ames test with RAEs. The H

Smoking out carcinogens

OpenAIRE

Baines, David; Griffiths, Huw; Parker, Jane

2016-01-01

Smoked foods are becoming increasingly popular and are being produced by large and small food operations, artisan producers, chefs and consumers themselves. Epidemiological studies conducted over a number of decades have linked the consumption of smoked foods with various cancers and these findings have been supported by animal testing. Smoke contains a group of dangerous carcinogens that are responsible for lung cancer in cigarette smokers and implicated as causative agents for colorectal an...

A new hybrid thermal comfort guideline for the Netherlands : Background and development

NARCIS (Netherlands)

Boerstra, A.C.; Van Hoof, J.; Van Weele, A.M.

2015-01-01

In 2004, the first adaptive thermal comfort guideline was introduced in the Netherlands. Recently, a new, upgraded version of this ISSO 74 (ATG) guideline has been developed. The new requirements are hybrid in nature as the 2014 version of the guideline combines elements of traditional non-adaptive

Guidelines for competency development and measurement in rehabilitation psychology postdoctoral training.

Science.gov (United States)

Stiers, William; Barisa, Mark; Stucky, Kirk; Pawlowski, Carey; Van Tubbergen, Marie; Turner, Aaron P; Hibbard, Mary; Caplan, Bruce

2015-05-01

This study describes the results of a multidisciplinary conference (the Baltimore Conference) that met to develop consensus guidelines for competency specification and measurement in postdoctoral training in rehabilitation psychology. Forty-six conference participants were chosen to include representatives of rehabilitation psychology training and practice communities, representatives of psychology accreditation and certification bodies, persons involved in medical education practice and research, and consumers of training programs (students). Consensus education and training guidelines were developed that specify the key competencies in rehabilitation psychology postdoctoral training, and structured observation checklists were developed for their measurement. This study continues the development of more than 50 years of thinking about education and training in rehabilitation psychology and builds on the existing work to further advance the development of guidelines in this area. The conference developed aspirational guidelines for competency specification and measurement in rehabilitation psychology postdoctoral training (i.e., for studying the outcomes of these training programs). Structured observation of trainee competencies allows examination of actual training outcomes in relation to intended outcomes and provides a methodology for studying how program outcomes are related to program structures and processes so that program improvement can occur. Best practices in applying program evaluation research methods to the study of professional training programs are discussed. (c) 2015 APA, all rights reserved).

Carcinogenicity of petroleum lubricating oil distillates: effects of solvent refining, hydroprocessing, and blending.

Science.gov (United States)

Halder, C A; Warne, T M; Little, R Q; Garvin, P J

1984-01-01

Certain refining processes were investigated to determine their influence on the dermal carcinogenic activity of petroleum-derived lubricating oil distillates. Specifically, the effects of solvent refining, hydroprocessing, a combination of both processes, and the blending of oils processed using each technique were evaluated in standard mouse skin-painting bioassays. The refining process used as well as the level or severity of treatment greatly influenced the carcinogenic outcome of processed lubricating oils. Solvent refining at severities normally used appeared to eliminate carcinogenicity. In contrast, hydroprocessing alone at mild levels of treatment was successful only in reducing the carcinogenic potency; severe hydroprocessing conditions were necessary to eliminate carcinogenic activity without the use of additional refining processes. Carcinogenic activity could also be eliminated by following moderate solvent refining with mild hydroprocessing. Blending of hydroprocessed oils with solvent-refined oils resulted in a substantial reduction or even elimination of carcinogenic activity. However, the degree of protection obtained varied with the particular distillates used and appeared largely dependent on the inherent biological activity of the hydroprocessed oil.

Energy indicators for sustainable development: Guidelines and methodologies

International Nuclear Information System (INIS)

2005-04-01

This publication is the product of an international initiative to define a set of Energy Indicators for Sustainable Development (EISD) and corresponding methodologies and guidelines. The successful completion of this work is the result of an intensive effort led by the International Atomic Energy Agency (IAEA) in cooperation with the United Nations Department of Economic and Social Affairs (UNDESA), the International Energy Agency (IEA), Eurostat and the European Environment Agency (EEA). The thematic framework, guidelines, methodology sheets and energy indicators set out in this publication reflect the expertise of these various agencies, recognized worldwide as leaders in energy and environmental statistics and analysis. While each agency has an active indicator programme, one goal of this joint endeavour has been to provide users with a consensus by leading experts on definitions, guidelines and methodologies for the development and worldwide use of a single set of energy indicators. No set of energy indicators can be final and definitive. To be useful, indicators must evolve over time to fit country-specific conditions, priorities and capabilities. The purpose of this publication is to present one set of EISD for consideration and use, particularly at the national level, and to serve as a starting point in the development of a more comprehensive and universally accepted set of energy indicators relevant to sustainable development. It is hoped that countries will use the EISD to assess their energy systems and to track their progress towards nationally defined sustainable development goals and objectives. It is also hoped that users of the information presented in this publication will contribute to refinements of energy indicators for sustainable development by adding their own unique perspectives to what is presented herein

Energy indicators for sustainable development: Guidelines and methodologies

International Nuclear Information System (INIS)

2008-01-01

This publication is the product of an international initiative to define a set of Energy Indicators for Sustainable Development (EISD) and corresponding methodologies and guidelines. The successful completion of this work is the result of an intensive effort led by the International Atomic Energy Agency (IAEA) in cooperation with the United Nations Department of Economic and Social Affairs (UNDESA), the International Energy Agency (IEA), Eurostat and the European Environment Agency (EEA). The thematic framework, guidelines, methodology sheets and energy indicators set out in this publication reflect the expertise of these various agencies, recognized worldwide as leaders in energy and environmental statistics and analysis. While each agency has an active indicator programme, one goal of this joint endeavour has been to provide users with a consensus by leading experts on definitions, guidelines and methodologies for the development and worldwide use of a single set of energy indicators. No set of energy indicators can be final and definitive. To be useful, indicators must evolve over time to fit country-specific conditions, priorities and capabilities. The purpose of this publication is to present one set of EISD for consideration and use, particularly at the national level, and to serve as a starting point in the development of a more comprehensive and universally accepted set of energy indicators relevant to sustainable development. It is hoped that countries will use the EISD to assess their energy systems and to track their progress towards nationally defined sustainable development goals and objectives. It is also hoped that users of the information presented in this publication will contribute to refinements of energy indicators for sustainable development by adding their own unique perspectives to what is presented herein

Comparative statistical analysis of carcinogenic and non-carcinogenic effects of uranium in groundwater samples from different regions of Punjab, India

International Nuclear Information System (INIS)

Saini, Komal; Singh, Parminder; Bajwa, Bikramjit Singh

2016-01-01

LED flourimeter has been used for microanalysis of uranium concentration in groundwater samples collected from six districts of South West (SW), West (W) and North East (NE) Punjab, India. Average value of uranium content in water samples of SW Punjab is observed to be higher than WHO, USEPA recommended safe limit of 30 µg l −1 as well as AERB proposed limit of 60 µg l −1 . Whereas, for W and NE region of Punjab, average level of uranium concentration was within AERB recommended limit of 60 µg l −1 . Average value observed in SW Punjab is around 3–4 times the value observed in W Punjab, whereas its value is more than 17 times the average value observed in NE region of Punjab. Statistical analysis of carcinogenic as well as non carcinogenic risks due to uranium have been evaluated for each studied district. - Highlights: • Uranium level in groundwater samples have been assessed in different regions of Punjab. • Comparative study of carcinogenic and non carcinogenic effects of uranium has been done. • Wide variation has been found for different geological regions. • It has been found that South west Punjab is worst affected by uranium contamination in its water. • For west and north east regions of Punjab, uranium levels in groundwater laid under recommended safe limits.

Relative potency estimation for synthetic petroleum skin carcinogens.

OpenAIRE

Holland, J M; Wolf, D A; Clark, B R

1981-01-01

A procedure for quantitative analysis of skin carcinogenesis data, for the purpose of establishing carcinogenic potency, has been applied to observations obtained from C3H mice exposed continuously to synthetic and natural petroleums. The importance of total polynuclear aromatic (PNA) content to the skin carcinogenic activity of the crude materials was also examined. Of three synthetic petroleums evaluated, all were shown capable of inducing skin neoplasms within a two-year exposure period. U...

24 CFR 570.209 - Guidelines for evaluating and selecting economic development projects.

Science.gov (United States)

2010-04-01

..., where the recreational benefit to users or members clearly outweighs employment or other benefits to low... DEVELOPMENT BLOCK GRANTS Eligible Activities § 570.209 Guidelines for evaluating and selecting economic... activities to be carried out for economic development purposes. Specifically, these guidelines are applicable...

Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

International Nuclear Information System (INIS)

Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.

2007-01-01

Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

Content and quality of workplace guidelines developed to prevent mental health problems

DEFF Research Database (Denmark)

Nexø, Mette Andersen; Kristensen, Josefine Vejlby; Grønvad, Majbritt Thorhauge

2018-01-01

Objectives A wide range of guidelines have been developed to prevent work-related mental health problems (MHP), but little is known about the quality of such guidelines. We systematically reviewed the content and quality of workplace guidelines aiming to prevent, detect, and/or manage work......-related MHP. Methods We conducted systematic online and database searches (MEDLINE; Web of Science; PsychNET; occupational safety and health databases) to identify guidelines. Eligibility criteria included guidelines recommending primary, secondary, or tertiary preventive interventions to be implemented...... at the workplace by employers, employees or organizational staff. A minimum of minimum three independent reviewers assessed the quality of guidelines using the Guidelines for Research and Evaluation (AGREE II). Guidelines rated ≥65% with regards to domain I, II, and III were considered to be of good developmental...

Carcinogen risk assessment

International Nuclear Information System (INIS)

Hazelwoold, R.N.

1987-01-01

This article describes the methods by which risk factors for carcinogenic hazards are determined and the limitations inherent in the process. From statistical and epidemiological studies, the major identifiable factors related to cancer in the United States were determined to be cigarette smoking, diet, reproductive and sexual behavior, infections, ultraviolet and ionizing radiation, and alcohol consumption. The incidence of lung cancer due to air pollutants was estimated to be less than 2%. Research needs were discussed

The influence of thresholds on the risk assessment of carcinogens in food.

Science.gov (United States)

Pratt, Iona; Barlow, Susan; Kleiner, Juliane; Larsen, John Christian

2009-08-01

The risks from exposure to chemical contaminants in food must be scientifically assessed, in order to safeguard the health of consumers. Risk assessment of chemical contaminants that are both genotoxic and carcinogenic presents particular difficulties, since the effects of such substances are normally regarded as being without a threshold. No safe level can therefore be defined, and this has implications for both risk management and risk communication. Risk management of these substances in food has traditionally involved application of the ALARA (As Low as Reasonably Achievable) principle, however ALARA does not enable risk managers to assess the urgency and extent of the risk reduction measures needed. A more refined approach is needed, and several such approaches have been developed. Low-dose linear extrapolation from animal carcinogenicity studies or epidemiological studies to estimate risks for humans at low exposure levels has been applied by a number of regulatory bodies, while more recently the Margin of Exposure (MOE) approach has been applied by both the European Food Safety Authority and the Joint FAO/WHO Expert Committee on Food Additives. A further approach is the Threshold of Toxicological Concern (TTC), which establishes exposure thresholds for chemicals present in food, dependent on structure. Recent experimental evidence that genotoxic responses may be thresholded has significant implications for the risk assessment of chemicals that are both genotoxic and carcinogenic. In relation to existing approaches such as linear extrapolation, MOE and TTC, the existence of a threshold reduces the uncertainties inherent in such methodology and improves confidence in the risk assessment. However, for the foreseeable future, regulatory decisions based on the concept of thresholds for genotoxic carcinogens are likely to be taken case-by-case, based on convincing data on the Mode of Action indicating that the rate limiting variable for the development of cancer

Common Guidelines for Education Research and Development

Science.gov (United States)

Institute of Education Sciences, 2013

2013-01-01

In January 2011, a Joint Committee of representatives from the U.S. Department of Education (ED) and the U.S. National Science Foundation (NSF) began work to establish cross-agency guidelines for improving the quality, coherence, and pace of knowledge development in science, technology, engineering and mathematics (STEM) education. Although the…

Carcinogen-induced damage to DNA

International Nuclear Information System (INIS)

Strauss, B.; Altamirano, M.; Bose, K.; Sklar, R.; Tatsumi, K.

1979-01-01

Human cells respond to carcinogen-induced damage in their DNA in at least two ways. The first response, excision repair, proceeds by at least three variations, depending on the nature of the damage. Nucleotide excision results in relatively large repair patches but few free DNA breaks, since the endonuclease step is limiting. Apurinic repair is characterized by the appearance of numerous breaks in the DNA and by short repair patches. The pathways behave as though they function independently. Lymphoic cells derived from a xeroderma pigmentosum complementation group C patient are deficient in their ability to perform nucleotide excision and also to excise 6 methoxyguanine adducts, but they are apurinic repair competent. Organisms may bypass damage in their DNA. Lymphoblastoid cells, including those derived from xeroderma pigmentosum treated with 3 H-anti-BPDE, can replicate their DNA at low doses of carcinogen. Unexcised 3 H is found in the light or parental strand of the resulting hybrid DNA when replication occurs in medium with BrdUrd. This observation indicates a bypass reaction occurring by a mechanism involving branch migration at DNA growing points. Branch migration in DNA preparations have been observed, but the evidence is that most occurs in BrdUrd-containing DNA during cell lysis. The measurement of the bifilarly substituted DNA resulting from branch migration is a convenient method of estimating the proportion of new synthesis remaining in the vicinity of the DNA growing point. Treatment with carcinogens or caffeine results in accumulation of DNA growing points accompanied by the synthesis of shortened pieces of daughter DNA

Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

Science.gov (United States)

Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

2015-03-01

Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

Foetal exposure to food and environmental carcinogens in human beings.

Science.gov (United States)

Myöhänen, Kirsi; Vähäkangas, Kirsi

2012-02-01

Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Identifying target audiences: who are the guidelines for? : article 1 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.

Science.gov (United States)

Yawn, Barbara P; Akl, Elie A; Qaseem, Amir; Black, Peter; Campos-Outcalt, Doug

2012-12-01

Professional societies, like many other organizations around the world, have recognized the need to use rigorous processes to ensure that health care recommendations are informed by the best available research evidence. Different clinical practice guidelines addressing the management of the same disease may vary widely in the evidence used and the format of the recommendations, with the result that not all are appropriate for all audiences. This is the first of a series of 14 articles that clinicians, methodologists, and researchers from around the world prepared to advise those developing guidelines in respiratory and other diseases about the potential impact of identifying the target audiences for their clinical practice guidelines. In this review we address the following questions. (1) Which audiences are interested in a chronic obstructive pulmonary disease (COPD) guideline? (2) How many audiences can be addressed in a single COPD guideline? (3) What is the purpose of the guidelines? (4) Who should be included on the guideline panel? We collected information by searching PubMed and reviewing information from groups that are currently making and using respiratory disease guidelines, as well as from workshop discussions. Our conclusions are based on available evidence, consideration of what guideline developers are doing, and the opinions of those who attended the workshop. Clinicians desire COPD and other guidelines that are concise, use evidence from practices similar to theirs, and whose authors have expertise in providing care in similar settings and with similar patients. In the case of COPD, barriers to generalists' use of guidelines include lack of awareness of the guidelines, failure to embrace the diagnostic methods as capable of providing definitive confirmation of COPD, and, most importantly, failure of previous guidelines to address the treatment of COPD in the context of the broad range of multiple morbidities that affect most people with COPD. COPD

A guide to guidelines for professional societies and other developers of recommendations: introduction to integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.

Science.gov (United States)

Schünemann, Holger J; Woodhead, Mark; Anzueto, Antonio; Buist, A Sonia; Macnee, William; Rabe, Klaus F; Heffner, John

2012-12-01

Organizations around the world are recognizing that guidelines should be based on the best available evidence, that the development of recommendations needs to be transparent, and that appropriate processes should be followed. In June 2007, we convened an American Thoracic Society (ATS)/European Respiratory Society (ERS)-sponsored workshop with over 60 representatives from 36 international organizations to provide advice to guideline developers about the required steps and processes for guideline development using the management of chronic obstructive pulmonary disease (COPD) as an example. Following the workshop, participants completed a series of 14 review articles that underwent peer review and incorporated key new literature until June 2011 for most articles in this series. The review articles evaluate the guideline cycle including: priority setting, question formulation, managing conflict of interest, defining appropriate outcomes, stakeholder involvement, grading the quality of evidence and strength of recommendations, integration of values and preferences, considering resource use, reporting of guidelines, implementation, and adaptation. In this Introduction we frame the background and methods of these reviews and provide the key conclusions of the workshop. A summary of the workshop's conclusions and recommendations was published in The Lancet. Given the enormous resources that are spent on research and the importance of providing the best guidance to healthcare decision makers, attributing appropriate funds to research syntheses and transparent, independent guidance for the development of evidence-based guidelines is justified. Furthermore, given the immense amount of work that is required, individuals and organizations need to collaborate to achieve the best possible and cost-effective coordination of these efforts.

Development of standard practice guidelines for open and closed system suctioning.

Science.gov (United States)

Özden, Dilek; Görgülü, R Selma

2012-05-01

This study was carried out to determine the knowledge and practice of nurses before and after training and the development of standard practice guidelines for open and closed system suctioning methods in patients with endotracheal tubes. Many life-threatening complications can occur when a suctioning procedure is not performed with the correct technique. It has been reported that standard practice guidelines for suctioning are insufficient in clinical practice. Non-participant structured observational study. We assessed a total of 48 nurses who were employed in the cardiovascular surgery intensive care unit of a state hospital in Turkey. We used a questionnaire and nurse observation forms to assess the use of the open and closed system suctioning. There was a significant difference between the mean scores of the answers ('true', 'wrong' and 'I do not know') for the use of open and closed system suctioning before and after training. In addition, all steps of both suctioning procedures were carried out correctly during the third observation. The compliance of the nurses to the standard practice guidelines for open and closed suctioning and their knowledge levels on the subject were increased after training, while the implementation of standards was satisfactory. The development of open and closed system suctioning standard practice guidelines directly contributed to the enhancement of patient safety and the quality of nursing care. It is suggested that, as in other nursing care practices, suctioning should be carried out in accordance with standard practice guidelines, and health institutions should develop their standard practice guidelines and work in accordance with them. © 2012 Blackwell Publishing Ltd.

Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

Science.gov (United States)

Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

Science.gov (United States)

Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

Induction of prophage lambda by chlorinated organics: Detection of some single-species/single-site carcinogens

Energy Technology Data Exchange (ETDEWEB)

DeMarini, D.M.; Brooks, H.G. (Environmental Protection Agency, Research Triangle Park, NC (United States))

1992-01-01

Twenty-eight chlorinated organic compounds were evaluated for their ability to induce DNA damage using the Microscreen prophage-induction assay in Escherichia coli. Comparison of the performance characteristics of the prophage-induction and Salmonella assays to rodent carcinogenicity assays showed that the prophage-induction assay had a somewhat higher specificity than did the Salmonella assay (70% vs. 50%); sensitivity, concordance, and positive and negative predictivity were similar for the two microbial assays. The Microscreen prophage-induction assay failed to detect eight carcinogens, perhaps due to toxicity or other unknown factors; five of these eight carcinogens were detected by the Salmonella assay. However, the prophage-induction assay did detect six carcinogens that were not detected by the Salmonella assay, and five of these were single-species, single-site carcinogens, mostly mouse liver carcinogens. Some of these carcinogens, such as the chloroethanes, produce free radicals, which may be the basis for their carcinogenicity and ability to induce prophage. The prophage-induction (or other SOS) assay may be useful in identifying some genotoxic chlorinated carcinogens that induce DNA damage that do not revert the standard Salmonella tester strains.

Development of standards for chemical and biological decontamination of buildings and structures affected by terrorism

Energy Technology Data Exchange (ETDEWEB)

Lumley, T.C.; Volchek, K.; Fingas, M. [Environment Canada, Ottawa, ON (Canada). Emergencies Science and Technology Division, Environmental Technology Centre, Science and Technology Branch; Hay, A.W.M. [Leeds Univ., Leeds (United Kingdom)

2006-07-01

Currently, there are no suitable standards for determining levels of safety when reoccupying a building that has been recommissioned following a biological or chemical attack. For that reason, this study focused on developing clean-up standards for decontaminating buildings and construction materials after acts of terrorism. Several parameters must be assessed when determining the course of action to decontaminate toxic agents and to rehabilitate facilities. First, the hazardous substance must be positively identified along with the degree of contamination and information on likely receptors. Potential exposure route is also a key consideration in the risk assessment process. A key objective of the study was to develop specific guidelines for ascertaining and defining clean. In particular, standards for chemical and biological agents that pose a real or potential risk for use as agents of terrorism will be developed. The selected agents for standards development were ammonia, fentanyl, malathion, mustard gas, potassium cyanide, ricin, sarin, hepatitis A virus, and bacillus anthracis. The standards will be developed by establishing the relationship between the amount of exposure and expected health effects; assessing real and potential risks by identifying individuals at risk and consideration of all exposure routes; and, characterizing the risk to determine the potential for toxicity or infectivity. For non-carcinogens, this was done through the analysis of other known guidelines. Cancer-slope factors will be considered for carcinogens. The standards will be assessed in the laboratory using animal models. The guidelines and standards are intended for first-responders and are scheduled for development by the end of 2006. 15 refs., 3 tabs.

Comparison of acrylamide intake from Western and guideline based diets using probabilistic techniques and linear programming.

Science.gov (United States)

Katz, Josh M; Winter, Carl K; Buttrey, Samuel E; Fadel, James G

2012-03-01

Western and guideline based diets were compared to determine if dietary improvements resulting from following dietary guidelines reduce acrylamide intake. Acrylamide forms in heat treated foods and is a human neurotoxin and animal carcinogen. Acrylamide intake from the Western diet was estimated with probabilistic techniques using teenage (13-19 years) National Health and Nutrition Examination Survey (NHANES) food consumption estimates combined with FDA data on the levels of acrylamide in a large number of foods. Guideline based diets were derived from NHANES data using linear programming techniques to comport to recommendations from the Dietary Guidelines for Americans, 2005. Whereas the guideline based diets were more properly balanced and rich in consumption of fruits, vegetables, and other dietary components than the Western diets, acrylamide intake (mean±SE) was significantly greater (Plinear programming and results demonstrate that linear programming techniques can be used to model specific diets for the assessment of toxicological and nutritional dietary components. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparing Inpatient Falls Guidelines to Develop an ICNP.

Science.gov (United States)

Jung, Miran; Cho, Insook; Chae, Jisun; Kim, Jihye; Kim, Yeunhee

2017-01-01

This study compared and synthesized clinical guidelines for inpatient falls with the aim of developing an ICNP®-based nursing catalogue for use in electronic nursing records. The identified content will influence nursing services provided to patients and the associated documentation.

Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

International Nuclear Information System (INIS)

Maga, J.A.

1983-01-01

The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

Development of safety and regulatory requirements for Korean next generation reactor - Development of human factors design review guidelines (II)

Energy Technology Data Exchange (ETDEWEB)

Lee, Jung Woon; Oh, In Suk; Lee, Hyun Chul; Cheon, Se Woo [Korea Atomic Energy Research Institute, Taejon (Korea)

1999-02-01

The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25. Human Factors Engineering Program Review Model' and '26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and the characteristics of the KNGR design, and reviewing the reference documents of NURGE-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides at KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system design review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we updated the guidelines by reviewing the literature related to alarm design that published after 1994. 12 refs., 11 figs., 2 tabs. (Author)

Development of safety and regulatory requirements for Korean next generation reactor - Development of human factors design review guidelines (II)

Energy Technology Data Exchange (ETDEWEB)

Lee, Jung Woon; Oh, In Suk; Lee, Hyun Chul; Cheon, Se Woo [Korea Atomic Energy Research Institute, Taejon (Korea)

1999-02-01

The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25. Human Factors Engineering Program Review Model' and '26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and the characteristics of the KNGR design, and reviewing the reference documents of NURGE-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides at KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system design review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we updated the guidelines by reviewing the literature related to alarm design that published after 1994. 12 refs., 11 figs., 2 tabs. (Author)

Food derived carcinogenic amnoimidazoazaarenes

DEFF Research Database (Denmark)

Frandsen, Henrik

Carcinogenic aminoimidazoazaarenes are formed during cooking of meat and fish. Important factors for the formation of these compounds are meat type, cooking temperature and time. The compounds are genotoxic in bacterial and mammalian cells. In animal feeding studies the compounds tested so far were...... of the exocyclic amino group. Estimations of human cancer risk have indicated that ingestion of food containing aminoimidazoazaarenes are of importance....

Guideline funding and conflicts of interest: article 4 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.

Science.gov (United States)

Boyd, Elizabeth A; Akl, Elie A; Baumann, Michael; Curtis, J Randall; Field, Marilyn J; Jaeschke, Roman; Osborne, Molly; Schünemann, Holger J

2012-12-01

Professional societies, like many other organizations around the world, have recognized the need to use more rigorous processes to ensure that healthcare recommendations are informed by the best available research evidence. This is the fourth of a series of 14 articles prepared to advise guideline developers in respiratory and other disease. It focuses on commercial funding of guidelines and managing conflict of interest effectively in the context of guidelines. In this review, we addressed the following topics and questions. (1) How are clinical practice guidelines funded? (2) What are the risks associated with commercial sponsorship of guidelines? (3) What relationships should guideline committee members be required to disclose? (4) What is the most efficient way to obtain complete and accurate disclosures? (5) How should disclosures be publicly shared? (6) When do relationships require management? (7) How should individual conflicts of interest be managed? (8) How could conflict of interest policies be enforced? The literature review included a search of PubMed and other databases for existing systematic reviews and relevant methodological research. Our conclusions are based on available evidence, consideration of what guideline developers are doing, and workshop discussions. Professional societies often depend on industry funding to support clinical practice guideline development. In addition, members of guideline committees frequently have financial relationships with commercial entities, are invested in their intellectual work, or have conflicts related to clinical revenue streams. No systematic reviews or other rigorous evidence regarding best practices for funding models, disclosure mechanisms, management strategies, or enforcement presently exist, but the panel drew several conclusions that could improve transparency and process.

Inconsistency... or why differentiate, where prevention is concerned, between radioactive substances and carcinogenic chemicals

International Nuclear Information System (INIS)

Choquet, R.; Vinit, J.

1982-01-01

Radiotracers, low-activity unsealed radioactive sources, and certain chemical products belong to the list of substances and agents known to promote cancers in humans. The dangers of radiotracers and carcinogenic chemicals being very similar, or even identical, it is inadmissible that preventive measures have not been equally developed and are not viewed in the same way in our country. It should be noted that the International Labour Bureau has long since included radioactive products in the list of carcinogenic substances and agents and treated preventive measures as a whole by proceeding in this way it would be easier to account for the possible combined effects of ionising radiations and chemical molecules. After a review of some facts about cancer the present situation is examined with regard to statutory measures applied on the one hand to radioelements and on the other to chemicals recognised as carcinogenic by international organisations. Proposals are made to remedy this illogical situation [fr

Development of guidelines for inelastic analysis in design of fast reactor components

International Nuclear Information System (INIS)

Nakamura, Kyotada; Kasahara, Naoto; Morishita, Masaki; Shibamoto, Hiroshi; Inoue, Kazuhiko; Nakayama, Yasunari

2008-01-01

The interim guidelines for the application of inelastic analysis to design of fast reactor components were developed. These guidelines are referred from 'Elevated Temperature Structural Design Guide for Commercialized Fast Reactor (FDS)'. The basic policies of the guidelines are more rational predictions compared with elastic analysis approach and a guarantee of conservative results for design conditions. The guidelines recommend two kinds of constitutive equations to estimate strains conservatively. They also provide the methods for modeling load histories and estimating fatigue and creep damage based on the results of inelastic analysis. The guidelines were applied to typical design examples and their results were summarized as exemplars to support users

Lesions induced in rodent pancreas by azaserine and other pancreatic carcinogens

Energy Technology Data Exchange (ETDEWEB)

Longnecker, D.S.

1984-06-01

Focal proliferative changes in the acinar cells of the pancreas of rats have been induced by several systemically administered carcinogens including azaserine, N-nitrosobis(2-oxopropyl)amine, N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, and Ndelta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine (MNCO). Foci, nodules, and adenomas induced by these carcinogens are usually made up of atypical-appearing acinar cells that maintain a high degree of differentiation, but a minority of these lesions exhibit anaplastic cellular changes that suggest the development of malignant potential. Such anaplasia may occupy the whole of smaller lesions or may occur as a secondary focal change within larger nodules or adenomas. Many foci and nodules per pancreas have been induced by single or multiple exposures to these known genotoxic carcinogens, but relatively few of them develop into carcinomas. Azaserine and MNCO have induced acinar cell carcinomas in rats. Those induced by azaserine have exhibited a broad spectrum of histologic variants, including ductlike, cystic and undifferentiated patterns. Higher doses of MNCO have induced a second pattern of change in the pancreatic lobules of rats, which includes cystic and tubular ductlike structures that have been called cystic and tubular ductal complexes. MNCO has also induced focal acinar cell lesions, cystic and tubular ductal complexes, and adenocarcinomas in the pancreas of Syrian golden hamsters. In this species, ductal complexes are much more numerous than are proliferative lesions of acinar cells, and the histologic appearance of the carcinomas is ductlike. Hyperplasia and atypical changes were also seen in the epithelium of the intralobular ducts of hamsters. 20 references, 5 figures, 1 table.

