Evaluation of DNA microarray results in the Toxicogenomics Project (TGP) consortium in Japan.

Science.gov (United States)

Noriyuki, Nakatsu; Igarashi, Yoshinobu; Ono, Atsushi; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

2012-01-01

An important technology used in toxicogenomic drug discovery research is the microarray, which enables researchers to simultaneously analyze the expression of a large number of genes. To build a database and data analysis system for use in assessing the safety of drugs and drug candidates, in 2002 we conducted a 5-year collaborative study in the Toxicogenomics Project (TGP1) in Japan. Experimental data generated by such studies must be validated by different laboratories for robust and accurate analysis. For this purpose, we conducted intra- and inter-laboratory validation studies with participating companies in the second collaborative study in the Toxicogenomics Project (TGP2). Gene expression in the liver of rats treated with acetaminophen (APAP) was independently examined by the participating companies using Affymetrix GeneChip microarrays. The intra- and inter-laboratory reproducibility of the data was evaluated using hierarchical clustering analysis. The toxicogenomics results were highly reproducible, indicating that the gene expression data generated in our TGP1 project is reliable and compatible with the data generated by the participating laboratories.

Text mining effectively scores and ranks the literature for improving chemical-gene-disease curation at the comparative toxicogenomics database.

Directory of Open Access Journals (Sweden)

Allan Peter Davis

Full Text Available The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/ is a public resource that curates interactions between environmental chemicals and gene products, and their relationships to diseases, as a means of understanding the effects of environmental chemicals on human health. CTD provides a triad of core information in the form of chemical-gene, chemical-disease, and gene-disease interactions that are manually curated from scientific articles. To increase the efficiency, productivity, and data coverage of manual curation, we have leveraged text mining to help rank and prioritize the triaged literature. Here, we describe our text-mining process that computes and assigns each article a document relevancy score (DRS, wherein a high DRS suggests that an article is more likely to be relevant for curation at CTD. We evaluated our process by first text mining a corpus of 14,904 articles triaged for seven heavy metals (cadmium, cobalt, copper, lead, manganese, mercury, and nickel. Based upon initial analysis, a representative subset corpus of 3,583 articles was then selected from the 14,094 articles and sent to five CTD biocurators for review. The resulting curation of these 3,583 articles was analyzed for a variety of parameters, including article relevancy, novel data content, interaction yield rate, mean average precision, and biological and toxicological interpretability. We show that for all measured parameters, the DRS is an effective indicator for scoring and improving the ranking of literature for the curation of chemical-gene-disease information at CTD. Here, we demonstrate how fully incorporating text mining-based DRS scoring into our curation pipeline enhances manual curation by prioritizing more relevant articles, thereby increasing data content, productivity, and efficiency.

Text Mining Effectively Scores and Ranks the Literature for Improving Chemical-Gene-Disease Curation at the Comparative Toxicogenomics Database

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Johnson, Robin J.; Lay, Jean M.; Lennon-Hopkins, Kelley; Saraceni-Richards, Cynthia; Sciaky, Daniela; Murphy, Cynthia Grondin; Mattingly, Carolyn J.

2013-01-01

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is a public resource that curates interactions between environmental chemicals and gene products, and their relationships to diseases, as a means of understanding the effects of environmental chemicals on human health. CTD provides a triad of core information in the form of chemical-gene, chemical-disease, and gene-disease interactions that are manually curated from scientific articles. To increase the efficiency, productivity, and data coverage of manual curation, we have leveraged text mining to help rank and prioritize the triaged literature. Here, we describe our text-mining process that computes and assigns each article a document relevancy score (DRS), wherein a high DRS suggests that an article is more likely to be relevant for curation at CTD. We evaluated our process by first text mining a corpus of 14,904 articles triaged for seven heavy metals (cadmium, cobalt, copper, lead, manganese, mercury, and nickel). Based upon initial analysis, a representative subset corpus of 3,583 articles was then selected from the 14,094 articles and sent to five CTD biocurators for review. The resulting curation of these 3,583 articles was analyzed for a variety of parameters, including article relevancy, novel data content, interaction yield rate, mean average precision, and biological and toxicological interpretability. We show that for all measured parameters, the DRS is an effective indicator for scoring and improving the ranking of literature for the curation of chemical-gene-disease information at CTD. Here, we demonstrate how fully incorporating text mining-based DRS scoring into our curation pipeline enhances manual curation by prioritizing more relevant articles, thereby increasing data content, productivity, and efficiency. PMID:23613709

Integrating genetic and toxicogenomic information for determining underlying susceptibility to developmental disorders.

Science.gov (United States)

Robinson, Joshua F; Port, Jesse A; Yu, Xiaozhong; Faustman, Elaine M

2010-10-01

To understand the complex etiology of developmental disorders, an understanding of both genetic and environmental risk factors is needed. Human and rodent genetic studies have identified a multitude of gene candidates for specific developmental disorders such as neural tube defects (NTDs). With the emergence of toxicogenomic-based assessments, scientists now also have the ability to compare and understand the expression of thousands of genes simultaneously across strain, time, and exposure in developmental models. Using a systems-based approach in which we are able to evaluate information from various parts and levels of the developing organism, we propose a framework for integrating genetic information with toxicogenomic-based studies to better understand gene-environmental interactions critical for developmental disorders. This approach has allowed us to characterize candidate genes in the context of variables critical for determining susceptibility such as strain, time, and exposure. Using a combination of toxicogenomic studies and complementary bioinformatic tools, we characterize NTD candidate genes during normal development by function (gene ontology), linked phenotype (disease outcome), location, and expression (temporally and strain-dependent). In addition, we show how environmental exposures (cadmium, methylmercury) can influence expression of these genes in a strain-dependent manner. Using NTDs as an example of developmental disorder, we show how simple integration of genetic information from previous studies into the standard microarray design can enhance analysis of gene-environment interactions to better define environmental exposure-disease pathways in sensitive and resistant mouse strains. © Wiley-Liss, Inc.

EPA'S TOXICOGENOMICS PARTNERSHIPS ACROSS GOVERNMENT, ACADEMIA AND INDUSTRY

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Genomics, proteomics and metabonomics technologies are transforming the science of toxicology, and concurrent advances in computing and informatics are providing management and analysis solutions for this onslaught of toxicogenomic data. EPA has been actively developing an intra...

TOXsIgN: a cross-species repository for toxicogenomic signatures.

Science.gov (United States)

Darde, Thomas A; Gaudriault, Pierre; Beranger, Rémi; Lancien, Clément; Caillarec-Joly, Annaëlle; Sallou, Olivier; Bonvallot, Nathalie; Chevrier, Cécile; Mazaud-Guittot, Séverine; Jégou, Bernard; Collin, Olivier; Becker, Emmanuelle; Rolland, Antoine D; Chalmel, Frédéric

2018-01-27

At the same time that toxicologists express increasing concern about reproducibility in this field, the development of dedicated databases has already smoothed the path toward improving the storage and exchange of raw toxicogenomic data. Nevertheless, none provides access to analyzed and interpreted data as originally reported in scientific publications. Given the increasing demand for access to this information, we developed TOXsIgN, a repository for TOXicogenomic sIgNatures. The TOXsIgN repository provides a flexible environment that facilitates online submission, storage, and retrieval of toxicogenomic signatures by the scientific community. It currently hosts 754 projects that describe more than 450 distinct chemicals and their 8491 associated signatures. It also provides users with a working environment containing a powerful search engine as well as bioinformatics/biostatistics modules that enable signature comparisons or enrichment analyses. The TOXsIgN repository is freely accessible at http://toxsign.genouest.org. Website implemented in Python, JavaScript, and MongoDB, with all major browsers supported. frederic.chalmel@inserm.fr. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Toxicogenomic analysis of the hepatic effects of perfluorooctanoic acid on rare minnows (Gobiocypris rarus)

International Nuclear Information System (INIS)

Wei Yanhong; Liu Yang; Wang Jianshe; Tao Yi; Dai Jiayin

2008-01-01

Perfluorooctanoic acid (PFOA) is a ubiquitous environmental contaminant that has been detected in a variety of terrestrial and aquatic organisms. To assess the effects of PFOA in fish and predict its potential mode of action, a toxicogenomic approach was applied to hepatic gene expression profile analysis in male and female rare minnows (Gobiocypris rarus) using a custom cDNA microarray containing 1773 unique genes. Rare minnows were treated with continuous flow-through exposure to PFOA at concentrations of 3, 10, and 30 mg/L for 28 days. Based on the observed histopathological changes, the livers from fish exposed to 10 mg/L PFOA were selected for further hepatic gene expression analysis. While 124 and 171 genes were significantly altered by PFOA in males and females, respectively, of which 43 genes were commonly regulated in both sexes. The affected genes are involved in multiple biological processes, including lipid metabolism and transport, hormone action, immune responses, and mitochondrial functions. PFOA exposure significantly suppressed genes involved in fatty acid biosynthesis and transport but induced genes associated with intracellular trafficking of cholesterol. Alterations in expression of genes associated with mitochondrial fatty acid β-oxidation were only observed in female rare minnows. In addition, PFOA inhibited genes responsible for thyroid hormone biosynthesis and significantly induced estrogen-responsive genes. These findings implicate PFOA in endocrine disruption. This work contributes not only to the elucidation of the potential mode of toxicity of PFOA to aquatic organisms but also to the use of toxicogenomic approaches to address issues in environmental toxicology

Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets.

Science.gov (United States)

Scott, D J; Devonshire, A S; Adeleye, Y A; Schutte, M E; Rodrigues, M R; Wilkes, T M; Sacco, M G; Gribaldo, L; Fabbri, M; Coecke, S; Whelan, M; Skinner, N; Bennett, A; White, A; Foy, C A

2011-11-28

The application of toxicogenomics as a predictive tool for chemical risk assessment has been under evaluation by the toxicology community for more than a decade. However, it predominately remains a tool for investigative research rather than for regulatory risk assessment. In this study, we assessed whether the current generation of microarray technology in combination with an in vitro experimental design was capable of generating robust, reproducible data of sufficient quality to show promise as a tool for regulatory risk assessment. To this end, we designed a prospective collaborative study to determine the level of inter- and intra-laboratory reproducibility between three independent laboratories. All test centres (TCs) adopted the same protocols for all aspects of the toxicogenomic experiment including cell culture, chemical exposure, RNA extraction, microarray data generation and analysis. As a case study, the genotoxic carcinogen benzo[a]pyrene (B[a]P) and the human hepatoma cell line HepG2 were used to generate three comparable toxicogenomic data sets. High levels of technical reproducibility were demonstrated using a widely employed gene expression microarray platform. While differences at the global transcriptome level were observed between the TCs, a common subset of B[a]P responsive genes (n=400 gene probes) was identified at all TCs which included many genes previously reported in the literature as B[a]P responsive. These data show promise that the current generation of microarray technology, in combination with a standard in vitro experimental design, can produce robust data that can be generated reproducibly in independent laboratories. Future work will need to determine whether such reproducible in vitro model(s) can be predictive for a range of toxic chemicals with different mechanisms of action and thus be considered as part of future testing regimes for regulatory risk assessment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Toxicogenomic analysis of gene expression changes in rat liver after a 28-day oral benzene exposure

NARCIS (Netherlands)

Heijne, W.H.M.; Jonker, D.; Stierum, R.H.; Ommen, van B.; Groten, J.P.

2005-01-01

Benzene is an industrial chemical, component of automobile exhaust and cigarette smoke. After hepatic bioactivation benzene induces bone marrow, blood and hepatic toxicity. Using a toxicogenomics approach this study analysed the effects of benzene at three dose levels on gene expression in the liver

An information-rich alternative, chemicals testing strategy using a high definition toxicogenomics and zebrafish (Danio rerio) embryos

NARCIS (Netherlands)

Sawle, Ashley D.; Wit, Ernst; Whale, Graham; Cossins, Andrew R.

2010-01-01

Large-scale toxicogenomic screening approaches offer great promise for generating a bias-free system-wide view of toxicological effects and modes-of-action of chemicals and ecotoxicants. However, early applications of microarray technology have identified relatively small groups of responding genes

EPA SCIENCE FORUM - EPA'S TOXICOGENOMICS PARTNERSHIPS ACROSS GOVERNMENT, ACADEMIA AND INDUSTRY

Science.gov (United States)

Over the past decade genomics, proteomics and metabonomics technologies have transformed the science of toxicology, and concurrent advances in computing and informatics have provided management and analysis solutions for this onslaught of toxicogenomic data. EPA has been actively...

Intersection of toxicogenomics and high throughput screening in the Tox21 program: an NIEHS perspective.

Science.gov (United States)

Merrick, B Alex; Paules, Richard S; Tice, Raymond R

Humans are exposed to thousands of chemicals with inadequate toxicological data. Advances in computational toxicology, robotic high throughput screening (HTS), and genome-wide expression have been integrated into the Tox21 program to better predict the toxicological effects of chemicals. Tox21 is a collaboration among US government agencies initiated in 2008 that aims to shift chemical hazard assessment from traditional animal toxicology to target-specific, mechanism-based, biological observations using in vitro assays and lower organism models. HTS uses biocomputational methods for probing thousands of chemicals in in vitro assays for gene-pathway response patterns predictive of adverse human health outcomes. In 1999, NIEHS began exploring the application of toxicogenomics to toxicology and recent advances in NextGen sequencing should greatly enhance the biological content obtained from HTS platforms. We foresee an intersection of new technologies in toxicogenomics and HTS as an innovative development in Tox21. Tox21 goals, priorities, progress, and challenges will be reviewed.

Prediction model of potential hepatocarcinogenicity of rat hepatocarcinogens using a large-scale toxicogenomics database

International Nuclear Information System (INIS)

Uehara, Takeki; Minowa, Yohsuke; Morikawa, Yuji; Kondo, Chiaki; Maruyama, Toshiyuki; Kato, Ikuo; Nakatsu, Noriyuki; Igarashi, Yoshinobu; Ono, Atsushi; Hayashi, Hitomi; Mitsumori, Kunitoshi; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

2011-01-01

The present study was performed to develop a robust gene-based prediction model for early assessment of potential hepatocarcinogenicity of chemicals in rats by using our toxicogenomics database, TG-GATEs (Genomics-Assisted Toxicity Evaluation System developed by the Toxicogenomics Project in Japan). The positive training set consisted of high- or middle-dose groups that received 6 different non-genotoxic hepatocarcinogens during a 28-day period. The negative training set consisted of high- or middle-dose groups of 54 non-carcinogens. Support vector machine combined with wrapper-type gene selection algorithms was used for modeling. Consequently, our best classifier yielded prediction accuracies for hepatocarcinogenicity of 99% sensitivity and 97% specificity in the training data set, and false positive prediction was almost completely eliminated. Pathway analysis of feature genes revealed that the mitogen-activated protein kinase p38- and phosphatidylinositol-3-kinase-centered interactome and the v-myc myelocytomatosis viral oncogene homolog-centered interactome were the 2 most significant networks. The usefulness and robustness of our predictor were further confirmed in an independent validation data set obtained from the public database. Interestingly, similar positive predictions were obtained in several genotoxic hepatocarcinogens as well as non-genotoxic hepatocarcinogens. These results indicate that the expression profiles of our newly selected candidate biomarker genes might be common characteristics in the early stage of carcinogenesis for both genotoxic and non-genotoxic carcinogens in the rat liver. Our toxicogenomic model might be useful for the prospective screening of hepatocarcinogenicity of compounds and prioritization of compounds for carcinogenicity testing. - Highlights: →We developed a toxicogenomic model to predict hepatocarcinogenicity of chemicals. →The optimized model consisting of 9 probes had 99% sensitivity and 97% specificity. �

Toxicogenomics: A New Paradigm for Nanotoxicity Evaluation.

Science.gov (United States)

Dwivedi, Sourabh; Saquib, Quaiser; Ahmad, Bilal; Ansari, Sabiha M; Azam, Ameer; Musarrat, Javed

2018-01-01

The wider applications of nanoparticles (NPs) has evoked a world-wide concern due to their possible risk of toxicity in humans and other organisms. Aggregation and accumulation of NPs into cell leads to their interaction with biological macromolecules including proteins, nucleic acids and cellular organelles, which eventually induce toxicological effects. Application of toxicogenomics to investigate molecular pathway-based toxicological consequences has opened new vistas in nanotoxicology research. Indeed, genomic approaches appeared as a new paradigm in terms of providing information at molecular levels and have been proven to be as a powerful tool for identification and quantification of global shifts in gene expression. Toxicological responses of NPs have been discussed in this chapter with the aim to provide a clear understanding of the molecular mechanism of NPs induced toxicity both in in vivo and in vitro test models.

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database.

Directory of Open Access Journals (Sweden)

Allan Peter Davis

Full Text Available Strategies for discovering common molecular events among disparate diseases hold promise for improving understanding of disease etiology and expanding treatment options. One technique is to leverage curated datasets found in the public domain. The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/ manually curates chemical-gene, chemical-disease, and gene-disease interactions from the scientific literature. The use of official gene symbols in CTD interactions enables this information to be combined with the Gene Ontology (GO file from NCBI Gene. By integrating these GO-gene annotations with CTD's gene-disease dataset, we produce 753,000 inferences between 15,700 GO terms and 4,200 diseases, providing opportunities to explore presumptive molecular underpinnings of diseases and identify biological similarities. Through a variety of applications, we demonstrate the utility of this novel resource. As a proof-of-concept, we first analyze known repositioned drugs (e.g., raloxifene and sildenafil and see that their target diseases have a greater degree of similarity when comparing GO terms vs. genes. Next, a computational analysis predicts seemingly non-intuitive diseases (e.g., stomach ulcers and atherosclerosis as being similar to bipolar disorder, and these are validated in the literature as reported co-diseases. Additionally, we leverage other CTD content to develop testable hypotheses about thalidomide-gene networks to treat seemingly disparate diseases. Finally, we illustrate how CTD tools can rank a series of drugs as potential candidates for repositioning against B-cell chronic lymphocytic leukemia and predict cisplatin and the small molecule inhibitor JQ1 as lead compounds. The CTD dataset is freely available for users to navigate pathologies within the context of extensive biological processes, molecular functions, and cellular components conferred by GO. This inference set should aid researchers, bioinformaticists, and

High-Density Real-Time PCR-Based in Vivo Toxicogenomic Screen to Predict Organ-Specific Toxicity

Directory of Open Access Journals (Sweden)

Laszlo G. Puskas

2011-09-01

Full Text Available Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present study our objective was to extend in vivo toxicogenomic screening from analyzing one or a few tissues to multiple organs, including heart, kidney, brain, liver and spleen. Nanocapillary quantitative real-time PCR (QRT-PCR was used in the study, due to its higher throughput, sensitivity and reproducibility, and larger dynamic range compared to DNA microarray technologies. Based on previous data, 56 gene markers were selected coding for proteins with different functions, such as proteins for acute phase response, inflammation, oxidative stress, metabolic processes, heat-shock response, cell cycle/apoptosis regulation and enzymes which are involved in detoxification. Some of the marker genes are specific to certain organs, and some of them are general indicators of toxicity in multiple organs. Utility of the nanocapillary QRT-PCR platform was demonstrated by screening different references, as well as discovery of drug-like compounds for their gene expression profiles in different organs of treated mice in an acute experiment. For each compound, 896 QRT-PCR were done: four organs were used from each of the treated four animals to monitor the relative expression of 56 genes. Based on expression data of the discovery gene set of toxicology biomarkers the cardio- and nephrotoxicity of doxorubicin and sulfasalazin, the hepato- and nephrotoxicity of rotenone, dihydrocoumarin and aniline, and the liver toxicity of 2,4-diaminotoluene could be confirmed. The acute heart and kidney toxicity of the active metabolite SN-38 from its less toxic prodrug, irinotecan could be differentiated, and two novel gene markers for hormone replacement therapy were identified

Design issues in toxicogenomics using DNA microarray experiment

International Nuclear Information System (INIS)

Lee, Kyoung-Mu; Kim, Ju-Han; Kang, Daehee

2005-01-01

The methods of toxicogenomics might be classified into omics study (e.g., genomics, proteomics, and metabolomics) and population study focusing on risk assessment and gene-environment interaction. In omics study, microarray is the most popular approach. Genes falling into several categories (e.g., xenobiotics metabolism, cell cycle control, DNA repair etc.) can be selected up to 20,000 according to a priori hypothesis. The appropriate type of samples and species should be selected in advance. Multiple doses and varied exposure durations are suggested to identify those genes clearly linked to toxic response. Microarray experiments can be affected by numerous nuisance variables including experimental designs, sample extraction, type of scanners, etc. The number of slides might be determined from the magnitude and variance of expression change, false-positive rate, and desired power. Instead, pooling samples is an alternative. Online databases on chemicals with known exposure-disease outcomes and genetic information can aid the interpretation of the normalized results. Gene function can be inferred from microarray data analyzed by bioinformatics methods such as cluster analysis. The population study often adopts hospital-based or nested case-control design. Biases in subject selection and exposure assessment should be minimized, and confounding bias should also be controlled for in stratified or multiple regression analysis. Optimal sample sizes are dependent on the statistical test for gene-to-environment or gene-to-gene interaction. The design issues addressed in this mini-review are crucial in conducting toxicogenomics study. In addition, integrative approach of exposure assessment, epidemiology, and clinical trial is required

Application of toxicogenomics in hepatic systems toxicology for risk assessment: Acetaminophen as a case study

NARCIS (Netherlands)

Kienhuis, A.S.; Bessems, J.G.M.; Pennings, J.L.A.; Driessen, M.; Luijten, M.; Delft, van J.H.M.; Ven, van der L.T.M.

2011-01-01

Hepatic systems toxicology is the integrative analysis of toxicogenomic technologies, e.g., transcriptomics, proteomics, and metabolomics, in combination with traditional toxicology measures to improve the understanding of mechanisms of hepatotoxic action. Hepatic toxicology studies that have

Evaluation of Bioinformatics Approaches for Next-Generation Sequencing Analysis of microRNAs with a Toxicogenomics Study Design

Directory of Open Access Journals (Sweden)

Halil Bisgin

2018-02-01

Full Text Available MicroRNAs (miRNAs are key post-transcriptional regulators that affect protein translation by targeting mRNAs. Their role in disease etiology and toxicity are well recognized. Given the rapid advancement of next-generation sequencing techniques, miRNA profiling has been increasingly conducted with RNA-seq, namely miRNA-seq. Analysis of miRNA-seq data requires several steps: (1 mapping the reads to miRBase, (2 considering mismatches during the hairpin alignment (windowing, and (3 counting the reads (quantification. The choice made in each step with respect to the parameter settings could affect miRNA quantification, differentially expressed miRNAs (DEMs detection and novel miRNA identification. Furthermore, these parameters do not act in isolation and their joint effects impact miRNA-seq results and interpretation. In toxicogenomics, the variation associated with parameter setting should not overpower the treatment effect (such as the dose/time-dependent effect. In this study, four commonly used miRNA-seq analysis tools (i.e., miRDeep2, miRExpress, miRNAkey, sRNAbench were comparatively evaluated with a standard toxicogenomics study design. We tested 30 different parameter settings on miRNA-seq data generated from thioacetamide-treated rat liver samples for three dose levels across four time points, followed by four normalization options. Because both miRExpress and miRNAkey yielded larger variation than that of the treatment effects across multiple parameter settings, our analyses mainly focused on the side-by-side comparison between miRDeep2 and sRNAbench. While the number of miRNAs detected by miRDeep2 was almost the subset of those detected by sRNAbench, the number of DEMs identified by both tools was comparable under the same parameter settings and normalization method. Change in the number of nucleotides out of the mature sequence in the hairpin alignment (window option yielded the largest variation for miRNA quantification and DEMs

A DATABASE FOR TRACKING TOXICOGENOMIC SAMPLES AND PROCEDURES WITH GENOMIC, PROTEOMIC AND METABONOMIC COMPONENTS

Science.gov (United States)

A Database for Tracking Toxicogenomic Samples and Procedures with Genomic, Proteomic and Metabonomic Components Wenjun Bao1, Jennifer Fostel2, Michael D. Waters2, B. Alex Merrick2, Drew Ekman3, Mitchell Kostich4, Judith Schmid1, David Dix1Office of Research and Developmen...

Yeast Toxicogenomics: genome-wide responses to chemical stresses with impact in Environmental Health, Pharmacology and Biotechnology

Directory of Open Access Journals (Sweden)

Sandra Costa dos Santos

2012-04-01

Full Text Available The emerging transdisciplinary field of Toxicogenomics aims to study the cell response to a given toxicant at the genome, transcriptome, proteome and metabolome levels. This approach is expected to provide earlier and more sensitive biomarkers of toxicological responses and help in the delineation of regulatory risk assessment. The use of model organisms to gather such genomic information, through the exploitation of Omics and Bioinformatics approaches and tools, together with more focused molecular and cellular biology studies are rapidly increasing our understanding and providing an integrative view on how cells interact with their environment. The use of the model eukaryote Saccharomyces cerevisiae in the field of Toxicogenomics is discussed in this review. Despite the limitations intrinsic to the use of such a simple single cell experimental model, S. cerevisiae appears to be very useful as a first screening tool, limiting the use of animal models. Moreover, it is also one of the most interesting systems to obtain a truly global understanding of the toxicological response and resistance mechanisms, being in the frontline of systems biology research and developments. The impact of the knowledge gathered in the yeast model, through the use of Toxicogenomics approaches, is highlighted here by its use in prediction of toxicological outcomes of exposure to pesticides and pharmaceutical drugs, but also by its impact in biotechnology, namely in the development of more robust crops and in the improvement of yeast strains as cell factories.

Parallelogram approach using rat-human In vitro and rat in vivo toxicogenomics predicts acetaminophen-induced hepatotoxicity in humans

NARCIS (Netherlands)

Kienhuis, A.S.; Poll, M.C.G. van de; Wortelboer, H.; Herwijnen, M. van; Gottschalk, R.; Jong, C.H.C. de; Boorsma, A.; Paules, R.S.; Kleinjans, J.C.S.; Stierum, R.H.; Delft, J.H.M. van

2009-01-01

The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these

75 FR 1770 - An Approach to Using Toxicogenomic Data in U.S. EPA Human Health Risk Assessments: A Dibutyl...

Science.gov (United States)

2010-01-13

... qualitative aspects of the risk assessment because of the type of genomic data available for DBP. It is... Assessment (NCEA) within EPA's Office of Research and Development (ORD). Toxicogenomics is the application of... exploratory methods for analyzing genomic data for application to risk assessment and some preliminary results...

Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity : a bioinformatics perspective

NARCIS (Netherlands)

Herwig, R; Gmuender, H; Corvi, Raffaella; Bloch, K.M.; Brandenburg, A.; Castell, J; Ceelen, L; Chesne, C; Doktorova, T Y; Jennen, D; Jennings, P; Limonciel, A; Lock, E A; McMorrow, T; Phrakonkham, P; Radford-Smith, G.; Slattery, C; Stierum, R; Vilardell, M; Wittenberger, T; Yildirimman, R; Ryan, M.; Rogiers, Vera; Kleinjans, Jos

The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems,

Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models

Energy Technology Data Exchange (ETDEWEB)

Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu [R& D, Safety Science Research, Kao Corporation, Tochigi (Japan); Yoshinari, Kouichi [Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan); Honda, Hiroshi, E-mail: honda.hiroshi@kao.co.jp [R& D, Safety Science Research, Kao Corporation, Tochigi (Japan)

2017-03-01

Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. - Highlights: • Hypertrophy (H) and hypertrophic

Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models

International Nuclear Information System (INIS)

Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu; Yoshinari, Kouichi; Honda, Hiroshi

2017-01-01

Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. - Highlights: • Hypertrophy (H) and hypertrophic

An Approach to Using Toxicogenomic Data in U.S. EPA Human Health Risk Assessments: A Dibutyl Phthalate Case Study (Final Report, 2010)

Science.gov (United States)

EPA announced the availability of the final report, An Approach to Using Toxicogenomic Data in U.S. EPA Human Health Risk Assessments: A Dibutyl Phthalate Case Study. This report outlines an approach to evaluate genomic data for use in risk assessment and a case study to ...

Toxicogenomic multigene biomarker for predicting the future onset of proximal tubular injury in rats

International Nuclear Information System (INIS)

Minowa, Yohsuke; Kondo, Chiaki; Uehara, Takeki; Morikawa, Yuji; Okuno, Yasushi; Nakatsu, Noriyuki; Ono, Atsushi; Maruyama, Toshiyuki; Kato, Ikuo; Yamate, Jyoji; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

2012-01-01

Drug-induced renal tubular injury is a major concern in the preclinical safety evaluation of drug candidates. Toxicogenomics is now a generally accepted tool for identifying chemicals with potential safety problems. The specific aim of the present study was to develop a model for use in predicting the future onset of drug-induced proximal tubular injury following repeated dosing with various nephrotoxicants. In total, 41 nephrotoxic and nonnephrotoxic compounds were used for the present analysis. Male Sprague-Dawley rats were dosed orally or intravenously once daily. Animals were exposed to three different doses (low, middle, and high) of each compound, and kidney tissue was collected at 3, 6, 9, and 24 h after single dosing, and on days 4, 8, 15, and 29 after repeated dosing. Gene expression profiles were generated from kidney total RNA using Affymetrix DNA microarrays. Filter-type gene selection and linear classification algorithms were employed to discriminate future onset of proximal tubular injury. We identified genomic biomarkers for use in future onset prediction using the gene expression profiles determined on day 1, when most of the nephrotoxicants had yet to produce detectable histopathological changes. The model was evaluated using a five-fold cross validation, and achieved a sensitivity of 93% and selectivity of 90% with 19 probes. We also found that the prediction accuracy of the optimized model was substantially higher than that produced by any of the single genomic biomarkers or histopathology. The genes included in our model were primarily involved in DNA replication, cell cycle control, apoptosis, and responses to oxidative stress and chemical stimuli. In summary, our toxicogenomic model is particularly useful for predicting the future onset of proximal tubular injury.

Functional toxicogenomic profiling expands insight into modulators of formaldehyde toxicity in yeast

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Matthew North

2016-11-01

Full Text Available Formaldehyde (FA is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways–including homologous recombination, single strand annealing, and postreplication repair–were sensitive to FA, indicating FA may cause various forms of DNA damage in yeast. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance, suggesting FA may have unappreciated effects on RNA stability. Furthermore, various strains involved in osmoregulation and stress response were sensitive to FA. Together, our results are generally consistent with FA-mediated damage to both DNA and RNA. Considering DNA repair and RNA degradation pathways are evolutionarily conserved from yeast to humans, mechanisms of FA toxicity identified in yeast may be relevant to human disease and genetic susceptibility.

Asymmetric author-topic model for knowledge discovering of big data in toxicogenomics.

Science.gov (United States)

Chung, Ming-Hua; Wang, Yuping; Tang, Hailin; Zou, Wen; Basinger, John; Xu, Xiaowei; Tong, Weida

2015-01-01

The advancement of high-throughput screening technologies facilitates the generation of massive amount of biological data, a big data phenomena in biomedical science. Yet, researchers still heavily rely on keyword search and/or literature review to navigate the databases and analyses are often done in rather small-scale. As a result, the rich information of a database has not been fully utilized, particularly for the information embedded in the interactive nature between data points that are largely ignored and buried. For the past 10 years, probabilistic topic modeling has been recognized as an effective machine learning algorithm to annotate the hidden thematic structure of massive collection of documents. The analogy between text corpus and large-scale genomic data enables the application of text mining tools, like probabilistic topic models, to explore hidden patterns of genomic data and to the extension of altered biological functions. In this paper, we developed a generalized probabilistic topic model to analyze a toxicogenomics dataset that consists of a large number of gene expression data from the rat livers treated with drugs in multiple dose and time-points. We discovered the hidden patterns in gene expression associated with the effect of doses and time-points of treatment. Finally, we illustrated the ability of our model to identify the evidence of potential reduction of animal use.

Asymmetric author-topic model for knowledge discovering of big data in toxicogenomics

Directory of Open Access Journals (Sweden)

Ming-Hua eChung

2015-04-01

Full Text Available The advancement of high-throughput screening technologies facilitates the generation of massive amount of biological data, a big data phenomena in biomedical science. Yet, researchers still heavily rely on keyword search and/or literature review to navigate the databases and analyses are often done in rather small-scale. As a result, the rich information of a database has not been fully utilized, particularly for the information embedded in the interactive nature between data points that are largely ignored and buried. For the past ten years, probabilistic topic modeling has been recognized as an effective machine learning algorithm to annotate the hidden thematic structure of massive collection of documents. The analogy between text corpus and large-scale genomic data enables the application of text mining tools, like probabilistic topic models, to explore hidden patterns of genomic data and to the extension of altered biological functions. In this paper, we developed a generalized probabilistic topic model to analyze a toxicogenomics dataset that consists of a large number of gene expression data from the rat livers treated with drugs in multiple dose and time-points. We discovered the hidden patterns in gene expression associated with the effect of doses and time-points of treatment. Finally, we illustrated the ability of our model to identify the evidence of potential reduction of animal use.

Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models.

Science.gov (United States)

Liu, Shujie; Kawamoto, Taisuke; Morita, Osamu; Yoshinari, Kouichi; Honda, Hiroshi

2017-03-01

Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds. Logistic regression models have previously been used in the quantification of epidemiological risk factors. DNA microarray data from the Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System were used to identify hypertrophy-related genes that are expressed differently in hypertrophy induced by carcinogens and non-carcinogens. Data were collected for 134 chemicals (72 non-hypertrophy-inducing chemicals, 27 hypertrophy-inducing non-carcinogenic chemicals, and 15 hypertrophy-inducing carcinogenic compounds). After applying logistic ridge regression analysis, 35 genes for liver hypertrophy (e.g., Acot1 and Abcc3) and 13 genes for hypertrophic hepatocarcinogenesis (e.g., Asns and Gpx2) were selected. The predictive models built using these genes were 94.8% and 82.7% accurate, respectively. Pathway analysis of the genes indicates that, aside from a xenobiotic metabolism-related pathway as an adaptive response for liver hypertrophy, amino acid biosynthesis and oxidative responses appear to be involved in hypertrophic hepatocarcinogenesis. Early detection and toxicogenomic characterization of liver hypertrophy using our models may be useful for predicting carcinogenesis. In addition, the identified genes provide novel insight into discrimination between adverse hypertrophy associated with carcinogenesis and adaptive hypertrophy in risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

In vitro immunotoxicity of bis(tri-n-butyltin)oxide (TBTO) studied by toxicogenomics

International Nuclear Information System (INIS)

Baken, Kirsten A.; Arkusz, Joanna; Pennings, Jeroen L.A.; Vandebriel, Rob J.; Loveren, Henk van

2007-01-01

The biocide and environmental pollutant bis(tri-n-butyltin)oxide (TBTO) causes thymus atrophy in rodents. Whether the depletion of thymic lymphocytes by tributyltin compounds may be the result of inhibition of cell proliferation or induction of apoptosis is subject of debate. We examined gene expression profiles in primary rat thymocytes exposed to TBTO in vitro at dose levels of 0, 0.1, 0.3, 0.5, and 1.0 μM. By measuring cell viability and apoptosis, exposure conditions were selected that would provide information on changes in gene expression preceding or accompanying functional effects of TBTO. Several processes related to TBTO-induced toxicity were detected at the transcriptome level. Effects on lipid metabolisms appeared to be the first indication of disruption of cellular function. Many transcriptional effects of TBTO at higher dose levels were related to apoptotic processes, which corresponded to present or subsequent thymocyte apoptosis observed phenotypically. The gene expression profile was, however, not unambiguous since expression of apoptosis-related genes was both increased and decreased. Stimulation of glucocorticoid receptor signaling appeared to be a relevant underlying mechanism of action. These findings suggest that TBTO exerts its toxic effects on the thymus primarily by affecting apoptotic processes, but the possibility is discussed that this may in fact represent an early effect that precedes inhibition of cell proliferation. At the highest dose level tested, TBTO additionally repressed mitochondrial function and immune cell activation. Our in vitro toxicogenomics approach thus identified several cellular and molecular targets of TBTO that may mediate the toxicity towards thymocytes and thereby its immunosuppressive effects

Toxicogenomic analysis identifies the apoptotic pathway as the main cause of hepatotoxicity induced by tributyltin.

Science.gov (United States)

Zhou, Mi; Feng, Mei; Fu, Ling-Ling; Ji, Lin-Dan; Zhao, Jin-Shun; Xu, Jin

2016-11-01

Tributyltin (TBT) is one of the most widely used organotin biocides, which has severe endocrine-disrupting effects on marine species and mammals. Given that TBT accumulates at higher levels in the liver than in any other organ, and it acts mainly as a hepatotoxic agent, it is important to clearly delineate the hepatotoxicity of TBT. However, most of the available studies on TBT have focused on observations at the cellular level, while studies at the level of genes and proteins are limited; therefore, the molecular mechanisms of TBT-induced hepatotoxicity remains largely unclear. In the present study, we applied a toxicogenomic approach to investigate the effects of TBT on gene expression in the human normal liver cell line HL7702. Gene expression profiling identified the apoptotic pathway as the major cause of hepatotoxicity induced by TBT. Flow cytometry assays confirmed that medium- and high-dose TBT treatments significantly increased the number of apoptotic cells, and more cells underwent late apoptosis in the high-dose TBT group. The genes encoding heat shock proteins (HSPs), kinases and tumor necrosis factor receptors mediated TBT-induced apoptosis. These findings revealed novel molecular mechanisms of TBT-induced hepatotoxicity, and the current microarray data may also provide clues for future studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database

International Nuclear Information System (INIS)

Kondo, Chiaki; Minowa, Yohsuke; Uehara, Takeki; Okuno, Yasushi; Nakatsu, Noriyuki; Ono, Atsushi; Maruyama, Toshiyuki; Kato, Ikuo; Yamate, Jyoji; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

2009-01-01

Drug-induced renal tubular injury is one of the major concerns in preclinical safety evaluations. Toxicogenomics is becoming a generally accepted approach for identifying chemicals with potential safety problems. In the present study, we analyzed 33 nephrotoxicants and 8 non-nephrotoxic hepatotoxicants to elucidate time- and dose-dependent global gene expression changes associated with proximal tubular toxicity. The compounds were administered orally or intravenously once daily to male Sprague-Dawley rats. The animals were exposed to four different doses of the compounds, and kidney tissues were collected on days 4, 8, 15, and 29. Gene expression profiles were generated from kidney RNA by using Affymetrix GeneChips and analyzed in conjunction with the histopathological changes. We used the filter-type gene selection algorithm based on t-statistics conjugated with the SVM classifier, and achieved a sensitivity of 90% with a selectivity of 90%. Then, 92 genes were extracted as the genomic biomarker candidates that were used to construct the classifier. The gene list contains well-known biomarkers, such as Kidney injury molecule 1, Ceruloplasmin, Clusterin, Tissue inhibitor of metallopeptidase 1, and also novel biomarker candidates. Most of the genes involved in tissue remodeling, the immune/inflammatory response, cell adhesion/proliferation/migration, and metabolism were predominantly up-regulated. Down-regulated genes participated in cell adhesion/proliferation/migration, membrane transport, and signal transduction. Our classifier has better prediction accuracy than any of the well-known biomarkers. Therefore, the toxicogenomics approach would be useful for concurrent diagnosis of renal tubular injury.

A Drosophila model for toxicogenomics: Genetic variation in susceptibility to heavy metal exposure.

Directory of Open Access Journals (Sweden)

Shanshan Zhou

2017-07-01

Full Text Available The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag. Drosophila melanogaster is a powerful model that enables genome-wide studies for the identification of allelic variants that contribute to variation in susceptibility to environmental toxins, since the genetic background, environmental rearing conditions and toxic exposure can be precisely controlled. Here, we used extreme QTL mapping in an outbred population derived from the D. melanogaster Genetic Reference Panel to identify alleles associated with resistance to lead and/or cadmium, two ubiquitous environmental toxins that present serious health risks. We identified single nucleotide polymorphisms (SNPs associated with variation in resistance to both heavy metals as well as SNPs associated with resistance specific to each of them. The effects of these SNPs were largely sex-specific. We applied mutational and RNAi analyses to 33 candidate genes and functionally validated 28 of them. We constructed networks of candidate genes as blueprints for orthologous networks of human genes. The latter not only provided functional contexts for known human targets of heavy metal toxicity, but also implicated novel candidate susceptibility genes. These studies validate Drosophila as a translational toxicogenomics gene discovery system.

Mechanism-based risk assessment strategy for drug-induced cholestasis using the transcriptional benchmark dose derived by toxicogenomics.

Science.gov (United States)

Kawamoto, Taisuke; Ito, Yuichi; Morita, Osamu; Honda, Hiroshi

2017-01-01

Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis. The transcriptional benchmark dose (tBMD) and tBMD 95% lower limit (tBMDL) were used for quantitative analyses, which revealed three compound sub-groups that produced different types of differential gene expression; these groups of genes were mainly involved in inflammation, cholesterol biosynthesis, and oxidative stress. Furthermore, the tBMDL values for each test compound were in good agreement with the relevant no observed adverse effect level. These results indicate that our novel strategy for drug safety evaluation using mechanism-based classification and tBMDL would facilitate the application of toxicogenomics for risk assessment of cholestatic DILI.

An approach for integrating toxicogenomic data in risk assessment: The dibutyl phthalate case study

Energy Technology Data Exchange (ETDEWEB)

Euling, Susan Y., E-mail: euling.susan@epa.gov [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC (United States); Thompson, Chad M. [ToxStrategies, Inc., 23501 Cinco Ranch Blvd., Suite G265, Katy, TX 77494 (United States); Chiu, Weihsueh A. [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC (United States); Benson, Robert [U.S. Environmental Protection Agency, Region 8, Mail code 8P-W, 1595 Wynkoop Street, Denver, CO 80202 (United States)

2013-09-15

An approach for evaluating and integrating genomic data in chemical risk assessment was developed based on the lessons learned from performing a case study for the chemical dibutyl phthalate. A case study prototype approach was first developed in accordance with EPA guidance and recommendations of the scientific community. Dibutyl phthalate (DBP) was selected for the case study exercise. The scoping phase of the dibutyl phthalate case study was conducted by considering the available DBP genomic data, taken together with the entire data set, for whether they could inform various risk assessment aspects, such as toxicodynamics, toxicokinetics, and dose–response. A description of weighing the available dibutyl phthalate data set for utility in risk assessment provides an example for considering genomic data for future chemical assessments. As a result of conducting the scoping process, two questions—Do the DBP toxicogenomic data inform 1) the mechanisms or modes of action?, and 2) the interspecies differences in toxicodynamics?—were selected to focus the case study exercise. Principles of the general approach include considering the genomics data in conjunction with all other data to determine their ability to inform the various qualitative and/or quantitative aspects of risk assessment, and evaluating the relationship between the available genomic and toxicity outcome data with respect to study comparability and phenotypic anchoring. Based on experience from the DBP case study, recommendations and a general approach for integrating genomic data in chemical assessment were developed to advance the broader effort to utilize 21st century data in risk assessment. - Highlights: • Performed DBP case study for integrating genomic data in risk assessment • Present approach for considering genomic data in chemical risk assessment • Present recommendations for use of genomic data in chemical risk assessment.

Toxicogenomic analysis of N-nitrosomorpholine induced changes in rat liver: Comparison of genomic and proteomic responses and anchoring to histopathological parameters

International Nuclear Information System (INIS)

Oberemm, A.; Ahr, H.-J.; Bannasch, P.; Ellinger-Ziegelbauer, H.; Glueckmann, M.; Hellmann, J.; Ittrich, C.; Kopp-Schneider, A.; Kramer, P.-J.; Krause, E.; Kroeger, M.; Kiss, E.; Richter-Reichhelm, H.-B.; Scholz, G.; Seemann, K.; Weimer, M.; Gundert-Remy, U.

2009-01-01

A common animal model of chemical hepatocarcinogenesis was used to examine the utility of transcriptomic and proteomic data to identify early biomarkers related to chemically induced carcinogenesis. N-nitrosomorpholine, a frequently used genotoxic model carcinogen, was applied via drinking water at 120 mg/L to male Wistar rats for 7 weeks followed by an exposure-free period of 43 weeks. Seven specimens of each treatment group (untreated control and 120 mg/L N-nitrosomorpholine in drinking water) were sacrificed at nine time points during and after N-nitrosomorpholine treatment. Individual samples from the liver were prepared for histological and toxicogenomic analyses. For histological detection of preneoplastic and neoplastic tissue areas, sections were stained using antibodies against the placental form of glutathione-S-transferase (GST-P). Gene and protein expression profiles of liver tissue homogenates were analyzed using RG-U34A Affymetrix rat gene chips and two-dimensional gel electrophoresis-based proteomics, respectively. In order to compare results obtained by histopathology, transcriptomics and proteomics, GST-P-stained liver sections were evaluated morphometrically, which revealed a parallel time course of the area fraction of preneoplastic lesions and gene plus protein expression patterns. On the transcriptional level, an increase of hepatic GST-P expression was detectable as early as 3 weeks after study onset. Comparing deregulated genes and proteins, eight species were identified which showed a corresponding expression profile on both expression levels. Functional analysis suggests that these genes and corresponding proteins may be useful as biomarkers of early hepatocarcinogenesis.

Use of genomic data in risk assessment case study: I. Evaluation of the dibutyl phthalate male reproductive development toxicity data set

Energy Technology Data Exchange (ETDEWEB)

Makris, Susan L., E-mail: makris.susan@epa.gov [U.S. Environmental Protection Agency, National Center for Environmental Assessment, Office of Research and Development, (Mail code 8623P), 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Euling, Susan Y. [U.S. Environmental Protection Agency, National Center for Environmental Assessment, Office of Research and Development, (Mail code 8623P), 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Gray, L. Earl [U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Office of Research and Development, (MD-72), Highway 54, Research Triangle Park, NC 27711 (United States); Benson, Robert [U.S. Environmental Protection Agency, Region 8, (Mail code 8P-W), 1595 Wynkoop Street, Denver, CO 80202 (United States); Foster, Paul M.D. [National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233 (MD K2-12), Research Triangle Park, NC 27709 (United States)

2013-09-15

A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action. In this manuscript, we describe the case study evaluation of the toxicological database for DBP, focusing on identifying the full spectrum of male reproductive developmental effects. The data were assessed to 1) evaluate low dose and low incidence findings and 2) identify male reproductive toxicity endpoints without well-established modes of action (MOAs). These efforts led to the characterization of data gaps and research needs for the toxicity and toxicogenomic studies in a risk assessment context. Further, the identification of endpoints with unexplained MOAs in the toxicity data set was useful in the subsequent evaluation of the mechanistic information that the toxicogenomic data set evaluation could provide. The extensive analysis of the toxicology data set within the MOA context provided a resource of information for DBP in attempts to hypothesize MOAs (for endpoints without a well-established MOA) and to phenotypically anchor toxicogenomic and other mechanistic data both to toxicity endpoints and to available toxicogenomic data. This case study serves as an example of the steps that can be taken to develop a toxicological data source for a risk assessment, both in general and especially for risk assessments that include toxicogenomic data.

Reconciled Rat and Human Metabolic Networks for Comparative Toxicogenomics and Biomarker Predictions

Science.gov (United States)

2017-02-08

reconstructions for comparative systems analysis. PLoS Comput. Biol. 7, e1001116 (2011). 26. Bartell, J. A., Yen, P., Varga, J. J., Goldberg , J. B. & Papin, J. A...Rat Genome Database 2015: genomic, phenotypic and environmental variations and disease. Nucleic Acids Res. 43, D743–D750 (2015). 34. NCBI Resource

CHEMICAL EFFECTS IN BIOLOGICAL SYSTEMS – DATA DICTIONARY (CEBS-DD): A COMPENDIUM OF TERMS FOR THE CAPTURE AND INTEGRATION OF BIOLOGICAL STUDY DESIGN DESCRIPTION, CONVENTIONAL PHENOTYPES AND ‘OMICS’ DATA

Science.gov (United States)

A critical component in the design of the Chemical Effects in Biological Systems (CEBS) Knowledgebase is a strategy to capture toxicogenomics study protocols and the toxicity endpoint data (clinical pathology and histopathology). A Study is generally an experiment carried out du...

Adaptation of a Bioinformatics Microarray Analysis Workflow for a Toxicogenomic Study in Rainbow Trout.

Directory of Open Access Journals (Sweden)

Sophie Depiereux

Full Text Available Sex steroids play a key role in triggering sex differentiation in fish, the use of exogenous hormone treatment leading to partial or complete sex reversal. This phenomenon has attracted attention since the discovery that even low environmental doses of exogenous steroids can adversely affect gonad morphology (ovotestis development and induce reproductive failure. Modern genomic-based technologies have enhanced opportunities to find out mechanisms of actions (MOA and identify biomarkers related to the toxic action of a compound. However, high throughput data interpretation relies on statistical analysis, species genomic resources, and bioinformatics tools. The goals of this study are to improve the knowledge of feminisation in fish, by the analysis of molecular responses in the gonads of rainbow trout fry after chronic exposure to several doses (0.01, 0.1, 1 and 10 μg/L of ethynylestradiol (EE2 and to offer target genes as potential biomarkers of ovotestis development. We successfully adapted a bioinformatics microarray analysis workflow elaborated on human data to a toxicogenomic study using rainbow trout, a fish species lacking accurate functional annotation and genomic resources. The workflow allowed to obtain lists of genes supposed to be enriched in true positive differentially expressed genes (DEGs, which were subjected to over-representation analysis methods (ORA. Several pathways and ontologies, mostly related to cell division and metabolism, sexual reproduction and steroid production, were found significantly enriched in our analyses. Moreover, two sets of potential ovotestis biomarkers were selected using several criteria. The first group displayed specific potential biomarkers belonging to pathways/ontologies highlighted in the experiment. Among them, the early ovarian differentiation gene foxl2a was overexpressed. The second group, which was highly sensitive but not specific, included the DEGs presenting the highest fold change and

Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure.

Science.gov (United States)

Bourdon, Julie A; Williams, Andrew; Kuo, Byron; Moffat, Ivy; White, Paul A; Halappanavar, Sabina; Vogel, Ulla; Wallin, Håkan; Yauk, Carole L

2013-01-07

New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose-response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

Cytotoxic and toxicogenomic effects of silibinin in bladder cancer

Indian Academy of Sciences (India)

Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness forpreventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activityof silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial ...

Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples

Directory of Open Access Journals (Sweden)

Robim M. Rodrigues

2016-06-01

Full Text Available This data set is composed of transcriptomics analyses of (i liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF and (ii hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC. Data from primary human hepatocytes was also added to the data set “Open TG-GATEs: a large-scale toxicogenomics database” (Igarashi et al., 2015 [1]. Changes in gene expression due to acetaminophen intoxication as well as comparative information between human in vivo and in vitro samples are provided. The microarray data have been deposited in NCBI׳s Gene Expression Omnibus and are accessible through GEO Series accession number GEO: GSE74000. The provided data is used to evaluate the predictive capacity of each hepatic in vitro system and can be directly compared with large-scale publically available toxicogenomics databases. Further interpretation and discussion of these data feature in the corresponding research article “Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems” (Rodrigues et al., 2016 [2].

Toxicogenomics in Environmental Science.

Science.gov (United States)

Brinke, Alexandra; Buchinger, Sebastian

This chapter reviews the current knowledge and recent progress in the field of environmental, aquatic ecotoxicogenomics with a focus on transcriptomic methods. In ecotoxicogenomics the omics technologies are applied for the detection and assessment of adverse effects in the environment, and thus are to be distinguished from omics used in human toxicology [Snape et al., Aquat Toxicol 67:143-154, 2004]. Transcriptomic methods in ecotoxicology are applied to gain a mechanistic understanding of toxic effects on organisms or populations, and thus aim to bridge the gap between cause and effect. A worthwhile effect-based interpretation of stressor induced changes on the transcriptome is based on the principle of phenotypic-anchoring [Paules, Environ Health Perspect 111:A338-A339, 2003]. Thereby, changes on the transcriptomic level can only be identified as effects if they are clearly linked to a specific stressor-induced effect on the macroscopic level. By integrating those macroscopic and transcriptomic effects, conclusions on the effect-inducing type of the stressor can be drawn. Stressor-specific effects on the transcriptomic level can be identified as stressor-specific induced pathways, transcriptomic patterns, or stressors-specific genetic biomarkers. In this chapter, examples of the combined application of macroscopic and transcriptional effects for the identification of environmental stressors, such as aquatic pollutants, are given and discussed. By means of these examples, challenges on the way to a standardized application of transcriptomics in ecotoxicology are discussed. This is also done against the background of the application of transcriptomic methods in environmental regulation such as the EU regulation Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

Evaluation of the zebrafish embryo as an alternative model for hepatotoxicity testing

NARCIS (Netherlands)

Driessen, Marja

2014-01-01

In this thesis we showed the applicability of the zebrafish embryo as an alternative model for hepatotoxicity testing using analysis of mechanisms through toxicogenomics. By applying a variety of toxicogenomics techniques, we were able to characterize specific responses. NGS revealed that

Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

Energy Technology Data Exchange (ETDEWEB)

Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

2013-12-01

Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

Science.gov (United States)

Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

2014-01-01

Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

International Nuclear Information System (INIS)

Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

2014-01-01

Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA

Comparison of L1000 and Affymetrix Microarray for In Vitro Concentration-Response Gene Expression Profiling (SOT)

Science.gov (United States)

Advances in high-throughput screening technologies and in vitro systems have opened doors for cost-efficient evaluation of chemical effects on a diversity of biological endpoints. However, toxicogenomics platforms remain too costly to evaluate large libraries of chemicals in conc...

UV radiation in marine ectotherms: Molecular effects and responses

International Nuclear Information System (INIS)

Dahms, Hans-U.; Lee, Jae-Seong

2010-01-01

This review summarizes current knowledge on ultraviolet radiation (UVR)-induced cellular and molecular damage in marine ectotherms (invertebrates and fish). UVR impairs sperm motility, reduces fertilization, and causes embryo malformation that in turn affects recruitment and therefore the sustainability of natural populations. The direct molecular effects of UVR are mediated by absorption of certain wavelengths by specific macromolecules and the dissipation of the absorbed energy via photochemical reactions. Most organisms have defense mechanisms that either prevent UVR-induced damage, or mechanisms that repair the damage. Photoprotective pigments, antioxidant defense compounds, and cell cycle development genes are some of the molecules involved in UVR defense. Photoenzymatic repair and nucleotide excision repair are the two primary DNA repair systems in marine ectotherms. We anticipate that toxicogenomic studies will gain importance in UVR research because they can elucidate the primary processes involved in UVR damage and the cellular response to this damage.

Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

International Nuclear Information System (INIS)

Coccini, T; Roda, E; Manzo, L; Barni, S

2013-01-01

Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl 2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl 2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

Science.gov (United States)

Coccini, T.; Roda, E.; Barni, S.; Manzo, L.

2013-04-01

Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

Impact of Genomics Platform and Statistical Filtering on Transcriptional Benchmark Doses (BMD and Multiple Approaches for Selection of Chemical Point of Departure (PoD.

Directory of Open Access Journals (Sweden)

A Francina Webster

Full Text Available Many regulatory agencies are exploring ways to integrate toxicogenomic data into their chemical risk assessments. The major challenge lies in determining how to distill the complex data produced by high-content, multi-dose gene expression studies into quantitative information. It has been proposed that benchmark dose (BMD values derived from toxicogenomics data be used as point of departure (PoD values in chemical risk assessments. However, there is limited information regarding which genomics platforms are most suitable and how to select appropriate PoD values. In this study, we compared BMD values modeled from RNA sequencing-, microarray-, and qPCR-derived gene expression data from a single study, and explored multiple approaches for selecting a single PoD from these data. The strategies evaluated include several that do not require prior mechanistic knowledge of the compound for selection of the PoD, thus providing approaches for assessing data-poor chemicals. We used RNA extracted from the livers of female mice exposed to non-carcinogenic (0, 2 mg/kg/day, mkd and carcinogenic (4, 8 mkd doses of furan for 21 days. We show that transcriptional BMD values were consistent across technologies and highly predictive of the two-year cancer bioassay-based PoD. We also demonstrate that filtering data based on statistically significant changes in gene expression prior to BMD modeling creates more conservative BMD values. Taken together, this case study on mice exposed to furan demonstrates that high-content toxicogenomics studies produce robust data for BMD modelling that are minimally affected by inter-technology variability and highly predictive of cancer-based PoD doses.

Cytotoxic and toxicogenomic effects of silibinin in bladder cancer ...

Indian Academy of Sciences (India)

2016-12-16

Dec 16, 2016 ... spectrum of chemical and biological properties, some plants have ..... RNase inhibitor 20 U/μL, 4.16 μL DNAse and RNAse free water, 3 μL RT ..... Mayr R, Fritsche HM, Pycha A and Pycha A 2014 Radical cystectomy and the ...

Comparability Effects of Mandatory IFRS Adoption

OpenAIRE

Stefano Cascino; Joachim Gassen

2012-01-01

The mandatory adoption of IFRS by many countries worldwide fuels the expectation that financial accounting information might become more comparable across countries. This expectation is opposed to an alternative view that stresses the importance of incentives in shaping accounting information. We provide early evidence on this debate by investigating the effects of mandatory IFRS adoption on the comparability of financial accounting information around the world. Using two comparability proxie...

