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Sample records for statistically significant dose-response

  1. Statistical strategies for averaging EC50 from multiple dose-response experiments.

    Science.gov (United States)

    Jiang, Xiaoqi; Kopp-Schneider, Annette

    2015-11-01

    In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments. Two statistical strategies, the mixed-effect modeling and the meta-analysis approach, can be applied to estimate average behavior of EC50 values over all experiments by considering the variabilities within and among experiments. We investigated these two strategies in two common cases of multiple dose-response experiments in (a) complete and explicit dose-response relationships are observed in all experiments and in (b) only in a subset of experiments. In case (a), the meta-analysis strategy is a simple and robust method to average EC50 estimates. In case (b), all experimental data sets can be first screened using the dose-response screening plot, which allows visualization and comparison of multiple dose-response experimental results. As long as more than three experiments provide information about complete dose-response relationships, the experiments that cover incomplete relationships can be excluded from the meta-analysis strategy of averaging EC50 estimates. If there are only two experiments containing complete dose-response information, the mixed-effects model approach is suggested. We subsequently provided a web application for non-statisticians to implement the proposed meta-analysis strategy of averaging EC50 estimates from multiple dose-response experiments.

  2. Effects of measurement strategy and statistical analysis on dose-response relations between physical workload and low back pain

    NARCIS (Netherlands)

    J.J.P. Jansen (Justin); A. Burdorf (Alex)

    2003-01-01

    textabstractBACKGROUND: In epidemiological studies on physical workloads and back complaints, among the important features in modelling dose-response relations are the measurement strategy of the exposure and the nature of the dose-response relation that is assumed. AIM: To evaluat

  3. Statistically significant relational data mining :

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Jonathan W.; Leung, Vitus Joseph; Phillips, Cynthia Ann; Pinar, Ali; Robinson, David Gerald; Berger-Wolf, Tanya; Bhowmick, Sanjukta; Casleton, Emily; Kaiser, Mark; Nordman, Daniel J.; Wilson, Alyson G.

    2014-02-01

    This report summarizes the work performed under the project (3z(BStatitically significant relational data mining.(3y (BThe goal of the project was to add more statistical rigor to the fairly ad hoc area of data mining on graphs. Our goal was to develop better algorithms and better ways to evaluate algorithm quality. We concetrated on algorithms for community detection, approximate pattern matching, and graph similarity measures. Approximate pattern matching involves finding an instance of a relatively small pattern, expressed with tolerance, in a large graph of data observed with uncertainty. This report gathers the abstracts and references for the eight refereed publications that have appeared as part of this work. We then archive three pieces of research that have not yet been published. The first is theoretical and experimental evidence that a popular statistical measure for comparison of community assignments favors over-resolved communities over approximations to a ground truth. The second are statistically motivated methods for measuring the quality of an approximate match of a small pattern in a large graph. The third is a new probabilistic random graph model. Statisticians favor these models for graph analysis. The new local structure graph model overcomes some of the issues with popular models such as exponential random graph models and latent variable models.

  4. The thresholds for statistical and clinical significance

    DEFF Research Database (Denmark)

    Jakobsen, Janus Christian; Gluud, Christian; Winkel, Per;

    2014-01-01

    BACKGROUND: Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does...... not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore...... of the probability that a given trial result is compatible with a 'null' effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance...

  5. Statistical Significance vs. Practical Significance: An Exploration through Health Education

    Science.gov (United States)

    Rosen, Brittany L.; DeMaria, Andrea L.

    2012-01-01

    The purpose of this paper is to examine the differences between statistical and practical significance, including strengths and criticisms of both methods, as well as provide information surrounding the application of various effect sizes and confidence intervals within health education research. Provided are recommendations, explanations and…

  6. Dose-response analysis using R

    DEFF Research Database (Denmark)

    Ritz, Christian; Baty, Florent; Streibig, Jens Carl;

    2015-01-01

    Dose-response analysis can be carried out using multi-purpose commercial statistical software, but except for a few special cases the analysis easily becomes cumbersome as relevant, non-standard output requires manual programming. The extension package drc for the statistical environment R provides...