Emergency Response Guideline Development

International Nuclear Information System (INIS)

Gary D Storrick

2007-01-01

Task 5 of the collaborative effort between ORNL, Brazil, and Westinghouse for the International Nuclear Energy Research Initiative entitled 'Development of Advanced Instrumentation and Control for an Integrated Primary System Reactor' focuses on operator control and protection system interaction, with particular emphasis on developing emergency response guidelines (ERGs). As in the earlier tasks, we will use the IRIS plant as a specific example of an integrated primary system reactor (IPSR) design. The present state of the IRIS plant design--specifically, the lack of a detailed secondary system design--precludes establishing detailed emergency procedures at this time. However, we can create a structure for their eventual development. This report summarizes our progress to date. Section 1.2 describes the scope of this effort. Section 2 compares IPSR ERG development to the recent AP1000 effort, and identifies three key plant differences that affect the ERGs and control room designs. The next three sections investigate these differences in more detail. Section 3 reviews the IRIS Safety-by-Design philosophy and its impact on the ERGs. Section 4 looks at differences between the IRIS and traditional loop PWR I and C Systems, and considers their implications for both control room design and ERG development. Section 5 examines the implications of having one operating staff control multiple reactor units. Section 6 provides sample IRIS emergency operating procedures (EOPs). Section 7 summarizes our conclusions

Morpho-chemical characterization and surface properties of carcinogenic zeolite fibers

International Nuclear Information System (INIS)

Mattioli, Michele; Giordani, Matteo; Dogan, Meral; Cangiotti, Michela; Avella, Giuseppe; Giorgi, Rodorico; Dogan, A. Umran; Ottaviani, Maria Francesca

2016-01-01

Highlights: • Differently carcinogenic zeolite fibers were investigated combining physico-chemical methods. • For the first time, zeolite fibers were studied by means of the EPR technique using different spin probes. • The structural properties and the adsorption capability are function of different types and distributions of adsorption sites. • The interacting ability of erionite is higher than that of other fibrous zeolites. • The surface interacting properties may be related with the carcinogenicity of the zeolite fibers. - Abstract: Erionite belonging to the zeolite family is a human health-hazard, since it was demonstrated to be carcinogenic. Conversely, offretite family zeolites were suspected carcinogenic. Mineralogical, morphological, chemical, and surface characterizations were performed on two erionites (GF1, MD8) and one offretite (BV12) fibrous samples and, for comparison, one scolecite (SC1) sample. The specific surface area analysis indicated a larger availability of surface sites for the adsorption onto GF1, while SC1 shows the lowest one and the presence of large pores in the poorly fibrous zeolite aggregates. Selected spin probes revealed a high adsorption capacity of GF1 compared to the other zeolites, but the polar/charged interacting sites were well distributed, intercalated by less polar sites (Si–O–Si). MD8 surface is less homogeneous and the polar/charged sites are more interacting and closer to each other compared to GF1. The interacting ability of BV12 surface is much lower than that found for GF1 and MD8 and the probes are trapped in small pores into the fibrous aggregates. In comparison with the other zeolites, the non-carcinogenic SC1 shows a poor interacting ability and a lower surface polarity. These results helped to clarify the chemical properties and the surface interacting ability of these zeolite fibers which may be related to their carcinogenicity.

QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity

Directory of Open Access Journals (Sweden)

Davy Guan

2018-04-01

Full Text Available Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.

Science.gov (United States)

Soffritti, Morando; Padovani, Michela; Tibaldi, Eva; Falcioni, Laura; Manservisi, Fabiana; Belpoggi, Fiorella

2014-04-01

Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health. © 2014 Wiley Periodicals, Inc.

CarcinoPred-EL: Novel models for predicting the carcinogenicity of chemicals using molecular fingerprints and ensemble learning methods.

Science.gov (United States)

Zhang, Li; Ai, Haixin; Chen, Wen; Yin, Zimo; Hu, Huan; Zhu, Junfeng; Zhao, Jian; Zhao, Qi; Liu, Hongsheng

2017-05-18

Carcinogenicity refers to a highly toxic end point of certain chemicals, and has become an important issue in the drug development process. In this study, three novel ensemble classification models, namely Ensemble SVM, Ensemble RF, and Ensemble XGBoost, were developed to predict carcinogenicity of chemicals using seven types of molecular fingerprints and three machine learning methods based on a dataset containing 1003 diverse compounds with rat carcinogenicity. Among these three models, Ensemble XGBoost is found to be the best, giving an average accuracy of 70.1 ± 2.9%, sensitivity of 67.0 ± 5.0%, and specificity of 73.1 ± 4.4% in five-fold cross-validation and an accuracy of 70.0%, sensitivity of 65.2%, and specificity of 76.5% in external validation. In comparison with some recent methods, the ensemble models outperform some machine learning-based approaches and yield equal accuracy and higher specificity but lower sensitivity than rule-based expert systems. It is also found that the ensemble models could be further improved if more data were available. As an application, the ensemble models are employed to discover potential carcinogens in the DrugBank database. The results indicate that the proposed models are helpful in predicting the carcinogenicity of chemicals. A web server called CarcinoPred-EL has been built for these models ( http://ccsipb.lnu.edu.cn/toxicity/CarcinoPred-EL/ ).

[Health evaluation of trichloroethylene in indoor air : communication from the German ad-hoc working group on indoor guidelines of the Indoor Air Hygiene Committee and of the states' supreme health authorities].

Science.gov (United States)

2015-07-01

In the European Hazardous Substances Regulation No 1272/2008 trichloroethylene has been classified as a probable human carcinogen and a suspected mutagen. According to several Committees (German Committee on Hazardous Substances, European Scientific Committee on Occupational Exposure Limits, European Chemicals Agency´s Committee for Risk Assessment (ECHA-RAC)) concentrations of trichloroethylene cytotoxic to renal tubuli may increase the risk to develop renal cancer. At non-cytotoxic concentrations of trichloroethylene a much lower cancer risk may be assumed. Therefore, evaluating the cancer risk to the public following inhalation of trichloroethylene ECHA-RAC has assumed a sublinear exposure-response relationship for carcinogenicity of trichloroethylene. Specifically, ECHA-RAC assessed a cancer risk of 6.4 × 10(- 5) (mg/m(3))(- 1) following life time exposure to trichloroethylene below a NOAEC for renal cytotoxicity of 6 mg trichloroethylene/m(3). Further evaluation yields a life-time risk of 10(- 6) corresponding to 0.02 mg trichloroethylene/m(3). This concentration is well above the reference (e.g. background) concentration of trichloroethylene in indoor air. Consequently the Ad-hoc Working Group on Indoor Guidelines recommends 0.02 mg trichloroethylene/m(3) as a risk-related guideline for indoor air. Measures to reduce exposure are considered inappropriate at concentrations below this guideline.

Toxic and carcinogenic agents in dry and moist snuff.

Science.gov (United States)

Hoffmann, D; Adams, J D; Lisk, D; Fisenne, I; Brunnemann, K D

1987-12-01

The oral use of snuff is causatively associated with cancer of the oral cavity. Since most epidemiologic studies to date relate to the long-term use of dry snuff, which has dominated the U.S. smokeless tobacco market in the past, the concentrations of several toxic and carcinogenic agents in the three most popular dry snuff brands have been compared with those in the five most popular moist snuff brands sold in the United States. All eight samples were analyzed for nitrate, alkaloids, polyphenols, volatile carbonyl compounds, lead, cadmium, selenium, and the carcinogenic compounds benzo[a]pyrene (CAS: 50-32-8), polonium-210 (CAS: 13981-52-7), volatile N-nitrosamines (VNAs), N-nitrosodiethanolamine (CAS: 1116-54-7), and the tobacco-specific N-nitrosamines (TSNAs). Most of the snuff brands were rich in nitrate (greater than or equal to 1.5%), total polyphenols (greater than 2%), and in nicotine (greater than or equal to 1.5%), which is the habituating factor in tobacco use. Concentrations of the VNAs were significantly above the permissible limits set for some food products; the concentrations of the TSNAs in both snuff types exceeded the levels of nitrosamines in other consumer products by at least two to three orders of magnitude. The extremely high levels of the TSNAs in snuff have remained unchanged during the last decade and present the major carcinogenic risk factor for the oral use of snuff. Polonium-210 contributes further to the carcinogenic risk associated with snuff. The chemical-analytical data presented in this study do not indicate marked differences in the carcinogenic potential of moist snuff compared to dry snuff.

Predictive Models for Carcinogenicity and Mutagenicity: Frameworks,State-of-the-Art, and Perspectives

Science.gov (United States)

Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendou...

Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

Science.gov (United States)

O'Brien, J; Renwick, A G; Constable, A; Dybing, E; Müller, D J G; Schlatter, J; Slob, W; Tueting, W; van Benthem, J; Williams, G M; Wolfreys, A

2006-10-01

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

INTEGRATION OF QSAR AND SAR METHODS FOR THE MECHANISTIC INTERPRETATION OF PREDICTIVE MODELS FOR CARCINOGENICITY

Directory of Open Access Journals (Sweden)

Natalja Fjodorova

2012-07-01

Full Text Available The knowledge-based Toxtree expert system (SAR approach was integrated with the statistically based counter propagation artificial neural network (CP ANN model (QSAR approach to contribute to a better mechanistic understanding of a carcinogenicity model for non-congeneric chemicals using Dragon descriptors and carcinogenic potency for rats as a response. The transparency of the CP ANN algorithm was demonstrated using intrinsic mapping technique specifically Kohonen maps. Chemical structures were represented by Dragon descriptors that express the structural and electronic features of molecules such as their shape and electronic surrounding related to reactivity of molecules. It was illustrated how the descriptors are correlated with particular structural alerts (SAs for carcinogenicity with recognized mechanistic link to carcinogenic activity. Moreover, the Kohonen mapping technique enables one to examine the separation of carcinogens and non-carcinogens (for rats within a family of chemicals with a particular SA for carcinogenicity. The mechanistic interpretation of models is important for the evaluation of safety of chemicals.

Mechanism-Based Classification of PAH Mixtures to Predict Carcinogenic Potential.

Science.gov (United States)

Tilton, Susan C; Siddens, Lisbeth K; Krueger, Sharon K; Larkin, Andrew J; Löhr, Christiane V; Williams, David E; Baird, William M; Waters, Katrina M

2015-07-01

We have previously shown that relative potency factors and DNA adduct measurements are inadequate for predicting carcinogenicity of certain polycyclic aromatic hydrocarbons (PAHs) and PAH mixtures, particularly those that function through alternate pathways or exhibit greater promotional activity compared to benzo[a]pyrene (BaP). Therefore, we developed a pathway-based approach for classification of tumor outcome after dermal exposure to PAH/mixtures. FVB/N mice were exposed to dibenzo[def,p]chrysene (DBC), BaP, or environmental PAH mixtures (Mix 1-3) following a 2-stage initiation/promotion skin tumor protocol. Resulting tumor incidence could be categorized by carcinogenic potency as DBC > BaP = Mix2 = Mix3 > Mix1 = Control, based on statistical significance. Gene expression profiles measured in skin of mice collected 12 h post-initiation were compared with tumor outcome for identification of short-term bioactivity profiles. A Bayesian integration model was utilized to identify biological pathways predictive of PAH carcinogenic potential during initiation. Integration of probability matrices from four enriched pathways (P PAH mixtures. These data further provide a 'source-to-outcome' model that could be used to predict PAH interactions during tumorigenesis and provide an example of how mode-of-action-based risk assessment could be employed for environmental PAH mixtures. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Carcinogenic effects of radiation-introduction

International Nuclear Information System (INIS)

Setlow, R.B.

1976-01-01

The weight of experimental evidence reviewed indicates that UV damage to DNA, probably pyrimidine dimers, is the best molecular candidate for the initiating damage that leads to skin cancer. It is postulated that the carcinogenic action spectrum should be similar to the DNA action spectrum filtered through the upper layer of skin

Physiotherapy in rheumatoid arthritis: development of a practice guideline.

Science.gov (United States)

Hurkmans, E J; van der Giesen, F J; Bloo, H; Boonman, D C; van der Esch, M; Fluit, M; Hilberdink, W K; Peter, W F; van der Stegen, H P; Veerman, E A; Verhoef, J; Vermeulen, H M; Hendriks, H M; Schoones, J W; Vliet Vlieland, T P

2011-01-01

To improve the quality of the physiotherapy management in patients with rheumatoid arthritis (RA) a Dutch practice guideline, based on current scientific evidence and best practice, was developed. This guideline comprised all elements of a structured approach (assessment, treatment and evaluation) and was based on the Internatio-nal Classification of Functioning, disability and Health (ICF) and the ICF core sets for RA. A guideline steering committee, comprising 10 expert physiotherapists, selected topics concerning the guideline chapters initial assessment, treatment and evaluation. With respect to treatment a systematic literature search was performed using various databases, and the evidence was graded (1-4). For the initial assessment and evaluation mainly review papers and textbooks were used. Based on evidence and expert opinion, recommendations were formulated. A first draft of the guideline was reviewed by 10 experts from different professional backgrounds resulting in the final guideline. In total 7 topics were selected. For the initial assessment, three recommendations were made. Based on the ICF core sets for RA a list of health problems relevant for the physiotherapist was made and completed with red flags and points of attention. Concerning treatment, three recommendations were formulated; both exercise therapy and education on physiotherapy were recommended, whereas passive interventions (delivery of heat or cold, mechanical, electric and electromagnetic energy, massage, passive mobilization/manipulation and balneotherapy) were neither recommended nor discouraged. For treatment evaluation at the level of activities and participation, the Health Assessment Questionnaire was recommended. For evaluating specific body structures and functions the handheld dynamometer, 6-minute walk test or Ästrand bicycle test (including Borg-scale for rating the perceived exertion), Escola Paulista de Medicina Range of Motion Scale and a Visual Analog Scale for pain and

Serving our communities better. Guidelines for planning and developing integrated delivery networks.

Science.gov (United States)

Prybil, L; Golden, P; Ballance, X

1995-04-01

In 1994 the Daughters of Charity National Health System-East Central (DCNHS-East Central) adopted 11 guidelines to help corporate staff and local leaders plan and develop integrated networks. Guideline 1 emphasizes needs-based strategic planning. Guideline 2 focuses on the community-based network planning process, recommending a team approach and ongoing communication with the local ordinary. In guidelines 3 through 5, the DCNHS-East Central Board of Directors spells out key issues that must be covered in proposals ultimately presented for governance action. Guideline 6 presents three core elements that should characterize all CBNs in which DCNHS-East Central institutions participate. Guideline 7 emphasizes that all CBN proposals and agreements must be clear with respect to the Catholic identity of DCNHS-East Central institutions. Guidelines 8 and 9 require that proposed changes to traditional policies and management practices be explicit in CBN proposals. The tenth guideline requires that all CBN proposals indicate an explicit evaluation function. The final guideline underscores that regardless of the strategic fit or how well a CBN is designed, it is unlikely to succeed unless both internal and external relationships are based on a solid foundation of honesty, mutual respect, and trust.

Moesin Is a Biomarker for the Assessment of Genotoxic Carcinogens in Mouse Lymphoma

Science.gov (United States)

Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

2012-01-01

1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. PMID:22358511

Moving forward in carcinogenicity assessment : Report of an EURL ECVAM/ESTIV workshop

NARCIS (Netherlands)

Corvi, Raffaella; Madia, Federica; Guyton, Kathryn Z; Kasper, Peter; Rudel, Ruthann; Colacci, Annamaria; Kleinjans, Jos; Jennings, Paul

2017-01-01

There is an increased need to develop novel alternative approaches to the two-year rodent bioassay for the carcinogenicity assessment of substances where the rodent bioassay is still a basic requirement, as well as for those substances where animal use is banned or limited or where information gaps

[Development of "assessment guideline of family power for healthy life"].

Science.gov (United States)

Fukushima, M; Shimanouchi, S; Kamei, T; Takagai, E; Hoshino, Y; Sugiyama, I

1997-12-01

The purpose of this study is to develop "assessment guideline of family power for healthy life" aiming at expanding self-care power of family in community nursing practice. The subjects of this study covered those families in one hundred and fifty six instances that we had seized as subject for nursing care and study. The method of this study had constructed assessment guideline inductively out of each case, and modified it by applying to cases of families with health problems and others. As a result, we had formed nine items of "family power for healthy life" and three items of "conditions influencing family power for healthy life" for "assessment guideline of family power for healthy life".

Development of guidelines for seismic isolation in Italy

International Nuclear Information System (INIS)

Olivieri, M.; Martelli, A.; Bettinali, F.; Bonacina, G.

1992-01-01

The first activities on seismic isolation that were performed in Italy concerned the preparation of a proposal for design guidelines for nuclear power plants using the high damping steel-laminated elastomer bearings (HDLRBs). They were jointly initiated by ENEA-RIN and GE Nuclear Energy in 1988, with the co-operation of ISMES and the support of experts of ENEA-DISP and Bechtel National Inc. The features of the guidelines proposal were outlined at the First Post-SMiRT Conference Seminar on Seismic Base Isolation of Nuclear Power Facilities (San Francisco, 1989). The full text of the document was published in the Journal 'Energia Nucleare' in 1990, in a tentative form, to allow for a broad review. A summary of the main items - together with some first results of R and D studies performed in support to guidelines development - was also reported in a paper which was recently published by the Journal 'Nuclear Technology' (February 1992). A first revision of the document is being prepared and will be soon published: it accounts for both comments received - for instance, by the American Society of Civil Engineers (ASCE), ENEA-DISP and the Malaysian Rubber Producers' Association (MRPRA) - and the first results of R and D studies in progress in Italy and the USA. These activities have recently been extended - as part of a cooperation with the Italian Standard Authority (UNI) - to other antiseismic devices, for application to civil buildings and non-nuclear plants. A co-operation of ENEA, ENEL and ISMES has also been started with the National Seismic Service to help it in the assessment of national regulations. Furthermore, extension of the aforesaid guidelines document to nuclear reactors using bearings different from the HDLRB has been planned, under the sponsorship of the Commission of the European communities: this work will be performed by ENEA, with the cooperation of ALGA, ISMES, ANSALDO and the Nuclear Engineering Laboratory (LIN) of the Bologna University, and the

Carcinogenicity of soil extracts

Energy Technology Data Exchange (ETDEWEB)

Shcherbak, N P

1970-01-01

A total of 270 3-mo-old mice, hybrids of the C57BL and CBA strains which are highly susceptible to carcinogens, were painted on the skin (2-3 admin./week) with 3-4 drops of (1) a concentrated benzene extract of soil taken near a petroleum refinery with a 3,4 benzpyrene (BP) content of 0.22%; (2) a 0.22% soln of pure BP in benzene; (3) a concentrated benzene extract of soil taken from an old residential area of Moscow (BP content 0.0004%); (4) a 0.0004% BP soln in benzene; and (5) pure benzene. Only mice in the first 2 groups developed tumors. In group (1), 8 mice had papillomas, 46 had skin cancer, 1 had a sarcoma and 2 had plasmocytomas. In group (2) all 60 animals had skin cancer. Lung metastases were present at autopsy in 5 mice in group (1) and in 10 mice in group (2); in some cases, these tumors were multiple. Lymph node metastases were found in 6 mice in group (1) and in 10 mice in group (2). Tumors developed more slowly in group (1) than in group (2).

Determination of carcinogenic threshold limit values using the tumorigenic dose rate 50% (TD50)

International Nuclear Information System (INIS)

Bonvalot, Y.; Oudiz, A.; Hubert, P.; Abenhaim, L.

1989-01-01

The objective of the present study is to propose a simple procedure for the determination of Occupational Limit Values (OLVs) based on the TD 50 concept (Tumorigenic Dose Rate 50%). The TD 50 concept was introduced by Peto R. and al. to help classify chemical substances according to their carcinogenic potency. The TD 50 is that dose rate (in mg/KXg body weight/day) which, if administered chronically for the standard lifespan of the species will halve the probability of remaining tumorless throughout that period. Using TD 50 values available for 776 substances, the procedure presented here allows one to determine OLVs corresponding to a fixed excess risk. It is based on a mathematical high-to-low doses extrapolation of the TD 50 . OLVs obtained with this procedure are compared with currently available TLVs and other occupational guidelines. (author)

Cannabis and tobacco smoke are not equally carcinogenic

Directory of Open Access Journals (Sweden)

Melamede Robert

2005-10-01

Full Text Available Abstract More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.

Carcinogenic effect of petroleum and its by-products

Energy Technology Data Exchange (ETDEWEB)

Gimadeev, M M

1962-01-01

A review of literature on the carcinogenic effect of petroleum and its by-products are briefly discussed. Many of the products can induce hyperkeratosis, folliculitis, verruca, pulmonary adenoma, skin cancer, etc. Their action is mainly local but they can also be multicentric. Although a number of groups have made chemical analyses of various petroleums and peroleum products, results were generally negative with respect to 3,4-benzypyrene, although 40 to 68 microg/g was found in 1 crude petroleum. At present it appears that much of the carcinogenic action of these materials resides in polycyclic hydrocarbons about which little is known.

Changing Current Practice in Urology: Improving Guideline Development and Implementation Through Stakeholder Engagement.

Science.gov (United States)

MacLennan, Sara J; MacLennan, Steven; Bex, Axel; Catto, James W F; De Santis, Maria; Glaser, Adam W; Ljungberg, Borje; N'Dow, James; Plass, Karin; Trapero-Bertran, Marta; Van Poppel, Hendrik; Wright, Penny; Giles, Rachel H

2017-08-01

Effective stakeholder integration for guideline development should improve outcomes and adherence to clinical practice guidelines. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The Carcinogenic Agent Azoxymethane (AOM) Enhances Early Inflammation-induced Colon Crypt Pathology

DEFF Research Database (Denmark)

Venning, Freja Albjerg; Claesson, Mogens Helweg; Kissow, Hannelouise

2013-01-01

Severe combined immunodeficiency (SCID) mice transplanted with CD4+ T cells depleted of CD25+ regulatory T cells develop colitis within 2-3 weeks after the T cell transfer. In the present study we studied the effect of the carcinogen azoxymethane (AOM) on the colon crypt pathology of normal SCID...

Wireless application guidelines for usability design and evaluation for developing countries

International Nuclear Information System (INIS)

Khoja, S.A.; Ursani, A.A.; Ali, A.

2009-01-01

The aim of this paper is to provide guidelines for designing wireless applications. These guidelines are developed with the help of Human Computer Interaction based Usability Evaluation surveys and tests results. These guidelines will help in making wireless applications more usable and attractive for users and will help designers to plan effective interactive applications. The guidelines presented in the paper have been derived from the results of surveys, usability tests and SET (Summative Evaluation Tests) carried out over 200 people of Karachi, Pakistan, from different walks of life with different academic and professional backgrounds, making imperative suggestions not only to improve the usability of exciting features given in wireless and mobile products, but also provide suggestions to improve usability of basic components such as, text, navigation, interactivity, multimedia, control and behavior. (author)

Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

Science.gov (United States)

Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

2016-02-01

We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

A call to expand regulation to all carcinogenic fibrous minerals

Science.gov (United States)

Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

2013-05-01

The regulatory term "asbestos" groups only the six fibrous minerals that were commercially used among approximately 400. The carcinogenicity of these six regulated minerals has been largely demonstrated and is related to fiber structure, fiber length/diameter ratio, and bio-persistence. From a public perception, the generic term "asbestos" refers to the fibrous minerals that cause asbestosis, mesothelioma and other cancers. However, other non-regulated fibrous minerals are potentially as dangerous as the regulatory asbestos because they share similar physical and chemical properties, epidemiological studies have demonstrated their relationship with asbestos-related diseases, and both in vitro and in vivo experiments have established the toxicity of these minerals. For example, the non-regulated asbestiform winchite and richterite minerals that contaminated the vermiculite mined from Libby, Montana, (USA) were associated with mesothelioma, lung cancer and asbestosis observed among the area's residents and miners. Many other examples of non-regulated carcinogenic fibrous minerals include, but are not limited to, antigorite, arfvedsonite, balangeroite, carlosturanite, erionite, fluoro-edenite, hornblende, mordenite, palygorskite, and sepiolite. To propose a regulatory definition that would provide protection from all carcinogenic fibers, we have conducted an interdisciplinary literature review to compare the characteristics of "asbestos" and of non-regulated mineral fibers that relate to carcinogenicity. We specifically studied two non-regulated fibrous minerals that are associated with asbestos-related diseases: the serpentine antigorite and the zeolite erionite. Both examples underscore the problem of regulation based on commercial, rather than scientific principles: 1) the occurrence of fibrous antigorite in materials used to pave roads has been correlated with high mesothelioma rates in New Caledonia. Antigorite was also the cause of asbestosis in Poland, and in

Relevance of urinary 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene to assess exposure to carcinogenic polycyclic aromatic hydrocarbon mixtures in metallurgy workers.

Science.gov (United States)

Barbeau, Damien; Persoons, Renaud; Marques, Marie; Hervé, Claire; Laffitte-Rigaud, Gilbert; Maitre, Anne

2014-06-01

In metallurgy, workers are exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs) in which some compounds are carcinogenic. Biomonitoring of PAH exposure has been performed by measuring urinary 1-hydroxypyrene (1-OHP), a metabolite of pyrene which is not carcinogenic. This study investigated the use of 3-hydroxybenzo(a)pyrene (3-OHBaP), a metabolite of benzo(a)pyrene (BaP) which is the main carcinogenic component in PAHs, to improve carcinogen exposure assessment. We included 129 metallurgy workers routinely exposed to PAHs during working hours. Urinary samples were collected at three sampling times at the beginning and at the end of the working week for 1-OHP and 3-OHBaP analyses. Workers in anode production showed greater exposure to both biomarkers than those in cathode or silicon production, with respectively, 71, 40, and 30% of 3-OHBaP concentrations exceeding the value of 0.4 nmol mol(-1) creatinine. No difference was observed between the 3-OHBaP levels found at the end of the penultimate workday shift and those at the beginning of the last workday shift. Within these plants, the 1-OHP/3-OHBaP ratios varied greatly according to the workers' activity and emission sources. Using linear regression between these two metabolites, the 1-OHP level corresponding to the guidance value for 3-OHBaP ranged from 0.7 to 2.4 µmol mol(-1) creatinine, depending on the industrial sector. This study emphasizes the interest of monitoring urinary 3-OHBaP at the end of the last workday shift when working week exposure is relatively steady, and the irrelevance of a single guideline value for 1-OHP when assessing occupational health risk. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

USING PROTEOMICS TO MONITOR PROTEIN EXPRESSION IN HUMAN CELLS EXPOSED TO CARCINOGENS

Science.gov (United States)

People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic properties in experimental systems. It has been estimated that exposure to environmental chemical carcinogens in the environment may contribute significantly to t...

Guidelines for developing effective health education service in a national health agency.

Science.gov (United States)

Ochor, J O

1983-01-01

The constraints facing health education include: the fragmentation and dispersal of health-educational services among different agencies and personnel; lack of policy guidelines; ineffectively organized and inefficiently managed health education systems; poor hierarchical status and inadequacy of resources. To resolve these constraints, national health education systems in health agencies should be developed on the basis of stipulated guidelines that could ensure their viability, efficiency and effectiveness. A study at the African Regional Health Education Centre, Ibadan, Nigeria, has yielded thirty synthesized guidelines. The "guidelines" were empirically tested as an evaluation tool by assessing the operational and organizational status of Oyo State Health Education Unit, Ibadan, Nigeria. These guidelines are adaptable to local conditions to enhance the re-organization, re-orientation and consolidation of health education in national health agencies.

Overview of the European Medicines Agency's Development of Product-Specific Bioequivalence Guidelines.

Science.gov (United States)

Sullivan, Jane O'; Blake, Kevin; Berntgen, Michael; Salmonson, Tomas; Welink, Jan

2017-12-05

The European Medicines Agency's (EMA) product-specific bioequivalence guidelines outline harmonized regulatory requirements for studies to demonstrate bioequivalence for products that may have particular needs due to their pharmacokinetics, in addition to those outlined in general guidance. As such they are potentially very useful to the pharmaceutical industry in the development of generic medicinal products and to regulatory authorities for harmonized decision-making. Since their introduction in 2013, EMA product-specific bioequivalence guidelines continue to increase in number, and as of June 2017, encompass a number of different pharmacotherapeutic groups and pharmaceutical forms. This article further elucidates the processes involved for stakeholders and reviews the Agency's experience with the development of these guidelines, including the scientific issues witnessed with their advancement. A comparison with the United States Food and Drug Administration approach to similar guidelines is also provided. © 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

OpenAIRE

Hurley, P M

1998-01-01

Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly ...

Best-practices guidelines for L2PSA development and applications. Volume 1 - General

International Nuclear Information System (INIS)

Raimond, E.; Pichereau, F.; Durin, T.; Rahni, N.; Loeffler, H.; Roesch, O.; Lajtha, G.; Santamaria, C.S.; Dienstbier, J.; Rydl, A.; Holmberg, J.E.; Lindholm, I.; Maennistoe, I.; Pauli, E.M.; Dirksen, G.; Grindon, L.; Peers, K.; Bassi, C.; Hulqvist, G.; Parozzi, F.; Polidoro, F.; Cazzoli, E.; Vitazkova, J.; Burgazzi, L.; Brinkman, H.; Seidel, A.; Schubert, B.; Wohlstein, R.; Guentay, S.; Oury, L.; Ngatchou, C.; Siltanen, S.; Niemela, I.; Routamo, T.; Vincon, L.; Helstroem, P.

2010-01-01

The objective of this coordinated action was to develop best practice guidelines for the performance and application of Level 2 PSA with a view to achieve harmonisation at EU level and to allow a meaningful and practical uncertainty evaluation in a Level 2 PSA. Specific relationships with communities in charge of nuclear reactor safety (utilities, safety authorities, vendors, and research or services companies) have been established in order to define the current needs in terms of guidelines for Level 2 PSA development and application. An international workshop was organised in Hamburg, with the support of VATTENFALL, in November 2008. The Level 2 PSA experts from ASAMPSA2 project partners have proposed some guidelines for the development and application of L2PSA based on their experience, open literature, and on information available from international cooperation (EC Severe Accident network of Excellence - SARNET, IAEA standards, OECD-NEA publications and workshop). There are a large number of technical issues addressed in the guideline which are not all covered with the same level of detail in the first version of the guideline. This version was submitted for external review in November 2010 by severe accident and PSA experts (especially from SARNET and OECD-NEA members). The feedback of the external review will be dis cussed during an international open works hop planned for March 2011 and all outcomes will be taken into consideration in the final version of this guideline (June 2011). The guideline includes 3 volumes: - Volume 1 - General considerations on L2PSA. - Volume 2 - Technical recommendations for Gen II and III reactors. - Volume 3 - Specific considerations for future reactors (Gen IV). The recommendations formulated in the guideline should not be considered as 'mandatory' but should help Level 2 PSA developers to achieve high quality studies with limited time and resources. It may also help Level 2 PSA reviewers by positioning one specific study in

A proposed framework for consistent regulation of public exposures to radionuclides and other carcinogens

International Nuclear Information System (INIS)

Kocher, D.C.; Hoffman, F.O.