Isoflurane is a suitable alternative to ether for anesthetizing rats prior to euthanasia for gene expression analysis.

Science.gov (United States)

Nakatsu, Noriyuki; Igarashi, Yoshinobu; Aoshi, Taiki; Hamaguchi, Isao; Saito, Masumichi; Mizukami, Takuo; Momose, Haruka; Ishii, Ken J; Yamada, Hiroshi

2017-01-01

Diethyl ether (ether) had been widely used in Japan for anesthesia, despite its explosive properties and toxicity to both humans and animals. We also had used ether as an anesthetic for euthanizing rats for research in the Toxicogenomics Project (TGP). Because the use of ether for these purposes will likely cease, it is required to select an alternative anesthetic which is validated for consistency with existing TGP data acquired under ether anesthesia. We therefore compared two alternative anesthetic candidates, isoflurane and pentobarbital, with ether in terms of hematological findings, serum biochemical parameters, and gene expressions. As a result, few differences among the three agents were observed. In hematological and serum biochemistry analysis, no significant changes were found. In gene expression analysis, four known genes were extracted as differentially expressed genes in the liver of rats anesthetized with ether, isoflurane, or pentobarbital. However, no significant relationships were detected using gene ontology, pathway, or gene enrichment analyses by DAVID and TargetMine. Surprisingly, although it was expected that the lung would be affected by administration via inhalation, only one differentially expressed gene was extracted in the lung. Taken together, our data indicate that there are no significant differences among ether, isoflurane, and pentobarbital with respect to effects on hematological parameters, serum biochemistry parameters, and gene expression. Based on its smallest affect to existing data and its safety profile for humans and animals, we suggest isoflurane as a suitable alternative anesthetic for use in rat euthanasia in toxicogenomics analysis.

What drives the comparability effect of mandatory IFRS adoption?

OpenAIRE

Stefano Cascino; Joachim Gassen

2015-01-01

We investigate the effects of mandatory IFRS adoption on the comparability of financial accounting information. Using two comparability proxies based on De Franco et al. [2011] and a comparability proxy based on the degree of information transfer, our results suggest that the overall comparability effect of mandatory IFRS adoption is marginal. We hypothesize that firm-level heterogeneity in IFRS compliance explains the limited comparability effect. To test this conjecture, we first hand-colle...

Toxicological responses of environmental mixtures: Environmental metal mixtures display synergistic induction of metal-responsive and oxidative stress genes in placental cells

Energy Technology Data Exchange (ETDEWEB)

Adebambo, Oluwadamilare A. [Department of Biological Sciences, North Carolina State University (United States); Ray, Paul D. [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (United States); Shea, Damian [Department of Biological Sciences, North Carolina State University (United States); Fry, Rebecca C., E-mail: rfry@unc.edu [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (United States)

2015-12-15

Exposure to elevated levels of the toxic metals inorganic arsenic (iAs) and cadmium (Cd) represents a major global health problem. These metals often occur as mixtures in the environment, creating the potential for interactive or synergistic biological effects different from those observed in single exposure conditions. In the present study, environmental mixtures collected from two waste sites in China and comparable mixtures prepared in the laboratory were tested for toxicogenomic response in placental JEG-3 cells. These cells serve as a model for evaluating cellular responses to exposures during pregnancy. One of the mixtures was predominated by iAs and one by Cd. Six gene biomarkers were measured in order to evaluate the effects from the metal mixtures using dose and time-course experiments including: heme oxygenase 1 (HO-1) and metallothionein isoforms (MT1A, MT1F and MT1G) previously shown to be preferentially induced by exposure to either iAs or Cd, and metal transporter genes aquaporin-9 (AQP9) and ATPase, Cu{sup 2+} transporting, beta polypeptide (ATP7B). There was a significant increase in the mRNA expression levels of ATP7B, HO-1, MT1A, MT1F, and MT1G in mixture-treated cells compared to the iAs or Cd only-treated cells. Notably, the genomic responses were observed at concentrations significantly lower than levels found at the environmental collection sites. These data demonstrate that metal mixtures increase the expression of gene biomarkers in placental JEG-3 cells in a synergistic manner. Taken together, the data suggest that toxic metals that co-occur may induce detrimental health effects that are currently underestimated when analyzed as single metals. - Highlights: • Toxicogenomic responses of environmental metal mixtures assessed • Induction of ATP7B, HO-1, MT1A, MT1F and MT1G by metal mixtures observed in placental cells • Higher gene induction in response to metal mixtures versus single metal treatments.

Toxicological responses of environmental mixtures: Environmental metal mixtures display synergistic induction of metal-responsive and oxidative stress genes in placental cells

International Nuclear Information System (INIS)

Adebambo, Oluwadamilare A.; Ray, Paul D.; Shea, Damian; Fry, Rebecca C.

2015-01-01

Exposure to elevated levels of the toxic metals inorganic arsenic (iAs) and cadmium (Cd) represents a major global health problem. These metals often occur as mixtures in the environment, creating the potential for interactive or synergistic biological effects different from those observed in single exposure conditions. In the present study, environmental mixtures collected from two waste sites in China and comparable mixtures prepared in the laboratory were tested for toxicogenomic response in placental JEG-3 cells. These cells serve as a model for evaluating cellular responses to exposures during pregnancy. One of the mixtures was predominated by iAs and one by Cd. Six gene biomarkers were measured in order to evaluate the effects from the metal mixtures using dose and time-course experiments including: heme oxygenase 1 (HO-1) and metallothionein isoforms (MT1A, MT1F and MT1G) previously shown to be preferentially induced by exposure to either iAs or Cd, and metal transporter genes aquaporin-9 (AQP9) and ATPase, Cu 2+ transporting, beta polypeptide (ATP7B). There was a significant increase in the mRNA expression levels of ATP7B, HO-1, MT1A, MT1F, and MT1G in mixture-treated cells compared to the iAs or Cd only-treated cells. Notably, the genomic responses were observed at concentrations significantly lower than levels found at the environmental collection sites. These data demonstrate that metal mixtures increase the expression of gene biomarkers in placental JEG-3 cells in a synergistic manner. Taken together, the data suggest that toxic metals that co-occur may induce detrimental health effects that are currently underestimated when analyzed as single metals. - Highlights: • Toxicogenomic responses of environmental metal mixtures assessed • Induction of ATP7B, HO-1, MT1A, MT1F and MT1G by metal mixtures observed in placental cells • Higher gene induction in response to metal mixtures versus single metal treatments

Altered global gene expression profiles in human gastrointestinal epithelial Caco2 cells exposed to nanosilver

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Saura C. Sahu

Full Text Available Extensive consumer exposure to food- and cosmetics-related consumer products containing nanosilver is of public safety concern. Therefore, there is a need for suitable in vitro models and sensitive predictive rapid screening methods to assess their toxicity. Toxicogenomic profile showing subtle changes in gene expressions following nanosilver exposure is a sensitive toxicological endpoint for this purpose. We evaluated the Caco2 cells and global gene expression profiles as tools for predictive rapid toxicity screening of nanosilver. We evaluated and compared the gene expression profiles of Caco-2 cells exposed to 20 nm and 50 nm nanosilver at a concentration 2.5 μg/ml. The global gene expression analysis of Caco2 cells exposed to 20 nm nanosilver showed that a total of 93 genes were altered at 4 h exposure, out of which 90 genes were up-regulated and 3 genes were down-regulated. The 24 h exposure of 20 nm silver altered 15 genes in Caco2 cells, out of which 14 were up-regulated and one was down-regulated. The most pronounced changes in gene expression were detected at 4 h. The greater size (50 nm nanosilver at 4 h exposure altered more genes by more different pathways than the smaller (20 nm one. Metallothioneins and heat shock proteins were highly up-regulated as a result of exposure to both the nanosilvers. The cellular pathways affected by the nanosilver exposure is likely to lead to increased toxicity. The results of our study presented here suggest that the toxicogenomic characterization of Caco2 cells is a valuable in vitro tool for assessing toxicity of nanomaterials such as nanosilver. Keywords: Nanosilver, Silver nanoparticles, Nanoparticles, Toxicogenomics, DNA microarray, Global gene expression profiles, Caco2 cells

ABC gene-ranking for prediction of drug-induced cholestasis in rats

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Yauheniya Cherkas

drugs that behaved very differently, and were distinct from both non-cholestatic and cholestatic drugs (ketoconazole, dipyridamole, cyproheptadine and aniline, and many postulated human cholestatic drugs that in rat showed no evidence of cholestasis (chlorpromazine, erythromycin, niacin, captopril, dapsone, rifampicin, glibenclamide, simvastatin, furosemide, tamoxifen, and sulfamethoxazole. Most of these latter drugs were noted previously by other groups as showing cholestasis only in humans. The results of this work suggest that the ABC procedure and similar statistical approaches can be instrumental in combining data to compare toxicants across toxicogenomics databases, extract similarities among responses and reduce unexplained data varation. Keywords: Cluster analysis, Cholestasis, Gene signature, Microarray, Prediction, Toxicogenomics

Contribution of new technologies to characterization and prediction of adverse effects.

Science.gov (United States)

Rouquié, David; Heneweer, Marjoke; Botham, Jane; Ketelslegers, Hans; Markell, Lauren; Pfister, Thomas; Steiling, Winfried; Strauss, Volker; Hennes, Christa

2015-02-01

Identification of the potential hazards of chemicals has traditionally relied on studies in laboratory animals where changes in clinical pathology and histopathology compared to untreated controls defined an adverse effect. In the past decades, increased consistency in the definition of adversity with chemically-induced effects in laboratory animals, as well as in the assessment of human relevance has been reached. More recently, a paradigm shift in toxicity testing has been proposed, mainly driven by concerns over animal welfare but also thanks to the development of new methods. Currently, in vitro approaches, toxicogenomic technologies and computational tools, are available to provide mechanistic insight in toxicological Mode of Action (MOA) of the adverse effects observed in laboratory animals. The vision described as Tox21c (Toxicity Testing in the 21st century) aims at predicting in vivo toxicity using a bottom-up-approach, starting with understanding of MOA based on in vitro data to ultimately predict adverse effects in humans. At present, a practical application of the Tox21c vision is still far away. While moving towards toxicity prediction based on in vitro data, a stepwise reduction of in vivo testing is foreseen by combining in vitro with in vivo tests. Furthermore, newly developed methods will also be increasingly applied, in conjunction with established methods in order to gain trust in these new methods. This confidence is based on a critical scientific prerequisite: the establishment of a causal link between data obtained with new technologies and adverse effects manifested in repeated-dose in vivo toxicity studies. It is proposed to apply the principles described in the WHO/IPCS framework of MOA to obtain this link. Finally, an international database of known MOAs obtained in laboratory animals using data-rich chemicals will facilitate regulatory acceptance and could further help in the validation of the toxicity pathway and adverse outcome pathway

Nanomedicinal products: a survey on specific toxicity and side effects

Directory of Open Access Journals (Sweden)

Brand W

2017-08-01

Full Text Available Walter Brand,1,* Cornelle W Noorlander,1,* Christina Giannakou,2,3 Wim H De Jong,2 Myrna W Kooi,1 Margriet VDZ Park,2 Rob J Vandebriel,2 Irene EM Bosselaers,4 Joep HG Scholl,5 Robert E Geertsma2 1Centre for Safety of Substances and Products, 2Centre for Health Protection, National Institute for Public Health and the Environment (RIVM, Bilthoven, 3Department of Toxicogenomics, Maastricht University, Maastricht, 4Section Pharmacology, Toxicology and Pharmacokinetics, Medicines Evaluation Board (CBG-MEB, Utrecht, 5Research & Analysis Department, Netherlands Pharmacovigilance Centre Lareb, ‘s-Hertogenbosch, the Netherlands *These authors contributed equally to this work Abstract: Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs. However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of potential nanomedicine-specific effects need to be

Application of computational systems biology to explore environmental toxicity hazards

DEFF Research Database (Denmark)

Audouze, Karine Marie Laure; Grandjean, Philippe

2011-01-01

Background: Computer-based modeling is part of a new approach to predictive toxicology.Objectives: We investigated the usefulness of an integrated computational systems biology approach in a case study involving the isomers and metabolites of the pesticide dichlorodiphenyltrichloroethane (DDT......) to ascertain their possible links to relevant adverse effects.Methods: We extracted chemical-protein association networks for each DDT isomer and its metabolites using ChemProt, a disease chemical biology database that includes both binding and gene expression data, and we explored protein-protein interactions...... using a human interactome network. To identify associated dysfunctions and diseases, we integrated protein-disease annotations into the protein complexes using the Online Mendelian Inheritance in Man database and the Comparative Toxicogenomics Database.Results: We found 175 human proteins linked to p,p´-DDT...

Toxicogenomic analysis reveals profibrogenic effects of trichloroethylene in autoimmune-mediated cholangitis in mice.

Science.gov (United States)

Kopec, Anna K; Sullivan, Bradley P; Kassel, Karen M; Joshi, Nikita; Luyendyk, James P

2014-10-01

Epidemiological studies suggest that exposure to environmental chemicals increases the risk of developing autoimmune liver disease. However, the identity of specific chemical perpetrators and the mechanisms whereby environmental chemicals modify liver disease is unclear. Previous studies link exposure to trichloroethylene (TCE) with the development of autoimmune liver disease and exacerbation of autoimmunity in lupus-prone MRL mice. In this study, we utilized NOD.c3c4 mice, which spontaneously develop autoimmune cholangitis bearing resemblance to some features of primary biliary cirrhosis. Nine-week-old female NOD.c3c4 mice were given TCE (0.5 mg/ml) or its vehicle (1% Cremophor-EL) in drinking water for 4 weeks. TCE had little effect on clinical chemistry, biliary cyst formation, or hepatic CD3+ T-cell accumulation. Hepatic microarray profiling revealed a dramatic suppression of early growth response 1 (EGR1) mRNA in livers of TCE-treated mice, which was verified by qPCR and immunohistochemical staining. Consistent with a reported link between reduced EGR1 expression and liver fibrosis, TCE increased hepatic type I collagen (COL1A1) mRNA and protein levels in livers of NOD.c3c4 mice. In contrast, TCE did not increase COL1A1 expression in NOD.ShiLtJ mice, which do not develop autoimmune cholangitis. These results suggest that in the context of concurrent autoimmune liver disease with a genetic basis, modification of hepatic gene expression by TCE may increase profibrogenic signaling in the liver. Moreover, these studies suggest that NOD.c3c4 mice may be a novel model to study gene-environment interactions critical for the development of autoimmune liver disease. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

Directory of Open Access Journals (Sweden)

Giannakou C

2016-06-01

Full Text Available Christina Giannakou,1,2 Margriet VDZ Park,1 Wim H de Jong,1 Henk van Loveren,1,2 Rob J Vandebriel,1 Robert E Geertsma1 1Centre for Health Protection, National Institute for Public Health and the Environment (RIVM, Bilthoven, 2Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands Abstract: Nanomaterials (NMs are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome

Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

International Nuclear Information System (INIS)

Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

2002-01-01

Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

Possibilities for application of comparative advertising and its effects

Directory of Open Access Journals (Sweden)

Starčević Slađana

2006-01-01

Full Text Available In recent years, it has been evident that one form of competitive advertising gained in its importance - comparative advertising. Although its extensive use has probably been inspired by the belief that the perception of relative superiority of a brand compared to competition could be encouraged in that way, research evidence suggested mixed conclusions about its effectiveness. The paper summarizes the results of previous studies in this area, and in particular those which point out the factors that can influence effectiveness of comparative advertising. Additionally,, the paper summarizes the opinions of some authors about the long-term influence of this form of advertising on brand, and gives the recommendations for its more effective use. .

Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

Energy Technology Data Exchange (ETDEWEB)

Jackson, Anna Francina, E-mail: Francina.Jackson@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada); Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa K1S 5B6 (Canada); Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada); Recio, Leslie, E-mail: lrecio@ils-inc.com [ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Waters, Michael D., E-mail: mwaters@ils-inc.com [ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Lambert, Iain B., E-mail: Iain.Lambert@carleton.ca [Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa K1S 5B6 (Canada); Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada)

2014-01-01

Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF

Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

International Nuclear Information System (INIS)

Jackson, Anna Francina; Williams, Andrew; Recio, Leslie; Waters, Michael D.; Lambert, Iain B.; Yauk, Carole L.

2014-01-01

Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF

Comparing effects of Winter Universiade (2011) and European ...

African Journals Online (AJOL)

Comparing effects of Winter Universiade (2011) and European Youth Olympic Festival (2011) ... The participating group was composed of 878 local spectators who watched the games. ... Sample group views on both positive and negative effects of these two events have high averages. ... AJOL African Journals Online.

Comparative Antioxidant, Antiproliferative and Apoptotic Effects of ...

African Journals Online (AJOL)

Purpose: To determine and compare the antioxidant, antiproliferative and apoptotic effects of leaf infusions of Ilex laurina and Ilex paraguariensis in colon cancer cells. Methods: Antioxidant activity was determined by ORAC (Oxygen Radical Absorbance Capacity) and FRAP (Ferric Reducing Antioxidant Power). Cytotoxic ...

Preliminary Competencies for Comparative Effectiveness Research

OpenAIRE

Segal, Jodi B.; Kapoor, Wishwa; Carey, Timothy; Mitchell, Pamela H.; Murray, Michael D.; Saag, Kenneth G.; Schumock, Glen; Jonas, Daniel; Steinman, Michael; Weinberger, Morris; Filart, Rosemarie; Selker, Harry

2012-01-01

The Clinical and Translational Science Award (CTSA) Workgroup for Comparative Effectiveness Research (CER) Education, Training, and Workforce Development identified a need to delineate the competencies that practitioners and users of CER for patient centered outcomes research, should acquire. With input from CTSA representatives and collaborators, we began by describing the workforce. We recognize the workforce that conduct CER and the end users who use CER to improve the health of individual...

Comparative effectiveness of malaria preventive measures on ...

African Journals Online (AJOL)

The burden of malaria and its associated problems in pregnancy can be reduced by the use of different malaria preventive measures. This study was conducted to determine the comparative effectiveness of three different malaria preventive measures on populations of parturient in Abeokuta, Ogun State, Nigeria.

COMPARATIVE EFFECTIVENESS RESEARCH AND ITS APPLICATION TO NURSING EDUCATION

Directory of Open Access Journals (Sweden)

Claire Su-Yeon Park

2016-07-01

Full Text Available This in-depth integrative literature review aimed to investigate comparative effectiveness research (CER methodologies applicable to nursing research and to propose a CER design relevant to nursing education. Integration and synthesis were conducted from August 20 to December 15, 2013 and from October 20 to December 05, 2015 using electronic databases and refereed published books. The key words were “comparative effectiveness research,” “education,” “patient outcomes,” “effectiveness,” “cost-effectiveness,” and “efficiency.” All selected literatures were initially scrutinized by the principal investigator in terms of scientific rigor and then synthesized on an ongoing basis. CER methodologies in nursing research were presented to be significant in terms of enabling the distinctiveness of the nursing profession to stand out. Three CER methodologies applicable to nursing research—a Pragmatic Clinical Trial, Observational Comparative Effectiveness Research and Cost Effectiveness Research—revealed each of their distinguishable strengths and weaknesses compared to the Randomized Controlled Trial. For ethical considerations, the importance of ensuring “equipoise” was identified. Lastly, in a head to head comparison of two nursing education programs, a single blind, randomized crossover study design was proposed as a type of Pragmatic Clinical Trial utilizing cost-utility analysis. A mixed method Analysis of Covariance and a Doubly Multivariate Repeated Analysis of Covariance were suggested as relevant statistical analyses. Considering that CER is still inchoate in nursing research and nurse scientists’ endeavors to address the gap are urgent, this study is compelling in that it proposed a rigorous CER design not only directly applicable to nursing education, but also to other disciplines in education.

Microarray analysis of toxicogenomic effects of Ortho-phenylphenol in Staphylococcus aureus

Directory of Open Access Journals (Sweden)

Toghrol Freshteh

2008-09-01

Full Text Available Abstract Background Staphylococcus aureus (S. aureus, is responsible for many infectious diseases, ranging from benign skin infections to life-threatening endocarditis and toxic shock syndrome. Ortho-phenylphenol (OPP is an antimicrobial agent and an active ingredient of EPA-registered disinfectants with wide human exposure in various agricultural, hospital and veterinary disinfectant products. Despite many uses, an understanding of a cellular response to OPP and it's mechanism of action, targeted genes, and the connectivity between targeted genes and the rest of cell metabolism remains obscure. Results Herein, we performed a genome-wide transcriptome analysis of the cellular responses of S. aureus when exposed to 0.82 mM of OPP for 20 and 60 min. Our data indicated that OPP downregulated the biosynthesis of many amino acids, which are required for protein synthesis. In particular, the genes encoding the enzymes of the diaminopimelate (DAP pathway which results in lysine biosynthesis were significantly downregualted. Intriguingly, we revealed that the transcription of genes encoding ribosomal proteins was upregulated by OPP and at the same time, the genes encoding iron acquisition and transport were downregulated. The genes encoding virulence factors were upregulated and genes encoding phospholipids were downregulated upon 20 min exposure to OPP. Conclusion By using microarray analysis that enables us to simultaneously and globally examine the complete transcriptome during cellular responses, we have revealed novel information regarding the mode of action of OPP on Staphylococcus: OPP inhibits anabolism of many amino acids and highly downregulates the genes that encode the enzymes involved in the DAP pathway. Lysine and DAP are essential for building up the peptidoglycan cell wall. It was concluded that the mode of action of OPP is similar to the mechanism of action of some antibiotics. The discovery of this phenomenon provides useful information that will benefit further antimicrobial research on S. aureus.

Instrumental variable methods in comparative safety and effectiveness research.

Science.gov (United States)

Brookhart, M Alan; Rassen, Jeremy A; Schneeweiss, Sebastian

2010-06-01

Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial.

Instrumental variable methods in comparative safety and effectiveness research†

Science.gov (United States)

Brookhart, M. Alan; Rassen, Jeremy A.; Schneeweiss, Sebastian

2010-01-01

Summary Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial. PMID:20354968

THE MAQC PROJECT: ESTABLISHING QC METRICS AND THRESHOLDS FOR MICROARRAY QUALITY CONTROL

Science.gov (United States)

Microarrays represent a core technology in pharmacogenomics and toxicogenomics; however, before this technology can successfully and reliably be applied in clinical practice and regulatory decision-making, standards and quality measures need to be developed. The Microarray Qualit...

Living network meta-analysis compared with pairwise meta-analysis in comparative effectiveness research: empirical study

Science.gov (United States)

Nikolakopoulou, Adriani; Mavridis, Dimitris; Furukawa, Toshi A; Cipriani, Andrea; Tricco, Andrea C; Straus, Sharon E; Siontis, George C M; Egger, Matthias

2018-01-01

Abstract Objective To examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) (“living” network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical interventions earlier than the updating of conventional, pairwise meta-analysis. Design Empirical study of the accumulating evidence about the comparative effectiveness of clinical interventions. Data sources Database of network meta-analyses of RCTs identified through searches of Medline, Embase, and the Cochrane Database of Systematic Reviews until 14 April 2015. Eligibility criteria for study selection Network meta-analyses published after January 2012 that compared at least five treatments and included at least 20 RCTs. Clinical experts were asked to identify in each network the treatment comparison of greatest clinical interest. Comparisons were excluded for which direct and indirect evidence disagreed, based on side, or node, splitting test (Pmeta-analysis. The frequency and time to strong evidence was compared against the null hypothesis between pairwise and network meta-analyses. Results 49 comparisons of interest from 44 networks were included; most (n=39, 80%) were between active drugs, mainly from the specialties of cardiology, endocrinology, psychiatry, and rheumatology. 29 comparisons were informed by both direct and indirect evidence (59%), 13 by indirect evidence (27%), and 7 by direct evidence (14%). Both network and pairwise meta-analysis provided strong evidence against the null hypothesis for seven comparisons, but for an additional 10 comparisons only network meta-analysis provided strong evidence against the null hypothesis (P=0.002). The median time to strong evidence against the null hypothesis was 19 years with living network meta-analysis and 23 years with living pairwise meta-analysis (hazard ratio 2.78, 95% confidence interval 1.00 to 7.72, P=0.05). Studies directly comparing

Comparative Analysis of the Effects of Organization Development ...

African Journals Online (AJOL)

Comparative Analysis of the Effects of Organization Development Interventions on Organizational Leadership and Management Practice: A Case Of Green Earth Program (GEP) ... Journal of Language, Technology & Entrepreneurship in Africa.

Comparative Effectiveness of Different Types of Cervical Laminoplasty

OpenAIRE

Heller, John G.; Raich, Annie L.; Dettori, Joseph R.; Riew, K. Daniel

2013-01-01

Study Design Systematic review. Study Rationale Numerous cervical laminoplasty techniques have been described but there are few studies that have compared these to determine the superiority of one over another. Clinical Questions The clinical questions include key question (KQ)1: In adults with cervical myelopathy from ossification of the posterior longitudinal ligament (OPLL) or spondylosis, what is the comparative effectiveness of open door cervical laminoplasty versus French door cervical ...

Comparative Antioxidant, Antiproliferative and Apoptotic Effects of ...

African Journals Online (AJOL)

Purpose: To determine and compare the antioxidant, antiproliferative and apoptotic effects of leaf infusions of Ilex laurina ... Both plant infusions inhibited viability and cell growth of SW480 and SW620 cells. .... 100 g of dry extract, from a gallic acid calibration curve [9]. ..... antioxidant capacity and in vitro inhibition of colon.

Comparative effects of imipramine, sertraline, nifedipine, furosemide ...

African Journals Online (AJOL)

The objective of the study was to evaluate the comparative effects of imipramine, sertraline, nifedipine, furosemide and bumetanide on ingestive behavior in rodents. Twelve groups (with six in each group) of male mice (25 to 35 g) were used in the experiments. They were housed in labelled plastic cages in the departmental ...

Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells

International Nuclear Information System (INIS)

Lambert, Carine B.; Spire, Catherine; Claude, Nancy; Guillouzo, Andre

2009-01-01

Phenobarbital (PB) induces or represses a wide spectrum of genes in rodent liver. Much less is known about its effects in human liver. We used pangenomic cDNA microarrays to analyze concentration- and time-dependent gene expression profile changes induced by PB in the well-differentiated human HepaRG cell line. Changes in gene expression profiles clustered at specific concentration ranges and treatment times. The number of correctly annotated genes significantly modulated by at least three different PB concentration ranges (spanning 0.5 to 3.2 mM) at 20 h exposure amounted to 77 and 128 genes (p ≤ 0.01) at 2- and 1.8-fold filter changes, respectively. At low concentrations (0.5 and 1 mM), PB-responsive genes included the well-recognized CAR- and PXR-dependent responsive cytochromes P450 (CYP2B6, CYP3A4), sulfotransferase 2A1 and plasma transporters (ABCB1, ABCC2), as well as a number of genes critically involved in various metabolic pathways, including lipid (CYP4A11, CYP4F3), vitamin D (CYP24A1) and bile (CYP7A1 and CYP8B1) metabolism. At concentrations of 3.2 mM or higher after 20 h, and especially 48 h, increased cytotoxic effects were associated with disregulation of numerous genes related to oxidative stress, DNA repair and apoptosis. Primary human hepatocyte cultures were also exposed to 1 and 3.2 mM PB for 20 h and the changes were comparable to those found in HepaRG cells treated under the same conditions. Taken altogether, our data provide further evidence that HepaRG cells closely resemble primary human hepatocytes and provide new information on the effects of PB in human liver. These data also emphasize the importance of investigating dose- and time-dependent effects of chemicals when using toxicogenomic approaches

Comparing Hall Effect and Field Effect Measurements on the Same Single Nanowire.

Science.gov (United States)

Hultin, Olof; Otnes, Gaute; Borgström, Magnus T; Björk, Mikael; Samuelson, Lars; Storm, Kristian

2016-01-13

We compare and discuss the two most commonly used electrical characterization techniques for nanowires (NWs). In a novel single-NW device, we combine Hall effect and back-gated and top-gated field effect measurements and quantify the carrier concentrations in a series of sulfur-doped InP NWs. The carrier concentrations from Hall effect and field effect measurements are found to correlate well when using the analysis methods described in this work. This shows that NWs can be accurately characterized with available electrical methods, an important result toward better understanding of semiconductor NW doping.

The value-based medicine comparative effectiveness and cost-effectiveness of penetrating keratoplasty for keratoconus.

Science.gov (United States)

Roe, Richard H; Lass, Jonathan H; Brown, Gary C; Brown, Melissa M

2008-10-01

To perform a base case, comparative effectiveness, and cost-effectiveness (cost-utility) analysis of penetrating keratoplasty for patients with severe keratoconus. Visual acuity data were obtained from a large, retrospective multicenter study in which patients with keratoconus with less than 20/40 best corrected visual acuity and/or the inability to wear contact lenses underwent penetrating keratoplasty, with an average follow-up of 2.1 years. The results were combined with other retrospective studies investigating complication rates of penetrating keratoplasty. The data were then incorporated into a cost-utility model using patient preference-based, time trade-off utilities, computer-based decision analysis, and a net present value model to account for the time value of outcomes and money. The comparative effectiveness of the intervention is expressed in quality-of-life gain and QALYs (quality-adjusted life-years), and the cost-effectiveness results are expressed in the outcome of $/QALY (dollars spent per QALY). Penetrating keratoplasty in 1 eye for patients with severe keratoconus results in a comparative effectiveness (value gain) of 16.5% improvement in quality of life every day over the 44-year life expectancy of the average patient with severe keratoconus. Discounting the total value gain of 5.36 QALYs at a 3% annual discount rate yields 3.05 QALYs gained. The incremental cost for penetrating keratoplasty, including all complications, is $5934 ($5913 discounted at 3% per year). Thus, the incremental cost-utility (discounted at 3% annually) for this intervention is $5913/3.05 QALYs = $1942/QALY. If both eyes undergo corneal transplant, the total discounted value gain is 30% and the overall cost-utility is $2003. Surgery on the second eye confers a total discounted value gain of 2.5 QALYs, yielding a quality-of-life gain of 11.6% and a discounted cost-utility of $2238/QALY. Penetrating keratoplasty for patients with severe keratoconus seems to be a

Cutting-edge technology for public health workforce training in comparative effectiveness research.

Science.gov (United States)

Salinas-Miranda, Abraham A; Nash, Michelle C; Salemi, Jason L; Mbah, Alfred K; Salihu, Hamisu M

2013-06-01

A critical mass of public health practitioners with expertise in analytic techniques and best practices in comparative effectiveness research is needed to fuel informed decisions and improve the quality of health care. The purpose of this case study is to describe the development and formative evaluation of a technology-enhanced comparative effectiveness research learning curriculum and to assess its potential utility to improve core comparative effectiveness research competencies among the public health workforce. Selected public health experts formed a multidisciplinary research collaborative and participated in the development and evaluation of a blended 15-week comprehensive e-comparative effectiveness research training program, which incorporated an array of health informatics technologies. Results indicate that research-based organizations can use a systematic, flexible, and rapid means of instructing their workforce using technology-enhanced authoring tools, learning management systems, survey research software, online communities of practice, and mobile communication for effective and creative comparative effectiveness research training of the public health workforce.

Comparable effects of exercise and analgesics for pain secondary to knee osteoarthritis

DEFF Research Database (Denmark)

Henriksen, Marius; Hansen, Julie B; Klokker, Louise

2016-01-01

administered analgesics for pain in patients with knee osteoarthritis. METHODS: The Cochrane Database of systematic reviews was searched for meta-analyses of randomized controlled studies comparing exercise or analgesics with a control group (placebo or usual care) and with pain as an outcome. Individual study......AIM: Evidence of comparative effectiveness of different treatment approaches is important for clinical decision-making, yet absent for most recommended treatments of knee osteoarthritis pain. The objective of this study was to estimate the comparative effectiveness of exercise versus orally...... estimates were identified and effect sizes were calculated from group differences. We combined study-level effects on pain with a random effects meta-analysis and compared effect sizes between exercise trials and trials with analgesic interventions. RESULTS: We included six Cochrane reviews (four...

Reduced biological effect of e-cigarette aerosol compared to cigarette smoke evaluated in vitro using normalized nicotine dose and RNA-seq-based toxicogenomics

OpenAIRE

Haswell, Linsey E.; Baxter, Andrew; Banerjee, Anisha; Verrastro, Ivan; Mushonganono, Jessica; Adamson, Jason; Thorne, David; Ga?a, Marianna; Minet, Emmanuel

2017-01-01

Electronic cigarettes (e-cigarettes) use has increased globally and could potentially offer a lower risk alternative to cigarette smoking. Here, we assessed the transcriptional response of a primary 3D airway model acutely exposed to e-cigarette aerosol and cigarette (3R4F) smoke. Aerosols were generated with standard intense smoking regimens with careful consideration for dose by normalizing the exposures to nicotine. Two e-cigarette aerosol dilutions were tested for equivalent and higher ni...

Ecotoxicogenomics to Support Ecological Risk Assessment: A Case Study with Bisphenol A in Fish

Science.gov (United States)

Toxicogenomic approaches are being increasingly applied in the field of ecotoxicology. Given the growing availability of ecotoxicogenomic data, the Agency and the broader scientific community are actively engaged in considering how best to use those data to support ecological ris...

ExpoCast: Exposure Science for Prioritization and Toxicity Testing (S)

Science.gov (United States)

The US EPA is completing the Phase I pilot for a chemical prioritization research program, called ToxCast. Here EPA is developing methods for using computational chemistry, high-throughput screening, and toxicogenomic technologies to predict potential toxicity and prioritize limi...

ExpoCast: Exposure Science for Prioritization and Toxicity Testing

Science.gov (United States)

The US EPA is completing the Phase I pilot for a chemical prioritization research program, called ToxCastTM. Here EPA is developing methods for using computational chemistry, high-throughput screening, and toxicogenomic technologies to predict potential toxicity and prioritize l...

Living network meta-analysis compared with pairwise meta-analysis in comparative effectiveness research: empirical study.

Science.gov (United States)

Nikolakopoulou, Adriani; Mavridis, Dimitris; Furukawa, Toshi A; Cipriani, Andrea; Tricco, Andrea C; Straus, Sharon E; Siontis, George C M; Egger, Matthias; Salanti, Georgia

2018-02-28

To examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) ("living" network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical interventions earlier than the updating of conventional, pairwise meta-analysis. Empirical study of the accumulating evidence about the comparative effectiveness of clinical interventions. Database of network meta-analyses of RCTs identified through searches of Medline, Embase, and the Cochrane Database of Systematic Reviews until 14 April 2015. Network meta-analyses published after January 2012 that compared at least five treatments and included at least 20 RCTs. Clinical experts were asked to identify in each network the treatment comparison of greatest clinical interest. Comparisons were excluded for which direct and indirect evidence disagreed, based on side, or node, splitting test (Pmeta-analyses were performed for each selected comparison. Monitoring boundaries of statistical significance were constructed and the evidence against the null hypothesis was considered to be strong when the monitoring boundaries were crossed. A significance level was defined as α=5%, power of 90% (β=10%), and an anticipated treatment effect to detect equal to the final estimate from the network meta-analysis. The frequency and time to strong evidence was compared against the null hypothesis between pairwise and network meta-analyses. 49 comparisons of interest from 44 networks were included; most (n=39, 80%) were between active drugs, mainly from the specialties of cardiology, endocrinology, psychiatry, and rheumatology. 29 comparisons were informed by both direct and indirect evidence (59%), 13 by indirect evidence (27%), and 7 by direct evidence (14%). Both network and pairwise meta-analysis provided strong evidence against the null hypothesis for seven comparisons, but for an additional 10 comparisons only network meta-analysis provided

Evaluation of a toxicogenomic approach to the local lymph node assay (LLNA).

Science.gov (United States)

Boverhof, Darrell R; Gollapudi, B Bhaskar; Hotchkiss, Jon A; Osterloh-Quiroz, Mandy; Woolhiser, Michael R

2009-02-01

Genomic technologies have the potential to enhance and complement existing toxicology endpoints; however, assessment of these approaches requires a systematic evaluation including a robust experimental design with genomic endpoints anchored to traditional toxicology endpoints. The present study was conducted to assess the sensitivity of genomic responses when compared with the traditional local lymph node assay (LLNA) endpoint of lymph node cell proliferation and to evaluate the responses for their ability to provide insights into mode of action. Female BALB/c mice were treated with the sensitizer trimellitic anhydride (TMA), following the standard LLNA dosing regimen, at doses of 0.1, 1, or 10% and traditional tritiated thymidine ((3)HTdR) incorporation and gene expression responses were monitored in the auricular lymph nodes. Additional mice dosed with either vehicle or 10% TMA and sacrificed on day 4 or 10, were also included to examine temporal effects on gene expression. Analysis of (3)HTdR incorporation revealed TMA-induced stimulation indices of 2.8, 22.9, and 61.0 relative to vehicle with an EC(3) of 0.11%. Examination of the dose-response gene expression responses identified 9, 833, and 2122 differentially expressed genes relative to vehicle for the 0.1, 1, and 10% TMA dose groups, respectively. Calculation of EC(3) values for differentially expressed genes did not identify a response that was more sensitive than the (3)HTdR value, although a number of genes displayed comparable sensitivity. Examination of temporal responses revealed 1760, 1870, and 953 differentially expressed genes at the 4-, 6-, and 10-day time points respectively. Functional analysis revealed many responses displayed dose- and time-specific induction patterns within the functional categories of cellular proliferation and immune response, including numerous immunoglobin genes which were highly induced at the day 10 time point. Overall, these experiments have systematically illustrated

Comparative effectiveness research: Challenges for medical journals

Directory of Open Access Journals (Sweden)

Tovey David

2010-04-01

Full Text Available Abstract Editors from a number of medical journals lay out principles for journals considering publication of Comparative Effectiveness Research (CER. In order to encourage dissemination of this editorial, this article is freely available in PLoS Medicine and will be also published in Medical Decision Making, Croatian Medical Journal, The Cochrane Library, Trials, The American Journal of Managed Care, and Journal of Clinical Epidemiology.

Comparing sensitivity of ecotoxicological effect endpoints between laboratory and field

DEFF Research Database (Denmark)

Selck, H.; Riemann, B.; Christoffersen, K.

2002-01-01

multispecies field tests using tributyltin (TBT) and linear alkylbenzene sulfonates (LAS) were compared with published laboratory single-species test results and measured in situ concentrations. Extrapolation methods were evaluated by comparing predicted no-effect concentrations (PNECs), calculated by AF...

Comparing Effectiveness of Undergraduate Course Delivery: A Student Perspective

Science.gov (United States)

Koenig, Robert J.

2009-01-01

Higher education students can and do take courses delivered in a variety of ways. But, to date, little research has been done on the effectiveness of different delivery modes. This study sought to fill that void by comparing the effectiveness of three undergraduate course delivery modes: classroom, online, and video conference at a technical…

Comparative Clinical Study on the Effectiveness of Homeopathic ...

African Journals Online (AJOL)

Purpose: To investigate the effectiveness of homeopathic combination remedy compared with standard maintenance therapy for the treatment of dengue fever. Method: A total of 50 patients with dengue fever were divided into two equal groups. Group 1 was treated with homeopathic combination remedy for consecutive 6 ...

Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

International Nuclear Information System (INIS)

McGuire, S.A.

1991-02-01

The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m 3 for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m 3 (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs

Chemical toxicity of uranium hexafluoride compared to acute effects of radiation

Energy Technology Data Exchange (ETDEWEB)

McGuire, S.A.

1991-02-01

The chemical effects from acute exposures to uranium hexafluoride are compared to the nonstochastic effects from acute radiation doses of 25 rems to the whole body and 300 rems to the thyroid. The analysis concludes that an intake of about 10 mg of uranium in soluble form is roughly comparable, in terms of early effects, to an acute whole body dose of 25 rems because both are just below the threshold for significant nonstochastic effects. Similarly, an exposure to hydrogen fluoride at a concentration of 25 mg/m{sup 3} for 30 minutes is roughly comparable because there would be no significant nonstochastic effects. For times t other than 30 minutes, the concentration C of hydrogen fluoride considered to have the same effect can be calculated using a quadratic equation: C = 25 mg/m{sup 3} (30 min/t). The purpose of these analyses is to provide information for developing design and siting guideline based on chemical toxicity for enrichment plants using uranium hexafluoride. These guidelines are to be similar, in terms of stochastic health effects, to criteria in NRC regulations of nuclear power plants, which are based on radiation doses. 26 refs., 1 fig., 5 tabs.

Study design elements for rigorous quasi-experimental comparative effectiveness research.

Science.gov (United States)

Maciejewski, Matthew L; Curtis, Lesley H; Dowd, Bryan

2013-03-01

Quasi-experiments are likely to be the workhorse study design used to generate evidence about the comparative effectiveness of alternative treatments, because of their feasibility, timeliness, affordability and external validity compared with randomized trials. In this review, we outline potential sources of discordance in results between quasi-experiments and experiments, review study design choices that can improve the internal validity of quasi-experiments, and outline innovative data linkage strategies that may be particularly useful in quasi-experimental comparative effectiveness research. There is an urgent need to resolve the debate about the evidentiary value of quasi-experiments since equal consideration of rigorous quasi-experiments will broaden the base of evidence that can be brought to bear in clinical decision-making and governmental policy-making.

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

DEFF Research Database (Denmark)

Poulsen, Sarah S.; Saber, Anne T.; Williams, Andrew

2015-01-01

Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instil...

Comparative Effect of Graphic Organiser and Expository teaching ...

African Journals Online (AJOL)

This paper focused on the comparative effects of graphic organiser and expository teaching strategies on the achievement of senior secondary school students in Economics. Graphic organiser is a teaching strategy used to visualise the structure of knowledge, instead of describing all concepts and their relations in text as in ...

Comparative study on the pathogenic effects of Diminazine ...

African Journals Online (AJOL)

The study was conducted in goats to compare the pathogenic effects of .... membrane was examined, the rectal temperature of the goats was recorded ... the plasma layer, the content was expressed on the slide and covered with slip. ... measure analysis of variance in SPSS version 15.0 (2000). ..... Canadanian Journal of.

Comparative effectiveness of inter-simple sequence repeat and ...

African Journals Online (AJOL)

A study to compare the effectiveness of inter-simple sequence repeats (ISSR) and randomly amplified polymorphic DNA (RAPD) profiling was carried out with a total of 65 DNA samples using 12 species of Indian Garcinia. ISSR and RAPD profiling were performed with 19 and 12 primers, respectively. ISSR markers ...

Stakeholder participation in comparative effectiveness research: defining a framework for effective engagement.

Science.gov (United States)

Deverka, Patricia A; Lavallee, Danielle C; Desai, Priyanka J; Esmail, Laura C; Ramsey, Scott D; Veenstra, David L; Tunis, Sean R

2012-03-01

AIMS: Stakeholder engagement is fundamental to comparative effectiveness research (CER), but lacks consistent terminology. This paper aims to define stakeholder engagement and present a conceptual model for involving stakeholders in CER. MATERIALS #ENTITYSTARTX00026; METHODS: The definitions and model were developed from a literature search, expert input and experience with the Center for Comparative Effectiveness Research in Cancer Genomics, a proof-of-concept platform for stakeholder involvement in priority setting and CER study design. RESULTS: Definitions for stakeholder and stakeholder engagement reflect the target constituencies and their role in CER. The 'analytic-deliberative' conceptual model for stakeholder engagement illustrates the inputs, methods and outputs relevant to CER. The model differentiates methods at each stage of the project; depicts the relationship between components; and identifies outcome measures for evaluation of the process. CONCLUSION: While the definitions and model require testing before being broadly adopted, they are an important foundational step and will be useful for investigators, funders and stakeholder groups interested in contributing to CER.

Comparative toxicity effect of bush tea leaves ( Hyptis suaveolens ...

African Journals Online (AJOL)

Hyptis suaveolens) were compared for their toxicity effect on the larvae of the yellow fever mosquito Aedes aegypti collected from disused tyres beside College of Natural Sciences building University of Agriculture, Abeokuta, Nigeria.

Alternatives to animal testing: research, trends, validation, regulatory acceptance.

Science.gov (United States)

Huggins, Jane

2003-01-01

Current trends and issues in the development of alternatives to the use of animals in biomedical experimentation are discussed in this position paper. Eight topics are considered and include refinement of acute toxicity assays; eye corrosion/irritation alternatives; skin corrosion/irritation alternatives; contact sensitization alternatives; developmental/reproductive testing alternatives; genetic engineering (transgenic) assays; toxicogenomics; and validation of alternative methods. The discussion of refinement of acute toxicity assays is focused primarily on developments with regard to reduction of the number of animals used in the LD(50) assay. However, the substitution of humane endpoints such as clinical signs of toxicity for lethality in these assays is also evaluated. Alternative assays for eye corrosion/irritation as well as those for skin corrosion/irritation are described with particular attention paid to the outcomes, both successful and unsuccessful, of several validation efforts. Alternative assays for contact sensitization and developmental/reproductive toxicity are presented as examples of methods designed for the examination of interactions between toxins and somewhat more complex physiological systems. Moreover, genetic engineering and toxicogenomics are discussed with an eye toward the future of biological experimentation in general. The implications of gene manipulation for research animals, specifically, are also examined. Finally, validation methods are investigated as to their effectiveness, or lack thereof, and suggestions for their standardization and improvement, as well as implementation are reviewed.

Alterations of gene expression indicating effects on estrogen signaling and lipid homeostasis in seabream hepatocytes exposed to extracts of seawater sampled from a coastal area of the central Adriatic Sea (Italy).

Science.gov (United States)

Cocci, Paolo; Capriotti, Martina; Mosconi, Gilberto; Campanelli, Alessandra; Frapiccini, Emanuela; Marini, Mauro; Caprioli, Giovanni; Sagratini, Gianni; Aretusi, Graziano; Palermo, Francesco Alessandro

2017-02-01

Recent evidences suggest that the toxicological effects of endocrine disrupting chemicals (EDCs) involve multiple nuclear receptor-mediated pathways, including estrogen receptor (ER) and peroxisome proliferator-activated receptor (PPAR) signaling systems. Thus, our objective in this study was to detect the summated endocrine effects of EDCs with metabolic activity in coastal waters of the central Adriatic Sea by means of a toxicogenomic approach using seabream hepatocytes. Gene expression patterns were also correlated with seawater levels of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). We found that seawater extracts taken at certain areas induced gene expression profiles of ERα/vitellogenin, PPARα/Stearoyl-CoA desaturase 1A, cytochrome P4501A (CYP1A) and metallothionein. These increased levels of biomarkers responses correlated with spatial distribution of PAHs/PCBs concentrations observed by chemical analysis in the different study areas. Collectively, our data give a snapshot of the presence of complex EDC mixtures that are able to perturb metabolic signaling in coastal marine waters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modern needs in health technology assessment: a study of comparative effectiveness

Directory of Open Access Journals (Sweden)

A. V. Pavlysh

2013-01-01

Full Text Available Health technology assessment is a key component of healthcare decision making in most of the developed countries. Comparative effectiveness research as one of the elements of such assessment is becoming increasingly important in recent years. It is based on the effectiveness analysis of health technologies in real clinical practice setting. The authors have analyzed publications dedicated to these issues and showed the main methods of such study, its peculiarities, advantages and disadvantages. It has been revealed that the most frequently used designs of expert analysis are observational and pragmatic randomized studies. The main recommendations on analyzing comparative effectiveness are given in view of the literary data.

Comparative Antitussive Effects of Medicinal Plants and Their Constituents.

Science.gov (United States)

Saadat, Saeideh; Shakeri, Farzaneh; Boskabady, Mohammad Hossein

2018-01-15

Context • The cough is a protective reflex, with 2 types, one being more sensitive to mechanical stimulation and the other to chemical stimulation, such as sulfur dioxide, ammonia, citric acid, and capsaicin. Some evidence is available that suppressant therapy is most effective when used for the short-term reduction of coughing. Today, use of herbal drugs is increasing all over the world for various ailments, including to provide antitussive activity. Objective • The study intended to review the antitussive effects of various extracts, some fractions, and some constituents of the studied medicinal plants. Design • Various databases, including the Medline, Science Direct, Scopus, and Google Scholar, were searched for studies published between 1978 and 2015, using the keywords antitussive and cough and the names of various medicinal plants and their constituents. Setting • The study took place in the districts related to Mashhad University of Medical Sciences (Mashhad, Iran). Outcome Measures • The antitussive effects of medicinal plants and their constituents were normalized to 50 mg/kg and 1 mg/mL against various cough stimulants and compared. Results • The most potent antitussive effect was observed for Nigella sativa and Linum usitatissimum on coughs induced by sulfur dioxide. Artemisia absinthium showed a higher antitussive effect on cough induced by ammonia compared with the other studied medicinal plants. The antitussive effects of Cuminum cyminum and Glycyrrhiza glabra were more potent on cough induced by citric acid than other medicinal plants. Conclusions • These results suggest the therapeutic potential of the studied medicinal plants as antitussive therapies. However, only a few clinical studies have examined the antitussive effects of medicinal plants, and more clinical studies are needed. The underlying mechanisms of the antitussive effects of medicinal plants should be also examined in further studies.

"Families" in International Context: Comparing Institutional Effects across Western Societies

Science.gov (United States)

Cooke, Lynn Prince; Baxter, Janeen

2010-01-01

We review comparative evidence of institutional effects on families in Western societies. We focus on 2 key aspects of family life: gendered divisions of labor and people's transitions into, within, and out of relationships. Many individual-level models assume the effects are robust across countries. The international evidence over the past decade…

Comparative effectiveness of non-print media and live CME

Directory of Open Access Journals (Sweden)

Kuldeep Singh

2015-01-01

Full Text Available Continuing Medical Education is an integral ingredient of professional development of health care providers. The educational activity can be delivered by different modes. Here we share our experience of using Digital Video Disc (DVD of a CME on Sleep Medicine as an alternative and cost effective mode.Objective: To assess improvement in knowledge and competencies in terms of comparative effectiveness of a model CME program using validated non-print medium for medical education.Methods: Recorded and validated DVD of talks delivered at NAMS-AIIMS Regional Symposium on Sleep Medicine was played to the participants in presence of one of the content experts. Video scripts of talk were also distributed to the participants. The assessment of participants and program evaluation of this CME was compared to the previously held live CME.Results: Eighty nine participants completed both pre and post test. Mean score increased from 9.91± 3.5 to 14.09 ± 2.85. Pass percentage based on an arbitrary cut off of 50%, increased from 8.3 to 43.8 (p< 0.001. Among the live CME group, mean score improved from 12.1±4.6 to 18.3 ± 3.8. Comparative analysis between live and DVD based CME showed improvement in scores of 6.17 and 4.18 respectively while pass percentage of 84.7 and 43.8 post CME among two modes were significant. The program evaluation showed identical level of satisfaction in all parameters except they were less satisfied vis-a-vis 'organizers made use of any critical comments I made' since all locally available resource persons were not present. Activity could be completed at just half the cost of live CME.Conclusions: The educational background and selection process of UG students between two medical institutes were strikingly different. While students at one institute were selected by highly competitive exam at All India level, the students at other institute were selected through state level competitive examination. In spite of that, results showed

Comparative effectiveness research and medical informatics.

Science.gov (United States)

D'Avolio, Leonard W; Farwell, Wildon R; Fiore, Louis D

2010-12-01

As is the case for environmental, ecological, astronomical, and other sciences, medical practice and research finds itself in a tsunami of data. This data deluge, due primarily to the introduction of digitalization in routine medical care and medical research, affords the opportunity for improved patient care and scientific discovery. Medical informatics is the subdiscipline of medicine created to make greater use of information in order to improve healthcare. The 4 areas of medical informatics research (information access, structure, analysis, and interaction) are used as a framework to discuss the overlap in information needs of comparative effectiveness research and potential contributions of medical informatics. Examples of progress from the medical informatics literature and the Veterans Affairs Healthcare System are provided. Published by Elsevier Inc.

The policy debate over public investment in comparative effectiveness research.

Science.gov (United States)

Rich, Eugene C

2009-06-01

Policy makers across the political spectrum, as well as many clinicians and physician professional associations, have proposed that better information on comparative clinical effectiveness should be a key element of any solution to the US health-care cost crisis. This superficial consensus hides intense disagreements over critical issues essential to any new public effort to promote more comparative effectiveness research (CER). This article reviews the background for these disputes, summarizes the different perspectives represented by policy makers and advocates, and offers a framework to aid both practicing and academic internists in understanding the key elements of the emerging debate. Regarding the fundamental question of "what is CER," disagreements rage over whether value or cost effectiveness should be a consideration, and how specific patient perspectives should be reflected in the development and the use of such research. The question of how to pay for CER invokes controversies over the role of the market in producing such information and the private (e.g., insurers and employers) versus public responsibility for its production. The financing debate further highlights the high stakes of comparative effectiveness research, and the risks of stakeholder interests subverting any public process. Accordingly there are a range of proposals for the federal government's role in prioritization, development, and dissemination of CER. The internal medicine community, with its long history of commitment to scientific medical practice and its leadership in evidence-based medicine, should have a strong interest and play an active role in this debate.

Antiseptic mouth rinses: an update on comparative effectiveness, risks and recommendations.

Science.gov (United States)

Osso, Diane; Kanani, Nehal

2013-02-01

Antiseptic mouth rinses are widely recommended and marketed to improve oral health. This article summarizes current studies on the comparative effectiveness of selected antiseptic mouth rinses in controlling plaque and gingivitis, as well as risks associated with daily exposure, including salivary flow rate, oral cancer and wear of composite restorations. Electronic database searches were conducted using Google Scholar and PubMed to identify articles comparing the effectiveness of 4 commercially marketed antiseptic mouth rinses differing in active ingredients (0.12% chlorhexidine gluconate, essential oils (menthol, thymol and eucalyptol) and methyl salicylate, 0.7% cetylpyridinium chloride and 20% aloe vera gel) for controlling plaque and gingivitis. Criteria for inclusion included controlled clinical trials and systematic reviews appearing in English language publications evaluating the comparative effectiveness of the mouth rinses in controlling plaque and gingivitis, as well as risks associated with daily usage. The majority of studies have shown mouth rinses containing chlorhexidine gluconate or essential oils and methyl salicylate provide clinically significant anti-gingivitis and anti-plaque benefits. Cetylpyridinium chloride has been found to provide only limited clinical benefits compared to inactive control mouth rinse. Inadequate evidence is available to evaluate the clinical effectiveness of aloe vera gel. Chlorhexidine, essential oils and cetylpyridinium have been found to be safe. However, limited data are available on the effects of the mouth rinse on wear patterns of dental restorations. Studies reviewed reported no significant difference in salivary flow rate related to alcohol based mouth rinse. Research supports the effectiveness of antiseptic mouth rinses in reducing plaque and gingivitis as an adjunct to home care. Insufficient evidence is available to support the claim that oral antiseptics can reduce the risk of developing periodontitis or the

Comparative Effects of Tri-Polar Eclectic Teaching Approach on ...

African Journals Online (AJOL)

This is an experimental study that examined the comparative effects of Tripolar Interactionist teaching strategy on the academic performance of Junior Secondary School III students of Adeyemi Demonstration secondary School Ondo in social studies. The instrument used for the study includes scheme of work, lesson notes ...

Preference-based comparative effectiveness and cost–effectiveness: a review and relevance of value-based medicine for vitreoretinal interventions.

Science.gov (United States)

Brown, Melissa M; Brown, Gary C; Lieske, Heidi B; Lieske, P Alexander

2012-05-01

This analysis discusses the comparative effectiveness and cost-effectiveness of vitreoretinal interventions, measured in quality-adjusted life years (QALYs) and percentage patient value (PPV gain, or improvement in quality of life and/or length of life). The material is relevant since the Patient Protection and Affordable Care Act enacted by Congress with the support of the President has emphasized the critical importance of patient-based preferences. The majority of preference-based, comparative effectiveness and cost-effectiveness vitreoretinal interventions assessed in the US healthcare literature are Value-Based Medicine analyses, thus comparable. These interventions confer a mean patient (human) value gain (improvement in quality of life) of 8.3% [SD 6.3%, 95% confidence interval (CI) + 2.6%]. The average cost-utility of these vitreoretinal interventions is US$23 026/QALY (SD US$24 508, 95% CI + US$8770). Most vitreoretinal interventions are very cost effective using a conventional US standard of US$50 000/QALY as the upper anchor for a very cost-effective intervention, and the World Health Organization of approximately US$142 200/QALY as the upper anchor for a cost-effective intervention. Most vitreoretinal interventions confer considerable patient value and are very cost effective. Further standardization across healthcare is needed in the preference-based, comparative and cost-utility (cost-effectiveness) arena. The metrics of PPV (percentage patient value) gain and US$/PPV (dollars expended per percentage patient value gain) or financial value gain may be more user-friendly than the QALY.

Comparative effects of Potash Sodium Chloride (PSC) mixture and ...

African Journals Online (AJOL)

Honey (Mellifica sp) is produced by Apis mellifera africana, widely consumed without prescription or restriction, and has been shown to possess wound healing and antitusive properties. Comparative study of the effects of honey paste and Potash Sodium Chloride (PSC) mixture on the healing of incisional wound on albino ...

Comparing the effect of bioflocculant with synthetic polymers on ...