  7. Assessing statistical significance in causal graphs

    Directory of Open Access Journals (Sweden)

    Chindelevitch Leonid

    2012-02-01

    Full Text Available Abstract Background Causal graphs are an increasingly popular tool for the analysis of biological datasets. In particular, signed causal graphs--directed graphs whose edges additionally have a sign denoting upregulation or downregulation--can be used to model regulatory networks within a cell. Such models allow prediction of downstream effects of regulation of biological entities; conversely, they also enable inference of causative agents behind observed expression changes. However, due to their complex nature, signed causal graph models present special challenges with respect to assessing statistical significance. In this paper we frame and solve two fundamental computational problems that arise in practice when computing appropriate null distributions for hypothesis testing. Results First, we show how to compute a p-value for agreement between observed and model-predicted classifications of gene transcripts as upregulated, downregulated, or neither. Specifically, how likely are the classifications to agree to the same extent under the null distribution of the observed classification being randomized? This problem, which we call "Ternary Dot Product Distribution" owing to its mathematical form, can be viewed as a generalization of Fisher's exact test to ternary variables. We present two computationally efficient algorithms for computing the Ternary Dot Product Distribution and investigate its combinatorial structure analytically and numerically to establish computational complexity bounds. Second, we develop an algorithm for efficiently performing random sampling of causal graphs. This enables p-value computation under a different, equally important null distribution obtained by randomizing the graph topology but keeping fixed its basic structure: connectedness and the positive and negative in- and out-degrees of each vertex. We provide an algorithm for sampling a graph from this distribution uniformly at random. We also highlight theoretical

  8. Significant Statistics: Viewed with a Contextual Lens

    Science.gov (United States)

    Tait-McCutcheon, Sandi

    2010-01-01

    This paper examines the pedagogical and organisational changes three lead teachers made to their statistics teaching and learning programs. The lead teachers posed the research question: What would the effect of contextually integrating statistical investigations and literacies into other curriculum areas be on student achievement? By finding the…

  9. Dose response relationship and Alara

    International Nuclear Information System (INIS)

    In this paper, it will be shown how dose-response relationships allow to give quantitative figures for the detriment of irradiation. At this stage, the detriment is expressed directly as a certain number of health effects, whose valuation is not dealt with here. The present tools for quantifying, their weaknesses and their strenghts, and their scientific basis will be developed

  10. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2001-06-01

    In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2{+-}7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non

  11. A Statistical Significance Simulation Study for the General Scientist

    OpenAIRE

    Levman, Jacob

    2011-01-01

    When a scientist performs an experiment they normally acquire a set of measurements and are expected to demonstrate that their results are "statistically significant" thus confirming whatever hypothesis they are testing. The main method for establishing statistical significance involves demonstrating that there is a low probability that the observed experimental results were the product of random chance. This is typically defined as p < 0.05, which indicates there is less than a 5% chance tha...

  12. On use of the multistage dose-response model for assessing laboratory animal carcinogenicity

    OpenAIRE

    Nitcheva, Daniella; Piegorsch, Walter W.; West, R. Webster

    2007-01-01

    We explore how well a statistical multistage model describes dose-response patterns in laboratory animal carcinogenicity experiments from a large database of quantal response data. The data are collected from the U.S. EPA’s publicly available IRIS data warehouse and examined statistically to determine how often higher-order values in the multistage predictor yield significant improvements in explanatory power over lower-order values. Our results suggest that the addition of a second-order par...

  13. The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview

    International Nuclear Information System (INIS)

    A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying a broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings

  14. The questioned p value: clinical, practical and statistical significance.

    Science.gov (United States)

    Jiménez-Paneque, Rosa

    2016-01-01

    The use of p-value and statistical significance have been questioned since the early 80s in the last century until today. Much has been discussed about it in the field of statistics and its applications, especially in Epidemiology and Public Health. As a matter of fact, the p-value and its equivalent, statistical significance, are difficult concepts to grasp for the many health professionals some way involved in research applied to their work areas. However, its meaning should be clear in intuitive terms although it is based on theoretical concepts of the field of Statistics. This paper attempts to present the p-value as a concept that applies to everyday life and therefore intuitively simple but whose proper use cannot be separated from theoretical and methodological elements of inherent complexity. The reasons behind the criticism received by the p-value and its isolated use are intuitively explained, mainly the need to demarcate statistical significance from clinical significance and some of the recommended remedies for these problems are approached as well. It finally refers to the current trend to vindicate the p-value appealing to the convenience of its use in certain situations and the recent statement of the American Statistical Association in this regard. PMID:27636600