1991-01-01

This paper discusses a proposed framework for consistent regulation of carcinogenic risks to the public based on establishing de manifestis (i.e., unacceptable) and de minimis (i.e., trivial) lifetime risks from exposure to any carcinogens at levels of about 10 -1 --10 -3 and 10 -4 --10 -6 , respectively, and reduction of risks above de minimis levels as low as reasonably achievable (ALARA). We then discuss certain differences in the way risks from exposure to radionuclides and other carcinogens currently are regulated or assessed which would need to be considered in implementing the proposed regulatory framework for all carcinogens

A method for developing standardised interactive education for complex clinical guidelines

Directory of Open Access Journals (Sweden)

Vaughan Janet I

2012-11-01

Full Text Available Abstract Background Although systematic use of the Perinatal Society of Australia and New Zealand internationally endorsed Clinical Practice Guideline for Perinatal Mortality (PSANZ-CPG improves health outcomes, implementation is inadequate. Its complexity is a feature known to be associated with non-compliance. Interactive education is effective as a guideline implementation strategy, but lacks an agreed definition. SCORPIO is an educational framework containing interactive and didactic teaching, but has not previously been used to implement guidelines. Our aim was to transform the PSANZ-CPG into an education workshop to develop quality standardised interactive education acceptable to participants for learning skills in collaborative interprofessional care. Methods The workshop was developed using the construct of an educational framework (SCORPIO, the PSANZ-CPG, a transformation process and tutor training. After a pilot workshop with key target and stakeholder groups, modifications were made to this and subsequent workshops based on multisource written observations from interprofessional participants, tutors and an independent educator. This participatory action research process was used to monitor acceptability and educational standards. Standardised interactive education was defined as the attainment of content and teaching standards. Quantitative analysis of positive expressed as a percentage of total feedback was used to derive a total quality score. Results Eight workshops were held with 181 participants and 15 different tutors. Five versions resulted from the action research methodology. Thematic analysis of multisource observations identified eight recurring education themes or quality domains used for standardisation. The two content domains were curriculum and alignment with the guideline and the six teaching domains; overload, timing, didacticism, relevance, reproducibility and participant engagement. Engagement was the most

Guidelines for responsible short-term global health activities: developing common principles.

Science.gov (United States)

Lasker, Judith N; Aldrink, Myron; Balasubramaniam, Ramaswami; Caldron, Paul; Compton, Bruce; Evert, Jessica; Loh, Lawrence C; Prasad, Shailendra; Siegel, Shira

2018-02-07

Growing concerns about the value and effectiveness of short-term volunteer trips intending to improve health in underserved Global South communities has driven the development of guidelines by multiple organizations and individuals. These are intended to mitigate potential harms and maximize benefits associated with such efforts. This paper analyzes 27 guidelines derived from a scoping review of the literature available in early 2017, describing their authorship, intended audiences, the aspects of short term medical missions (STMMs) they address, and their attention to guideline implementation. It further considers how these guidelines relate to the desires of host communities, as seen in studies of host country staff who work with volunteers. Existing guidelines are almost entirely written by and addressed to educators and practitioners in the Global North. There is broad consensus on key principles for responsible, effective, and ethical programs--need for host partners, proper preparation and supervision of visitors, needs assessment and evaluation, sustainability, and adherence to pertinent legal and ethical standards. Host country staff studies suggest agreement with the main elements of this guideline consensus, but they add the importance of mutual learning and respect for hosts. Guidelines must be informed by research and policy directives from host countries that is now mostly absent. Also, a comprehensive strategy to support adherence to best practice guidelines is needed, given limited regulation and enforcement capacity in host country contexts and strong incentives for involved stakeholders to undertake or host STMMs that do not respect key principles.

Carcinogenicity of chromium and chemoprevention: a brief update

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Wang Y

2017-08-01

Full Text Available Yafei Wang,1,* Hong Su,1,* Yuanliang Gu,1 Xin Song,1 Jinshun Zhao1,2 1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People’s Republic of China; 2Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA *These authors contributed equally to this work Abstract: Chromium has two main valence states: hexavalent chromium (Cr[VI] and trivalent chromium (Cr[III]. Cr(VI, a well-established human carcinogen, can enter cells by way of a sulfate/phosphate anion-transport system, and then be reduced to lower-valence intermediates consisting of pentavalent chromium (Cr[V], tetravalent chromium (Cr[IV] or Cr(III via cellular reductants. These intermediates may directly or indirectly result in DNA damage or DNA–protein cross-links. Although Cr(III complexes cannot pass easily through cell membranes, they have the ability to accumulate around cells to induce cell-surface morphological alteration and result in cell-membrane lipid injuries via disruption of cellular functions and integrity, and finally to cause DNA damage. In recent years, more research, including in vitro, in vivo, and epidemiological studies, has been conducted to evaluate the genotoxicity/carcinogenicity induced by Cr(VI and/or Cr(III compounds. At the same time, various therapeutic agents, especially antioxidants, have been explored through in vitro and in vivo studies for preventing chromium-induced genotoxicity/carcinogenesis. This review aims to provide a brief update on the carcinogenicity of Cr(VI and Cr(III and chemoprevention with different antioxidants. Keywords: hexavalent chromium, Cr(VI, trivalent chromium, Cr(III, genotoxicity, carcinogenicity, chemoprevention, antioxidant 

Developing a practice guideline for the occupational health services by using a community of practice approach: a process evaluation of the development process

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Lydia Kwak

2017-01-01

Full Text Available Abstract Background One way to facilitate the translation of research into the occupational health service practice is through clinical practice guidelines. To increase the implementability of guidelines it is important to include the end-users in the development, for example by a community of practice approach. This paper describes the development of an occupational health practice guideline aimed at the management of non-specific low back pain (LBP by using a community of practice approach. The paper also includes a process evaluation of the development providing insight into the feasibility of the process. Methods A multidisciplinary community of practice group (n = 16 consisting of occupational nurses, occupational physicians, ergonomists/physical therapists, health and safety engineers, health educators, psychologists and researchers from different types of occupational health services and geographical regions within Sweden met eleven times (June 2012–December 2013 to develop the practice guideline following recommendations of guideline development handbooks. Process-outcomes recruitment, reach, context, satisfaction, feasibility and fidelity were assessed by questionnaire, observations and administrative data. Results Group members attended on average 7.5 out of 11 meetings. Half experienced support from their workplace for their involvement. Feasibility was rated as good, except for time-scheduling. Most group members were satisfied with the structure of the process (e.g. presentations, multidisciplinary group. Fidelity was rated as fairly high. Conclusions The described development process is a feasible process for guideline development. For future guideline development expectations of the work involved should be more clearly communicated, as well as the purpose and tasks of the CoP-group. Moreover, possibilities to improve support from managers and colleagues should be explored. This paper has important implications for future

Moving forward in carcinogenicity assessment: Report of an EURL ECVAM/ESTIV workshop.

Science.gov (United States)

Corvi, Raffaella; Madia, Federica; Guyton, Kathryn Z; Kasper, Peter; Rudel, Ruthann; Colacci, Annamaria; Kleinjans, Jos; Jennings, Paul

2017-12-01

There is an increased need to develop novel alternative approaches to the two-year rodent bioassay for the carcinogenicity assessment of substances where the rodent bioassay is still a basic requirement, as well as for those substances where animal use is banned or limited or where information gaps are identified within legislation. The current progress in this area was addressed in a EURL ECVAM- ESTIV workshop held in October 2016, in Juan les Pins. A number of initiatives were presented and discussed, including data-driven, technology-driven and pathway-driven approaches. Despite a seemingly diverse range of strategic developments, commonalities are emerging. For example, providing insight into carcinogenicity mechanisms is becoming an increasingly appreciated aspect of hazard assessment and is suggested to be the best strategy to drive new developments. Thus, now more than ever, there is a need to combine and focus efforts towards the integration of available information between sectors. Such cross-sectorial harmonisation will aid in building confidence in new approach methods leading to increased implementation and thus a decreased necessity for the two-year rodent bioassay. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of occupational carcinogens on lung cancer risk in a general population

NARCIS (Netherlands)

De Matteis, S.; Consonni, D.; Lubin, J.H.; Tucker, M.; Peters, S.; Vermeulen, R.; Kromhout, H.; Bertazzi, P.A.; Caporaso, N.E.; Pesatori, A.C.; Wacholder, S.; Landi, M.T.

2012-01-01

BACKGROUND: Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most of the previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. METHODS: We applied

The challenge of developing ethical guidelines for a research infrastructure

Science.gov (United States)

Kutsch, Werner Leo

2016-04-01

The mission of the Integrated Carbon Observation System (ICOS RI) is to enable research to understand the greenhouse gas (GHG) budgets and perturbations. The ICOS RI provides the long-term observations required to understand the present state and predict future behaviour of the global carbon cycle and GHG emissions. Technological developments and implementations, related to GHGs, will be promoted by the linking of research, education and innovation. In order to provide this data ICOS RI is a distributed research infrastructure. The backbones of ICOS RI are the national measurement stations such as ICOS atmosphere, ecosystem and ocean stations. ICOS Central Facilities are the European level ICOS RI Centres, which have the specific tasks in collecting and processing the data and samples received from the national measurement networks. During the establishment of ICOS RI ethical guidelines were developed. These guidelines describe principles of ethics in the research activities that should be applied within ICOS RI. They should be acknowledged and followed by all researchers affiliated to ICOS RI and should be supported by all participating institutions. The presentation describes (1) the general challenge to develop ethical guidelines in a complex international infrastructure and (2) gives an overview about the content that includes different kinds of conflicts of interests, data ethics and social responsibility.

[The development of clinical guidelines for the diagnosis and treatment of chronic periodontitis in Belgium].

Science.gov (United States)

Cosyn, Jan; De Bruyn, Hugo

2008-01-01

In many disciplines of medicine guidelines are developed for the diagnosis and treatment of disease. These are essentially intended to standardize care and to optimize communication between the general practitioner and the specialist. Guidelines have already been described in the literature for chronic periodontitis. However, given the unique conditions in Belgium, these may not be appropriate for the average dental practice. In this manuscript the development of Belgian clinical guidelines for the diagnosis and treatment of chronic periodontitis is described. Basically, ten clinical questions were used as a basis for a thorough literature search. Evidence-based clinical guidelines were developed and adapted during three peer review sessions. In the final session Belgian specialists, who had all been invited, participated. This made sure that the scientific input was sufficiently transformed into clinical guidelines which are actually feasible today in Belgium.

Chemical carcinogenic and mutagenic agents in the workplace, Poland, 2008–2010

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Katarzyna Konieczko

2013-04-01

Full Text Available Background: The aim of this paper is to present a concise but comprehensive information on the occurrence of carcinogenic or mutagenic agents in Polish enterprises and the number of workers exposed to those agents reported to the central register by employers. Objectives and responsibilities of the register, as well as the range and methods of data gathering are discussed. Material and Methods: Data concerning carcinogenic or mutagenic chemical substances and technological processes reported to central register in 2008-2010 were analyzed. Results: In 2008-2010 more than 300 carcinogenic or mutagenic chemical substances were reported to the register. Approximately 2500 plants reported above 150 000 per-person-exposures annually. Among all technological processes regarded as occupational carcinogens, hardwood dusts exposure (about 660 companies; 11 000-13 000 exposed workers each year and exposure to polycyclic aromatic hydrocarbons (PAHs present in coal products (117-125 plantsl 3000 exposed per year were reported. Conclusions: The most widespread carcinogenic/mutagenic substances were: benzene, chromium(VI compounds: potassium dichromate and chromate, chromium(VI trioxide and other chromium compounds, ethylene oxide, asbestos, benzo[a]pyrene and gasoline. The highest number of men was exposed to particular PAHs and benzene , and the majority of women was exposed to benzene, potassium dichromate and chromate, acrylamide, ethylene oxide and gasoline. The lack of clear-cut definitione of occupational exposure to carcinogen creates a problem faced by employers in defining the accurate number of exposed workers. Med Pr 2013;64(2:181–192

Proposed changes in the classification of carcinogenic chemicals in the work area.

Science.gov (United States)

Neumann, H G; Thielmann, H W; Filser, J G; Gelbke, H P; Greim, H; Kappus, H; Norpoth, K H; Reuter, U; Vamvakas, S; Wardenbach, P; Wichmann, H E

1997-12-01

Carcinogenic chemicals in the work area are currently classified into three categories in Section III of the German List of MAK and BAT Values. This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these Categories--IIIA1, IIIA2, and IIIB--be retained as Categories 1, 2, and 3, to conform with EU regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, it is now proposed that these three categories be supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not convey a significant risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. It is proposed that chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures be classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics and for which risk at low doses can be assessed will be classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented. The proposed changes in classifying carcinogenic chemicals in the work area are presented for further discussion.

Designing, Developing, and Implementing Diversity Training: Guidelines for Practitioners.

Science.gov (United States)

Kincaid, Tanna M.; Horner, Erin R.

1997-01-01

Discusses diversity in the workplace and offers guidelines for practitioners in designing, developing, and implementing diversity training. Highlights include linking the diversity initiative to the organization's mission, cultural climate assessments, reviewing policies and procedures, needs assessment, learner analysis, establishing objectives,…

Antimicrobial stewardship: a qualitative study of the development of national guidelines for antibiotic use in hospitals

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Eli Feiring

2017-11-01

Full Text Available Abstract Background As effective antibiotics are becoming a scarce resource, governmental regulation is needed to promote responsible use. Implementation of antibiotic stewardship and practice guidelines in health care facilities seems to be crucial to this effort. Empirical studies suggest, however, that guidelines have limited influence on health professionals’ behavior and practice. Barriers and facilitators to guideline implementability are much studied, but little attention has been given to health professionals’ perceptions of normative acceptability of guidelines as a condition for compliance. The aim of the present study was first, to examine if and how aspects potentially promoting acceptability and compliance among clinical target users were addressed during development of Norwegian national guidelines for antibiotic use in hospitals and second, to identify procedural characteristics of the development process that were perceived by target users to yield legitimate guidelines. Methods Qualitative deductive thematic analysis was used. A theoretical framework inspired by the AGREE II Instrument and the Accountability for reasonableness framework assisted data gathering and interpretation. Archival data was collected and used to detail the guideline development process. Semi-structured, in-depth interviews with eight clinicians with extensive knowledge of the guidelines were carried out. Results Guideline development was characterized by i broad agreement about scope and purpose, ii broad involvement of stakeholders in the development process, iii use of systematic methods to search for and apply evidence, iv easily identifiable and specific recommendations, v provision of tools on how to put recommendations into practice, and vi editorial independence. Several procedural characteristics were perceived by the interviewees as promoting guideline legitimacy; i diverse perspectives systematically involved in the process, ii accessibility

Antimicrobial stewardship: a qualitative study of the development of national guidelines for antibiotic use in hospitals.

Science.gov (United States)

Feiring, Eli; Walter, Anne Berit

2017-11-21

As effective antibiotics are becoming a scarce resource, governmental regulation is needed to promote responsible use. Implementation of antibiotic stewardship and practice guidelines in health care facilities seems to be crucial to this effort. Empirical studies suggest, however, that guidelines have limited influence on health professionals' behavior and practice. Barriers and facilitators to guideline implementability are much studied, but little attention has been given to health professionals' perceptions of normative acceptability of guidelines as a condition for compliance. The aim of the present study was first, to examine if and how aspects potentially promoting acceptability and compliance among clinical target users were addressed during development of Norwegian national guidelines for antibiotic use in hospitals and second, to identify procedural characteristics of the development process that were perceived by target users to yield legitimate guidelines. Qualitative deductive thematic analysis was used. A theoretical framework inspired by the AGREE II Instrument and the Accountability for reasonableness framework assisted data gathering and interpretation. Archival data was collected and used to detail the guideline development process. Semi-structured, in-depth interviews with eight clinicians with extensive knowledge of the guidelines were carried out. Guideline development was characterized by i) broad agreement about scope and purpose, ii) broad involvement of stakeholders in the development process, iii) use of systematic methods to search for and apply evidence, iv) easily identifiable and specific recommendations, v) provision of tools on how to put recommendations into practice, and vi) editorial independence. Several procedural characteristics were perceived by the interviewees as promoting guideline legitimacy; i) diverse perspectives systematically involved in the process, ii) accessibility and transparency of the rationales for decision

Studies on carcinogenicity or anticarcinogenicity of isonicotinic acid hydrazide and caffeine by nine-week assay system

International Nuclear Information System (INIS)

Yun, Taik Koo; Oh, Yeong Ram; Kim, Sung Ho

1986-12-01

According to many surveys, cancer is one of the major causes of death in most developed countries and the incidence of cancer appears to be on the increase. Therefore, many studies on detection of carcinogenic or anticarcinogenic agents need urgently. The purpose of this investigation is evaluation the carcinogenic or anticarcinogenic effect of INH and caffeine, which were interpreted as showing either the presence or the absence of a carcinogenic or anticarcinogenic effect, using nine-week assay system. The non-inbred NIH(GP) newborn mice were injected subcutaneously with NIH(400,425, 450 or 480 μg/ head) or caffeine (75 or 100 μg/head) for evaluation of carcinogenicity. Caffeine (1 or 2 mg/ml of drinking water) was administered orally to the mice, which were injected subcutaneously with BP(500μg/head) at new-born, during 6 weeks after weaning for evaluation of anticarcinogenicity. Each group was killed at 9 weeks after the start of exanination. All major organs were examined grossly and histopathologically. Decreased lung adenoma incidence was observed statistically significant in mice fed with caffeine 1 mg(18.8%) or 2 mg(5.1%) per ml of drinking water compared to BP control group (41.3%). However, there was no statistical difference in the incidence of lung and other site tumor between the INH group and the normal control group or between caffeine injection group and normal control group. This result will be contribute to the prevention of cancer from the viewpoint of identifying carcinogenic or anticarcinogenic agents from the environment. (Author)

Development of comprehensive HFE guidelines for the evaluation of NPP human systems interfaces

International Nuclear Information System (INIS)

O'Hara, J.M.; Brown, W.S.; Wachtel, J.

1994-01-01

Advanced control room (ACR) concepts are being developed in the commercial nuclear power industry as part of future reactor designs. The ACRs will use advanced human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the ways in which the operator interacts with and supervises an increasingly complex system. The US Nuclear Regulatory Commission (NRC) reviews the HSI aspects of control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported to protect public health and safety. The NRC is developing guidelines to support its review of these advanced designs. This paper discusses (1) the development of guidelines for advanced HSI review, (2) the integration of those guidelines with existing guidance, and (3) a methodology for further guidance development

Detection of genotoxic and non-genotoxic carcinogens in Xpc−/−p53+/− mice

International Nuclear Information System (INIS)

Melis, Joost P.M.; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

2013-01-01

An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

Development and promotion of Malaysian Dietary Guidelines.

Science.gov (United States)

Tee, E-Siong

2011-01-01

Development and promotion of dietary guidelines is one of the key activities outlined in the National Plan of Action for Nutrition of Malaysia for the prevention of nutrition-related disorders. The first official Malaysian Dietary Guidelines (MDG) was published in 1999 and was thoroughly reviewed and launched on 25 March 2010. The new MDG 2010 is a compilation of science-based nutrition and physical activity recommendations. These guidelines form the basis of consistent and scientifically sound nutrition messages for the public. There are 14 key messages and 55 recommendations, covering the whole range of food and nutrition issues, from importance of consuming a variety of foods to guidance on specific food groups, messages to encourage physical activities, consuming safe food and beverages and making effective use of nutrition information on food labels. The MDG also has an updated food pyramid. Various efforts have been made to ensure that the revised MDG is disseminated to all stakeholders. The Ministry of Health has organised a series of workshops for nutritionists and other health care professionals, and the food industry. In collaboration with other professional bodies and the private sector, the Nutrition Society of Malaysia has been promoting the dissemination and usage of the MDG to the public through a variety of formats and channels. These include the publication of a series of leaflets, educational press articles, educational booklets, as well as through educational activities for children. It is imperative to monitor the usage and evaluation of these dietary messages.

Molecular basis of carcinogenicity of tungsten alloy particles

Energy Technology Data Exchange (ETDEWEB)

Harris, Robert M.; Williams, Tim D.; Waring, Rosemary H.; Hodges, Nikolas J., E-mail: n.hodges@bham.ac.uk

2015-03-15

The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91–6–3) induces rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91–6–3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91–6–3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91–6–3 occurred in rat but not in human cells. In both rat and human cells, the transcriptional response to WNC 91–6–3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97–2–1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97–2–1 elicited similar responses to WNC 91–6–3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes. - Highlights: • Use of transcriptomics to identify likely carcinogenic tungsten alloys in vitro • Cobalt containing alloys cause oxidative stress, DNA-damage and perturb apoptosis. • Presence of cobalt causes changes in gene expression

Development of suicide postvention guidelines for secondary schools: a Delphi study

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Georgina R. Cox

2016-02-01

Full Text Available Abstract Background Suicide of school-aged adolescents is a significant problem, with serious implications for students and staff alike. To date, there is a lack of evidence regarding the most effective way for a secondary school to respond to the suicide of a student, termed postvention [(Crisis 33:208-214, 2012, (Crisis 34:164-182, 2013]. The aim of this study was to employ the expert consensus (Delphi methodology to the development of a set of guidelines, to assist English-speaking secondary schools to develop a plan to respond to a student suicide, or to respond to a suicide in the absence of a predetermined plan. Methods The Delphi methodology was employed, which involved a two-stage process. Firstly, medical and research databases, existing postvention guidelines developed for schools, and lay literature were searched in order to identify potential actions that school staff could carry out following the suicide of a student. Based on this search, an online questionnaire was produced. Secondly, 40 experts in the area of suicide postvention from English-speaking countries were recruited and asked to rate each action contained within this questionnaire, in terms of how important they felt it was to be included in the postvention guidelines. A set of guidelines was developed based on these responses. In total, panel members considered 965 actions across three consensus rounds. Results Five hundred fourty-eight actions were endorsed for inclusion into the postvention guidelines based on an 80 % consensus agreement threshold. These actions were groups according to common themes, which are presented in the following sections: 1. Developing an Emergency Response Plan; 2. Forming an Emergency Response Team; 3. Activating the Emergency Response Team; 4. Managing a suspected suicide that occurs on school grounds; 5. Liaising with the deceased student’s family; 6. Informing staff of the suicide; 7. Informing students of the suicide; 8. Informing

Guidelines to PET measurements of the target occupancy in the brain for drug development

Energy Technology Data Exchange (ETDEWEB)

Takano, Akihiro; Varrone, Andrea; Gulyas, Balazs; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm (Sweden); Salvadori, Piero [CNR Istituto di Fisiologia Clinica, Pisa (Italy); Gee, Antony [Kings College London, Department of Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Windhorst, Albert; Lammertsma, Adriaan A. [VU University Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Vercouillie, Johnny [Universite Francois Rabelais de Tours, UMR Inserm U930, Tours (France); Bormans, Guy [KU Leuven, Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Leuven (Belgium)

2016-11-15

This guideline summarizes the current view of the European Association of Nuclear Medicine Drug Development Committee. The purpose of this guideline is to guarantee a high standard of PET studies that are aimed at measuring target occupancy in the brain within the framework of development programs of drugs that act within the central nervous system (CNS drugs). This guideline is intended to present information specifically adapted to European practice. The information provided should be applied within the context of local conditions and regulations. (orig.)

75 FR 10438 - Effluent Limitations Guidelines and Standards for the Construction and Development Point Source...

Science.gov (United States)

2010-03-08

... Effluent Limitations Guidelines and Standards for the Construction and Development Point Source Category... technology-based Effluent Limitations Guidelines and New Source Performance Standards for the Construction... technology-based Effluent Limitations Guidelines and New Source Performance Standards for the Construction...

Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.

Science.gov (United States)

Sugimura, Takashi; Wakabayashi, Keiji; Nakagama, Hitoshi; Nagao, Minako

2004-04-01

Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public

OVERVIEW OF DRINKING WATER MUTAGENICITY AND CARCINOGENICITY AND RISK FOR BLADDER CANCER

Science.gov (United States)

Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroacetic acid and chlorite) are not carcinogenic-in either of 2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxici...

Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

OpenAIRE

Hecht, S

2004-01-01

Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

A review of biosensing techniques for detection of trace carcinogen contamination in food products.

Science.gov (United States)

Li, Zhanming; Yu, Yue; Li, Zhiliang; Wu, Tao

2015-04-01

Carcinogen contaminations in the food chain, for example heavy metal ions, pesticides, acrylamide, and mycotoxins, have caused serious health problems. A major objective of food-safety research is the identification and prevention of exposure to these carcinogens, because of their impossible-to-reverse tumorigenic effects. However, carcinogen detection is difficult because of their trace-level presence in food. Thus, reliable and accurate separation and determination methods are essential to protect food safety and human health. This paper summarizes the state of the art in separation and determination methods for analyzing carcinogen contamination, especially the advances in biosensing methods. Furthermore, the application of promising technology including nanomaterials, imprinted polymers, and microdevices is detailed. Challenges and perspectives are also discussed.

Development of a tailored strategy to improve postpartum hemorrhage guideline adherence.

Science.gov (United States)

de Visser, Suzan M; Woiski, Mallory D; Grol, Richard P; Vandenbussche, Frank P H A; Hulscher, Marlies E J L; Scheepers, Hubertina C J; Hermens, Rosella P M G

2018-02-08

Despite the introduction of evidence based guidelines and practical courses, the incidence of postpartum hemorrhage shows an increasing trend in developed countries. Substandard care is often found, which implies an inadequate implementation in high resource countries. We aimed to reduce the gap between evidence-based guidelines and clinical application, by developing a strategy, tailored to current barriers for implementation. The development of the implementation strategy consisted of three phases, supervised by a multidisciplinary expert panel. In the first phase a framework of the strategy was created, based on barriers to optimal adherence identified among professionals and patients together with evidence on effectiveness of strategies found in literature. In the second phase, the tools within the framework were developed, leading to a first draft. In the third phase the strategy was evaluated among professionals and patients. The professionals were asked to give written feedback on tool contents, clinical usability and inconsistencies with current evidence care. Patients evaluated the tools on content and usability. Based on the feedback of both professionals and patients the tools were adjusted. We developed a tailored strategy to improve guideline adherence, covering the trajectory of the third trimester of pregnancy till the end of the delivery. The strategy, directed at professionals, comprehending three stop moments includes a risk assessment checklist, care bundle and time-out procedure. As patient empowerment tools, a patient passport and a website with patient information was developed. The evaluation among the expert panel showed all professionals to be satisfied with the content and usability and no discrepancies or inconsistencies with current evidence was found. Patients' evaluation revealed that the information they received through the tools was incomplete. The tools were adjusted accordingly to the missing information. A usable, tailored

Prioritization strategies in clinical practice guidelines development: a pilot study

Directory of Open Access Journals (Sweden)

Torres Marcela

2010-03-01

Full Text Available Abstract Objective Few methodological studies address the prioritization of clinical topics for the development of Clinical Practice Guidelines (CPGs. The aim of this study was to validate a methodology for Priority Determination of Topics (PDT of CPGs. Methods and results Firstly, we developed an instrument for PDT with 41 criteria that were grouped under 10 domains, based on a comprehensive systematic search. Secondly, we performed a survey of stakeholders involved in CPGs development, and end users of guidelines, using the instrument. Thirdly, a pilot testing of the PDT procedure was performed in order to choose 10 guideline topics among 34 proposed projects; using a multi-criteria analysis approach, we validated a mechanism that followed five stages: determination of the composition of groups, item/domain scoring, weights determination, quality of the information used to support judgments, and finally, topic selection. Participants first scored the importance of each domain, after which four different weighting procedures were calculated (including the survey results. The process of weighting was determined by correlating the data between them. We also reported the quality of evidence used for PDT. Finally, we provided a qualitative analysis of the process. The main domains used to support judgement, having higher quality scores and weightings, were feasibility, disease burden, implementation and information needs. Other important domains such as user preferences, adverse events, potential for health promotion, social effects, and economic impact had lower relevance for clinicians. Criteria for prioritization were mainly judged through professional experience, while good quality information was only used in 15% of cases. Conclusion The main advantages of the proposed methodology are supported by the use of a systematic approach to identify, score and weight guideline topics selection, limiting or exposing the influence of personal biases

Potential carcinogenicity predicted by computational toxicity evaluation of thiophosphate pesticides using QSTR/QSCarciAR model.

Science.gov (United States)

Petrescu, Alina-Maria; Ilia, Gheorghe

2017-07-01

This study presents in silico prediction of toxic activities and carcinogenicity, represented by the potential carcinogenicity DSSTox/DBS, based on vector regression with a new Kernel activity, and correlating the predicted toxicity values through a QSAR model, namely: QSTR/QSCarciAR (quantitative structure toxicity relationship/quantitative structure carcinogenicity-activity relationship) described by 2D, 3D descriptors and biological descriptors. The results showed a connection between carcinogenicity (compared to the structure of a compound) and toxicity, as a basis for future studies on this subject, but each prediction is based on structurally similar compounds and the reactivation of the substructures of these compounds.

It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco

Science.gov (United States)

Hecht, Stephen S.

2014-01-01

The Family Smoking Prevention and Tobacco Control Act gives the Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerful carcinogens in laboratory animals, have been evaluated as “carcinogenic to humans” by the International Agency for Research on Cancer. NNK and NNN are present in the tobacco of virtually all marketed cigarettes; levels in cigarette smoke are directly proportional to the amounts in tobacco. The NNK metabolite NNAL, itself a strong carcinogen, is present in the urine of smokers and non-smokers exposed to secondhand smoke. Some of the highest levels of NNK and NNN are found in U.S. products. It is well established that factors such as choice of tobacco blend, agricultural conditions, and processing methods influence levels of NNK and NNN in cigarette tobacco and cigarette smoke. Therefore, it is time to control these factors and produce cigarettes with 100 ppb or less each of NNK and NNN in tobacco, which would result in an approximate 15-20 fold reduction of these carcinogens in the mainstream smoke of popular cigarettes sold in the United States. PMID:24806664

Developing Guidelines for the Use of Nontraditional Educational Interventions.