African Journals Online (AJOL)

This study was aimed at introducing a novel bioflocculant to enhance anaerobic granulation in a UASB reactor for lowstrength synthetic wastewater and comparing the effect with synthetic polymers. A laboratory-scale study was undertaken to achieve this goal. Four identical UASB reactors were operated in parallel in the ...

A Comparative Effectiveness Education Trial for Lifestyle Health Behavior Change in African Americans

Science.gov (United States)

Halbert, Chanita Hughes; Bellamy, Scarlett; Briggs, Vanessa; Delmoor, Ernestine; Purnell, Joseph; Rogers, Rodney; Weathers, Benita; Johnson, Jerry C.

2017-01-01

Obesity and excess weight are significant clinical and public health issues that disproportionately affect African Americans because of physical inactivity and unhealthy eating. We compared the effects of alternate behavioral interventions on obesity-related health behaviors. We conducted a comparative effectiveness education trial in a…

Toxicogenomics-based identification of mechanisms for direct immunotoxicity.

Science.gov (United States)

Shao, Jia; Katika, Madhumohan R; Schmeits, Peter C J; Hendriksen, Peter J M; van Loveren, Henk; Peijnenburg, Ad A C M; Volger, Oscar L

2013-10-01

Compounds with direct immunotoxic properties, including metals, mycotoxins, agricultural pesticides, and industrial chemicals, form potential human health risks due to exposure through food, drinking water, and the environment. Insights into the mechanisms of action are currently lacking for the majority of these direct immunotoxicants. Therefore, the present work aimed to gain insights into the molecular mechanisms underlying direct immunotoxicity. To this end, we assessed in vitro the effects of 31 test compounds on the transcriptome of the human Jurkat T-cell line. These compounds included direct immunotoxicants, immunosuppressive drugs with different mode of actions, and nonimmunotoxic control chemicals. Pathway analysis of the microarray data allowed us to identify canonical pathways and Gene Ontology processes that were transcriptionally regulated in common by immunotoxicants (1) with structural similarities, such as tributyltin chloride and tributyltin oxide that activated the retinoic acid/X receptor signaling pathway and (2) without structural similarities, such as As2O3, dibutyltin chloride, diazinon, MeHg, ochratoxin A (OTA), S9-treated OTA, S9-treated cyclophosphamide, and S9-treated benzo[a]pyrene, which activated unfolded protein response, and FTY720, lindane, and propanil, which activated the cholesterol biosynthesis pathway. In addition, processes uniquely affected by individual immunotoxicants were identified, such as the induction of Notch receptor signaling and the downregulation of acute-phase response genes by OTA. These findings were validated by quantitative real-time PCR analysis of genes involved in these processes. Our study indicated that diverse modes of action are involved in direct immunotoxicity and that a set of pathways or genes, rather than one single gene, can be used to screen compounds for direct immunotoxicity.

Assessment of the usefulness of the murine cytotoxic T cell line CTLL-2 for immunotoxicity screening by transcriptomics

NARCIS (Netherlands)

Schmeits, P.C.; Volger, O.L.; Zandvliet, E.T.; Loveren, van H.; Peijnenburg, A.; Hendriksen, P.J.

2013-01-01

A toxicogenomics approach was applied to assess the usefulness of the mouse cytotoxic T cell line CTLL-2 for in vitro immunotoxicity testing. CTLL-2 cells were exposed for 6 h to two model immunotoxic compounds: (1) the mycotoxin deoxynivalenol (DON, 1 and 2 µM), a ribotoxic stress inducer, and (2)

Composite scores in comparative effectiveness research: counterbalancing parsimony and dimensionality in patient-reported outcomes.

Science.gov (United States)

Schwartz, Carolyn E; Patrick, Donald L

2014-07-01

When planning a comparative effectiveness study comparing disease-modifying treatments, competing demands influence choice of outcomes. Current practice emphasizes parsimony, although understanding multidimensional treatment impact can help to personalize medical decision-making. We discuss both sides of this 'tug of war'. We discuss the assumptions, advantages and drawbacks of composite scores and multidimensional outcomes. We describe possible solutions to the multiple comparison problem, including conceptual hierarchy distinctions, statistical approaches, 'real-world' benchmarks of effectiveness and subgroup analysis. We conclude that comparative effectiveness research should consider multiple outcome dimensions and compare different approaches that fit the individual context of study objectives.

Comparative effectiveness of different types of cervical laminoplasty.

Science.gov (United States)

Heller, John G; Raich, Annie L; Dettori, Joseph R; Riew, K Daniel

2013-10-01

Study Design Systematic review. Study Rationale Numerous cervical laminoplasty techniques have been described but there are few studies that have compared these to determine the superiority of one over another. Clinical Questions The clinical questions include key question (KQ)1: In adults with cervical myelopathy from ossification of the posterior longitudinal ligament (OPLL) or spondylosis, what is the comparative effectiveness of open door cervical laminoplasty versus French door cervical laminoplasty? KQ2: In adults with cervical myelopathy from OPLL or spondylosis, are postoperative complications, including pain and infection, different for the use of miniplates versus the use of no plates following laminoplasty? KQ3: Do these results vary based on early active postoperative cervical motion? Materials and Methods A systematic review of the English-language literature was undertaken for articles published between 1970 and March 11, 2013. Electronic databases and reference lists of key articles were searched to identify studies evaluating (1) open door cervical laminoplasty and French door cervical laminoplasty and (2) the use of miniplates or no plates in cervical laminoplasty for the treatment of cervical spondylotic myelopathy or OPLL in adults. Studies involving traumatic onset, cervical fracture, infection, deformity, or neoplasms were excluded, as were noncomparative studies. Two independent reviewers (A.L.R., J.R.D.) assessed the level of evidence quality using the Grades of Recommendations Assessment, Development and Evaluation system, and disagreements were resolved by consensus. Results We identified three studies (one of class of evidence [CoE] II and two of CoE III) meeting our inclusion criteria comparing open door cervical laminoplasty with French door laminoplasty and two studies (one CoE II and one CoE III) comparing the use of miniplates with no plates. Data from one randomized controlled trial (RCT) and two retrospective cohort

Genome wide analyses of metal responsive genes in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Michael eAschner

2012-04-01

Full Text Available Metals are major contaminants that influence human health. Many metals have physiologic roles, but excessive levels can be harmful. Advances in technology have made toxicogenomic analyses possible to characterize the effects of metal exposure on the entire genome. Much of what is known about cellular responses to metals has come from mammalian systems; however the use of non-mammalian species is gaining wider attention. Caenorhabditis elegans (C. elegans is a small round worm whose genome has been fully sequenced and its development from egg to adult is well characterized. It is an attractive model for high throughput screens due to its short lifespan, ease of genetic mutability, low cost and high homology with humans. Research performed in C. elegans has led to insights in apoptosis, gene expression and neurodegeneration, all of which can be altered by metal exposure. Additionally, by using worms one can potentially study how the mechanisms that underline differential responses to metals in nematodes and humans, allowing for identification of novel pathways and therapeutic targets. In this review, toxicogenomic studies performed in C. elegans exposed to various metals will be discussed, highlighting how this non-mammalian system can be utilized to study cellular processes and pathways induced by metals. Recent work focusing on neurodegeneration in Parkinson’s disease will be discussed as an example of the usefulness of genetic screens in C. elegans and the novel findings that can be produced.

Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood.

Science.gov (United States)

Pennings, Jeroen L A; Jennen, Danyel G J; Nygaard, Unni C; Namork, Ellen; Haug, Line S; van Loveren, Henk; Granum, Berit

2016-01-01

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds that have widespread use in consumer and industrial applications. PFAS are considered environmental pollutants that have various toxic properties, including effects on the immune system. Recent human studies indicate that prenatal exposure to PFAS leads to suppressed immune responses in early childhood. In this study, data from the Norwegian BraMat cohort was used to investigate transcriptomics profiles in neonatal cord blood and their association with maternal PFAS exposure, anti-rubella antibody levels at 3 years of age and the number of common cold episodes until 3 years. Genes associated with PFAS exposure showed enrichment for immunological and developmental functions. The analyses identified a toxicogenomics profile of 52 PFAS exposure-associated genes that were in common with genes associated with rubella titers and/or common cold episodes. This gene set contains several immunomodulatory genes (CYTL1, IL27) as well as other immune-associated genes (e.g. EMR4P, SHC4, ADORA2A). In addition, this study identified PPARD as a PFAS toxicogenomics marker. These markers can serve as the basis for further mechanistic or epidemiological studies. This study provides a transcriptomics connection between prenatal PFAS exposure and impaired immune function in early childhood and supports current views on PPAR- and NF-κB-mediated modes of action. The findings add to the available evidence that PFAS exposure is immunotoxic in humans and support regulatory policies to phase out these substances.

Simulating changes to emergency care resources to compare system effectiveness.

Science.gov (United States)

Branas, Charles C; Wolff, Catherine S; Williams, Justin; Margolis, Gregg; Carr, Brendan G

2013-08-01

To apply systems optimization methods to simulate and compare the most effective locations for emergency care resources as measured by access to care. This study was an optimization analysis of the locations of trauma centers (TCs), helicopter depots (HDs), and severely injured patients in need of time-critical care in select US states. Access was defined as the percentage of injured patients who could reach a level I/II TC within 45 or 60 minutes. Optimal locations were determined by a search algorithm that considered all candidate sites within a set of existing hospitals and airports in finding the best solutions that maximized access. Across a dozen states, existing access to TCs within 60 minutes ranged from 31.1% to 95.6%, with a mean of 71.5%. Access increased from 0.8% to 35.0% after optimal addition of one or two TCs. Access increased from 1.0% to 15.3% after optimal addition of one or two HDs. Relocation of TCs and HDs (optimal removal followed by optimal addition) produced similar results. Optimal changes to TCs produced greater increases in access to care than optimal changes to HDs although these results varied across states. Systems optimization methods can be used to compare the impacts of different resource configurations and their possible effects on access to care. These methods to determine optimal resource allocation can be applied to many domains, including comparative effectiveness and patient-centered outcomes research. Copyright © 2013 Elsevier Inc. All rights reserved.

Value-based medicine, comparative effectiveness, and cost-effectiveness analysis of topical cyclosporine for the treatment of dry eye syndrome.

Science.gov (United States)

Brown, Melissa M; Brown, Gary C; Brown, Heidi C; Peet, Jonathan; Roth, Zachary

2009-02-01

To assess the comparative effectiveness and cost-effectiveness (cost-utility) of a 0.05% emulsion of topical cyclosporine (Restasis; Allergan Inc, Irvine, California) for the treatment of moderate to severe dry eye syndrome that is unresponsive to conventional therapy. Data from 2 multicenter, randomized, clinical trials and Food and Drug Administration files for topical cyclosporine, 0.05%, emulsion were used in Center for Value-Based Medicine analyses. Analyses included value-based medicine as a comparative effectiveness analysis and average cost-utility analysis using societal and third-party insurer cost perspectives. Outcome measures of comparative effectiveness were quality-adjusted life-year (QALY) gain and percentage of improvement in quality of life, and for cost-effectiveness were cost-utility ratio (CUR) using dollars per QALY. Topical cyclosporine, 0.05%, confers a value gain (comparative effectiveness) of 0.0319 QALY per year compared with topical lubricant therapy, a 4.3% improvement in quality of life for the average patient with moderate to severe dry eye syndrome that is unresponsive to conventional lubricant therapy. The societal perspective incremental CUR for cyclosporine over vehicle therapy is $34,953 per QALY and the societal perspective average CUR is $11,199 per QALY. The third-party-insurer incremental CUR is $37,179 per QALY, while the third-party-insurer perspective average CUR is $34,343 per QALY. Topical cyclosporine emulsion, 0.05%, confers considerable patient value and is a cost-effective therapy for moderate to severe dry eye syndrome that is unresponsive to conventional therapy.

Comparing fixed effects and covariance structure estimators for panel data

DEFF Research Database (Denmark)

Ejrnæs, Mette; Holm, Anders

2006-01-01

In this article, the authors compare the traditional econometric fixed effect estimator with the maximum likelihood estimator implied by covariance structure models for panel data. Their findings are that the maximum like lipoid estimator is remarkably robust to certain types of misspecifications...

Practical guide to understanding Comparative Effectiveness Research (CER).

Science.gov (United States)

Neely, J Gail; Sharon, Jeffrey D; Graboyes, Evan M; Paniello, Randal C; Nussenbaum, Brian; Grindler, David J; Dassopoulos, Themistocles

2013-12-01

"Comparative effectiveness research" (CER) is not a new concept; however, recently it has been popularized as a method to develop scientifically sound actionable data by which patients, physicians, payers, and policymakers may make informed health care decisions. Fundamental to CER is that the comparative data are derived from large diverse populations of patients assembled from point-of-care general primary care practices and that measured outcomes include patient value judgments. The challenge is to obtain scientifically valid data to be acted upon by decision-making stakeholders with potentially quite diversely different agenda. The process requires very thoughtful research designs modulated by complex statistical and analytic methods. This article is composed of a guiding narrative with an extensive set of tables outlining many of the details required in performing and understanding CER. It ends with short discussions of three example papers, limitations of the method, and how a practicing physician may view such reports.

A Study of the Social Effects in a Comparative Assessment among the Electricity Generating Systems

International Nuclear Information System (INIS)

Kim, Kil Yoo; Kim, Tae Woon

2007-01-01

A comparative assessment among 7 electricity generating systems by considering their environmental impacts, risks, health effects, and social effects was studied last year. The compared electricity generating systems are nuclear, coal, LNG, hydro, oil, wind, photovoltaic (=solar) ones. In last year's work, the social effects were handled by a public acceptance based on an aversion. However, in this paper, the social effects were also studied by a preference in view of the 'willingness to pay' (WTP). With the new social effects study, a comparative analysis of the 7 electricity generation systems was performed in this paper

Quantifying and Comparing Effects of Climate Engineering Methods on the Earth System

Science.gov (United States)

Sonntag, Sebastian; Ferrer González, Miriam; Ilyina, Tatiana; Kracher, Daniela; Nabel, Julia E. M. S.; Niemeier, Ulrike; Pongratz, Julia; Reick, Christian H.; Schmidt, Hauke

2018-02-01

To contribute to a quantitative comparison of climate engineering (CE) methods, we assess atmosphere-, ocean-, and land-based CE measures with respect to Earth system effects consistently within one comprehensive model. We use the Max Planck Institute Earth System Model (MPI-ESM) with prognostic carbon cycle to compare solar radiation management (SRM) by stratospheric sulfur injection and two carbon dioxide removal methods: afforestation and ocean alkalinization. The CE model experiments are designed to offset the effect of fossil-fuel burning on global mean surface air temperature under the RCP8.5 scenario to follow or get closer to the RCP4.5 scenario. Our results show the importance of feedbacks in the CE effects. For example, as a response to SRM the land carbon uptake is enhanced by 92 Gt by the year 2100 compared to the reference RCP8.5 scenario due to reduced soil respiration thus reducing atmospheric CO2. Furthermore, we show that normalizations allow for a better comparability of different CE methods. For example, we find that due to compensating processes such as biogeophysical effects of afforestation more carbon needs to be removed from the atmosphere by afforestation than by alkalinization to reach the same global warming reduction. Overall, we illustrate how different CE methods affect the components of the Earth system; we identify challenges arising in a CE comparison, and thereby contribute to developing a framework for a comparative assessment of CE.

Comparing the effect of various pipe materials on biofilm formation ...

African Journals Online (AJOL)

Comparing the effect of various pipe materials on biofilm formation in chlorinated and combined chlorine-chloraminated water systems. ... The capability of bacterial regrowth occurring on the surface of test pipe materials during this period was linked to the depletion of the concentration of monochloramine residual.

Comparative Effects Of “Do It” Creativity And Emotional Mastery ...

African Journals Online (AJOL)

This study investigated the comparative effects of “DO IT” creativity and Emotional Mastery techniques in fostering emotional intelligence among adolescents with physical impairments in Oyo State, Nigeria. There were ninety participants randomly selected from three special institutions in the state, namely: Cheshire High ...

How well do commonly used data presentation formats support comparative effectiveness evaluations?

Science.gov (United States)

Dolan, James G; Qian, Feng; Veazie, Peter J

2012-01-01

Good decisions depend on an accurate understanding of the comparative effectiveness of decision alternatives. The best way to convey data needed to support these comparisons is unknown. To determine how well 5 commonly used data presentation formats convey comparative effectiveness information. The study was an Internet survey using a factorial design. Participants consisted of 279 members of an online survey panel. Study participants compared outcomes associated with 3 hypothetical screening test options relative to 5 possible outcomes with probabilities ranging from 2 per 5000 (0.04%) to 500 per 1000 (50%). Data presentation formats included a table, a "magnified" bar chart, a risk scale, a frequency diagram, and an icon array. Outcomes included the number of correct ordinal judgments regarding the more likely of 2 outcomes, the ratio of perceived versus actual relative likelihoods of the paired outcomes, the intersubject consistency of responses, and perceived clarity. The mean number of correct ordinal judgments was 12 of 15 (80%), with no differences among data formats. On average, there was a 3.3-fold difference between perceived and actual likelihood ratios (95% confidence interval = 3.0-3.6). Comparative judgments based on flowcharts, icon arrays, and tables were all significantly more accurate and consistent than those based on risk scales and bar charts (P charts, and flow diagrams. None of the data presentation formats studied can reliably provide patients, especially those with low subjective numeracy, with an accurate understanding of comparative effectiveness information.

The economics of comparative effectiveness studies: societal and private perspectives and their implications for prioritizing public investments in comparative effectiveness research.

Science.gov (United States)

Meltzer, David; Basu, Anirban; Conti, Rena

2010-01-01

Comparative effectiveness research (CER) can provide valuable information for patients, providers and payers. These stakeholders differ in their incentives to invest in CER. To maximize benefits from public investments in CER, it is important to understand the value of CER from the perspectives of these stakeholders and how that affects their incentives to invest in CER. This article provides a conceptual framework for valuing CER, and illustrates the potential benefits of such studies from a number of perspectives using several case studies. We examine cases in which CER provides value by identifying when one treatment is consistently better than others, when different treatments are preferred for different subgroups, and when differences are small enough that decisions can be made based on price. We illustrate these findings using value-of-information techniques to assess the value of research, and by examining changes in pharmaceutical prices following publication of a comparative effectiveness study. Our results suggest that CER may have high societal value but limited private return to providers or payers. This suggests the importance of public efforts to promote the production of CER. We also conclude that value-of-information tools may help inform policy decisions about how much public funds to invest in CER and how to prioritize the use of available public funds for CER, in particular targeting public CER spending to areas where private incentives are low relative to social benefits.

Differences among consumer segments with regard to perceptions of comparative effectiveness research.

Science.gov (United States)

Williams, Sunyna S; Frost, Sloane L

2014-11-01

To examine differences among health-related decision-making consumer segments with regard to knowledge, skills, attitudes, and behaviors pertinent to comparative effectiveness research. Data were collected via an online survey from 603 adults with chronic conditions. Consumer segment was determined using a two-item tool. Active consumers (high skills and motivation) reported the highest levels of engagement in various behaviors. Passive consumers (low skills and motivation) reported the lowest levels of engagement in various behaviors. High-effort consumers (low skills, high motivation) reported more positive attitudes and opinions and more engagement in various behaviors than did complacent consumers (high skills, low motivation). Effective translation and dissemination of comparative effectiveness research will require the development of approaches tailored to consumers with varying levels of skills and motivation.

Radon as a medicine. Therapeutic effectiveness, biological mechanism and comparative risk assessment

International Nuclear Information System (INIS)

Deetjen, Peter; Falkenbach, Albrecht; Harder, Dietrich; Joeckel, Hans; Kaul, Alexander; Philipsborn, Henning von

2014-01-01

Proofs of the therapeutic efficiency of balneological radon applications administered to patients suffering from rheumatic diseases, investigations into the biological action mechanism associated with the alpha particles emitted by radon and its radioactive daughter products, and the comparative risk assessment of radon treatment and medicinal pain therapy have been the research projects whose results are summarized in this book. Controlled clinical studies, if possible performed as prospective, randomized and placebo-controlled double blind studies, have given evidence that the therapeutic effects of balneological radon applications - long-lasting pain reduction and reduced consumption of medicines compared with controls - are significantly persisting over many post-treatment months. The molecular and cellular mechanism of action underlying these long-lasting therapeutic effects has been identified as the down-regulation of cellular immune responses, initiated by cellular apoptosis sequential to low alpha particle doses and by the subsequent release of anti-inflammatory cytokines. The unwanted side-effects of non-steroidal anti-rheumatic drug treatments have to be compared with the absence of side effects from the balneological radon applications which merely involve radiation doses well below the mean value and the fluctuation width of the annual doses attributable to everybody's natural radiation exposure.

Radon as a medicine. Therapeutic effectiveness, biological mechanism and comparative risk assessment

Energy Technology Data Exchange (ETDEWEB)

Deetjen, Peter; Falkenbach, Albrecht; Harder, Dietrich; Joeckel, Hans; Kaul, Alexander; Philipsborn, Henning von

2014-07-01

Proofs of the therapeutic efficiency of balneological radon applications administered to patients suffering from rheumatic diseases, investigations into the biological action mechanism associated with the alpha particles emitted by radon and its radioactive daughter products, and the comparative risk assessment of radon treatment and medicinal pain therapy have been the research projects whose results are summarized in this book. Controlled clinical studies, if possible performed as prospective, randomized and placebo-controlled double blind studies, have given evidence that the therapeutic effects of balneological radon applications - long-lasting pain reduction and reduced consumption of medicines compared with controls - are significantly persisting over many post-treatment months. The molecular and cellular mechanism of action underlying these long-lasting therapeutic effects has been identified as the down-regulation of cellular immune responses, initiated by cellular apoptosis sequential to low alpha particle doses and by the subsequent release of anti-inflammatory cytokines. The unwanted side-effects of non-steroidal anti-rheumatic drug treatments have to be compared with the absence of side effects from the balneological radon applications which merely involve radiation doses well below the mean value and the fluctuation width of the annual doses attributable to everybody's natural radiation exposure.

COMPARATIVE ANALYSIS OF QUANTUM EFFECTS IN NANOSCALE MULTIGATE MOSFETS USING VARIATIONAL APPROACH

Directory of Open Access Journals (Sweden)

V. PALANICHAMY

2015-02-01

Full Text Available In this work, the performance of multiple-gate SOI MOSFETs is analysed using variational approach including quantum effects. An analytical model is derived to accounting the quantum effects at the silicon (Si/silicon dioxide (SiO2 interface. A general procedure is used for calculating the quantum inversion charge density. Using this inversion charge density, the drain current is obtained. Our model results are compared with the simulation results and its shows very good agreement. Our results highlighted that cylindrical surrounding gate MOSFET is a good candidate to obtain the high drain current compared with other two devices.

Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

International Nuclear Information System (INIS)

Theunissen, P.T.; Robinson, J.F.; Pennings, J.L.A.; Herwijnen, M.H. van; Kleinjans, J.C.S.; Piersma, A.H.

2012-01-01

Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

Energy Technology Data Exchange (ETDEWEB)

Theunissen, P.T., E-mail: Peter.Theunissen@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Robinson, J.F. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Pennings, J.L.A. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Herwijnen, M.H. van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Kleinjans, J.C.S. [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Piersma, A.H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht (Netherlands)

2012-08-01

Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

Comparative analysis of two community stressors' long-term mental health effects

International Nuclear Information System (INIS)

Dew, M.A.; Bromet, E.J.; Schulberg, H.C.

1987-01-01

The investigation directly compared the long-term mental health consequences of two community-wide stressors, the Three Mile Island (TMI) nuclear accident and widespread unemployment due to layoff, in demographically comparable samples of women. Results showed a marked degree of similarity in the stressors' effects: Levels of subclinical symptomatology were elevated to similar degrees in each sample during the year following stressor onset, and symptom levels remained elevated in each sample 2 to 3 1/2 years later. Moreover, variables identified as predictors of enduring psychological distress were virtually identical for the two samples. Additional analyses revealed that the mental health status of unemployed husbands mediated the negative psychological effects of layoff on their wives. Implications of these results for understanding the long-term consequences of exposure to community-wide stress are discussed

Observational studies in systematic [corrected] reviews of comparative effectiveness: AHRQ and the Effective Health Care Program.

Science.gov (United States)

Norris, Susan L; Atkins, David; Bruening, Wendy; Fox, Steven; Johnson, Eric; Kane, Robert; Morton, Sally C; Oremus, Mark; Ospina, Maria; Randhawa, Gurvaneet; Schoelles, Karen; Shekelle, Paul; Viswanathan, Meera

2011-11-01

Systematic reviewers disagree about the ability of observational studies to answer questions about the benefits or intended effects of pharmacotherapeutic, device, or procedural interventions. This study provides a framework for decision making on the inclusion of observational studies to assess benefits and intended effects in comparative effectiveness reviews (CERs). The conceptual model and recommendations were developed using a consensus process by members of the methods workgroup of the Effective Health Care Program of the Agency for Healthcare Research and Quality. In considering whether to use observational studies in CERs for addressing beneficial effects, reviewers should answer two questions: (1) Are there gaps in the evidence from randomized controlled trials (RCTs)? (2) Will observational studies provide valid and useful information? The latter question involves the following: (a) refocusing the study questions on gaps in the evidence from RCTs, (b) assessing the risk of bias of the body of evidence of observational studies, and (c) assessing whether available observational studies address the gap review questions. Because it is unusual to find sufficient evidence from RCTs to answer all key questions concerning benefit or the balance of benefits and harms, comparative effectiveness reviewers should routinely assess the appropriateness of inclusion of observational studies for questions of benefit. Furthermore, reviewers should explicitly state the rationale for inclusion or exclusion of observational studies when conducting CERs. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparative effectiveness research for the clinician researcher: a framework for making a methodological design choice.

Science.gov (United States)

Williams, Cylie M; Skinner, Elizabeth H; James, Alicia M; Cook, Jill L; McPhail, Steven M; Haines, Terry P

2016-08-17

Comparative effectiveness research compares two active forms of treatment or usual care in comparison with usual care with an additional intervention element. These types of study are commonly conducted following a placebo or no active treatment trial. Research designs with a placebo or non-active treatment arm can be challenging for the clinician researcher when conducted within the healthcare environment with patients attending for treatment.A framework for conducting comparative effectiveness research is needed, particularly for interventions for which there are no strong regulatory requirements that must be met prior to their introduction into usual care. We argue for a broader use of comparative effectiveness research to achieve translatable real-world clinical research. These types of research design also affect the rapid uptake of evidence-based clinical practice within the healthcare setting.This framework includes questions to guide the clinician researcher into the most appropriate trial design to measure treatment effect. These questions include consideration given to current treatment provision during usual care, known treatment effectiveness, side effects of treatments, economic impact, and the setting in which the research is being undertaken.

Gene expression analysis in rat lungs after intratracheal exposure to nanoparticles doped with cadmium

International Nuclear Information System (INIS)

Coccini, Teresa; Manzo, Luigi; Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura; Roda, Elisa

2011-01-01

Silica nanoparticles (NPs) incorporating cadmium (Cd) have been developed for a range of potential application including drug delivery devices. Occupational Cd inhalation has been associated with emphysema, pulmonary fibrosis and lung tumours. Mechanistically, Cd can induce oxidative stress and mediate cell-signalling pathways that are involved in inflammation.This in vivo study aimed at investigating pulmonary molecular effects of NPs doped with Cd (NP-Cd, 1 mg/animal) compared to soluble CdCl 2 (400 μg/animal), in Sprague Dawley rats treated intra-tracheally, 7 and 30 days after administration. NPs of silica containing Cd salt were prepared starting from commercial nano-size silica powder (HiSil T M T700 Degussa) with average pore size of 20 nm and surface area of 240 m 2 /g. Toxicogenomic analysis was performed by the DNA microarray technology (using Agilent Whole Rat Genome Microarray 4x44K) to evaluate changes in gene expression of the entire genome. These findings indicate that the whole genome analysis may represent a valuable approach to assess the whole spectrum of biological responses to cadmium containing nanomaterials.

Gene expression analysis in rat lungs after intratracheal exposure to nanoparticles doped with cadmium

Science.gov (United States)

Coccini, Teresa; Fabbri, Marco; Roda, Elisa; Grazia Sacco, Maria; Manzo, Luigi; Gribaldo, Laura

2011-07-01

Silica nanoparticles (NPs) incorporating cadmium (Cd) have been developed for a range of potential application including drug delivery devices. Occupational Cd inhalation has been associated with emphysema, pulmonary fibrosis and lung tumours. Mechanistically, Cd can induce oxidative stress and mediate cell-signalling pathways that are involved in inflammation.This in vivo study aimed at investigating pulmonary molecular effects of NPs doped with Cd (NP-Cd, 1 mg/animal) compared to soluble CdCl2 (400 μg/animal), in Sprague Dawley rats treated intra-tracheally, 7 and 30 days after administration. NPs of silica containing Cd salt were prepared starting from commercial nano-size silica powder (HiSil™ T700 Degussa) with average pore size of 20 nm and surface area of 240 m2/g. Toxicogenomic analysis was performed by the DNA microarray technology (using Agilent Whole Rat Genome Microarray 4×44K) to evaluate changes in gene expression of the entire genome. These findings indicate that the whole genome analysis may represent a valuable approach to assess the whole spectrum of biological responses to cadmium containing nanomaterials.

Comparative effectiveness of the SNaP™ Wound Care System.

Science.gov (United States)

Hutton, David W; Sheehan, Peter

2011-04-01

Diabetic lower extremity wounds cause substantial burden to healthcare systems, costing tens of thousands of dollars per episode. Negative pressure wound therapy (NPWT) devices have been shown to be cost-effective at treating these wounds, but the traditional devices use bulky electrical pumps that require a durable medical equipment rental-based procurement process. The Spiracur SNaP™ Wound Care System is an ultraportable NPWT system that does not use an electric pump and is fully disposable. It has superior healing compared to standard of care with modern dressings and comparable healing to traditional NPWT devices while giving patients greater mobility and giving clinicians a simpler procurement process. We used a mathematical model to analyse the costs of the SNaP™ system and compare them to standard of care and electrically powered NPWT devices. When compared to standard of care, the SNaP™ system saves over $9000 per wound treated and more than doubles the number of patients healed. The SNaP system has similar healing time to powered NPWT devices, but saves $2300 in Medicare payments or $2800 for private payers per wound treated. Our analysis shows that the SNaP™ system could save substantial treatment costs in addition to allowing patients greater freedom and mobility. © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review

DEFF Research Database (Denmark)

Hyllested, M; Jones, S; Pedersen, J L

2002-01-01

BACKGROUND: Quantitative reviews of postoperative pain management have demonstrated that the number of patients needed to treat for one patient to achieve at least 50% pain relief (NNT) is 2.7 for ibuprofen (400 mg) and 4.6 for paracetamol (1000 mg), both compared with placebo. However, direct...... comparisons between paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) have not been extensively reviewed. The aims of this review are (i) to compare the analgesic and adverse effects of paracetamol with those of other NSAIDs in postoperative pain, (ii) to compare the effects of combined...... paracetamol and NSAID with those of either drug alone, and (iii) to discuss whether the adverse effects of NSAIDs in short-term use are justified by their analgesic effects, compared with paracetamol. METHODS: Medline (1966 to January 2001) and the Cochrane Library (January 2001) were used to perform...

Comparing interactive videodisc training effectiveness to traditional training methods

International Nuclear Information System (INIS)

Kenworthy, N.W.

1987-01-01

Videodisc skills training programs developed by Industrial Training Corporation are being used and evaluated by major industrial facilities. In one such study, interactive videodisc training programs were compared to videotape and instructor-based training to determine the effectiveness of videodisc in terms of performance, training time and trainee attitudes. Results showed that when initial training was done using the interactive videodisc system, trainee performance was superior to the performance of trainees using videotape, and approximately equal to the performance of those trained by an instructor. When each method was used in follow-up training, interactive videodisc was definitely the most effective. Results also indicate that training time can be reduced using interactive videodisc. Attitudes of both trainees and instructors toward the interactive videodisc training were positive

Comparative Study on the Effects of Crude Extracts of Pterocarpus ...

African Journals Online (AJOL)

A comparative study on the effects of crude extracts of pterocarpus soyauxii and Telfairia occidentalis on haematological parameters of albino wistar rats was carried out. Forty nine albino rats of both sexes, weighing between 150 and 250 g were used for the study. The rats were divided into seven groups of seven rats each.

Comparative effectiveness of instructional methods: oral and pharyngeal cancer examination.

Science.gov (United States)

Clark, Nereyda P; Marks, John G; Sandow, Pamela R; Seleski, Christine E; Logan, Henrietta L

2014-04-01

This study compared the effectiveness of different methods of instruction for the oral and pharyngeal cancer examination. A group of thirty sophomore students at the University of Florida College of Dentistry were randomly assigned to three training groups: video instruction, a faculty-led hands-on instruction, or both video and hands-on instruction. The training intervention involved attending two sessions spaced two weeks apart. The first session used a pretest to assess students' baseline didactic knowledge and clinical examination technique. The second session utilized two posttests to assess the comparative effectiveness of the training methods on didactic knowledge and clinical technique. The key findings were that students performed the clinical examination significantly better with the combination of video and faculty-led hands-on instruction (p<0.01). All students improved their clinical exam skills, knowledge, and confidence in performing the oral and pharyngeal cancer examination independent of which training group they were assigned. Utilizing both video and interactive practice promoted greater performance of the clinical technique on the oral and pharyngeal cancer examination.

A call for action: comparative effectiveness research in asthma

OpenAIRE

Krishnan, Jerry A.; Schatz, Michael X.; Apter, Andrea J.

2010-01-01

Comparative effectiveness research (CER) has received considerable research attention in recent months, and efforts to promote CER are part of the newly enacted Patient Protection and Affordable Care Act. In this paper, we define CER, how it complements traditional efficacy research in asthma, and discuss how CER can help provide the basis for rational decision-making about the care of individual patients with asthma and how best to deliver this care in real-world settings. We present informa...

PRIVATE MANUFACTURERS’ THRESHOLDS TO INVEST IN COMPARATIVE EFFECTIVENESS TRIALS

OpenAIRE

Basu, Anirban; Meltzer, David

2012-01-01

The recent rush of enthusiasm for public investment in comparative effectiveness research (CER) in the United States has focused attention on these public investments. However, little attention has been given to how changing public investment in CER may affect private manufacturers’ incentives for CER, which has long been a major source of CER. In this work, based on a simple revenue maximizing economic framework, we generate predictions on thresholds to invest in CER for a private manufactur...

13 Comparative Effects of Cassava Starch and Simple Sugar in ...

African Journals Online (AJOL)

Arc. Usman A. Jalam

Abstract. Comparative effects of simple laboratory quality sugar and cassava starch on grade C35 concrete were studied in the laboratory. The simple white sugar was used at concentrations of 0 to 1% by weight of cement in concrete cured at 3, 7, 14 and 28 days using ordinary Portland cement. Cassava starch of the same ...

A review of toxicity and mechanisms of individual and mixtures of heavy metals in the environment.

Science.gov (United States)

Wu, Xiangyang; Cobbina, Samuel J; Mao, Guanghua; Xu, Hai; Zhang, Zhen; Yang, Liuqing

2016-05-01

The rational for the study was to review the literature on the toxicity and corresponding mechanisms associated with lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As), individually and as mixtures, in the environment. Heavy metals are ubiquitous and generally persist in the environment, enabling them to biomagnify in the food chain. Living systems most often interact with a cocktail of heavy metals in the environment. Heavy metal exposure to biological systems may lead to oxidation stress which may induce DNA damage, protein modification, lipid peroxidation, and others. In this review, the major mechanism associated with toxicities of individual metals was the generation of reactive oxygen species (ROS). Additionally, toxicities were expressed through depletion of glutathione and bonding to sulfhydryl groups of proteins. Interestingly, a metal like Pb becomes toxic to organisms through the depletion of antioxidants while Cd indirectly generates ROS by its ability to replace iron and copper. ROS generated through exposure to arsenic were associated with many modes of action, and heavy metal mixtures were found to have varied effects on organisms. Many models based on concentration addition (CA) and independent action (IA) have been introduced to help predict toxicities and mechanisms associated with metal mixtures. An integrated model which combines CA and IA was further proposed for evaluating toxicities of non-interactive mixtures. In cases where there are molecular interactions, the toxicogenomic approach was used to predict toxicities. The high-throughput toxicogenomics combines studies in genetics, genome-scale expression, cell and tissue expression, metabolite profiling, and bioinformatics.

75 FR 41867 - Request for Information on Development of an Inventory of Comparative Effectiveness Research

Science.gov (United States)

2010-07-19

... Federal Coordinating Council for Comparative Effectiveness Research, which defined CER as the: Conduct and... stakeholders; and assist in identifying priorities and gaps for future research. The goal is to routinize the... Comparative Effectiveness Research AGENCY: Office of the Assistant Secretary for Planning and Evaluation...

The cost-effectiveness of single-row compared with double-row arthroscopic rotator cuff repair.

Science.gov (United States)

Genuario, James W; Donegan, Ryan P; Hamman, Daniel; Bell, John-Erik; Boublik, Martin; Schlegel, Theodore; Tosteson, Anna N A

2012-08-01

Interest in double-row techniques for arthroscopic rotator cuff repair has increased over the last several years, presumably because of a combination of literature demonstrating superior biomechanical characteristics and recent improvements in instrumentation and technique. As a result of the increasing focus on value-based health-care delivery, orthopaedic surgeons must understand the cost implications of this practice. The purpose of this study was to examine the cost-effectiveness of double-row arthroscopic rotator cuff repair compared with traditional single-row repair. A decision-analytic model was constructed to assess the cost-effectiveness of double-row arthroscopic rotator cuff repair compared with single-row repair on the basis of the cost per quality-adjusted life year gained. Two cohorts of patients (one with a tear of row compared with single-row arthroscopic rotator cuff repair was $571,500 for rotator cuff tears of row repair was less than $287 for small or moderate tears and less than $352 for large or massive tears compared with the cost of single-row repair, then double-row repair would represent a cost-effective surgical alternative. On the basis of currently available data, double-row rotator cuff repair is not cost-effective for any size rotator cuff tears. However, variability in the values for costs and probability of retear can have a profound effect on the results of the model and may create an environment in which double-row repair becomes the more cost-effective surgical option. The identification of the threshold values in this study may help surgeons to determine the most cost-effective treatment.

Drosophila melanogaster as a Model for Lead Neurotoxicology and Toxicogenomics Research

Directory of Open Access Journals (Sweden)

Douglas Mark Ruden

2012-05-01

Full Text Available Drosophila melanogaster is an excellent model animal for studying the neurotoxicology of lead. It has been known since ancient Roman times that long-term exposure to low levels of lead results in behavioral abnormalities, such as what is now known as attention deficit hyperactivity disorder (ADHD. Because lead alters mechanisms that underlie developmental neuronal plasticity, chronic exposure of children, even at blood lead levels below the current CDC community action level (10 µg/dl, can result in reduced cognitive ability, increased likelihood of delinquency, behaviors associated with ADHD, changes in activity level, altered sensory function, delayed onset of sexual maturity in girls, and changes in immune function. In order to better understand how lead affects neuronal plasticity, we will describe recent findings from a Drosophila behavioral genetics laboratory, a Drosophila neurophysiology laboratory, and a Drosophila quantitative genetics laboratory who have joined forces to study the effects of lead on the Drosophila nervous system. Studying the effects of lead on Drosophila nervous system development will give us a better understanding of the mechanisms of Pb neurotoxicity in the developing human nervous system.

Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial

Science.gov (United States)

Schmid, Christopher H; Fielding, Roger A; Harvey, William F; Reid, Kieran F; Price, Lori Lyn; Driban, Jeffrey B; Kalish, Robert; Rones, Ramel; McAlindon, Timothy

2018-01-01

Abstract Objectives To determine the effectiveness of tai chi interventions compared with aerobic exercise, a current core standard treatment in patients with fibromyalgia, and to test whether the effectiveness of tai chi depends on its dosage or duration. Design Prospective, randomized, 52 week, single blind comparative effectiveness trial. Setting Urban tertiary care academic hospital in the United States between March 2012 and September 2016. Participants 226 adults with fibromyalgia (as defined by the American College of Rheumatology 1990 and 2010 criteria) were included in the intention to treat analyses: 151 were assigned to one of four tai chi groups and 75 to an aerobic exercise group. Interventions Participants were randomly assigned to either supervised aerobic exercise (24 weeks, twice weekly) or one of four classic Yang style supervised tai chi interventions (12 or 24 weeks, once or twice weekly). Participants were followed for 52 weeks. Adherence was rigorously encouraged in person and by telephone. Main outcome measures The primary outcome was change in the revised fibromyalgia impact questionnaire (FIQR) scores at 24 weeks compared with baseline. Secondary outcomes included changes of scores in patient’s global assessment, anxiety, depression, self efficacy, coping strategies, physical functional performance, functional limitation, sleep, and health related quality of life. Results FIQR scores improved in all five treatment groups, but the combined tai chi groups improved statistically significantly more than the aerobic exercise group in FIQR scores at 24 weeks (difference between groups=5.5 points, 95% confidence interval 0.6 to 10.4, P=0.03) and several secondary outcomes (patient’s global assessment=0.9 points, 0.3 to 1.4, P=0.005; anxiety=1.2 points, 0.3 to 2.1, P=0.006; self efficacy=1.0 points, 0.5 to 1.6, P=0.0004; and coping strategies, 2.6 points, 0.8 to 4.3, P=0.005). Tai chi treatment compared with aerobic exercise administered with

Comparative effects of commercial lime (CaCO 3 ) and ground ...

African Journals Online (AJOL)

Greenhouse study was carried out to investigate the comparative effect of commercial lime (CaCO3) and ground eggshell on the uptake of calcium and dry matter yield of maize in an ultisol of Southeastern Nigeria using maize (variety Oba supper 92) as the test crop. The soil was acidic and deficient in N, O.C., K, Ca and ...

Radiation effects, nuclear energy and comparative risks

International Nuclear Information System (INIS)

Gopinath, D.V.

2007-01-01

Nuclear energy had a promising start as an unlimited, inexpensive and environmentally benign source of energy for electricity generation. However, over the decades its growth was severely retarded due to concerns about its possible detrimental effects on the well-being of mankind and the environment. Since such concerns are essentially due to the gigantic magnitude of radioactivity and ionizing radiations associated with nuclear energy, this article starts with a comprehensive account of effects of the ionizing radiation on living systems. Quantitative description of types of radiation exposure and their varied effects is given. The origin, type and magnitude of mutagenic effects of radiation are described. The concept of radiation risk factors, basis for their evaluation and their currently accepted values are presented. With this background, origin and magnitude of radioactivity and associated ionizing radiations in nuclear reactors are presented and the elaborate measures to contain them are described. It is recognized that notwithstanding all the measures taken in the nuclear industry, certain amount of radiation exposure, however small, is inevitable and the values, based on the experience world over, are presented. Estimated health risk due to such exposures is evaluated. For a comparative analysis, risks in other options of electricity generation such as hydel and fossil-fuelled plants are described. It is seen that on an overall basis, the nuclear option is no more risky than the other commonly employed options, and is in fact, significantly less. Lastly, since every option of electricity generation entails some risk, the case of 'no addition of electricity, and its impact on the society are considered. Based on the analysis of extensive data provided by UNDP on the human development parameters for different countries in the world, it is shown that at least for developing countries, any option of addition of electricity would be far more desirable than the

Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial.

Science.gov (United States)

Wang, Chenchen; Schmid, Christopher H; Fielding, Roger A; Harvey, William F; Reid, Kieran F; Price, Lori Lyn; Driban, Jeffrey B; Kalish, Robert; Rones, Ramel; McAlindon, Timothy

2018-03-21

To determine the effectiveness of tai chi interventions compared with aerobic exercise, a current core standard treatment in patients with fibromyalgia, and to test whether the effectiveness of tai chi depends on its dosage or duration. Prospective, randomized, 52 week, single blind comparative effectiveness trial. Urban tertiary care academic hospital in the United States between March 2012 and September 2016. 226 adults with fibromyalgia (as defined by the American College of Rheumatology 1990 and 2010 criteria) were included in the intention to treat analyses: 151 were assigned to one of four tai chi groups and 75 to an aerobic exercise group. Participants were randomly assigned to either supervised aerobic exercise (24 weeks, twice weekly) or one of four classic Yang style supervised tai chi interventions (12 or 24 weeks, once or twice weekly). Participants were followed for 52 weeks. Adherence was rigorously encouraged in person and by telephone. The primary outcome was change in the revised fibromyalgia impact questionnaire (FIQR) scores at 24 weeks compared with baseline. Secondary outcomes included changes of scores in patient's global assessment, anxiety, depression, self efficacy, coping strategies, physical functional performance, functional limitation, sleep, and health related quality of life. FIQR scores improved in all five treatment groups, but the combined tai chi groups improved statistically significantly more than the aerobic exercise group in FIQR scores at 24 weeks (difference between groups=5.5 points, 95% confidence interval 0.6 to 10.4, P=0.03) and several secondary outcomes (patient's global assessment=0.9 points, 0.3 to 1.4, P=0.005; anxiety=1.2 points, 0.3 to 2.1, P=0.006; self efficacy=1.0 points, 0.5 to 1.6, P=0.0004; and coping strategies, 2.6 points, 0.8 to 4.3, P=0.005). Tai chi treatment compared with aerobic exercise administered with the same intensity and duration (24 weeks, twice weekly) had greater benefit (between group

Degradation of natural habitats by roads: Comparing land-take and noise effect zone

International Nuclear Information System (INIS)

Madadi, Hossein; Moradi, Hossein; Soffianian, Alireza; Salmanmahiny, Abdolrassoul; Senn, Josef; Geneletti, Davide

2017-01-01

Roads may act as barriers, negatively influencing the movement of animals, thereby causing disruption in landscapes. Roads cause habitat loss and fragmentation not only through their physical occupation, but also through traffic noise. The aim of this study is to provide a method to quantify the habitat degradation including habitat loss and fragmentation due to road traffic noise and to compare it with those of road land-take. Two types of fragmentation effects are determined: structural fragmentation (based on road land-take only), and functional fragmentation (noise effect zone fragmentation, buffer using a threshold of 40 dB). Noise propagation for roads with a traffic volume of more than 1000 vehicles per day was simulated by Calculation of Road Traffic Noise (CRTN) model. Habitat loss and fragmentation through land-take and noise effect zone were calculated and compared in Zagros Mountains in western Iran. The study area is characterized by three main habitat types (oak forest, scattered woodland and temperate grassland) which host endangered and protected wildlife species. Due to topographic conditions, land cover type, and the traffic volume in the region, the noise effect zone ranged from 50 to 2000 m which covers 18.3% (i.e. 516,929.95 ha) of the total study area. The results showed that the habitat loss due to noise effect zone is dramatically higher than that due to road land-take only (35% versus 1.04% of the total area). Temperate grasslands lost the highest proportion of the original area by both land-take and noise effect zone, but most area was lost in scattered woodland as compared to the other two habitat types. The results showed that considering the noise effect zone for habitat fragmentation resulted in an increase of 25.8% of the area affected (316,810 ha) as compared to using the land-take only (555,874 ha vs. 239,064 ha, respectively). The results revealed that the degree of habitat fragmentation is increasing by considering the noise

Epidemiological survey of the effects of low level radiation dose: a comparative assessment

Energy Technology Data Exchange (ETDEWEB)

Rose, K.S.B.

1993-10-01

This volume presents the collations tables of a six volume comparative epidemiological survey of the effects of low level radiation dose. Data are collated for the effects observed in the following irradiated groups:- Preconception irradiation, intra-uterine irradiation, childhood irradiation, adult irradiation. (UK).

Comparative effectiveness of correction strategies in connected discourse tracking.

Science.gov (United States)

Lunato, K E; Weisenberger, J M

1994-10-01

The effectiveness of four correction strategies commonly used in connected discourse tracking was investigated in the present study. The strategies were 1) verbatim repetition of a word or phrase; 2) use of antonyms or synonyms as cues; 3) use of phonemic cues, with no whole word repetition; and 4) going back or ahead in the text, with no repetition of the missed segment. Four normal-hearing adults served as listeners. Live-voice presentation of text by two female talkers was employed for all conditions. Listeners were tested in two stimulus presentation modes, speechreading alone and speechreading plus a multichannel tactile aid. Results indicated that strategy 1, repetition of the missed segment, produced the highest tracking rates, significantly higher than any of the other strategies. Strategy 2 produced the lowest tracking rates. Strategies 1 and 3 yielded the lowest percentage of initially missed words, or blockages, and strategy 4 the highest percentage. Significantly higher tracking rates were found under the speechreading plus tactile aid presentation mode, compared with speechreading alone. Further, tracking rates increased significantly from the beginning to the end of training. Data were compared with a more typical CDT task, in which all correction strategies were operative, and results showed little difference in tracking rates between this task and the constrained CDT employing only strategy 1. Overall, results suggest that simple repetition of missed segments is an effective correction strategy for CDT and argue for its inclusion in computer-assisted tracking implementations.

Predicting the Effects of Comparable Worth Programs on Female Labor Supply.

Science.gov (United States)

Nakamura, Alice; Nakamura, Masao

1989-01-01

Surveys theories in labor economics about how the female labor supply is affected by the wage offers that women receive. Summarizes the implications concerning expected effects of comparable worth wage adjustments on female labor supply. Examines empirical evidence pertaining to the theory of female labor supply. (JS)

Global comparative healthcare effectiveness research: Evaluating sustainable programmes in low & middle resource settings

Directory of Open Access Journals (Sweden)

Rajesh Balkrishnan

2013-01-01

Full Text Available The need to focus healthcare expenditures on innovative and sustainable health systems that efficiently use existing effective therapies are the major drivers stimulating Comparative Effectiveness Research (CER across the globe. Lack of adequate access and high cost of essential medicines and technologies in many countries increases morbidity and mortality and cost of care that forces people and families into poverty due to disability and out-of-pocket expenses. This review illustrates the potential of value-added global health care comparative effectiveness research in shaping health systems and health care delivery paradigms in the "global south". Enabling the development of effective CER systems globally paves the way for tangible local and regional definitions of equity in health care because CER fosters the sharing of critical assets, resources, skills, and capabilities and the development of collaborative of multi-sectorial frameworks to improve health outcomes and metrics globally.

Hepatitis C Treatment Regimens Are Cost-Effective: But Compared With What?

Science.gov (United States)

Mattingly, T Joseph; Slejko, Julia F; Mullins, C Daniel

2017-11-01

Numerous economic models have been published evaluating treatment of chronic hepatitis C virus (HCV) infection, but none provide a comprehensive comparison among new antiviral agents. Evaluate the cost-effectiveness of all recommended therapies for treatment of genotypes 1 and 4 chronic HCV. Using data from clinical trials, observational analyses, and drug pricing databases, Markov decision models were developed for HCV genotypes 1 and 4 to compare all recommended drugs from the perspective of the third-party payer over a 5-, 10-, and 50-year time horizon. A probabilistic sensitivity analysis (PSA) was conducted by assigning distributions for clinical cure, age entering the model, costs for each health state, and quality-adjusted life years (QALYs) for each health state in a Monte Carlo simulation of 10 000 repetitions of the model. In the lifetime model for genotype 1, effects ranged from 18.08 to 18.40 QALYs and total costs ranged from $88 107 to $184 636. The lifetime model of genotype 4 treatments had a range of effects from 18.23 to 18.43 QALYs and total costs ranging from $87 063 to $127 637. Grazoprevir/elbasvir was the optimal strategy followed by velpatasvir/sofosbuvir as the second-best strategy in most simulations for both genotypes 1 and 4, with drug costs and efficacy of grazoprevir/elbasvir as the primary model drivers. Grazoprevir/elbasvir was cost-effective compared with all strategies for genotypes 1 and 4. Effects for all strategies were similar with cost of drug in the initial year driving the results.

We can do better than effective dose for estimating or comparing low-dose radiation risks

International Nuclear Information System (INIS)

Brenner, D.J.

2012-01-01

The effective dose concept was designed to compare the generic risks of exposure to different radiation fields. More commonly these days, it is used to estimate or compare radiation-induced cancer risks. For various reasons, effective dose represents flawed science: for instance, the tissue-specific weighting factors used to calculate effective dose are a subjective mix of different endpoints; and the marked and differing age and gender dependencies for different health detriment endpoints are not taken into account. This paper suggests that effective dose could be replaced with a new quantity, ‘effective risk’, which, like effective dose, is a weighted sum of equivalent doses to different tissues. Unlike effective dose, where the tissue-dependent weighting factors are a set of generic, subjective committee-defined numbers, the weighting factors for effective risk are simply evaluated tissue-specific lifetime cancer risks per unit equivalent dose. Effective risk, which has the potential to be age and gender specific if desired, would perform the same comparative role as effective dose, be just as easy to estimate, be less prone to misuse, be more directly understandable, and would be based on solid science. An added major advantage is that it gives the users some feel for the actual numerical values of the radiation risks they are trying to control.

Does Acupuncture Needling Induce Analgesic Effects Comparable to Diffuse Noxious Inhibitory Controls?

Directory of Open Access Journals (Sweden)

Juerg Schliessbach

2012-01-01

Full Text Available Diffuse noxious inhibitory control (DNIC is described as one possible mechanism of acupuncture analgesia. This study investigated the analgesic effect of acupuncture without stimulation compared to nonpenetrating sham acupuncture (NPSA and cold-pressor-induced DNIC. Forty-five subjects received each of the three interventions in a randomized order. The analgesic effect was measured using pressure algometry at the second toe before and after each of the interventions. Pressure pain detection threshold (PPDT rose from 299 kPa (SD 112 kPa to 364 kPa (SD 144, 353 kPa (SD 135, and 467 kPa (SD 168 after acupuncture, NPSA, and DNIC test, respectively. There was no statistically significant difference between acupuncture and NPSA at any time, but a significantly higher increase of PPDT in the DNIC test compared to acupuncture and NPSA. PPDT decreased after the DNIC test, whereas it remained stable after acupuncture and NPSA. Acupuncture needling at low pain stimulus intensity showed a small analgesic effect which did not significantly differ from placebo response and was significantly less than a DNIC-like effect of a painful noninvasive stimulus.

Comparative antibacterial effectiveness of alcohol and herbal based commercially available hand antiseptics

Directory of Open Access Journals (Sweden)

K Vipin Jain

2013-01-01

Full Text Available Background: Human skin is a reservoir of numerous microorganisms. Even though hand washing with soap and water alone reduces the microbial load, the complementary uses of hand antiseptics enhance the antimicrobial effect. Aim: To compare the antimicrobial effectiveness of two commercially available hand antiseptics, routinely used in dental practice, after hand washing with antiseptic soap. Method: A clinical trial with cross over design was carried out on 12 health care workers (HCWs. The antibacterial effectiveness of two hand antiseptics (Alcohol based -Sterillium and Herbal Based-Himalaya′s ′Pure Hands′ compared using fingerprint contact sampling on blood agar. Bacterial samples were obtained before and after hand washing (with antiseptic soap and after hand disinfection. The data was tabulated and analyzed using one way ANOVA and Tukey′s post hoc test for pair-wise comparison. Result: There was a slight decrease in the Colony forming units (CFUs count following use of antiseptic soap when compared to the baseline values. A statistically significant reduction (p<0.000 in the CFUs count was seen following use of both hand antiseptics but the mean number of CFUs reduction was more in case of alcohol based hand antiseptic(sterillium than herbal based hand antiseptic(Himalaya′s ′PureHands". Conclusion: Using alcohol based antiseptic soap before hygienic hand disinfection will provide maximum benefit in reducing the microbial count.

Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses.

Science.gov (United States)

Lewis, Ruth A; Williams, Nefyn H; Sutton, Alex J; Burton, Kim; Din, Nafees Ud; Matar, Hosam E; Hendry, Maggie; Phillips, Ceri J; Nafees, Sadia; Fitzsimmons, Deborah; Rickard, Ian; Wilkinson, Clare

2015-06-01

There are numerous treatment approaches for sciatica. Previous systematic reviews have not compared all these strategies together. To compare the clinical effectiveness of different treatment strategies for sciatica simultaneously. Systematic review and network meta-analysis. We searched 28 electronic databases and online trial registries, along with bibliographies of previous reviews for comparative studies evaluating any intervention to treat sciatica in adults, with outcome data on global effect or pain intensity. Network meta-analysis methods were used to simultaneously compare all treatment strategies and allow indirect comparisons of treatments between studies. The study was funded by the UK National Institute for Health Research Health Technology Assessment program; there are no potential conflict of interests. We identified 122 relevant studies; 90 were randomized controlled trials (RCTs) or quasi-RCTs. Interventions were grouped into 21 treatment strategies. Internal and external validity of included studies was very low. For overall recovery as the outcome, compared with inactive control or conventional care, there was a statistically significant improvement following disc surgery, epidural injections, nonopioid analgesia, manipulation, and acupuncture. Traction, percutaneous discectomy, and exercise therapy were significantly inferior to epidural injections or surgery. For pain as the outcome, epidural injections and biological agents were significantly better than inactive control, but similar findings for disc surgery were not statistically significant. Biological agents were significantly better for pain reduction than bed rest, nonopioids, and opioids. Opioids, education/advice alone, bed rest, and percutaneous discectomy were inferior to most other treatment strategies; although these findings represented large effects, they were statistically equivocal. For the first time, many different treatment strategies for sciatica have been compared in the

The Effect of External Representations on Compare Word Problems: Supporting Mental Model Construction

Science.gov (United States)

Munez, David; Orrantia, Josetxu; Rosales, Javier

2013-01-01

This study explored the effectiveness of external representations presented together with compare word problems, and whether such effectiveness was moderated by working memory. Participants were 49 secondary school students. Each participant solved 48 problems presented in 4 presentation types that included 2 difficulty treatments (number of steps…

Revisiting the effect of colonial institutions on comparative economic development.