  15. Caveats for using statistical significance tests in research assessments

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg

    2013-01-01

    controversial and numerous criticisms have been leveled against their use. Based on examples from articles by proponents of the use statistical significance tests in research assessments, we address some of the numerous problems with such tests. The issues specifically discussed are the ritual practice of such...... tests, their dichotomous application in decision making, the difference between statistical and substantive significance, the implausibility of most null hypotheses, the crucial assumption of randomness, as well as the utility of standard errors and confidence intervals for inferential purposes. We...... argue that applying statistical significance tests and mechanically adhering to their results are highly problematic and detrimental to critical thinking. We claim that the use of such tests do not provide any advantages in relation to deciding whether differences between citation indicators are...

  16. Systematic reviews of anesthesiologic interventions reported as statistically significant

    DEFF Research Database (Denmark)

    Imberger, Georgina; Gluud, Christian; Boylan, John;

    2015-01-01

    be implemented by an anesthesiologist during the perioperative period. We randomly selected 50 meta-analyses that reported a statistically significant dichotomous outcome in their abstract. We applied TSA to these meta-analyses by using 2 main TSA approaches: relative risk reduction 20% and relative risk...... reduction consistent with the conventional 95% confidence limit closest to null. We calculated the power achieved by each included meta-analysis, by using each TSA approach, and we calculated the proportion that maintained statistical significance when allowing for sparse data and repeated updates. RESULTS...

  17. On detection and assessment of statistical significance of Genomic Islands

    Directory of Open Access Journals (Sweden)

    Chaudhuri Probal

    2008-04-01

    Full Text Available Abstract Background Many of the available methods for detecting Genomic Islands (GIs in prokaryotic genomes use markers such as transposons, proximal tRNAs, flanking repeats etc., or they use other supervised techniques requiring training datasets. Most of these methods are primarily based on the biases in GC content or codon and amino acid usage of the islands. However, these methods either do not use any formal statistical test of significance or use statistical tests for which the critical values and the P-values are not adequately justified. We propose a method, which is unsupervised in nature and uses Monte-Carlo statistical tests based on randomly selected segments of a chromosome. Such tests are supported by precise statistical distribution theory, and consequently, the resulting P-values are quite reliable for making the decision. Results Our algorithm (named Design-Island, an acronym for Detection of Statistically Significant Genomic Island runs in two phases. Some 'putative GIs' are identified in the first phase, and those are refined into smaller segments containing horizontally acquired genes in the refinement phase. This method is applied to Salmonella typhi CT18 genome leading to the discovery of several new pathogenicity, antibiotic resistance and metabolic islands that were missed by earlier methods. Many of these islands contain mobile genetic elements like phage-mediated genes, transposons, integrase and IS elements confirming their horizontal acquirement. Conclusion The proposed method is based on statistical tests supported by precise distribution theory and reliable P-values along with a technique for visualizing statistically significant islands. The performance of our method is better than many other well known methods in terms of their sensitivity and accuracy, and in terms of specificity, it is comparable to other methods.

  18. Skull base chordomas: analysis of dose-response characteristics

    International Nuclear Information System (INIS)