Science.gov (United States)

Wood, Frank

The paper outlines guidelines for developing policy on use of nontraditional educational interventions (such as timeout, aversive stimulation, biofeedback, behavior modification, relaxation therapy, and group meetings) with behavior disordered students. A model policy statement on the use of isolation rooms is presented. Such a statement should…

Development of guidelines to review advanced human-system interfaces

International Nuclear Information System (INIS)

O'Hara, J.M.

1993-01-01

Advanced control rooms (ACRS) will utilize advanced human-system interface (HSI) technologies that may have significant implications for plant safety in that they will affect the operators overall role in the system, the method of information presentation, and the ways in which operators interact with the system. The US Nuclear Regulatory Commission (NRC) reviews the HSI aspects of control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported in order to protect public health and safety. The principal guidance available to the NRC, however, was developed more than ten years ago, well prior to these technological changes. Accordingly, the human factors guidance needs to be updated to serve as the basis for NRC review of these advanced designs. The purpose of this paper is to discuss the development, evaluation, and current status of the Advanced HSI Design Review Guideline, hereafter referred to as the ''Guideline.''

Prevalence of occupational exposure to carcinogens among workers of Arabic, Chinese and Vietnamese ancestry in Australia.

Science.gov (United States)

Boyle, Terry; Carey, Renee N; Glass, Deborah C; Peters, Susan; Fritschi, Lin; Reid, Alison

2015-09-01

Although job-related diseases result in more deaths per year than job-related injuries, most research concerning ethnic minority workers has concerned accidents and injuries rather than disease-causing exposures such as carcinogens. We conducted a telephone-based cross-sectional survey to estimate the prevalence of occupational exposure to carcinogens among a sample of ethnic minority workers in Australia, and compared their exposure prevalence to that of a sample of the general Australian-born working population ('Australian workers'). One-third of the ethnic minority workers were exposed to at least one carcinogen at work. The likelihood of exposure to carcinogens was not significantly different from that of Australian workers, although the likelihood of exposure to individual carcinogens varied by ethnicity. Knowing the prevalence of exposure to carcinogens in the workplace in different ethnic groups will allow better targeted and informed occupational health and safety measures to be implemented where necessary. © 2015 Wiley Periodicals, Inc.

Integrating values and consumer involvement in guidelines with the patient at the center: article 8 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.

Science.gov (United States)

Kelson, Marcia; Akl, Elie A; Bastian, Hilda; Cluzeau, Françoise; Curtis, J Randall; Guyatt, Gordon; Montori, Victor M; Oliver, Sandy; Schünemann, Holger J

2012-12-01

Professional societies, like many other organizations around the world, have recognized the need to use rigorous processes to ensure that healthcare recommendations are informed by the best available research evidence. They are also realizing the need to involve consumers of healthcare (patients, caregivers, and the public) and integrate their values and preferences in clinical guideline development. This is the eighth of a series of 14 articles that were prepared to advise guideline developers in respiratory and other diseases. It focuses on where to find information about consumer values and preferences, at what points in the guideline development process to integrate their values and preferences, and why. In this review, we addressed the following questions: (1) What do we mean by "consumers"? (2) Why integrate the values and preferences of consumers of healthcare (patients, caregivers, and the public) into clinical practice guidelines? (3) What are the sources of information on consumer values? (4) When and how should consumer values and preferences be integrated into chronic obstructive pulmonary disease guideline recommendations? We defined consumers as patients, caregivers, and members of the public, excluding groups that may also be identified as consumers of guidelines including health professionals, providers, and commissioners of services. We searched PubMed and other databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on available evidence, supplemented by a rapid appraisal of a selection of qualitative studies, experience of what guideline developers are doing, and workshop discussions. A clear distinction needs to be made between the use of information on consumer values and preferences by guideline developers, and the direct involvement of consumers in guideline development processes. Sources of information on consumer

Development of Manitoba Hydro's public water safety around dams management guidelines

Energy Technology Data Exchange (ETDEWEB)

Bonin, Dave; McPhail, Gord; Murphy, Shayla; Schellenberg, Gord [KGS Acres, Winnipeg, (Canada); Read, Nick [Manitoba Hydro, Winnipeg, (Canada)

2010-07-01

Several drowning fatalities and safety incidents have occurred around dams in Ontario, Manitoba and other jurisdictions in Canada. Following these incidents, Manitoba Hydro implemented several measures to improve public safety around its dams with the development of a warning signs manual. Manitoba Hydro found that a standard centralized approach to the process of improving public safety is better for ensuring compliance and consistency, even though they have safety measures in place. This paper described the process that Manitoba Hydro has followed in developing a formal set of public water safety around dams (PWSD) guidelines and a program for implementing these guidelines. This program was developed with the intent of providing a high standard of public protection and continuous improvement and monitoring on par with the effect spent on similar dam safety type programs. This paper focused on the development of the pilot PWSD management plan for Pine Falls generating station in order to test the effectiveness and usability of the guidelines.

Derivation of beryllium guidelines for use in establishing cleanup levels at the Peek Street and Sacandaga sites, New York

International Nuclear Information System (INIS)

Hartmann, H.M.; Avci, H.I.; Ditmars, J.D.

1992-02-01

Guideline levels are derived for beryllium in soil and on indoor surfaces at the Peek Street and Sacandaga sites in the state of New York. On the basis of highly conservative assumptions, the soil beryllium concentration that corresponds to a 10 - 4 carcinogenic risk level is estimated to be 13 mg/kg at both sites. Calculations indicate that the proposed US Department of Energy guideline of 2 μg/ft 2 for beryllium in dust on indoor surfaces would be sufficiently protective of human health. For occupational protection of workers during cleanup operations, Office of Safety and Health Administration standards for beryllium are referenced and restated

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

Science.gov (United States)

Chappell, Grace; Pogribny, Igor P.; Guyton, Kathryn Z.; Rusyn, Ivan

2016-01-01

Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

Guidelines for health technology assessment in Thailand (second edition)--the development process.

Science.gov (United States)

Chaikledkaew, Usa; Kittrongsiri, Kankamon

2014-05-01

The first Thai-specific HTA guidelines were completed in 2008 with the aim of ensuring that all HTA data was accurate, of high quality, and relevant for making decisions pertaining to healthcare resource allocation. Based on a quality assessment of 89 economic evaluation studies in the Thai context published in international academic journals between 1982 and 2012, the analysis revealed a significant increase in quality of data sources and result reporting in studies published after the dissemination of the first Thai HTA guidelines. As the first Thai HTA guidelines were developed in 2008, a number of areas for improvement have been identified. Therefore, the objective of this chapter is to describe the development process of this second edition of HTA guidelines for Thailand which builds on the success of the first edition, while attempting to address some of the identified limitations of the first edition and reflect the changes that the health care and policy contexts have undergone in the intervening years. It is hoped that this second edition will continue to build on these successes so that policy decision making becomes increasingly evidence-based.

Mequindox Induced Genotoxicity and Carcinogenicity in Mice

Directory of Open Access Journals (Sweden)

Qianying Liu

2018-04-01

Full Text Available Mequindox (MEQ, acting as an inhibitor of deoxyribonucleic acid (DNA synthesis, is a synthetic heterocyclic N-oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM mice (50 mice/sex/group were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity in vivo, and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice.

Morpho-chemical characterization and surface properties of carcinogenic zeolite fibers.

Science.gov (United States)

Mattioli, Michele; Giordani, Matteo; Dogan, Meral; Cangiotti, Michela; Avella, Giuseppe; Giorgi, Rodorico; Dogan, A Umran; Ottaviani, Maria Francesca

2016-04-05

Erionite belonging to the zeolite family is a human health-hazard, since it was demonstrated to be carcinogenic. Conversely, offretite family zeolites were suspected carcinogenic. Mineralogical, morphological, chemical, and surface characterizations were performed on two erionites (GF1, MD8) and one offretite (BV12) fibrous samples and, for comparison, one scolecite (SC1) sample. The specific surface area analysis indicated a larger availability of surface sites for the adsorption onto GF1, while SC1 shows the lowest one and the presence of large pores in the poorly fibrous zeolite aggregates. Selected spin probes revealed a high adsorption capacity of GF1 compared to the other zeolites, but the polar/charged interacting sites were well distributed, intercalated by less polar sites (Si-O-Si). MD8 surface is less homogeneous and the polar/charged sites are more interacting and closer to each other compared to GF1. The interacting ability of BV12 surface is much lower than that found for GF1 and MD8 and the probes are trapped in small pores into the fibrous aggregates. In comparison with the other zeolites, the non-carcinogenic SC1 shows a poor interacting ability and a lower surface polarity. These results helped to clarify the chemical properties and the surface interacting ability of these zeolite fibers which may be related to their carcinogenicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Modification of carcinogenic and antitumor radiation effects (biomedical aspects)

International Nuclear Information System (INIS)

Vilenchik, M.M.

1985-01-01

In the book the data on modification of carcinogenic radiation effects by physiologicaly active compounds (caffeine, hormones, promoters and others) as well as on potentiation of antitumor radiation effects by means of hyperthermia are systematized. It is shown that as a basis of synergetic (superadditive) carcinogenic or antitumor radiation effects combined with other factor can be the inhibiting effects of the latter on the reparation process of radiation-induced DNA injuries. The results of experimental investigations and the data on quantitative analysis can be used as a theoretical basis for improvement of the ways and means of the prophylaxis of tumor diseases as well as for increasing the efficiency of radiotherapy

Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project.

Science.gov (United States)

2003-02-01

International interest in clinical practice guidelines has never been greater but many published guidelines do not meet the basic quality requirements. There have been renewed calls for validated criteria to assess the quality of guidelines. To develop and validate an international instrument for assessing the quality of the process and reporting of clinical practice guideline development. The instrument was developed through a multi-staged process of item generation, selection and scaling, field testing, and refinement procedures. 100 guidelines selected from 11 participating countries were evaluated independently by 194 appraisers with the instrument. Following refinement the instrument was further field tested on three guidelines per country by a new set of 70 appraisers. The final version of the instrument contained 23 items grouped into six quality domains with a 4 point Likert scale to score each item (scope and purpose, stakeholder involvement, rigour of development, clarity and presentation, applicability, editorial independence). 95% of appraisers found the instrument useful for assessing guidelines. Reliability was acceptable for most domains (Cronbach's alpha 0.64-0.88). Guidelines produced as part of an established guideline programme had significantly higher scores on editorial independence and, after the publication of a national policy, had significantly higher quality scores on rigour of development (pinternationally. The instrument is sensitive to differences in important aspects of guidelines and can be used consistently and easily by a wide range of professionals from different backgrounds. The adoption of common standards should improve the consistency and quality of the reporting of guideline development worldwide and provide a framework to encourage international comparison of clinical practice guidelines.

The engineering of microprocessor systems guidelines on system development

CERN Document Server

1979-01-01

The Engineering of Microprocessor Systems: Guidelines on System Development provides economical and technical guidance for use when incorporating microprocessors in products or production processes and assesses the alternatives that are available. This volume is part of Project 0251 undertaken by The Electrical Research Association, which aims to give managers and development engineers advice and comment on the development process and the hardware and software needed to support the engineering of microprocessor systems. The results of Phase 1 of the five-phase project are contained in this fir

Mutagenic and carcinogenic structural alerts and their mechanisms of action.

Science.gov (United States)

Plošnik, Alja; Vračko, Marjan; Dolenc, Marija Sollner

2016-09-01

Knowing the mutagenic and carcinogenic properties of chemicals is very important for their hazard (and risk) assessment. One of the crucial events that trigger genotoxic and sometimes carcinogenic effects is the forming of adducts between chemical compounds and nucleic acids and histones. This review takes a look at the mechanisms related to specific functional groups (structural alerts or toxicophores) that may trigger genotoxic or epigenetic effects in the cells. We present up-to-date information about defined structural alerts with their mechanisms and the software based on this knowledge (QSAR models and classification schemes).

Sharing life-altering information: development of pediatric hospital guidelines and team training.

Science.gov (United States)

Wolfe, Adam D; Frierdich, Sharon A; Wish, Joel; Kilgore-Carlin, Joyce; Plotkin, Julie A; Hoover-Regan, Margo

2014-09-01

Abstract Background: Despite parent and physician reports of inadequate skill development, there are few guidelines for training the pediatric care team in sharing life-altering information (SLAI), i.e., "breaking bad news." The necessary skills for SLAI differ between pediatric and adult medical environments. We set out to establish evidence-based guidelines and multidisciplinary team training for SLAI in pediatrics, and to demonstrate an improvement in immediate self-efficacy of training participants. A multidisciplinary task force, which included parent participation and feedback, and which received input from parents of patients in multiple pediatric subspecialties, crafted children's hospitalwide guidelines for SLAI. A one-hour training module on the guidelines was presented to several multidisciplinary pediatric team audiences; 159 voluntary pre- and post-presentation self-efficacy surveys were collected. Responses were analyzed by paired t-test (within groups) and ANOVA (between groups). All evaluated groups of care team members reported significant improvements in self-efficacy among four learning objectives after the training. Medical trainees, newer physicians, and nonphysician (e.g., midlevel providers including nurses) team members reported the greatest improvements, regardless of whether they had received previous training in SLAI. We propose pediatric-focused SLAI guidelines based on a modified SPIKES protocol. Focus on patient- and family-centered, culturally sensitive pediatric practices should be the basis for development of training that can be periodically reinforced. Future comprehensive training will incorporate experiential learning. SLAI requires a skill set that benefits from lifelong learning.

Developing diagnostic guidelines for the acute radiation syndrome

International Nuclear Information System (INIS)

Densow, D.; Fliedner, T.M.; Kindler, H.

1996-01-01

Diagnostic guidelines seem to be promising for improving medical care. One aspect of a diagnostic guideline for the acute radiation syndrome has been tested against an extensive case history database. Subsequently, the guideline has been optimized for a small set of case histories. The improved performance has been proven by a test against the rest of the case history database

Development of a guideline-based decision support system with explanation facilities for outpatient therapy

NARCIS (Netherlands)

Goud, Rick; Hasman, Arie; Peek, Niels

2008-01-01

For effective guideline implementation it is recommended to develop and apply carefully designed implementation strategies and instruments. Computerized decision support systems (CDSSs) are such instruments as they can improve guideline adherence by providing advice at the point of care. To improve

Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons ...

African Journals Online (AJOL)

Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons (cPAHs) and Heavy Metal in Crude Oil from Gokana Area, Rivers State, Nigeria. ... Considerable caution should be applied in exploration, exposure and distribution of the crude oil through protected and well maintained pipelines to avoid the possible ...

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

International Nuclear Information System (INIS)

Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M.; Ahr, Hans-Juergen; Schmidt, Ulrich; Enzmann, Harald H.

2004-01-01

Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using 32 P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had 32 P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

Energy Technology Data Exchange (ETDEWEB)

Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M. [New York Medical College, Department of Pathology, Valhalla (United States); Ahr, Hans-Juergen; Schmidt, Ulrich [Bayer AG, Institute of Toxicology, Wuppertal (Germany); Enzmann, Harald H. [Federal Institute for Drugs and Medical Devices, Bonn (Germany)

2004-10-01

Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using {sup 32}P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had {sup 32}P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

Proposal for the development of ICNIRP guidelines on limits for optical radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Siekmann, H. [Berufsgenossenschaftliches Institut fuer Arbeitsschutz - FIA, Sankt Augustin (Germany); Reidenbach, H.D. [Fachhochschule Koeln (Germany)

2004-07-01

Guidelines on limits of exposure to incoherent ultraviolet radiation, to incoherent visible and infrared radiation and to laser radiation have been published by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). These guidelines are accepted globally and form the basis for risk assessment procedures for optical radiation in many countries. With the appearance of new scientific cognition the ICNIRP guidelines will be revised from time to time. A revision may also concern more formal aspects. Some proposals for the development of the ICNIRP limit value recommendations for optical radiation exposures follow. (orig.)

Sewage epidemiology and illicit drug research: the development of ethical research guidelines.

Science.gov (United States)

Prichard, Jeremy; Hall, Wayne; de Voogt, Pim; Zuccato, Ettore

2014-02-15

To discuss the need to develop ethical guidelines for researchers using sewage epidemiology to monitor drug use in the general population and specific precincts, including prisons, schools and workplaces. Describe current applications of sewage epidemiology, identify potential ethical risks associated with this science, and identify key means by which these risks may be mitigated through proportionate ethical guidance that allows this science to be fully developed. A rapidly advancing field of research is sewage epidemiology (SE) - the analysis of wastewater samples to monitor illicit drug use and other substances. Typically this research involves low ethical risks because individual participants cannot be identified and, consequently, review has been waived by human research ethics committees. In the absence of such oversight, ethical research guidelines are recommended for SE teams, peer reviewers and journal editors; guidelines will assist them to mitigate any risks in general population studies and studies of prisons, schools and workplaces. Potential harms include the stigmatisation of participants and, in the prison setting, austere policy responses to SE data that impact negatively upon inmate-participants. The risk of harm can be managed through research planning, awareness of the socio-political context in which results will be interpreted (or, in the case of media, sensationalised) and careful relations with industry partners. Ethical guidelines should be developed in consultation with SE scholars and be periodically amended. They should include publication processes that safeguard scientific rigour and be promulgated through existing research governance structures. Guidelines will assist to promote an ethical research culture among SE teams and scholars involved in the publication process and this will work to protect the reputation of the field. Copyright © 2014 Elsevier B.V. All rights reserved.

Summary guidelines

Energy Technology Data Exchange (ETDEWEB)

Halsnaes, K.; Painuly, J.P.; Turkson, J.; Meyer, H.J.; Markandya, A.

1999-09-01

This document is a summary version of the methodological guidelines for climate change mitigation assessment developed as part of the Global Environment Facility (GEF) project Economics of Greenhouse Gas Limitations; Methodological Guidelines. The objectives of this project have been to develop a methodology, an implementing framework and a reporting system which countries can use in the construction of national climate change mitigation policies and in meeting their future reporting obligations under the FCCC. The methodological framework developed in the Methodological Guidelines covers key economic concepts, scenario building, modelling tools and common assumptions. It was used by several country studies included in the project. (au) 13 refs.

Critical effective methods to detect genotoxic carcinogens and neoplasm-promoting agents.

OpenAIRE

Weisburger, J H; Williams, G M

1991-01-01

Neoplasia in fish can result from contamination of waters with carcinogens and promoters. Cancer in fish, therefore, is a possible indicator of cancer risk to man and serves as a guide to the need for preventive approaches involving improved means of waste disposal and environmental hygiene. Moreover, cancer in fish indicates that this important food source may be contaminated. Detection of genotoxic carcinogens to which fish are exposed can be achieved quickly and efficiently by carefully se...

Experimental study on display-control stereotype and development of human factors guidelines

International Nuclear Information System (INIS)

Lee, Jung Woon; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul; Cha, Woo Chang

2003-01-01

It is very important to develop the design guidelines which can be applicable for Korean operators for the purpose of designing the KSNP more safely. The objective of this project is to provide the standards, guidelines and bases applicable for HF-010 through the within-subject experiment for obtaining Korean operators' population stereotype for direction-of-movement of controls associated with displays on the control panels. Through the survey of researches on display compatibility and the classification of types of displays and controls in the main control room of Uljin units 3 and 4, methods for an experiment on the stereotype were established. Experimental interface prototypes for a total of 108 combinations of display and control types were implemented. Experimental data collection and analysis system was built in association with the interface prototypes. The experiment was performed with participation of 250 students as subjects. About 20 guideline items were developed based on the results obtained from our analysis of experimental data

Experimental study on display-control stereotype and development of human factors guidelines

Energy Technology Data Exchange (ETDEWEB)

Lee, Jung Woon; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul [KAERI, Taejon (Korea, Republic of); Cha, Woo Chang [Kumoh National Univ. of Technolgy, Gumi (Korea, Republic of)

2003-01-01

It is very important to develop the design guidelines which can be applicable for Korean operators for the purpose of designing the KSNP more safely. The objective of this project is to provide the standards, guidelines and bases applicable for HF-010 through the within-subject experiment for obtaining Korean operators' population stereotype for direction-of-movement of controls associated with displays on the control panels. Through the survey of researches on display compatibility and the classification of types of displays and controls in the main control room of Uljin units 3 and 4, methods for an experiment on the stereotype were established. Experimental interface prototypes for a total of 108 combinations of display and control types were implemented. Experimental data collection and analysis system was built in association with the interface prototypes. The experiment was performed with participation of 250 students as subjects. About 20 guideline items were developed based on the results obtained from our analysis of experimental data.

Development of Quality Management Systems for Clinical Practice Guidelines in Korea.

Science.gov (United States)

Jo, Heui-Sug; Kim, Dong Ik; Chang, Sung-Goo; Shin, Ein-Soon; Oh, Moo-Kyung

2015-11-01

This study introduces the Clinical practice guidelines (CPGs) appraisal system by the Korean Academy of Medical Sciences (KAMS). Quality management policies for CPGs vary among different countries, which have their own cultures and health care systems. However, supporting developers in guideline development and appraisals using standardized tools are common practices. KAMS, an organization representing the various medical societies of Korea, has been striving to establish a quality management system for CPGs, and has established a CPGs quality management system that reflects the characteristics of the Korean healthcare environment and the needs of its users. KAMS created a foundation for the development of CPGs, set up an independent appraisal organization, enacted regulations related to the appraisals, and trained appraisers. These efforts could enhance the ability of each individual medical society to develop CPGs, to increase the quality of the CPGs, and to ultimately improve the quality of the information available to decision-makers.

Systematic network assessment of the carcinogenic activities of cadmium

International Nuclear Information System (INIS)

Chen, Peizhan; Duan, Xiaohua; Li, Mian; Huang, Chao; Li, Jingquan; Chu, Ruiai; Ying, Hao; Song, Haiyun; Jia, Xudong; Ba, Qian; Wang, Hui

2016-01-01

Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human. - Highlights: • A cadmium-influenced network with 850 nodes and 8770 edges was established. • The cadmium-rewired gene network was scale-free and highly connected. • Nine modules were identified, and 60 key signaling pathways related to cadmium-induced carcinogenesis were found. • Key mediators in the network were validated in multiple cellular models.

Systematic network assessment of the carcinogenic activities of cadmium

Energy Technology Data Exchange (ETDEWEB)

Chen, Peizhan; Duan, Xiaohua; Li, Mian; Huang, Chao [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Li, Jingquan; Chu, Ruiai; Ying, Hao; Song, Haiyun [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Jia, Xudong [Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Ba, Qian, E-mail: qba@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wang, Hui, E-mail: huiwang@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); School of Life Science and Technology, ShanghaiTech University, Shanghai (China)

2016-11-01

Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human. - Highlights: • A cadmium-influenced network with 850 nodes and 8770 edges was established. • The cadmium-rewired gene network was scale-free and highly connected. • Nine modules were identified, and 60 key signaling pathways related to cadmium-induced carcinogenesis were found. • Key mediators in the network were validated in multiple cellular models.

Index-TB Guidelines: Guidelines on extrapulmonary tuberculosis for India

Science.gov (United States)

Sharma, Surendra K.; Ryan, H.; Khaparde, Sunil; Sachdeva, K. S.; Singh, Achintya D.; Mohan, Alladi; Sarin, Rohit; Paramasivan, C N; Kumar, Prahlad; Nischal, Neeraj; Khatiwada, Saurav; Garner, Paul; Tharyan, Prathap

2017-01-01

Extrapulmonary tuberculosis (EPTB) is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB. Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i) use of Xpert MTB/RIF in diagnosis, (ii) use of adjunct corticosteroids in treatment, and (iii) duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research. PMID:28862176

Biomonitoring human exposure to environmental carcinogenic chemicals

DEFF Research Database (Denmark)

Farmer, P.B.; Sepai, O.; Lawrence, R.

1996-01-01

for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers...

Development of mental health first aid guidelines for panic attacks: a Delphi study

Directory of Open Access Journals (Sweden)

Jorm Anthony F

2009-08-01

Full Text Available Abstract Background Panic attacks are common, and while they are not life-threatening events, they can lead to the development of panic disorder and agoraphobia. Appropriate help at the time that a panic attack occurs may decrease the fear associated with the attack and reduce the risk of developing an anxiety disorder. However, few people have the knowledge and skills required to assist. Simple first aid guidelines may help members of the public to offer help to people who experience panic attacks. Methods The Delphi method was used to reach consensus in a panel of experts. Experts included 50 professionals and 6 people who had experience of panic attacks and were active in mental health advocacy. Statements about how to assist someone who is having a panic attack were sourced through a systematic search of both professional and lay literature. These statements were rated for importance as first aid guidelines by the expert and consumer panels and guidelines were written using the items most consistently endorsed. Results Of 144 statements presented to the panels, 27 were accepted. These statements were used to develop the guidelines appended to this paper. Conclusion There are a number of actions which are considered to be useful for members of the public to do if they encounter someone who is having a panic attack. These guidelines will be useful in revision of curricula of mental health first aid programs. They can also be used by members of the public who want immediate information about how to assist someone who is experiencing panic attacks.

Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins.

Science.gov (United States)

Montgomery, Beverly A; Murphy, Jessica; Chen, James J; Desai, Varsha G; McGarrity, Lynda; Morris, Suzanne M; Casciano, Daniel A; Aidoo, Anane

2002-01-01

The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E), on food-borne mutagenes/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of beta-carotene and vitamin C without the carcinogen resulted in an increase (P food or taken as supplements could, in part, counteract such mutagenic activities.

Guidelines for the Development of Instructional Materials Selection Policies. Handbook I.

Science.gov (United States)

Motomatsu, Nancy, Ed.

This manual was developed to assist school district personnel in the development of policies and procedures for selecting instructional materials. The manual describes State of Washington laws and regulations that govern the selection, use, and disposal of instructional materials and presents criteria and guidelines for selecting materials. Also…

Development of standards, codes of practice and guidelines at the national level

International Nuclear Information System (INIS)

Swindon, T.N.

1989-01-01

Standards, codes of practice and guidelines are defined and their different roles in radiation protection specified. The work of the major bodies that develop such documents in Australia - the National Health and Medical Research Council and the Standards Association of Australia - is discussed. The codes of practice prepared under the Environment Protection (Nuclear Codes) Act, 1978, an act of the Australian Federal Parliament, are described and the guidelines associated with them outlined. 5 refs

Carcinogen specific dosimetry model for passive smokers of various ages

International Nuclear Information System (INIS)

Robinson, Risa J.

2005-01-01

Studies indicate that being exposed to second hand smoke increases the chance of developing lung cancer. Understanding the deposition of carcinogenic particles present in second hand smoke is necessary to understand the development of specific histologic type cancers. In this study, a deposition model is presented for subjects of various ages exposed to sidestream smoke. The model included particle dynamics of coagulation, hygroscopic growth, charge and cloud behavior. Concentrations were varied from the maximum measured indoor concentrations (10 6 particles/cm 3 ) to what would be expected from wisps of smoke (10 8 particles/cm 3 ). Model results agreed well with experimental data taken from human subject deposition measurements (four studies). The model results were used to determine the dose intensity (dose per unit airway surface area) of Benzo[a]pyrene (BaP) in the respiratory tract for subjects of various ages. Model predictions for BaP surface concentration on the airway walls paralleled incident rates of tumors by location in the upper tracheobronchial region. Mass deposition efficiency was found to be larger for younger subjects, consistent with diffusion being the predominant mechanism for this particle size range. However, the actual dose intensity of BaP was found to be smaller for children than adults. This occurred due to the predominant effect of the smaller initial inhaled mass for children resulting from smaller tidal volumes. The resulting model is a useful tool to predict carcinogen specific particle deposition

CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

Science.gov (United States)

Carcinogenic Effects of Low Doses of Ionizing RadiationR Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711The form of the dose-response curve for radiation-induced cancers, particu...

78 FR 16681 - International Conference on Harmonisation; Proposed Change to Rodent Carcinogenicity Testing of...

Science.gov (United States)

2013-03-18

...-evidence (WOE) factors proposed for inclusion in CADs. II. Past Experience With Carcinogenicity Assessment... Medicines Agency; and the Japanese Ministry of Health, Labour and Welfare. We would request that CADs be... WOE factors proposed for inclusion in carcinogenicity assessment documents. Submit either electronic...

Chemistry of mutagens and carcinogens in broiled food.

Science.gov (United States)

Nishimura, S

1986-01-01

From a chemical point of view, the following subjects are important areas in studies on mutagens and carcinogens in broiled foods. In addition to heterocyclic amines which need microsomal activation, the structural elucidation of more labile direct-acting mutagens is necessary. It is known that there are still various unknown minor mutagens in broiled foods. Although the structural characterization of such compounds is more difficult, it is important since they might be hazardous in spite of their low mutagenicity. A more feasible and easier method for quantitative analysis of mutagens, in addition to HPLC and GC/MS methods presently employed, must be developed. The mechanism of formation of mutagens by broiling of food should be studied. An effective chemical method to prevent formation of mutagens or to destroy them, once formed, should be developed. PMID:3757944

Identifying carcinogenic activity of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) through electronic and topological indices

CERN Document Server

Braga, R S; Barone, P M V B

2000-01-01

Polycyclic aromatic hydrocarbons (PAHs) are a class of planar molecules, abundant in urban environment, which can induce chemical carcinogenesis. Their carcinogenic power varies in a large range, from very strong carcinogens to inactive ones. In a previous study, we proposed a methodology to identify the PAHs carcinogenic activity exploring electronic and topological indices. In the present work, we show that it is possible to simplify that methodology and expand its applicability to include methylated PAHs compounds. Using very simple rules, we can predict their carcinogenic activity with high accuracy (approx 89%).

Determination of carcinogenic polycyclic aromatic hydrocarbons in ...

African Journals Online (AJOL)

Determination of carcinogenic polycyclic aromatic hydrocarbons in air samples in Irbid, north Jordan. A Al-Gawadreh Sat, M.B. Gasim, A.R. Hassan, A Azid. Abstract. Air samples were collected at an urban site and a rural (BERQESH) site during February (2017) until March (2017) to determine concentrations of polycyclic ...