Directory of Open Access Journals (Sweden)

Valentina A Assenova

Full Text Available European settler mortality has been proposed as an instrument to predict the causal effect of colonial institutions on differences in economic development. We examine the relationship between mortality, temperature, and economic development in former European colonies in Asia, Africa, and the Americas. We find that (i European settler mortality rates increased with regional temperatures and (ii economic output decreased with regional temperatures. Conditioning on the continent of settlement and accounting for colonies that were not independent as of 1900 undermines the causal effect of colonial institutions on comparative economic development. Our findings run counter to the institutions hypothesis of economic development, showing instead that geography affected both historic mortality rates and present-day economic output.

Falsification Testing of Instrumental Variables Methods for Comparative Effectiveness Research.

Science.gov (United States)

Pizer, Steven D

2016-04-01

To demonstrate how falsification tests can be used to evaluate instrumental variables methods applicable to a wide variety of comparative effectiveness research questions. Brief conceptual review of instrumental variables and falsification testing principles and techniques accompanied by an empirical application. Sample STATA code related to the empirical application is provided in the Appendix. Comparative long-term risks of sulfonylureas and thiazolidinediones for management of type 2 diabetes. Outcomes include mortality and hospitalization for an ambulatory care-sensitive condition. Prescribing pattern variations are used as instrumental variables. Falsification testing is an easily computed and powerful way to evaluate the validity of the key assumption underlying instrumental variables analysis. If falsification tests are used, instrumental variables techniques can help answer a multitude of important clinical questions. © Health Research and Educational Trust.

Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.

Science.gov (United States)

Hall, Wayne

2017-04-01

The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced. Copyright © 2016 Elsevier B.V. All rights reserved.

Cost-effectiveness of indwelling pleural catheter compared with talc in malignant pleural effusion.

Science.gov (United States)

Olfert, Jordan A P; Penz, Erika D; Manns, Braden J; Mishra, Eleanor K; Davies, Helen E; Miller, Robert F; Luengo-Fernandez, Ramon; Gao, Song; Rahman, Najib M

2017-05-01

Malignant pleural effusion is associated with morbidity and mortality. A randomized controlled trial previously compared clinical outcomes and resource use with indwelling pleural catheter (IPC) and talc pleurodesis in this population. Using unpublished quality of life data, we estimate the cost-effectiveness of IPC compared with talc pleurodesis. Healthcare utilization and costs were captured during the trial. Utility weights produced by the EuroQol Group five-dimensional three-level questionnaire and survival were used to determine quality-adjusted life-years (QALYs) gained. The incremental cost-effectiveness ratio (ICER) was calculated over the 1-year trial period. Sensitivity analysis used patient survival data and modelled additional nursing time required per week for catheter drainage. Utility scores, cost and QALYs gained did not differ significantly between groups. The ICER for IPC compared with talc was favorable at $US10 870 per QALY gained. IPC was less costly with a probability exceeding 95% of being cost-effective when survival was pleural effusion in patients without history of prior pleurodesis, with consideration for patient survival, support and preferences. © 2016 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.

Essure hysteroscopic sterilization versus interval laparoscopic bilateral tubal ligation: a comparative effectiveness review.

Science.gov (United States)

Ouzounelli, Myrsini; Reaven, Nancy L

2015-01-01

A comparative effectiveness analysis was performed to examine the risks and benefits of laparoscopic bilateral tubal ligation compared with hysteroscopic sterilization using the Essure Permanent Birth Control System (Bayer HealthCare AG, Whippany, NJ). Existing evidence shows that both LBTL and Essure are safe and effective methods of female sterilization. Both have high rates of efficacy and low rates of complications although when complications do occur, those related to the Essure procedure are more likely to be minor in nature. The analysis was limited by the restricted number of studies involving head-to-head comparisons of the 2 approaches. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

A comparative study of the effect of diet and soda carbonated drinks ...

African Journals Online (AJOL)

EB

2013-09-03

Sep 3, 2013 ... Objectives: A comparative effect of the diet and regular soda carbonated drinks on the histology of the cerebellum of ... contains caffeine, depending on the quantities .... and health: a systematic review and meta-analysis.

Facilitating comparative effectiveness research in cancer genomics: evaluating stakeholder perceptions of the engagement process.

Science.gov (United States)

Deverka, Patricia A; Lavallee, Danielle C; Desai, Priyanka J; Armstrong, Joanne; Gorman, Mark; Hole-Curry, Leah; O'Leary, James; Ruffner, B W; Watkins, John; Veenstra, David L; Baker, Laurence H; Unger, Joseph M; Ramsey, Scott D

2012-07-01

The Center for Comparative Effectiveness Research in Cancer Genomics completed a 2-year stakeholder-guided process for the prioritization of genomic tests for comparative effectiveness research studies. We sought to evaluate the effectiveness of engagement procedures in achieving project goals and to identify opportunities for future improvements. The evaluation included an online questionnaire, one-on-one telephone interviews and facilitated discussion. Responses to the online questionnaire were tabulated for descriptive purposes, while transcripts from key informant interviews were analyzed using a directed content analysis approach. A total of 11 out of 13 stakeholders completed both the online questionnaire and interview process, while nine participated in the facilitated discussion. Eighty-nine percent of questionnaire items received overall ratings of agree or strongly agree; 11% of responses were rated as neutral with the exception of a single rating of disagreement with an item regarding the clarity of how stakeholder input was incorporated into project decisions. Recommendations for future improvement included developing standard recruitment practices, role descriptions and processes for improved communication with clinical and comparative effectiveness research investigators. Evaluation of the stakeholder engagement process provided constructive feedback for future improvements and should be routinely conducted to ensure maximal effectiveness of stakeholder involvement.

Comparative Effectiveness of Two Walking Interventions on Participation, Step Counts, and Health.

Science.gov (United States)

Smith-McLallen, Aaron; Heller, Debbie; Vernisi, Kristin; Gulick, Diana; Cruz, Samantha; Snyder, Richard L

2017-03-01

To (1) compare the effects of two worksite-based walking interventions on employee participation rates; (2) compare average daily step counts between conditions, and; (3) examine the effects of increases in average daily step counts on biometric and psychologic outcomes. We conducted a cluster-randomized trial in which six employer groups were randomly selected and randomly assigned to condition. Four manufacturing worksites and two office-based worksite served as the setting. A total of 474 employees from six employer groups were included. A standard walking program was compared to an enhanced program that included incentives, feedback, competitive challenges, and monthly wellness workshops. Walking was measured by self-reported daily step counts. Survey measures and biometric screenings were administered at baseline and 3, 6, and 9 months after baseline. Analysis used linear mixed models with repeated measures. During 9 months, participants in the enhanced condition averaged 726 more steps per day compared with those in the standard condition (p women (-2.1 lbs.), and reductions in body mass index (-0.41 men, -0.31 women). Higher step counts were also associated with improvements in mood, having more energy, and higher ratings of overall health. An enhanced walking program significantly increases participation rates and daily step counts, which were associated with weight loss and reductions in body mass index.

Comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: a randomized trial

Science.gov (United States)

Background: Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. Objective: To compare Tai Chi with standard physical therapy f...

STITCH 2: an interaction network database for small molecules and proteins

DEFF Research Database (Denmark)

Kuhn, Michael; Szklarczyk, Damian; Franceschini, Andrea

2010-01-01

Over the last years, the publicly available knowledge on interactions between small molecules and proteins has been steadily increasing. To create a network of interactions, STITCH aims to integrate the data dispersed over the literature and various databases of biological pathways, drug......-target relationships and binding affinities. In STITCH 2, the number of relevant interactions is increased by incorporation of BindingDB, PharmGKB and the Comparative Toxicogenomics Database. The resulting network can be explored interactively or used as the basis for large-scale analyses. To facilitate links to other...... chemical databases, we adopt InChIKeys that allow identification of chemicals with a short, checksum-like string. STITCH 2.0 connects proteins from 630 organisms to over 74,000 different chemicals, including 2200 drugs. STITCH can be accessed at http://stitch.embl.de/....

Recent controversies on comparative effectiveness research investigations: Challenges, opportunities, and pitfalls.

Science.gov (United States)

Kirpalani, Haresh; Truog, William E; D'Angio, Carl T; Cotten, Michael

2016-10-01

The purpose of comparative effectiveness research (CER) is to improve health outcomes by developing and disseminating evidence-based information about which currently available interventions and practices are most effective for patients. Randomized Controlled Trials (RCT) are the hallmark of scientific proof, and have been used to compare interventions used in variable ways by different clinicians (comparative effectiveness RCTs, CER-RCTs). But such CER-RCTs have at times generated controversy. Usually the background for the CER-RCT is a range of "standard therapy" or "standard of care." This may have been adopted on observational data alone, or pilot data. At times, such prior data may derive from populations that differ from the population in which the widely variable standard approach is being applied. We believe that controversies related to these CER-RCTs result from confusing "accepted" therapies and "rigorously evaluated therapies." We first define evidence-based medicine and consider how well neonatology conforms to that definition. We then contrast the approach of testing new therapies and those already existing and widely adopted, as in CER-RCTs. We next examine a central challenge in incorporating the control arm within CER-RCTs and aspects of the "titrated" trial. We finally briefly consider some ethical issues that have arisen, and discuss the wide range of neonatology practices that could be tested by CER-RCTs or alternative CER-based strategies that might inform practice. Throughout, we emphasize the lack of awareness of the lay community, and indeed many researchers or commentators, in appreciating the wide variation of standard of care. There is a corresponding need to identify the best uses of available resources that will lead to the best outcomes for our patients. We conclude that CER-RCTs are an essential methodology in modern neonatology to address many unanswered questions and test unproven therapies in newborn care. Copyright © 2016

Recent Controversies on Comparative Effectiveness Research Investigations: Challenges, Opportunities and Pitfalls

Science.gov (United States)

Kirpalani, Haresh; Truog, William E.; D'Angio, Carl T.; Cotten, M.

2016-01-01

The purpose of comparative effectiveness research (CER) is to improve health outcomes by developing and disseminating evidence-based information about which currently available interventions and practices are most effective for patients. While Randomized Controlled Trials (RCT) are the hallmark of scientific proof, when they have been used to compare interventions used in variable ways by different clinicians (Comparative Effectiveness RCTs, CER RCTs) they have at times, generated controversy. Usually the background for the CER RCT is a range of ‘standard therapy’ or ‘standard of care’. This may have been adopted on observational data alone, pilot data. At times, such prior data may derive from populations that differ from the population in which the widely variable standard approach is being applied. We believe controversies related to these CER-RCTs result from confusing ‘accepted’ therapies and ‘rigorously evaluated therapies”. We first define evidence based medicine, and consider how well neonatology conforms to that definition. We then contrast the approach of testing new therapies and those already existing and widely adopted, as in CER-RCTs. We next examine a central challenge in incorporating the control arm within CER, and aspects of the ‘titrated’ trial. We finally briefly consider some ethical issues that have arisen, and briefly discuss the wide range of neonatology practices that could be subject to CER-RCTs or alternative CER-based strategies that might inform practice in the absence of RCTs. Throughout, we emphasize the lack of awareness of the lay community, and indeed many researchers or commentators, in appreciating the wide variation of standard of care. There is a corresponding need to identify the best uses of available resources that will lead to the best outcomes for our patients. We conclude that CER is an essential methodology in modern neonatology to address many unanswered questions and test unproven therapies in

Comparative effectiveness of colony-stimulating factors in febrile neutropenia prophylaxis: how results are affected by research design.

Science.gov (United States)

Henk, Henry J; Li, Xiaoyan; Becker, Laura K; Xu, Hairong; Gong, Qi; Deeter, Robert G; Barron, Richard L

2015-01-01

To examine the impact of research design on results in two published comparative effectiveness studies. Guidelines for comparative effectiveness research have recommended incorporating disease process in study design. Based on the recommendations, we develop a checklist of considerations and apply the checklist in review of two published studies on comparative effectiveness of colony-stimulating factors. Both studies used similar administrative claims data, but different methods, which resulted in directionally different estimates. Major design differences between the two studies include: whether the timing of intervention in disease process was identified and whether study cohort and outcome assessment period were defined based on this temporal relationship. Disease process and timing of intervention should be incorporated into the design of comparative effectiveness studies.

An overview of methods for comparative effectiveness research.

Science.gov (United States)

Meyer, Anne-Marie; Wheeler, Stephanie B; Weinberger, Morris; Chen, Ronald C; Carpenter, William R

2014-01-01

Comparative effectiveness research (CER) is a broad category of outcomes research encompassing many different methods employed by researchers and clinicians from numerous disciplines. The goal of cancer-focused CER is to generate new knowledge to assist cancer stakeholders in making informed decisions that will improve health care and outcomes of both individuals and populations. There are numerous CER methods that may be used to examine specific questions, including randomized controlled trials, observational studies, systematic literature reviews, and decision sciences modeling. Each has its strengths and weaknesses. To both inform and serve as a reference for readers of this issue of Seminars in Radiation Oncology as well as the broader oncology community, we describe CER and several of the more commonly used approaches and analytical methods. © 2013 Published by Elsevier Inc.

Comparative Effects of Retinoic Acid or Glycolic Acid Vehiculated in Different Topical Formulations

Science.gov (United States)

Maia Campos, Patrícia Maria Berardo Gonçalves; Gaspar, Lorena Rigo; Gonçalves, Gisele Mara Silva; Pereira, Lúcia Helena Terenciane Rodrigues; Semprini, Marisa; Lopes, Ruberval Armando

2015-01-01

Retinoids and hydroxy acids have been widely used due to their effects in the regulation of growth and in the differentiation of epithelial cells. However, besides their similar indication, they have different mechanisms of action and thus they may have different effects on the skin; in addition, since the topical formulation efficiency depends on vehicle characteristics, the ingredients of the formulation could alter their effects. Thus the objective of this study was to compare the effects of retinoic acid (RA) and glycolic acid (GA) treatment on the hairless mouse epidermis thickness and horny layer renewal when added in gel, gel cream, or cream formulations. For this, gel, gel cream, and cream formulations (with or without 6% GA or 0.05% RA) were applied in the dorsum of hairless mice, once a day for seven days. After that, the skin was analyzed by histopathologic, morphometric, and stereologic techniques. It was observed that the effects of RA occurred independently from the vehicle, while GA had better results when added in the gel cream and cream. Retinoic acid was more effective when compared to glycolic acid, mainly in the cell renewal and the exfoliation process because it decreased the horny layer thickness. PMID:25632398

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

Science.gov (United States)

Prabhu, Vimalanand S; Dubberke, Erik R; Dorr, Mary Beth; Elbasha, Elamin; Cossrow, Nicole; Jiang, Yiling; Marcella, Stephen

2018-01-18

Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Comparative effectiveness of personalized lifestyle management strategies for cardiovascular disease risk reduction

NARCIS (Netherlands)

P. Chu (Paula); A. Pandya; J.A. Salomon (Joshua A); S.J. Goldie (Sue J); Hunink, M.G.M. (M.G. Myriam)

2015-01-01

textabstractBackground-Evidence shows that healthy diet, exercise, smoking interventions, and stress reduction reduce cardiovascular disease risk. We aimed to compare the effectiveness of these lifestyle interventions for individual risk profiles and determine their rank order in reducing 10-year

Towards Comparative Leadership

DEFF Research Database (Denmark)

Jensen, Merete Storgaard

Globalization is the imitation and adaptation of knowledgesolutions or innovations, as they are diffused from one country to another” (Peter Jarvis 2007) Conducting comparative, educational research of school leadership that effects student achievement in an international perspective is of scient......Globalization is the imitation and adaptation of knowledgesolutions or innovations, as they are diffused from one country to another” (Peter Jarvis 2007) Conducting comparative, educational research of school leadership that effects student achievement in an international perspective...... is of scientific value in qualifying the international and national knowledgebase on effective school leadership. In a methodological perspective comparative analysis in an international setting creates specifically a scientific demand of comparability and a theory based leadership - framework to guide...... the empirical, qualitative research of effective leadership....

Is the perceived placebo effect comparable between adults and children? A meta-regression analysis.

Science.gov (United States)

Janiaud, Perrine; Cornu, Catherine; Lajoinie, Audrey; Djemli, Amina; Cucherat, Michel; Kassai, Behrouz

2017-01-01

A potential larger perceived placebo effect in children compared with adults could influence the detection of the treatment effect and the extrapolation of the treatment benefit from adults to children. This study aims to explore this potential difference, using a meta-epidemiological approach. A systematic review of the literature was done to identify trials included in meta-analyses evaluating a drug intervention with separate data for adults and children. The standardized mean change and the proportion of responders (binary outcomes) were used to calculate the perceived placebo effect. A meta-regression analysis was conducted to test for the difference between adults and children of the perceived placebo effect. For binary outcomes, the perceived placebo effect was significantly more favorable in children compared with adults (β = 0.13; P = 0.001). Parallel group trials (β = -1.83; P < 0.001), subjective outcomes (β = -0.76; P < 0.001), and the disease type significantly influenced the perceived placebo effect. The perceived placebo effect is different between adults and children for binary outcomes. This difference seems to be influenced by the design, the disease, and outcomes. Calibration of new studies for children should consider cautiously the placebo effect in children.

Comparing the Effects of Elementary Music and Visual Arts Lessons on Standardized Mathematics Test Scores

Science.gov (United States)

King, Molly Elizabeth

2016-01-01

The purpose of this quantitative, causal-comparative study was to compare the effect elementary music and visual arts lessons had on third through sixth grade standardized mathematics test scores. Inferential statistics were used to compare the differences between test scores of students who took in-school, elementary, music instruction during the…

Supporting Imagers' VOICE: A National Training Program in Comparative Effectiveness Research and Big Data Analytics.

Science.gov (United States)

Kang, Stella K; Rawson, James V; Recht, Michael P

2017-12-05

Provided methodologic training, more imagers can contribute to the evidence basis on improved health outcomes and value in diagnostic imaging. The Value of Imaging Through Comparative Effectiveness Research Program was developed to provide hands-on, practical training in five core areas for comparative effectiveness and big biomedical data research: decision analysis, cost-effectiveness analysis, evidence synthesis, big data principles, and applications of big data analytics. The program's mixed format consists of web-based modules for asynchronous learning as well as in-person sessions for practical skills and group discussion. Seven diagnostic radiology subspecialties and cardiology are represented in the first group of program participants, showing the collective potential for greater depth of comparative effectiveness research in the imaging community. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Comparing the relative cost-effectiveness of diagnostic studies: a new model

International Nuclear Information System (INIS)

Patton, D.D.; Woolfenden, J.M.; Wellish, K.L.

1986-01-01

We have developed a model to compare the relative cost-effectiveness of two or more diagnostic tests. The model defines a cost-effectiveness ratio (CER) for a diagnostic test as the ratio of effective cost to base cost, only dollar costs considered. Effective cost includes base cost, cost of dealing with expected side effects, and wastage due to imperfect test performance. Test performance is measured by diagnostic utility (DU), a measure of test outcomes incorporating the decision-analytic variables sensitivity, specificity, equivocal fraction, disease probability, and outcome utility. Each of these factors affecting DU, and hence CER, is a local, not universal, value; these local values strongly affect CER, which in effect becomes a property of the local medical setting. When DU = +1 and there are no adverse effects, CER = 1 and the patient benefits from the test dollar for dollar. When there are adverse effects effective cost exceeds base cost, and for an imperfect test DU 1. As DU approaches 0 (worthless test), CER approaches infinity (no effectiveness at any cost). If DU is negative, indicating that doing the test at all would be detrimental, CER also becomes negative. We conclude that the CER model is a useful preliminary method for ranking the relative cost-effectiveness of diagnostic tests, and that the comparisons would best be done using local values; different groups might well arrive at different rankings. (Author)

COMPARATIVE EFFECTIVENESS OF DIFFERENT METHODS OF CANDIDAL DYSBACTERIOSIS THERAPY

Directory of Open Access Journals (Sweden)

S.V. Nikolaeva

2009-01-01

Full Text Available The study of effectiveness of different methods of microbiological disorders correction in children after 3 years old with candidal dysbacteriosis are presented in this article. The study compared probiotical sour milk-made stuff («Actimel» and sour milk-made stuff, not fortified with probiotical cultures («Rastishka» and traditional kefir. It was shown that an inclusion of probiotical sour milkmade stuff in diet of children with candidal dysbacteriosis results in normalization of lacto- and bifidobacteria level and decreasing of Candida level.Key words: children, candidal dysbacteriosis, probiotics.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(6:31-35

Methodological considerations in observational comparative effectiveness research for implantable medical devices: an epidemiologic perspective.

Science.gov (United States)

Jalbert, Jessica J; Ritchey, Mary Elizabeth; Mi, Xiaojuan; Chen, Chih-Ying; Hammill, Bradley G; Curtis, Lesley H; Setoguchi, Soko

2014-11-01

Medical devices play a vital role in diagnosing, treating, and preventing diseases and are an integral part of the health-care system. Many devices, including implantable medical devices, enter the market through a regulatory pathway that was not designed to assure safety and effectiveness. Several recent studies and high-profile device recalls have demonstrated the need for well-designed, valid postmarketing studies of medical devices. Medical device epidemiology is a relatively new field compared with pharmacoepidemiology, which for decades has been developed to assess the safety and effectiveness of medications. Many methodological considerations in pharmacoepidemiology apply to medical device epidemiology. Fundamental differences in mechanisms of action and use and in how exposure data are captured mean that comparative effectiveness studies of medical devices often necessitate additional and different considerations. In this paper, we discuss some of the most salient issues encountered in conducting comparative effectiveness research on implantable devices. We discuss special methodological considerations regarding the use of data sources, exposure and outcome definitions, timing of exposure, and sources of bias. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparing the effects of shallomin lotion and cryotherapy on treating plane warts

Directory of Open Access Journals (Sweden)

Reza Yaaghubi

2018-01-01

Full Text Available Background: Wart is a common transferable skin disease that is caused by human papilloma virus. Choosing the best treatment method can vary based on age, therapeutic goal, complications, and wart place. Due to antibacterial effect of shallomin (hirtifolium Boiss extract and since its effect has not been studied yet, it was compared to cryotherapy therapeutic methods for treating patients with plane warts. Methods: The present study was a randomized clinical trial that was carried out on 40 patients. Sampling was conducted simply by 4 block randomization method. The selected patients were assigned into two Groups of A and B. Data analysis was conducted by descriptive methods, and then, statistical tests including Chi-square, Fisher's exact test, and t-test were run to determine the relationship between qualitative and quantitative variables. In so doing, SPSS software version 16.0 was utilized. Results: Comparing the means showed that as opposed to cryotherapy, shallomin could not lead to a significant decrease in the size and number of warts. Conclusion: According to the results of this study, which is the first and the only investigation into the effects of shallomin on treating plane warts, it can be stated that despite of its antibacterial, antifungal, and anti-herpetic properties, shallamin cannot be a clinically effective option for treating plane warts.

Comparative animal experimental studies of the effects of different radiopharmaceuticals on the electroencephalogram

International Nuclear Information System (INIS)

Bretschneider, T.; Gundlach, H.J.; Krueger, M.; Reincke, R.; Schwebke, R.

1979-01-01

Some of the radiopharmaceuticals recently recommended for isotope cisternography were compared as to their effects on the bioelectric activity. Relaxed cats did not reveal any effects of 198 Au or 169 Yb-Ca-DTPA on the bioelectric activity. Following suboccipital administration, 169 Yb-DTPA and 131 I-HSA caused changes of the electroencephalogram in one of 7 and 6 cases, respectively. (author)

Comparative effectiveness research (CER): a summary of AHRQ's CER on therapies for rheumatoid arthritis.

Science.gov (United States)

Oderda, Gary M; Balfe, Lisa M

2011-01-01

In recent years, the U.S. government has designated funding of several large-scale initiatives for comparative effectiveness research (CER) in health care. The American Recovery and Reinvestment Act (ARRA) of 2009 apportioned more than $1 billion to support CER programs administered by the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), and the Agency for Healthcare Research and Quality (AHRQ). CER is generally defined as the undertaking of original research or systematic reviews of published literature in order to compare the benefits and risks of different approaches to preventing, diagnosing, or treating diseases. These approaches may include diagnostic tests, medications, medical devices, and surgeries. The overall goals of CER are to support informed health care decisions by patients, clinicians, payers, and policy makers and to apply its evidence to ultimately improve the quality, effectiveness, and efficiency of health care. To (a) provide managed care professionals with general definitions of CER, specifically as it is administered by AHRQ; (b) discuss the importance of CER to clinical and managed care pharmacists; and (c) summarize key methods and findings from AHRQ's 2007 comparative effectiveness review on therapies for rheumatoid arthritis (RA). As supported by AHRQ, CER is conducted in order to synthesize comprehensive evidence on the comparative benefits and harms of treatment interventions. The findings from comparative effectiveness reviews can thus contribute to informing therapeutic strategies and treatment decisions. In 2007, a multitude of RA treatment options and studies motivated AHRQ to commission a systematic comparative effectiveness review. Conducted by investigators at the RTI-University of North Carolina Evidence-Based Practice Center, the review included comparisons of synthetic disease-modifying antirheumatic drugs (DMARDs), biologic agents, synthetic DMARDs versus biologic agents, and various

COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

Science.gov (United States)

The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

Payer decision-making with limited comparative and cost effectiveness data: the case of new pharmacological treatments for gout.

Science.gov (United States)

Meltzer, Michele; Pizzi, Laura T; Jutkowitz, Eric

2012-08-01

The need for comparative effectiveness (CE) data continues to grow, fuelled by market demand as well as health reform. There may be an assumption that new drugs result in improved efficacy compared with the standard of care, therefore warranting premium prices. Gout treatment has recently become controversial, as expensive new drugs enter the market with limited CE data. The authors reviewed published clinical trials and conducted a cost effectiveness analysis on a new drug (febuxostat) versus the standard (allopurinol) to illustrate the limitations in using these data to inform evidence-based decision-making. Although febuxostat trials included allopurinol as a comparator, methodological limitations make comparative effectiveness evaluations difficult. However, when available trial data were input to a decision analytic model, the authors found that a significant reduction in febuxostat cost would be required in order for it to dominate allopurinol in cost effectiveness analysis. This case exemplifies the challenges of using clinical trial data in comparative and cost effectiveness analyses.

Comparative effectiveness of liraglutide in the treatment of type 2 diabetes

Directory of Open Access Journals (Sweden)

Rigato M

2014-03-01

Full Text Available Mauro Rigato, Gian Paolo Fadini Department of Medicine, University Hospital of Padova, Padova, Italy Abstract: Type 2 diabetes is characterized by a progressive decline in beta cell function, with consequent worsening of glycemic control. The ideal antihyperglycemic treatment should achieve good and sustained glycemic control, with a low risk of hypoglycemia and no weight gain. This paper reviews the efficacy and tolerability of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes. Once-daily injection of liraglutide (at doses of 1.2 mg and 1.8 mg, as monotherapy or in combination with one or two oral antihyperglycemic agents, was associated with greater improvements in glycemic control compared with active comparators or placebo in several controlled, randomized Phase III trials, including the six trials of the LEAD (Liraglutide Effect and Action in Diabetes program. Liraglutide also improved beta cell function, body weight, systolic blood pressure, and lipid profile, thereby achieving many of the goals of ideal antihyperglycemic therapy. Liraglutide was generally well tolerated in the Phase III trials. The most common adverse events were nausea, vomiting, and diarrhea, usually of mild to moderate intensity. The observed rate of pancreatitis was low and comparable with that of the general diabetic population. In conclusion, although most trials were relatively short and focused on surrogate endpoints, liraglutide emerges as an effective and well tolerated treatment for type 2 diabetes, carrying a low risk of hypoglycemia, weight loss, and possible reduction of cardiovascular risk. Keywords: body weight, hypoglycemia, cardiovascular, incretin

Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle.

Science.gov (United States)

Kim, C-S; Jang, W S; Son, I P; Nam, S H; Kim, Y I; Park, K Y; Kim, B J; Kim, M N

2013-09-01

New cosmetic applications and products based on the effects of botulinum toxin (BTX) treatment have stimulated demand for this class of natural compounds. This demand generates the need for appropriate standardized protocols to test and compare the effectiveness of new BTX preparations. Based on the previously described electrophysiological methods, we measured and compared the inhibitory effects of two BTX type A (BTX-A) preparations on neuromuscular transmission through split-body test. The effectiveness was evaluated in terms of the compound muscle action potential (CMAP) and conduction velocity after BTX-A injection. We used a split-body method to compare two different BTX-As in the rat. Based on the changes in the CMAP, the two different BTX-As induced paralytic effect on the rat tibialis anterior muscle. However, the two different BTX-A preparations did not differ significantly in effectiveness and did not induce a delay in conduction velocity. The new BTX-A preparation used in this electrophysiological study had similar effect compared with the previously marketed BTX-A.[AQ: Please approve the edits made to the sentence "The new BTX-A preparation…") We propose that a split-body electrophysiological protocol will be useful in establishing the comparative effectiveness of new BTX products.

A comparative study of the effect of diet and soda carbonated drinks ...

African Journals Online (AJOL)

EB

2013-09-03

Sep 3, 2013 ... Objectives: A comparative effect of the diet and regular soda carbonated drinks on the histology of the cerebellum of female albino Wistar rats was ... contains caffeine, depending on the quantities consumed5. Caffeine is linked ... consumption might result in seizures, memory loss, dizziness, headache and ...

Use of toxicogenomics for identifying genetic markers of pulmonary oedema

International Nuclear Information System (INIS)

Balharry, Dominique; Oreffo, Victor; Richards, Roy

2005-01-01

This study was undertaken primarily to identify genetic markers of oedema and inflammation. Mild pulmonary injury was induced following the instillation of the oedema-producing agent, bleomycin (0.5 units). Oedema was then confirmed by conventional toxicology (lavage protein levels, free cell counts and lung/body weight ratios) and histology 3 days post-bleomycin instillation.The expression profile of 1176 mRNA species was determined for bleomycin-exposed lung (Clontech Atlas macroarray, n = 9). To obtain pertinent results from these data, it was necessary to develop a simple, effective method for bioinformatic analysis of altered gene expression. Data were log 10 transformed followed by global normalisation. Differential gene expression was accepted if: (a) genes were statistically significant (P ≤ 0.05) from a two-tailed t test; (b) genes were consistently outside a two standard deviation (SD) range from control levels. A combination of these techniques identified 31 mRNA transcripts (approximately 3%) which were significantly altered in bleomycin treated tissue. Of these genes, 26 were down-regulated whilst only five were up-regulated. Two distinct clusters were identified, with 17 genes classified as encoding hormone receptors, and nine as encoding ion channels. Both these clusters were consistently down-regulated.The magnitude of the changes in gene expression were quantified and confirmed by Q-PCR (n = 6), validating the macroarray data and the bioinformatic analysis employed.In conclusion, this study has developed a suitable macroarray analysis procedure and provides the basis for a better understanding of the gene expression changes occurring during the early phase of drug-induced pulmonary oedema

The comparative study of the effect of some radionuclides on chlorella populations

International Nuclear Information System (INIS)

Shvobene, R.Ya.; Marchyulenene, D.P.; Shuliene, R.I.

1984-01-01

In this report the data are presented of the comparative study of physiological and genetic effects on chlorella populations (Chlorella vUlgaris Beijer, strain LARG-1) of 90 Sr, 137 Cs and 144 Ce (equal concentrations) distinguished by the radiation dose produced, the physico-chemical properties, and the levels of accumulation and deposition thereof in plant cells. The effects of the radionuclides on chlorella populations were estimated with a reference to the rate of photosynthesis, cell density, and the number of mutant and lethally affected cells

Similarity queries for temporal toxicogenomic expression profiles.

Directory of Open Access Journals (Sweden)

Adam A Smith

2008-07-01

Full Text Available We present an approach for answering similarity queries about gene expression time series that is motivated by the task of characterizing the potential toxicity of various chemicals. Our approach involves two key aspects. First, our method employs a novel alignment algorithm based on time warping. Our time warping algorithm has several advantages over previous approaches. It allows the user to impose fairly strong biases on the form that the alignments can take, and it permits a type of local alignment in which the entirety of only one series has to be aligned. Second, our method employs a relaxed spline interpolation to predict expression responses for unmeasured time points, such that the spline does not necessarily exactly fit every observed point. We evaluate our approach using expression time series from the Edge toxicology database. Our experiments show the value of using spline representations for sparse time series. More significantly, they show that our time warping method provides more accurate alignments and classifications than previous standard alignment methods for time series.

Toxicogenomics Investigation Under the eTOX Project

DEFF Research Database (Denmark)

Taboureau, Olivier; Hersey, Anne; Audouze, Karine Marie Laure

2012-01-01

Attrition of drug candidates during pre-clinical development due to toxicity, especially hepatotoxicity and nephrotoxicity, is an important and continuing problem in the pharmaceutical industry. The reasons for this trend may be multifactorial and there is a need to improve toxicity testing parad...

Nano-risk Science: application of toxicogenomics in an adverse outcome pathway framework for risk assessment of multi-walled carbon nanotubes

DEFF Research Database (Denmark)

Labib, Sarah; Williams, Andrew; Yauk, Carole L.

2016-01-01

-based points of departure (PODs) for multi-walled carbon nanotube (MWCNT)-induced lung fibrosis, a non-cancer endpoint of regulatory importance. Methods: Gene expression profiles from the lungs of mice exposed to three individual MWCNTs with different physical-chemical properties were used within the framework...... with fibrosis were 14.0-30.4 mu g/mouse, which are comparable to the BMDs derived by NIOSH for MWCNT-induced lung fibrotic lesions (21.0-27.1 mu g/mouse). Conclusions: The results demonstrate that transcriptomic data can be used to as an effective mechanism-based method to derive acceptable levels of exposure...

Gene expression analysis in rat lungs after intratracheal exposure to nanoparticles doped with cadmium

Energy Technology Data Exchange (ETDEWEB)

Coccini, Teresa; Manzo, Luigi [Toxicology Division, Salvatore Maugeri Foundation IRCCS, Pavia (Italy); Fabbri, Marco; Sacco, Maria Grazia; Gribaldo, Laura [European Commission, Joint Research Centre, IHCP- 21027 Ispra (Italy); Roda, Elisa [European Centre for Nanomedicine, University of Pavia, 27100 Pavia (Italy)

2011-07-06

Silica nanoparticles (NPs) incorporating cadmium (Cd) have been developed for a range of potential application including drug delivery devices. Occupational Cd inhalation has been associated with emphysema, pulmonary fibrosis and lung tumours. Mechanistically, Cd can induce oxidative stress and mediate cell-signalling pathways that are involved in inflammation.This in vivo study aimed at investigating pulmonary molecular effects of NPs doped with Cd (NP-Cd, 1 mg/animal) compared to soluble CdCl{sub 2} (400 {mu}g/animal), in Sprague Dawley rats treated intra-tracheally, 7 and 30 days after administration. NPs of silica containing Cd salt were prepared starting from commercial nano-size silica powder (HiSil{sup TM} T700 Degussa) with average pore size of 20 nm and surface area of 240 m{sup 2}/g. Toxicogenomic analysis was performed by the DNA microarray technology (using Agilent Whole Rat Genome Microarray 4x44K) to evaluate changes in gene expression of the entire genome. These findings indicate that the whole genome analysis may represent a valuable approach to assess the whole spectrum of biological responses to cadmium containing nanomaterials.

Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that Bind Estrogen Receptors

Science.gov (United States)

Ye, Hao; Ng, Hui Wen; Sakkiah, Sugunadevi; Ge, Weigong; Perkins, Roger; Tong, Weida; Hong, Huixiao

2016-01-01

Flavonoids are frequently used as dietary supplements in the absence of research evidence regarding health benefits or toxicity. Furthermore, ingested doses could far exceed those received from diet in the course of normal living. Some flavonoids exhibit binding to estrogen receptors (ERs) with consequential vigilance by regulatory authorities at the U.S. EPA and FDA. Regulatory authorities must consider both beneficial claims and potential adverse effects, warranting the increases in research that has spanned almost two decades. Here, we report pathway enrichment of 14 targets from the Comparative Toxicogenomics Database (CTD) and the Herbal Ingredients’ Targets (HIT) database for 22 flavonoids that bind ERs. The selected flavonoids are confirmed ER binders from our earlier studies, and were here found in mainly involved in three types of biological processes, ER regulation, estrogen metabolism and synthesis, and apoptosis. Besides cancers, we conjecture that the flavonoids may affect several diseases via apoptosis pathways. Diseases such as amyotrophic lateral sclerosis, viral myocarditis and non-alcoholic fatty liver disease could be implicated. More generally, apoptosis processes may be importantly evolved biological functions of flavonoids that bind ERs and high dose ingestion of those flavonoids could adversely disrupt the cellular apoptosis process. PMID:27023590

Pathway Analysis Revealed Potential Diverse Health Impacts of Flavonoids that Bind Estrogen Receptors

Directory of Open Access Journals (Sweden)

Hao Ye

2016-03-01

Full Text Available Flavonoids are frequently used as dietary supplements in the absence of research evidence regarding health benefits or toxicity. Furthermore, ingested doses could far exceed those received from diet in the course of normal living. Some flavonoids exhibit binding to estrogen receptors (ERs with consequential vigilance by regulatory authorities at the U.S. EPA and FDA. Regulatory authorities must consider both beneficial claims and potential adverse effects, warranting the increases in research that has spanned almost two decades. Here, we report pathway enrichment of 14 targets from the Comparative Toxicogenomics Database (CTD and the Herbal Ingredients’ Targets (HIT database for 22 flavonoids that bind ERs. The selected flavonoids are confirmed ER binders from our earlier studies, and were here found in mainly involved in three types of biological processes, ER regulation, estrogen metabolism and synthesis, and apoptosis. Besides cancers, we conjecture that the flavonoids may affect several diseases via apoptosis pathways. Diseases such as amyotrophic lateral sclerosis, viral myocarditis and non-alcoholic fatty liver disease could be implicated. More generally, apoptosis processes may be importantly evolved biological functions of flavonoids that bind ERs and high dose ingestion of those flavonoids could adversely disrupt the cellular apoptosis process.

Comparative Effects of Injectable and Oral Hormonal Contraceptives on Lipid Profile

OpenAIRE

Adebayor Adegoke; Pascal C. Eneh; Roseanne Okafor; Benjamin N. Okolonkwo; Solomon A. Braide; Chukwubike U.Okeke; Holy Brown; Ngozika B. Okwandu

2012-01-01

Background and AimsThe continual use of hormonal contraceptives among women within reproductive age has been on the increase. The effects of these contraceptives on lipid metabolism vary depending on the type of hormonal contraceptive. This study was carried out among Nigerian women, to compare theeffects of injectable hormonal contraceptives to that of combined oral contraceptives on lipid profile (triglyceride, total cholesterol, high density lipoprotein-cholesterol and low density lipo-pro...

Comparing the Cost-Effectiveness of Simulation Modalities: A Case Study of Peripheral Intravenous Catheterization Training

Science.gov (United States)

Isaranuwatchai, Wanrudee; Brydges, Ryan; Carnahan, Heather; Backstein, David; Dubrowski, Adam

2014-01-01

While the ultimate goal of simulation training is to enhance learning, cost-effectiveness is a critical factor. Research that compares simulation training in terms of educational- and cost-effectiveness will lead to better-informed curricular decisions. Using previously published data we conducted a cost-effectiveness analysis of three…

Database Description - Open TG-GATEs Pathological Image Database | LSDB Archive [Life Science Database Archive metadata

Lifescience Database Archive (English)

Full Text Available List Contact us Open TG-GATEs Pathological Image Database Database Description General information of database Database... name Open TG-GATEs Pathological Image Database Alternative name - DOI 10.18908/lsdba.nbdc00954-0...iomedical Innovation 7-6-8, Saito-asagi, Ibaraki-city, Osaka 567-0085, Japan TEL:81-72-641-9826 Email: Database... classification Toxicogenomics Database Organism Taxonomy Name: Rattus norvegi... Article title: Author name(s): Journal: External Links: Original website information Database

Data sources for heart failure comparative effectiveness research.

Science.gov (United States)

Xian, Ying; Hammill, Bradley G; Curtis, Lesley H

2013-01-01

Existing data sources for heart failure research offer advantages and disadvantages for CER. Clinical registries collect detailed information about disease presentation, treatment, and outcomes on a large number of patients and provide the "real-world" population that is the hallmark of CER. Data are not collected longitudinally, however, and follow-up is often limited. Large administrative datasets provide the broadest population coverage with longitudinal outcomes follow-up but lack clinical detail. Linking clinical registries with other databases to assess longitudinal outcomes holds great promise. The Federal Coordinating Council for Comparative Effectiveness Research recommends further efforts on longitudinal linking of administrative or EHR-based databases, patient registries, private sector databases (particularly those with commercially insured populations that are not covered under federal and state databases), and other relevant data sources containing pharmacy, laboratory, adverse events, and mortality information. Advancing the infrastructure to provide robust, scientific data resources for patient-centered CER must remain a priority. Copyright © 2013 Elsevier Inc. All rights reserved.

Toxicogenomic Response of Rhodospirillum rubrum S1H to the Micropollutant Triclosan▿

OpenAIRE

Pycke, Benny F. G.; Vanermen, Guido; Monsieurs, Pieter; De Wever, Heleen; Mergeay, Max; Verstraete, Willy; Leys, Natalie

2010-01-01

In the framework of the Micro-Ecological Life Support System Alternative (MELiSSA) project, a pilot study was performed to identify the effects of triclosan on the MELiSSA carbon-mineralizing microorganism Rhodospirillum rubrum S1H. Triclosan is a biocide that is commonly found in human excrement and is considered an emerging pollutant in wastewater and the environment. Chronic exposure to MELiSSA-relevant concentrations (≥25 μg liter−1) of triclosan resulted in a significant extension of the...

Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

Directory of Open Access Journals (Sweden)

Hettne Kristina M

2013-01-01

Full Text Available Abstract Background Availability of chemical response-specific lists of genes (gene sets for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM, and that these can be used with gene set analysis (GSA methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. Methods We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human and 588 (mouse gene sets from the Comparative Toxicogenomics Database (CTD. We tested for significant differential expression (SDE (false discovery rate -corrected p-values Results Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants had a similar toxicity pattern as the triazoles. We confirmed embryotoxic effects, and discriminated triazoles from other chemicals. Conclusions Gene set analysis with next-gen TM-derived chemical response-specific gene sets is a scalable method for identifying similarities in gene responses to other chemicals, from which one may infer potential mode of action and/or toxic effect.

Dose–response analysis of phthalate effects on gene expression in rat whole embryo culture

Energy Technology Data Exchange (ETDEWEB)

Robinson, Joshua F. [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Verhoef, Aart; Beelen, Vincent A. van; Pennings, Jeroen L.A. [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Piersma, Aldert H., E-mail: aldert.piersma@rivm.nl [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht (Netherlands)

2012-10-01

The rat postimplantation whole embryo culture (WEC) model serves as a potential screening tool for developmental toxicity. In this model, cultured rat embryos are exposed during early embryogenesis and evaluated for morphological effects. The integration of molecular-based markers may lead to improved objectivity, sensitivity and predictability of WEC in assessing developmental toxic properties of compounds. In this study, we investigated the concentration-dependent effects of two phthalates differing in potency, mono(2-ethylhexyl) phthalate (MEHP) and monomethyl phthalate (MMP, less toxic), on the transcriptome in WEC to examine gene expression in relation with dysmorphogenesis. MEHP was more potent than MMP in inducing gene expression changes as well as changes on morphology. MEHP induced significant enrichment of cholesterol/lipid/steroid (CLS) metabolism and apoptosis pathways which was associated with developmental toxicity. Regulation of genes within CLS metabolism pathways represented the most sensitive markers of MEHP exposure, more sensitive than classical morphological endpoints. As shown in direct comparisons with toxicogenomic in vivo studies, alterations in the regulation of CLS metabolism pathways has been previously identified to be associated with developmental toxicity due to phthalate exposure in utero. Our results support the application of WEC as a model to examine relative phthalate potency through gene expression and morphological responses. Additionally, our results further define the applicability domain of the WEC model for developmental toxicological investigations. -- Highlights: ► We examine the effect of two phthalates on gene expression and morphology in WEC. ► MEHP is more potent than MMP in inducing gene expression changes and dysmorphogenesis. ► MEHP significantly disrupts cholesterol metabolism pathways in a dose-dependent manner. ► Specific phthalate-related mechanisms in WEC are relevant to mechanisms in vivo.

Comparing and counting logs in direct and effective methods of QCD resummation

Energy Technology Data Exchange (ETDEWEB)

Almeida, Leandro G. [Laboratoire de Physique Théorique, Université Paris-Sud 11 and CNRS,91405 Orsay Cedex (France); Institut de Biologie de l’École Normale Supérieure (IBENS),Inserm 1024-CNRS 8197, 46 rue d’Ulm, 75005 Paris (France); Ellis, Stephen D. [Department of Physics, University of Washington,Seattle, WA 98195 (United States); Lee, Christopher [Theoretical Division, MS B283, Los Alamos National Laboratory,Los Alamos, NM 87544 (United States); Sterman, George [C.N. Yang Institute for Theoretical Physics, Stony Brook University,Stony Brook, NY 11794 (United States); Sung, Ilmo [Department of Applied Physics, New York University,Brooklyn, NY 11201 (United States); Queens College, City University of New York,Flushing, NY 11367 (United States); Walsh, Jonathan R. [Lawrence Berkeley National Laboratory, University of California,Berkeley, CA 94720 (United States); Berkeley Center for Theoretical Physics, University of California,Berkeley, CA 94720 (United States)

2014-04-29

We compare methods to resum logarithms in event shape distributions as they have been used in perturbative QCD directly and in effective field theory. We demonstrate that they are equivalent. In showing this equivalence, we are able to put standard soft-collinear effective theory (SCET) formulae for cross sections in momentum space into a novel form more directly comparable with standard QCD formulae, and endow the QCD formulae with dependence on separated hard, jet, and soft scales, providing potential ways to improve estimates of theoretical uncertainty. We show how to compute cross sections in momentum space to keep them as accurate as the corresponding expressions in Laplace space. In particular, we point out that that care is required in truncating differential distributions at N{sup k}LL accuracy to ensure they match the accuracy of the corresponding cumulant or Laplace transform. We explain how to avoid such mismatches at N{sup k}LL accuracy, and observe why they can also be avoided by working to N{sup k}LL{sup ′} accuracy.

A comparative study of the effect of diet and soda carbonated drinks ...

African Journals Online (AJOL)

A comparative study of the effect of diet and soda carbonated drinks on the histology of the cerebellum of adult female albino Wistar rats. ... African Health Sciences ... Group B was administered 50 ml of regular soda (RS), and group C was administered 50 ml of diet soda (DS) each per day for 21 days, and the rats were ...

Comparative effectiveness of mepolizumab and omalizumab in severe asthma: An indirect treatment comparison.

Science.gov (United States)

Cockle, Sarah M; Stynes, Gillian; Gunsoy, Necdet B; Parks, Daniel; Alfonso-Cristancho, Rafael; Wex, Jaro; Bradford, Eric S; Albers, Frank C; Willson, Jenny

2017-02-01

Severe asthma is a heterogeneous disease. Patients with both eosinophilic and allergic asthma phenotypes may be eligible for treatment with mepolizumab and omalizumab. Evidence on the relative effectiveness of these treatments in this 'overlap' population would be informative for clinical and payer decision making. A systematic literature review and indirect treatment comparison (Bayesian framework) were performed to assess the comparative effectiveness and tolerability of mepolizumab and omalizumab, as add-ons to standard of care. Studies included in the primary analysis were double-blind, randomized controlled trials, ≥12 weeks' duration enrolling patients with severe asthma with a documented exacerbation history and receiving high-dose inhaled corticosteroids plus ≥1 additional controller. Two populations were examined: patients potentially eligible for 1) both treatments (Overlap population) and 2) either treatment (Trial population). In the Overlap population, no differences between treatments in clinically significant exacerbations and exacerbations requiring hospitalization were found, although trends favored mepolizumab (rate ratio [RR]:0.66 [95% credible intervals (Crl):0.37,1.19]; 0.19[0.02,2.32], respectively). In the Trial population, mepolizumab treatment produced greater reductions in clinically significant exacerbations (RR:0.63 [95% CrI:0.45,0.89]) but not exacerbations requiring hospitalization compared with omalizumab (RR:0.58 [95% Crl: 0.16,2.13]), although the trend favored mepolizumab. Both treatments had broadly comparable effects on lung function, and similar tolerability profiles. Whilst this analysis has limitations due to a restricted evidence base and residual heterogeneity, it showed that in patients with severe asthma, mepolizumab seems to be at least as effective as omalizumab and that the tolerability profiles of the two treatments did not meaningfully differentiate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nickel and binary metal mixture responses in Daphnia magna: Molecular fingerprints and (sub)organismal effects

International Nuclear Information System (INIS)

Vandenbrouck, Tine; Soetaert, Anneleen; Ven, Karlijn van der; Blust, Ronny; Coen, Wim de

2009-01-01

the complex nature of mixture toxicity evaluation, underline the potential of a toxicogenomics approach in gaining more mechanistic information on the effects of single compounds and mixtures

[Cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of rheumatoid arthritis].

Science.gov (United States)

Salinas-Escudero, Guillermo; Vargas-Valencia, Juan; García-García, Erika Gabriela; Munciño-Ortega, Emilio; Galindo-Suárez, Rosa María

2013-01-01

to conduct cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of moderate or severe rheumatoid arthritis in patients with previous unresponse to immune selective anti-inflammatory derivatives failure. a pharmacoeconomic model based on decision analysis to assess the clinical outcome after giving etanercept, infliximab, adalimumab or tocilizumab to treat moderate or severe rheumatoid arthritis was employed. Effectiveness of medications was assessed with improvement rates of 20 % or 70 % of the parameters established by the American College of Rheumatology (ACR 20 and ACR 70). the model showed that etanercept had the most effective therapeutic response rate: 79.7 % for ACR 20 and 31.4 % for ACR 70, compared with the response to other treatments. Also, etanercept had the lowest cost ($149,629.10 per patient) and had the most cost-effective average ($187,740.40 for clinical success for ACR 20 and $476,525.80 for clinical success for ACR 70) than the other biologic therapies. we demonstrated that treatment with etanercept is more effective and less expensive compared to the other drugs, thus making it more efficient therapeutic option both in terms of means and incremental cost-effectiveness ratios for the treatment of rheumatoid arthritis.

Consensus of recommendations guiding comparative effectiveness research methods.

Science.gov (United States)

Morton, Jacob B; McConeghy, Robert; Heinrich, Kirstin; Gatto, Nicolle M; Caffrey, Aisling R

2016-12-01

Because of an increasing demand for quality comparative effectiveness research (CER), methods guidance documents have been published, such as those from the Agency for Healthcare Research and Quality (AHRQ) and the Patient-Centered Outcomes Research Institute (PCORI). Our objective was to identify CER methods guidance documents and compare them to produce a summary of important recommendations which could serve as a consensus of CER method recommendations. We conducted a systematic literature review to identify CER methods guidance documents published through 2014. Identified documents were analyzed for methods guidance recommendations. Individual recommendations were categorized to determine the degree of overlap. We identified nine methods guidance documents, which contained a total of 312 recommendations, 97% of which were present in two or more documents. All nine documents recommended transparency and adaptation for relevant stakeholders in the interpretation and dissemination of results. Other frequently shared CER methods recommendations included: study design and operational definitions should be developed a priori and allow for replication (n = 8 documents); focus on areas with gaps in current clinical knowledge that are relevant to decision-makers (n = 7); validity of measures, instruments, and data should be assessed and discussed (n = 7); outcomes, including benefits and harms, should be clinically meaningful, and objectively measured (n = 7). Assessment for and strategies to minimize bias (n = 6 documents), confounding (n = 6), and heterogeneity (n = 4) were also commonly shared recommendations between documents. We offer a field-consensus guide based on nine CER methods guidance documents that will aid researchers in designing CER studies and applying CER methods. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

AHRQ series paper 3: identifying, selecting, and refining topics for comparative effectiveness systematic reviews: AHRQ and the effective health-care program.

Science.gov (United States)

Whitlock, Evelyn P; Lopez, Sarah A; Chang, Stephanie; Helfand, Mark; Eder, Michelle; Floyd, Nicole

2010-05-01

This article discusses the identification, selection, and refinement of topics for comparative effectiveness systematic reviews within the Agency for Healthcare Research and Quality's Effective Health Care (EHC) program. The EHC program seeks to align its research topic selection with the overall goals of the program, impartially and consistently apply predefined criteria to potential topics, involve stakeholders to identify high-priority topics, be transparent and accountable, and continually evaluate and improve processes. A topic prioritization group representing stakeholder and scientific perspectives evaluates topic nominations that fit within the EHC program (are "appropriate") to determine how "important" topics are as considered against seven criteria. The group then judges whether a new comparative effectiveness systematic review would be a duplication of existing research syntheses, and if not duplicative, if there is adequate type and volume of research to conduct a new systematic review. Finally, the group considers the "potential value and impact" of a comparative effectiveness systematic review. As the EHC program develops, ongoing challenges include ensuring the program addresses truly unmet needs for synthesized research because national and international efforts in this arena are uncoordinated, as well as engaging a range of stakeholders in program decisions while also achieving efficiency and timeliness.

Cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC in myelodysplastic syndrome (MDS

Directory of Open Access Journals (Sweden)

Myrna Candelaria-Hernández

2017-06-01

Full Text Available ABSTRACTIntroductionMyelodysplastic syndrome (MDS comprises a group of clonal hematological disorders, characterized by ineffective hematopoiesis and progressive bone marrow failure. It increases the risk of transformation to acute myeloid leukemia (AML. Therapeutic benefit should include overall survival increase (OS, hematological improvement, transfusion dependence and time to progression to AML decrease.ObjectiveAssess, from a Mexican health-care perspective, the cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC plus best supportive care (BSC for the treatment of adult patients with intermediate-2 and high-risk MDS, who are not eligible for hematopoietic stem-cell transplantation. We developed a cost-effectiveness survival analysis model of three stages: MDS, AML, and death. OS and costs are extrapolated beyond three-year time horizon. Discount rate of 5% was applied. To estimate the model cycle probability transition to mortality state, survival curves were constructed for each treatment arm using individual patient-level data from Study AZA-001. Unitary costs are from public price list, and profiles for the management of MDS and AML were collected separately using a structured questionnaire. Probabilistic sensitivity analyses (PSA were conducted by simultaneously sampling from estimated probability distributions of model parameters.ResultsOverall survival was projected to increase by 72.26 weeks with azacitidine. Incremental expected total costs for azacitidine compared to LDC was MXN$68,045. However, the cost of the drug therapy was lower with azacitidine. The incremental cost-effectiveness ratio (ICER for azacitidine compared to LDC was MXN$48,932 per life-year gained (LYG. PSA showed that azacitidine was a highly cost-effective option in 96.49% of the simulated cases in MXN$180,000/LYG willingness-to-pay.ConclusionsCompared with LDC, azacitidine represents a cost-effective treatment alternative in patients

Comparing Effects of Biologic Agents in Treating Patients with Rheumatoid Arthritis: A Multiple Treatment Comparison Regression Analysis.

Directory of Open Access Journals (Sweden)

Ingunn Fride Tvete

Full Text Available Rheumatoid arthritis patients have been treated with disease modifying anti-rheumatic drugs (DMARDs and the newer biologic drugs. We sought to compare and rank the biologics with respect to efficacy. We performed a literature search identifying 54 publications encompassing 9 biologics. We conducted a multiple treatment comparison regression analysis letting the number experiencing a 50% improvement on the ACR score be dependent upon dose level and disease duration for assessing the comparable relative effect between biologics and placebo or DMARD. The analysis embraced all treatment and comparator arms over all publications. Hence, all measured effects of any biologic agent contributed to the comparison of all biologic agents relative to each other either given alone or combined with DMARD. We found the drug effect to be dependent on dose level, but not on disease duration, and the impact of a high versus low dose level was the same for all drugs (higher doses indicated a higher frequency of ACR50 scores. The ranking of the drugs when given without DMARD was certolizumab (ranked highest, etanercept, tocilizumab/ abatacept and adalimumab. The ranking of the drugs when given with DMARD was certolizumab (ranked highest, tocilizumab, anakinra/rituximab, golimumab/ infliximab/ abatacept, adalimumab/ etanercept [corrected]. Still, all drugs were effective. All biologic agents were effective compared to placebo, with certolizumab the most effective and adalimumab (without DMARD treatment and adalimumab/ etanercept (combined with DMARD treatment the least effective. The drugs were in general more effective, except for etanercept, when given together with DMARDs.