    Objective: To extract dose-response characteristics from dose-volume histograms and corresponding actuarial survival statistics for 115 patients with skull base chordomas. Materials and Methods: We analyzed data for 115 patients with skull base chordoma treated with combined photon and proton conformal radiotherapy to doses in the range 66.6Gy - 79.2Gy. Data set for each patient included gender, histology, age, tumor volume, prescribed dose, overall treatment time, time to recurrence or time to last observation, target dose-volume histogram, and several dosimetric parameters (minimum/mean/median/maximum target dose, percent of the target volume receiving the prescribed dose, dose to 90% of the target volume, and the Equivalent Uniform Dose (EUD). Data were analyzed using the Kaplan-Meier survivor function estimate, the proportional hazards (Cox) model, and parametric modeling of the actuarial probability of recurrence. Parameters of dose-response characteristics were obtained using the maximum likelihood method. Results: Local failure developed in 42 (36%) of patients, with actuarial local control rates at 5 years of 59.2%. The proportional hazards model revealed significant dependence of gender on the probability of recurrence, with female patients having significantly poorer prognosis (hazard ratio of 2.3 with the p value of 0.008). The Wilcoxon and the log-rank tests of the corresponding Kaplan-Meier recurrence-free survival curves confirmed statistical significance of this effect. The Cox model with stratification by gender showed significance of tumor volume (p=0.01), the minimum target dose (p=0.02), and the EUD (p=0.02). Other parameters were not significant at the α level of significance of 0.05, including the prescribed dose (p=0.21). Parametric analysis using a combined model of tumor control probability (to account for non-uniformity of target dose distribution) and the Weibull failure time model (to account for censoring) allowed us to estimate

  19. Common pitfalls in statistical analysis: "P" values, statistical significance and confidence intervals

    Directory of Open Access Journals (Sweden)

    Priya Ranganathan

    2015-01-01

    Full Text Available In the second part of a series on pitfalls in statistical analysis, we look at various ways in which a statistically significant study result can be expressed. We debunk some of the myths regarding the ′P′ value, explain the importance of ′confidence intervals′ and clarify the importance of including both values in a paper

  20. Dose-Response Calculator for ArcGIS

    Science.gov (United States)

    Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

    2011-01-01

    The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

  1. Curious cases: Altered dose-response relationships in addiction genetics.

    Science.gov (United States)

    Uhl, George R; Drgonova, Jana; Hall, F Scott

    2014-03-01

    Dose-response relationships for most addictive substances are "inverted U"-shaped. Addictive substances produce both positive features that include reward, euphoria, anxiolysis, withdrawal-relief, and negative features that include aversion, dysphoria, anxiety and withdrawal symptoms. A simple model differentially associates ascending and descending limbs of dose-response curves with rewarding and aversive influences, respectively. However, Diagnostic and Statistical Manual (DSM) diagnoses of substance dependence fail to incorporate dose-response criteria and don't directly consider balances between euphoric and dysphoric drug effects. Classical genetic studies document substantial heritable influences on DSM substance dependence. Linkage and genome-wide association studies identify modest-sized effects at any locus. Nevertheless, clusters of SNPs within selected genes display 10(-2)>p>10(-8) associations with dependence in many independent samples. For several of these genes, evidence for cis-regulatory, level-of-expression differences supports the validity of mouse models in which levels of expression are also altered. This review documents surprising, recently defined cases in which convergent evidence from humans and mouse models supports central influences of altered dose-response relationships in mediating the impact of relevant genomic variation on addiction phenotypes. For variation at loci for the α5 nicotinic acetylcholine receptor, cadherin 13, receptor type protein tyrosine phosphatase Δ and neuronal cell adhesion molecule genes, changed dose-response relationships conferred by gene knockouts in mice are accompanied by supporting human data. These observations emphasize desirability of carefully elucidating dose-response relationships for both rewarding and aversive features of abused substances wherever possible. They motivate consideration of individual differences in dose-response relationships in addiction nosology and therapeutics.

  2. Sibling Competition & Growth Tradeoffs. Biological vs. Statistical Significance

    Science.gov (United States)