Carcinogenicity study of 3-monochloropropane-1, 2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential.

Science.gov (United States)

Jeong, Jayoung; Han, Beom Seok; Cho, Wan-Seob; Choi, Mina; Ha, Chang-Su; Lee, Byoung-Seok; Kim, Yong-Bum; Son, Woo-Chan; Kim, Choong-Yong

2010-09-01

3-Monochloropropane-1, 2-diol (or 3-chloro-1,2-propanediol, 3-MCPD) is a well-known food processing contaminant found in a wide range of foods and ingredients. It has been classified as non-genotoxic carcinogen but its carcinogenic potential in the rodents has been controversial. The carcinogenicity to B6C3F1 mice by drinking water administration was assessed over a period of 104 weeks. Three groups, each comprising 50 male and 50 female mice received 3-MCPD at dosages of 30, 100 or 300 ppm up to Day 100 and 200 ppm onward (4.2, 14.3 and 33.0 mg/kg for males; 3.7, 12.2, and 31.0 mg/kg for females), were allocated. Survival was good, with at least 80% of males and 72% of females in each group surviving 104 weeks. Body weights and body weight gain were decreased in males and females receiving 200 ppm. Water and food consumptions of both sexes at 300/200 ppm were lowered. Emaciated or crouching position was observed for animals of both sexes exposed to 200 ppm. There were some differences in hematology and serum biochemistry compared with controls, although there was no histopathological evidence to support those changes. Histopathological examination did not reveal any neoplastic or non-neoplastic findings attributable to treatment with 3-MCPD. It is concluded that drinking water administration of 3-MCPD for 104 weeks revealed no evidence of carcinogenic potential.

Comparative statistical analysis of carcinogenic and non-carcinogenic effects of uranium in groundwater samples from different regions of Punjab, India.

Science.gov (United States)

Saini, Komal; Singh, Parminder; Bajwa, Bikramjit Singh

2016-12-01

LED flourimeter has been used for microanalysis of uranium concentration in groundwater samples collected from six districts of South West (SW), West (W) and North East (NE) Punjab, India. Average value of uranium content in water samples of SW Punjab is observed to be higher than WHO, USEPA recommended safe limit of 30µgl -1 as well as AERB proposed limit of 60µgl -1 . Whereas, for W and NE region of Punjab, average level of uranium concentration was within AERB recommended limit of 60µgl -1 . Average value observed in SW Punjab is around 3-4 times the value observed in W Punjab, whereas its value is more than 17 times the average value observed in NE region of Punjab. Statistical analysis of carcinogenic as well as non carcinogenic risks due to uranium have been evaluated for each studied district. Copyright © 2016 Elsevier Ltd. All rights reserved.

Approaches to radiation guidelines for space travel

International Nuclear Information System (INIS)

Fry, R.J.M.

1984-01-01

There are obvious risks in space travel that have loomed larger than any risk from radiation. Nevertheless, NASA has maintained a radiation program that has involved maintenance of records of radiation exposure, and planning so that the astronauts' exposures are kept as low as possible, and not just within the current guidelines. These guidelines are being reexamined currently by NCRP Committee 75 because new information is available, for example, risk estimates for radiation-induced cancer and about the effects of HZE particles. Furthermore, no estimates of risk or recommendations were made for women in 1970 and must now be considered. The current career limit is 400 rem. The appropriateness of this limit and its basis are being examined as well as the limits for specific organs. There is now considerably more information about age-dependency for radiation and this will be taken into account. Work has been carried out on the so-called microlesions caused by HZE particles and on the relative carcinogenic effect of heavy ions, including iron. A remaining question is whether the fluence of HZE particles could reach levels of concern in missions under consideration. Finally, it is the intention of the committee to indicate clearly the areas requiring further research. 21 references, 1 figure, 7 tables

Changing the field of carcinogenicity testing of human pharmaceuticals by emphasizing mode of action

NARCIS (Netherlands)

Laan, J.W. van der; Duijndam, B.; Hoorn, T. van den; Woutersen, R.; Water, B. van de

2017-01-01

Lifetime testing for carcinogenicity of pharmaceuticals in rodents has been a controversial issue since the start of the International Conference on Harmonisation in 1990. Since 2010 the debate reached a new level following the proposal that a negative outcome of carcinogenicity studies can be

The use of dose-response data in a margin of exposure approach to carcinogenic risk assessment for genotoxic chemicals in food.

Science.gov (United States)

Benford, Diane J

2016-05-01

Genotoxic substances are generally not permitted for deliberate use in food production. However, an appreciable number of known or suspected genotoxic substances occur unavoidably in food, e.g. from natural occurrence, environmental contamination and generation during cooking and processing. Over the past decade a margin of exposure (MOE) approach has increasingly been used in assessing the exposure to substances in food that are genotoxic and carcinogenic. The MOE is defined as a reference point on the dose-response curve (e.g. a benchmark dose lower confidences limit derived from a rodent carcinogenicity study) divided by the estimated human intake. A small MOE indicates a higher concern than a very large MOE. Whilst the MOE cannot be directly equated to risk, it supports prioritisation of substances for further research or for possible regulatory action, and provides a basis for communicating to the public. So far, the MOE approach has been confined to substances for which carcinogenicity data are available. In the absence of carcinogenicity data, evidence of genotoxicity is used only in hazard identification. The challenge to the genetic toxicology community is to develop approaches for characterising risk to human health based on data from genotoxicity studies. In order to achieve wide acceptance, it would be important to further address the issues that have been discussed in the context of dose-response modelling of carcinogenicity data in order to assign levels of concern to particular MOE values, and also whether it is possible to make generic conclusions on how potency in genotoxicity assays relates to carcinogenic potency. © Crown copyright 2015.

Development of quality indicators based on a multidisciplinary, evidence-based guideline on pediatric constipation

NARCIS (Netherlands)

Stienen, J.J.C.; Tabbers, M.M.; Benninga, M.A.; Harmsen, M.; Ouwens, M.M.T.J.

2011-01-01

Several clinical guidelines for childhood functional constipation have been developed, but none of them is accompanied by a set of quality indicators. It is important to gain insight into the quality of care in daily practice in order to improve the implementation of clinical guidelines. This can be

Index-TB guidelines: Guidelines on extrapulmonary tuberculosis for India

Directory of Open Access Journals (Sweden)

Surendra K Sharma

2017-01-01

Full Text Available Extrapulmonary tuberculosis (EPTB is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB. Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i use of Xpert MTB/RIF in diagnosis, (ii use of adjunct corticosteroids in treatment, and (iii duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research.

To the application of the emission Mössbauer and positron annihilation spectroscopies for detection of carcinogens

Science.gov (United States)

Bokov, A. V.; Byakov, V. M.; Kulikov, L. A.; Perfiliev, Yu. D.; Stepanov, S. V.

2017-11-01

Being the main cause of cancer, almost all chemical carcinogens are strong electrophiles, that is, they have a high affinity for the electron. We have shown that positron annihilation lifetime spectroscopy (PALS) is able to detect chemical carcinogens by their inhibition of positronium (Ps) formation in liquid media. Electrophilic carcinogens intercept thermalized track electrons, which are precursors of Ps, and as a result, when they are present Ps atom does not practically form. Available biophysical data seemingly indicate that frozen solutions model better an intracellular medium than the liquid ones. So it is reasonable to use emission Mössbauer spectroscopy (EMS) to detect chemical carcinogens, measuring the yield of 57Fe2+ions formed in reactions of Auger electrons and other secondary electrons they produced with 57Fe3+. These reactions are similar to the Ps formation process in the terminal part the positron track: e++ e- =>Ps. So EMS and PALS are complementary methods for detection of carcinogenic compounds.

Developing a questionnaire to identify perceived barriers for implementing the Dutch physical therapy COPD clinical practice guideline.

Science.gov (United States)

van der Wees, Philip J; Zagers, Cor A M; de Die, Sara E; Hendriks, Erik J M; Nijhuis-van der Sanden, Maria W G; de Bie, Rob A

2013-05-01

Clinical practice guidelines have been developed to assist healthcare practitioners in clinical decision making. Publication of clinical practice guidelines does not automatically lead to their uptake and barrier identification has been recognized as an important step in implementation planning. This study aimed at developing a questionnaire to identify perceived barriers for implementing the Dutch COPD guideline for physical therapists and its recommended measurement instruments. An overall questionnaire, based on two existing questionnaires, was constructed to identify barriers and facilitators for implementing the COPD guideline. The construct of the questionnaire was assessed in a cross-sectional study among 246 chest physical therapists. Factor analysis was conducted to explore underlying dimensions. Psychometric properties were analyzed using Cronbach's alpha. Barriers and facilitators were assessed using descriptive statistics. Some 139 physical therapists (57%) responded. Factor analysis revealed 4-factor and 5-factor solutions with an explained variance of 36% and 39% respectively. Cronbach's alpha of the overall questionnaire was 0.90, and varied from 0.66 to 0.92 for the different factors. Underlying domains of the 5-factor solution were characterized as: attitude towards using measurement instruments, knowledge and skills of the physical therapist, applicability of the COPD guideline, required investment of time & money, and patient characteristics. Physical therapists showed a positive attitude toward using the COPD guideline. Main barriers for implementation were required time investment and financial constraints. The construct of the questionnaire revealed relevant underlying domains for the identification of barriers and facilitators for implementing the COPD guideline. The questionnaire allowed for tailoring to the target group and may be used across health care professionals as basis for in-depth analysis of barriers to specific recommendations in

Efficient clinical evaluation of guideline quality: development and testing of a new tool

Science.gov (United States)

2014-01-01

Background Evaluating the methodological quality of clinical practice guidelines is essential before deciding which ones which could best inform policy or practice. One current method of evaluating clinical guideline quality is the research-focused AGREE II instrument. This uses 23 questions scored 1–7, arranged in six domains, which requires at least two independent testers, and uses a formulaic weighted domain scoring system. Following feedback from time-poor clinicians, policy-makers and managers that this instrument did not suit clinical need, we developed and tested a simpler, shorter, binary scored instrument (the iCAHE Guideline Quality Checklist) designed for single users. Methods Content and construct validity, inter-tester reliability and clinical utility were tested by comparing the new iCAHE Guideline Quality Checklist with the AGREE II instrument. Firstly the questions and domains in both instruments were compared. Six randomly-selected guidelines on a similar theme were then assessed by three independent testers with different experience in guideline quality assessment, using both instruments. Per guideline, weighted domain and total AGREE II scores were calculated, using the scoring rubric for three testers. Total iCAHE scores were calculated per guideline, per tester. The linear relationship between iCAHE and AGREE II scores was assessed using Pearson r correlation coefficients. Score differences between testers were assessed for the iCAHE Guideline Quality Checklist. Results There were congruent questions in each instrument in four domains (Scope & Purpose, Stakeholder involvement, Underlying evidence/Rigour, Clarity). The iCAHE and AGREE II scores were moderate to strongly correlated for the six guidelines. There was generally good agreement between testers for iCAHE scores, irrespective of their experience. The iCAHE instrument was preferred by all testers, and took significantly less time to administer than the AGREE II instrument. However

39-week carcinogenicity study with cyclosporin A in XPA-/- mice, wild type mice and XPA-/-.P53+/- double transgenic mice. Part of the ILSI/HESI Program on Alternative Methods for Carcinogenicity Testing

NARCIS (Netherlands)

Beems RB; Kreijl CF van; Steeg H van; LPI; LEO

2002-01-01

The objective of this study was to evaluate the carcinogenic response of cyclosporin A in XPA-/- mice having a C57BL/6 background. XPA-/- mice are deficient in nucleotide excision repair and have shown increased susceptibility to genotoxic carcinogens and uv-light. The study was part of a world-wide

Factors modifying sensitivity to carcinogens and the problem of threshold in carcinogenesis

International Nuclear Information System (INIS)

Anisimov, V.N.

1983-01-01

Maximum allowable concentrations of chemical carcinogens and dose rates of ionizing radiation have been under extensive study both experimentally and epidemiologically. The problem of the carcinogenic hazards of low-level radiation is a very difficult one: in epidemiological studies it is hard to take into account the many factors (e.g. diseases, diet, genetic peculiarities) that may affect sensitivity to radiation; in experimental studies it is hard to extrapolate with accuracy from one species to another or from the individual threshold to that of the whole population. Age, enzyme activity, sex, and DNA repair capability also modify sensitivity to radiation; when factors such as these are better understood it is expected that epidemiological studies will give a solution that allows estimation of the carcinogenic risk from low-level radiation and hence establishment of a threshold dose. (author)

Development of a meta-algorithm for guiding primary care encounters for patients with multimorbidity using evidence-based and case-based guideline development methodology.

Science.gov (United States)

Muche-Borowski, Cathleen; Lühmann, Dagmar; Schäfer, Ingmar; Mundt, Rebekka; Wagner, Hans-Otto; Scherer, Martin

2017-06-22

The study aimed to develop a comprehensive algorithm (meta-algorithm) for primary care encounters of patients with multimorbidity. We used a novel, case-based and evidence-based procedure to overcome methodological difficulties in guideline development for patients with complex care needs. Systematic guideline development methodology including systematic evidence retrieval (guideline synopses), expert opinions and informal and formal consensus procedures. Primary care. The meta-algorithm was developed in six steps:1. Designing 10 case vignettes of patients with multimorbidity (common, epidemiologically confirmed disease patterns and/or particularly challenging health care needs) in a multidisciplinary workshop.2. Based on the main diagnoses, a systematic guideline synopsis of evidence-based and consensus-based clinical practice guidelines was prepared. The recommendations were prioritised according to the clinical and psychosocial characteristics of the case vignettes.3. Case vignettes along with the respective guideline recommendations were validated and specifically commented on by an external panel of practicing general practitioners (GPs).4. Guideline recommendations and experts' opinions were summarised as case specific management recommendations (N-of-one guidelines).5. Healthcare preferences of patients with multimorbidity were elicited from a systematic literature review and supplemented with information from qualitative interviews.6. All N-of-one guidelines were analysed using pattern recognition to identify common decision nodes and care elements. These elements were put together to form a generic meta-algorithm. The resulting meta-algorithm reflects the logic of a GP's encounter of a patient with multimorbidity regarding decision-making situations, communication needs and priorities. It can be filled with the complex problems of individual patients and hereby offer guidance to the practitioner. Contrary to simple, symptom-oriented algorithms, the meta

Development, Validation, and Implementation of a Clinic Nurse Staffing Guideline.

Science.gov (United States)

Deeken, Debra Jean; Wakefield, Douglas; Kite, Cora; Linebaugh, Jeanette; Mitchell, Blair; Parkinson, Deidre; Misra, Madhukar

2017-10-01

Ensuring that the level of nurse staffing used to care for patients is appropriate to the setting and service intensity is essential for high-quality and cost-effective care. This article describes the development, validation, and implementation of the clinic technical skills permission list developed specifically to guide nurse staffing decisions in physician clinics of an academic medical center. Results and lessons learned in using this staffing guideline are presented.

Critical effective methods to detect genotoxic carcinogens and neoplasm-promoting agents.

Science.gov (United States)

Weisburger, J H; Williams, G M

1991-01-01

Neoplasia in fish can result from contamination of waters with carcinogens and promoters. Cancer in fish, therefore, is a possible indicator of cancer risk to man and serves as a guide to the need for preventive approaches involving improved means of waste disposal and environmental hygiene. Moreover, cancer in fish indicates that this important food source may be contaminated. Detection of genotoxic carcinogens to which fish are exposed can be achieved quickly and efficiently by carefully selected batteries of complementary in vitro and in vivo bioassays. One such battery consists of the Ames test, a reverse mutation assay in prokaryotic Salmonella typhimurium, and the Williams test, involving DNA repair in freshly explanted metabolically highly competent liver cells from diverse species, including humans. Determination of DNA-carcinogen adducts by varied techniques, including 32P-postlabeling, as well as DNA breakage, mammalian cell mutagenicity, chromosome aberrations, sister chromatid exchange, or cell transformation represent additional approaches, each with its own advantages and disadvantages. More research is needed on systems to apprehend neoplasm promoters, but tests to determine interruption of intercellular communications through gap junctions appear promising. Other approaches rely on measurement of enzymes such as ornithine decarboxylase and protein kinase C. Approaches to the definition of risk to fish or humans require characterization of the genotoxic or nongenotoxic properties of a chemical, relative potency data obtained in select, limited rodent bioassays, and knowledge of prevailing environmental concentrations of specific carcinogens.

Glyphosate rodent carcinogenicity bioassay expert panel review.

Science.gov (United States)

Williams, Gary M; Berry, Colin; Burns, Michele; de Camargo, Joao Lauro Viana; Greim, Helmut

2016-09-01

Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study. Application of criteria for causality considerations to the above mentioned tumor types and given the overall weight-of-evidence (WoE), the expert panel concluded that glyphosate is not a carcinogen in laboratory animals.

Identification of EBP50 as a Specific Biomarker for Carcinogens Via the Analysis of Mouse Lymphoma Cellular Proteome

Science.gov (United States)

Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

2012-01-01

To identify specific biomarkers generated upon exposure of L5178Y mouse lymphoma cells to carcinogens, 2-DE and MALDI-TOF MS analysis were conducted using the cellular proteome of L5178Y cells that had been treated with the known carcinogens, 1,2-dibromoethane and O-nitrotoluene and the noncarcinogens, emodin and D-mannitol. Eight protein spots that showed a greater than 1.5-fold increase or decrease in intensity following carcinogen treatment compared with treatment with noncarcinogens were selected. Of the identified proteins, we focused on the candidate biomarker ERM-binding phosphoprotein 50 (EBP50), the expression of which was specifically increased in response to treatment with the carcinogens. The expression level of EBP50 was determined by western analysis using polyclonal rabbit anti-EBP50 antibody. Further, the expression level of EBP50 was increased in cells treated with seven additional carcinogens, verifying that EBP50 could serve as a specific biomarker for carcinogens. PMID:22434383

Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States.

Science.gov (United States)

Zhou, Ying; Li, Chaoyang; Huijbregts, Mark A J; Mumtaz, M Moiz

2015-01-01

Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs) combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA) by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary), and three-component (ternary) combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs). We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although there are many

Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States.

Directory of Open Access Journals (Sweden)

Ying Zhou

Full Text Available Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary, and three-component (ternary combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs. We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although

DNA-adducts in fish exposed to alkylating carcinogens

International Nuclear Information System (INIS)

Giam, C.S.; Holliday, T.L.; Williams, J.L.; Bahnson, A.; Weller, R.; Hinton, D.E.

1988-01-01

There are limited studies on DNA-adduct formation following exposure of fish or fish cells to carcinogens. It will be essential to determine if procarcinogens and carcinogens form the same DNA-adducts in different liver cells and how these compare to those reported in mammalian livers. They are also interested in the influence of different alkylating agents on the type and quantity of DNA-adduct formation and repair in fish. While eggs or small fish are ideal for routine screening, large fish such as trout (Salmo gairdneri) is needed initially for the development of analytical procedures for the isolation, quantitation and identification of various adducts. Trout (Salmo gairdneri) weighing approximately 250 grams were acclimatized at 13 degree C before being given i.p. injection of diethylnitrosoamine (DEN). The exposure period varied, though most animals were sacrificed after 24 hours. Their livers were excised and DNA was isolated mainly according the procedure of Croy et al. The neutral thermal hydrolysate and the acid hydrolysate were analyzed by HPLC-Fluorescent detector for 7-ethylguanine and O 6 -ethylguanine, respectively. O 6 -ethylguanine was detected, 7-ethylguanine was not detected. Attempts are being made to improve the detection of the latter compound. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to establish nanogram quantities of the ethylated bases. Laser desorption FT-IC-MS is particularly useful for characterizing thermally-labile and involatile nucleosides or nucleotides. Excretion of DEN was rapid and high. Exposure of trout (and other fish) to various ethylating agents will be discussed

Carcinogenicity and mutagenicity of chromium.

Science.gov (United States)

Léonard, A; Lauwerys, R R

1980-11-01

Occupational exposure represents the main source of human contamination by chromium. For non-occupationally exposed people the major environmental exposure to chromium occurs as a consequence of its presence in food. Chromium must be considered as an essential element. Its deficiency impairs glucose metabolism. Trivalent chromium salts are poorly absorbed through the gastro-intestinal and respiratory tracts because they do not cross membranes easily. Hexavalent chromium can be absorbed by the oral and pulmonary routes and probably also through the skin. After its absorption, hexavalent chromium is rapidly reduced to the trivalent form which is probably the only form to be found in biological material. Epidemiological studies have shown that some chromium salts (mainly the slightly soluble hexavalent salts) are carcinogens. Lung cancers have, indeed, often been reported among workers in chromate-producing industry and, to a lesser extent, in workers from the chrome-pigment industry. The first attempts to produce cancers in experimental animals by inhalation or parenteral introduction gave negative or equivocal results but, from 1960, positive results have been obtained with various chromium compounds. As for the carcinogenic activity, the mutagenicity of chromium has mainly been found with hexavalent salts. In the majority of assay systems used, trivalent chromium appears inactive. It can be considered as evident, however, that the ultimate mutagen which binds to the genetic material is the trivalent form produced intracellularly from hexavalent chromium, the apparent lack of activity of the trivalent form being due to its poor cellular uptake.

Developing evidence-based clinical practice guidelines in hospitals in Australia, Indonesia, Malaysia, the Philippines and Thailand: values, requirements and barriers

Directory of Open Access Journals (Sweden)

Turner Tari J

2009-12-01

Full Text Available Abstract Background Evidence-based clinical practice guidelines support clinical decision-making by making recommendations to guide clinical practice. These recommendations are developed by integrating the expertise of a multidisciplinary group of clinicians with the perspectives of consumers and the best available research evidence. However studies have raised concerns about the quality of guideline development, and particularly the link between research and recommendations. The reasons why guideline developers are not following the established development methods are not clear. We aimed to explore the barriers to developing evidence-based guidelines in eleven hospitals in Australia, Indonesia, Malaysia, the Philippines and Thailand, so as to better understand how evidence-based guideline development could be facilitated in these settings. The research aimed to identify the value clinicians place on guidelines, what clinicians want in guidelines developed in hospital settings and what factors limit rigorous evidence-based guideline development in these settings. Methods Semi-structured, face-to-face interviews were undertaken with senior and junior healthcare providers (nurses, midwives, doctors, allied health from the maternal and neonatal services of the eleven participating hospitals. Interviews were audio-recorded, transcribed and a thematic analysis undertaken. Results Ninety-three individual, 25 pair and eleven group interviews were conducted. Participants were clear that they want guidelines that are based on evidence and updated regularly. They were also clear that there are major barriers to this. Most of the barriers were shared across countries, and included lack of time, lack of skills in finding, appraising and interpreting evidence, lack of access to relevant evidence and difficulty arranging meetings and achieving consensus. Barriers that were primarily identified in Australian hospitals include cumbersome organisational

Implementation of an evidence-based guideline on fluid resuscitation: lessons learnt for future guidelines

NARCIS (Netherlands)

Tabbers, M.M.; Boluyt, N.; Offringa, M.

2010-01-01

There is little experience with the nationwide implementation of an evidence-based pediatric guideline on first-choice fluid for resuscitation in hypovolemia. We investigated fluid prescribing behavior at (1) guideline development, (2) after guideline development, and (3) after active implementation

Attorney General forces Infectious Diseases Society of America to redo Lyme guidelines due to flawed development process.

Science.gov (United States)

Johnson, L; Stricker, R B

2009-05-01

Lyme disease is one of the most controversial illnesses in the history of medicine. In 2006 the Connecticut Attorney General launched an antitrust investigation into the Lyme guidelines development process of the Infectious Diseases Society of America (IDSA). In a recent settlement with IDSA, the Attorney General noted important commercial conflicts of interest and suppression of scientific evidence that had tainted the guidelines process. This paper explores two broad ethical themes that influenced the IDSA investigation. The first is the growing problem of conflicts of interest among guidelines developers, and the second is the increasing centralisation of medical decisions by insurance companies, which use treatment guidelines as a means of controlling the practices of individual doctors and denying treatment for patients. The implications of the first-ever antitrust investigation of medical guidelines and the proposed model to remediate the tainted IDSA guidelines process are also discussed.

78 FR 44117 - Notice of a Public Comment Period on the Draft IRIS Carcinogenicity Assessment for Ethylene Oxide

Science.gov (United States)

2013-07-23

... Public Comment Period on the Draft IRIS Carcinogenicity Assessment for Ethylene Oxide AGENCY... Carcinogenicity of Ethylene Oxide'' (EPA/635/R-13/128a) and on the draft peer review charge questions. The draft... on the draft Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide and on the draft peer...

Ethics Guidelines in Environmental Epidemiology: Their Development and Challenges We Face.

Science.gov (United States)

Kramer, Shira; Soskolne, Colin L

2017-06-01

This review integrates historical developments and key events in bringing ethics into epidemiology in general and into environmental epidemiology in particular. The goal is to provide context for and discern among the various approaches and motivations that drive the need for ethical conduct in support of the public interest. The need for ethics guidelines in epidemiology is different from developments in other biomedical-related fields by virtue of its focus on populations rather than on individuals. The need for ethics guidelines in environmental epidemiology as a subspecialty of epidemiology stems from the larger scale of its mission than that of epidemiology per se. Ethics guidelines in the field of environmental epidemiology have been established. They articulate not only the profession's core values and mission, but more specifically, they address the environmental epidemiologist's obligations to the participants in research, to colleagues, and to employers. They are the product of consensus, scholarship, and diligent stewardship over several decades. The next challenge is ensuring their value and impact. The forces that support professional and institutional success, and the power of special interests, are the major threats to achieving the goals of ethical conduct and research for the public good. In environmental epidemiology, these threats have global implications.

Carcinogenicity/tumour promotion by NDL PCB

Energy Technology Data Exchange (ETDEWEB)

Schrenk, D. [Kaiserslautern Univ. (Germany). Food Chemistry and Environmental Toxicology

2004-09-15

Polychlorinated biphenyls (PCBs) belong to the group of persistent environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting effects in experimental animal models. PCB congeners can be divided into 'dioxinlike' and 'non-dioxinlike' congeners on the basis of their ability to act as aryl hydrocarbon receptor (AhR) agonists. Like the most toxic dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 'dioxinlike' PCBs bind to the AhR and show characteristic effects on the expression of AhR-regulated genes including the induction of cytochrome P450 (CYP) 1A1. On the other hand, 'non-dioxinlike' PCB congeners have a lower or no binding affinity to the AhR, but exhibit a 'phenobarbital-type' induction of CYP 2B1/2 activity. A carcinogenic potential of PCBs has been demonstrated with technical mixtures such as Aroclors or Clophens. In these studies the liver and the thyroid gland were found to be the principal target organs of PCB-mediated carcinogenesis in rodents. No studies have been published, however, on the carcinogenicity of individual congeners. In two-stage initiation-promotion protocols in rats, both technical mixtures and individual 'dioxinlike' and 'non-dioxinlike' congeners were reported to act as liver tumour promoters.

Parental Exposure to Workplace Carcinogens and the Risk of Development of Acute Leukemia in Infants. Case-Control Study.

Science.gov (United States)

Pérez-Saldivar, María Luisa; Fajardo-Gutiérrez, Arturo; Sierra-Ramírez, José Alfredo; Núñez-Villegas, Nancy; Pérez-Lorenzana, Héctor; Dorantes-Acosta, Elisa María; Román-Zepeda, Pedro Francisco; Rodríguez-Zepeda, María Del Carmen; González-Ulivarri, Juana Esther; López-Santiago, Norma; Martínez-Silva, Sofía Irene; Paredes-Aguilera, Rogelio; Velázquez-Aviña, Martha Margarita; Flores-Lujano, Janet; Jiménez-Hernández, Elva; Núñez-Enríquez, Juan Carlos; Bekker-Méndez, Vilma Carolina; Mejía-Aranguré, Juan Manuel

2016-11-01

Occupational exposure of parents to carcinogens is of great interest in the etiology of leukemias. Evidence of the impact of such exposure on infants or small children is scarce. Here we estimated whether occupational exposure of parents to carcinogens could be a risk factor for leukemias in their children. Cases of acute leukemia (AL) in infants ≤24 months old diagnosed in Mexico City (1998-2013) were included in a population-based, case-control study. Each of the 195 cases was matched with at least one healthy child (n = 369). For each of four exposure windows studied, the degree of exposure to carcinogens was determined for both parents by using a validated occupational exposure index. An unconditional logistic regression was carried out. Odds ratios (OR) and the 95% confidence intervals (CI) of the overall occupational exposure for parents during the four exposure windows indicated no association with risk of AL in their children. Pre-conception, the OR by the father 0.77 (0.49-1.21), by the mother 1.03 (0.50-2.11); during pregnancy, father 0.66 (0.38-1.15), mother 1.79 (0.46-6.90); during breastfeeding, father 0.75 (0.43-1.30), mother 0.96 (0.21-4.30); and after birth, father 0.74 (0.45-1.22), mother 0.90 (0.24-3.32). The statistical power of the sample size to identify an OR ≥2 and an exposure of ≥10% among controls was 78%. These data support the idea that parents' occupational exposure during any of the periods studied was not a risk factor contributing to the etiology of AL in infants ≤24 months of age. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Methodology in use for the assessment of carcinogenic risk. II. Radiation. Oncology overview

International Nuclear Information System (INIS)

1983-04-01

Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Assessment of carcinogenic risk from environmental and occupational exposures to ionizing radiation; Assessment of carcinogenic risk from exposure to ionizing radiation used for medical diagnosis or treatment; Assessment of carcinogenic risk from exposure to ionizing radiation following nuclear bomb explosions; Comparison of risk from radiation sources with risk from nonradiation sources; Experimental studies to assess risk of carcinogenesis following exposure to ionizing radiation; Theoretical aspects of dose-response relationships in the assessment of carcinogenic risk from exposure to ionizing radiation; Public policy and standards for acceptable risk from exposure to ionizing radiation; General reviews on the assessment of risk from exposure to ionizing radiation

The development of seismic guidelines for the Stanford Linear Accelerator Center

International Nuclear Information System (INIS)

Huggins, R.