Cost-effectiveness of cardiotocography plus ST analysis of the fetal electrocardiogram compared with cardiotocography only

NARCIS (Netherlands)

Vijgen, Sylvia M. C.; Westerhuis, Michelle E. M. H.; Opmeer, Brent C.; Visser, Gerard H. A.; Moons, Karl G. M.; Porath, Martina M.; Oei, Guid S.; van Geijn, Herman P.; Bolte, Antoinette C.; Willekes, Christine; Nijhuis, Jan G.; van Beek, Erik; Graziosi, Giuseppe C. M.; Schuitemaker, Nico W. E.; van Lith, Jan M. M.; van den Akker, Eline S. A.; Drogtrop, Addy P.; van Dessel, Hendrikus J. H. M.; Rijnders, Robbert J. P.; Oosterbaan, Herman P.; Mol, Ben Willem J.; Kwee, Anneke

2011-01-01

To assess the cost-effectiveness of addition of ST analysis of the fetal electrocardiogram (ECG; STAN) to cardiotocography (CTG) for fetal surveillance during labor compared with CTG only. Cost-effectiveness analysis based on a randomized clinical trial on ST analysis of the fetal ECG. Obstetric

Comparing antifungal effects of Zatariamultiflora and Punicagranatum extract with Nystatin on Candida Albicans

Directory of Open Access Journals (Sweden)

F. Nouri

2016-12-01

Full Text Available Background: Despite all the progress that has been made in the manufacture of synthetic drugs, herbal drugs are increasingly taken into account. This is due to the growing belief that they have fewer side effects compared to synthetic ones. Objective: To compare the antifungal effects of extracts of Zatariamultiflora and Punicagranatum with Nystatin on Candida Albicans. Methods: This inviro trial accomplished in the school of dentistry of Tehran University in 2012. From the mouths of 25 patients with denture stomatitis were sampled using sterile swabs. Candida Albicans strains were isolated from samples and standard Candida Albicans PTCC 5027 were cultured too. Then extract of Zatariamultiflora and Punicagranatum to be obtained and antifungal of extract studied with disk diffusion method. Antifungal power of each of the extracts on the inhibition zone diameter was created in the medium. Data were analyzed by ANOVA and Friedman statistical tests. Findings: Results showed extracts of Zataria and pomegranate flowers have antifungal significant effects (P<0.001. Diameter of inhabitation zone was 17.66±./75 mm in Nystatin group and in the Zataria and pomegranate flowers extracts groups was lower (P<0.001. None of the negative control disc did inhibition zone in the medium. Conclusion: With due attention of Zataria and pomegranate flowers extracts exhibited antifungal effects on Candida Albincans.

MODELLING OF FINANCIAL EFFECTIVENESS AND COMPARATIVE ANALYSIS OF PUBLIC-PRIVATE PARTNERSHIP PROJECTS AND PUBLIC PROCUREMENT

Directory of Open Access Journals (Sweden)

Kuznetsov Aleksey Alekseevich

2017-10-01

Full Text Available The article substantiates the necessity of extension and development of tools for methodological evaluation of effectiveness of public-private partnership (PPP projects both individually and in comparison of effectiveness of various mechanisms of projects realization on the example of traditional public procurement. The author proposed an original technique of modelling cash flows of private and public partners when realizing the projects based on PPP and on public procurement. The model enables us promptly and with sufficient accuracy to reveal comparative advantages of project forms of PPP and public procurement, and also assess financial effectiveness of the PPP projects for each partner. The modelling is relatively straightforward and reliable. The model also enables us to evaluate public partner's expenses for availability, find the terms and thresholds for interest rates of financing attracted by the partners and for risk probabilities to ensure comparative advantage of PPP project. Proposed criteria of effectiveness are compared with methodological recommendations provided by the Ministry of Economic Development of the Russian Federation. Subject: public and private organizations, financial institutions, development institutions and their theoretical and practical techniques for effectiveness evaluation of public-private partnership (PPP projects. Complexity of effectiveness evaluation and the lack of unified and accepted methodology are among the factors that limit the development of PPP in the Russian Federation nowadays. Research objectives: development of methodological methods for assessing financial efficiency of PPP projects by creating and justifying application of new principles and methods of modelling, and also criteria for effectiveness of PPP projects both individually and in comparison with the public procurement. Materials and methods: open database of ongoing PPP projects in the Russian Federation and abroad was used. The

Comparative Effectiveness of Personalized Lifestyle Management Strategies for Cardiovascular Disease Risk Reduction.

Science.gov (United States)

Chu, Paula; Pandya, Ankur; Salomon, Joshua A; Goldie, Sue J; Hunink, M G Myriam

2016-03-29

Evidence shows that healthy diet, exercise, smoking interventions, and stress reduction reduce cardiovascular disease risk. We aimed to compare the effectiveness of these lifestyle interventions for individual risk profiles and determine their rank order in reducing 10-year cardiovascular disease risk. We computed risks using the American College of Cardiology/American Heart Association Pooled Cohort Equations for a variety of individual profiles. Using published literature on risk factor reductions through diverse lifestyle interventions-group therapy for stopping smoking, Mediterranean diet, aerobic exercise (walking), and yoga-we calculated the risk reduction through each of these interventions to determine the strategy associated with the maximum benefit for each profile. Sensitivity analyses were conducted to test the robustness of the results. In the base-case analysis, yoga was associated with the largest 10-year cardiovascular disease risk reductions (maximum absolute reduction 16.7% for the highest-risk individuals). Walking generally ranked second (max 11.4%), followed by Mediterranean diet (max 9.2%), and group therapy for smoking (max 1.6%). If the individual was a current smoker and successfully quit smoking (ie, achieved complete smoking cessation), then stopping smoking yielded the largest reduction. Probabilistic and 1-way sensitivity analysis confirmed the demonstrated trend. This study reports the comparative effectiveness of several forms of lifestyle modifications and found smoking cessation and yoga to be the most effective forms of cardiovascular disease prevention. Future research should focus on patient adherence to personalized therapies, cost-effectiveness of these strategies, and the potential for enhanced benefit when interventions are performed simultaneously rather than as single measures. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Linking genomic responses of gonads with reproductive impairment in marine medaka (Oryzias melastigma) exposed chronically to the chemopreventive and antifouling agent, 3,3′-diindolylmethane (DIM)

Energy Technology Data Exchange (ETDEWEB)

Chen, Lianguo [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Au, Doris W.T. [State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR (China); Hu, Chenyan [School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430072 (China); Zhang, Weipeng [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Zhou, Bingsheng [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Cai, Lin [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Giesy, John P. [Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3 (Canada); Department of Zoology, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI (United States); Qian, Pei-Yuan, E-mail: boqianpy@ust.hk [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China)

2017-02-15

Highlights: • Marine medaka were exposed chronically to low-doses of DIM. • Toxicogenomic responses of gonads were profiled at transcript and protein levels. • Molecular initiating events were linked to adverse apical outcomes. • VTG mobilization was blocked by lower abundance of cathepsin enzyme in ovary. • Eggshell proteins were more indicative of reproductive failure than VTG. - Abstract: 3,3′-Diindolylmethane (DIM) has been promoted as an effective chemopreventive and antifouling additive. However, the concurrent risks or side effects of DIM are not fully understood, especially on tissues responsive to estrogen. Therefore, this study employed marine medaka (Oryzias melastigma) as a test model to evaluate relative safety and explore mechanisms of toxic action of DIM on development and function of gonad after chronic (28 days) aqueous exposure to relatively low doses (0 μg/L or 8.5 μg/L). Integration of comprehensive toxicogenomic analysis at the transcriptome and proteome levels with apical endpoints, such as production of eggs and swimming performance of larvae, elucidated the molecular linkage in gonad from bottom up along the reproductive adverse outcome pathway. A series of sequential changes at the transcript and protein levels were linked to lesser fecundity and viability of larvae exposed to DIM. Anomalous production of vitellogenin (VTG) and eggshell proteins in testis confirmed the estrogenic potency of DIM. In the ovary, although storage of VTG was greater, lesser expressions of cathepsin enzymes blocked cleavage and incorporation of VTG into oocytes as yolk, which acted together with lower eggshell proteins to inhibit maturation of primary oocyte and thus contributed to impairment of fecundity. Overall, this study demonstrated that exposure to DIM impaired reproductive fitness. Diverse molecular initiating changes in gonads were linked to apical endpoints that could be used in assessment of risks posed by DIM on gametogenesis. In

Linking genomic responses of gonads with reproductive impairment in marine medaka (Oryzias melastigma) exposed chronically to the chemopreventive and antifouling agent, 3,3′-diindolylmethane (DIM)

International Nuclear Information System (INIS)

Chen, Lianguo; Au, Doris W.T.; Hu, Chenyan; Zhang, Weipeng; Zhou, Bingsheng; Cai, Lin; Giesy, John P.; Qian, Pei-Yuan

2017-01-01

Highlights: • Marine medaka were exposed chronically to low-doses of DIM. • Toxicogenomic responses of gonads were profiled at transcript and protein levels. • Molecular initiating events were linked to adverse apical outcomes. • VTG mobilization was blocked by lower abundance of cathepsin enzyme in ovary. • Eggshell proteins were more indicative of reproductive failure than VTG. - Abstract: 3,3′-Diindolylmethane (DIM) has been promoted as an effective chemopreventive and antifouling additive. However, the concurrent risks or side effects of DIM are not fully understood, especially on tissues responsive to estrogen. Therefore, this study employed marine medaka (Oryzias melastigma) as a test model to evaluate relative safety and explore mechanisms of toxic action of DIM on development and function of gonad after chronic (28 days) aqueous exposure to relatively low doses (0 μg/L or 8.5 μg/L). Integration of comprehensive toxicogenomic analysis at the transcriptome and proteome levels with apical endpoints, such as production of eggs and swimming performance of larvae, elucidated the molecular linkage in gonad from bottom up along the reproductive adverse outcome pathway. A series of sequential changes at the transcript and protein levels were linked to lesser fecundity and viability of larvae exposed to DIM. Anomalous production of vitellogenin (VTG) and eggshell proteins in testis confirmed the estrogenic potency of DIM. In the ovary, although storage of VTG was greater, lesser expressions of cathepsin enzymes blocked cleavage and incorporation of VTG into oocytes as yolk, which acted together with lower eggshell proteins to inhibit maturation of primary oocyte and thus contributed to impairment of fecundity. Overall, this study demonstrated that exposure to DIM impaired reproductive fitness. Diverse molecular initiating changes in gonads were linked to apical endpoints that could be used in assessment of risks posed by DIM on gametogenesis. In

Comparative Effectiveness of Treatments for Binge-Eating Disorder: Systematic Review and Network Meta-Analysis.

Science.gov (United States)

Peat, Christine M; Berkman, Nancy D; Lohr, Kathleen N; Brownley, Kimberly A; Bann, Carla M; Cullen, Katherine; Quattlebaum, Mary J; Bulik, Cynthia M

2017-09-01

Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we aimed to expand that literature with a review of comparative effectiveness. We searched MEDLINE,® EMBASE,® Cochrane Library, Academic OneFile, CINAHL® for binge-eating disorder treatment articles and selected studies using predetermined inclusion and exclusion criteria. Data were sufficient for network meta-analysis comparing two pharmacological interventions; psychological interventions were analysed qualitatively. In all, 28 treatment comparisons were included in this review: one pharmacological comparison (second-generation antidepressants versus lisdexamfetamine) and 26 psychological comparisons. Only three statistically significant differences emerged: lisdexamfetamine was better at increasing binge abstinence than second-generation antidepressants; therapist-led cognitive behavioural therapy was better at reducing binge-eating frequency than behavioural weight loss, but behavioural weight loss was better at reducing weight. The majority of other treatment comparisons revealed few significant differences between groups. Thus, patients and clinicians can choose from several effective treatment options. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

The effects of physiotherapy for female urinary incontinence: individual compared with group treatment

NARCIS (Netherlands)

Janssen, C.C.M.; Lagro-Janssen, A.L.M.; Felling, A.J.A.

2001-01-01

OBJECTIVES: To compare, in a randomized trial, the effects of individual and group physiotherapy for urinary incontinence in women referred by their general practitioner (GP). PATIENTS AND METHODS: The study included women of all ages (mean 47.8 years) with stress, urge or mixed incontinence; 126

The effects of physiotherapy for female urinary incontinence: individual compared with group treatment.

NARCIS (Netherlands)

Janssen, C.C.M.; Lagro-Janssen, A.L.M.; Felling, A.J.A.

2001-01-01

OBJECTIVES: To compare, in a randomized trial, the effects of individual and group physiotherapy for urinary incontinence in women referred by their general practitioner (GP). PATIENTS AND METHODS: The study included women of all ages (mean 47.8 years) with stress, urge or mixed incontinence; 126

Comparative cardiopulmonary effects of particulate matter- and ozone-enhanced smog atmospheres in mice

Science.gov (United States)

This study was conducted to compare the cardiac effects of particulate matter (PM)-enhanced and ozone(O3)-enhanced smog atmospheres in mice. We hypothesized that O3-enhanced smog would cause greater cardiac dysfunction than PM-enhanced smog due to the higher concentrations of irr...

Comparative effectiveness of instructional design features in simulation-based education: systematic review and meta-analysis.

Science.gov (United States)

Cook, David A; Hamstra, Stanley J; Brydges, Ryan; Zendejas, Benjamin; Szostek, Jason H; Wang, Amy T; Erwin, Patricia J; Hatala, Rose

2013-01-01

Although technology-enhanced simulation is increasingly used in health professions education, features of effective simulation-based instructional design remain uncertain. Evaluate the effectiveness of instructional design features through a systematic review of studies comparing different simulation-based interventions. We systematically searched MEDLINE, EMBASE, CINAHL, ERIC, PsycINFO, Scopus, key journals, and previous review bibliographies through May 2011. We included original research studies that compared one simulation intervention with another and involved health professions learners. Working in duplicate, we evaluated study quality and abstracted information on learners, outcomes, and instructional design features. We pooled results using random effects meta-analysis. From a pool of 10,903 articles we identified 289 eligible studies enrolling 18,971 trainees, including 208 randomized trials. Inconsistency was usually large (I2 > 50%). For skills outcomes, pooled effect sizes (positive numbers favoring the instructional design feature) were 0.68 for range of difficulty (20 studies; p simulation-based education.

Comparative effect of coffee robusta and coffee arabica (Qahwa) on memory and attention.

Science.gov (United States)

Alharbi, Waheeb D M; Azmat, Aisha; Ahmed, Muhammad

2018-04-13

The comparative effects of coffee robusta and coffee arabica (Qahwa) on different attention and memory related assignments were measured in a double-blind study of 300 healthy young adult women who were randomly assigned to one of three different drinks: Group I (coffee robusta sachet dissolved in 100 ml of hot water): Group II (coffee arabica): and group III (100 ml water only). Cognitive function was assessed by standardized tests. Several monitoring cognitive tests and tasks were specifically chosen and performed to investigate the comparative effects of coffee robusta (CR) and coffee arabica (Qahwa; AC) on sleepiness (sleep and clear headed scale), attention (trail A & B, symbol digit, letter cancellation), general cognitive ability (stroop test) and memory (card test). Data was interpreted by analysis of variance (ANOVA). The present study revealed that coffee robusta has beneficial effects on attention, general cognitive ability and memory. Higher though non-significant cognitive scores were associated with coffee robusta consumption. Although, consumption of coffee arabica (Qahwa) has significant effects (P < 0.05) on sleepiness, attention, general cognitive ability and memory and it significantly improve reaction time and correct responses. Since different tasks were related to the sustained attention and working memory processes, results would suggest that coffee arabica (qahwa) could increase the memory and efficiency of the attentional system might be due to the presence of chlorogenic acids (CGA) which are found in less quantity in coffee robusta. However, more studies using larger samples and different tasks are necessary to better understand the effects of coffee robusta and arabica (Qahwa) on attention and memory.

Thermo-Kinetic Investigation of Comparative Ligand Effect on Cysteine Iron Redox Reaction

OpenAIRE

Rizvi, Masood Ahmad; Teshima, Norio; Maqsood, Syed Raashid; Akhoon, Showket Ahmad; Peerzada, Ghulam Mustafa

2015-01-01

Transition metal ions in their free state bring unwanted biological oxidations generating oxidative stress. The ligand modulated redox potential can be indispensable in prevention of such oxidative stress by blocking the redundant bio-redox reactions. In this study we investigated the comparative ligand effect on the thermo-kinetic aspects of biologically important cysteine iron (III) redox reaction using spectrophotometric and potentiometric methods. The results were corroborated...

Effects of stimulus order on discrimination processes in comparative and equality judgements: data and models.

Science.gov (United States)

Dyjas, Oliver; Ulrich, Rolf

2014-01-01

In typical discrimination experiments, participants are presented with a constant standard and a variable comparison stimulus and their task is to judge which of these two stimuli is larger (comparative judgement). In these experiments, discrimination sensitivity depends on the temporal order of these stimuli (Type B effect) and is usually higher when the standard precedes rather than follows the comparison. Here, we outline how two models of stimulus discrimination can account for the Type B effect, namely the weighted difference model (or basic Sensation Weighting model) and the Internal Reference Model. For both models, the predicted psychometric functions for comparative judgements as well as for equality judgements, in which participants indicate whether they perceived the two stimuli to be equal or not equal, are derived and it is shown that the models also predict a Type B effect for equality judgements. In the empirical part, the models' predictions are evaluated. To this end, participants performed a duration discrimination task with comparative judgements and with equality judgements. In line with the models' predictions, a Type B effect was observed for both judgement types. In addition, a time-order error, as indicated by shifts of the psychometric functions, and differences in response times were observed only for the equality judgement. Since both models entail distinct additional predictions, it seems worthwhile for future research to unite the two models into one conceptual framework.

Comparing the effects of low-dose contraceptive pills to control dysfunctional uterine bleeding by oral and vaginal methods.

Science.gov (United States)

Mehrabian, Ferdous; Abbassi, Fariba

2013-09-01

Background and Objective : Contraceptive pills are generally taken orally and can cause side effects such as nausea, vomiting and hypertension. The vaginal use of these pills can reduce such complications. Our objective was to compare the efficacy and side effects of low dose contraceptive pills by oral and vaginal route in the management of dysfunctional uterine bleeding-(DUB) Methods: This comparative observational study was conducted at Beheshti and Alzahra (SA) teaching hospitals, affiliated to Isfahan University of Medical Sciences in 2010-2011. One hundred women who presented with DUB were randomly assigned into two groups of equal number, receiving the low dose oral contraceptive pills by oral or vaginal route for three month. The amount and duration of bleeding were compared at the beginning and at the end of the study and side effects by these two methods compared. The results of this study showed that both oral and vaginal routes effectively reduced the duration and amount of bleeding due to DUB after three courses of treatment. This effect was better in the vaginal method compared with oral administration (P = 0.03). Regarding the side effects, nausea and vomiting were significantly higher in the oral group than in the vaginal group (P = 0.03). Vulvovaginitis infection was more frequent in the vaginal group than in the oral group (P = 0.03). Low dose contraceptive pills are effective in reducing the amount, time, and duration of bleeding in patients with DUB. In addition, reduction of gastrointestinal side effects by vaginal route helps to use these pills by the patient with proper training of physicians, midwives and patients.

Effectiveness of the homeopathic preparation Zeel compared with carprofen in dogs with osteoarthritis.

Science.gov (United States)

Neumann, Stephan; Stolt, Pelle; Braun, Gabriele; Hellmann, Klaus; Reinhart, Erich

2011-01-01

The authors compared the symptomatic effectiveness of a complex homeopathic preparation Zeel (1-3 tablets orally per day depending on body weight) to carprofen (4 mg/kg body weight) in dogs (n=68) aged >1 yr diagnosed with osteoarthritis in a multicenter, prospective, observational open-label cohort study in 12 German veterinary clinics. The active treatment period was 56 days. Symptomatic effectiveness, lameness, stiffness of movements, and pain on palpation were evaluated by treating veterinarians and owners. Clinical signs of osteoarthritis improved significantly (Pcarprofen group.

Effectiveness of the Gold Standard Programme compared with other smoking cessation interventions in Denmark

DEFF Research Database (Denmark)

Rasmussen, Mette; Fernández, Esteve; Tønnesen, Hanne

2017-01-01

Objectives: We compared the effectiveness of the Gold Standard Programme (a comprehensive smoking cessation intervention commonly used in Denmark) with other face-to-face smoking cessation programmes in Denmark after implementation in real life, and we identified factors associated with successful...... did not want further contact, who intentionally were not followed up or who lacked information about the intervention they received were excluded. A total of 46 287 smokers were included. Interventions: Various real-life smoking cessation interventions were identified and compared: The Gold Standard...... smokers. The follow-up rate was 74%. Women were less likely to remain abstinent, OR 0.83 (CI 0.79 to 0.87). Short interventions were more effective among men. After adjusting for confounders, the Gold Standard Programme was the only intervention with significant results across sex, increasing the odds...

Stakeholder engagement for comparative effectiveness research in cancer care: experience of the DEcIDE Cancer Consortium.

Science.gov (United States)

Greenberg, Caprice C; Wind, Jennifer K; Chang, George J; Chen, Ronald C; Schrag, Deborah

2013-03-01

Stakeholder input is a critical component of comparative effectiveness research. To ensure that the research activities of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Network, supported by the Agency for Healthcare Research and Quality, translate into the greatest impact for everyday practice and policy-making in cancer, we were tasked with soliciting stakeholder input regarding priority areas in cancer-related comparative effectiveness research for the DEcIDE Cancer Consortium. Given the increasing emphasis on stakeholder engagement in research, many investigators are facing a similar task, yet there is limited literature to guide such efforts, particularly in cancer care. To help fill this gap, we present our approach to operationalizing stakeholder engagement and discuss it in the context of other recent developments in the area. We describe challenges encountered in convening stakeholders from multiple vantage points to prioritize topics and strategies used to mitigate these barriers. We offer several recommendations regarding how to best solicit stakeholder input to inform comparative effectiveness research in cancer care. These recommendations can inform other initiatives currently facing the challenges of engaging stakeholders in priority setting for cancer.

The effects of ionizing radiation on food, compared to the effects of conventional food treatment: A literature study. Pt. 1

International Nuclear Information System (INIS)

Leister, W.; Boegl, K.W.

1987-08-01

The extent and quality of changes due to irradiation is described and compared with conventional methods. Effects of radiation treatment on vegetable products as well as pork, beef, any type of fish and poultry product are compared with conventional thermic, micro-wave or smoke treatments, drying processes, ethylene oxide gas treatment, as well as effects from storage, temperature and sealed packaging. In this context the influences of the different treatment methods on various food components and on sensory, physical-chemical or biochemical characteristics were compared. The following tendencies were observed: conventional treatment methods produce partly more pronounced changes than irradiation with standard doses. Heat treatment, for instance, results in a greater weight loss, in altered sugar content, and in higher content of carbonyl and aldehyde releasing compounds. Gas treatment will cut the volatile oil content in half, while it remains nearly constant after irradiation. However, in some cases, an irradiation with standard doses may cause changes which should not be disregarded. In onions, for instance, irradiation is causing a stronger decomposition during storage than only cold storage. (orig./MG) [de

Comparative Thermal Aging Effects on PM-HIP and Forged Inconel 690

Science.gov (United States)

Bullens, Alexander L.; Bautista, Esteban; Jaye, Elizabeth H.; Vas, Nathaniel L.; Cain, Nathan B.; Mao, Keyou; Gandy, David W.; Wharry, Janelle P.

2018-03-01

This study compares thermal aging effects in Inconel 690 (IN690) produced by forging and powder metallurgy with hot isostatic pressing (PM-HIP). Isothermal aging is carried out over 400-800°C for up to 1000 h and then metallography and nanoindentation are utilized to relate grain microstructure with hardness and yield strength. The PM-HIP IN690 maintains a constant grain size through all aging conditions, while the forged IN690 exhibits limited grain growth at the highest aging temperature and longest aging time. The PM-HIP IN690 exhibits comparable mechanical integrity as the forged material throughout aging: hardness and yield strength are unchanged with 100 h aging, but increase after 1000 h aging at all temperatures. In both the PM-HIP and forged IN690, the Hall-Petch relationship for Ni-based superalloys predicts yield strength for 0-100 h aged specimens, but underestimates yield strength in the 1000 h aged specimens because of thermally induced precipitation.

Estimating the cost-effectiveness of stroke units in France compared with conventional care.

Science.gov (United States)

Launois, R; Giroud, M; Mégnigbêto, A C; Le Lay, K; Présenté, G; Mahagne, M H; Durand, I; Gaudin, A F

2004-03-01

The incidence of stroke in France is estimated at between 120 000 and 150 000 cases per year. This modeling study assessed the clinical and economic benefits of establishing specialized stroke units compared with conventional care. Data from the Dijon stroke registry were used to determine healthcare trajectories according to the degree of autonomy and organization of patient care. The relative risks of death or institutionalization or death or dependence after passage through a stroke unit were compared with conventional care. These risks were then inserted with the costing data into a Markov model to estimate the cost-effectiveness of stroke units. Patients cared for in a stroke unit survive more trimesters without sequelae in the 5 years after hospitalization than those cared for conventionally (11.6 versus 8.28 trimesters). The mean cost per patient at 5 years was estimated at 30 983 for conventional care and 34 638 in a stroke unit. An incremental cost-effectiveness ratio for stroke units of 1359 per year of life gained without disability was estimated. The cost-effectiveness ratio for stroke units is much lower than the threshold (53 400 ) of acceptability recognized by the international scientific community. This finding justifies organizational changes in the management of stroke patients and the establishment of stroke units in France.

Effective dose assessment in the maxillofacial region using thermoluminescent (TLD) and metal oxide semiconductor field-effect transistor (MOSFET) dosemeters: a comparative study

NARCIS (Netherlands)

Koivisto, J.; Schulze, D.; Wolff, J.E.H.; Rottke, D.

2014-01-01

Objectives: The objective of this study was to compare the performance of metal oxide semiconductor field-effect transistor (MOSFET) technology dosemeters with thermoluminescent dosemeters (TLDs) (TLD 100; Thermo Fisher Scientific, Waltham, MA) in the maxillofacial area. Methods: Organ and effective

Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools.

Science.gov (United States)

Chaiyakunapruk, Nathorn; Somkrua, Ratchadaporn; Hutubessy, Raymond; Henao, Ana Maria; Hombach, Joachim; Melegaro, Alessia; Edmunds, John W; Beutels, Philippe

2011-05-12

Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example

CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials

OpenAIRE

Patrick, Kevin; Wolszon, Laura; Basen-Engquist, Karen M; Demark-Wahnefried, Wendy; Prokhorov, Alex V; Barrera, Stephanie; Baru, Chaitan; Farcas, Emilia; Krueger, Ingolf; Palmer, Doug; Raab, Fred; Rios, Phil; Ziftci, Celal; Peterson, Susan

2010-01-01

ABSTRACT Improved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of kn...

Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Compared With Radiofrequency Ablation for Inoperable Colorectal Liver Metastases

Energy Technology Data Exchange (ETDEWEB)

Kim, Hayeon, E-mail: kimh2@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Gill, Beant; Beriwal, Sushil; Huq, M. Saiful [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Roberts, Mark S. [Department of Health Policy and Management, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania (United States); Smith, Kenneth J. [Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (United States)

2016-07-15

Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account for model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.

Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Compared With Radiofrequency Ablation for Inoperable Colorectal Liver Metastases

International Nuclear Information System (INIS)

Kim, Hayeon; Gill, Beant; Beriwal, Sushil; Huq, M. Saiful; Roberts, Mark S.; Smith, Kenneth J.

2016-01-01

Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account for model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.

Way forward in case of a false positive in vitro genotoxicity result for a cosmetic substance?

Science.gov (United States)

Doktorova, Tatyana Y; Ates, Gamze; Vinken, Mathieu; Vanhaecke, Tamara; Rogiers, Vera

2014-02-01

The currently used regulatory in vitro mutagenicity/genotoxicity test battery has a high sensitivity for detecting genotoxicants, but it suffers from a large number of irrelevant positive results (i.e. low specificity) thereby imposing the need for additional follow-up by in vitro and/or in vivo genotoxicity tests. This could have a major impact on the cosmetic industry in Europe, seen the imposed animal testing and marketing bans on cosmetics and their ingredients. Afflicted, but safe substances could therefore be lost. Using the example of triclosan, a cosmetic preservative, we describe here the potential applicability of a human toxicogenomics-based in vitro assay as a potential mechanistically based follow-up test for positive in vitro genotoxicity results. Triclosan shows a positive in vitro chromosomal aberration test, but is negative during in vivo follow-up tests. Toxicogenomics analysis unequivocally shows that triclosan is identified as a compound acting through non-DNA reactive mechanisms. This proof-of-principle study illustrates the potential of genome-wide transcriptomics data in combination with in vitro experimentation as a possible weight-of-evidence follow-up approach for de-risking a positive outcome in a standard mutagenicity/genotoxicity battery. As such a substantial number of cosmetic compounds wrongly identified as genotoxicants could be saved for the future. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis of baseline gene expression levels from ...

Science.gov (United States)

The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in gene expression. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selectiv

Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium.

Science.gov (United States)

Hiligsmann, Mickaël; Reginster, Jean-Yves

2011-10-01

Denosumab has recently been shown to be well tolerated, to increase bone mineral density (BMD) and to significantly reduce the risk of hip, vertebral and non-vertebral fractures in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial. It is becoming increasingly important to evaluate not only the therapeutic value of a new drug but also the cost effectiveness compared with the most relevant treatment alternatives. The objective of this study was to estimate the cost effectiveness of denosumab compared with oral bisphosphonates (branded and generic drugs) in the treatment of post-menopausal osteoporotic women in Belgium. Cost effectiveness of 3 years of treatment with denosumab was compared with branded risedronate and branded and generic alendronate using an updated version of a previously validated Markov microsimulation model. The model was populated with relevant cost, adherence and epidemiological data for Belgium from a payer perspective and the results were presented as costs per QALY gained (&U20AC;, year 2009 values). Analyses were performed in populations (aged ≥60 years) in which osteoporosis medications are currently reimbursed in many European countries, i.e. those with BMD T-score of -2.5 or less or prevalent vertebral fracture. Patients receiving denosumab were assumed to have a 46% lower risk of discontinuation than those receiving oral bisphosphonates, and the effect of denosumab after treatment cessation was assumed to decline linearly to zero over a maximum of 1 year. Denosumab was cost effective compared with all other therapies, assuming a willingness to pay of &U20AC;40 000 per QALY gained. In particular, denosumab was found to be cost effective compared with branded alendronate and risedronate at a threshold value of &U20AC;30 000 per QALY and denosumab was dominant (i.e. lower cost and greater effectiveness) compared with risedronate from the age of 70 years in women with a T-score of -2.5 or

Use of comparative effectiveness research in drug coverage and pricing decisions: a six-country comparison.

Science.gov (United States)

Sorenson, Corinna

2010-07-01

Comparative effectiveness research (CER) has assumed an increasing role in drug coverage and, in some cases, pricing decisions in Europe, as decision-makers seek to obtain better value for money. This issue brief comparatively examines the use of CER across six countries--Denmark, England, France, Germany, the Netherlands, and Sweden. With CER gaining traction in the United States, these international experiences offer insights and potential lessons. Investing in CER can help address the current gap in publicly available, credible, up-to-date, and scientifically based comparative information on the effectiveness of drugs and other health interventions. This information can be used to base coverage and pricing decisions on evidence of value, thereby facilitating access to and public and private investment in the most beneficial new drugs and technologies. In turn, use of CER creates incentives for more efficient, high-quality health care and encourages development of innovative products that offer measurable value to patients.

Faculty Satisfaction with Distance Education: A Comparative Analysis on Effectiveness of Undergraduate Course Delivery Modes

Science.gov (United States)

Koenig, Robert J.

2010-01-01

Higher education faculty can and do teach courses delivered in a variety of ways. But, to date, little research has been done on the effectiveness of different delivery modes. This study sought to fill that void by comparing the effectiveness of three undergraduate course delivery modes: classroom, online, and video conference at a technical…

Population-based versus practice-based recall for childhood immunizations: a randomized controlled comparative effectiveness trial.

Science.gov (United States)

Kempe, Allison; Saville, Alison; Dickinson, L Miriam; Eisert, Sheri; Reynolds, Joni; Herrero, Diana; Beaty, Brenda; Albright, Karen; Dibert, Eva; Koehler, Vicky; Lockhart, Steven; Calonge, Ned

2013-06-01

We compared the effectiveness and cost-effectiveness of population-based recall (Pop-recall) versus practice-based recall (PCP-recall) at increasing immunizations among preschool children. This cluster-randomized trial involved children aged 19 to 35 months needing immunizations in 8 rural and 6 urban Colorado counties. In Pop-recall counties, recall was conducted centrally using the Colorado Immunization Information System (CIIS). In PCP-recall counties, practices were invited to attend webinar training using CIIS and offered financial support for mailings. The percentage of up-to-date (UTD) and vaccine documentation were compared 6 months after recall. A mixed-effects model assessed the association between intervention and whether a child became UTD. Ten of 195 practices (5%) implemented recall in PCP-recall counties. Among children needing immunizations, 18.7% became UTD in Pop-recall versus 12.8% in PCP-recall counties (P immunization rates in preschool children.

A comparative study of the effect of soft and hard cervical collars on static postural

Directory of Open Access Journals (Sweden)

Minoo Khalkhali Zavieh

2013-01-01

Full Text Available AbstractBackground and Aim: Using cervical collars is one of the treatment methods for releaving cervical pain. The effect of limb orthotics on proprioception and postural stability has been suggested. There is not sufficient studies about the effect of cervical collars on static and dynamic stability, and the effect of soft and hard collars have not been compared with one another. The objective of this study is investigating and comparing the immediate effect of soft and hard cervical collars on static postural stability in healthy young subjects. Methods & Materials: In standing position on firm surface with closed eyes, both soft and hard collars decreased the stability and there was not any significant difference among collars. In standing positions on soft surface with closed and opened eyes, using none of the soft and hard collars did not change the stability. This quasi experimental study through repeated measure method has been conducted on 65 healthy young male and female college students. Static stability was evaluated by modified Clinical Test for Sensory Interaction and Balance (CTSIB in conditions without collar and by soft and hard cervical collars and were compared between the conditions. Results: Conclusion: Our results suggest that in static conditions, without vision, both collars decrease the stability in healthy young subjects. So considering the evaluation of stability and prevention of balance disturbance during the collar prescription seems to be necessary.

Effectiveness of Mindfulness-Based Group Therapy Compared to the Usual Opioid Dependence Treatment.

Science.gov (United States)

Imani, Saeed; Atef Vahid, Mohammad Kazem; Gharraee, Banafsheh; Noroozi, Alireza; Habibi, Mojtaba; Bowen, Sarah

2015-06-01

This study investigated the effectiveness of mindfulness-based group therapy (MBGT) compared to the usual opioid dependence treatment (TAU).Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS) were randomly assigned into experimental (Mindfulness-Based Group Therapy) and control groups (the Usual Treatment).The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program. The Five Factor Mindfulness Questionnaire (FFMQ) and the Addiction Sevier Index (ASI) were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders.

Effectiveness of Mindfulness-Based Group Therapy Compared to the Usual Opioid Dependence Treatment

Directory of Open Access Journals (Sweden)

Saeed Imani

2015-11-01

Full Text Available  Objective: This study investigated the effectiveness of mindfulness-based group therapy (MBGT compared to the usual opioid dependence treatment (TAU.Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS were randomly assigned into experimental (Mindfulness-Based Group Therapy and control groups (the Usual Treatment.The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program.  Methods:The Five Factor Mindfulness Questionnaire (FFMQ and the Addiction Sevier Index (ASI were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. Results:The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. Conclusion:The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders.

Stakeholder engagement in comparative effectiveness research: how will we measure success?

Science.gov (United States)

Lavallee, Danielle C; Williams, Carla J; Tambor, Ellen S; Deverka, Patricia A

2012-09-01

Stakeholder engagement in comparative effectiveness research continues to gain national attention. While various methods are used to gather stakeholder expertise and form recommendations, evaluation of the stakeholder experience is often missing. The lack of evaluation prohibits assessing how effective and meaningful engagement practices are for enhancing research efforts and limits the ability to identify areas for future improvement. We propose that an evaluation plan of engagement processes be developed before stakeholder involvement begins and be required as part of a request for proposal or research grant where stakeholder input is being sought. Furthermore, we recommend the inclusion of six meta-criteria that represent normative goals of multiple studies: respect, trust, legitimacy, fairness, competence and accountability. To aid in the development of future evaluations, we have developed definitions for and matched specific examples of measuring each meta-criterion to serve a guide for others in the field.

[The prospect of application of toxicogenetics/pharmcogenetics theory and methods in forensic practice].

Science.gov (United States)

Shen, Dan-na; Yi, Xu-fu; Chen, Xiao-gang; Xu, Tong-li; Cui, Li-juan

2007-10-01

Individual response to drugs, toxicants, environmental chemicals and allergens varies with genotype. Some respond well to these substances without significant consequences, while others may respond strongly with severe consequences and even death. Toxicogenetics and toxicogenomics as well as pharmacogenetics explain the genetic basis for the variations of individual response to toxicants by sequencing the human genome and large-scale identification of genome polymorphism. The new disciplines will provide a new route for forensic specialists to determine the cause of death.

75 FR 990 - HHS Intent To Publish Grant and Contract Solicitations for Comparative Effectiveness Research...

Science.gov (United States)

2010-01-07

... Prescription Drug, Improvement, and Modernization Act of 2003, (2) 100 Institute of Medicine topic... Coordinating Council for Comparative Effectiveness Research (FCC), and the Institute of Medicine Report on CER...

Establishing the infrastructure to conduct comparative effectiveness research toward the elimination of disparities: a community-based participatory research framework.

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Wilson, Danyell S; Dapic, Virna; Sultan, Dawood H; August, Euna M; Green, B Lee; Roetzheim, Richard; Rivers, Brian

2013-11-01

In Tampa, Florida, researchers have partnered with community- and faith-based organizations to create the Comparative Effectiveness Research for Eliminating Disparities (CERED) infrastructure. Grounded in community-based participatory research, CERED acts on multiple levels of society to enhance informed decision making (IDM) of prostate cancer screening among Black men. CERED investigators combined both comparative effectiveness research and community-based participatory research to design a trial examining the effectiveness of community health workers and a digitally enhanced patient decision aid to support IDM in community settings as compared with "usual care" for prostate cancer screening. In addition, CERED researchers synthesized evidence through the development of systematic literature reviews analyzing the effectiveness of community health workers in changing knowledge, attitudes and behaviors of African American adults toward cancer prevention and education. An additional systematic review analyzed chemoprevention agents for prostate cancer as an emerging technique. Both of these reviews, and the comparative effectiveness trial supporting the IDM process, add to CERED's goal of providing evidence to eliminate cancer health disparities.

COMPARATIVE EFFECT OF STATIC AND DYNAMIC STRETCHING EXERCISE TO IMPROVE FLEXIBILITY OF HAMSTRING MUSCLES AMONG NON ATHLETES

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Jibi Paul

2014-10-01

Full Text Available Background: Stretching exercises have been routinely used in persons with hamstring tightness and athletes to increase flexibility of muscle and to reduce joint injuries. Many studies have reported effect of static and dynamic stretching on flexibility of this muscle. Finding the best method to improve flexibility of hamstring muscle is important for athletes and individuals to reduce their injuries. Objective of the study was to find out the effect of static stretching exercise and dynamic stretching exercise on flexibility of hamstring muscle and also to compare the effect of static and dynamic stretching exercise on flexibility of hamstring muscle. Methods: This was a comparative experimental study with seventy four female healthy subjects from physiotherapy department of KPJ Healthcare University College, Malaysia. Convenient sampling method used to select the samples. The subjects were selected by inclusion criteria and randomly divided equally in to two with 37 subjects in each group. Static stretching exercise and dynamic stretching exercise were given as intervention program for four weeks respectively for experimental and control group. Pre and post data of restricted range of movement for knee extension was measured using goniometry and documented separately for both group. Result: In experimental and control group, pre-post statistical analysis found significant effect in increase of hamstring flexibility with P<0.0001, for right and left side. Comparative study between experimental and control group found that static stretching exercise have significant effect in increase of hamstring flexibility for right and left side with P<0.04. Conclusion: This study concluded that static stretching exercise is more effective to improve hamstring flexibility compared to dynamic stretching exercise.

Assessing the comparative effectiveness of newly marketed medications: methodological challenges and implications for drug development.

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Schneeweiss, S; Gagne, J J; Glynn, R J; Ruhl, M; Rassen, J A

2011-12-01

Comparative-effectiveness research (CER) aims to produce actionable evidence regarding the effectiveness and safety of medical products and interventions as they are used outside of controlled research settings. Although CER evidence regarding medications is particularly needed shortly after market approval, key methodological challenges include (i) potential bias due to channeling of patients to the newly marketed medication because of various patient-, physician-, and system-related factors; (ii) rapid changes in the characteristics of the user population during the early phase of marketing; and (iii) lack of timely data and the often small number of users in the first few months of marketing. We propose a mix of approaches to generate comparative-effectiveness data in the early marketing period, including sequential cohort monitoring with secondary health-care data and propensity score (PS) balancing, as well as extended follow-up of phase III and phase IV trials, indirect comparisons of placebo-controlled trials, and modeling and simulation of virtual trials.

Comparing Single Case Design Overlap-Based Effect Size Metrics from Studies Examining Speech Generating Device Interventions

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Chen, Mo; Hyppa-Martin, Jolene K.; Reichle, Joe E.; Symons, Frank J.

2016-01-01

Meaningfully synthesizing single case experimental data from intervention studies comprised of individuals with low incidence conditions and generating effect size estimates remains challenging. Seven effect size metrics were compared for single case design (SCD) data focused on teaching speech generating device use to individuals with…

Endoscopic treatments for Barrett's esophagus: a systematic review of safety and effectiveness compared to esophagectomy

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Lau Darren

2010-09-01

Full Text Available Abstract Background Recently, several new endoscopic treatments have been used to treat patients with Barrett's esophagus with high grade dysplasia. This systematic review aimed to determine the safety and effectiveness of these treatments compared with esophagectomy. Methods A comprehensive literature search was undertaken to identify studies of endoscopic treatments for Barrett's esophagus or early stage esophageal cancer. Information from the selected studies was extracted by two independent reviewers. Study quality was assessed and information was tabulated to identify trends or patterns. Results were pooled across studies for each outcome. Safety (occurrence of adverse events and effectiveness (complete eradication of dysplasia were compared across different treatments. Results The 101 studies that met the selection criteria included 8 endoscopic techniques and esophagectomy; only 12 were comparative studies. The quality of evidence was generally low. Methods and outcomes were inconsistently reported. Protocols, outcomes measured, follow-up times and numbers of treatment sessions varied, making it difficult to calculate pooled estimates. The surgical mortality rate was 1.2%, compared to 0.04% in 2831 patients treated endoscopically (1 death. Adverse events were more severe and frequent with esophagectomy, and included anastomotic leaks (9.4%, wound infections (4.1% and pulmonary complications (4.1%. Four patients (0.1% treated endoscopically experienced bleeding requiring transfusions. The stricture rate with esophagectomy (5.3% was lower than with porfimer sodium photodynamic therapy (18.5%, but higher than aminolevulinic acid (ALA 60 mg/kg PDT (1.4%. Dysphagia and odynophagia varied in frequency across modalities, with the highest rates reported for multipolar electrocoagulation (MPEC. Photosensitivity, an adverse event that occurs only with photodynamic therapy, was experienced by 26.4% of patients who received porfimer sodium. Some

Randomized, Evaluator-Blinded Study Comparing Safety and Effect of Two Hyaluronic Acid Gels for Lips Enhancement.

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Hilton, Said; Sattler, Gerhard; Berg, Anna-Karin; Samuelson, Ulf; Wong, Cindy

2018-02-01

Hyaluronic acid (HA) fillers may differ in terms of gel characteristics and ease of use and it is of interest whether this might affect safety and duration of effect. To compare the long-term safety and effect of 2 HA fillers produced by 2 different technologies for lip enhancement. Subjects with very thin to moderately thick lips were randomized and treated with HA-RK (N = 31) or HA-JV (N = 29) to improve lip fullness by ≥ 1 grade on a 5-point scale, using a maximum of 3 mL of product. A smaller volume of HA-RK compared with HA-JV was required to improve lip fullness by ≥ 1 grade (mean: 1.54 mL vs 1.94 mL, p < .001). Despite the smaller volume, lip fullness and global aesthetic improvement were comparably sustained in both groups. At 6 months, 60.0% versus 57.7% of subjects (HA-RK vs HA-JV) had improved lip fullness. At 12 months, 71.4% versus 76.0% had aesthetic improvement (blinded evaluations) and 85.7% versus 86.2% felt more attractive. Both products were well tolerated. Both products achieved durable improvement in lip fullness and aesthetic appearance. A significantly smaller amount of HA-RK was required compared with HA-JV to achieve optimal treatment effect.

Firm insoles effectively reduce hemolysis in runners during long distance running - a comparative study.

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Janakiraman, Kamal; Shenoy, Shweta; Sandhu, Jaspal Singh

2011-06-09

Shock absorbing insoles are effective in reducing the magnitude and rate of loading of peak impact forces generated at foot strike during running, whereas the foot impact force during running has been considered to be an important cause of intravascular hemolysis in long distance runners. Objective of this study was to evaluate the intravascular hemolysis during running and compare the effect of two different types of insoles (Soft and Firm) on hemolysis. Twenty male long and middle distance runners volunteered to participate in this study. We selected two insoles (Soft and Firm) according to their hardness level (SHORE 'A' scale). Participants were randomly assigned to the soft insole (group 1) and firm insole (group 2) group with ten athletes in each group. Each athlete completed one hour of running at the calculated target heart rate (60-70%). Venous blood samples were collected before and immediately after running. We measured unconjucated bilirubin (mg/dl), lactate dehydrogenase (μ/ml), hemoglobin (g/l) and serum ferritin (ng/ml) as indicators of hemolysis. Our study revealed a significant increase in the mean values of unconjucated bilirubin (P firm insoles effectively reduces the amount of hemolysis in runners compared to soft insoles.

Comparing the Effectivities of Chitosan Citrate and Chitosan Acetate in Eradicating Enterococcus faecalis Biofilm

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Uppalavanna Witedja

2018-01-01

Full Text Available Introduction: Adequate biomechanical preparations, antibacterial irrigants, and intracanal medications to promote the elimination of bacteria and their products are required to succeed root canal treatment. Enterococcus faecalis with its biofilm is known as an important etiological agent in endodontic treatment failures. Chitosan, as a natural product, has an antibacterial activity and is considered less toxic to the periapical tissue than other irrigants. However, the use of this natural product needs to be examined to determine its effectiveness as a root canal irrigant in endodontic treatment; this can be done by comparing it with the most common endodontic irrigant (NaOCl 5.25% as a positive control. Objective: The objective of the study was to compare the effectiveness between 1–3% chitosan acetate (CA and 1–3% chitosan citrate (CC against E. faecalis biofilm formation after treatment for 15, 30, and 60 minutes. Methods: The study was conducted using 12 groups, including 1–3% CA, 1–3% CC, and control groups. E. faecalis biofilms in 96-well plates were exposed to each sample for 15, 30, or 60 minutes. Subsequently, the biofilms were stained with crystal violet solution, and the optical density value was measured using a microtiter plate reader at a wavelength of 600nm. Results: CA and CC were effective in eradicating E. faecalis biofilm. However, the levels of effectiveness of CC and CA depended on the concentration and application time. Three-way analysis of variance (ANOVA showed a significant difference between the irrigants (F = 5.92; p<0.05 and three application times (F = 6.50; p< 0.05. The CA was effective in eradicating biofilm after 15 minutes of application, whereas the CC was more effective after 30 and 60 minutes of application. Conclusion: CC and CA are both effective in eradicating E. faecalis biofilm.

Comparative effectiveness of combined digital mammography and tomosynthesis screening for women with dense breasts.

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Lee, Christoph I; Cevik, Mucahit; Alagoz, Oguzhan; Sprague, Brian L; Tosteson, Anna N A; Miglioretti, Diana L; Kerlikowske, Karla; Stout, Natasha K; Jarvik, Jeffrey G; Ramsey, Scott D; Lehman, Constance D

2015-03-01

To evaluate the effectiveness of combined biennial digital mammography and tomosynthesis screening, compared with biennial digital mammography screening alone, among women with dense breasts. An established, discrete-event breast cancer simulation model was used to estimate the comparative clinical effectiveness and cost-effectiveness of biennial screening with both digital mammography and tomosynthesis versus digital mammography alone among U.S. women aged 50-74 years with dense breasts from a federal payer perspective and a lifetime horizon. Input values were estimated for test performance, costs, and health state utilities from the National Cancer Institute Breast Cancer Surveillance Consortium, Medicare reimbursement rates, and medical literature. Sensitivity analyses were performed to determine the implications of varying key model parameters, including combined screening sensitivity and specificity, transient utility decrement of diagnostic work-up, and additional cost of tomosynthesis. For the base-case analysis, the incremental cost per quality-adjusted life year gained by adding tomosynthesis to digital mammography screening was $53 893. An additional 0.5 deaths were averted and 405 false-positive findings avoided per 1000 women after 12 rounds of screening. Combined screening remained cost-effective (less than $100 000 per quality-adjusted life year gained) over a wide range of incremental improvements in test performance. Overall, cost-effectiveness was most sensitive to the additional cost of tomosynthesis. Biennial combined digital mammography and tomosynthesis screening for U.S. women aged 50-74 years with dense breasts is likely to be cost-effective if priced appropriately (up to $226 for combined examinations vs $139 for digital mammography alone) and if reported interpretive performance metrics of improved specificity with tomosynthesis are met in routine practice.

Cost-effectiveness analysis of left atrial appendage occlusion compared with pharmacological strategies for stroke prevention in atrial fibrillation.

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Lee, Vivian Wing-Yan; Tsai, Ronald Bing-Ching; Chow, Ines Hang-Iao; Yan, Bryan Ping-Yen; Kaya, Mehmet Gungor; Park, Jai-Wun; Lam, Yat-Yin

2016-08-31

Transcatheter left atrial appendage occlusion (LAAO) is a promising therapy for stroke prophylaxis in non-valvular atrial fibrillation (NVAF) but its cost-effectiveness remains understudied. This study evaluated the cost-effectiveness of LAAO for stroke prophylaxis in NVAF. A Markov decision analytic model was used to compare the cost-effectiveness of LAAO with 7 pharmacological strategies: aspirin alone, clopidogrel plus aspirin, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban, and rivaroxaban. Outcome measures included quality-adjusted life years (QALYs), lifetime costs and incremental cost-effectiveness ratios (ICERs). Base-case data were derived from ACTIVE, RE-LY, ARISTOTLE, ROCKET-AF, PROTECT-AF and PREVAIL trials. One-way sensitivity analysis varied by CHADS2 score, HAS-BLED score, time horizons, and LAAO costs; and probabilistic sensitivity analysis using 10,000 Monte Carlo simulations was conducted to assess parameter uncertainty. LAAO was considered cost-effective compared with aspirin, clopidogrel plus aspirin, and warfarin, with ICER of US$5,115, $2,447, and $6,298 per QALY gained, respectively. LAAO was dominant (i.e. less costly but more effective) compared to other strategies. Sensitivity analysis demonstrated favorable ICERs of LAAO against other strategies in varied CHADS2 score, HAS-BLED score, time horizons (5 to 15 years) and LAAO costs. LAAO was cost-effective in 86.24 % of 10,000 simulations using a threshold of US$50,000/QALY. Transcatheter LAAO is cost-effective for prevention of stroke in NVAF compared with 7 pharmacological strategies. The transcatheter left atrial appendage occlusion (LAAO) is considered cost-effective against the standard 7 oral pharmacological strategies including acetylsalicylic acid (ASA) alone, clopidogrel plus ASA, warfarin, dabigatran 110 mg, dabigatran 150 mg, apixaban, and rivaroxaban for stroke prophylaxis in non-valvular atrial fibrillation management.

Comparative effects of gamma-rays and electron beams on peroxide formation in phosphatidylcholine

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Todoriki, S.; Hayashi, T.

1994-01-01

Phosphatidylcholine was irradiated in the state of a film or liposome with gamma-rays or electron beams, and the amount of peroxide was determined to compare the effects of the two types of radiation. The amounts of peroxide formed in both the film and liposome with gamma-rays were significantly larger than those with electron beams, when the samples were irradiated at the same dose. Proteins such as bacteriorhodopsin reduced the degree of peroxide formation in liposome, and the effect of gamma-rays was much larger than that of electron beams, even in the presence of protein. The results of the present investigation indicate that the effects of gamma-rays on peroxide formation in phosphatidylcholine were significantly larger than those of electron beams, irrespective of the state of the lipid

Effect of S186 for decoporated radiostrontium compared with BADE in rats

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Zhang Meizhen; Luo Meichu; Chen Guibao; Liu Shijing; Tong Shungao; Sun Meizhen

1995-01-01

The efficacy of S186 for decorporated radiostrontium compared with BADE in rats was studied. The experimental results showed that administered S186 (in 100∼800 mg/kg) increased the 85+89 Sr excretion in urine and reduced 85+89 Sr retention in body being distinctly superior to that of the equal dose BADE (P<0.05). When administered the dose of S186 that was the half dose of BADE could produce the same effect of BADE for removing radiostrontium

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

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Poulsen, Sarah S., E-mail: spo@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Saber, Anne T., E-mail: ats@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Williams, Andrew, E-mail: Andrew.williams@hc-sc.gc.ca [Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario K1A 0K9 (Canada); Andersen, Ole, E-mail: oa@ruc.dk [Department of Science, Systems and Models, Roskilde University, DK-4000 Roskilde (Denmark); Købler, Carsten, E-mail: carko@nanotech.dtu.dk [Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark); Atluri, Rambabu, E-mail: rba@nrcwe.dk [Nanologica AB, SE-114 28 Stockholm (Sweden); Pozzebon, Maria E., E-mail: mariaelena.pozzebon@yahoo.it [Veneto Nanotech SCpA, ECSIN — European Centre for the Sustainable Impact of Nanotechnology, I-45100 Rovigo (Italy); Mucelli, Stefano P., E-mail: stefano.pozzimucelli@venetonanotech.it [Veneto Nanotech SCpA, ECSIN — European Centre for the Sustainable Impact of Nanotechnology, I-45100 Rovigo (Italy); Simion, Monica, E-mail: moni304ro@gmail.com [Laboratory of Nanobiotechnology, National Institute for Research and Development in Microtechnologies, 077190 Bucharest (Romania); Rickerby, David, E-mail: david.rickerby@jrc.ec.europa.eu [European Commission Joint Research Centre Institute for Environment and Sustainability, I-21027 Ispra, VA (Italy); Mortensen, Alicja, E-mail: almo@food.dtu.dk [National Food Institute, Technical University of Denmark, Søborg (Denmark); Jackson, Petra, E-mail: pja@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); Kyjovska, Zdenka O., E-mail: zky@nrcwe.dk [National Research Centre for the Working Environment, Copenhagen DK-2100 (Denmark); and others

2015-04-01

Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of a small, curled (CNT{sub Small}, 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNT{sub Large}, 4 ± 0.4 μm in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer–Emmett–Teller surface area analysis. Lung tissues were harvested 24 h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNT{sub Small} or CNT{sub Large} were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNT{sub Large} elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNT{sub Small}. The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNT{sub Large}, which may eventually lead to the different responses observed at day 28. - Highlights: • We evaluate the toxicogenomic response in mice following MWCNT instillation. • Two MWCNTs of different properties were examined and thoroughly characterized. • MWCNT exposure leads to increased pulmonary

MWCNTs of different physicochemical properties cause similar inflammatory responses, but differences in transcriptional and histological markers of fibrosis in mouse lungs

International Nuclear Information System (INIS)

Poulsen, Sarah S.; Saber, Anne T.; Williams, Andrew; Andersen, Ole; Købler, Carsten; Atluri, Rambabu; Pozzebon, Maria E.; Mucelli, Stefano P.; Simion, Monica; Rickerby, David; Mortensen, Alicja; Jackson, Petra; Kyjovska, Zdenka O.

2015-01-01

Multi-walled carbon nanotubes (MWCNTs) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of a small, curled (CNT Small , 0.8 ± 0.1 μm in length) or large, thick MWCNT (CNT Large , 4 ± 0.4 μm in length). The two MWCNTs were extensively characterized by SEM and TEM imaging, thermogravimetric analysis, and Brunauer–Emmett–Teller surface area analysis. Lung tissues were harvested 24 h, 3 days and 28 days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNT Small or CNT Large were similar. Both MWCNTs elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28 days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNT Large elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNT Small . The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNT Large , which may eventually lead to the different responses observed at day 28. - Highlights: • We evaluate the toxicogenomic response in mice following MWCNT instillation. • Two MWCNTs of different properties were examined and thoroughly characterized. • MWCNT exposure leads to increased pulmonary inflammation and acute phase

A CTSA Agenda to Advance Methods for Comparative Effectiveness Research

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Helfand, Mark; Tunis, Sean; Whitlock, Evelyn P.; Pauker, Stephen G.; Basu, Anirban; Chilingerian, Jon; Harrell Jr., Frank E.; Meltzer, David O.; Montori, Victor M.; Shepard, Donald S.; Kent, David M.