    Kramer, Karen L.; Veile, Amanda; Otárola-Castillo, Erik

    2016-01-01

    Early childhood growth has many downstream effects on future health and reproduction and is an important measure of offspring quality. While a tradeoff between family size and child growth outcomes is theoretically predicted in high-fertility societies, empirical evidence is mixed. This is often attributed to phenotypic variation in parental condition. However, inconsistent study results may also arise because family size confounds the potentially differential effects that older and younger siblings can have on young children’s growth. Additionally, inconsistent results might reflect that the biological significance associated with different growth trajectories is poorly understood. This paper addresses these concerns by tracking children’s monthly gains in height and weight from weaning to age five in a high fertility Maya community. We predict that: 1) as an aggregate measure family size will not have a major impact on child growth during the post weaning period; 2) competition from young siblings will negatively impact child growth during the post weaning period; 3) however because of their economic value, older siblings will have a negligible effect on young children’s growth. Accounting for parental condition, we use linear mixed models to evaluate the effects that family size, younger and older siblings have on children’s growth. Congruent with our expectations, it is younger siblings who have the most detrimental effect on children’s growth. While we find statistical evidence of a quantity/quality tradeoff effect, the biological significance of these results is negligible in early childhood. Our findings help to resolve why quantity/quality studies have had inconsistent results by showing that sibling competition varies with sibling age composition, not just family size, and that biological significance is distinct from statistical significance. PMID:26938742

  3. Lexical Co-occurrence, Statistical Significance, and Word Association

    CERN Document Server

    Chaudhari, Dipak; Laxman, Srivatsan

    2010-01-01

    Lexical co-occurrence is an important cue for detecting word associations. We present a theoretical framework for discovering statistically significant lexical co-occurrences from a given corpus. In contrast with the prevalent practice of giving weightage to unigram frequencies, we focus only on the documents containing both the terms (of a candidate bigram). We detect biases in span distributions of associated words, while being agnostic to variations in global unigram frequencies. Our framework has the fidelity to distinguish different classes of lexical co-occurrences, based on strengths of the document and corpuslevel cues of co-occurrence in the data. We perform extensive experiments on benchmark data sets to study the performance of various co-occurrence measures that are currently known in literature. We find that a relatively obscure measure called Ochiai, and a newly introduced measure CSA capture the notion of lexical co-occurrence best, followed next by LLR, Dice, and TTest, while another popular m...

  4. A Tutorial on Hunting Statistical Significance by Chasing N

    Science.gov (United States)

    Szucs, Denes

    2016-01-01

    There is increasing concern about the replicability of studies in psychology and cognitive neuroscience. Hidden data dredging (also called p-hacking) is a major contributor to this crisis because it substantially increases Type I error resulting in a much larger proportion of false positive findings than the usually expected 5%. In order to build better intuition to avoid, detect and criticize some typical problems, here I systematically illustrate the large impact of some easy to implement and so, perhaps frequent data dredging techniques on boosting false positive findings. I illustrate several forms of two special cases of data dredging. First, researchers may violate the data collection stopping rules of null hypothesis significance testing by repeatedly checking for statistical significance with various numbers of participants. Second, researchers may group participants post hoc along potential but unplanned independent grouping variables. The first approach ‘hacks’ the number of participants in studies, the second approach ‘hacks’ the number of variables in the analysis. I demonstrate the high amount of false positive findings generated by these techniques with data from true null distributions. I also illustrate that it is extremely easy to introduce strong bias into data by very mild selection and re-testing. Similar, usually undocumented data dredging steps can easily lead to having 20–50%, or more false positives.

  5. Statistical significance of precisely repeated intracellular synaptic patterns.

    Directory of Open Access Journals (Sweden)

    Yuji Ikegaya

    Full Text Available Can neuronal networks produce patterns of activity with millisecond accuracy? It may seem unlikely, considering the probabilistic nature of synaptic transmission. However, some theories of brain function predict that such precision is feasible and can emerge from the non-linearity of the action potential generation in circuits of connected neurons. Several studies have presented evidence for and against this hypothesis. Our earlier work supported the precision hypothesis, based on results demonstrating that precise patterns of synaptic inputs could be found in intracellular recordings from neurons in brain slices and in vivo. To test this hypothesis, we devised a method for finding precise repeats of activity and compared repeats found in the data to those found in surrogate datasets made by shuffling the original data. Because more repeats were found in the original data than in the surrogate data sets, we argued that repeats were not due to chance occurrence. Mokeichev et al. (2007 challenged these conclusions, arguing that the generation of surrogate data was insufficiently rigorous. We have now reanalyzed our previous data with the methods introduced from Mokeichev et al. (2007. Our reanalysis reveals that repeats are statistically significant, thus supporting our earlier conclusions, while also supporting many conclusions that Mokeichev et al. (2007 drew from their recent in vivo recordings. Moreover, we also show that the conditions under which the membrane potential is recorded contributes significantly to the ability to detect repeats and may explain conflicting results. In conclusion, our reevaluation resolves the methodological contradictions between Ikegaya et al. (2004 and Mokeichev et al. (2007, but demonstrates the validity of our previous conclusion that spontaneous network activity is non-randomly organized.