1996-08-01

This paper describes the development of Seismic Guidelines for the Stanford Linear Accelerator Center (SLAC). Although structures have always been built conservatively, SLAC management decided to review and update their seismic guidelines. SLAC is about mid-way between the epicenters of the 8.3 Richter magnitude 1906 San Francisco and the 7.2 Loma Prieta Earthquakes. The west end of the two mile long electron/positron particle accelerator lies a half mile from the large San Andreas Fault. Suggestions for seismic planning processes were solicited from local computer manufacturing firms, universities, and federal laboratories. A Committee of the various stakeholders in SLAC's seismic planning retained an internationally known Seismic Planning Consultant and reviewed relevant standards and drafted Guidelines. A panel of seismic experts was convened to help define the hazard, site response spectra, probabilistic analysis of shaking, and near field effects. The Facility's structures were assigned to seismic classes of importance, and an initial assessment of a sample of a dozen buildings conducted. This assessment resulted in emergency repairs to one structure, and provided a open-quotes reality basisclose quotes for establishing the final Guidelines and Administrative Procedures, and a program to evaluate remaining buildings, shielding walls, tunnels, and other special structures

The development of seismic guidelines for the Stanford Linear Accelerator Center

Energy Technology Data Exchange (ETDEWEB)

Huggins, R.

1996-08-01

This paper describes the development of Seismic Guidelines for the Stanford Linear Accelerator Center (SLAC). Although structures have always been built conservatively, SLAC management decided to review and update their seismic guidelines. SLAC is about mid-way between the epicenters of the 8.3 Richter magnitude 1906 San Francisco and the 7.2 Loma Prieta Earthquakes. The west end of the two mile long electron/positron particle accelerator lies a half mile from the large San Andreas Fault. Suggestions for seismic planning processes were solicited from local computer manufacturing firms, universities, and federal laboratories. A Committee of the various stakeholders in SLAC`s seismic planning retained an internationally known Seismic Planning Consultant and reviewed relevant standards and drafted Guidelines. A panel of seismic experts was convened to help define the hazard, site response spectra, probabilistic analysis of shaking, and near field effects. The Facility`s structures were assigned to seismic classes of importance, and an initial assessment of a sample of a dozen buildings conducted. This assessment resulted in emergency repairs to one structure, and provided a {open_quotes}reality basis{close_quotes} for establishing the final Guidelines and Administrative Procedures, and a program to evaluate remaining buildings, shielding walls, tunnels, and other special structures.

Retraction: Evaluation of Carcinogenic Effects of Electromagnetic Fields (Emf

Directory of Open Access Journals (Sweden)

Bakir Mehic

2010-08-01

Full Text Available This retracts the article "EVALUATION OF CARCINOGENIC EFFECTS OF ELECTROMAGNETIC FIELDS (EMF" on page 245. The Editor-in-chief of the Bosnian Journal ofBasic Medical Sciences has decided to retract the article from Bayazit V et al. [1] entitled as: “Evaluation of carcinogenic effects of electromagnetic fields (EMF” published in Bosn J Basic Med Sci. 2010 Aug;10(3:245-50.After the editorial office was alerted of possible plagiarism in the article, it conducted thorough investigation and concluded that the article apparently represents plagiarized material from two World Health Organization reports, one European Commission report and other sources. Since this is considered scientific plagiarism and scientific misconduct, Editor-in-chief has decided to withdraw the article. The authors have agreed with the editorial office decision.

Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

Science.gov (United States)

Papamokos, George; Silins, Ilona

2016-01-01

There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action

Science.gov (United States)

Papamokos, George; Silins, Ilona

2016-01-01

There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

Genotoxicity and potential carcinogenicity of cyanobacterial toxins - a review.

Science.gov (United States)

Zegura, Bojana; Straser, Alja; Filipič, Metka

2011-01-01

The occurrence of cyanobacterial blooms has increased significantly in many regions of the world in the last century due to water eutrophication. These blooms are hazardous to humans, animals, and plants due to the production of cyanotoxins, which can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). There is evidence that certain cyanobacterial toxins are genotoxic and carcinogenic; however, the mechanisms of their potential carcinogenicity are not well understood. The most frequently occurring and widespread cyanotoxins in brackish and freshwater blooms are the cyclic heptapeptides, i.e., microcystins (MCs), and the pentapeptides, i.e., nodularins (NODs). The main mechanism associated with potential carcinogenic activity of MCs and NOD is the inhibition of protein phosphatases, which leads to the hyperphosphorylation of cellular proteins, which is considered to be associated with their tumor-promoting activity. Apart from this, MCs and NOD induce increased formation of reactive oxygen species and, consequently, oxidative DNA damage. There is also evidence that MCs and NOD induce micronuclei, and NOD was shown to have aneugenic activity. Both cyanotoxins interfere with DNA damage repair pathways, which, along with DNA damage, is an important factor involved in the carcinogenicity of these agents. Furthermore, these toxins increase the expression of TNF-α and early-response genes, including proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis. Rodent studies indicate that MCs and NOD are tumor promotors, whereas NOD is thought to have also tumor-initiating activity. Another cyanobacterial toxin, cylindrospermopsin (CYN), which has been neglected for a long time, is lately being increasingly found in the freshwater environment. The principal mechanism of its toxicity is the irreversible inhibition of protein synthesis. It is pro

Developing an Ethical Framework for All Geoscientists: AGI Guidelines for Ethical Professional Conduct

Science.gov (United States)

Boland, Maeve A.; Leahy, P. Patrick; Keane, Christopher M.

2016-04-01

In 1997, a group of geoscientists and others recognized the need for a broad-based set of ethical standards for the geosciences that would be an expression of the highest common denominator of values for the profession. The American Geosciences Institute (AGI) coordinated the development of the 1999 AGI Guidelines for Ethical Professional Conduct and their subsequent revision in 2015. AGI is a nonprofit federation of 51 geoscientific and professional organizations that span the geosciences and have approximately 250,000 members. AGI serves as a voice for shared interests in the geoscience community and one of its roles is to facilitate collaboration and discussion among its member societies on matters of common or overarching concern. In this capacity, AGI convened a working group to create the 1999 Guidelines for Ethical Professional Conduct and a further working group to revise the Guidelines in 2015 through a consensus process involving all member societies. The Guidelines are an aspirational document, setting out ideals and high levels of achievement for the profession. They have no provision for disciplinary of enforcement action and they do not supersede the ethics statements or codes of any member society. The 1999 Guidelines pay considerable attention to the professional behavior of geoscientists. The 2015 Guidelines place greater emphasis on the societal context of the geosciences and the responsibilities of geoscientists in areas such as communication, education, and the challenges of understanding complex natural systems. The 2015 Guidelines have been endorsed by 29 member societies to date. To translate the aspirations in the Guidelines into specific actions, AGI has facilitated discussions on the practical implications of aspects of the Guidelines. One outcome of these discussions has been a Consensus Statement Regarding Access and Inclusion of Individuals Living with Disabilities in the Geosciences.

Policies on Conflicts of Interest in Health Care Guideline Development: A Cross-Sectional Analysis

Science.gov (United States)

Morciano, Cristina; Basevi, Vittorio; Faralli, Carla; Hilton Boon, Michele; Tonon, Sabina; Taruscio, Domenica

2016-01-01

Objective To assess whether organisations that develop health care guidelines have conflict of interest (COI) policies and to review the content of the available COI policies. Methods Survey and content analysis of COI policies available in English, French, Spanish, and Italian conducted between September 2014 and June 2015. A 24-item data abstraction instrument was created on the basis of guideline development standards. Results The survey identified 29 organisations from 19 countries that met the inclusion criteria. From these organisations, 19 policies were eligible for inclusion in the content analysis. Over one-third of the policies (7/19, 37%) did not report or did not clearly report whether disclosure was a prerequisite for membership of the guideline panel. Strategies for the prevention of COI such as divestment were mentioned by only two organisations. Only 21% of policies (4/19) used criteria to determine whether an interest constitutes a COI and to assess the severity of the risk imposed. Conclusions The finding that some organisations, in contradiction of widely available standards, still do not have COI policies publicly available is concerning. Also troubling were the findings that some policies did not clearly report critical steps in obtaining, managing and communicating disclosure of relationships of interest. This in addition to the variability encountered in content and accessibility of COI policies may cause confusion and distrust among guideline users. It is in the interest of guideline users and developers to design an agreed-upon, comprehensive, clear, and accessible COI policy. PMID:27846255

[Considerations on the development of nutrition-related guidelines by the World Health Organization and their implementation].

Science.gov (United States)

Zamora, Gerardo; Meneses, Daniela; De-Regil, Luz Maria; Neufeld, Lynnette; Peña-Rosas, Juan Pablo; Sinisterra, Odalis Teresa

2015-03-01

The World Health Organization (WHO) follows a complex and rigorous process to develop global guidelines. With regard to nutrition-related guidelines, the joint participation of national authorities from Member States and their partners, including those of the social economy, is key to strengthening the process of evidence-informed guideline development and the subsequent implementation as part of national public health strategies. WHO puts forward a series of tools that can assist national authorities on health and social development in the elaboration of evidence-informed policies, considering their pertinence, relevance and implementability. This adoption and adaptation process must consider equity in order to avoid widening existing inequities. WHO global nutrition guidelines contribute to the effective implementation of nutrition interventions in Member States. Two experiences of implementation, one in Panama and one in Peru, exemplify this process. The paper ends by suggesting a deeper understanding and utilization of implementation research during programmes to identify what factors ensure effective interventions, appropriate scale up strategies and greater health equity.

Appraising and comparing pressure ulcer guidelines.

Science.gov (United States)

Wimpenny, Peter; van Zelm, Ruben

2007-01-01

Whilst considerable activity has been related to guideline development for nurses regarding pressure ulcer prevention and management, no attempt has been made to comparatively evaluate these guidelines against some form of quality indicators. To compare and contrast four national pressure ulcer guidelines, and identify similarities and differences in their quality and content. An international comparative appraisal method, using the AGREE (Appraisal of Guidelines Research and Evaluation) instrument, was undertaken to appraise four published pressure ulcer guidelines. Two further domains were added to the AGREE instrument to assess comparability of the guidelines and their perceived contribution to practice. An international group undertook the comparative appraisal. The domain scores for each guideline show some but not total agreement among reviewers. One particular set of guidelines was identified as scoring highest in a majority of AGREE domains. Overall, evidence of variability exists between pressure ulcer guidelines and common areas of development to consider for all guidelines. The results raise many questions concerning the "best" pressure ulcer guideline to use, particularly related to the AGREE scoring. Some notable shortcomings exist in all the pressure ulcer guidelines reviewed and these shortcomings need to be addressed from a quality perspective. However, other issues such as style of reporting and potential contribution to practice might more fully affect choice by practitioners as opposed to guideline developers. Notable differences exist among the four guidelines that are possibly explained by different approaches to development and also because of different cultural factors and intentions for use. Whilst the AGREE tool identifies the quality of the guideline development process it still requires local engagement with practitioners to determine which guideline should be implemented.

The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 1: Background and Methods of the Development of Guidelines.

Science.gov (United States)

Fountoulakis, Konstantinos N; Young, Allan; Yatham, Lakshmi; Grunze, Heinz; Vieta, Eduard; Blier, Pierre; Moeller, Hans Jurgen; Kasper, Siegfried

2017-02-01

This paper includes a short description of the important clinical aspects of Bipolar Disorder with emphasis on issues that are important for the therapeutic considerations, including mixed and psychotic features, predominant polarity, and rapid cycling as well as comorbidity. The workgroup performed a review and critical analysis of the literature concerning grading methods and methods for the development of guidelines. The workgroup arrived at a consensus to base the development of the guideline on randomized controlled trials and related meta-analyses alone in order to follow a strict evidence-based approach. A critical analysis of the existing methods for the grading of treatment options was followed by the development of a new grading method to arrive at efficacy and recommendation levels after the analysis of 32 distinct scenarios of available data for a given treatment option. The current paper reports details on the design, method, and process for the development of CINP guidelines for the treatment of Bipolar Disorder. The rationale and the method with which all data and opinions are combined in order to produce an evidence-based operationalized but also user-friendly guideline and a specific algorithm are described in detail in this paper. © The Author 2016. Published by Oxford University Press on behalf of CINP.

A decision tree approach to screen drinking water contaminants for multiroute exposure potential in developing guideline values.

Science.gov (United States)

Krishnan, Kannan; Carrier, Richard

2017-07-03

The consideration of inhalation and dermal routes of exposures in developing guideline values for drinking water contaminants is important. However, there is no guidance for determining the eligibility of a drinking water contaminant for its multiroute exposure potential. The objective of the present study was to develop a 4-step framework to screen chemicals for their dermal and inhalation exposure potential in the process of developing guideline values. The proposed framework emphasizes the importance of considering basic physicochemical properties prior to detailed assessment of dermal and inhalation routes of exposure to drinking water contaminants in setting guideline values.

Guideline-based development of quality indicators for hypertensive diseases in pregnancy

NARCIS (Netherlands)

Luitjes, S.H.; Wouters, M.G.A.J.; Franx, A.; Bolte, A.C.; Groot, C.J. de; Tulder, M.W. van; Hermens, R.P.M.G.

2013-01-01

Objective. Hypertensive disorders in pregnancy are one of the main causes of maternal morbidity and mortality. Internationally, several organizations have developed clinical guidelines to assist professionals and to supply patients with the best possible care. To improve the care for this group of

Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat

International Nuclear Information System (INIS)

Mally, Angela; Chipman, James Kevin

2002-01-01

Non-genotoxic carcinogens are thought to induce tumour formation by disturbing the balance between cell growth and cell death. Gap junctions (GJ) contribute to the maintenance of tissue homeostasis by allowing the intercellular exchange of growth regulatory signals and potential inhibition of GJ intercellular communication through loss of connexin (Cx) plaques has been shown to be involved in the cancer process. We have investigated the time- and dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap junction plaque expression in relation to proliferation and apoptosis. With the exception of limonene, all non-genotoxic carcinogens significantly reduced the expression of GJ plaques containing Cx32 in their respective target tissue. No dose-dependent, significant effects were seen in non-target organs. Although alteration of Cx32 expression did not appear to correlate with induction of cell proliferation, out data suggest that the interaction of both processes--interference of GJ coupled with a proliferative stimulus (at the carcinogenic dose)--may be important in non-genotoxic carcinogenesis and provide a potential alert for non-genotoxic carcinogens in short-term toxicity tests

Decrease of 5-Hydroxymethylcytosine in Rat Liver with Subchronic Exposure to Genotoxic Carcinogens Riddelliine and Aristolochic Acid

Science.gov (United States)

Lian, Christine Guo; Xu, Shuyun; Guo, Weimin; Yan, Jian; Frank, Maximilian Y M; Liu, Robert; Liu, Cynthia; Chen, Ying; Murphy, George F.; Chen, Tao

2018-01-01

The level of 5-hydroxymethylcytosine (5-hmC) converted by ten-eleven translocation (TET) family is decreased in cancers. However, whether 5-hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5-hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5-hmC and TET2 expression decreased in the liver of the carcinogens-treated rats. Loss of 5-hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2-mediated 5-hydroxymethylation plays an epigenetic role in early state of carcinogenesis. PMID:25154389

Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder Carcinogenesis.

Science.gov (United States)

Mondal, Bikash; Maulik, Dhrubajyoti; Mandal, Mousumi; Sarkar, Gautam Narayan; Sengupta, Sanjay; Ghosh, Debidas

2017-12-01

Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy. Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone. EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones. Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.

Capturing Labile Sulfenamide and Sulfinamide Serum Albumin Adducts of Carcinogenic Arylamines by Chemical Oxidation

Science.gov (United States)

Peng, Lijuan; Turesky, Robert J.

2013-01-01

Aromatic amines and heterocyclic aromatic amines (HAAs) are a class of structurally related carcinogens that are formed during the combustion of tobacco or during the high temperature cooking of meats. These procarcinogens undergo metabolic activation by N-oxidation of the exocyclic amine group to produce N-hydroxylated metabolites, which are critical intermediates implicated in toxicity and DNA damage. The arylhydroxylamines and their oxidized arylnitroso derivatives can also react with cysteine (Cys) residues of glutathione or proteins to form, respectively, sulfenamide and sulfinamide adducts. However, sulfur-nitrogen linked adducted proteins are often difficult to detect because they are unstable and undergo hydrolysis during proteolytic digestion. Synthetic N-oxidized intermediates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogenic HAA produced in cooked meats, and 4-aminobiphenyl, a carcinogenic aromatic amine present in tobacco smoke were reacted with human serum albumin (SA) and formed labile sulfenamide or sulfinamide adducts at the Cys34 residue. Oxidation of the carcinogen-modified SA with m-chloroperoxybenzoic acid (m-CPBA) produced the arylsulfonamide adducts, which were stable to heat and the chemical reduction conditions employed to denature SA. The sulfonamide adducts of PhIP and 4-ABP were identified, by liquid chromatography/mass spectrometry, in proteolytic digests of denatured SA. Thus, selective oxidation of arylamine-modified SA produces stable arylsulfonamide-SA adducts, which may serve as biomarkers of these tobacco and dietary carcinogens. PMID:23240913

Genome-wide characterization of microsatelittes and marker development in the carcinogenic liver fluke Clonorchis sinensis

Science.gov (United States)

Nguyen, Thao T.B.; Arimatsu, Yuji; Hong, Sung-Jong; Brindley, Paul J.; Blair, David; Laha, Thewarach; Sripa, Banchob

2015-01-01

Clonorchis sinensis is an important carcinogenic human liver fluke endemic in East and Southeast Asia. There are several conventional molecular markers have been used for identification and genetic diversity, however, no information about microsatellites of this liver fluke published so far. We here report microsatellite characterization and marker development for genetic diversity study in C. sinensis using genome-wide bioinformatics approach. Based on our search criteria, a total of 256,990 microsatellites (≥ 12 base pairs) were identified from genome database of C. sinensis with hexa-nucleotide motif being the most abundant (51%) followed by penta-nucleotide (18.3%) and tri-nucleotide (12.7%). The tetra-nucleotide, di-nucleotide and mononucleotide motifs accounted for 9.75 %, 7.63% and 0.14%, respectively. The total length of all microsatellites accounts for 0. 72 % of 547 Mb of the whole genome size and the frequency of microsatellites were found to be one microsatellite in every 2.13 kb of DNA. For the di-, tri, and tetra-nucleotide, the repeat numbers redundant are six (28%), four (45%) and three (76%), respectively. The ATC repeat is the most abundant microsatellites followed by AT, AAT and AC, respectively. Within 40 microsatellite loci developed, 24 microsatellite markers showed potential to differentiate between C. sinensis and O. viverrini. Seven out of 24 loci showed heterozygous with observed heterozygosity ranged from 0.467 to 1. Four-primer sets could amplify both C. sinensis and O. viverrini DNA with different sizes. This study provides basic information of C. sinensis microsatellites and the genome-wide markers developed may be a useful tool for genetic study of C. sinensis. PMID:25782682

Genome-wide characterization of microsatellites and marker development in the carcinogenic liver fluke Clonorchis sinensis.

Science.gov (United States)

Nguyen, Thao T B; Arimatsu, Yuji; Hong, Sung-Jong; Brindley, Paul J; Blair, David; Laha, Thewarach; Sripa, Banchob

2015-06-01

Clonorchis sinensis is an important carcinogenic human liver fluke endemic in East and Southeast Asia. There are several conventional molecular markers that have been used for identification and genetic diversity; however, no information about microsatellites of this liver fluke is published so far. We here report microsatellite characterization and marker development for a genetic diversity study in C. sinensis, using a genome-wide bioinformatics approach. Based on our search criteria, a total of 256,990 microsatellites (≥12 base pairs) were identified from a genome database of C. sinensis, with hexanucleotide motif being the most abundant (51%) followed by pentanucleotide (18.3%) and trinucleotide (12.7%). The tetranucleotide, dinucleotide, and mononucleotide motifs accounted for 9.75, 7.63, and 0.14%, respectively. The total length of all microsatellites accounts for 0. 72% of 547 Mb of the whole genome size, and the frequency of microsatellites was found to be one microsatellite in every 2.13 kb of DNA. For the di-, tri-, and tetranucleotide, the repeat numbers redundant are six (28%), four (45%), and three (76%), respectively. The ATC repeat is the most abundant microsatellites followed by AT, AAT, and AC, respectively. Within 40 microsatellite loci developed, 24 microsatellite markers showed potential to differentiate between C. sinensis and Opisthorchis viverrini. Seven out of 24 loci showed to be heterozygous with observed heterozygosity that ranged from 0.467 to 1. Four primer sets could amplify both C. sinensis and O. viverrini DNA with different sizes. This study provides basic information of C. sinensis microsatellites, and the genome-wide markers developed may be a useful tool for the genetic study of C. sinensis.

The political anatomy of a guideline: a collaborative effort to develop the AHCPR-sponsored practice guideline on otitis media with effusion.

Science.gov (United States)

Sebring, R H; Herrerias, C T

1996-06-01

In July 1991 the Agency for Health Care Policy and Research (AHCPR) invited private organizations to develop a practice guideline on otitis media. The American Academy of Pediatrics (AAP) collaborated with the American Academy of Family Physicians, the American Academy of Otolaryngology-Head and Neck Surgery, and the Department of Pediatric Otolaryngology at the University of Pittsburgh in preparing a proposal. The AAP--the prime contractor--and the consortium were awarded the contract in October 1991. The 19-member panel assessed evidence and achieved consensus on most recommendations and maintained positive relationships that helped them function as a group. The practice guideline project has influenced the AAP's own evidence-based practice parameter methodology. Many lessons were learned. For example, since any project is only as strong as its weakest link, it was important to build the proposal on organizational strengths--including access to a combined 244,000 members and other resources. The weak links were the large number of persons involved in the project, their varying time commitments, and the wide geographic distribution of those involved. Also, neither AHCPR nor any of the organizations involved in the consortium had previous government contract experience in developing practice guidelines, so that much of the process became "on-the-job training". Research is needed to determine the extent to which the otitis media guideline is being used. The three academies are conducting a follow-up practice pattern variation study of pediatricians, family physicians, and otolaryngologists, which may provide data on behavior change with regard to managing the condition.

The use of plants containing genotoxic carcinogens as foods and medicine.

Science.gov (United States)

Prinsloo, Gerhard; Nogemane, Noluyolo; Street, Renee

2018-04-05

In many developing countries, populations rely on traditional medicine for primary health care, which have infiltrated commercial markets globally as natural remedies are generally regarded as safe. Traditional and natural remedies are adapted and expanded in commercial products and product ranges to provide alternatives for various diseases and illnesses. These products resemble very little of the traditional use and application and adverse effects are observed in several cases. Some of the herbs and botanical formulations therefore, are not as safe as are commonly contemplated. This paper discusses some plants that are used as food or medicine. These plants are known to contain chemical components that have been identified as genotoxic carcinogens. Often contradictory results are obtained with beneficial and adverse effects reported. The concentration, biotransformation and metabolism of these compounds, as well as the matrix effect, affect the outcome of these results, therefore not providing a clear picture of the risk associated with the use and consumption of these plants. This paper focuses on plants that are accepted as healthy, however contain compounds that are genotoxic and carcinogenic. We further highlight the risks in use of these plants where thorough studies have been conducted in various food and plant products. Copyright © 2018 Elsevier Ltd. All rights reserved.

36 CFR 910.67 - Square guidelines.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Square guidelines. 910.67... GUIDELINES AND UNIFORM STANDARDS FOR URBAN PLANNING AND DESIGN OF DEVELOPMENT WITHIN THE PENNSYLVANIA AVENUE DEVELOPMENT AREA Glossary of Terms § 910.67 Square guidelines. Square Guidelines establish the Corporation's...

Respiratory carcinogenicity assessment of soluble nickel compounds.

OpenAIRE

Oller, Adriana R

2002-01-01

The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear...

Effectiveness of a Mass Media Campaign on Oral Carcinogens and Their Effects on the Oral Cavity

Science.gov (United States)

Shrestha, Ashish; Rimal, Jyotsna

2018-03-27

Objective: To develop a mass media campaign on oral carcinogens and their effects on the oral cavity in order to increase awareness among the general population. Methods: Documentary and public service announcements highlighting the effects of tobacco and its products were designed and developed based on principles of behavior change. A questionnaire, designed to determine the knowledge, attitude and practice of people regarding oral carcinogens, was used to conduct a baseline survey at various sites in eastern Nepal. Local television channels and radio stations broadcasted the documentary and public service announcements. An evaluation survey was then performed to assess the effectiveness of the campaign. Results: Baseline and evaluation surveys covered 1,972 and 2,140 individuals, respectively. A third of the baseline population consumed quid, 22% chewing tobacco, 16% gutka (commercial preparation of arecanut, tobacco, lime and chemicals) and 25% cigarettes. Tobacco consumption differed significantly between 3 ecologic regions with greater use in the Terai region. The knowledge prevalence regarding the oral carcinogens quid (70%), chewing tobacco (82%), gutka (58%) and cigarettes (93%) significantly increased in the evaluation population. Females were more aware about the various tobacco products and their effects on health. More people knew about the harmful effects of tobacco on their health and oral cavity, and had their mouth examined and the frequency of consumption of these products reduced significantly after the campaign. Attitudes towards production, sale and advertisements of tobacco also improved significantly. Conclusions: The mass media campaign was an effective tool for increasing awareness among the population. Creative Commons Attribution License

Development of clinical practice guidelines for supportive care in childhood cancer-prioritization of topics using a Delphi approach

NARCIS (Netherlands)

Loeffen, E. A. H.; Mulder, R. L.; Kremer, L. C. M.; Michiels, E. M. C.; Abbink, F. C. H.; Ball, L. M.; Segers, H.; Mavinkurve-Groothuis, A. M. C.; Smit, F. J.; Vonk, I. J. M.; vd Wetering, M. D.; Tissing, W. J. E.

Currently, very few guidelines for supportive care for children with cancer exist. In the Netherlands, nationwide guidelines are over 10 years old and mostly based on expert opinion. Consequently, there is growing support and need for clinical practice guidelines (CPGs), which ought to be developed

Development of clinical practice guidelines for supportive care in childhood cancer--prioritization of topics using a Delphi approach

NARCIS (Netherlands)

Loeffen, E. A. H.; Mulder, R. L.; Kremer, L. C. M.; Michiels, E. M. C.; Abbink, F. C. H.; Ball, L. M.; Segers, H.; Mavinkurve-Groothuis, A. M. C.; Smit, F. J.; Vonk, I. J. M.; Vd Wetering, M. D.; Tissing, W. J. E.

2015-01-01

Currently, very few guidelines for supportive care for children with cancer exist. In the Netherlands, nationwide guidelines are over 10 years old and mostly based on expert opinion. Consequently, there is growing support and need for clinical practice guidelines (CPGs), which ought to be developed

A mode-of-action approach for the identification of genotoxic carcinogens.

Directory of Open Access Journals (Sweden)

Lya G Hernández

Full Text Available Distinguishing between clastogens and aneugens is vital in cancer risk assessment because the default assumption is that clastogens and aneugens have linear and non-linear dose-response curves, respectively. Any observed non-linearity must be supported by mode of action (MOA analyses where biological mechanisms are linked with dose-response evaluations. For aneugens, the MOA has been well characterised as disruptors of mitotic machinery where chromosome loss via micronuclei (MN formation is an accepted endpoint used in risk assessment. In this study we performed the cytokinesis-block micronucleus assay and immunofluorescence mitotic machinery visualisation in human lymphoblastoid (AHH-1 and Chinese Hamster fibroblast (V79 cell lines after treatment with the aneugen 17-β-oestradiol (E₂. Results were compared to previously published data on bisphenol-A (BPA and Rotenone data. Two concentration-response approaches (the threshold-[Td] and benchmark-dose [BMD] approaches were applied to derive a point of departure (POD for in vitro MN induction. BMDs were also derived from the most sensitive carcinogenic endpoint. Ranking comparisons of the PODs from the in vitro MN and the carcinogenicity studies demonstrated a link between these two endpoints for BPA, E₂ and Rotenone. This analysis was extended to include 5 additional aneugens, 5 clastogens and 3 mutagens and further concentration and dose-response correlations were observed between PODs from the in vitro MN and carcinogenicity. This approach is promising and may be further extended to other genotoxic carcinogens, where MOA and quantitative information from the in vitro MN studies could be used in a quantitative manner to further inform cancer risk assessment.

Quality of the Development of Traumatic Brain Injury Clinical Practice Guidelines: A Systematic Review.

Directory of Open Access Journals (Sweden)

Anjni Patel

Full Text Available Traumatic brain injury (TBI is a leading cause of death worldwide and is increasing exponentially particularly in low and middle income countries (LMIC. To inform the development of a standard Clinical Practice Guideline (CPG for the acute management of TBI that can be implemented specifically for limited resource settings, we conducted a systematic review to identify and assess the quality of all currently available CPGs on acute TBI using the AGREE II instrument. In accordance with PRISMA guidelines, from April 2013 to December 2015 we searched MEDLINE, EMBASE, Google Scholar and the Duke University Medical Center Library Guidelines for peer-reviewed published Clinical Practice Guidelines on the acute management of TBI (less than 24 hours, for any level of traumatic brain injury in both high and low income settings. A comprehensive reference and citation analysis was performed. CPGs found were assessed using the AGREE II instrument by five independent reviewers and scores were aggregated and reported in percentage of total possible score. An initial 2742 articles were evaluated with an additional 98 articles from the citation and reference analysis, yielding 273 full texts examined. A total of 24 final CPGs were included, of which 23 were from high income countries (HIC and 1 from LMIC. Based on the AGREE II instrument, the best score on overall assessment was 100.0 for the CPG from the National Institute for Health and Clinical Excellence (NIHCE, 2007, followed by the New Zealand Guidelines Group (NZ, 2006 and the National Clinical Guideline (SIGN, 2009 both with a score of 96.7. The CPG from a LMIC had lower scores than CPGs from higher income settings. Our study identified and evaluated 24 CPGs with the highest scores in clarity and presentation, scope and purpose, and rigor of development. Most of these CPGs were developed in HICs, with limited applicability or utility for resource limited settings. Stakeholder involvement, Applicability

Economic benefits of final effluent limitations guidelines and standards for the offshore oil and gas industry. Final report

International Nuclear Information System (INIS)

1993-01-01

The report provides an overview of the benefits analysis of the effluent limitation guidelines for offshore oil and gas facilities. Regulatory options were evaluated for two wastestreams: (1) drilling fluids (muds) and cuttings; and (2) produced water. The analysis focuses on the human health-related benefits of the regulatory options considered. These health risk reduction benefits are associated with reduced human exposure to various carcinogenic and noncarcinogenic contaminants, including lead, by way of consumption of shrimp and recreationally caught finfish from the Gulf of Mexico. Most of the health-risk reduction benefits analysis is based upon a previous report (RCG/Hagler, Bailly, January 1991), developed in support of the proposed rulemaking. Recreational, commercial, and nonuse benefits have not been estimated for these regulations, due to data limitations and the difficulty of estimating these values for effluent controls in the open-water marine environment

A proposal to develop a high temperature structural design guideline for HTGR components

International Nuclear Information System (INIS)

Hada, K.