2011-01-01

Abstract Clinical research needs to be more useful to patients, clinicians, and other decision makers. To meet this need, more research should focus on patient‐centered outcomes, compare viable alternatives, and be responsive to individual patients’ preferences, needs, pathobiology, settings, and values. These features, which make comparative effectiveness research (CER) fundamentally patient‐centered, challenge researchers to adopt or develop methods that improve the timeliness, relevance, and practical application of clinical studies. In this paper, we describe 10 priority areas that address 3 critical needs for research on patient‐centered outcomes (PCOR): (1) developing and testing trustworthy methods to identify and prioritize important questions for research; (2) improving the design, conduct, and analysis of clinical research studies; and (3) linking the process and outcomes of actual practice to priorities for research on patient‐centered outcomes. We argue that the National Institutes of Health, through its clinical and translational research program, should accelerate the development and refinement of methods for CER by linking a program of methods research to the broader portfolio of large, prospective clinical and health system studies it supports. Insights generated by this work should be of enormous value to PCORI and to the broad range of organizations that will be funding and implementing CER. Clin Trans Sci 2011; Volume 4: 188–198 PMID:21707950

Comparative Effectiveness of After-School Programs to Increase Physical Activity

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Sabina B. Gesell

2013-01-01

Full Text Available Background. We conducted a comparative effectiveness analysis to evaluate the difference in the amount of physical activity children engaged in when enrolled in a physical activity-enhanced after-school program based in a community recreation center versus a standard school-based after-school program. Methods. The study was a natural experiment with 54 elementary school children attending the community ASP and 37 attending the school-based ASP. Accelerometry was used to measure physical activity. Data were collected at baseline, 6 weeks, and 12 weeks, with 91% retention. Results. At baseline, 43% of the multiethnic sample was overweight/obese, and the mean age was 7.9 years (SD = 1.7. Linear latent growth models suggested that the average difference between the two groups of children at Week 12 was 14.7 percentage points in moderate-vigorous physical activity (P<.001. Cost analysis suggested that children attending traditional school-based ASPs—at an average cost of $17.67 per day—would need an additional daily investment of $1.59 per child for 12 weeks to increase their moderate-vigorous physical activity by a model-implied 14.7 percentage points. Conclusions. A low-cost, alternative after-school program featuring adult-led physical activities in a community recreation center was associated with increased physical activity compared to standard-of-care school-based after-school program.

Stem cell test: A practical tool in toxicogenomics

International Nuclear Information System (INIS)

Ahuja, Y.R.; Vijayalakshmi, V.; Polasa, K.

2007-01-01

During early embryonic development, at blastocyst stage, the embryo has an outer coat of cells and an inner cell mass (ICM). ICM is the reservoir of embryonic stem (ES) cells, which are pluripotent, i.e., have the potential to differentiate into all cell types of the body. Cell lines have been developed from ES cells. In addition, there are embryonic germ (EG) cell lines developed from progenitor germ cells, and embryonic carcinoma (EC) cell lines developed from teratomas. These cell lines are being used for the study of basic and applied aspects in medical therapeutics, and disease management. Another potential of these cell lines is in the field of environmental mutagenesis. In addition to ES cells, there are adult stem cells in and around different organs and tissues of the body. It is now possible to grow pure populations of specific cell types from these adult stem cells. Treating specific cell types with chemical or physical agents and measuring their response offers a shortcut to test the toxicity in various organ systems in the adult organism. For example, to evaluate the genotoxicity of a chemical (e.g., drug or pesticide) or a physical agent (e.g., ionizing radiation or non-ionizing electromagnetic radiation) during embryonic development, a large number of animals are being used. As an alternative, use of stem cell lines would be a feasible proposition. Using stem cell lines, efforts are being made to standardize the protocols, which will not only be useful in testing the toxicity of a chemical or a physical agent, but also in the field of drug development, environmental mutagenesis, biomonitoring and other studies

Effectiveness testing of some vegetal extracts comparing with clasical anthelmintics

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Ilie M.S.,

2007-12-01

Full Text Available We have tested the efficacy of some vegetal extracts (Parazitol –Medica Laboratories, a natural product with an anthelmintic effect and a Cucurbita sp. oil extract compared to the classic anthelmintics (Rombendazol – Romvac and Dehelman – KRKA Slovenia at domestic poultry, whose parasitical status had been previously established through animal killing and necropsies. Parazitol and the pumpkin oil have had a lower efficacy than the levamisole and albendazole upon the species Ascaridia galli. Heterakis gallinarum was not affected by the pumpkin oil. Parazitol have a moderate efficacy (36%, while levamisole and albendazole were very efficient (100%. The treatments with albendazole upon the cestods belonging to the genus Raillietina have had a 100% efficacy. In cestods, Parazitol had a better efficacy (57% than the pumpkin oil (14%.

Stakeholder assessment of comparative effectiveness research needs for Medicaid populations

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Fischer, Michael A; Allen-Coleman, Cora; Farrell, Stephen F; Schneeweiss, Sebastian

2015-01-01

Patients, providers and policy-makers rely heavily on comparative effectiveness research (CER) when making complex, real-world medical decisions. In particular, Medicaid providers and policy-makers face unique challenges in decision-making because their program cares for traditionally underserved populations, especially children, pregnant women and people with mental illness. Because these patient populations have generally been underrepresented in research discussions, CER questions for these groups may be understudied. To address this problem, the Agency for Healthcare Research and Quality commissioned our team to work with Medicaid Medical Directors and other stakeholders to identify relevant CER questions. Through an iterative process of topic identification and refinement, we developed relevant, feasible and actionable questions based on issues affecting Medicaid programs nationwide. We describe challenges and limitations and provide recommendations for future stakeholder engagement. PMID:26388438

Pharmacokinetics in Mouse and Comparative Effects of Frondosides in Pancreatic Cancer

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Jasem Al Shemaili

2016-06-01

Full Text Available The frondosides are triterpenoid glycosides from the Atlantic sea cucumber Cucumaria frondosa. Frondoside A inhibits growth, invasion, metastases and angiogenesis and induces apoptosis in diverse cancer types, including pancreatic cancer. We compared the growth inhibitory effects of three frondosides and their aglycone and related this to the pharmocokinetics and route of administration. Frondoside A potently inhibited growth of pancreatic cancer cells with an EC50 of ~1 µM. Frondoside B was less potent (EC50 ~2.5 µM. Frondoside C and the aglycone had no effect. At 100 µg/kg, frondoside A administered to CD2F1 mice as an i.v. bolus, the Cpmax was 129 nM, Cltb was 6.35 mL/min/m2, and half-life was 510 min. With i.p. administration the Cpmax was 18.3 nM, Cltb was 127 mL/min/m2 and half-life was 840 min. Oral dosing was ineffective. Frondoside A (100 µg/kg/day i.p. markedly inhibited growth cancer xenografts in nude mice. The same dose delivered by oral gavage had no effect. No evidence of acute toxicity was seen with frondoside A. Frondoside A is more potent inhibitor of cancer growth than other frondosides. The glycoside component is essential for bioactivity. Frondoside A is only effective when administered systemically. Based on the current and previous studies, frondoside A appears safe and may be valuable in the treatment of cancer.

Investigation of comparative effectiveness research in Asia, Europe, and North America.

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Patel, Isha; Rarus, Rachel; Tan, Xi; Lee, E K; Guy, Jason; Ahmad, Akram; Chang, Jongwha

2015-01-01

Comparative effectiveness research (CER) is an important branch of pharmacoeconomics that systematically studies and evaluates the cost-effectiveness of medical interventions. CER plays instrumental roles in guiding government public health policy programs and insurance. Countries throughout the world use different methods of CER to help make medical decisions based on providing optimal therapy at a reduced cost. Expenses to the healthcare system continue to rise, and CER is one-way in which expenses could be curbed in the future by applying cost-effectiveness evidence to clinical decisions. China, India, South Korea, and the United Kingdom are of essential focus because these country's economies and health care expenses continue to expand. The structures and use of CER are diverse throughout these countries, and each is of prime importance. By conducting this thorough comparison of CER in different nations, strategies and organizational setups from different countries can be applied to help guide public health and medical decision-making in order to continue to expand the establishment and role of CER programs. The patient-centered medical home has been created to help reduce costs in the primary care sector and to help improve the effectiveness of therapy. Barriers to CER are also important as many stakeholders need to be able to work together to provide the best CER evidence. The advancement of CER in multiple countries throughout the world provides a possible way of reducing costs to the healthcare system in an age of expanding expenses.

Comparing the effects of aerobic exercise and Foeniculum vulgare on pre-menstrual syndrome

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Hassan Pazoki

2016-03-01

Full Text Available Introduction: Premenstrual syndrome (PMS has been identified by a number of psychological and physical symptoms which occur cyclically in the luteal phase of the menstrual cycle. The present study has been carried out to compare the effects of regular exercise and Foeniculum vulgare extract (fennel together and separately on PMS in high school girls. Materials and methods: In this randomized clinical trial 48 students aged 16–18 years were selected by filling the daily record of severity of problem questionnaire (DRSP-Q. The participants were divided into four equal groups: the first group received fennel, the second group had aerobic exercise, the third group received fennel along with exercise and the last group was control group without fennel and exercise. Participants filled DRSP-Q three times: the first menstrual cycle before the intervention, the first menstrual cycle after four weeks and finally the first menstrual cycle after eight weeks of intervention. Results: After 8 weeks of intervention the severity of PMS symptoms reduced significantly in experimental groups (fennel, exercise and fennel + exercise compared to control group (P < 0.05. Meanwhile, there were not any significant differences in age, body mass index, age at menarche, age at dysmenorrhea onset and duration of menstruation among the four groups. Discussions: The result of this study indicated that fennels and exercise could reduce the severity of premenstrual syndrome. In addition, fennel extract and exercise together seem to be more effective on symptoms of anxiety and depression compared with using them alone.

Relations and effects of transformational leadership: a comparative analysis with traditional leadership styles.

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Molero, Fernando; Cuadrado, Isabel; Navas, Marisol; Morales, J Francisco

2007-11-01

This study has two main goals: (a) to compare the relationship between transformational leadership and other important leadership styles (i.e., democratic versus autocratic or relations- and task-oriented leadership) and (b) to compare the effects of transformational leadership and the other styles on some important organizational outcomes such as employees' satisfaction and performance. For this purpose, a sample of 147 participants, working in 35 various work-teams, was used. Results show high correlations between transformational leadership, relations-oriented, democratic, and task-oriented leadership. On the other hand, according to the literature, transformational leadership, especially high levels, significantly increases the percentage of variance accounted for by other leadership styles in relevant organizational outcome variables (subordinates' performance, satisfaction and extra effort).

Comparative analysis of nonperturbative effects in B→Xulνl decays

International Nuclear Information System (INIS)

Kniehl, Bernd A.; Kramer, Gustav; Yang Jifeng

2007-01-01

In order to extract the Cabibbo-Kobayashi-Maskawa matrix element |V ub | from B→X u lν l decays, the overwhelming background from B→X c lν l decays must be reduced by appropriate acceptance cuts. We study the nonperturbative effects due to the motion of the b quark inside the B meson on the phenomenologically relevant decay distributions of B→X u lν l in the presence of such cuts in a comparative analysis based on shape functions and the parton model in the light cone limit. Comparisons with recent data from the CLEO, BABAR, and BELLE collaborations favor the shape-function approach

A Comparative Study on Power Point Presentation and Traditional Lecture Method in Material Understandability, Effectiveness and Attitude

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Sewasew, Daniel; Mengestle, Missaye; Abate, Gebeyehu

2015-01-01

The aim of this study was to compare PPT and traditional lecture method in material understandability, effectiveness and attitude among university students. Comparative descriptive survey research design was employed to answer the research questions raised. Four hundred and twenty nine participants were selected randomly using stratified sampling…

Comparative costs and cost-effectiveness of behavioural interventions as part of HIV prevention strategies.

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Hsu, Justine; Zinsou, Cyprien; Parkhurst, Justin; N'Dour, Marguerite; Foyet, Léger; Mueller, Dirk H

2013-01-01

Behavioural interventions have been widely integrated in HIV/AIDS social marketing prevention strategies and are considered valuable in settings with high levels of risk behaviours and low levels of HIV/AIDS awareness. Despite their widespread application, there is a lack of economic evaluations comparing different behaviour change communication methods. This paper analyses the costs to increase awareness and the cost-effectiveness to influence behaviour change for five interventions in Benin. Cost and cost-effectiveness analyses used economic costs and primary effectiveness data drawn from surveys. Costs were collected for provider inputs required to implement the interventions in 2009 and analysed by 'person reached'. Cost-effectiveness was analysed by 'person reporting systematic condom use'. Sensitivity analyses were performed on all uncertain variables and major assumptions. Cost-per-person reached varies by method, with public outreach events the least costly (US$2.29) and billboards the most costly (US$25.07). Influence on reported behaviour was limited: only three of the five interventions were found to have a significant statistical correlation with reported condom use (i.e. magazines, radio broadcasts, public outreach events). Cost-effectiveness ratios per person reporting systematic condom use resulted in the following ranking: magazines, radio and public outreach events. Sensitivity analyses indicate rankings are insensitive to variation of key parameters although ratios must be interpreted with caution. This analysis suggests that while individual interventions are an attractive use of resources to raise awareness, this may not translate into a cost-effective impact on behaviour change. The study found that the extensive reach of public outreach events did not seem to influence behaviour change as cost-effectively when compared with magazines or radio broadcasts. Behavioural interventions are context-specific and their effectiveness influenced by a

Nano-risk Science: application of toxicogenomics in an adverse outcome pathway framework for risk assessment of multi-walled carbon nanotubes.

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Labib, Sarah; Williams, Andrew; Yauk, Carole L; Nikota, Jake K; Wallin, Håkan; Vogel, Ulla; Halappanavar, Sabina

2016-03-15

A diverse class of engineered nanomaterials (ENMs) exhibiting a wide array of physical-chemical properties that are associated with toxicological effects in experimental animals is in commercial use. However, an integrated framework for human health risk assessment (HHRA) of ENMs has yet to be established. Rodent 2-year cancer bioassays, clinical chemistry, and histopathological endpoints are still considered the 'gold standard' for detecting substance-induced toxicity in animal models. However, the use of data derived from alternative toxicological tools, such as genome-wide expression profiling and in vitro high-throughput assays, are gaining acceptance by the regulatory community for hazard identification and for understanding the underlying mode-of-action. Here, we conducted a case study to evaluate the application of global gene expression data in deriving pathway-based points of departure (PODs) for multi-walled carbon nanotube (MWCNT)-induced lung fibrosis, a non-cancer endpoint of regulatory importance. Gene expression profiles from the lungs of mice exposed to three individual MWCNTs with different physical-chemical properties were used within the framework of an adverse outcome pathway (AOP) for lung fibrosis to identify key biological events linking MWCNT exposure to lung fibrosis. Significantly perturbed pathways were categorized along the key events described in the AOP. Benchmark doses (BMDs) were calculated for each perturbed pathway and were used to derive transcriptional BMDs for each MWCNT. Similar biological pathways were perturbed by the different MWCNT types across the doses and post-exposure time points studied. The pathway BMD values showed a time-dependent trend, with lower BMDs for pathways perturbed at the earlier post-exposure time points (24 h, 3d). The transcriptional BMDs were compared to the apical BMDs derived by the National Institute for Occupational Safety and Health (NIOSH) using alveolar septal thickness and fibrotic lesions

Targeted Therapies Compared to Dacarbazine for Treatment of BRAFV600E Metastatic Melanoma: A Cost-Effectiveness Analysis

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Vanessa Shih

2015-01-01

Full Text Available Purpose. Two BRAFV600E targeted therapies, dabrafenib and vemurafenib, have received US approval for treatment of metastatic melanoma in BRAFV600E patients, a mutation that affects ~50% of patients. We evaluated the cost-effectiveness of BRAF inhibitors and traditional chemotherapy for treatment of metastatic melanoma. Methods. A Markov model was developed using a societal perspective. Transition probabilities were derived from two Phase III registration trials comparing each BRAF inhibitor against dacarbazine. Costs were obtained from literature, national databases, and Medicare fee schedules. Utilities were obtained from published literature. Deterministic and probabilistic sensitivity analyses were run to test the impact of uncertainties. Results. The incremental cost-effectiveness ratio of dabrafenib was $149,035/QALY compared to dacarbazine. Vemurafenib was dominated by dabrafenib. Probabilistic sensitivity analysis showed that, at a willingness-to-pay (WTP threshold of ≤$100,000/QALY, dacarbazine was the optimal treatment in ~85% of simulations. At a WTP threshold of ≥$150,000/QALY, dabrafenib was the optimal treatment. Conclusion. Compared with dacarbazine, dabrafenib and vemurafenib were not cost-effective at a willingness-to-pay threshold of $100,000/QALY. Dabrafenib is more efficient compared to vemurafenib. With few treatment options, dabrafenib is an option for qualifying patients if the overall cost of dabrafenib is reduced to $30,000–$31,000 or a WTP threshold of ≥$150,000/QALY is considered. More comparative data is needed.

The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy.

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Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Sung, Joseph J Y

2015-09-04

Faecal immunochemical tests (FITs) and colonoscopy are two common screening tools for colorectal cancer(CRC). Most cost-effectiveness studies focused on survival as the outcome, and were based on modeling techniques instead of real world observational data. This study evaluated the cost-effectiveness of these two tests to detect colorectal neoplastic lesions based on data from a 5-year community screening service. The incremental cost-effectiveness ratio (ICER) was assessed based on the detection rates of neoplastic lesions, and costs including screening compliance, polypectomy, colonoscopy complications, and staging of CRC detected. A total of 5,863 patients received yearly FIT and 4,869 received colonoscopy. Compared with FIT, colonoscopy detected notably more adenomas (23.6% vs. 1.6%) and advanced lesions or cancer (4.2% vs. 1.2%). Using FIT as control, the ICER of screening colonoscopy in detecting adenoma, advanced adenoma, CRC and a composite endpoint of either advanced adenoma or stage I CRC was US$3,489, US$27,962, US$922,762 and US$23,981 respectively. The respective ICER was US$3,597, US$439,513, -US$2,765,876 and US$32,297 among lower-risk subjects; whilst the corresponding figure was US$3,153, US$14,852, US$184,162 and US$13,919 among higher-risk subjects. When compared to FIT, colonoscopy is considered cost-effective for screening adenoma, advanced neoplasia, and a composite endpoint of advanced neoplasia or stage I CRC.

A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis.

Directory of Open Access Journals (Sweden)

Shahram Solaymani-Mohammadi

2010-05-01

Full Text Available Metronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans.We performed a search in the PubMed, Scopus, EMBASE, the ISI Web of Science, LILIACS, and Cochrane Controlled Trials Register for trials published before February 2010 as well as in references of relevant research and review articles. Eight randomized clinical trials (including 900 patients comparing the effectiveness of albendazole with that of metronidazole were included in meta-analysis. After extracting and validating the data, the pooled risk ratio (RR was calculated using an inverse-variance random-effects model. Albendazole was found to be equally as effective as metronidazole in the treatment of giardiasis in humans (RR 0.97; 95% CI, 0.93, 1.01. In addition, safety analysis suggested that patients treated with albendazole had a lower risk of adverse effects compared with those who received metronidazole (RR 0.36; 95% CI, 0.10, 1.34, but limitations of the sample size precluded a definite conclusion.The effectiveness of albendazole, when given as a single dose of 400 mg/day for 5 days, was comparable to that of metronidazole. Patients treated with albendazole tended to have fewer side effects compared with those who took metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug could be potentially used as an alternative and/or a replacement for the existing metronidazole therapy protocols in the

The Varied Educational Effects of Parent-Child Communication: A Comparative Study of Fourteen Countries

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Park, Hyunjoon

2008-01-01

In this article, the author compares the ways in which parent-child communication--a major indicator of parental involvement--influences children's educational achievement across 14 countries. Using data from the Programme for International Student Assessment (PISA), the author examines the extent to which social class differences in the effect of…

What Are the Perceived Effects of Telecollaboration Compared to Other Communication-Scenarios with Peers?

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Nissen, Elke

2016-01-01

What are the perceived effects of Telecollaboration (TC), compared to other types of communication-scenarios with peers (i.e. local peers in small groups and Erasmus students abroad)? This is the question this exploratory study tackles within a blended language learning course. The analysis of students' perceptions paints a rather contrastive…

comparative study on the effects of cadmium and gamma radiation on three aspergillus species

International Nuclear Information System (INIS)

Adam, Y.M.; Abulyazid, I.; Fathi, I.A.

2004-01-01

The effect of cadmium on the ability of fungi to survive in the rhizosphere of Ambrosia miritima plant at different concentrations was studied. With respect to the frequency of occurrence of Aspergillus species in the field even at the highest Cd concentration, the following sequence of decreasing tolerance to Cd was obtained: A. tamarii > A. sydowi > A. niger. On studying the effect of different concentrations of Cd in vitro culture on the growth parameters (dry weight and mycelial linear growth) of these three selected fungi, it was noticed that the most tolerant fungus was A. tamarii, while A. sydowi was moderately tolerant and A. niger was sensitive to the effect of Cd. Amino acids analysis revealed that Cd treatment was accompanied with increasing in the total free amino acids contents of both A. tamarii and A. sydowi compared to A. niger cells, where a reduction in this component was observed. Moreover, SDS-PAGE indicated high content of protein under Cd stress compared to non-treated culture of both A. tamarii and A. sydowi. In contrast, a decrease in protein content in Cd-treated cells of A. niger was recorded. Furthermore, SDS-PAGE revealed that Cd treated fungal cells of A. tamarii can synthesized new three stress proteins (hsp 's) while A. sydowi synthesized new four stress proteins. In cell culture of A. niger, cadmium induced new four stress proteins. Regarding the nucleic acids (RNA and DNA) content, it is clear that presence of Cd led to significant decrease in the RNA contents of the three tested fungi, while only the DNA content of A. niger was significantly decreased by Cd treatment compared to the corresponding control. The data also showed that Cd-gamma radiation combination acted synergistically at the low doses of gamma radiation, while an antagonistic effect was recorded at the higher one for both A. tamarii and A. sydowi. Both treatments acted synergistically at all doses of gamma radiation on the growth of A. niger

The Economic Effects of Cognitive and Educational Differences Among Low-Ability and Blue-Collar Origin Men: A Comparative Analysis.

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Olneck, Michael R.

This study used five data sets to investigate the effects of measured cognitive skills on educational attainment, and the effects of cognitive skills and educational attainment on occupational status and earning among men with low test scores, as compared to men with high test scores, and among men with blue-collar fathers, as compared to men with…

Stigma, Discrimination, Treatment Effectiveness and Policy Support: Comparing Public Views about Drug Addiction with Mental Illness

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Barry, Colleen L; McGinty, Emma Elizabeth; Pescosolido, Bernice; Goldman, Howard H.

2014-01-01

Objective This study compares current public attitudes about drug addiction with attitudes about mental illness. Methods A web-based national public opinion survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support. Results Respondents hold significantly more negative views toward persons with drug addiction compared to those with mental illness. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them on a job. Respondents were more willing to accept discriminatory practices, more skeptical about the effectiveness of available treatments, and more likely to oppose public policies aimed at helping persons with drug addiction. Conclusions Drug addiction is often treated as a sub-category of mental illness, and health insurance benefits group these conditions together under the rubric of behavioral health. Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches for advancing stigma reduction and public policy. PMID:25270497

SU-E-J-192: Comparative Effect of Different Respiratory Motion Management Systems

Energy Technology Data Exchange (ETDEWEB)

Nakajima, Y; Kadoya, N; Ito, K; Kanai, T; Jingu, K [Tohoku University School of Medicine, Sendai, Miyagi (Japan); Kida, S [Tohoku University Hospital, Sendai City, Miyagi (Japan); Kishi, K; Sato, K [Tohoku University Hospital, Sendai, Miyagi (Japan); Dobashi, S; Takeda, K [Tohoku University, Sendai, Miyagi (Japan)

2015-06-15

Purpose: Irregular breathing can influence the outcome of four-dimensional computed tomography imaging for causing artifacts. Audio-visual biofeedback systems associated with patient-specific guiding waveform are known to reduce respiratory irregularities. In Japan, abdomen and chest motion self-control devices (Abches), representing simpler visual coaching techniques without guiding waveform are used instead; however, no studies have compared these two systems to date. Here, we evaluate the effectiveness of respiratory coaching to reduce respiratory irregularities by comparing two respiratory management systems. Methods: We collected data from eleven healthy volunteers. Bar and wave models were used as audio-visual biofeedback systems. Abches consisted of a respiratory indicator indicating the end of each expiration and inspiration motion. Respiratory variations were quantified as root mean squared error (RMSE) of displacement and period of breathing cycles. Results: All coaching techniques improved respiratory variation, compared to free breathing. Displacement RMSEs were 1.43 ± 0.84, 1.22 ± 1.13, 1.21 ± 0.86, and 0.98 ± 0.47 mm for free breathing, Abches, bar model, and wave model, respectively. Free breathing and wave model differed significantly (p < 0.05). Period RMSEs were 0.48 ± 0.42, 0.33 ± 0.31, 0.23 ± 0.18, and 0.17 ± 0.05 s for free breathing, Abches, bar model, and wave model, respectively. Free breathing and all coaching techniques differed significantly (p < 0.05). For variation in both displacement and period, wave model was superior to free breathing, bar model, and Abches. The average reduction in displacement and period RMSE compared with wave model were 27% and 47%, respectively. Conclusion: The efficacy of audio-visual biofeedback to reduce respiratory irregularity compared with Abches. Our results showed that audio-visual biofeedback combined with a wave model can potentially provide clinical benefits in respiratory management

SU-E-J-192: Comparative Effect of Different Respiratory Motion Management Systems

International Nuclear Information System (INIS)

Nakajima, Y; Kadoya, N; Ito, K; Kanai, T; Jingu, K; Kida, S; Kishi, K; Sato, K; Dobashi, S; Takeda, K

2015-01-01

Purpose: Irregular breathing can influence the outcome of four-dimensional computed tomography imaging for causing artifacts. Audio-visual biofeedback systems associated with patient-specific guiding waveform are known to reduce respiratory irregularities. In Japan, abdomen and chest motion self-control devices (Abches), representing simpler visual coaching techniques without guiding waveform are used instead; however, no studies have compared these two systems to date. Here, we evaluate the effectiveness of respiratory coaching to reduce respiratory irregularities by comparing two respiratory management systems. Methods: We collected data from eleven healthy volunteers. Bar and wave models were used as audio-visual biofeedback systems. Abches consisted of a respiratory indicator indicating the end of each expiration and inspiration motion. Respiratory variations were quantified as root mean squared error (RMSE) of displacement and period of breathing cycles. Results: All coaching techniques improved respiratory variation, compared to free breathing. Displacement RMSEs were 1.43 ± 0.84, 1.22 ± 1.13, 1.21 ± 0.86, and 0.98 ± 0.47 mm for free breathing, Abches, bar model, and wave model, respectively. Free breathing and wave model differed significantly (p < 0.05). Period RMSEs were 0.48 ± 0.42, 0.33 ± 0.31, 0.23 ± 0.18, and 0.17 ± 0.05 s for free breathing, Abches, bar model, and wave model, respectively. Free breathing and all coaching techniques differed significantly (p < 0.05). For variation in both displacement and period, wave model was superior to free breathing, bar model, and Abches. The average reduction in displacement and period RMSE compared with wave model were 27% and 47%, respectively. Conclusion: The efficacy of audio-visual biofeedback to reduce respiratory irregularity compared with Abches. Our results showed that audio-visual biofeedback combined with a wave model can potentially provide clinical benefits in respiratory management

Cost-effectiveness of endobronchial valve treatment in patients with severe emphysema compared to standard medical care.

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Hartman, Jorine E; Klooster, Karin; Groen, Henk; Ten Hacken, Nick H T; Slebos, Dirk-Jan

2018-03-25

Bronchoscopic lung volume reduction using endobronchial valves (EBV) is an effective new treatment option for severe emphysema patients without interlobar collateral ventilation. The objective of this study was to perform an economic evaluation including the costs and cost-effectiveness of EBV treatment compared with standard medical care (SoC) from the hospital perspective in the short term and long term. For the short-term evaluation, incremental cost-effectiveness ratios (ICER) were calculated based on the 6-month end point data from the STELVIO randomized trial. For the long-term evaluation, a Markov simulation model was constructed based on STELVIO and literature. The clinical outcome data were quality-adjusted life-years (QALY) based on the EuroQol5-Dimensions (EQ5D) questionnaire, the 6-min walking distance (6MWD) and the St George's Respiratory Questionnaire (SGRQ). The mean difference between the EBV group and controls was €16 721/patient. In the short-term (6 months), costs per additional QALY was €205 129, the ICER for 6MWD was €160 and for SGRQ was €1241. In the long term, the resulting cost-effectiveness ratios indicate additional costs of €39 000 per QALY gained with a 5-year time horizon and €21 500 per QALY gained at 10 years. In comparison, historical costs per additional QALY 1 year after the coil treatment are €738 400, 5 years after lung volume reduction surgery are €48 415 and 15 years after double-lung transplantation are €29 410. The positive clinical effects of EBV treatment are associated with increased costs compared with SoC. Our results suggest that the EBV treatment has a favourable cost-effectiveness profile, also when compared with other treatment modalities for this patient group. © 2018 Asian Pacific Society of Respirology.

Neural signature of tDCS, tPCS and their combination: Comparing the effects on neural plasticity

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Thibaut, Aurore; Russo, Cristina; Morales-Quezada, Leon; Hurtado-Puerto, Aura; Deitos, Alícia; Freedman, Steven; Carvalho, Sandra; Fregni, Felipe

2017-01-01

Transcranial pulsed current stimulation (tPCS) and transcranial direct current stimulation (tDCS) are two noninvasive neuromodulatory brain stimulation techniques whose effects on human brain and behavior have been studied individually. In the present study we aimed to quantify the effects of tDCS and tPCS, individually and in combination, on cortical activity, sensitivity and pain-related assessments in healthy individuals in order to understand their neurophysiological mechanisms and potential applications in clinical populations. A total of 48 healthy individuals participated in this randomized double blind sham controlled study. Participants were randomized to receive a single stimulation session of either: active or sham tPCS and active or sham tDCS. Quantitative electroencephalography (qEEG), sensitivity and pain assessments were used before and after each stimulation session. We observed that tPCS had a higher effect on power, as compared to tDCS, in several bandwidths on various cortical regions: the theta band in the parietal region (p = 0.021), the alpha band in the temporal (p = 0.009), parietal (p = 0.0063), and occipital (p tDCS significantly decreased power in the low beta bandwidth of the frontal (p = 0.0006), central (p = 0.0001), and occipital (p = 0.0003) regions, when compared to sham stimulation. Additionally, tDCS significantly increased power in high beta over the temporal (p = 0.0015) and parietal (p = 0.0007) regions, as compared to sham. We found no effect on sensitivity or pain-related assessments. We concluded that tPCS and tDCS have different neurophysiological mechanisms, elicit distinct signatures, and that the combination of the two leads to no effect or a decrease on qEEG power. Further studies are required to examine the effects of these techniques on clinical populations in which EEG signatures have been found altered. PMID:27765610

Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

International Nuclear Information System (INIS)

Moreira, Estefania G.; Yu Xiaozhong; Robinson, Joshua F.; Griffith, Willian; Hong, Sung Woo; Beyer, Richard P.; Bammler, Theo K.; Faustman, Elaine M.

2010-01-01

Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.

Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

NARCIS (Netherlands)

Loymans, Rik J. B.; Gemperli, Armin; Cohen, Judith; Rubinstein, Sidney M.; Sterk, Peter J.; Reddel, Helen K.; Jüni, Peter; ter Riet, Gerben

2014-01-01

To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Systematic review and network meta-analysis using Bayesian statistics. Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate.

Identifying configurations of behavior change techniques in effective medication adherence interventions: a qualitative comparative analysis.

Science.gov (United States)

Kahwati, Leila; Viswanathan, Meera; Golin, Carol E; Kane, Heather; Lewis, Megan; Jacobs, Sara

2016-05-04

Interventions to improve medication adherence are diverse and complex. Consequently, synthesizing this evidence is challenging. We aimed to extend the results from an existing systematic review of interventions to improve medication adherence by using qualitative comparative analysis (QCA) to identify necessary or sufficient configurations of behavior change techniques among effective interventions. We used data from 60 studies in a completed systematic review to examine the combinations of nine behavior change techniques (increasing knowledge, increasing awareness, changing attitude, increasing self-efficacy, increasing intention formation, increasing action control, facilitation, increasing maintenance support, and motivational interviewing) among studies demonstrating improvements in adherence. Among the 60 studies, 34 demonstrated improved medication adherence. Among effective studies, increasing patient knowledge was a necessary but not sufficient technique. We identified seven configurations of behavior change techniques sufficient for improving adherence, which together accounted for 26 (76 %) of the effective studies. The intervention configuration that included increasing knowledge and self-efficacy was the most empirically relevant, accounting for 17 studies (50 %) and uniquely accounting for 15 (44 %). This analysis extends the completed review findings by identifying multiple combinations of behavior change techniques that improve adherence. Our findings offer direction for policy makers, practitioners, and future comparative effectiveness research on improving adherence.

The metabolic and performance effects of caffeine compared to coffee during endurance exercise.

Science.gov (United States)

Hodgson, Adrian B; Randell, Rebecca K; Jeukendrup, Asker E

2013-01-01

There is consistent evidence supporting the ergogenic effects of caffeine for endurance based exercise. However, whether caffeine ingested through coffee has the same effects is still subject to debate. The primary aim of the study was to investigate the performance enhancing effects of caffeine and coffee using a time trial performance test, while also investigating the metabolic effects of caffeine and coffee. In a single-blind, crossover, randomised counter-balanced study design, eight trained male cyclists/triathletes (Mean ± SD: Age 41 ± 7 y, Height 1.80 ± 0.04 m, Weight 78.9 ± 4.1 kg, VO2 max 58 ± 3 ml • kg(-1) • min(-1)) completed 30 min of steady-state (SS) cycling at approximately 55% VO2max followed by a 45 min energy based target time trial (TT). One hour prior to exercise each athlete consumed drinks consisting of caffeine (5 mg CAF/kg BW), instant coffee (5 mg CAF/kg BW), instant decaffeinated coffee or placebo. The set workloads produced similar relative exercise intensities during the SS for all drinks, with no observed difference in carbohydrate or fat oxidation. Performance times during the TT were significantly faster (~5.0%) for both caffeine and coffee when compared to placebo and decaf (38.35 ± 1.53, 38.27 ± 1.80, 40.23 ± 1.98, 40.31 ± 1.22 min respectively, pperformance times were similar for both caffeine and coffee. Average power for caffeine and coffee during the TT was significantly greater when compared to placebo and decaf (294 ± 21 W, 291 ± 22 W, 277 ± 14 W, 276 ± 23 W respectively, pcaffeine (5 mg/kg/BW) and coffee (5 mg/kg/BW) consumed 1 h prior to exercise can improve endurance exercise performance.

Comparative Effect of Memory and Cognitive Strategies Training on EFL Intermediate Learners' Vocabulary Learning

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Banisaeid, Maryam

2013-01-01

The present study was conducted to compare the effect of memory and cognitive strategies training on vocabulary learning of intermediate proficiency group of Iranian learners of English as a foreign language. It is to check how memory and cognitive strategies training affect word learning of EFL intermediate learners (N = 60) who were homogenized…

A Study of the Comparative Effectiveness of Zoology Prerequisites at Slippery Rock State College.

Science.gov (United States)

Morrison, William Sechler

This study compared the effectiveness of three sequences of prerequisite courses required before taking zoology. Sequence 1 prerequisite courses consisted of general biology and human biology; Sequence 2 consisted of general biology; and Sequence 3 required cell biology. Zoology students in the spring of 1972 were pretest and a posttest. The mean…

Comparative Evaluation of Effect of Water Absorption on the Surface Properties of Heat Cure Acrylic: An in vitro Study

OpenAIRE

Chandu, G S; Asnani, Pooja; Gupta, Siddarth; Faisal Khan, Mohd.

2015-01-01

Background: Use of alkaline peroxide denture cleanser with different temperature of water could cause a change in surface hardness of the acrylic denture and also has a bleaching effect. The purpose of the study was to determine the effect of increased water content during thermal cycling of hot water-treated acrylic on the surface hardness of acrylic denture base when compared to warm water treated acrylic. And to compare the bleaching effect of alkaline peroxide solution on the acrylic dent...

Comparing the effect of pressure and temperature on ion mobilities

International Nuclear Information System (INIS)

Tabrizchi, Mahmoud; Rouholahnejad, Fereshteh

2005-01-01

The effect of pressure on ion mobilities has been investigated and compared with that of temperature. In this connection, an ion mobility spectrometry (IMS) cell, which employs a corona discharge as the ionization source, has been designed and constructed to allow varying pressure inside the drift region. IMS spectra were recorded at various pressures ranging from 15 Torr up to atmospheric pressure. The results show that IMS peaks shift perfectly linear with pressure which is in excellent agreement with the ion mobility theory. However, experimental ion mobilities versus temperature show deviation from the theoretical trend. The deviation is attributed to formation of clusters. The different behaviour of pressure and temperature was explained on the basis of the different impact of pressure and temperature on hydration and clustering of ions. Pressure affects the clustering reactions linearly but temperature affects it exponentially

The Comparative Effectiveness of Variants of Construction of Electricity Export Projects

Directory of Open Access Journals (Sweden)

Anatoly Vladimirovich Lagerev

2014-06-01

Full Text Available The study describes a methodological approach that evaluates the comparative efficiency of construction of export-oriented power plants and transmission lines taking into account the development of power industry in the region and uncertainty (ambiguity of initial information. At the first stage the authors determine socio-economic effects of each project of construction of export-oriented power plants. With the help of optimization models they choose options that can guarantee the balanced and cost-effective development of the regional electric power system. Then using a simulation model the researchers assess commercial viability of previously selected projects. The article applies this approach for selecting the preferred option of electricity export from Eastern Siberia to China. This study shows that the project of CPP based on Kovykta natural gas with electricity transmission line to Chinese border (near Zabaikalsk is more preferable one in comparison with other projects (CPP based on Kansk-Achinsk coal in Krasnoyarsky krai; CPP based on coal in the Republic of Buryatia and Zabaikalsky krai (Olon-Shibirskaya CPP; New Kharanorskaya CPP; CPP based on Mugunsky coal in Irkutskaya oblast

Comparing Repetition Priming Effects in Words and Arithmetic Equations: Robust Priming Regardless of Color or Response Hand Change

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Ailsa Humphries

2018-01-01

Full Text Available Previous studies have shown that stimulus repetition can lead to reliable behavioral improvements. Although this repetition priming (RP effect has been reported in a number of paradigms using a variety of stimuli including words, objects, and faces, only a few studies have investigated mathematical cognition involving arithmetic computation, and no prior research has directly compared RP effects in a linguistic task with an arithmetic task. In two experiments, we used a within-subjects design to investigate and compare the magnitude of RP, and the effects of changing the color or the response hand for repeated, otherwise identical, stimuli in a word and an arithmetic categorization task. The results show that the magnitude of RP was comparable between the two tasks and that changing the color or the response hand had a negligible effect on priming in either task. These results extended previous findings in mathematical cognition. They also indicate that priming does not vary with stimulus domain. The implications of the results were discussed with reference to both facilitation of component processes and episodic memory retrieval of stimulus–response binding.

Comparing Repetition Priming Effects in Words and Arithmetic Equations: Robust Priming Regardless of Color or Response Hand Change.

Science.gov (United States)

Humphries, Ailsa; Chen, Zhe; Neumann, Ewald

2017-01-01

Previous studies have shown that stimulus repetition can lead to reliable behavioral improvements. Although this repetition priming (RP) effect has been reported in a number of paradigms using a variety of stimuli including words, objects, and faces, only a few studies have investigated mathematical cognition involving arithmetic computation, and no prior research has directly compared RP effects in a linguistic task with an arithmetic task. In two experiments, we used a within-subjects design to investigate and compare the magnitude of RP, and the effects of changing the color or the response hand for repeated, otherwise identical, stimuli in a word and an arithmetic categorization task. The results show that the magnitude of RP was comparable between the two tasks and that changing the color or the response hand had a negligible effect on priming in either task. These results extended previous findings in mathematical cognition. They also indicate that priming does not vary with stimulus domain. The implications of the results were discussed with reference to both facilitation of component processes and episodic memory retrieval of stimulus-response binding.

The Cost-Effectiveness of Conventional Discectomy Compared to Other Surgical Techniques for Lumbar Disk Herniation. A Systematic Review

DEFF Research Database (Denmark)

Thorsen, May Tone; Ødegaard-Olsen, Øystein; Leboeuf-Yde, Charlotte

2018-01-01

Background: The current study reviews the literature on the cost-effectiveness of conventional diskectomy compared to other surgical techniques, by assessing studies with economical evaluation and studies using proxy measures of cost-effectiveness. Methods: In April 2016, a comprehensive search w...... studies. The available evidence, however, suggests that any cost-effectiveness difference between conventional diskectomy and the alternatives is unlikely to be great.......Background: The current study reviews the literature on the cost-effectiveness of conventional diskectomy compared to other surgical techniques, by assessing studies with economical evaluation and studies using proxy measures of cost-effectiveness. Methods: In April 2016, a comprehensive search......-four articles were included in the review, 9 retrieved from the original search, and an additional 15 from reference lists. Four studies included an economical evaluation and 20 reported proxy measures of cost-effectiveness. The quality of studies varied considerably and results were ambiguous; the four...

Anticonflict effect of alpidem as compared with the benzodiazepine alprazolam in rats.

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Hascoët, M; Bourin, M

1997-02-01

A comparative study between two drugs acting on the GABAA receptor, alprazolam and alpidem was undertaken, using simple tests such as measurement of spontaneous locomotor activity, four plates test and rotarod in mice. Additional conflict test was further performed using a new conflict paradigm where the opportunity existed for rats to choose during punished periods between immediate, punished reinforcement and delayed non-punished reinforcement. The benzodiazepine alprazolam, demonstrated, as expected, strong anxiolytic effects in mice and increased punished response in rats at non sedative doses (0.5, 1 mg/kg). High doses of alprazolam decreased spontaneous locomotor activity and induced myorelaxant effects in mice. Alpidem, an imidazopyridine derivative, induced motor impairment in mice and only very weak anxiolytic effects in the four plates test in mice (4 mg/kg) and in punished procedure in rats (32 mg/kg). As alprazolam is a full agonist for the GABAA receptor complex and alpidem is a partial agonist acting with specificity on omega 1 GABAA receptor subtypes, the results are discussed. Activity on omega 1 receptor subtypes is perhaps not sufficient in order to obtain a true anti-conflict effect and compounds such as alpidem only relieve some of the symptoms of anxiety disorders.

Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis.

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Sinnott, Sarah-Jo; Tomlinson, Laurie A; Root, Adrian A; Mathur, Rohini; Mansfield, Kathryn E; Smeeth, Liam; Douglas, Ian J

2017-02-01

Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I 2 test and corresponding 95% confidence intervals. From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth-line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensin-aldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4 mmHg (95%CI 3.2 - 11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9 mmHg (95% CI 9.3 - 14.4) more than the active comparator. Conclusion On the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other fourth-line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke, now needs to be determined.

A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache.

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Jeffrey L Jackson

Full Text Available To compare the effectiveness and side effects of migraine prophylactic medications.We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models.PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014.We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration.Placebo controlled trials included alpha blockers (n = 9, angiotensin converting enzyme inhibitors (n = 3, angiotensin receptor blockers (n = 3, anticonvulsants (n = 32, beta-blockers (n = 39, calcium channel blockers (n = 12, flunarizine (n = 7, serotonin reuptake inhibitors (n = 6, serotonin norepinephrine reuptake inhibitors (n = 1 serotonin agonists (n = 9 and tricyclic antidepressants (n = 11. In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82, -flunarizine (-1.1 headaches/month (ha/month, 95% CI: -1.6 to -0.67, fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17, metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46, pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21, propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62, topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73 and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8. Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril, two angiotensin receptor blockers (candesartan, telmisartan, two anticonvulsants (lamotrigine, levetiracetam, and several beta-blockers (atenolol, bisoprolol, timolol. Network meta-analysis found amitriptyline to be better than several other medications including candesartan, fluoxetine, propranolol, topiramate and valproate and no different than

A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache

Science.gov (United States)

2015-01-01

Objective To compare the effectiveness and side effects of migraine prophylactic medications. Design We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models. Data Sources PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014. Eligibility Criteria for Selecting Studies We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration. Results Placebo controlled trials included alpha blockers (n = 9), angiotensin converting enzyme inhibitors (n = 3), angiotensin receptor blockers (n = 3), anticonvulsants (n = 32), beta-blockers (n = 39), calcium channel blockers (n = 12), flunarizine (n = 7), serotonin reuptake inhibitors (n = 6), serotonin norepinephrine reuptake inhibitors (n = 1) serotonin agonists (n = 9) and tricyclic antidepressants (n = 11). In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82), -flunarizine (-1.1 headaches/month (ha/month), 95% CI: -1.6 to -0.67), fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17), metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46), pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21), propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62), topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73) and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8). Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril), two angiotensin receptor blockers (candesartan, telmisartan), two anticonvulsants (lamotrigine, levetiracetam), and several beta-blockers (atenolol, bisoprolol, timolol). Network meta-analysis found amitriptyline to be better than several other medications including

Creating a Common Data Model for Comparative Effectiveness with the Observational Medical Outcomes Partnership.

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FitzHenry, F; Resnic, F S; Robbins, S L; Denton, J; Nookala, L; Meeker, D; Ohno-Machado, L; Matheny, M E

2015-01-01

Adoption of a common data model across health systems is a key infrastructure requirement to allow large scale distributed comparative effectiveness analyses. There are a growing number of common data models (CDM), such as Mini-Sentinel, and the Observational Medical Outcomes Partnership (OMOP) CDMs. In this case study, we describe the challenges and opportunities of a study specific use of the OMOP CDM by two health systems and describe three comparative effectiveness use cases developed from the CDM. The project transformed two health system databases (using crosswalks provided) into the OMOP CDM. Cohorts were developed from the transformed CDMs for three comparative effectiveness use case examples. Administrative/billing, demographic, order history, medication, and laboratory were included in the CDM transformation and cohort development rules. Record counts per person month are presented for the eligible cohorts, highlighting differences between the civilian and federal datasets, e.g. the federal data set had more outpatient visits per person month (6.44 vs. 2.05 per person month). The count of medications per person month reflected the fact that one system's medications were extracted from orders while the other system had pharmacy fills and medication administration records. The federal system also had a higher prevalence of the conditions in all three use cases. Both systems required manual coding of some types of data to convert to the CDM. The data transformation to the CDM was time consuming and resources required were substantial, beyond requirements for collecting native source data. The need to manually code subsets of data limited the conversion. However, once the native data was converted to the CDM, both systems were then able to use the same queries to identify cohorts. Thus, the CDM minimized the effort to develop cohorts and analyze the results across the sites.

Design of VA Cooperative Study #591: CERV-PTSD, comparative effectiveness research in veterans with PTSD.

Science.gov (United States)

Schnurr, Paula P; Chard, Kathleen M; Ruzek, Josef I; Chow, Bruce K; Shih, Mei-Chiung; Resick, Patricia A; Foa, Edna B; Marx, Brian P; Huang, Grant D; Lu, Ying

2015-03-01

CERV-PTSD is a randomized controlled trial of two of the most effective treatments for PTSD, Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT). Despite solid evidence that both treatments are effective, there is limited evidence about their effectiveness relative to one another. The primary objective is to compare the effectiveness of PE and CPT for reducing PTSD symptom severity in a healthcare system that offers both treatments. The secondary objective is to compare the effectiveness of PE and CPT for reducing the severity of comorbid mental health problems and service utilization as well as improving functioning and quality of life. The tertiary objective is to examine whether discrepancy between patient preferences and treatment assignment reduces the effectiveness of each treatment. Exploratory analyses will examine whether demographic and clinical characteristics predict differential response to PE and CPT. The study is designed to randomize 900 male and female veterans with PTSD due to any traumatic military event to receive PE or CPT. The standard dose of treatment is 12 weekly sessions but veterans who improve more rapidly may finish in fewer sessions and veterans who improve more slowly may have additional sessions. The primary outcome is improvement in PTSD symptoms, measured during and after treatment and then 3 and 6 months later. As a large multi-site trial with men and women, CERV-PTSD is designed to advance the delivery of care for PTSD by providing conclusive information about whether one treatment is better than the other, overall, and for different types of patients. Published by Elsevier Inc.

Epidemiological surveys on the effects of low-level radiation dose: a comparative assessment

International Nuclear Information System (INIS)

Rose, K.S.B.

1988-01-01

In this report, the health effects of low-level doses of radiation are considered by reference to published epidemiological surveys. The work was carried out with three objectives in mind: 1. to provide a comprehensive and critical review of the subject; 2. to seek consistent indications of particular health effects by collating results and comparing with those from surveys at moderate-level doses; 3. to provide an authoritative view on the epidemiology of low-level radiation-induced health effects. Vol E (DRAFT A) is appended and contains group collation tables. Epidemiological surveys can be conveniently divided into four classes (A, B, C, D) according to the phase of life when irradiation occurs or the effect is diagnosed. The first of the classes (A) is addressed here; this class is concerned with possible effects arising from radiation received by a parent before conception. Possible effects of preconception irradiation were identified under four broad groupings. These are Down's syndrome, ''Indicators of Reproductive Damage'' (mainly Primary Sterility, Congenital Abnormalities, Sex Ratio, Fetal Mortality, Infant Mortality), Childhood Malignancies, and Chromosomal Changes in Abortuses. Information about each survey, and comparisons with results from moderate-level dose surveys, are contained in synopses that are set out in the Appendix. (author)

Antibacterial properties of tualang honey and its effect in burn wound management: a comparative study

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Nasir Nur-Azida

2010-06-01

Full Text Available Abstract Background The use of honey as a natural product of Apis spp. for burn treatment has been widely applied for centuries. Tualang honey has been reported to have antibacterial properties against various microorganisms, including those from burn-related diagnoses, and is cheaper and easier to be absorbed by Aquacel dressing. The aim of this study is to evaluate the potential antibacterial properties of tualang honey dressing and to determine its effectiveness as a partial thickness burn wound dressing. Methods In order to quantitate the bioburden of the swabs, pour plates were performed to obtain the colony count (CFU/ml. Swabs obtained from burn wounds were streaked on blood agar and MacConkey agar for bacterial isolation and identification. Later, antibacterial activity of Aquacel-tualang honey, Aquacel-Manuka honey, Aquacel-Ag and Aquacel- plain dressings against bacteria isolated from patients were tested (in-vitro to see the effectiveness of those dressings by zone of inhibition assays. Results Seven organisms were isolated. Four types of Gram-negative bacteria, namely Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas spp. and Acinetobacter spp., and three Gram-positive bacteria, namely Staphylococcus aureus, coagulase-negative Staphylococcus aureus (CONS and Streptococcus spp., were isolated. Total bacterial count decreased on day 6 and onwards. In the in-vitro antibacterial study, Aquacel-Ag and Aquacel-Manuka honey dressings gave better zone of inhibition for Gram positive bacteria compared to Aquacel-Tualang honey dressing. However, comparable results were obtained against Gram negative bacteria tested with Aquacel-Manuka honey and Aquacel-Tualang honey dressing. Conclusions Tualang honey has a bactericidal as well as bacteriostatic effect. It is useful as a dressing, as it is easier to apply and is less sticky compared to Manuka honey. However, for Gram positive bacteria, tualang honey is not as effective as usual care

Comparative Effects of Education and Bilingualism on the Onset of Mild Cognitive Impairment.

Science.gov (United States)

Ramakrishnan, Subasree; Mekala, Shailaja; Mamidipudi, Annapurna; Yareeda, Sireesha; Mridula, Rukmini; Bak, Thomas H; Alladi, Suvarna; Kaul, Subhash

2017-01-01

Increasing evidence suggests that life course factors such as education and bilingualism may have a protective role against dementia due to Alzheimer disease. This study aimed to compare the effects of education and bilingualism on the onset of cognitive decline at the stage of mild cognitive impairment (MCI). A total of 115 patients with MCI evaluated in a specialty memory clinic in Hyderabad, India, formed the cohort. MCI was diagnosed according to Petersen's criteria following clinical evaluation and brain imaging. Age at onset of MCI was compared between bilinguals and monolinguals, and across subjects with high and low levels of education, adjusting for possible confounding variables. The bilingual MCI patients were found to have a clinical onset of cognitive complaints 7.4 years later than monolinguals (65.2 vs. 58.1 years; p = 0.004), while years of education was not associated with delayed onset (1-10 years of education, 59.1 years; 11-15 years of education, 62.6 years; >15 years of education, 62.2 years; p = 0.426). The effect of bilingualism is protective against cognitive decline, and lies along a continuum from normal to pathological states. In comparison, the role of years of education is less robust. © 2017 S. Karger AG, Basel.

International comparison of comparative effectiveness research in five jurisdictions: insights for the US.

Science.gov (United States)

Levy, Adrian R; Mitton, Craig; Johnston, Karissa M; Harrigan, Brian; Briggs, Andrew H

2010-01-01

Spurred by a desire to improve quality of care and to understand the relative value of medical treatments, there has been a recent surge of interest in publicly funded comparative effectiveness research (CER) in the US. As health technology assessment (HTA) shares some of the same goals as CER, and publicly funded HTA has been a feature within other industrialized countries for many years, a review of HTA activities in some of these countries can be a helpful source of information for the US debate. Informed by a literature review, and in two cases augmented by informant interviews, we reviewed the organization of HTA activities in five jurisdictions: Canada, Sweden, Scotland, the Netherlands and Australia. We provide a summary description of the healthcare system in each country as well as a description of the key features of their HTA bodies, with a particular focus on the processes of HTA for listing medications on public formularies. Four of the committees evaluating medications for formulary inclusion are funded by, but remain at arm's length from, the government (Canada, Australia, Sweden and Scotland), while the process is fully embedded within the government in the Netherlands. Each of these jurisdictions has a stated preference for comparative outcomes evidence from randomized controlled trials, but will, under certain circumstances, accept randomized evidence using surrogate markers, other comparators that are not directly relevant or non-randomized evidence. Health technology evaluation committees largely comprise health professionals, with public representatives included in the Canadian, Australian and Scottish committees. Scotland is the only one of the five jurisdictions reviewed to have industry representation on the evaluation committee. We identified seven characteristics that are shared across the jurisdictions reviewed and that potentially serve as insights for development of CER in the US: (i) the process must be responsive to stakeholders

Teachers' Perceptions of Effective Teaching: A Comparative Study of Elementary School Teachers from China and the USA

Science.gov (United States)

Meng, Lingqi; Muñoz, Marco

2016-01-01

This international study investigated Chinese and American elementary school teachers' perceptions of effective teaching. The sample comprised Chinese (n = 108) and US (n = 110) participating teachers. The Effective Teaching Quality Survey (ETQS) was adopted for this comparative education research, an instrument that operationalized Stronge's…

Comparative study of the antitumor effect of natural monoterpenes: relationship to cell cycle analysis

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Abdeslam Jaafari

2012-06-01

Full Text Available Monoterpenes have been identified as responsible of important therapeutic effects of plant-extracts. In this work, we try to compare the cytotoxic effect of six monoterpenes (carvacrol, thymol, carveol, carvone, eugenol and isopulegol as well as their molecular mechanisms. The in vitro antitumor activity of the tested products, evaluated against five tumor cell lines, show that the carvacrol is the most cytotoxic monoterpene. The investigation of an eventual synergistic effect of the six natural monoterpenes with two anticancer drugs revealed that there is a significant synergy between them (p<5%. On the other hand, the effect of the tested products on cell cycle progression was examined by flow cytometry after DNA staining in order to investigate the molecular mechanism of their cytotoxic activity. The results revealed that carvacrol and carveol stopped the cell cycle progression in S phase; however, thymol and isopulegol stopped it in G0/G1 phase. Regarding carvone and eugenol, no effect on cell cycle was observed.

Comparative effectiveness of gamma-rays and electron beams in food irradiation

International Nuclear Information System (INIS)

Hayashi, Toru

1991-01-01

Ionizing radiations which can be used for the treatment of foods are gamma-rays from Co-60 and Cs-137, accelerated electrons from a machine at an energy of 10 MeV or lower and X-rays from a machine at an energy of 5 MeV or lower. The Joint FAO/IAEA/WHO Expert Committee on the Wholesomeness of Irradiated Food held in 1980 concluded that the foods irradiated at overall average doses up to 10 kGy with the radiation listed above are wholesome for human consumption. While most of the commercial food irradiations are conducted with gamma-rays from Co-60, accelerated electrons are increasingly utilized for treating foods. An important difference between gamma-rays and accelerated electrons is the penetration capacity in materials. The penetration capacity of gamma-rays is much higher than that of accelerated electrons. Another important difference is the dose rate. The dose rates of gamma-rays from commercial Co-60 sources are 1-100 Gy/min, while those of electron beams from electron accelerators are 10 3 -10 6 Gy/s. Ideally a comparison of the effect of different types of ionizing radiation should be carried out at the same dose rate but this has been difficult due to the design of irradiators. It is very difficult to draw a definite conclusion on the difference in the effectiveness in food irradiation between gamma-rays and electron beams based on published data. This chapter deals with as many reports as possible on the comparative effectiveness of gamma-rays and electron beams and on the effect of dose rate on chemical reactions and living organisms, whether or not they demonstrate any dependency of the effect of irradiation on dose rate and type of radiation. (author)

Comparing the Effects of Group and Home-based Physical Activity on Mental Health in the Elderly.