  6. Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease

    Energy Technology Data Exchange (ETDEWEB)

    Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mabuchi, Kiyohiko [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States)

    2012-12-01

    Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  7. Dose/response relationships and policy formulation

    International Nuclear Information System (INIS)

    The ICRP 26 cost/benefit approach to establishing operational radiation protection guidelines is discussed. The purpose is to aid the policy maker in the decision making process, using as a basis the dose-response curve

  8. Perception and annoyance due to wind turbine noise-a dose-response relationship

    Science.gov (United States)

    Pedersen, Eja; Persson Waye, Kerstin

    2004-12-01

    Installed global wind power increased by 26% during 2003, with U.S and Europe accounting for 90% of the cumulative capacity. Little is known about wind turbines' impact on people living in their vicinity. The aims of this study were to evaluate the prevalence of annoyance due to wind turbine noise and to study dose-response relationships. Interrelationships between noise annoyance and sound characteristics, as well as the influence of subjective variables such as attitude and noise sensitivity, were also assessed. A cross-sectional study was performed in Sweden in 2000. Responses were obtained through questionnaires (n=351; response rate 68.4%), and doses were calculated as A-weighted sound pressure levels for each respondent. A statistically significant dose-response relationship was found, showing higher proportion of people reporting perception and annoyance than expected from the present dose-response relationships for transportation noise. The unexpected high proportion of annoyance could be due to visual interference, influencing noise annoyance, as well as the presence of intrusive sound characteristics. The respondents' attitude to the visual impact of wind turbines on the landscape scenery was found to influence noise annoyance. .

  9. Perception and annoyance due to wind turbine noise--a dose-response relationship.

    Science.gov (United States)

    Pedersen, Eja; Waye, Kerstin Persson

    2004-12-01

    Installed global wind power increased by 26% during 2003, with U.S and Europe accounting for 90% of the cumulative capacity. Little is known about wind turbines' impact on people living in their vicinity. The aims of this study were to evaluate the prevalence of annoyance due to wind turbine noise and to study dose-response relationships. Interrelationships between noise annoyance and sound characteristics, as well as the influence of subjective variables such as attitude and noise sensitivity, were also assessed. A cross-sectional study was performed in Sweden in 2000. Responses were obtained through questionnaires (n = 351; response rate 68.4%), and doses were calculated as A-weighted sound pressure levels for each respondent. A statistically significant dose-response relationship was found, showing higher proportion of people reporting perception and annoyance than expected from the present dose-response relationships for transportation noise. The unexpected high proportion of annoyance could be due to visual interference, influencing noise annoyance, as well as the presence of intrusive sound characteristics. The respondents' attitude to the visual impact of wind turbines on the landscape scenery was found to influence noise annoyance. PMID:15658697

  10. Bayesian multimodel inference for dose-response studies

    Science.gov (United States)

    Link, W.A.; Albers, P.H.

    2007-01-01

    Statistical inference in dose?response studies is model-based: The analyst posits a mathematical model of the relation between exposure and response, estimates parameters of the model, and reports conclusions conditional on the model. Such analyses rarely include any accounting for the uncertainties associated with model selection. The Bayesian inferential system provides a convenient framework for model selection and multimodel inference. In this paper we briefly describe the Bayesian paradigm and Bayesian multimodel inference. We then present a family of models for multinomial dose?response data and apply Bayesian multimodel inferential methods to the analysis of data on the reproductive success of American kestrels (Falco sparveriuss) exposed to various sublethal dietary concentrations of methylmercury.