1989-01-01

This paper presents some proposals for developing a high-temperature structural design guideline for HTGR structural components. It is appropriate that a basis for developing high-temperature structural design rules is rested on well-established elevated-temperature design guidelines, if the same failure modes are expected for high-temperature components as considered in such design guidelines. As for the applicability of ASME B and PV Code Case N-47 to structural design rules for high-temperature components (service temperatures ≥ 900 deg. C), the following critical issues on material properties and service life evaluation rules have been pointed out. (i) no work-hardening of stress-strain curves at high temperatures due to dynamic recrystallization; (ii) issues relating to very significant creep; (iii) ductility loss after long-term ageing at high temperatures; (iv) validity of life-fraction rule (Robinson-Taira rule) as creep-fatigue damage evaluation rule. Furthermore, the validity of design margins of elevated-temperature structural design guidelines to high-temperature design rules should be clarified. Solutions and proposals to these issues are presented in this paper. Concerning no work-hardening due to dynamic recrystallization, it is shown that viscous effects cannot be neglected even at high extension rate for tensile tests, and that changes in viscous deformation rates by dynamic recrystallization should be taken into account. The extension rate for tensile tests is proposed to change at high temperatures. The solutions and proposals to the above-mentioned issues lead to the conclusion that the design methodologies of N-47 are basically applicable to the high-temperature structural design guideline for HTGR structural components in service at about 900 deg. C. (author). 9 refs, 5 figs

Ethical principles and guidelines for the development of cognitive systems.

Energy Technology Data Exchange (ETDEWEB)

Shaneyfelt, Wendy

2006-05-01

As cognitive systems technologies emerge, so too do the ethical issues surrounding their development and use. To develop cognitive systems technologies responsibly, Sandia National Laboratories is establishing a framework to proactively address both real and potential ethical issues. This report contains the principles and guidelines developers can use to guide them as they are confronted with ethical issues related to developing cognitive systems technologies as they apply to U.S. national security. A process to apply these principles offers a practical way to transfer these principles from paper to a working strategy. Case studies are presented to reflect upon potential scenarios and to consider resolution strategies.

Site-specific induction of nuclear anomalies (apoptotic bodies and micronuclei) by carcinogens in mice

International Nuclear Information System (INIS)

Ronen, A.; Heddle, J.A.

1984-01-01

The usefulness of nuclear anomalies (NA) as a short-term test for indication of carcinogens in the mouse colon has been suggested previously by experiments in which colon-specific carcinogens induced NA in the colon, whereas non-colon carcinogens were, in general, impotent in that organ. We have extended this work to other sites in the digestive tract of female C57BL/6 mice treated with gamma-rays, 1,2-dimethylhydrazine dihydrochloride, or N-methylnitrosourea. Each agent induced NA at all of the sites examined. The frequency of NA at different times after treatment depended upon both the agent used and the site examined. 1,2-Dimethylhydrazine dihydrochloride (which is known to induce tumors predominantly in the colon) induces NA with the highest efficiency (relative to gamma-rays) in the descending colon. N-Methylnitrosourea (which induces tumors mainly in the forestomach) induces NA with the highest efficiency in the forestomach. These results further support the usefulness of the assay in that the frequency of NA produced at the various sites by 1,2-dimethylhydrazine dihydrochloride and N-methylnitrosourea correlates with that found in the carcinogenicity studies

Developing the Australasian Hepatology Association's Consensus-based Guidelines for the Nursing Care of Patients with Liver Disease.

Science.gov (United States)

Richmond, Jacqueline; Wheeler, Emily; Warner, Sherryne; Mason, Susan

2014-05-03

Abstract Purpose: Hepatology nursing is an emerging speciality. To define best practice, the Australasian Hepatology Association developed consensus-based guidelines for the nursing care of patients with liver disease. Methods: Using the Delphi technique, six rounds of consultation were conducted with Australian hepatology nurses and non-nursing hepatology professionals. Input was captured through face-to-face and electronic communication and questionnaires. Results: The experts' opinions were collated and consensus on the delivery of hepatology nursing care was achieved. In total, 90 consensus guidelines were developed. The principles underpinning the Guidelines include patient-centred care, non-discriminatory practice, cultural competence, collaboration and partnership and working within own scope of practice. Conclusion: Internationally, the Australasian Hepatology Association Guidelines are the first to document a consensus on the scope of hepatology nursing practice. The Guidelines reflect the expansion of hepatology nursing, from viral hepatitis to caring for patients with advanced liver disease and hepatocellular carcinoma, and provides a framework for future nursing practice.

Design guidelines for rapid and simple context-aware mobile application development – an android case study

Directory of Open Access Journals (Sweden)

Hossein Shams

2015-11-01

Full Text Available Presenting a context-aware service and information is a key aspect of ubiquitous computing, but development of such applications is quite complicated. Context-aware applications should be able to obtain raw data fromsensors, create highlevel context information, detect the user’s situation, and adapt the behavior of the application to the recognized situation . These complexities caused to reduce the impact of context -awareness in mobile computing while sensors of smartphones have made huge potential for developing context aware mobile applications. In this paper, we explain some guidelines to overcome the existing obstacles by separating the context -aware application layers and make a loosely coupled connection between them. These guidelines will bring easy and rapid development, reusability of the code and flexibility for developers. Finally, we provide a case study example in the Android platform to demonstrate how the guidelines can be used in a real application.

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

International Nuclear Information System (INIS)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

2014-01-01

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

Energy Technology Data Exchange (ETDEWEB)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); He, Xiaoyun; Huang, Kunlun; Luo, Yunbo [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentao@cau.edu.cn [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

2014-11-01

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.

Methodological Guidelines for Reducing the Complexity of Data Warehouse Development for Transactional Blood Bank Systems.

Science.gov (United States)

Takecian, Pedro L; Oikawa, Marcio K; Braghetto, Kelly R; Rocha, Paulo; Lucena, Fred; Kavounis, Katherine; Schlumpf, Karen S; Acker, Susan; Carneiro-Proietti, Anna B F; Sabino, Ester C; Custer, Brian; Busch, Michael P; Ferreira, João E

2013-06-01

Over time, data warehouse (DW) systems have become more difficult to develop because of the growing heterogeneity of data sources. Despite advances in research and technology, DW projects are still too slow for pragmatic results to be generated. Here, we address the following question: how can the complexity of DW development for integration of heterogeneous transactional information systems be reduced? To answer this, we proposed methodological guidelines based on cycles of conceptual modeling and data analysis, to drive construction of a modular DW system. These guidelines were applied to the blood donation domain, successfully reducing the complexity of DW development.

FNCA guideline on development of hydrogel and oligosaccharides by radiation processing

International Nuclear Information System (INIS)

Kudo, Hisaaki; Yoshii, Fumio; Kume, Tamikazu

2009-10-01

This report summarizes the current status of development of hydrogel and oligosaccharides by radiation (electron beams and gamma rays) processing in Asian countries, as an outcome of activities of the FNCA (Forum for Nuclear Co-operation in Asia)-industry group during the phase 2 (2006-2008), as one of FNCA Guidelines. The nine countries, Bangladesh (since 2007), China, Indonesia, Japan, Korea, Malaysia, Philippines, Thailand and Vietnam, participates in the phase 2 of the FNCA-industry group, focusing on radiation processing of natural polymers. Participating countries have been studying radiation processing of natural polymers such as chitosan from shrimp/crab shells and carrageenan taken from seaweeds, in terms of cross-linking for gel and degradation for oligosaccharides. The former obtains hydrogel which can absorb a lot of water, and application for wound dressing and super water absorbent in the fields of medical and environmental conservation are expected. The latter obtained oligosaccharides have functions as growth promoter and elicitor activator of plants, sea-creatures and livestocks etc., and application in the fields of agri- and aqua- cultures are expected. This Guideline consists of 3 parts; part 1 describes the outline of radiation chemistry of polymers; part 2 compiles the protocols of versatile applications; part 3 refers the examples of cost analysis and current status of the technology. This Guideline would facilitate development, commercialization and technical transfer to end-users of radiation processing of natural polymers. (author)

Comparative experimental study of cancer induced by ionizing radiations or by chemical carcinogens

International Nuclear Information System (INIS)

Lafuma, J.

1983-01-01

Animal experiments have contributed to specify a number of parameters used in setting human safety limits for ionizing radiation. In the same way, comparisons have been made between cancers induced in man and in animals in well-defined conditions. In order to use the same experimental data for chemical carcinogens, the mechanisms of carcinogenesis should be the same, i.e. additivity of responses instead of synergy of effects, which requires the development of a new experimental method [fr

The role of microRNAs in the development and progression of chemical-associated cancers

International Nuclear Information System (INIS)

Pogribny, Igor P.; Beland, Frederick A.; Rusyn, Ivan

2016-01-01

Human exposure to certain natural and man-made chemical carcinogens is one of the major risk factors for cancer development. The effect of chemical carcinogens on genetic and epigenetic alterations and their significance in the development of cancer has been well-established. In contrast, the role of microRNAs (miRNAs) in the etiology of chemical-associated cancers remains relatively unexplored despite extensive reports on changes in miRNA expression upon carcinogen exposure. This review summarizes the current knowledge for the role of miRNAs as drivers of chemical-induced carcinogenesis by bridging the gap between carcinogen exposure and cancer development through functional studies. It also emphasizes the potential for miRNA changes as early indicators of the carcinogenic process, markers for carcinogen exposure, and identification of chemical carcinogenic hazards. - Highlights: • Exposure to chemical carcinogens alters microRNA expression. • MicroRNA alterations may have significance in the development of cancer. • MicroRNAs may be early indicators of the carcinogenic process and carcinogen exposure.

The role of microRNAs in the development and progression of chemical-associated cancers

Energy Technology Data Exchange (ETDEWEB)

Pogribny, Igor P., E-mail: igor.pogribny@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079 (United States); Beland, Frederick A. [Division of Biochemical Toxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR 72079 (United States); Rusyn, Ivan [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX 77843 (United States)

2016-12-01

Human exposure to certain natural and man-made chemical carcinogens is one of the major risk factors for cancer development. The effect of chemical carcinogens on genetic and epigenetic alterations and their significance in the development of cancer has been well-established. In contrast, the role of microRNAs (miRNAs) in the etiology of chemical-associated cancers remains relatively unexplored despite extensive reports on changes in miRNA expression upon carcinogen exposure. This review summarizes the current knowledge for the role of miRNAs as drivers of chemical-induced carcinogenesis by bridging the gap between carcinogen exposure and cancer development through functional studies. It also emphasizes the potential for miRNA changes as early indicators of the carcinogenic process, markers for carcinogen exposure, and identification of chemical carcinogenic hazards. - Highlights: • Exposure to chemical carcinogens alters microRNA expression. • MicroRNA alterations may have significance in the development of cancer. • MicroRNAs may be early indicators of the carcinogenic process and carcinogen exposure.

Development and validation of OECD test guidelines on mollusc reproductive toxicity tests

DEFF Research Database (Denmark)

Lagadic, Laurent; Holbech, Henrik; hutchinson, tom

the comparison of endpoints relevant for reproduction in invertebrates often shows a much higher sensitivity in molluscs vs. e.g. daphnids. The OECD test guideline programme has thus been extended to cover reproduction effects of chemicals in molluscs. Existing mollusc toxicity test protocols have been reviewed...... in an OECD Detailed Review Paper that identifies two relevant candidate species for developing freshwater tests: Potamopyrgus antipodarum and Lymnaea stagnalis. However, this review did not clarify which toxicity test design/conditions are the most appropriate for chemicals assessment. Therefore, a mollusc...... reproduction test guideline will be developed describing partial- and full- life-cycle test protocols in these species, so as to propose a balanced suite of apical mollusc toxicity tests applicable for the assessment of any type of chemical, including endocrine disruptors, as level 4 and 5 assays of the EDTA...

Assessment of respiratory carcinogenicity associated with exposure to metallic nickel: a review.

Science.gov (United States)

Sivulka, Donna J

2005-11-01

Human studies prior to 1990 have shown an association between respiratory cancer and exposure to some nickel compounds, but not to metallic nickel. Numerous reviews have examined the nature of the association between nickel compounds and respiratory cancer, but little has been published on metallic nickel. This paper reviews the animal and human cancer-related data on metallic nickel to determine whether the conclusions regarding metallic nickel reached a decade ago still apply. Based upon past and current human studies, metallic nickel appears to show little evidence of carcinogenicity when present at the same or higher concentrations than those seen in current workplace environments. By comparison, animal studies currently available have shown mixed results. A number of studies have shown evidence of carcinogenicity in animals exposed to nickel powders via injection, but other studies have shown no or inconsistent results in animals exposed via inhalation or intratracheal instillation. Further studies in animals via inhalation and humans would be helpful in elucidating the respiratory carcinogenic potential of metallic nickel.

Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

Science.gov (United States)

Hurley, P M

1998-08-01

Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly acetochlor; evidence is less convincing for ethylene thiourea and etridiazole. Studies on thyroid-pituitary functioning, including indications of thyroid cell growth and/or changes in thyroxine, triiodothyronine, or thyroid-stimulating hormone levels, are available on 19 pesticides. No such antithyroid information is available for etridiazole, N-octyl bicycloheptene dicarboximide, terbutryn, triadimefon, and trifluralin. Of the studied chemicals, only bromacil lacks antithyroid activity under study conditions. Intrathyroidal and extrathyroidal sites of action are found: amitrole, ethylene thiourea, and mancozeb are thyroid peroxidase inhibitors; and acetochlor, clofentezine, fenbuconazole, fipronil, pendimethalin, pentachloronitrobenzene, prodiamine, pyrimethanil, and thiazopyr seem to enhance the hepatic metabolism and excretion of thyroid hormone. Thus, with 12 pesticides that mode of action judgments can be made, 11 disrupt thyroid-pituitary homeostasis only; no chemical is mutagenic only; and acetochlor may have both antithyroid and some mutagenic activity. More information is needed to identify other potential antithyroid modes of thyroid carcinogenic action.

[Cardiovascular risk, occupation and exposure to occupational carcinogens in a group of workers in Salamanca].

Science.gov (United States)

González-Sánchez, Jesús

2015-01-01

Identify the cardiovascular risk factors in a group of workers in the province of Salamanca, protected by external prevention services, as regards exposure to occupational carcinogens, by sector of activity and gender. An observational descriptive epidemiological study was conducted. The sample selection was by stratified random sampling in each entity. The variables collected by questionnaire were, sociodemographic characteristics, exposure to occupational carcinogens, and cardiovascular risk factors (smoking, hypertension, dyslipidemia, and diabetes), using the clinical-work histories as a source of information. Statistically significant differences were observed in cardiovascular risk according to the exposure to occupational carcinogens (p cardiovascular risk in the work place. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

National Priority Setting of Clinical Practice Guidelines Development for Chronic Disease Management.

Science.gov (United States)

Jo, Heui-Sug; Kim, Dong Ik; Oh, Moo-Kyung

2015-12-01

By November 2013, a total of 125 clinical practice guidelines (CPGs) have been developed in Korea. However, despite the high burden of diseases and the clinical importance of CPGs, most chronic diseases do not have available CPGs. Merely 83 CPGs are related to chronic diseases, and only 40 guidelines had been developed in the last 5 yr. Considering the rate of the production of new evidence in medicine and the worsening burden from chronic diseases, the need for developing CPGs for more chronic diseases is becoming increasingly pressing. Since 2011, the Korean Academy of Medical Sciences and the Korea Centers for Disease Control and Prevention have been jointly developing CPGs for chronic diseases. However, priorities have to be set and resources need to be allocated within the constraint of a limited funding. This study identifies the chronic diseases that should be prioritized for the development of CPGs in Korea. Through an objective assessment by using the analytic hierarchy process and a subjective assessment with a survey of expert opinion, high priorities were placed on ischemic heart disease, cerebrovascular diseases, Alzheimer's disease and other dementias, osteoarthritis, neck pain, chronic kidney disease, and cirrhosis of the liver.

Temporal aspects of tumorigenic response to individual and mixed carcinogens. Progress report, October 1, 1978-September 30, 1979

International Nuclear Information System (INIS)

Albert, R.E.; Burns, F.J.; Altshuler, B.

1979-06-01

The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the carcinogens, promoters, and cocarcinogens

Evaluation of the carcinogenic risks at the influence of POPs.

Science.gov (United States)

Nazhmetdinova, Aiman; Kassymbayev, Adlet; Chalginbayeva, Altinay

2017-12-20

Kazakhstan is included in the list of environmentally vulnerable countries and Kyzylorda oblast in particular. This is due to its geographical, spatial and temporal and socioeconomic features. As part of the program "Integrated approaches in the management of public health in the Aral region", we have carried out an expertise on many samples of natural environments and products. Samples were selected in accordance with sampling procedures according to regulatory documents by specialists of the Pesticide Toxicology Laboratory. It is accredited by the State Standard of the Republic of Kazakhstan, for compliance with ST RK ISO/IEC 17025-2007 "General requirements for the competence of test and calibration laboratories". Gas chromatograph was used for the determination of residues of organochlorine pesticides. For the determination of dioxins, polychlorinated biphenyl was conducted on the gas chromatomass spectrometer with quadruple detector produce by Agilent Company, USA. To assess the risk, we carried out the mathematical calculations according to the risk of chemicals polluting (No P 2.1.10.1920-04, Russia). Calculation of the carcinogenic risk was carried out with the use of data on the size of the exposure and meanings of carcinogenic potential factors (slope factor and unit risk). The evaluation of persistent organic pollutants (POPs), based on the previous results of the research concerning water, soil and food products, was held in five population settlements in Kyzylorda oblast villages: Ayteke bi, Zhalagash, Zhosaly, Shieli and Aralsk town. Pollution with the POPs in the environmental objects by means of exposition and evaluation of the carcinogenic risk to human health is confirmed by the data of the statistical reporting about some morbidity in Kyzylorda oblast, such as skin diseases and subcutaneous tissue, endocrine system diseases, pregnancy complications etc. The received levels of carcinogenic risks, which were first carried out in the Republic of

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Directory of Open Access Journals (Sweden)

Katherine von Stackelberg

2013-01-01

Full Text Available Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D and 4-chloro-2-methylphenoxyacetic acid (MCPA, are amongst the most widely used herbicides in the United States for both agricultural and residential applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may be associated with increased risk non-Hodgkins lymphoma (NHL, Hodgkin’s disease (HD, leukemia, and soft-tissue sarcoma (STS. Toxicological studies in rodents show no evidence of carcinogenicity, and regulatory agencies worldwide consider chlorophenoxies as not likely to be carcinogenic or unclassifiable as to carcinogenicity. This systematic review assembles the available data to evaluate epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring studies with respect to key cellular events noted in disease etiology and how those relate to hypothesized modes of action for these constituents to determine the plausibility of an association between exposure to environmentally relevant concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined evidence does not support a genotoxic mode of action. Although plausible hypotheses for other carcinogenic modes of action exist, a comparison of biomonitoring data to oral equivalent doses calculated from bioassay data shows that environmental exposures are not sufficient to support a causal relationship. Genetic polymorphisms exist that are known to increase the risk of developing NHL. The potential interaction between these polymorphisms and exposures to chlorophenoxy compounds, particularly in occupational settings, is largely unknown.

Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC.

Science.gov (United States)

Tarazona, Jose V; Court-Marques, Daniele; Tiramani, Manuela; Reich, Hermine; Pfeil, Rudolf; Istace, Frederique; Crivellente, Federica

2017-08-01

Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence. Glyphosate is not the first topic of disagreement between IARC and regulatory evaluations, but has received greater attention. This review presents the scientific basis of the glyphosate health assessment conducted within the European Union (EU) renewal process, and explains the differences in the carcinogenicity assessment with IARC. Use of different data sets, particularly on long-term toxicity/carcinogenicity in rodents, could partially explain the divergent views; but methodological differences in the evaluation of the available evidence have been identified. The EU assessment did not identify a carcinogenicity hazard, revised the toxicological profile proposing new toxicological reference values, and conducted a risk assessment for some representatives uses. Two complementary exposure assessments, human-biomonitoring and food-residues-monitoring, suggests that actual exposure levels are below these reference values and do not represent a public concern.

Transparent Guideline Methodology Needed

DEFF Research Database (Denmark)

Lidal, Ingeborg; Norén, Camilla; Mäkelä, Marjukka

2013-01-01

As part of learning at the Nordic Workshop of Evidence-based Medicine, we have read with interest the practice guidelines for central venous access, published in your Journal in 2012.1 We appraised the quality of this guideline using the checklist developed by The Evidence-Based Medicine Working ...... are based on best currently available evidence. Our concerns are in two main categories: the rigor of development, including methodology of searching, evaluating, and combining the evidence; and editorial independence, including funding and possible conflicts of interest....... Group.2 Similar criteria for guideline quality have been suggested elsewhere.3 Our conclusion was that this much needed guideline is currently unclear about several aspects of the methodology used in developing the recommendations. This means potential users cannot be certain that the recommendations...

The new hypertension guidelines.

Science.gov (United States)

Stern, Ralph H

2013-10-01

The Canadian Hypertension Education Program (CHEP) has published guidelines annually since 2000. The CHEP guidelines are a model of concise, comprehensive, up-to-date, evidence-rated guidelines for physicians who diagnose and treat hypertension. The guidelines address measurement of blood pressure and the definition of hypertension, secondary hypertension evaluation and treatment, and blood pressure targets and medication choices in patients with and without compelling indications. This review describes CHEP's process for developing guidelines and provides an overview of the 2013 recommendations. ©2013 Wiley Periodicals, Inc.

On the International Agency for Research on Cancer classification of glyphosate as a probable human carcinogen.

Science.gov (United States)

Tarone, Robert E

2018-01-01

The recent classification by International Agency for Research on Cancer (IARC) of the herbicide glyphosate as a probable human carcinogen has generated considerable discussion. The classification is at variance with evaluations of the carcinogenic potential of glyphosate by several national and international regulatory bodies. The basis for the IARC classification is examined under the assumptions that the IARC criteria are reasonable and that the body of scientific studies determined by IARC staff to be relevant to the evaluation of glyphosate by the Monograph Working Group is sufficiently complete. It is shown that the classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence evaluated by the Working Group. Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents. Implications of the erroneous classification of glyphosate with respect to the IARC Monograph Working Group deliberative process are discussed.

[Comparative carcinogenic properties of basalt fiber and chrysotile-asbestos].

Science.gov (United States)

Nikitina, O V; Kogan, F M; Vanchugova, N N; Frash, V N

1989-01-01

In order to eliminate asbestos adverse effect on workers' health it was necessary to use mineral rayon, primarily basalt fibre, instead of asbestos. During a chronic experiment on animals the oncogenicity of 2 kinds of basalt fibre was studied compared to chrysotile asbestos. The dust dose of 25 mg was twice administered by intraperitonial route. All types of dust induced the onset of intraperitonial mesotheliomas but neoplasm rates were significantly lower in the groups exposed to basalt fibre. There was no credible data on the differences between the groups exposed to various types of basalt fibre. Since the latter produced some oncogenic effect, it was necessary to develop a complex of antidust measures, fully corresponding to the measures adopted for carcinogenic dusts.

Oral carcinogenesis is not achieved in different carcinogen-treated PAI-1 transgenic and wild-type mouse models.

Science.gov (United States)

Avgoustidis, Dimitris; Nisyrios, Themistoklis; Nkenke, Emeka; Lijnen, Roger; Ragos, Vassilis; Perrea, Despina; Donta, Ismini; Vaena, Apostolia; Yapijakis, Christos; Vairaktaris, Eleftherios

2012-01-01

In an effort to assess the role of plasminogen activator inhibitor-1 (PAI-1) in oral squamous cancer development and progression, two different carcinogen treatment protocols were conducted. Protocol I included mice from a PAI-1 transgenic (Tg) breed (n=56) and their wild-type (WT) counterparts (n=56), divided into one control group and two main experimental groups, treated with 7,12-dimethylbenz[a]anthracene (DMBA) for 8 and 16 weeks, respectively. Protocol II included the same number and types of animals and groups, which were similarly treated with 4-Nitroquinoline 1-oxide (4-NQO) in drinking water. Two drugs that affect plasma PAI-1 levels, enalapril and pravastatin, were administered to certain subgroups of animals in both protocols. None of the animals developed macroscopically-visible oral cancer lesions. Eleven animals under Protocol I and 52 animals under Protocol II died. Skin lesions were noted only in DMBA-treated animals (n=9). Almost all animals administered with 4-NQO developed alopecia and lost weight, while two of them developed stomach tumours, and one female mouse developed a large ovarian cyst. Transgenic mice may respond differently when used in well-established carcinogen models and oral carcinogenesis is hard to achieve in these rodents.

Development of an Official Guideline for the Economic Evaluation of Drugs/Medical Devices in Japan.

Science.gov (United States)

Shiroiwa, Takeru; Fukuda, Takashi; Ikeda, Shunya; Takura, Tomoyuki; Moriwaki, Kensuke

2017-03-01

In Japan, cost-effectiveness evaluation was implemented on a trial basis from fiscal year 2016. The results will be applied to the future repricing of drugs and medical devices. On the basis of a request from the Central Social Insurance Medical Council (Chuikyo), our research team drafted the official methodological guideline for trial implementation. Here, we report the process of developing and the contents of the official guideline for cost-effectiveness evaluation. The guideline reflects discussions at the Chuikyo subcommittee (e.g., the role of quality-adjusted life-year) and incorporates our academic perspective. Team members generated research questions for each section of the guideline and discussions on these questions were carried out. A draft guideline was prepared and submitted to the Ministry of Health, Labour and Welfare (MHLW), and then to the subcommittee. The draft guideline was revised on the basis of the discussions at the subcommitte, if appropriate. Although the "public health care payer's perspective" is standard in this guideline, other perspectives can be applied as necessary depending on the objective of analysis. On the basis of the discussions at the subcommittee, quality-adjusted life-year will be used as the basic outcome. A discount rate of 2% per annum for costs and outcomes is recommended. The final guideline was officially approved by the Chuikyo general assembly in February 2016. This is the first officially approved guideline for the economic evaluation of drugs and medical devices in Japan. The guideline is expected to improve the quality and comparability of submitted cost-effectiveness data for decision making. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

The development of assessment and remediation guidelines for contaminated soils, a review of the science

International Nuclear Information System (INIS)

Sheppard, S.C.; Gaudet, C.; Sheppard, M.I.; Cureton, P.M.; Wong, M.P.

1992-01-01

Soil contamination is no longer restricted to isolated incidents and locations; it is a general and contentious problem. However, the problem is complex, starting with the very definition of what level and type of contamination is unacceptable. A myriad of regulatory and de facto guidelines have emerged, and they are extremely fragmented, inconsistent and incomplete. This review attempts to summarize the historical development of assessment and remediation guidelines, to highlight the unique difficulties of the problem, and then to discuss the scientific information that exists and that is needed to improve guidelines. This is an unlimited scope for research on this subject. (author)

Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project.

NARCIS (Netherlands)

Cluzeau, F.A.; Burgers, J.S.; Brouwers, M.M.; Grol, R.P.T.M.; et al.,

2003-01-01

BACKGROUND: International interest in clinical practice guidelines has never been greater but many published guidelines do not meet the basic quality requirements. There have been renewed calls for validated criteria to assess the quality of guidelines. OBJECTIVE: To develop and validate an

Chemical procedures to detect carcinogenic compound in domestic wastewater

International Nuclear Information System (INIS)

Abd Manan T S; Malakahmad A

2013-01-01

This review presents chemical methods to detect carcinogenic compound in wastewater. Atomic absorption spectroscopy (AAS), high performance liquid chromatography (HPLC) and gas chromatography mass spectroscopy (GCMS) and their alternative attached equipments were discussed. The application of each method is elaborated using related studies in the field.

The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole

Energy Technology Data Exchange (ETDEWEB)

Miller, J A; Miller, E C

1983-07-01

A small (approximately 30) but varied group of organic and inorganic compounds appear to be carcinogenic in both humans and experimental animals. A much larger number and wider variety of chemical carcinogens, primarily synthetic organic compounds, are known for experimental animals. These agents include a small (approximately 30) and varied group of metabolites of green plants and fungi. Many more of these carcinogens must exist in the living world. As with the synthetic carcinogens, the majority of these naturally occurring carcinogens are procarcinogens that require metabolic conversion into reactive electrophilic and mutagenic ultimate carcinogens. These strong electrophiles combine covalently and non-enzymatically with nucleophilic sites in DNAs, RNAs, proteins, and small molecules in target tissues. One or more of the DNA adducts appear to initiate carcinogenesis in an irreversible manner. The subsequent promotion step leading to gross tumours may be completed by further administration of carcinogen or by treatment with non-carcinogenic promoters. Roles for the RNA and protein adducts in the carcinogenic process have not been excluded. Recent data on the metabolic activation and reactivity in vivo of the naturally occurring carcinogens ethyl carbamate and certain of the alkenylbenzene spice flavours are illustrative of these principles. These agents can initiate the carcinogenic process in male mouse liver with small doses given prior to weaning. Subsequent growth of the liver and male hormonal factors appear to function as promoters leading to gross hepatic tumors after one year. Reactive electrophilic metabolites of ethyl carbamate and of safrole and estragole and their nucleic acid adducts formed during initiation in mouse liver have been characterized.