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Mortazavi, Seyede Salehe; Shati, Mohsen; Ardebili, Hassan Eftekhar; Mohammad, Kazem; Beni, Reza Dorali; Keshteli, A H

2013-11-01

The present study focuses on comparing the effects of home-based (HB) and group-based (GB) physical activity on mental health in a sample of older adults in Shahr-e-kord. In this quasi-experimental study, a twice-weekly physical activity program for 2 months was provided either individually at home or in a group format for 181 people who were divided into two groups (HB and GB). The outcome, mental health, was measured with the 28-item General Health Questionnaire (GHQ-28). Mental health status improved after participation in the physical activity program. The decrease in GHQ-28 total score in GB group, 3 months after intervention, was 3.61 ± 2.28 (P effects of GB physical activity on mental health compared with HB physical activity, adjusted for related baseline variables, were significant. These findings reveal the probable effects of GB rather than HB physical activity on mental health among the elderly.

Cost-effectiveness analysis of HPV vaccination: comparing the general population with socially vulnerable individuals.

Science.gov (United States)

Han, Kyu-Tae; Kim, Sun Jung; Lee, Seo Yoon; Park, Eun-Cheol

2014-01-01

After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea.

Effects of Worked Examples, Example-Problem Pairs, and Problem-Example Pairs Compared to Problem Solving

NARCIS (Netherlands)

Van Gog, Tamara; Kester, Liesbeth; Paas, Fred

2010-01-01

Van Gog, T., Kester, L., & Paas, F. (2010, August). Effects of worked examples, example-problem pairs, and problem-example pairs compared to problem solving. Paper presented at the Biannual EARLI SIG meeting of Instructional design and Learning and instruction with computers, Ulm, Germany.

Comparing treatment effects after adjustment with multivariable Cox proportional hazards regression and propensity score methods

NARCIS (Netherlands)

Martens, Edwin P; de Boer, Anthonius; Pestman, Wiebe R; Belitser, Svetlana V; Stricker, Bruno H Ch; Klungel, Olaf H

PURPOSE: To compare adjusted effects of drug treatment for hypertension on the risk of stroke from propensity score (PS) methods with a multivariable Cox proportional hazards (Cox PH) regression in an observational study with censored data. METHODS: From two prospective population-based cohort

Cost-effectiveness of nurse-delivered cognitive behavioural therapy (CBT) compared to supportive listening (SL) for adjustment to multiple sclerosis.

Science.gov (United States)

Mosweu, I; Moss-Morris, R; Dennison, L; Chalder, T; McCrone, P

2017-10-10

Cognitive Behavioural Therapy (CBT) reduces distress in multiple sclerosis, and helps manage adjustment, but cost-effectiveness evidence is lacking. An economic evaluation was conducted within a multi-centre trial. 94 patients were randomised to either eight sessions of nurse-led CBT or supportive listening (SL). Costs were calculated from the health, social and indirect care perspectives, and combined with additional quality-adjusted life years (QALY) or improvement on the GHQ-12 score, to explore cost-effectiveness at 12 months. CBT had higher mean health costs (£1610, 95% CI, -£187 to 3771) and slightly better QALYs (0.0053, 95% CI, -0.059 to 0.103) compared to SL but these differences were not statistically significant. This yielded £301,509 per QALY improvement, indicating that CBT is not cost-effective according to established UK NHS thresholds. The extra cost per patient improvement on the GHQ-12 scale was £821 from the same perspective. Using a £20,000, threshold, CBT in this format has a 9% probability of being cost effective. Although subgroup analysis of patients with clinical levels of distress at baseline showed an improvement in the position of CBT compared to SL, CBT was still not cost-effective. Nurse delivered CBT is more effective in reducing distress among MS patients compared to SL, but is highly unlikely to be cost-effective using a preference-based measure of health (EQ-5D). Results from a disease-specific measure (GHQ-12) produced comparatively lower Incremental Cost-Effectiveness Ratios, but there is currently no acceptable willingness-to-pay threshold for this measure to guide decision-making.

SNARC Effects with Numerical and Non-Numerical Symbolic Comparative Judgments: Instructional and Cultural Dependencies

Science.gov (United States)

Shaki, Samuel; Petrusic, William M.; Leth-Steensen, Craig

2012-01-01

With English-language readers in an experiment requiring pairwise comparative judgments of the sizes of animals, the nature of the association between the magnitudes of the animal pairs and the left or right sides of response (i.e., the SNARC effect) was reversed depending on whether the participants had to choose either the smaller or the larger…

Thermo-Kinetic Investigation of Comparative Ligand Effect on Cysteine Iron Redox Reaction

Directory of Open Access Journals (Sweden)

Masood Ahmad Rizvi

2015-03-01

Full Text Available Transition metal ions in their free state bring unwanted biological oxidations generating oxidative stress. The ligand modulated redox potential can be indispensable in prevention of such oxidative stress by blocking the redundant bio-redox reactions. In this study we investigated the comparative ligand effect on the thermo-kinetic aspects of biologically important cysteine iron (III redox reaction using spectrophotometric and potentiometric methods. The results were corroborated with the complexation effect on redox potential of iron(III-iron(II redox couple. The selected ligands were found to increase the rate of cysteine iron (III redox reaction in proportion to their stability of iron (II complex (EDTA < terpy < bipy < phen. A kinetic profile and the catalytic role of copper (II ions by means of redox shuttle mechanism for the cysteine iron (III redox reaction in presence of 1,10-phenanthroline (phen ligand is also reported.

Inhibitory Effect of Curcumin on Candida-albicans compared with Nystatin: an in-vitro Study

Directory of Open Access Journals (Sweden)

Neda Babaii

2016-10-01

Full Text Available Introduction: Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa. Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. on basis of recent studies; it has antifungal and antibacterial effects. The aim of this study was in-vitro evaluation of antifungal effect of curcumin on candida albicans and comparing it with nystatin. Methods: after preparing curcumin powder, 3 laboratory methods were used to evaluate antifungal effect. The first method was cell count technique, used to evaluate the amount of candida albicans after time, in different concentrations of curcumin in Dimethyl sulfoxide (DMSO. The second was cup bioassay, in which inhibitory a zone of curcumin in DMSO was evaluated in sabouraud culture plates; and in third method, inhibitory zones of dried disks; which contained curcumin in DMSO were evaluated. Results: the result of all three methods showed that curcumin has antifungal effect and this effect increases in more concentrations. Conclusion: curcumin has apparent and dose dependent antifungal effect on candida albicans.

Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat

International Nuclear Information System (INIS)

Hendriksen, Peter J.M.; Freidig, Andreas P.; Jonker, Diana; Thissen, Uwe; Bogaards, Jan J.P.; Mumtaz, Moiz M.; Groten, John P.; Stierum, Rob H.

2007-01-01

The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest-Observed-Adverse-Effect-Level (LOAEL) or at a two- or threefold lower concentration individually or in binary or ternary mixtures. The compounds had strong antagonistic effects on each other's gene expression changes, which included several genes encoding Phase I and II metabolizing enzymes. On the other hand, the mixtures affected the expression of 'novel' genes that were not or little affected by the individual compounds. The three compounds exhibited a synergistic interaction on gene expression changes at the LOAEL in the liver and both at the sub-LOAEL and LOAEL in the kidney. Many of the genes induced by mixtures but not by single compounds, such as Id2, Nr2f6, Tnfrsf1a, Ccng1, Mdm2 and Nfkb1 in the liver, are known to affect cellular proliferation, apoptosis and tissue-specific function. This indicates a shift from compound specific response on exposure to individual compounds to a more generic stress response to mixtures. Most of the effects on cell viability as concluded from transcriptomics were not detected by classical toxicological endpoints illustrating the benefit of increased sensitivity of assessing gene expression profiling. These results emphasize the benefit of applying toxicogenomics in mixture interaction studies, which yields biomarkers for joint toxicity and eventually can result in an interaction model for most known toxicants

Effects of microwaves on changes in foodstuffs as compared with conventional heat treatment. Pt. 2

International Nuclear Information System (INIS)

Kalb, M.; Dehne, L.; Boegl, W.

1980-01-01

It is purpose of this study to contribute to the discussion and to answer the question as to whether changes are caused by microwave-heating of foodstuffs, which differ from those caused by conventional heating. This is achieved by summarizing extensive test materials. In the relevant literature, a great number of tests are listed on the cooking and reheating of foodstuffs by means of micro-waves, as compared to conventional methods. The subject of these tests is the determination of quantitative changes of certain ingredients (vitamins, fatty acids etc.) and sensory characteristics (flavour, colour etc.) due to the different heating methods. In addition to cooking and heating, a more comprehensive use of microwaves in preparation of food is discussed in this study. Works on the thawing, blanching, freeze-drying, and pasteurization are taken into account when comparing the different heating methods. Moreover, this study includes a comaprison as to the formation of volatile aromatic compounds, the thermic decomposition of pesticide residues, and the physiological effect of lipids. It was determined that there is no indication of radiation-specific effects, i. e. athermic effects, of microwaves contained in any of the studies reviewed up to now. (orig./MG) [de

Cost-effectiveness of intensive multifactorial treatment compared with routine care for individuals with screen-detected Type 2 diabetes

DEFF Research Database (Denmark)

Tao, L; Wilson, E C F; Wareham, N J

2015-01-01

, falling to £37 500 over 30 years. The ICER fell below £30 000 only when the intervention cost was below £631 per patient: we estimated the cost at £981. Conclusion Given conventional thresholds of cost-effectiveness, the intensive treatment delivered in ADDITION was not cost-effective compared......Aims To examine the short- and long-term cost-effectiveness of intensive multifactorial treatment compared with routine care among people with screen-detected Type 2 diabetes. Methods Cost–utility analysis in ADDITION-UK, a cluster-randomized controlled trial of early intensive treatment in people...... at 3.5%). Adjusted incremental QALYs were 0.0000, – 0.0040, 0.0140 and 0.0465 over the same time horizons. Point estimate incremental cost-effectiveness ratios (ICERs) suggested that the intervention was not cost-effective although the ratio improved over time: the ICER over 10 years was £82 250...

A systematic review of cost-effectiveness studies comparing conventional, biological and surgical interventions for inflammatory bowel disease.

Science.gov (United States)

Pillai, Nadia; Dusheiko, Mark; Burnand, Bernard; Pittet, Valérie

2017-01-01

Inflammatory bowel disease (IBD) is a chronic disease placing a large health and economic burden on health systems worldwide. The treatment landscape is complex with multiple strategies to induce and maintain remission while avoiding long-term complications. The extent to which rising treatment costs, due to expensive biologic agents, are offset by improved outcomes and fewer hospitalisations and surgeries needs to be evaluated. This systematic review aimed to assess the cost-effectiveness of treatment strategies for IBD. A systematic literature search was performed in March 2017 to identify economic evaluations of pharmacological and surgical interventions, for adults diagnosed with Crohn's disease (CD) or ulcerative colitis (UC). Costs and incremental cost-effectiveness ratios (ICERs) were adjusted to reflect 2015 purchasing power parity (PPP). Risk of bias assessments and a narrative synthesis of individual study findings are presented. Forty-nine articles were included; 24 on CD and 25 on UC. Infliximab and adalimumab induction and maintenance treatments were cost-effective compared to standard care in patients with moderate or severe CD; however, in patients with conventional-drug refractory CD, fistulising CD and for maintenance of surgically-induced remission ICERs were above acceptable cost-effectiveness thresholds. In mild UC, induction of remission using high dose mesalazine was dominant compared to standard dose. In UC refractory to conventional treatments, infliximab and adalimumab induction and maintenance treatment were not cost-effective compared to standard care; however, ICERs for treatment with vedolizumab and surgery were favourable. We found that, in general, while biologic agents helped improve outcomes, they incurred high costs and therefore were not cost-effective, particularly for use as maintenance therapy. The cost-effectiveness of biologic agents may improve as market prices fall and with the introduction of biosimilars. Future research

Health technology assessment and comparative effectiveness research: a pharmaceutical industry perspective.

Science.gov (United States)

Hao, Yanni; Thomas, Adrian

2013-08-01

We briefly review the characteristics of several established health technology assessment (HTA) programs in industrialized societies including Germany, the UK and France. Special attention is paid on two issues: the position of HTA in coverage decision making and the role of economic assessment in evaluation processes. Although law makers in the USA have barred the use of NICE's cost/quality-adjusted life year or similar health economics approaches by public payers for coverage decision making, there are suggestions of prioritizing relative efficacy evaluation over economic assessment under a comparative effectiveness research (CER) framework to inform payment rates of public payers (an approach similar to German and French HTA processes). However, such an approach is unlikely to prove viable. It should also be noted that, if cost considerations are made explicit in US CER policy decisions, CER may become an unsustainable approach undermined by a conflicting emphasis on both cost containment and a demand for costly comparative evidence. On the other hand, properly designed CER initiatives can serve as a facilitator of more efficient research activities and drug development models. With these points in mind, the likely pathway of US CER is explored and the plausible impact on industry innovation is discussed.

Comparative effectiveness of guidelines for the management of hyperlipidemia and hypertension for type 2 diabetes patients.

Directory of Open Access Journals (Sweden)

Nilay D Shah

Full Text Available BACKGROUND: Several guidelines to reduce cardiovascular risk in diabetes patients exist in North America, Europe, and Australia. Their ability to achieve this goal efficiently is unclear. METHODS AND FINDINGS: Decision analysis was used to compare the efficiency and effectiveness of international contemporary guidelines for the management of hypertension and hyperlipidemia for patients aged 40-80 with type 2 diabetes. Measures of comparative effectiveness included the expected probability of a coronary or stroke event, incremental medication costs per event, and number-needed-to-treat (NNT to prevent an event. All guidelines are equally effective, but they differ significantly in their medication costs. The range of NNT to prevent an event was small across guidelines (6.5-7.6 for males and 6.5-7.5 for females; a larger range of differences were observed for expected cost per event avoided (ranges, $117,269-$157,186 for males and $115,999-$163,775 for females. Australian and U.S. guidelines result in the highest and lowest expected costs, respectively. CONCLUSIONS: International guidelines based on the same evidence and seeking the same goal are similar in their effectiveness; however, there are large differences in expected medication costs.

Comparative effects of carbohydrate versus fat restriction on metabolic profiles, biomarkers of inflammation and oxidative stress in overweight patients with Type 2 diabetic and coronary heart disease: a randomized clinical trialComparative effects of car

Directory of Open Access Journals (Sweden)

Fariba Raygan

2017-02-01

Full Text Available BACKGROUND: This study was conducted to establish the comparative effects of carbohydrate versus fat restriction on metabolic indices in Type 2 diabetic (T2D patients with coronary heart disease (CHD. METHODS: This randomized, clinical trial was done among 56 overweight persons with T2D and CHD aged 40-85 years old. The patients were randomly allocated to take either a high-carbohydrate (HC diet (60-65% carbohydrates and 20-25% fats (n = 28 or a restricted carbohydrate (RC diet (43-49% carbohydrate and 36-40% fats (n = 28 for 8 weeks to determine metabolic status. RESULTS: After 8 weeks of treatment, RC diet decreased fasting plasma glucose (FPG (−11.5 ± 28.3 vs. +7.0 ± 26.9 mg/dl, P = 0.010 and high-sensitivity C-reactive protein (hs-CRP (−564.3 ± 1280.1 vs. +286.1 ± 1789.2 ng/ml, P = 0.040 compared with a HC diet. Moreover, compared with a HC diet, RC diet increased total antioxidant capacity (TAC (+274.8 ± 111.5 vs. +20.2 ± 82.5 mmol/l, P < 0.001 and glutathione (GSH levels (+51.6 ± 111.5 vs. −32.6 ± 88.5 µmol/l, P = 0.003. No significant alterations between the two groups were found in terms of their effect on other metabolic profiles. CONCLUSION: RC diet in overweight T2D with CHD had beneficial effects on FPG, hs-CRP, TAC, and GSH values. 

Specific spheres of application of ionising radiation effects, some realized results and comparative advantages

International Nuclear Information System (INIS)

Benderac, R.

2007-01-01

The papers discusses some results of ionizing radiation effects in realization of non-destructive methods, achieved progress from the aspect of innovation, comparative results with previously used methods, etc. A review is given of methods based on alpha-radiography, auto-alpha radiography, beta-radiography, X-ray-fluorescent analysis, X- and gamma radiography, and photos of specific samples of neutron radiography [sr

Effects of plasma radiation on wound healing compared with X-ray

Energy Technology Data Exchange (ETDEWEB)

Azorin V, E.; Pena E, R. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Azorin V, J. C., E-mail: erica.azorin@inin.gob.mx [Universidad de Guanajuato, Campus Leon, Departamento de Ingenieria Fisica, Blvd. Prol. Calz. de los Heroes No. 908, Col. La Martinica, Leon, Guanajuato (Mexico)

2015-10-15

Full text: The radiation emitted by the plasma needle has shown high efficiency in the inactivation of microorganisms and the acceleration of the healing process; apparently such effects are related to the antioxidant activity, induction of cell damage and the generation of free radicals. To take advantage of plasma clinical applications it is essential to understand the cellular mechanisms activated by the exposure of human cells to radiation emitted by cold plasma. In this work we present the results of the characterization of the responses of human skin fibroblasts exposed to the radiation emitted by a plasma by varying the magnitude of flow, electrical power, time and composition of the cell culture medium comparing it with the response of these fibroblasts to low energy X-rays. (Author)

Effects of plasma radiation on wound healing compared with X-ray

International Nuclear Information System (INIS)

Azorin V, E.; Pena E, R.; Azorin V, J. C.

2015-10-01

Full text: The radiation emitted by the plasma needle has shown high efficiency in the inactivation of microorganisms and the acceleration of the healing process; apparently such effects are related to the antioxidant activity, induction of cell damage and the generation of free radicals. To take advantage of plasma clinical applications it is essential to understand the cellular mechanisms activated by the exposure of human cells to radiation emitted by cold plasma. In this work we present the results of the characterization of the responses of human skin fibroblasts exposed to the radiation emitted by a plasma by varying the magnitude of flow, electrical power, time and composition of the cell culture medium comparing it with the response of these fibroblasts to low energy X-rays. (Author)

Cost-effectiveness of vedolizumab compared with conventional therapy for ulcerative colitis patients in the UK

Directory of Open Access Journals (Sweden)

Wilson MR

2017-10-01

Full Text Available Michele R Wilson,1 Ismail Azzabi Zouraq,2 Helene Chevrou-Severac,2 Ross Selby,3 Matthew C Kerrigan4 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Takeda Pharmaceuticals International AG, Zurich, Switzerland; 3Takeda UK Ltd., Bucks, UK; 4PHMR Limited, London, UK Objective: To examine the clinical and economic impact of vedolizumab compared with conventional therapy in the treatment of moderately-to-severely active ulcerative colitis (UC in the UK based on results of the GEMINI I trial. Methods: A decision-analytic model in Microsoft Excel was used to compare vedolizumab with conventional therapy (aminosalicylates, corticosteroids, immunomodulators for the treatment of patients with UC in the UK. We considered the following three populations: the overall intent-to-treat population from the GEMINI I trial, patients naïve to anti-TNF therapy, and those who had failed anti-TNF-therapy. Population characteristics and efficacy data were obtained from the GEMINI I trial. Other inputs (eg, unit costs, probability of surgery, mortality were obtained from published literature. Time horizon was a lifetime horizon, with costs and outcomes discounted by 3.5% per year. One-way and probabilistic sensitivity analyses were conducted to measure the impact of parameter uncertainty. Results: Vedolizumab had incremental cost-effectiveness ratios of £4,095/quality-adjusted life-year (QALY, £4,423/QALY, and £5,972/QALY compared with conventional therapy in the intent-to-treat, anti-TNF-naïve, and anti-TNF-failure populations, respectively. Patients on vedolizumab accrued more QALYs while incurring more costs than patients on conventional therapy. The sensitivity analyses showed that the results were most sensitive to induction response and transition probabilities for each treatment. Conclusion: The results suggest that vedolizumab results in more QALYs and may be a cost-effective treatment option compared with conventional therapy for both anti

Multisystemic Therapy and Functional Family Therapy Compared on their Effectiveness Using the Propensity Score Method.

Science.gov (United States)

Eeren, Hester V; Goossens, Lucas M A; Scholte, Ron H J; Busschbach, Jan J V; van der Rijken, Rachel E A

2018-01-09

Multisystemic Therapy (MST) and Functional Family Therapy (FFT) have overlapping target populations and treatment goals. In this study, these interventions were compared on their effectiveness using a quasi-experimental design. Between October, 2009 and June, 2014, outcome data were collected from 697 adolescents (mean age 15.3 (SD 1.48), 61.9% male) assigned to either MST or FFT (422 MST; 275 FFT). Data were gathered during Routine Outcome Monitoring. The primary outcome was externalizing problem behavior (Child Behavior Checklist and Youth Self Report). Secondary outcomes were the proportion of adolescents living at home, engaged in school or work, and who lacked police contact during treatment. Because of the non-random assignment, a propensity score method was used to control for observed pre-treatment differences. Because the risk-need-responsivity (RNR) model guided treatment assignment, effectiveness was also estimated in youth with and without a court order as an indicator of their risk level. Looking at the whole sample, no difference in effect was found with regard to externalizing problems. For adolescents without a court order, effects on externalizing problems were larger after MST. Because many more adolescents with a court order were assigned to MST compared to FFT, the propensity score method could not balance the treatment groups in this subsample. In conclusion, few differences between MST and FFT were found. In line with the RNR model, higher risk adolescents were assigned to the more intensive treatment, namely MST. In the group with lower risk adolescents, this more intensive treatment was more effective in reducing externalizing problems.

Investigating the visual span in comparative search: the effects of task difficulty and divided attention.

Science.gov (United States)

Pomplun, M; Reingold, E M; Shen, J

2001-09-01

In three experiments, participants' visual span was measured in a comparative visual search task in which they had to detect a local match or mismatch between two displays presented side by side. Experiment 1 manipulated the difficulty of the comparative visual search task by contrasting a mismatch detection task with a substantially more difficult match detection task. In Experiment 2, participants were tested in a single-task condition involving only the visual task and a dual-task condition in which they concurrently performed an auditory task. Finally, in Experiment 3, participants performed two dual-task conditions, which differed in the difficulty of the concurrent auditory task. Both the comparative search task difficulty (Experiment 1) and the divided attention manipulation (Experiments 2 and 3) produced strong effects on visual span size.

The comparative effect of fasting with and without caloric restriction in Rat on oxidative stress parameters

OpenAIRE

Nurina Tyagita; Taufiqurrachman Nasihun; Titiek Sumarawati

2016-01-01

Introduction: Fasting, like Islamic Ramadan Fasting, has been associated with health benefits. Islamic Ramadan fasting, a form of caloric restriction (CR) or alternate day fasting that. Studies suggest a comparable effect of ADF and caloric restriction. Despite the fact that fasting can be considered as a form of dietary restriction, fasters tend to have difficulty to reduce their food intake during non-fasting period by overeating leading to the excessive calorie intake. To compare the effec...

Comparative study of the effects of bupropion and escitalopram on Internet gaming disorder.

Science.gov (United States)

Song, Jinuk; Park, Jeong Ha; Han, Doug Hyun; Roh, Sungwon; Son, Ji Hyun; Choi, Tae Young; Lee, Hyuk; Kim, Tae Ho; Lee, Young Sik

2016-11-01

We compared the efficacy of bupropion and escitalopram treatments in Internet gaming disorder (IGD) patients. We recruited 119 adolescents and adults with IGD. We treated these participants for 6 weeks in three groups as follows: 44 participants were treated with bupropion SR (bupropion group), 42 participants were treated with escitalopram (escitalopram group), and 33 patients without any medication were observed in the community (observation group). At baseline and at the 6-week follow-up visit, all subjects were evaluated using the Clinical Global Impression-Severity Scale, the Young Internet Addiction Scale, the Beck Depression Inventory, the ADHD Rating Scale, and the Behavioral Inhibition and Activation Scales. Both the escitalopram group and the bupropion group showed improvement on all clinical symptom scales after 6 weeks of treatment compared to the observation group. Additionally, the bupropion group showed greater improvement on scores for the Clinical Global Impression-Severity Scale, the Young Internet Addiction Scale, the ADHD Rating Scale, and the Behavioral Inhibition Scale than the escitalopram group. Both bupropion and escitalopram were effective in treating and managing IGD symptoms. Moreover, bupropion appeared to be more effective than escitalopram in improving attention and impulsivity in IGD patients. In addition, attention and impulsivity seem to be important for the management of IGD. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Comparative Effectiveness of Published Interventions for Elderly Fall Prevention: A Systematic Review and Network Meta-Analysis

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Peixia Cheng

2018-03-01

Full Text Available Background: Falls are a major threat to older adults worldwide. Although various effective interventions have been developed, their comparative effectiveness remains unreported. Methods: A systematic review and network meta-analysis was conducted to determine the most effective interventions to prevent falls in community-dwelling adults aged 60 and over. Combined odds ratio (OR and 95% credible interval (95% CrI were calculated. Results: A total of 49 trials involving 27,740 participants and 9271 fallers were included. Compared to usual care, multifactorial interventions (MFI demonstrated the greatest efficacy (OR: 0.64, 95% CrI: 0.53 to 0.77 followed by interventions combining education and exercise (EDU + EXC (OR: 0.65, 95% CrI: 0.38 to 1.00 and interventions combining exercise and hazard assessment and modification (EXC + HAM (OR: 0.66, 95% CrI: 0.40 to 1.04. The effect of medical care performed the worst (OR: 1.02, 95% CrI: 0.78 to 1.34. Model fit was good, inconsistency was low, and publication bias was considered absent. The overall quality of included trials was high. The pooled odds ratios and ranking probabilities remained relatively stable across all sensitivity analyses. Conclusions: MFI and exercise appear to be effective to reduce falls among older adults, and should be considered first as service delivery options. Further investigation is necessary to verify effectiveness and suitableness of the strategies to at-risk populations.

CHoosing Options for Insomnia in Cancer Effectively (CHOICE): Design of a patient centered comparative effectiveness trial of acupuncture and cognitive behavior therapy for insomnia.

Science.gov (United States)

Garland, Sheila N; Gehrman, Philip; Barg, Frances K; Xie, Sharon X; Mao, Jun J

2016-03-01

Insomnia is a prevalent and persistent side effect of cancer, which if left unaddressed, can be unremitting and negatively influence physical and mental well-being. Acupuncture and Cognitive Behavioral Therapy (CBT) are commonly used non-pharmacological treatments that are efficacious for treating insomnia in cancer patients; however, little is known about the comparative effectiveness of these options. The goal of personalized medicine is to determine which treatments are most effective for which individuals, and patient preference for treatment is a particularly important contributor to adherence and outcomes. Here we describe the design of a clinical trial that begins to determine how best to personalize the treatment of insomnia for cancer survivors. This project is a randomized controlled comparative effectiveness trial with a nested qualitative study comparing acupuncture and CBT for insomnia and co-morbid symptoms in a heterogeneous sample of 160 cancer survivors. The primary aim is to determine which treatment is associated with the largest reduction in insomnia severity. The secondary aim is to examine the demographic, clinical, and psychological characteristics that predict and/or moderate treatment effect. Patients will receive ten treatments of acupuncture or 7 sessions of CBT over eight weeks and complete validated patient-reported outcome measures of sleep and co-morbid symptoms at baseline, mid-treatment, post-treatment, and at three-months to assess durability of effect. The results of the proposed study have the potential to improve healthcare outcomes by helping cancer survivors and their caregivers make informed and evidence-based decisions, leading to patient-centered and personalized care for cancer survivors with insomnia. Copyright © 2016 Elsevier Inc. All rights reserved.

Predicting the hepatocarcinogenic potential of alkenylbenzene flavoring agents using toxicogenomics and machine learning

International Nuclear Information System (INIS)

Auerbach, Scott S.; Shah, Ruchir R.; Mav, Deepak; Smith, Cynthia S.; Walker, Nigel J.; Vallant, Molly K.; Boorman, Gary A.; Irwin, Richard D.

2010-01-01

Identification of carcinogenic activity is the primary goal of the 2-year bioassay. The expense of these studies limits the number of chemicals that can be studied and therefore chemicals need to be prioritized based on a variety of parameters. We have developed an ensemble of support vector machine classification models based on male F344 rat liver gene expression following 2, 14 or 90 days of exposure to a collection of hepatocarcinogens (aflatoxin B1, 1-amino-2,4-dibromoanthraquinone, N-nitrosodimethylamine, methyleugenol) and non-hepatocarcinogens (acetaminophen, ascorbic acid, tryptophan). Seven models were generated based on individual exposure durations (2, 14 or 90 days) or a combination of exposures (2 + 14, 2 + 90, 14 + 90 and 2 + 14 + 90 days). All sets of data, with the exception of one yielded models with 0% cross-validation error. Independent validation of the models was performed using expression data from the liver of rats exposed at 2 dose levels to a collection of alkenylbenzene flavoring agents. Depending on the model used and the exposure duration of the test data, independent validation error rates ranged from 47% to 10%. The variable with the most notable effect on independent validation accuracy was exposure duration of the alkenylbenzene test data. All models generally exhibited improved performance as the exposure duration of the alkenylbenzene data increased. The models differentiated between hepatocarcinogenic (estragole and safrole) and non-hepatocarcinogenic (anethole, eugenol and isoeugenol) alkenylbenzenes previously studied in a carcinogenicity bioassay. In the case of safrole the models correctly differentiated between carcinogenic and non-carcinogenic dose levels. The models predict that two alkenylbenzenes not previously assessed in a carcinogenicity bioassay, myristicin and isosafrole, would be weakly hepatocarcinogenic if studied at a dose level of 2 mmol/kg bw/day for 2 years in male F344 rats; therefore suggesting that these

Comparative study on effect of blending, thermal barrier coating ...

African Journals Online (AJOL)

The brake thermal efficiency, specific fuel consumption, carbon monoxide, unburned hydrocarbon and oxides of nitrogen emissions of both diesel and UOME and its blends were measured before and after coating and the results are compared. B20 fuelled biodiesel and PSZ coated engine provides almost comparable ...

Comparative performance of high-fidelity training models for flexible ureteroscopy: Are all models effective?

Directory of Open Access Journals (Sweden)

Shashikant Mishra

2011-01-01

Full Text Available Objective: We performed a comparative study of high-fidelity training models for flexible ureteroscopy (URS. Our objective was to determine whether high-fidelity non-virtual reality (VR models are as effective as the VR model in teaching flexible URS skills. Materials and Methods: Twenty-one trained urologists without clinical experience of flexible URS underwent dry lab simulation practice. After a warm-up period of 2 h, tasks were performed on a high-fidelity non-VR (Uro-scopic Trainer TM ; Endo-Urologie-Modell TM and a high-fidelity VR model (URO Mentor TM . The participants were divided equally into three batches with rotation on each of the three stations for 30 min. Performance of the trainees was evaluated by an expert ureteroscopist using pass rating and global rating score (GRS. The participants rated a face validity questionnaire at the end of each session. Results: The GRS improved statistically at evaluation performed after second rotation (P<0.001 for batches 1, 2 and 3. Pass ratings also improved significantly for all training models when the third and first rotations were compared (P<0.05. The batch that was trained on the VR-based model had more improvement on pass ratings on second rotation but could not achieve statistical significance. Most of the realistic domains were higher for a VR model as compared with the non-VR model, except the realism of the flexible endoscope. Conclusions: All the models used for training flexible URS were effective in increasing the GRS and pass ratings irrespective of the VR status.

Comparing welfare effects of different regulation schemes: An application to the electricity distribution industry

International Nuclear Information System (INIS)

Kopsakangas-Savolainen, Maria; Svento, Rauli

2010-01-01

We compare the welfare effects of different regulation schemes of electricity distribution utilities. The compared regulation schemes are Fixed Price regulation, Cost of Service regulation, Menu of Cost-Contingent Contracts and Simple Menu of Contracts. In our calculations we utilize the information of a firm's potential to improve cost efficiency. The firm-specific cost information of Finnish electricity distribution utilities is obtained by using various Stochastic Frontier models. Our basic result is that welfare can be improved by changing the Cost of Service regulation scheme to the Menu of Contracts regulation. Welfare also increases in the case of Fixed Price regulation and Simple Menu of Contract regulation. There is however, a significant difference among regulation regimes on how this improved welfare is distributed to consumers and producers.

Comparing Efficacy and Side Effects of Memantine vs. Risperidone in the Treatment of Autistic Disorder.

Science.gov (United States)

Nikvarz, Nikvarz; Alaghband-Rad, Javad; Tehrani-Doost, Mehdi; Alimadadi, Abbas; Ghaeli, Padideh

2017-01-01

Introduction: This study was aimed to compare the efficacy and side effects of memantine, an antagonist of the NMDA receptor of glutamate, with risperidone given the fact that glutamate has been noted for its possible effects in the pathogenesis of autism. Risperidone, an atypical antipsychotic, has been approved by FDA for the management of irritability associated with autism. Methods: 30 children, aged 4-17 years, entered an 8-week, randomized trial. Patients were randomly assigned to receive either risperidone or memantine. Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Clinical Global Impressions - Improvement (CGI-I) and Clinical Global Impression-Severity (CGI-S) scales were used to assess behavioral symptoms of the patients. Results: Both risperidone and memantine reduced the scores of 4 subscales of ABC as well as the 10-item and the total score of CARS significantly. However, differences between the 2 drugs in the scores of each evaluating scale were not found to be significant. Relatively, larger number of patients on risperidone showed "very much improvement" when assessed by CGI-I scale when compared with those on memantine. Discussion and conclusion: The present study suggests that memantine may have beneficial effects in the treatment of many core symptoms of autism. Therefore, memantine may be considered as a potential medication in the treatment of those autistic children who do not respond or cannot tolerate side effects of risperidone. © Georg Thieme Verlag KG Stuttgart · New York.

Toxicogenomic responses of nanotoxicity in Daphnia magna exposed to silver nitrate and coated silver nanoparticles

Science.gov (United States)

Applications for silver nanomaterials in consumer products are rapidly expanding, creating an urgent need for toxicological examination of the exposure potential and ecological effects of silver nanoparticles (AgNPs). The integration of genomic techniques into environmental toxic...

Which research is needed to support clinical decision-making on integrative medicine?- Can comparative effectiveness research close the gap?

Science.gov (United States)

Witt, Claudia M; Huang, Wen-jing; Lao, Lixing; Bm, Berman

2012-10-01

In clinical research on complementary and integrative medicine, experts and scientists have often pursued a research agenda in spite of an incomplete understanding of the needs of end users. Consequently, the majority of previous clinical trials have mainly assessed the efficacy of interventions. Scant data is available on their effectiveness. Comparative effectiveness research (CER) promises to support decision makers by generating evidence that compares the benefits and harms of the best care options. This evidence, more generalizable than the evidence generated by traditional randomized controlled trials (RCTs), is better suited to inform real-world care decisions. An emphasis on CER supports the development of the evidence base for clinical and policy decision-making. Whereas in most areas of complementary and integrative medicine data on comparative effectiveness is scarce, available acupuncture research already contributes to CER evidence. This paper will introduce CER and make suggestions for future research.

Comparative Cost-Effectiveness Analysis of Three Different Automated Medication Systems Implemented in a Danish Hospital Setting.

Science.gov (United States)

Risør, Bettina Wulff; Lisby, Marianne; Sørensen, Jan

2018-02-01

Automated medication systems have been found to reduce errors in the medication process, but little is known about the cost-effectiveness of such systems. The objective of this study was to perform a model-based indirect cost-effectiveness comparison of three different, real-world automated medication systems compared with current standard practice. The considered automated medication systems were a patient-specific automated medication system (psAMS), a non-patient-specific automated medication system (npsAMS), and a complex automated medication system (cAMS). The economic evaluation used original effect and cost data from prospective, controlled, before-and-after studies of medication systems implemented at a Danish hematological ward and an acute medical unit. Effectiveness was described as the proportion of clinical and procedural error opportunities that were associated with one or more errors. An error was defined as a deviation from the electronic prescription, from standard hospital policy, or from written procedures. The cost assessment was based on 6-month standardization of observed cost data. The model-based comparative cost-effectiveness analyses were conducted with system-specific assumptions of the effect size and costs in scenarios with consumptions of 15,000, 30,000, and 45,000 doses per 6-month period. With 30,000 doses the cost-effectiveness model showed that the cost-effectiveness ratio expressed as the cost per avoided clinical error was €24 for the psAMS, €26 for the npsAMS, and €386 for the cAMS. Comparison of the cost-effectiveness of the three systems in relation to different valuations of an avoided error showed that the psAMS was the most cost-effective system regardless of error type or valuation. The model-based indirect comparison against the conventional practice showed that psAMS and npsAMS were more cost-effective than the cAMS alternative, and that psAMS was more cost-effective than npsAMS.

Comparative Research of Residents’ Effect Perception and Participation Capacity and Willingness on Pro-poor Tourism

Institute of Scientific and Technical Information of China (English)

Guoqing; HUANG; Hong; SHU

2014-01-01

In this article,comparative research on residents’ effect perception,participation capacity and willingness on Pro-poor Tourism( PPT) is given based on the questionnaire carried out in Wulong County and Fengjie County in Three Gorges Area,Chongqing,China. Some technologies,such as SPSS 13. 0,ANOVA and T-test are applied to analyze the data and results show Wulong residents’ perception behavior is better than that of Fengjie residents. Moreover,the residents with different demographic characteristics have different participation behavior.Finally,multiple regression analysis is applied to identify the key factors influencing residents’ perception behavior,that is participation willingness and positive economic effect perception,positive social and cultural effect perception and participation capacity.

Cost-effectiveness of Low-dose Submicron Diclofenac Compared With Generic Diclofenac.

Science.gov (United States)

Mladsi, Deirdre; Ronquest, Naoko; Odom, Dawn; Miles, LaStella; Saag, Kenneth

2016-11-01

NSAIDs are commonly prescribed for the treatment of pain and inflammation. Despite the effectiveness of NSAIDs, concerns exist regarding their tolerability. Worldwide health authorities, including the European Medicines Agency, Health Canada, and the US Food and Drug Administration, have advised that NSAIDs be prescribed at the lowest effective dosage and for the shortest duration. Effective lowering of NSAID dosage without compromising pain relief has been demonstrated in randomized, controlled trials of the recently approved NSAID lower-dose submicron diclofenac. Building on previously published work from an independently published systematic review and meta-analysis, a linear dose-toxicity relationship between diclofenac dose and serious gastrointestinal (GI) events was recently demonstrated, indicating that reductions in adverse events (AEs) may be seen even with modest dose reductions in many patients. The objective of the present study was to estimate the potential reduction in risk for NSAID dose-related AEs, corresponding savings in health care costs, and the incremental cost-effectiveness of submicron diclofenac compared with generic diclofenac in the United States. Our decision-analytic cost-effectiveness model considered a subset of potential AEs that may be avoided by lowering NSAID dosage. To estimate the expected reductions in upper GI bleeding/perforation and major cardiovascular events with submicron diclofenac, our model used prediction equations estimated by meta-regressions using data from systematic literature reviews. Utilities, lifetime costs, and health outcomes associated with AEs were estimated using data from the literature. The face validity of the model structure and inputs was confirmed by clinical experts in the United States. Results were evaluated in 1-way and probabilistic sensitivity analyses. The model predicted that submicron diclofenac versus generic diclofenac could reduce the occurrence of modeled GI events (by 18

Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.

Science.gov (United States)

Holubar, Marisa; Stavroulakis, Maria Christina; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina

2017-01-01

Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target

Cold Nuclear Matter effects on J/psi production at RHIC: comparing shadowing models

Energy Technology Data Exchange (ETDEWEB)

Ferreiro, E.G.; /Santiago de Compostela U.; Fleuret, F.; /Ecole Polytechnique; Lansberg, J.P.; /SLAC; Rakotozafindrabe, A.; /SPhN, DAPNIA, Saclay

2009-06-19

We present a wide study on the comparison of different shadowing models and their influence on J/{psi} production. We have taken into account the possibility of different partonic processes for the c{bar c}-pair production. We notice that the effect of shadowing corrections on J/{psi} production clearly depends on the partonic process considered. Our results are compared to the available data on dAu collisions at RHIC energies. We try different break up cross section for each of the studied shadowing models.

Comparative cost-effectiveness of Option B+ for prevention of mother-to-child transmission of HIV in Malawi.

Science.gov (United States)

Tweya, Hannock; Keiser, Olivia; Haas, Andreas D; Tenthani, Lyson; Phiri, Sam; Egger, Matthias; Estill, Janne

2016-03-27

To estimate the cost-effectiveness of prevention of mother-to-child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared with ART during pregnancy or breastfeeding only unless clinically indicated ('Option B'). Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme. Individual-based simulation model. We simulated cohorts of 10 000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterized the model with data from the literature and by analysing programmatic data. We compared total costs of antenatal and postnatal care, and lifetime costs and disability-adjusted life-years of the infected infants between Option B+ and Option B. During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared with 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted. Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.

Toxicological Responses of Environmental Mixtures: Environmental Metals Mixtures Display Synergistic Induction of Metal-Responsive and Oxidative Stress Genes in Placental Cells

Science.gov (United States)

Adebambo, Oluwadamilare A.; Ray, Paul D.; Shea, Damian; Fry, Rebecca C.

2016-01-01

Exposure to elevated levels of the toxic metals inorganic arsenic (iAs) and cadmium (Cd) represents a major global health problem. These metals often occur as mixtures in the environment, creating the potential for interactive or synergistic biological effects different from those observed in single exposure conditions. In the present study, environmental mixtures collected from two waste sites in China and comparable mixtures prepared in the laboratory were tested for toxicogenomic response in placental JEG-3 cells. These cells serve as a model for evaluating cellular responses to exposures during pregnancy. One of the mixtures was predominated by iAs and one by Cd. Six gene biomarkers were measured in order to evaluate the effects from the metals mixtures using dose and time-course experiments including: heme oxygenase 1 (HO-1) and metallothionein isoforms (MT1A, MT1F and MT1G) previously shown to be preferentially induced by exposure to either iAs or Cd, and metal transporter genes aquaporin-9 (AQP9) and ATPase, Cu2+ transporting, beta polypeptide (ATP7B). There was a significant increase in the mRNA expression levels of ATP7B, HO-1, MT1A, MT1F, and MT1G in mixture-treated cells compared to the iAs or Cd only-treated cells. Notably, the genomic responses were observed at concentrations significantly lower than levels found at the environmental collection sites. These data demonstrate that metal mixtures increase the expression of gene biomarkers in placental JEG-3 cells in a synergistic manner. Taken together, the data suggest that toxic metals that co-occur may induce detrimental health effects that are currently underestimated when analyzed as single metals. PMID:26472158

Cost-effective cloud computing: a case study using the comparative genomics tool, roundup.

Science.gov (United States)

Kudtarkar, Parul; Deluca, Todd F; Fusaro, Vincent A; Tonellato, Peter J; Wall, Dennis P

2010-12-22

Comparative genomics resources, such as ortholog detection tools and repositories are rapidly increasing in scale and complexity. Cloud computing is an emerging technological paradigm that enables researchers to dynamically build a dedicated virtual cluster and may represent a valuable alternative for large computational tools in bioinformatics. In the present manuscript, we optimize the computation of a large-scale comparative genomics resource-Roundup-using cloud computing, describe the proper operating principles required to achieve computational efficiency on the cloud, and detail important procedures for improving cost-effectiveness to ensure maximal computation at minimal costs. Utilizing the comparative genomics tool, Roundup, as a case study, we computed orthologs among 902 fully sequenced genomes on Amazon's Elastic Compute Cloud. For managing the ortholog processes, we designed a strategy to deploy the web service, Elastic MapReduce, and maximize the use of the cloud while simultaneously minimizing costs. Specifically, we created a model to estimate cloud runtime based on the size and complexity of the genomes being compared that determines in advance the optimal order of the jobs to be submitted. We computed orthologous relationships for 245,323 genome-to-genome comparisons on Amazon's computing cloud, a computation that required just over 200 hours and cost $8,000 USD, at least 40% less than expected under a strategy in which genome comparisons were submitted to the cloud randomly with respect to runtime. Our cost savings projections were based on a model that not only demonstrates the optimal strategy for deploying RSD to the cloud, but also finds the optimal cluster size to minimize waste and maximize usage. Our cost-reduction model is readily adaptable for other comparative genomics tools and potentially of significant benefit to labs seeking to take advantage of the cloud as an alternative to local computing infrastructure.

Comparative effects of red and white grapes on oxidative markers and lipidemic parameters in adult hypercholesterolemic humans.

Science.gov (United States)

Rahbar, Ali Reza; Mahmoudabadi, Mohammad Mehdi Shakouri; Islam, Md Shahidul

2015-06-01

The present study compared the effects of consuming red versus white whole grapes on oxidative and lipidemic indices in people with hypercholesterolemia. Sixty nine patients were randomized into three groups. The two treatment groups consumed 500 g of either Condori red grapes or Shahroodi white grapes daily for 8 weeks, and the third group served as a control. Plasma glucose, triacylglycerol (TG), cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were determined by colorimetric methods at baseline and at the end of the study. In addition, the polyphenol and fiber content of the two grape varieties was measured. TBARS was reduced in both study groups compared to the control group, and the reduction was greater in the group that consumed red grapes compared to the white grapes. TAC was increased significantly in both red and white grape consuming groups compared to the control group. Total cholesterol and LDL-C were decreased in the red grape group compared to the control group. No significant changes in fasting blood glucose, TG or HDL-C were observed among the groups. The results of this study suggest that consumption of the whole fruit of red grapes has more potent anti-oxidative and hypolipidemic effects compared to the white grapes in hyperlipidemic adult humans. Hence, the whole fruit of red grapes may be an excellent fruit choice not only to prevent oxidative stress related metabolic disorders but also cholesterol related cardiovascular diseases, particularly in hyperlipidemic adult humans.

Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness.

Science.gov (United States)

Cohen, Steven P; Peterlin, B Lee; Fulton, Larry; Neely, Edward T; Kurihara, Connie; Gupta, Anita; Mali, Jimmy; Fu, Diana C; Jacobs, Michael B; Plunkett, Anthony R; Verdun, Aubrey J; Stojanovic, Milan P; Hanling, Steven; Constantinescu, Octav; White, Ronald L; McLean, Brian C; Pasquina, Paul F; Zhao, Zirong

2015-12-01

Occipital neuralgia (ON) is characterized by lancinating pain and tenderness overlying the occipital nerves. Both steroid injections and pulsed radiofrequency (PRF) are used to treat ON, but few clinical trials have evaluated efficacy, and no study has compared treatments. We performed a multicenter, randomized, double-blind, comparative-effectiveness study in 81 participants with ON or migraine with occipital nerve tenderness whose aim was to determine which treatment is superior. Forty-two participants were randomized to receive local anesthetic and saline, and three 120 second cycles of PRF per targeted nerve, and 39 were randomized to receive local anesthetic mixed with deposteroid and 3 rounds of sham PRF. Patients, treating physicians, and evaluators were blinded to interventions. The PRF group experienced a greater reduction in the primary outcome measure, average occipital pain at 6 weeks (mean change from baseline -2.743 ± 2.487 vs -1.377 ± 1.970; P occipital pain through 3 months (mean change from baseline -1.925 ± 3.204 vs -0.541 ± 2.644; P = 0.043), and average overall headache pain through 6 weeks (mean change from baseline -2.738 ± 2.753 vs -1.120 ± 2.1; P = 0.037). Adverse events were similar between groups, and few significant differences were noted for nonpain outcomes. We conclude that although PRF can provide greater pain relief for ON and migraine with occipital nerve tenderness than steroid injections, the superior analgesia may not be accompanied by comparable improvement on other outcome measures.

Comparative placental transfer, localization, and effects of radionuclides in experimental animal and human pregnancies

International Nuclear Information System (INIS)

Sikov, M.R.; Traub, R.J.; Meznarich, H.K.

1992-01-01

Estimating radiation doses to the human embryo/fetus from radionuclides and predicting effects requires extrapolation of data from studies of laboratory species with scaling for species-specific developmental stage and gestational time relationships and maturities at birth. Combinations of fetal-to-maternal ratios of concentrations, patterns of deposition, transfer kinetics, and compartmental and physiologic models are used to predict radioactivity levels and radiation doses to the conceptus. There is agreement between values expressing fractional transfer across the placenta with values for fractional absorption from gastrointestinal tract or lung for most substances. Information about three elements - cesium, strontium, and iodine - serve to present comparative approaches to predicting radiation dose and effect. 25 refs., 11 figs., tab

Comparing the Effects of Negative and Mixed Emotional Messages on Predicted Occasional Excessive Drinking

Directory of Open Access Journals (Sweden)

Pilar Carrera

2008-01-01

Full Text Available In this work we present two types of emotional message, negative (sadness versus mixed (joy and sadness, with the aim of studying their differential effect on attitude change and the probability estimated by participants of repeating the behavior of occasional excessive drinking in the near future. The results show that for the group of participants with moderate experience in this behavior the negative message, compared to the mixed one, is associated with higher probability of repeating the risk behavior and a less negative attitude toward it. These results suggest that mixed emotional messages (e.g. joy and sadness messages could be more effective in campaigns for the prevention of this risk behavior.

Comparing the effects of negative and mixed emotional messages on predicted occasional excessive drinking.

Science.gov (United States)

Carrera, Pilar; Caballero, Amparo; Muñoz, Dolores

2008-01-01

In this work we present two types of emotional message, negative (sadness) versus mixed (joy and sadness), with the aim of studying their differential effect on attitude change and the probability estimated by participants of repeating the behavior of occasional excessive drinking in the near future. The results show that for the group of participants with moderate experience in this behavior the negative message, compared to the mixed one, is associated with higher probability of repeating the risk behavior and a less negative attitude toward it. These results suggest that mixed emotional messages (e.g. joy and sadness messages) could be more effective in campaigns for the prevention of this risk behavior.

Comparative and Mixture Effect of Cynodon Dactylon, ElectroMagnetic Field and Insulin on Diabetic Mouse.

Science.gov (United States)

Nafisi, Saeid; Nezhady, Mohammad Ali Mohammad; Asghari, Mohammad Hossein

2012-12-01

New investigations are in progress to find some alternative treatments for diabetes mellitus. Herbs are some of the interesting medications in this regard. Cynodon dactylon (C.d) is a potential plant to be considered as a new medication. On the other hand, the effect of the Electromagnetic Field (EMF) on bio organisms is becoming clearer. In this study, the effect of C.d, EMF and insulin have been investigated on the diabetic mouse. Diabetes was induced by a combination of ketamine (60 mg/Kg) and xylazine (10 mg/Kg) which induces a sustained hyperglycemia. Mice were divided into 12 groups: 1) control, 2) normal saline, 3 and 4) 50mg/Kg C.d, 5 and 6) 100 mg/Kg C.d, 7) insulin, 8) insulin and C.d, 9) EMF (110 KHz, 700±20 mG), 10) insulin and EMF, 11) EMF plus C.d and 12) insulin plus C.d and EMF. Blood glucose level was measured after 5 and 60 minutes in C.d administrated groups, and 5 minutes in the other groups by a glucometer set. The data were analyzed by ANOVA and different means were compared by Tukey and Bonferroni tests (p<0.05). According to results, both dosages of C.d had significant lowering effect on blood glucose level. The first dose was more effective than the second, and its impact was just like insulin. The 6(th), 9(th) and 10(th) groups were significant, also. However, they did not show a higher effect than insulin or C.d. The application of EMF had a significant effect compared to the second group, but it did not reduce the glucose level to the normal range. The effect of the 8th group was very impressive and the mean glucose levels in this group were lower than the control group. Considering the data, C.d is a good alternative medication for diabetes mellitus.

Comparing the Effects of Four Instructional Treatments on EFL Students' Achievement in Writing Classified Ads

Science.gov (United States)

Khodabandeh, Farzaneh

2016-01-01

The current study set out to compare the effect of traditional and non-traditional instructional treatments; i.e. explicit, implicit, task-based and no-instruction approaches on students' abilities to learn how to write classified ads. 72 junior students who have all taken a course in Reading Journalistic Texts at the Payame-Noor University…

Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: An in vitro study.

Science.gov (United States)

Sawardekar, Swapna B; Patel, Tejal C; Uchil, Dinesh

2016-01-01

The objective was to compare antiplatelet effect of lycopene with aspirin and to study effect of combination of the two on platelet aggregation in vitro, using platelets from healthy volunteers. Platelets were harvested; platelet count of platelet-rich plasma adjusted to 2.5 Χ 10(5)/μL. Aspirin (140 μmol/L) and lycopene (4, 6, 8, 10, and 12 μmol/L) were studied in vitro against adenosine-5'- diphosphate (ADP) (2.5 μM/L) and collagen. All the concentrations of lycopene (4-12 μmol/L) exhibited reduction in maximum platelet aggregation induced by aggregating agents ADP and collagen (P Lycopene at concentration 10 μmol/L showed maximum platelet inhibition (47.05% ± 19.56%) against ADP, whereas lycopene at concentration 8 μmol/L showed maximum platelet inhibition (54.26% ± 30.71%) against collagen. Four μmol/L of lycopene combined with 140 μmol/L and 70 μmol/L aspirin showed greater inhibition of platelets as compared to aspirin 140 μmol/L alone, against both ADP and collagen. The study favorably compares lycopene and aspirin with respect to their antiplatelet activities against ADP and collagen. Lycopene can be considered as a potential target for modifying the thrombotic and pro-inflammatory events associated with platelet activation.

Comparing effectiveness of top-down and bottom-up strategies in containing influenza.

Directory of Open Access Journals (Sweden)

Achla Marathe

Full Text Available This research compares the performance of bottom-up, self-motivated behavioral interventions with top-down interventions targeted at controlling an "Influenza-like-illness". Both types of interventions use a variant of the ring strategy. In the first case, when the fraction of a person's direct contacts who are diagnosed exceeds a threshold, that person decides to seek prophylaxis, e.g. vaccine or antivirals; in the second case, we consider two intervention protocols, denoted Block and School: when a fraction of people who are diagnosed in a Census Block (resp., School exceeds the threshold, prophylax the entire Block (resp., School. Results show that the bottom-up strategy outperforms the top-down strategies under our parameter settings. Even in situations where the Block strategy reduces the overall attack rate well, it incurs a much higher cost. These findings lend credence to the notion that if people used antivirals effectively, making them available quickly on demand to private citizens could be a very effective way to control an outbreak.

Comparing Usage and Cost- Effectiveness Analysis of English Printed and Electronic Books for University of Tehran

OpenAIRE

Davoud Haseli; Nader Naghshineh; fatemeh Fahimnia

2014-01-01

Libraries operate in a competitive environment, and this is essentially needed to prove its benefits for stockholders, and continuously evaluate and compare advantages for printed and electronic resources. In these cases, economic evaluation methods such as cost- effectiveness analysis, is one of the best methods, because of a comprehensive study of the use and cost of library sources. The purpose of this study is to discovery of use and cost- effectiveness analysis of English printed and ebo...

Comparative effects of partial rootzone drying and deficit irrigation on growth and physiology of tomato plants

Directory of Open Access Journals (Sweden)

Savić Slađana

2009-01-01

Full Text Available The effects of partial rootzone drying (PRD, deficit irrigation (DI, and full irrigation (FI on tomato physiology were investigated. In PRD and DI plants, leaf water potential values and stomatal conductance were significantly lower, while xylem ABA concentration was greater compared to FI plants. Photosynthesis was similar for all treatments. Water use efficiency was improved by PRD and DI, which reduced fruit dry weight, but had no effect on dry weight of leaves and stems.

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan.

Directory of Open Access Journals (Sweden)

Po-Yin Chang

Full Text Available Relative effectiveness of smoking cessation medications-varenicline, bupropion and nicotine replacement therapy (NRT-remains unclear among smokers in real-world settings. Evidence in females and smokers with light/moderate nicotine dependence is particularly insufficient. This study compared the effectiveness of varenicline, bupropion or NRT gum relative to NRT patch, in achieving abstinence among recent quitters.In a national smoking cessation program in Taiwan (2012-2015, a cohort of 11,968 participants received varenicline (n = 5,052, bupropion (n = 823, NRT gum (n = 1944 or NRT patch (n = 4,149. The 7-day, 1-month or 6-month point-prevalence was calculated based on self-reported last smoking event via telephone interview after 6 months. Logistic regression modellings estimated odds ratios (OR and 95% confidence intervals (CI for achieving abstinence using different modalities (NRT patch as referent. Models included age, sex, education, marital status, geographic region, smoke-years, nicotine-dependence level, medical institution, number of clinic visits and medication use duration. Analyses were further stratified by sex and dependence severity.Participants were predominantly male (83% with a mean age of 43.7±12.6 years. Varenicline users were more likely than NRT patch users to achieve abstinence, based on 7-day point-prevalence (OR = 1.30, CI: 1.19-1.44, 1-month point-prevalence (OR = 1.36, CI: 1.24-1.50 or 6-month point-prevalence (OR = 1.30, CI: 1.14-1.47. Compared with NRT patch, varenicline was associated with greater odds of being abstinent in women (OR = 1.29, CI: 1.01-1.65, men (OR = 1.31, CI: 1.18-1.46, those with light/moderate dependence (OR = 1.42, CI: 1.24-1.63 or smokers with severe dependence (OR = 1.19, CI: 1.04-1.37, based on 7-day point-prevalence. Differences in effectiveness were not observed between users of bupropion, NRT gum and NRT patch.In smoking cessation clinics in Taiwan, varenicline users reported higher

Smoking-Cessation Interventions for Urban Hospital Patients: A Randomized Comparative Effectiveness Trial.

Science.gov (United States)

Sherman, Scott E; Link, Alissa R; Rogers, Erin S; Krebs, Paul; Ladapo, Joseph A; Shelley, Donna R; Fang, Yixin; Wang, Binhuan; Grossman, Ellie

2016-10-01

Hospitalization is a unique opportunity for smoking cessation, but prior interventions have measured efficacy with narrowly defined populations. The objective of this study was to enroll smokers admitted to two "safety net" hospitals and compare the effectiveness of two post-discharge cessation interventions. A randomized comparative effectiveness trial was conducted. At two New York City public hospitals, every hospitalized patient identified as a smoker (based on admission records) was approached. Inclusion criteria were: smoked cigarettes in the past 30 days; spoke English, Spanish, or Mandarin; had a U.S. phone number; not discharged to an institution where follow-up or smoking was limited; and not pregnant/breastfeeding. Of 18,797 patients identified as current smokers between July 2011 and April 2014, a total of 3,047 (16%) were discharged before being approached, 3,273 (17%) were not current smokers, 4,026 (21%) had no U.S. phone number, 2,831 (15%) were ineligible for other reasons, and 3,983 (21%) refused participation. In total, 1,618 (9%) participants enrolled in the study. During follow-up, 69% of participants were reached at 2 months and 68% at 6 months. At discharge, participants were randomized to multisession telephone counseling from study staff (n=804) or referral to the state quitline for proactive outreach and counseling (n=814). Self-reported abstinence at 6 months was measured. Analyses were conducted in late 2015. One quarter of participants were homeless or in unstable housing, 60% had a history of substance abuse, 43% reported current hazardous drinking, and half had a psychiatric diagnosis other than substance abuse. At follow-up, the rate of abstinence (30-day point prevalence) was higher in the intensive counseling arm than the quitline arm at 2 months (29.0% vs 20.7%; relative risk=1.40; 95% CI=1.13, 1.73) and 6 months (37.4% vs 31.5%; relative risk=1.19; 95% CI=1.01, 1.40). Intensive counseling was more effective than referral to the

Comparative Cost-Effectiveness of Stereotactic Body Radiation Therapy Versus Intensity-Modulated and Proton Radiation Therapy for Localized Prostate Cancer

International Nuclear Information System (INIS)

Parthan, Anju; Pruttivarasin, Narin; Davies, Diane; Taylor, Douglas C. A.; Pawar, Vivek; Bijlani, Akash; Lich, Kristen Hassmiller; Chen, Ronald C.

2012-01-01

Objective: To determine the cost-effectiveness of several external beam radiation treatment modalities for the treatment of patients with localized prostate cancer. Methods: A lifetime Markov model incorporated the probabilities of experiencing treatment-related long-term toxicity or death. Toxicity probabilities were derived from published sources using meta-analytical techniques. Utilities and costs in the model were obtained from publicly available secondary sources. The model calculated quality-adjusted life expectancy and expected lifetime cost per patient, and derived ratios of incremental cost per quality-adjusted life year (QALY) gained between treatments. Analyses were conducted from both payer and societal perspectives. One-way and probabilistic sensitivity analyses were performed. Results: Compared to intensity-modulated radiation therapy (IMRT) and proton beam therapy (PT), stereotactic body radiation therapy (SBRT) was less costly and resulted in more QALYs. Sensitivity analyses showed that the conclusions in the base-case scenario were robust with respect to variations in toxicity and cost parameters consistent with available evidence. At a threshold of $50,000/QALY, SBRT was cost-effective in 75% and 94% of probabilistic simulations compared to IMRT and PT, respectively, from a payer perspective. From a societal perspective, SBRT was cost-effective in 75% and 96% of simulations compared to IMRT and PT, respectively, at a threshold of $50,000/QALY. In threshold analyses, SBRT was less expensive with better outcomes compared to IMRT at toxicity rates 23% greater than the SBRT base-case rates. Conclusion: Based on the assumption that each treatment modality results in equivalent long-term efficacy, SBRT is a cost-effective strategy resulting in improved quality-adjusted survival compared to IMRT and PT for the treatment of localized prostate cancer.

Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer.

Science.gov (United States)

Alawadi, Zeinab; Phatak, Uma R; Hu, Chung-Yuan; Bailey, Christina E; You, Y Nancy; Kao, Lillian S; Massarweh, Nader N; Feig, Barry W; Rodriguez-Bigas, Miguel A; Skibber, John M; Chang, George J

2017-04-01

Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society. © 2016 American Cancer Society.

CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials.

Science.gov (United States)

Patrick, Kevin; Wolszon, Laura; Basen-Engquist, Karen M; Demark-Wahnefried, Wendy; Prokhorov, Alex V; Barrera, Stephanie; Baru, Chaitan; Farcas, Emilia; Krueger, Ingolf; Palmer, Doug; Raab, Fred; Rios, Phil; Ziftci, Celal; Peterson, Susan

2011-03-01

Improved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of knowledge about patients' lifestyle behaviors that may affect cancer's progression and recurrence, and limited ability to compile and interpret the wide range of variables that must be considered in the cancer treatment. This lack of data integration limits the potential for patients and clinicians to engage in fully informed decision-making regarding cancer prevention, treatment, and survivorship care, and the translation of research results into mainstream medical care. Particularly important, as noted in a 2009 report on CER to the President and Congress, the limited focus on health behavior-change interventions was a major hindrance in this research landscape (DHHS 2009). This paper describes an initiative to improve CER for cancer by addressing several of these limitations. The Cyberinfrastructure for Comparative Effectiveness Research (CYCORE) project, informed by the National Science Foundation's 2007 report "Cyberinfrastructure Vision for 21(st) Century Discovery" has, as its central aim, the creation of a prototype for a user-friendly, open-source cyberinfrastructure (CI) that supports acquisition, storage, visualization, analysis, and sharing of data important for cancer-related CER. Although still under development, the process of gathering requirements for CYCORE has revealed new ways in which CI design can significantly improve the collection and analysis of a wide variety of data types, and has resulted in new and important partnerships among cancer researchers engaged in

Big data, advanced analytics and the future of comparative effectiveness research.

Science.gov (United States)

Berger, Marc L; Doban, Vitalii

2014-03-01

The intense competition that accompanied the growth of internet-based companies ushered in the era of 'big data' characterized by major innovations in processing of very large amounts of data and the application of advanced analytics including data mining and machine learning. Healthcare is on the cusp of its own era of big data, catalyzed by the changing regulatory and competitive environments, fueled by growing adoption of electronic health records, as well as efforts to integrate medical claims, electronic health records and other novel data sources. Applying the lessons from big data pioneers will require healthcare and life science organizations to make investments in new hardware and software, as well as in individuals with different skills. For life science companies, this will impact the entire pharmaceutical value chain from early research to postcommercialization support. More generally, this will revolutionize comparative effectiveness research.

Comparing the effects of Calendula officinalis and clotrimazole on vaginal Candidiasis: A randomized controlled trial.

Science.gov (United States)

Saffari, Elnaz; Mohammad-Alizadeh-Charandabi, Sakineh; Adibpour, Mohammad; Mirghafourvand, Mojgan; Javadzadeh, Yousef

2017-01-01

This triple-blind trial examined the effects of Calendula officinalis vaginal cream on the treatment of vaginal Candidiasis (primary outcome) and sexual function (secondary outcome). Married women aged 18-45 years with vaginal Candidiasis (n = 150) were recruited from April to October 2014 and randomized into Calendula and clotrimazole groups, using 5-g vaginal cream every night for seven nights. Clinical and laboratory assessments were conducted at 10-15 and 30-35 days after intervention and the female sexual function index was assessed at 30-35 days. Six women were lost to follow-up. The frequency of testing negative for Candidiasis in the Calendula group was significantly lower at the first (49% vs. 74%; odds ratio (OR) 0.32; 95% confidence interval (CI) 0.16-0.67) but higher at the second (77% vs. 34%; OR 3.1; 95% CI 1.5-6.2) follow-up compared to the clotrimazole group. The frequency of most signs and symptoms were almost equal in the two groups at the first follow-up, but were significantly lower in the Calendula group at the second follow-up. Sexual function had almost equal significant improvement in both groups. Calendula vaginal cream appears to have been effective in the treatment of vaginal Candidiasis and to have a delayed but greater long-term effect compared to clotrimazole.

Comparing the Effect of Mefenamic Acid and Vitex Agnus on Intrauterine Device Induced Bleeding

OpenAIRE

Yavarikia, Parisa; Shahnazi, Mahnaz; Hadavand Mirzaie, Samira; Javadzadeh, Yousef; Lutfi, Razieh

2013-01-01

Introduction: Increased bleeding is the most common cause of intrauterine device (IUD) removal. The use of alternative therapies to treat bleeding has increased due to the complications of medications. But most alternative therapies are not accepted by women. Therefore, conducting studies to find the right treatment with fewer complications and being acceptable is necessary. This study aimed to compare the effect of mefenamic acid and vitex agnus castus on IUD induced bleeding.

Comparing the Effect of Mefenamic Acid and Vitex Agnus on Intrauterine Device Induced Bleeding

OpenAIRE

Parisa Yavarikia; Mahnaz Shahnazi; Samira Hadavand Mirzaie; Yousef Javadzadeh; Razieh Lutfi

2013-01-01

Introduction: Increased bleeding is the most common cause of intrauterine device (IUD) removal. The use of alternative therapies to treat bleeding has increased due to the complications of medications. But most alternative therapies are not accepted by women. Therefore, conducting studies to find the right treatment with fewer complications and being acceptable is necessary. This study aimed to compare the effect of mefenamic acid and vitex agnus castus on IUD induced bleeding.Methods: This w...

Comparing the effects of reflexology and foot bath on sleep quality in the elderly

OpenAIRE

Seyyedrasooli

2015-01-01

Introduction: Sleep disturbances are common mental problems reported among elders. It seems some non-pharmacological interventions, can improve their sleep quality. The aim of this study is to compare the effectiveness of two interventions, reflexology and foot bath, on sleep quality in elderly people. Methods: This is a clinical trial without control group, conducted on 46 elderly men in two groups of reflexology and foot bath. Written informed consent was completed by subjects. Reflexolo...

A short-term cost-effectiveness study comparing robot-assisted laparoscopic and open retropubic radical prostatectomy

DEFF Research Database (Denmark)

Hohwü, Lena; Borre, Michael; Ehlers, Lars

2011-01-01

OBJECTIVE: To evaluate cost effectiveness and cost utility comparing robot-assisted laparoscopic prostatectomy (RALP) versus retropubic radical prostatectomy (RRP). METHODS: In a retrospective cohort study a total of 231 men between the age of 50 and 69 years and with clinically localised prostate....... An economic evaluation was made to estimate direct costs of the first postoperative year and an incremental cost-effectiveness ratio (ICER) per successful surgical treatment and per quality-adjusted life-year (QALY). A successful RP was defined as: no residual cancer (PSA ... high volume urology centres and utilise the full potential of each robot....

A comparative study of the antacid effect of raw spinach juice and spinach extract in an artificial stomach model.

Science.gov (United States)

Panda, Vandana Sanjeev; Shinde, Priyanka Mangesh

2016-12-01

BackgroundSpinacia oleracea known as spinach is a green-leafy vegetable consumed by people across the globe. It is reported to possess potent medicinal properties by virtue of its numerous antioxidant phytoconstituents, together termed as the natural antioxidant mixture (NAO). The present study compares the antacid effect of raw spinach juice with an antioxidant-rich methanolic extract of spinach (NAOE) in an artificial stomach model. MethodsThe pH of NAOE at various concentrations (50, 100 and 200 mg/mL) and its neutralizing effect on artificial gastric acid was determined and compared with that of raw spinach juice, water, the active control sodium bicarbonate (SB) and a marketed antacid preparation ENO. A modified model of Vatier's artificial stomach was used to determine the duration of consistent neutralization of artificial gastric acid for the test compounds. The neutralizing capacity of test compounds was determined in vitro using the classical titration method of Fordtran. Results NAOE (50, 100 and 200 mg/mL), spinach juice, SB and ENO showed significantly better acid-neutralizing effect, consistent duration of neutralization and higher antacid capacity when compared with water. Highest antacid activity was demonstrated by ENO and SB followed by spinach juice and NAOE200. Spinach juice exhibited an effect comparable to NAOE (200 mg/mL). ConclusionsThus, it may be concluded that spinach displays significant antacid activity be it in the raw juice form or as an extract in methanol.

A comparative study of effect of sevoflurane on intubating conditions with rocuronium in neurosurgical patients

Directory of Open Access Journals (Sweden)

Saikat Mitra

2015-01-01

Full Text Available Background and Aims: Rocuronium may not always be the preferred relaxant for rapid sequence intubation. When 2% sevoflurane is used in conjunction with rocuronium, it may reduce the time required for achieving complete skeletal muscle relaxation with the intubating dose of rocuronium. Methods: This study was prospective, randomised, double-blind in nature and compared the effect of sevoflurane on intubation time and intubating conditions when used along with rocuronium. Thirty adult patients belonging to American Society of Anesthesiologists physical status Grades 1 and 2, of either gender aged between 30 and 65 years undergoing neurosurgical operations were randomly allocated into two equal groups: Group R received 0.8 mg/kg rocuronium, and Group RS received 0.8 mg/kg of rocuronium with 2% sevoflurane. Onset time of intubation was assessed using train-of-four stimuli. The intubating conditions were compared using the Cooper scoring system and the haemodynamic responses were compared between the two groups. Results: The onset time of intubation was 101.73 ± 10.28 s in Group R and 60.4 ± 4.1 s in Group RS (P < 0.001, with excellent intubating conditions in both groups and without any adverse effects. Significant differences in heart rate and mean arterial pressure were seen immediately after intubation, at 1 and 3 min (P < 0.05 between the two groups. Conclusion: Rocuronium 0.8 mg/kg along with 2% sevoflurane provides excellent intubating conditions within 60-66 s from its administration.

Comparative effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta-analysis.

Science.gov (United States)

Hung, Chen-Yu; Hsiao, Ming-Yen; Chang, Ke-Vin; Han, Der-Sheng; Wang, Tyng-Guey

2016-01-01

Increasing evidence has supported the use of dextrose prolotherapy for patients with osteoarthritis. However, the real benefits may be affected by differences in injection protocols, comparative regimens, and evaluation scales. PubMed and Scopus were searched from the earliest record until February 2016. One single-arm study and five randomized controlled trials were included, comprising 326 participants. We estimated the effect sizes of pain reduction before and after serial dextrose injections and compared the values between dextrose prolotherapy, comparative regimens, and exercise 6 months after the initial injection. Regarding the treatment arm using dextrose prolotherapy, the effect sizes compared with baseline were 0.65 (95% confidence interval [CI], 0.14-1.17), 0.84 (95% CI, 0.40-1.27), 0.85 (95% CI, 0.60-1.10), and 0.87 (95% CI, 0.53-1.21) after the first, second, third, and fourth or more injections, respectively. The overall effect of dextrose was better than control injections (effect size, 0.36; 95% CI, 0.10-0.63). Dextrose prolotherapy had a superior effect compared with local anesthesia (effect size, 0.38; 95% CI, 0.07-0.70) and exercise (effect size, 0.71; 95% CI, 0.30-1.11). There was an insignificant advantage of dextrose over corticosteroids (effect size, 0.31; 95% CI, -0.18 to 0.80) which was only estimated from one study. Dextrose injections decreased pain in osteoarthritis patients but did not exhibit a positive dose-response relationship following serial injections. Dextrose prolotherapy was found to provide a better therapeutic effect than exercise, local anesthetics, and probably corticosteroids when patients were retested 6 months following the initial injection.

Effectiveness of tramadol/paracetamol compared with etoricoxib as ...

African Journals Online (AJOL)

paracetamol combination when compared with etoricoxib as postoperative analgesia following day care surgery. Design: This was a prospective, randomised, single-blind study. Setting and subjects: Sixty-two patients were randomised to receive ...

Comparing the Effects of Teen Mentors to Adult Teachers on Child Lifestyle Behaviors and Health Outcomes in Appalachia

Science.gov (United States)

Smith, Laureen H.; Holloman, Christopher

2013-01-01

Childhood obesity prevalence rates in the United States are the highest in the rural Appalachian areas. Teens mentoring younger children to reverse obesity health risks are an understudied approach. This randomized-controlled trial compared the effects of two curriculum delivery methods and assessed the mediating effects of the number of sessions…

Propensity score estimation to address calendar time-specific channeling in comparative effectiveness research of second generation antipsychotics.

Directory of Open Access Journals (Sweden)

Stacie B Dusetzina

Full Text Available Channeling occurs when a medication and its potential comparators are selectively prescribed based on differences in underlying patient characteristics. Drug safety advisories can provide new information regarding the relative safety or effectiveness of a drug product which might increase selective prescribing. In particular, when reported adverse effects vary among drugs within a therapeutic class, clinicians may channel patients toward or away from a drug based on the patient's underlying risk for an adverse outcome. If channeling is not identified and appropriately managed it might lead to confounding in observational comparative effectiveness studies.To demonstrate channeling among new users of second generation antipsychotics following a Food and Drug Administration safety advisory and to evaluate the impact of channeling on cardiovascular risk estimates over time.Florida Medicaid data from 2001-2006.Retrospective cohort of adults initiating second generation antipsychotics. We used propensity scores to match olanzapine initiators with other second generation antipsychotic initiators. To evaluate channeling away from olanzapine following an FDA safety advisory, we estimated calendar time-specific propensity scores. We compare the performance of these calendar time-specific propensity scores with conventionally-estimated propensity scores on estimates of cardiovascular risk.Increased channeling away from olanzapine was evident for some, but not all, cardiovascular risk factors and corresponded with the timing of the FDA advisory. Covariate balance was optimized within period and across all periods when using the calendar time-specific propensity score. Hazard ratio estimates for cardiovascular outcomes did not differ across models (Conventional PS: 0.97, 95%CI: 0.81-3.18 versus calendar time-specific PS: 0.93, 95%CI: 0.77-3.04.Changes in channeling over time was evident for several covariates but had limited impact on cardiovascular risk

A cost-effectiveness analysis of radon protection methods in domestic properties: a comparative case study in Brixworth, Northamptonshire, UK

International Nuclear Information System (INIS)

Coskeran, Thomas; Denman, Antony; Phillips, Paul; Tornberg, Roger

2006-01-01

Building regulations in the UK have since 1992 required that radon-proof membranes be installed in new domestic properties to protect residents against the adverse effects of radon. This study compares the cost-effectiveness of the current regulatory regime with an alternative that would entail new properties being tested for radon after construction, and being remediated if necessary. The alternative regime is found to be more cost-effective for a sample of properties in Brixworth, Northamptonshire, UK. For this regime, the central estimate of cost per quality-adjusted life-year gained, the measure of cost-effectiveness used, is Pounds 2869 compared to Pounds 6182 for installing membranes, results suggesting a case for re-examining the current regulations on radon protection in new properties. Pilot studies will, however, be needed to consider how different means of protecting residents of new properties against radon might operate in practice and to provide improved evidence on their relative cost-effectiveness

Effects of lidocaine and droxicainide on myocardial necrosis: a comparative study

International Nuclear Information System (INIS)

Faria, D.B.; Cheung, W.M.; Ribeiro, L.G.; Maroko, P.R.

1983-01-01

Lidocaine has been shown to protect ischemic myocardium, but the degree of its effectiveness is not yet well established. Therefore, in this study, the effects of this drug on ultimate infarct size were examined quantitatively. Another member of the same class of drugs, droxicainide (ALS1249), DL-N-(2-hydroxyethyl)-pipecolinyl-2,6-dimethylanilide hydrochloride, is a new antiarrhythmic agent that has shown a good therapeutic index in the initial experimental studies. Accordingly, the effects of this drug on ultimate infarct size were examined and compared with those of lidocaine. Coronary artery occlusion was performed on 29 dogs. One minute later, technetium-99m labeled microspheres were injected into the left atrium for assessment of the hypoperfused zone (the zone at risk of infarction). Fifteen minutes after occlusion, the dogs were randomized into three groups: 9 dogs served as a control group, 10 were given lidocaine and 10 were given the same dosage of droxicainide. Six hours after occlusion, the dogs were sacrificed and the hearts cut into 3 mm thick slices and incubated in triphenyltetrazolium chloride to delineate the area of myocardial damage. Autoradiography of the same slices provided images of the areas of myocardial hypoperfusion. Thereafter, in each dog, the percent of hypoperfused area that evolved to necrosis was calculated. In control dogs, it was 85.6 +/- 2.0%; in lidocaine-treated dogs, 68.1 +/- 4.1% (p less than 0.01), a reduction of 20%; and in droxicainide-treated dogs, 50.1 +/- 5.3%, a reduction of 41% (p less than 0.001 versus control and p less than 0.005 versus lidocaine)

A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats

Directory of Open Access Journals (Sweden)

Talha Jawaid

2015-01-01

Full Text Available The comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats was studied. Male albino rats were administered with scopolamine to induce memory impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.], perindopril (0.1 mg/kg b.w., [i.p.], enalapril (0.1 mg/kg b.w., [i.p.], and ramipril (0.1 mg/kg b.w., [i.p.] were administered in different group of animals for 5 days. On 5 th day, scopolamine (1 mg/kg b.w., i.p. was administered after 60 min of the last dose of test drug. Memory function was evaluated in Morris water maze (MWM test and pole climbing test (PCT. Biochemical estimations like glutathione (GSH, malondialdehyde (MDA, and acetylcholinesterase activity in the brain were estimated after completion of behavior study. All three test groups shows improvement in learning and memory in comparison to control group. Perindopril treated group showed a more effective significant decrease in escape latency time and transfer latency time compared to enalapril and ramipril treated group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant reduction in MDA level and acetylcholinesterase activity and a significant rise in GSH level compared to enalapril and ramipril. The finding of this study indicates that Perindopril is more effective in memory retention compared to enalapril and ramipril.

Comparative Potential Protect Effect of HSCAS, Diatomite and ...

African Journals Online (AJOL)

mdenli

bentonite (Rosa et al., 2001), zeolite (Miazzo et al., 2000), hydrated sodium calcium aluminosilicate. (HSCAS) ... Due to these properties diatomite was selected for use in this experiment to compare ..... Aflatoxins in animal and human health.

The effective atomic numbers of some biomolecules calculated by two methods: A comparative study

Energy Technology Data Exchange (ETDEWEB)

Manohara, S. R.; Hanagodimath, S. M.; Gerward, L. [Department of Physics, Gulbarga University, Gulbarga, Karnataka 585 106 (India); Department of Physics, Technical University of Denmark, Lyngby DK-2800 (Denmark)

2009-01-15

The effective atomic numbers Z{sub eff} of some fatty acids and amino acids have been calculated by two numerical methods, a direct method and an interpolation method, in the energy range of 1 keV-20 MeV. The notion of Z{sub eff} is given a new meaning by using a modern database of photon interaction cross sections (WinXCom). The results of the two methods are compared and discussed. It is shown that for all biomolecules the direct method gives larger values of Z{sub eff} than the interpolation method, in particular at low energies (1-100 keV) At medium energies (0.1-5 MeV), Z{sub eff} for both methods is about constant and equal to the mean atomic number of the material. Wherever possible, the calculated values of Z{sub eff} are compared with experimental data.

The effective atomic numbers of some biomolecules calculated by two methods: A comparative study

International Nuclear Information System (INIS)

Manohara, S. R.; Hanagodimath, S. M.; Gerward, L.

2009-01-01

The effective atomic numbers Z eff of some fatty acids and amino acids have been calculated by two numerical methods, a direct method and an interpolation method, in the energy range of 1 keV-20 MeV. The notion of Z eff is given a new meaning by using a modern database of photon interaction cross sections (WinXCom). The results of the two methods are compared and discussed. It is shown that for all biomolecules the direct method gives larger values of Z eff than the interpolation method, in particular at low energies (1-100 keV) At medium energies (0.1-5 MeV), Z eff for both methods is about constant and equal to the mean atomic number of the material. Wherever possible, the calculated values of Z eff are compared with experimental data.

Cost-effectiveness analysis of metformin+dipeptidyl peptidase-4 inhibitors compared to metformin+sulfonylureas for treatment of type 2 diabetes.

Science.gov (United States)

Kwon, Christina S; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa

2018-02-01

Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D. A Markov model was developed with four health states, 1 year cycle, and a 25-year time horizon. Clinical and cost data were collected from previous studies and other readily available secondary data sources. The incremental cost-effectiveness ratio (ICER) was estimated from the US third party payer perspective. Both, costs and outcomes, were discounted at a 3% annual discount rate. One way and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainty on the base-case results. The discounted incremental cost of metformin+DPP-4i compared to metformin+SU was $11,849 and the incremental life-years gained were 0.61, resulting in an ICER of $19,420 per life-year gained for patients in the metformin+DPP-4i treatment pathway. The ICER estimated in the probabilistic sensitivity analysis was $19,980 per life-year gained. Sensitivity analyses showed that the results of the study were not sensitive to changes in the parameters used in base-case. The metformin+DPP-4i treatment pathway was cost-effective compared to metformin+SU as a long-term second-line therapy in the treatment of T2D from the US health care payer perspective. Study findings have the potential to provide clinicians and third party payers valuable evidence for the prescription and utilization of cost-effective

Comparative Tuberculosis (TB) Prevention Effectiveness in Children of Bacillus Calmette-Guérin (BCG) Vaccines from Different Sources, Kazakhstan

Science.gov (United States)

Favorov, Michael; Ali, Mohammad; Tursunbayeva, Aigul; Aitmagambetova, Indira; Kilgore, Paul; Ismailov, Shakhimurat; Chorba, Terence

2012-01-01

Background Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. Methods/Findings We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Limitations Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. Conclusions/Significance All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by

Comparative tuberculosis (TB prevention effectiveness in children of Bacillus Calmette-Guérin (BCG vaccines from different sources, Kazakhstan.

Directory of Open Access Journals (Sweden)

Michael Favorov

Full Text Available BACKGROUND: Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. METHODS/FINDINGS: We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan, the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. LIMITATIONS: Potential limitations included considerations that 1 the methodology used was retrospective, 2 multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3 most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4 small variations in reported population TB burden could have affected relative risk of exposure for cohorts. CONCLUSIONS/SIGNIFICANCE: All three BCG vaccines evaluated were protective against TB, and prevention effectiveness

Comparative tuberculosis (TB) prevention effectiveness in children of Bacillus Calmette-Guérin (BCG) vaccines from different sources, Kazakhstan.

Science.gov (United States)

Favorov, Michael; Ali, Mohammad; Tursunbayeva, Aigul; Aitmagambetova, Indira; Kilgore, Paul; Ismailov, Shakhimurat; Chorba, Terence

2012-01-01

Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by manufacturer. When setting national immunization policy, consideration

A COMPARATIVE STUDY ON THE EFFECTIVENESS OF THE FILMSTRIP, SOUND FILMSTRIP, AND FILMOGRAPH FOR TEACHING FACTS AND CONCEPTS.

Science.gov (United States)

FINN, JAMES D.; MCBEATH, RONALD J.

THIS STUDY COMPARED THE RELATIVE EFFECTIVENESS IN FACTUAL LEARNING OF (1) A CAPTIONED FILMSTRIP, (2) A CAPTIONED FILMSTRIP WITH NARRATION, (3) A SOUND FILMSTRIP, AND (4) A FILMOGRAPH. (THE FILMOGRAPH WAS MADE BY PHOTOGRAPHING STILL PICTURES ON MOTION PICTURE FILM.) THE STUDY TESTED THE HYPOTHESIS THAT THE FILMOGRAPHY COULD TEACH MORE EFFECTIVELY.…

The effect of a forearm/hand splint compared with an elbow band as a treatment for lateral epicondylitis

NARCIS (Netherlands)

van de Streek, M.D.; van der Schans, C.P.; de Greef, M.H.G.; Postema, K.

2004-01-01

The aim of the present study was to compare the effect of a new prefabricated Thamert forearm/hand splint with the effect of a simple elbow band as a treatment for lateral epicondylitis. Forty-three (43) patients that met the inclusion criteria were randomly assigned to the elbow band group and the

Comparing the Effects of Negative and Mixed Emotional Messages on Predicted Occasional Excessive Drinking

OpenAIRE

Carrera, Pilar; Caballero, Amparo; Mu?oz, Dolores

2008-01-01

In this work we present two types of emotional message, negative (sadness) versus mixed (joy and sadness), with the aim of studying their differential effect on attitude change and the probability estimated by participants of repeating the behavior of occasional excessive drinking in the near future. The results show that for the group of participants with moderate experience in this behavior the negative message, compared to the mixed one, is associated with higher probability of repeating t...

Comparing the effects of negative and mixed emotional messages on predicted occasional excessive drinking

OpenAIRE

Carrera Levillain, Pilar; Caballero González, Amparo; Muñoz Cáceres, María Dolores

2008-01-01

In this work we present two types of emotional message, negative (sadness) versus mixed (joy and sadness), with the aim of studying their differential effect on attitude change and the probability estimated by participants of repeating the behavior of occasional excessive drinking in the near future. The results show that for the group of participants with moderate experience in this behavior the negative message, compared to the mixed one, is associated with higher probability of repeating t...

Comparative effectiveness of Calabadion and sugammadex to reverse non-depolarizing neuromuscular blocking agents

Science.gov (United States)

Haerter, Friederike; Simons, Jeroen Cedric Peter; Foerster, Urs; Duarte, Ingrid Moreno; Diaz-Gil, Daniel; Ganapati, Shweta; Eikermann-Haerter, Katharina; Ayata, Cenk; Zhang, Ben; Blobner, Manfred; Isaacs, Lyle; Eikermann, Matthias

2015-01-01

Background We evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular blocking agents (NMBAs) by binding and inactivation. Methods The dose-response relationship of drugs to reverse vecuronium, rocuronium, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n=34; phrenic nerve hemidiaphragm preparation) and in vivo (n=108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at steady-state deep NMB. In living rats, we studied the dose-response relationship of the test drugs to reverse deep block under physiological conditions and we measured the amount of calabadion 2 excreted in the urine. Results In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 109 M−1 and Ka = 3.8 × 107 M−1). Urine analysis (proton nuclear magnetic resonance), competition binding assays and ex vivo study results obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared to sugammadex. Calabadion 2 was eliminated renally, and did not affect blood pressure or heart rate. Conclusion Calabadion 2 reverses NMB-induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e. faster, than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats. PMID:26418697

Comparative cost-effectiveness of stereotactic body radiation therapy versus intensity-modulated and proton radiation therapy for localized prostate cancer.

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Anju eParthan

2012-08-01

Full Text Available Objective. To determine the cost-effectiveness of several external beam radiation treatment modalities for the treatment of patients with localized prostate cancer.Methods. A lifetime Markov model incorporated the probabilities of experiencing treatment-related long-term toxicity or death. Toxicity probabilities were derived from published sources using meta-analytical techniques. Utilities and costs in the model were obtained from publically available secondary sources. The model calculated quality-adjusted life expectancy and expected lifetime cost per patient, and derived ratios of incremental cost per quality-adjusted life year (QALY gained between treatments. Analyses were conducted from both a payer and societal perspectives. One-way and probabilistic sensitivity analyses were performed.Results. Compared to intensity modulated radiation therapy (IMRT and proton beam therapy (PT, stereotactic body radiation therapy (SBRT was less costly and resulted in more QALYs. Sensitivity analyses showed that the conclusions in the base-case scenario were robust with respect to variations in toxicity and cost parameters consistent with available evidence. At a threshold of $50,000/QALY, SBRT was cost effective in 75%, and 94% of probabilistic simulations compared to IMRT and PT, respectively, from a payer perspective. From a societal perspective, SBRT was cost-effective in 75%, and 96% of simulations compared to IMRT and PT, respectively, at a threshold of $50,000/QALY. In threshold analyses, SBRT was less expensive with better outcomes compared to IMRT at toxicity rates 23% greater than the SBRT base-case rates. Conclusions. Based on the assumption that each treatment modality results in equivalent long-term efficacy, SBRT is a cost-effective strategy resulting in improved quality-adjusted survival compared to IMRT and PT for the treatment of localized prostate cancer.

A comparative study of radioprotective effect of several antioxidants on human blood lymphocytes

International Nuclear Information System (INIS)

Wang Mingsuo; Zhu Gengbai; Gu Xuandi

1992-01-01

By means of improved fluorometric method with 2-thiobarbituric acid (TBA) as the fluorometric agent, radioprotective effects of four kinds of antioxidants on 60 Co γ-ray induced lipid peroxidation (LPO) level, i.e. Malondialdehyde (MDA) content changes in human blood lymphocytes were in human blood lymphocytes were compared by using relative protective efficiency (RPE) as an indicator. The LPO level in human lymphocytes which had been treated with an antioxidant at an concentration of 5 x 10 -3 g/L for 1 hr was measured 2 hr after exposure to 4 Gy of γ-rays, and the RPE values of antioxidants were calculated under these conditions: SOD, 38.23; VE, 23.75:VC, 19.32 and Se +4 , 18.27, thus the anticipation that the compounds, superoxide dismutase (SOD), 2-tocopherols (VE), ascorbic acid (VC) and Na 2 SeO 3 (Se +4 ) had radioprotective effects was confirmed. It was found that the radioprotective beneficial sequences of four kinds of antioxidants were arranged as SOD>VE>VC,Se +4 . The results show that radioprotective effects of exogenous antioxidants on radiation induced LPO damage are dependent not only on irradiation dosage, but also especially on property of antioxidants, drug concentration, pretreatment and monitoring time, etc. The mechanism of these antioxidants effecting as radioprotectants on human lymphocytes is discussed in connection with LPO damage and radioprotection

Decomposing the trade-environment nexus for Malaysia: what do the technique, scale, composition, and comparative advantage effect indicate?

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Ling, Chong Hui; Ahmed, Khalid; Binti Muhamad, Rusnah; Shahbaz, Muhammad

2015-12-01

This paper investigates the impact of trade openness on CO2 emissions using time series data over the period of 1970QI-2011QIV for Malaysia. We disintegrate the trade effect into scale, technique, composition, and comparative advantage effects to check the environmental consequence of trade at four different transition points. To achieve the purpose, we have employed augmented Dickey-Fuller (ADF) and Phillips-Perron (PP) unit root tests in order to examine the stationary properties of the variables. Later, the long-run association among the variables is examined by applying autoregressive distributed lag (ARDL) bounds testing approach to cointegration. Our results confirm the presence of cointegration. Further, we find that scale effect has positive and technique effect has negative impact on CO2 emissions after threshold income level and form inverted U-shaped relationship-hence validates the environmental Kuznets curve hypothesis. Energy consumption adds in CO2 emissions. Trade openness and composite effect improve environmental quality by lowering CO2 emissions. The comparative advantage effect increases CO2 emissions and impairs environmental quality. The results provide the innovative approach to see the impact of trade openness in four sub-dimensions of trade liberalization. Hence, this study attributes more comprehensive policy tool for trade economists to better design environmentally sustainable trade rules and agreements.

An Integrative data mining approach to identifying Adverse ...

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The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP

Investigating the Mechanisms of Action of Depside Salt from Salvia miltiorrhiza Using Bioinformatic Analysis

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Hua Li

2017-01-01

Full Text Available Salvia miltiorrhiza is a traditional Chinese medicinal herb used for treating cardiovascular diseases. Depside salt from S. miltiorrhiza (DSSM contains the following active components: magnesium lithospermate B, lithospermic acid, and rosmarinic acid. This study aimed to reveal the mechanisms of action of DSSM. After searching for DSSM-associated genes in GeneCards, Search Tool for Interacting Chemicals, SuperTarget, PubChem, and Comparative Toxicogenomics Database, they were subjected to enrichment analysis using Multifaceted Analysis Tool for Human Transcriptome. A protein-protein interaction (PPI network was visualised; module analysis was conducted using the Cytoscape software. Finally, a transcriptional regulatory network was constructed using the TRRUST database and Cytoscape. Seventy-three DSSM-associated genes were identified. JUN, TNF, NFKB1, and FOS were hub nodes in the PPI network. Modules 1 and 2 were identified from the PPI network, with pathway enrichment analysis, showing that the presence of NFKB1 and BCL2 in module 1 was indicative of a particular association with the NF-κB signalling pathway. JUN, TNF, NFKB1, FOS, and BCL2 exhibited notable interactions among themselves in the PPI network. Several regulatory relationships (such as JUN → TNF/FOS, FOS → NFKB1 and NFKB1 → BCL2/TNF were also found in the regulatory network. Thus, DSSM exerts effects against cardiovascular diseases by targeting JUN, TNF, NFKB1, FOS, and BCL2.

Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

International Nuclear Information System (INIS)

Rotoli, Bianca Maria; Bussolati, Ovidio; Costa, Anna Luisa; Blosi, Magda; Di Cristo, Luisana; Zanello, Pier Paolo; Bianchi, Massimiliano G.; Visigalli, Rossana; Bergamaschi, Enrico

2012-01-01

Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO 2 NPs (size range 4–33 nm), two preparations of CeO 2 NPs (9–36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15–240 μg/cm 2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm 2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm 2 , in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO 2 and CeO 2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured

Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

Science.gov (United States)

Rotoli, Bianca Maria; Bussolati, Ovidio; Costa, Anna Luisa; Blosi, Magda; Di Cristo, Luisana; Zanello, Pier Paolo; Bianchi, Massimiliano G.; Visigalli, Rossana; Bergamaschi, Enrico

2012-09-01

Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO2 NPs (size range 4-33 nm), two preparations of CeO2 NPs (9-36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15-240 μg/cm2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm2, in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO2 and CeO2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured nanomaterials.

Toxicogenomic markers for corticosteroid treatment in beef cattle: integrated analysis of transcriptomic data.

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Pegolo, Sara; Di Camillo, Barbara; Montesissa, Clara; Cannizzo, Francesca Tiziana; Biolatti, Bartolomeo; Bargelloni, Luca

2015-03-01

In the present work, an integrated analysis was performed on DNA-microarray data of bovine muscle samples belonging to controls, animals treated with various growth promoters (GPs) and unknown commercial samples. The aim was identify a robust gene expression signature of corticosteroid treatment for the classification of commercial samples, despite the effects of biological variation and other confounding factors. DNA-Microarray data from 5 different batches of bovine skeletal muscle samples were analyzed (146 samples). After preprocessing, expression data from animals treated with corticosteroids and controls from the different batches (89 samples) were used to train a Support Vector Machines (SVMs) classifier. The optimal number of gene probes chosen by our classification framework was 73. The SVMs with linear kernel built on these 73 biomarker genes was predicted to perform on novel samples with a high classification accuracy (Matthew's correlation coefficient equal to 0.77) and an average percentage of false positive and false negative equal to 5% and 6%, respectively. Concluding, a relatively small set of genes was able to discriminate between controls and corticosteroid-treated animals, despite different breeds, animal ages, and combination of GPs. The results are extremely promising, suggesting that integrated analysis provides robust transcriptomic signatures for GP abuse. Copyright © 2014 Elsevier Ltd. All rights reserved.

The cost-effectiveness of rotavirus vaccination: Comparative analyses for five European countries and transferability in Europe.

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Jit, Mark; Bilcke, Joke; Mangen, Marie-Josée J; Salo, Heini; Melliez, Hugues; Edmunds, W John; Yazdan, Yazdanpanah; Beutels, Philippe

2009-10-19

Cost-effectiveness analyses are usually not directly comparable between countries because of differences in analytical and modelling assumptions. We investigated the cost-effectiveness of rotavirus vaccination in five European Union countries (Belgium, England and Wales, Finland, France and the Netherlands) using a single model, burden of disease estimates supplied by national public health agencies and a subset of common assumptions. Under base case assumptions (vaccination with Rotarix, 3% discount rate, health care provider perspective, no herd immunity and quality of life of one caregiver affected by a rotavirus episode) and a cost-effectiveness threshold of euro30,000, vaccination is likely to be cost effective in Finland only. However, single changes to assumptions may make it cost effective in Belgium and the Netherlands. The estimated threshold price per dose for Rotarix (excluding administration costs) to be cost effective was euro41 in Belgium, euro28 in England and Wales, euro51 in Finland, euro36 in France and euro46 in the Netherlands.

Towards Building a Bridge between Community Engagement in Research (CEnR) and Comparative Effectiveness Research (CER).

Science.gov (United States)

Ahmed, Syed M; Nelson, David; Kissack, Anne; Franco, Zeno; Whittle, Jeff; Kotchen, Theodore; Meurer, John R; Morzinski, Jeffrey; Brandenburg, Terry

2015-04-01

A major national priority is establishing an effective infrastructure for translation of scientific discoveries into the community. Knowledge and practice continue to accelerate in health research yet healthcare recommendation adoption remains slow for practitioners, patients, and communities. Two areas of research placed in the later stages of the translational research spectrum, Community Engagement in Research and Comparative Effectiveness Research, are ideal for approaching this challenge collaboratively. The Clinical and Translational Science Institute of Southeastern Wisconsin convened academics and community-based organizations familiar with these fields of research in a 1-day workshop to establish an initial dialogue on similarities and differences with a goal of exploring ways to operationalize a collective effort. Participants represented four academic institutions and twelve other healthcare and community-based service organizations. Primary fields of study included community engaged research, comparative effectiveness research, psychology, clinical research, administration, nursing, public health, education, and other professionals. This initial report outlines the results of this diverse discussion and provides insights into the priorities, diverging issues, and areas for future examination and practice. Key discoveries reveal clear crosscutting issues, value in philosophical and provocative discussions among investigators, a need for practice and lessons learned, and bidirectional exchange with community representation. © 2014 Wiley Periodicals, Inc.

Comparative effects of vitamin K2 and vitamin E on experimental arteriosclerosis.

Science.gov (United States)

Seyama, Y; Hayashi, M; Takegami, H; Usami, E

1999-01-01

The comparative effects of vitamin K2 and vitamin E on aortic calcium (Ca) and inorganic phosphorus (P) levels in the aorta and the elastin fraction (fr.) were investigated in male rats after experimental arteriosclerosis was induced by vitamin D2 with atherogenic diet. Both vitamin K2 (100 mg/kg b.w.) and vitamin E (40 mg/kg b.w.) inhibited the increase of Ca and P in the aorta and the elastin fr. from the arteriosclerotic rats. Vitamin K2 (50 mg/kg b.w.) also suppressed the deposition of Ca and P in the aorta, but there was no change due to vitamin K3 or geranylgeraniol (side chain of vitamin K2) administration. Both vitamin K2 and vitamin E showed lipid radical scavenging activity in the in vitro experiment. However, neither vitamin K3 nor geranylgeraniol exhibited anti-arteriosclerotic or radical scavenging activity under the above experimental conditions. It is suggested that vitamin K2 and vitamin E promoted an antiarteriosclerotic effect by radical scavenging activity. These actions of vitamin K2 are required in the structure of 2-methylnaphtoquinone and its side chain (geranylgeraniol).

Comparative research on decommissioning disposal effect of two uranium mines at home and abroad

International Nuclear Information System (INIS)

Shi Yuke; Peng Daofeng; Liu Qingcheng

2014-01-01

Taking two typical decommissioned uranium mines at home and abroad for an example, disposal means and effects of two uranium mines were compared and analyzed in three aspects of waste dump disposal, mine sealing treatment, and wastewater disposal. The results showed that two uranium mines were basically identical in the disposal standards and disposal means, but the works in the source survey, wastewater disposal and long-term supervision done by oversea uranium mine were more detailed than domestic uranium mine. (authors)

Comparative effects of partial root-zone irrigation and deficit irrigation on phosphorus uptake in tomato plants

DEFF Research Database (Denmark)

Wang, Yaosheng; Liu, Fulai; Jensen, Christian Richardt

2012-01-01

The comparative effects of partial root-zone irrigation (PRI) and deficit irrigation (DI) on phosphorus (P) uptake in tomato (Lycopersicon esculentum Mill.) plants were investigated in a split-root pot experiment. The results showed that PRI treatment improved water-use efficiency (WUE) compared...... to the DI treatment. PRI-treated plants accumulated significantly higher amounts of P in their shoots than DI plants under organic maize straw N fertilisation, whereas similar levels of shoot P accumulation were observed under mineral N fertilisation. Thus, the form of N fertiliser, and thereby...... the different plant N status, affected the accumulation of P in shoots, as reflected by a higher plant N:P ratio following mineral N fertilisation than after organic N fertilisation. Compared to the DI treatment, PRI significantly increased both the physiological and agronomic efficiencies of P-use under...

The effectiveness and cost-effectiveness of intraoperative imaging in high-grade glioma resection; a comparative review of intraoperative ALA, fluorescein, ultrasound and MRI.

Science.gov (United States)

Eljamel, M Sam; Mahboob, Syed Osama

2016-12-01

Surgical resection of high-grade gliomas (HGG) is standard therapy because it imparts significant progression free (PFS) and overall survival (OS). However, HGG-tumor margins are indistinguishable from normal brain during surgery. Hence intraoperative technology such as fluorescence (ALA, fluorescein) and intraoperative ultrasound (IoUS) and MRI (IoMRI) has been deployed. This study compares the effectiveness and cost-effectiveness of these technologies. Critical literature review and meta-analyses, using MEDLINE/PubMed service. The list of references in each article was double-checked for any missing references. We included all studies that reported the use of ALA, fluorescein (FLCN), IoUS or IoMRI to guide HGG-surgery. The meta-analyses were conducted according to statistical heterogeneity between studies. If there was no heterogeneity, fixed effects model was used; otherwise, a random effects model was used. Statistical heterogeneity was explored by χ 2 and inconsistency (I 2 ) statistics. To assess cost-effectiveness, we calculated the incremental cost per quality-adjusted life-year (QALY). Gross total resection (GTR) after ALA, FLCN, IoUS and IoMRI was 69.1%, 84.4%, 73.4% and 70% respectively. The differences were not statistically significant. All four techniques led to significant prolongation of PFS and tended to prolong OS. However none of these technologies led to significant prolongation of OS compared to controls. The cost/QALY was $16,218, $3181, $6049 and $32,954 for ALA, FLCN, IoUS and IoMRI respectively. ALA, FLCN, IoUS and IoMRI significantly improve GTR and PFS of HGG. Their incremental cost was below the threshold for cost-effectiveness of HGG-therapy, denoting that each intraoperative technology was cost-effective on its own. Copyright © 2016 Elsevier B.V. All rights reserved.

Antiproliferative effects of an analog of curcumin in Hep-2 cells: a comparative study with curcumin.

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Kumaravel, Mohankumar; Sankar, Pajaniradje; Latha, Periyasamy; Benson, Chellakan S; Rukkumani, Rajagopalan

2013-02-01

Curcumin, the major active principle of Curcuma longa, is one of the promising, plant-derived, chemopreventive agents being studied for its anticarcinogenic and antioxidant properties. Hence, in our study, we aimed at testing the antiproliferative efficacy of an o-hydroxyl substituted analog of curcumin, bis demethoxy curcumin analog (BDMC-A), and comparing its efficacy with that of curcumin. BDMC-A was synthesised with a yield of 78% and 98% purity. Hep-2 cells and the MTT cell viability assay were used to examine cell proliferation. LDH assay and cell counts were performed to assess the cytotoxicity and anti-proliferative effects of the compound, respectively. Flow cytometry followed by Western blot were performed to investigate the cell cycle distribution. BDMC-A inhibited cell proliferation at a much lower concentration (IC50 20 microM) than curcumin (IC50 50 microM). Similar effects were observed in the LDH release and cell count assays. Flow cytometric studies using propidium iodide showed accumulation of cells in the G0/G1 phase and the arrest was further confirmed by immunoblotting of protein cyclin D1. BDMC-A was more potent in inhibiting the cells at a lower dose when compared with curcumin. Our results showed that the analog of curcumin is likely to possess more efficacy compared with curcumin in inhibiting cancer.

Comparing the happiness effects of real and on-line friends.

Directory of Open Access Journals (Sweden)

John F Helliwell

Full Text Available A recent large Canadian survey permits us to compare face-to-face ('real-life' and on-line social networks as sources of subjective well-being. The sample of 5,000 is drawn randomly from an on-line pool of respondents, a group well placed to have and value on-line friendships. We find three key results. First, the number of real-life friends is positively correlated with subjective well-being (SWB even after controlling for income, demographic variables and personality differences. Doubling the number of friends in real life has an equivalent effect on well-being as a 50% increase in income. Second, the size of online networks is largely uncorrelated with subjective well-being. Third, we find that real-life friends are much more important for people who are single, divorced, separated or widowed than they are for people who are married or living with a partner. Findings from large international surveys (the European Social Surveys 2002-2008 are used to confirm the importance of real-life social networks to SWB; they also indicate a significantly smaller value of social networks to married or partnered couples.

Ciclosporin compared with prednisolone therapy for patients with pyoderma gangrenosum: cost-effectiveness analysis of the STOP GAP trial.

Science.gov (United States)

Mason, J M; Thomas, K S; Ormerod, A D; Craig, F E; Mitchell, E; Norrie, J; Williams, H C

2017-12-01

Pyoderma gangrenosum (PG) is a painful, ulcerating skin disease with poor evidence for management. Prednisolone and ciclosporin are the most commonly used treatments, although not previously compared within a randomized controlled trial (RCT). To compare the cost-effectiveness of ciclosporin and prednisolone-initiated treatment for patients with PG. Quality of life (QoL, EuroQoL five dimensions three level questionnaire, EQ-5D-3L) and resource data were collected as part of the STOP GAP trial: a multicentre, parallel-group, observer-blind RCT. Within-trial analysis used bivariate regression of costs and quality-adjusted life years (QALYs), with multiple imputation of missing data, informing a probabilistic assessment of incremental treatment cost-effectiveness from a health service perspective. In the base case analysis, when compared with prednisolone, ciclosporin was cost-effective due to a reduction in costs [net cost: -£1160; 95% confidence interval (CI) -2991 to 672] and improvement in QoL (net QALYs: 0·055; 95% CI 0·018-0·093). However, this finding appears driven by a minority of patients with large lesions (≥ 20 cm 2 ) (net cost: -£5310; 95% CI -9729 to -891; net QALYs: 0·077; 95% CI 0·004-0·151). The incremental cost-effectiveness of ciclosporin for the majority of patients with smaller lesions was £23 374/QALY, although the estimate is imprecise: the probability of being cost-effective at a willingness-to-pay of £20 000/QALY was 43%. Consistent with the clinical findings of the STOP GAP trial, patients with small lesions should receive treatment guided by the side-effect profiles of the drugs and patient preference - neither strategy is clearly a preferred use of National Health Service resources. However, ciclosporin-initiated treatment may be more cost-effective for patients with large lesions. © 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Toxicogenomic response of Mycobacterium bovis BCG to peracetic acid and a comparative analysis of the M. bovis BCG response to three oxidative disinfectants.

Science.gov (United States)

Nde, Chantal W; Toghrol, Freshteh; Jang, Hyeung-Jin; Bentley, William E

2011-04-01

Tuberculosis is a leading cause of death worldwide and infects thousands of Americans annually. Mycobacterium bovis causes tuberculosis in humans and several animal species. Peracetic acid is an approved tuberculocide in hospital and domestic environments. This study presents for the first time the transcriptomic changes in M. bovis BCG after treatment with 0.1 mM peracetic acid for 10 and 20 min. This study also presents for the first time a comparison among the transcriptomic responses of M. bovis BCG to three oxidative disinfectants: peracetic acid, sodium hypochlorite, and hydrogen peroxide after 10 min of treatment. Results indicate that arginine biosynthesis, virulence, and oxidative stress response genes were upregulated after both peracetic acid treatment times. Three DNA repair genes were downregulated after 10 and 20 min and cell wall component genes were upregulated after 20 min. The devR-devS signal transduction system was upregulated after 10 min, suggesting a role in the protection against peracetic acid treatment. Results also suggest that peracetic acid and sodium hypochlorite both induce the expression of the ctpF gene which is upregulated in hypoxic environments. Further, this study reveals that in M. bovis BCG, hydrogen peroxide and peracetic acid both induce the expression of katG involved in oxidative stress response and the mbtD and mbtI genes involved in iron regulation/virulence.

SemFunSim: a new method for measuring disease similarity by integrating semantic and gene functional association.

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Liang Cheng

Full Text Available Measuring similarity between diseases plays an important role in disease-related molecular function research. Functional associations between disease-related genes and semantic associations between diseases are often used to identify pairs of similar diseases from different perspectives. Currently, it is still a challenge to exploit both of them to calculate disease similarity. Therefore, a new method (SemFunSim that integrates semantic and functional association is proposed to address the issue.SemFunSim is designed as follows. First of all, FunSim (Functional similarity is proposed to calculate disease similarity using disease-related gene sets in a weighted network of human gene function. Next, SemSim (Semantic Similarity is devised to calculate disease similarity using the relationship between two diseases from Disease Ontology. Finally, FunSim and SemSim are integrated to measure disease similarity.The high average AUC (area under the receiver operating characteristic curve (96.37% shows that SemFunSim achieves a high true positive rate and a low false positive rate. 79 of the top 100 pairs of similar diseases identified by SemFunSim are annotated in the Comparative Toxicogenomics Database (CTD as being targeted by the same therapeutic compounds, while other methods we compared could identify 35 or less such pairs among the top 100. Moreover, when using our method on diseases without annotated compounds in CTD, we could confirm many of our predicted candidate compounds from literature. This indicates that SemFunSim is an effective method for drug repositioning.

Toxicogenomic study in rat thymus of F1 generation offspring following maternal exposure to silver ion

Directory of Open Access Journals (Sweden)

Xiugong Gao

2015-01-01

Full Text Available Male and female rats (26-day-old were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc in drinking water for 10 weeks prior to and during mating. Sperm-positive females remained within their dose groups and were exposed to silver acetate during gestation and lactation. At postnatal day 26, the effect of silver ions on the developing F1 generation rat thymus was evaluated at the transcriptional level using whole-genome microarrays. Gene expression profiling analyses identified a dozen differentially expressed genes (DEGs in each dose group using a loose criterion of fold change (FC >1.5 and unadjusted p < 0.05, regardless of whether the analysis was conducted within each gender group or with both gender groups combined. No dose-dependent effect was observed on the number of DEGs. In addition, none of these genes had a false discovery rate (FDR <0.05 after correction for multiple testing. These results in combination with the observation that thymus-to-body-weight ratios were not affected and no histopathological abnormalities were identified indicate that in utero exposure to silver ions up to 26.0 mg/kg (equivalent to 40.0 mg/kg silver acetate did not have an adverse effect on the developing thymus.

Comparing treatment effects of oral THC on simulated and on-the-road driving performance: testing the validity of driving simulator drug research.

Science.gov (United States)

Veldstra, J L; Bosker, W M; de Waard, D; Ramaekers, J G; Brookhuis, K A

2015-08-01

The driving simulator provides a safe and controlled environment for testing driving behaviour efficiently. The question is whether it is sensitive to detect drug-induced effects. The primary aim of the current study was to investigate the sensitivity of the driving simulator for detecting drug effects. As a case in point, we investigated the dose-related effects of oral ∆(9)-tetrahydrocannabinol (THC), i.e. dronabinol, on simulator and on-the-road driving performance in equally demanding driving tasks. Twenty-four experienced driver participants were treated with dronabinol (Marinol®; 10 and 20 mg) and placebo. Dose-related effects of the drug on the ability to keep a vehicle in lane (weaving) and to follow the speed changes of a lead car (car following) were compared within subjects for on-the-road versus in-simulator driving. Additionally, the outcomes of equivalence testing to alcohol-induced effects were investigated. Treatment effects found on weaving when driving in the simulator were comparable to treatment effects found when driving on the road. The effect after 10 mg dronabinol was however less strong in the simulator than on the road and inter-individual variance seemed higher in the simulator. There was, however, a differential treatment effect of dronabinol on reactions to speed changes of a lead car (car following) when driving on the road versus when driving in the simulator. The driving simulator was proven to be sensitive for demonstrating dronabinol-induced effects particularly at higher doses. Treatment effects of dronabinol on weaving were comparable with driving on the road but inter-individual variability seemed higher in the simulator than on the road which may have potential effects on the clinical inferences made from simulator driving. Car following on the road and in the simulator were, however, not comparable.