Guidelines to Develop Efficient Photocatalysts for Water Splitting

KAUST Repository

Garcia Esparza, Angel T.

2016-04-03

Photocatalytic overall water splitting is the only viable solar-to-fuel conversion technology. The research discloses an investigation process wherein by dissecting the photocatalytic water splitting device, electrocatalysts, and semiconductor photocatalysts can be independently studied, developed and optimized. The assumption of perfect catalysts leads to the realization that semiconductors are the limiting factor in photocatalysis. This dissertation presents a guideline for efficient photocatalysis using semiconductor particles developed from idealized theoretical simulations. No perfect catalysts exist; then the discussion focus on the development of efficient non-noble metal electrocatalysts for hydrogen evolution from water reduction. Tungsten carbide (WC) is selective for the catalysis of hydrogen without the introduction of the reverse reaction of water formation, which is critical to achieving photocatalytic overall water splitting as demonstrated in this work. Finally, photoelectrochemistry is used to characterize thoroughly Cu-based p-type semiconductors with potential for large-scale manufacture. Artificial photosynthesis may be achieved by following the recommendations herein presented.

A Review of the Carcinogenic Potential of Bisphenol A

Science.gov (United States)

Seachrist, Darcie D; Bonk, Kristen W.; Ho, Shuk-Mei; Prins, Gail S.; Soto, Ana M.; Keri, Ruth A.

2015-01-01

The estrogenic properties of bisphenol A (BPA), a ubiquitous synthetic monomer that can leach into the food and water supply, have prompted considerable research into exposure-associated health risks in humans. Endocrine-disrupting properties of BPA suggest it may impact developmental plasticity during early life, predisposing individuals to disease at doses below the oral reference dose (RfD) established by the Environmental Protection Agency in 1982. Herein, we review the current in vivo literature evaluating the carcinogenic properties of BPA. We conclude that there is substantial evidence from rodent studies indicating that early-life BPA exposures below the RfD lead to increased susceptibility to mammary and prostate cancer. Based on the definitions of “carcinogen” put forth by the International Agency for Research on Cancer and the National Toxicology Program, we propose that BPA may be reasonably anticipated to be a human carcinogen in the breast and prostate due to its tumor promoting properties. PMID:26493093

Carcinogenic action of polycyclic hydrocarbons in animals and man

Energy Technology Data Exchange (ETDEWEB)

Shabad, L M

1976-01-01

Polycyclic hydrocarbons are universally present in the atmosphere, soil, lakes and streams, vegetation, and human and animal tissues, the concentrations varying with distance from the sources (heating systems, industrial plants, automobile highways and airports, petroleum refineries, etc.). The most potent of the carcinogens is benz(a)pyrene whose presence in an object, as shown by studies done in the author's laboratory, is an indication that other polycyclic hydrocarbons are also present. These studies also demonstrated that while benz(a)pyrene may accumulate in soil with seasonal fluctuations, it can also be destroyed by certain microorganisms. Other experiments showed that benz(a)pyrene and other such compounds can be destroyed in tissue culture as well as in vivo (e.g., benz(a)pyrene given to cows with fodder was found in their milk but not in meat after they were slaughtered). It is suggested that maximum permissible concentrations be set for benz(a)pyrene in air and water to minimize its potential carcinogenic effects.

Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard assessment.

Science.gov (United States)

Fukushima, Shoji; Kasai, Tatsuya; Umeda, Yumi; Ohnishi, Makoto; Sasaki, Toshiaki; Matsumoto, Michiharu

2018-01-25

This report reviews the carcinogenicity of multi-walled carbon nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight fibrous MWCNT. MWCNTs were administered to mice and rats by intraperitoneal injection, intrascrotal injection, subcutaneous injection, intratracheal instillation and inhalation. Intraperitoneal injection of MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N (another straight fibrous MWCNT) induced both lung carcinoma and pleural mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7 promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with increasing concentration of airborne MWNT-7 and increasing duration of exposure. Straight, fibrous MWCNTs exerted carcinogenicity in experimental animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect level-based approach, we calculated that the occupational exposure limit (OEL) of MWNT-7 for cancer protection is 0.15 μg/m 3 for a human worker. Further studies on the effects of the shape and size of MWCNT fibers and mode of action on the carcinogenicity are required.

Wearables for all : development of guidelines to stimulate accessible wearable technology design

NARCIS (Netherlands)

Wentzel, Jobke; Velleman, Eric; van der Geest, Thea

2016-01-01

In this paper, we present the rationale and approach for establishing guidelines for the development of accessible wearables. Wearable technology is increasingly integrated in our everyday lives. Therefore, ensuring accessibility is pivotal to prevent a digital divide between persons who have and

Prospective comparison of three guideline development methods for treatment of actinic keratosis

NARCIS (Netherlands)

Borgonjen, Rinke J.; van Everdingen, Jannes J.; Bik, Cathelijne M.; Tuut, Mariska K.; Spuls, Phyllis I.; van de Kerkhof, Peter C.

2011-01-01

To compare three methods of guideline development, to see whether using alternative evidence-based methods resulted in variation of recommendations for treating actinic keratosis. Method 1 followed a standard multiple session evidence-based approach with a working group. In method 2 recommendations

Development of South African water quality guidelines for the natural aquatic environment

CSIR Research Space (South Africa)

MacKay, HM

1995-01-01

Full Text Available This paper describes the progress made by the Department of Water Affairs and Forestry in the development of documented water quality guidelines for aquatic ecosystems in South Africa, which will be able to take into account local and site...

Developing a questionnaire to identify perceived barriers for implementing the Dutch physical therapy COPD clinical practice guideline

NARCIS (Netherlands)

Wees, P.J. van der; Zagers, C.A.; Die, S.E. de; Hendriks, E.J.; Nijhuis-Van der Sanden, M.W.G.; Bie, R.A. de

2013-01-01

BACKGROUND: Clinical practice guidelines have been developed to assist healthcare practitioners in clinical decision making. Publication of clinical practice guidelines does not automatically lead to their uptake and barrier identification has been recognized as an important step in implementation

Preliminary report on operational guidelines developed for use in emergency preparedness and response to a radiological dispersal device incident.

Energy Technology Data Exchange (ETDEWEB)

Yu, C.; Cheng, J.-J.; Kamboj, S.; Domotor, S.; Wallo, A.; Environmental Science Division; DOE

2006-12-15

This report presents preliminary operational guidelines and supporting work products developed through the interagency Operational Guidelines Task Group (OGT). The report consolidates preliminary operational guidelines, all ancillary work products, and a companion software tool that facilitates their implementation into one reference source document. The report is intended for interim use and comment and provides the foundation for fostering future reviews of the operational guidelines and their implementation within emergency preparedness and response initiatives in the event of a radiological dispersal device (RDD) incident. The report principally focuses on the technical derivation and presentation of the operational guidelines. End-user guidance providing more details on how to apply these operational guidelines within planning and response settings is being considered and developed elsewhere. The preliminary operational guidelines are categorized into seven groups on the basis of their intended application within early, intermediate, and long-term recovery phases of emergency response. We anticipate that these operational guidelines will be updated and refined by interested government agencies in response to comments and lessons learned from their review, consideration, and trial application. This review, comment, and trial application process will facilitate the selection of a final set of operational guidelines that may be more or less inclusive of the preliminary operational guidelines presented in this report. These and updated versions of the operational guidelines will be made available through the OGT public Web site (http://ogcms.energy.gov) as they become finalized for public distribution and comment.

Standards and Guidelines in Telemedicine and Telehealth

Science.gov (United States)

Krupinski, Elizabeth A.; Bernard, Jordana

2014-01-01

The development of guidelines and standards for telemedicine is an important and valuable process to help insure effective and safe delivery of quality healthcare. Some organizations, such as the American Telemedicine Association (ATA), have made the development of standards and guidelines a priority. The practice guidelines developed so far have been well received by the telemedicine community and are being adopted in numerous practices, as well as being used in research to support the practice and growth of telemedicine. Studies that utilize published guidelines not only help bring them into greater public awareness, but they also provide evidence needed to validate existing guidelines and guide the revision of future versions. Telemedicine will continue to grow and be adopted by more healthcare practitioners and patients in a wide variety of forms not just in the traditional clinical environments, and practice guidelines will be a key factor in fostering this growth. Creation of guidelines is important to payers and regulators as well as increasingly they are adopting and integrating them into regulations and policies. This paper will review some of the recent ATA efforts in developing telemedicine practice guidelines, review the role of research in guidelines development, review data regarding their use, and discuss some of areas where guidelines are still needed. PMID:27429261

Impact of environmental exposures on the mutagenicity/carcinogenicity of heterocyclic amines

Energy Technology Data Exchange (ETDEWEB)

Felton, James S; Knize, Mark G; Bennett, L Michelle; Malfatti, Michael A; Colvin, Michael E; Kulp, Kristen S

2004-05-20

Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines.

Impact of environmental exposures on the mutagenicity/carcinogenicity of heterocyclic amines

International Nuclear Information System (INIS)

Felton, James S.; Knize, Mark G.; Bennett, L. Michelle; Malfatti, Michael A.; Colvin, Michael E.; Kulp, Kristen S.

2004-01-01

Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines

A study on the development of the radiation protection numerical guideline

International Nuclear Information System (INIS)

Park, M. S.; Kang, C. S.

1998-01-01

The present paper intends to develope the radiation protection numerical guideline for next generation nuclear power plants. For the determining a value for a societal life, medical costs method, wages and investments method, and GNP method are used. In assessing the risk factors due to radiation exposure, it is accepted that fatal cancer risk, nonfatal cancer risk, and genetic risk factors proposed by ICRP 60. It is calculated that the societal value of life with corresponding range of from $886,500 to $3,406,000 in 1996 U.S. dollars. The person-rem cost estimates can be found to range from $650 per person-rem to $2,500 per person-rem. The radiation protection numerical guideline for next generation nuclear power plants is proposed by $1,600 per person-rem

Guidelines in lower-middle income countries.

Science.gov (United States)

Olayemi, Edeghonghon; Asare, Eugenia V; Benneh-Akwasi Kuma, Amma A

2017-06-01

Guidelines include recommendations intended to optimize patient care; used appropriately, they make healthcare consistent and efficient. In most lower-middle income countries (LMICs), there is a paucity of well-designed guidelines; as a result, healthcare workers depend on guidelines developed in Higher Income Countries (HICs). However, local guidelines are more likely to be implemented because they are applicable to the specific environment; and consider factors such as availability of resources, specialized skills and local culture. If guidelines developed in HICs are to be implemented in LMICs, developers need to incorporate local experts in their development. Involvement of local stakeholders may improve the rates of implementation by identifying and removing barriers to implementation in LMICs. Another option is to encourage local experts to adapt them for use in LMICs; these guidelines may recommend strategies different from those used in HICs, but will be aimed at achieving the best practicable standard of care. Infrastructural deficits in LMICs could be improved by learning from and building on the successful response to the human immunodeficiency virus/acquired immunodeficiency syndrome pandemic through interactions between HICs and LMICs. Similarly, collaborations between postgraduate medical colleges in both HICs and LMICs may help specialist doctors training in LMICs develop skills required for guideline development and implementation. © 2017 John Wiley & Sons Ltd.

Asian Americans and disproportionate exposure to carcinogenic hazardous air pollutants: A national study.

Science.gov (United States)

Grineski, Sara E; Collins, Timothy W; Morales, Danielle X

2017-07-01

Studies have demonstrated disparate exposures to carcinogenic hazardous air pollutants (HAPs) in neighborhoods with high densities of Black and Hispanic residents in the US. Asians are the fastest growing racial/ethnic group in the US, yet they have been underemphasized in previous studies of environmental health and injustice. This cross-sectional study investigated possible disparities in residential exposure to carcinogenic HAPs among Asian Americans, including Asian American subgroups in the US (including all 50 states and the District of Columbia, n = 71,208 US census tracts) using National Air Toxics Assessment and US Census data. In an unadjusted analysis, Chinese and Korean Americans experience the highest mean cancer risks from HAPs, followed by Blacks. The aggregated Asian category ranks just below Blacks and above Hispanics, in terms of carcinogenic HAP risk. Multivariate models adjusting for socioeconomic status, population density, urban location, and geographic clustering show that an increase in proportion of Asian residents in census tracts is associated with significantly greater cancer risk from HAPs. Neighborhoods with higher proportions (as opposed to lower proportions) of Chinese, Korean, and South Asian residents have significantly greater cancer risk burdens relative to Whites. Tracts with higher concentrations of Asians speaking a non-English language and Asians that are US-born have significantly greater cancer risk burdens. Asian Americans experience substantial residential exposure to carcinogenic HAPs in US census tracts and in the US more generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

Supporting industrial equipment development through a set of design-for-maintenance guidelines

NARCIS (Netherlands)

Mulder, W.; Basten, Robertus Johannes Ida; Jauregui Becker, Juan Manuel; Blok, Jeroen; Hoekstra, Sipke; Kokkeler, Frans; Marjanovic, Dorian; Storga, Mario; Pavkovic, Neven; Bojcetic, Nenad

2014-01-01

This paper presents a leaflet with design-for-maintenance guidelines. It aims at supporting developers of industrial equipment in their design-for-maintenance practices. The use of this leaflet should lead to increased attention for design-for-maintenance aspects and to improve idea generation. The

The appraisal of clinical guidelines in dentistry.

Science.gov (United States)

Glenny, Anne-Marie; Worthington, Helen V; Clarkson, Jan E; Esposito, Marco

2009-01-01

To appraise the reported processes involved in the development of published dental guidelines. Electronic databases were searched to identify guidelines making recommendations for any health professional within dentistry. All included guidelines were appraised using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. A total of 105 guidelines met the inclusion criteria. The appraised guidelines showed lack of rigour in their development (median score 14.3%; range 0% to 100%). Only 10 (9.5%) were coded as 'strongly recommend' by at least two assessors. If recommendations within clinical guidelines are to be relied upon, the methods used in their development must be explicit and free from bias. When using the AGREE checklist to make decisions on whether or not to implement individual sets of guidelines, the findings of the present assessment reinforce the need for more than two assessors to be included in the appraisal of each set of guidelines.

A Guideline for Game Development-Based Learning: A Literature Review

Directory of Open Access Journals (Sweden)

Bian Wu

2012-01-01

Full Text Available This study aims at reviewing the published scientific literature on the topics of a game development-based learning (GDBL method using game development frameworks (GDFs with the perspective of (a summarizing a guideline for using GDBL in a curriculum, (b identifying relevant features of GDFs, and (c presenting a synthesis of impact factors with empirical evidence on the educational effectiveness of the GDBL method. After systematically going through the available literature on the topic, 34 relevant articles were selected for the final study. We analyzed the articles from three perspectives: (1 pedagogical context and teaching process, (2 selection of GDFs, and (3 evaluation of the GDBL method. The findings from the 34 articles suggest that GDFs have many potential benefits as an aid to teach computer science, software engineering, art design, and other fields and that such GDFs combined with the motivation from games can improve the students’ knowledge, skills, attitudes, and behaviors in contrast to the traditional classroom teaching. Furthermore, based on the results of the literature review, we extract a guideline of how to apply the GDBL method in education. The empirical evidence of current findings gives a positive overall picture and can provide a useful reference to educators, practitioners, and researchers in the area of game-based learning.

Absence of multiplicative interactions between occupational lung carcinogens and tobacco smoking: a systematic review involving asbestos, crystalline silica and diesel engine exhaust emissions

Directory of Open Access Journals (Sweden)

Mohamad El Zoghbi

2017-02-01

Full Text Available Abstract Background Tobacco smoking is the main cause of lung cancer, but it is not the sole causal factor. Significant proportions of workers are smokers and exposed to occupational lung carcinogens. This study aims to systematically review the statistical interaction between occupational lung carcinogens and tobacco smoking, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Methods Articles were identified using Scopus, PubMed, and Web of Science, and were limited to those published in English or French, without limitation of time. The reference list of selected studies was reviewed to identify other relevant papers. One reviewer selected the articles based on the inclusion and exclusion criteria. Two reviewers checked the eligibility of articles to be included in the systematic review. Data were extracted by one reviewer and revised by two other reviewers. Cohorts and case–control studies were analyzed separately. The risk of bias was evaluated for each study based on the outcome. The results of the interaction between the tobacco smoking and each carcinogen was evaluated and reported separately. Results Fifteen original studies were included for asbestos-smoking interaction, seven for silica-smoking interaction and two for diesel-smoking interaction. The results suggested the absence of multiplicative interaction between the three occupational lung carcinogens and smoking. There is no enough evidence from the literature to conclude for the additive interaction. We believe there is a limited risk of publication bias as several studies reporting negative results were published. Conclusion There are no multiplicative interactions between tobacco smoking and occupational lung carcinogens, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Even though, specific programs should be developed and promoted to reduce concomitantly the exposure to occupational lung carcinogens and tobacco

Approaches to radiation guidelines for space travel

International Nuclear Information System (INIS)

Fry, R.J.M.

1984-01-01

There are obvious risks in space travel that have loomed larger than any risk from radiation. Nevertheless, NASA has maintained a radiation program that has involved maintenance of records of radiation exposure, and planning so that the astronauts' exposures are kept as low as possible, and not just within the current guidelines. These guidelines are being reexamined currently by NCRP Committee 75 because new information is available, for example, risk estimates for radiation-induced cancer and about the effects of HZE particles. The current career limit is 400 rem to the blood forming organs. The appropriateness of this limit and its basis are being examined as well as the limits for specific organs. There is now considerably more information about age-dependency for radiation effects and this will be taken into account. In 1973 a committee of the National Research Council made a separate study of HZE particle effects and it was concluded that the attendant risks did not pose a hazard for low inclination near-earth orbit missions. Since that time work has been carried out on the so-called microlesions caused by HZE particles and on the relative carcinogenic effect of heavy ions, including iron. A remaining question is whether the fluence of HZE particles could reach levels of concern in missions under consideration. Finally, it is the intention of the committee to indicate clearly the areas requiring further research. 26 references, 1 figure, 7 tables

Compliance with practice guidelines: clinical autonomy revisited

NARCIS (Netherlands)

Klazinga, N.

1994-01-01

The development of practice guidelines is gaining popularity in both North America and Europe. This review article explores the different reasons behind guideline development, the methodologies used and the effects assessed so far. Experience since 1982 with a guideline development programme at CBO

Inspector qualification guidelines

International Nuclear Information System (INIS)

Batty, A.C.; Van Binnebeek, J.J.; Ericsson, P.O.; Fisher, J.C.; Geiger, P.; Grandame, M.; Grimes, B.K.; Joode, A. de; Kaufer, B.; Kinoshita, M.; Klonk, H.; Koizumi, H.; Maeda, N.; Maqua, M.; Perez del Moral, C.; Roselli, F.; Warren, T.; Zimmerman, R.

1994-07-01

The OECD Nuclear Energy Agency Committee on Nuclear Regulatory Activities (CNRA) has a Working Group on Inspection Practices (WGIP). The WGIP provides a forum for the exchange of Information and experience on the safety Inspection practices of regulatory authorities In the CNRA member countries. A consistent qualification process and well defined level of training for all Inspectors who participate In the safety Inspections are needed to provide consistent Inspections and reliable Inspection results. The WGIP organized in 1992 a workshop on the conduct of inspections, inspector qualification and training, and shutdown inspections at the Technical Training Center of the US NRC in Chattanooga, Tennessee. In the connection of workshop the WGIP identified a need to develop guidance for inspector qualification which could be used as a model by those who are developing their qualification practices. The inspector qualification journals of US NRC provided a good basis for the work. The following inspector qualification guideline has been developed for guidance of qualification of a new inspector recruited to the regulatory body. This guideline has been developed for helping the supervisors and training officers to give the initial training and familiarization to the duties of a new inspector in a controlled manner. US NRC inspector qualification journals have been used to define the areas of attention. This guideline provides large flexibility for application in different type organizations. Large organizations can develop separate qualification journals for each inspector positions. Small regulatory bodies can develop individual training programmes by defining the necessary training topics on case by case basis. E.g. the guideline can be used to define the qualifications of contracted inspectors used in some countries. The appropriate part would apply. Annex 1 gives two examples how this guideline could be applied

Inspector qualification guidelines

Energy Technology Data Exchange (ETDEWEB)

Batty, A. C.; Van Binnebeek, J. J.; Ericsson, P. O.; Fisher, J. C.; Geiger, P.; Grandame, M.; Grimes, B. K.; Joode, A. de; Kaufer, B.; Kinoshita, M.; Klonk, H.; Koizumi, H.; Maeda, N.; Maqua, M.; Perez del Moral, C.; Roselli, F.; Warren, T.; Zimmerman, R.

1994-07-15

The OECD Nuclear Energy Agency Committee on Nuclear Regulatory Activities (CNRA) has a Working Group on Inspection Practices (WGIP). The WGIP provides a forum for the exchange of Information and experience on the safety Inspection practices of regulatory authorities In the CNRA member countries. A consistent qualification process and well defined level of training for all Inspectors who participate In the safety Inspections are needed to provide consistent Inspections and reliable Inspection results. The WGIP organized in 1992 a workshop on the conduct of inspections, inspector qualification and training, and shutdown inspections at the Technical Training Center of the US NRC in Chattanooga, Tennessee. In the connection of workshop the WGIP identified a need to develop guidance for inspector qualification which could be used as a model by those who are developing their qualification practices. The inspector qualification journals of US NRC provided a good basis for the work. The following inspector qualification guideline has been developed for guidance of qualification of a new inspector recruited to the regulatory body. This guideline has been developed for helping the supervisors and training officers to give the initial training and familiarization to the duties of a new inspector in a controlled manner. US NRC inspector qualification journals have been used to define the areas of attention. This guideline provides large flexibility for application in different type organizations. Large organizations can develop separate qualification journals for each inspector positions. Small regulatory bodies can develop individual training programmes by defining the necessary training topics on case by case basis. E.g. the guideline can be used to define the qualifications of contracted inspectors used in some countries. The appropriate part would apply. Annex 1 gives two examples how this guideline could be applied.

Considerations in the development of generic human health-based soil quality guidelines for uranium

International Nuclear Information System (INIS)

Richardson, G.M.; Petrovic, S.; Purtill, C.; Wilson, R.

2006-01-01

At the current time in Canada, no human health-based generic (national) soil quality guidelines (SQG HH ) exist for uranium. This paper explores some of the various methods that could be used to develop human health soil guideline values for this element. To determine possible values that may be appropriate for use in Canada, the authors have applied both the existing CCME approach (1996) and the draft revised CCME approach (2005) to estimate possible SQG HH for uranium for various land uses. (author)

Carcinogenicity of a medicinal ozokerite and its constituents

Energy Technology Data Exchange (ETDEWEB)

Ruchkovskii, B; Borisiuk, I P; Tiktin, L A

1970-01-01

Fluorimetric analysis and skin painting tests on mice demonstrated that ceresin (a medicinal ozokerite) contains carcinogens. In the USSR, ceresin is applied to the skin or rectal and vaginal mucosa for the treatment of a variety of diseases. Ceresin and its components were tested on 460 male non-inbred mice (aged 2 to 2.5 mo) by applying either the melted substance or a 60% benzene solution of it to the skin in 30-mg doses (2 admin./week x 10 mo). Skin papillomas were produced after latent periods of 4.5 to 9 mo by paraffin, petrolatum, heavy mineral oil and 1/2 ceresin samples. Squamous cell carcinomas of the skin were seen in 2 mice painted with mineral oil. Fluorimetric analysis of ceresin demonstrated several polycyclic hydrocarbons, identified as 3,4-benzpyrene (BP) benzo(ghi) perylene, and perylene. An aqueous extract of crude ozokerite contained traces of BP, while a benzene extract contained 70 to 77 microg/kg. It is recommended that petroleum products which are commonly used to improve the consistency of ceresin be analyzed for the presence of carcinogens before use.

Quantification of the carcinogenic effect of polycyclic aromatic hydrocarbons in used engine oil by topical application onto the skin of mice.

Science.gov (United States)

Grimmer, G; Dettbarn, G; Brune, H; Deutsch-Wenzel, R; Misfeld, J

1982-01-01

The purpose of this investigation was to identify the substances mainly responsible for the carcinogenic effect of used engine oil from gasoline engines using topical application as a carcinogen-specific bioassay. This was performed by comparison of the tumorigenic effect of single fractions with that of an unseparated sample of the lubricating oil. The probit analysis of the results shows: 1) The used engine oil, from gasoline-driven automobiles, investigated provoked local tumors after long-term application to the dorsal skin of mice. The incidence of carcinoma depended on the dose of the oil. 2) The fraction of the polycyclic aromatic hydrocarbons (PAH) containing more than three rings accounts for about 70% of the total carcinogenicity in the case of crankcase oil. This fraction constitutes only up to 1.14% by weight of the total oil sample. 3) The content of benzo(a)pyrene (216.8 mg/kg) accounts for 18% of the total carcinogenicity of the used oil. 4) Regarding the reduced carcinogenicity of the oil sample, which was reconstituted from all fractions, it seems possible that some of the carcinogenic substances were lost due to volatility, with evaporation of the solvents from the oil-fractionation processes. 5) Regarding the small effect of the PAH-free fraction, as well as the equal carcinogenic effects of the PAH-fraction (containing more than three rings) and the reconstituted oil sample, no hints for a co-carcinogenic activity were obtained.

Commentary on Stiers and colleagues' guidelines for competency development and measurement in rehabilitation psychology postdoctoral training.

Science.gov (United States)

Hatcher, Robert L

2015-05-01

Comments on the article, "Guidelines for competency development and measurement in rehabilitation psychology postdoctoral training," by Stiers et al. (see record 2014-55195-001). Stiers and colleagues have provided a thorough and well-conceived set of guidelines that lay out the competencies expected for graduates of postdoctoral residencies in rehabilitation psychology, accompanied by a set of more specific, observable indicators of the residents' competence level. This work is an important aspect of the broader project of the Rehabilitation Psychology Specialty Council (APA Division 22, the American Board of Rehabilitation Psychology, the Foundation for Rehabilitation Psychology, the Academy of Rehabilitation Psychology, and the Council of Rehabilitation Psychology Postdocotral Training Programs) to develop overall guidelines for programs providing postdoctoral training in this field (Stiers et al., 2012). (c) 2015 APA, all rights reserved).

Reaching beyond the review of research evidence: a qualitative study of decision making during the development of clinical practice guidelines for disease prevention in healthcare.

Science.gov (United States)

Richter Sundberg, Linda; Garvare, Rickard; Nyström, Monica Elisabeth

2017-05-11

The judgment and decision making process during guideline development is central for producing high-quality clinical practice guidelines, but the topic is relatively underexplored in the guideline research literature. We have studied the development process of national guidelines with a disease-prevention scope produced by the National board of Health and Welfare (NBHW) in Sweden. The NBHW formal guideline development model states that guideline recommendations should be based on five decision-criteria: research evidence; curative/preventive effect size, severity of the condition; cost-effectiveness; and ethical considerations. A group of health profession representatives (i.e. a prioritization group) was assigned the task of ranking condition-intervention pairs for guideline recommendations, taking into consideration the multiple decision criteria. The aim of this study was to investigate the decision making process during the two-year development of national guidelines for methods of preventing disease. A qualitative inductive longitudinal case study approach was used to investigate the decision making process. Questionnaires, non-participant observations of nine two-day group meetings, and documents provided data for the analysis. Conventional and summative qualitative content analysis was used to analyse data. The guideline development model was modified ad-hoc as the group encountered three main types of dilemmas: high quality evidence vs. low adoptability of recommendation; insufficient evidence vs. high urgency to act; and incoherence in assessment and prioritization within and between four different lifestyle areas. The formal guideline development model guided the decision-criteria used, but three new or revised criteria were added by the group: 'clinical knowledge and experience', 'potential guideline consequences' and 'needs of vulnerable groups'. The frequency of the use of various criteria in discussions varied over time. Gender, professional status

Chronic Dermal Toxicity of Epoxy Resins I. Skin Carcinogenic Potency and General Toxicity

Energy Technology Data Exchange (ETDEWEB)

Holland, J.M.

2001-01-16

Epoxy resins are a diverse class of chemicals that differ in structure, physical properties, and, presumably, biological activity. The purpose of these experiments was to compare the chronic dermal toxicity and carcinogenicity of selected commercial epoxy resins and to determine the potential for positive synergistic carcinogenic interactions between different resins. This work is an extension and continuation of a Department of Energy sponsored program to evaluate epoxy resins for potential occupational health risks. The materials examined were chosen on the basis of their interest to the U.S. government. They are representative of the manufacturer's production at the time, and therefore the data are completely valid only for the specific production period. Results of the experimental exposures will be reported in two parts. This report describes the test materials, their chemical and physical characteristics and the experimental design. General (systemic) toxicity will be evaluated and the skin carcinogenicity of the materials compared. A subsequent report will provide morphological descriptions of skin and significant internal pathology induced by the various treatments.

An overview of the report: Correlation between carcinogenic potency and the maximum tolerated dose: Implications for risk assessment

International Nuclear Information System (INIS)

Krewski, D.; Gaylor, D.W.; Soms, A.P.; Szyszkowicz, M.

1993-01-01

Current practice in carcinogen bioassay calls for exposure of experimental animals at doses up to and including the maximum tolerated dose (MTD). Such studies have been used to compute measures of carcinogenic potency such as the TD 50 as well as unit risk factors such as q 1 for predicting low-dose risks. Recent studies have indicated that these measures of carcinogenic potency are highly correlated with the MTD. Carcinogenic potency has also been shown to be correlated with indicators of mutagenicity and toxicity. Correlation of the MTDs for rats and mice implies a corresponding correlation in TD 50 values for these two species. The implications of these results for cancer risk assessment are examined in light of the large variation in potency among chemicals known to induce tumors in rodents. 119 refs., 2 figs., 4 tabs

AREVA sustainable development indicators guidelines; Guide methodologique des indicateurs developpement durable AREVA

Energy Technology Data Exchange (ETDEWEB)

NONE

2003-12-01

These guidelines set out the procedures used to measure and report the sustainable development and continuous progress data and indicators used within the Areva Group. It defines the scope of the guide, the list of indicators, the measurement and calculation procedures, the internal and external audits. (A.L.B.)