  11. After statistics reform : Should we still teach significance testing?

    NARCIS (Netherlands)

    A. Hak (Tony)

    2014-01-01

    textabstractIn the longer term null hypothesis significance testing (NHST) will disappear because p- values are not informative and not replicable. Should we continue to teach in the future the procedures of then abolished routines (i.e., NHST)? Three arguments are discussed for not teaching NHST in

  12. Changing Statistical Significance with the Amount of Information: The Adaptive α Significance Level.

    Science.gov (United States)

    Pérez, María-Eglée; Pericchi, Luis Raúl

    2014-02-01

    We put forward an adaptive alpha which changes with the amount of sample information. This calibration may be interpreted as a Bayes/non-Bayes compromise, and leads to statistical consistency. The calibration can also be used to produce confidence intervals whose size take in consideration the amount of observed information.

  13. Changing Statistical Significance with the Amount of Information: The Adaptive α Significance Level☆

    Science.gov (United States)

    Pérez, María-Eglée; Pericchi, Luis Raúl

    2014-01-01

    We put forward an adaptive alpha which changes with the amount of sample information. This calibration may be interpreted as a Bayes/non-Bayes compromise, and leads to statistical consistency. The calibration can also be used to produce confidence intervals whose size take in consideration the amount of observed information. PMID:24511173

  14. Modeling of dose-response relationships.

    OpenAIRE

    Altshuler, B

    1981-01-01

    The main dose-response models for chronic toxicity are considered. For dichotomous response, the log probit, multi-hit, and multistage models are presented. For time-to-occurrence response, the log-normal and three variations of multistage models are presented. Finally, the Cornfield hockey-stick model is considered, and, for low-dose extrapolation, it is suggested that response be taken to be proportional to dose and to a power of time determined by background response.

  15. Early radiation dose-response in lung: an ultrastructural study

    International Nuclear Information System (INIS)

    A systematic fine-structural study of dog lungs was undertaken to ascertain the radiation dose response in the lungs of large animals. The capillary endothelium appeared to be the initial site of the post-irradiation pulmonary damage. This subpheural response included diffuse septal thickening, fibrosis, edema, and reduced alveolar lumina. The deep parenchymal response involved perivascular fibrosis, which was associated with perivascular hyperplasia of Type II pneumocytes, increased number and sizes of lamellar bodies, increased production and release of lamellar surfactant. No changes of alveolar luminar size were noted. The most significant changes were observed in those dose zones exposed to greater than 2400 rad, suggesting the possibility of an identifiable dose-response relationship. Early detection of radiation pneumonitis by electron microscopy is demonstrated, and qualitative and quantitative correlation of injury with both postirradiation time and dose is presented

  16. Understanding the Sampling Distribution and Its Use in Testing Statistical Significance.

    Science.gov (United States)

    Breunig, Nancy A.

    Despite the increasing criticism of statistical significance testing by researchers, particularly in the publication of the 1994 American Psychological Association's style manual, statistical significance test results are still popular in journal articles. For this reason, it remains important to understand the logic of inferential statistics. A…

  17. Toward a unified approach to dose-response modeling in ecotoxicology.

    Science.gov (United States)

    Ritz, Christian

    2010-01-01

    This study reviews dose-response models that are used in ecotoxicology. The focus lies on clarification of differences and similarities between models, and as a side effect, their different guises in ecotoxicology are unravelled. A look at frequently used dose-response models reveals major discrepancies, among other things in naming conventions. Therefore, there is a need for a unified view on dose-response modeling in order to improve the understanding of it and to facilitate communication and comparison of findings across studies, thus realizing its full potential. This study attempts to establish a general framework that encompasses most dose-response models that are of interest to ecotoxicologists in practice. The framework includes commonly used models such as the log-logistic and Weibull models, but also features entire suites of models as found in various guidance documents. An outline on how the proposed framework can be implemented in statistical software systems is also provided.

  18. "What If" Analyses: Ways to Interpret Statistical Significance Test Results Using EXCEL or "R"

    Science.gov (United States)

    Ozturk, Elif

    2012-01-01

    The present paper aims to review two motivations to conduct "what if" analyses using Excel and "R" to understand the statistical significance tests through the sample size context. "What if" analyses can be used to teach students what statistical significance tests really do and in applied research either prospectively to estimate what sample size…

  19. Confidence bounds for nonlinear dose-response relationships

    DEFF Research Database (Denmark)

    Baayen, C; Hougaard, P

    2015-01-01

    test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence......An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve...

  20. Quantitative Dose-Response Curves from Subcellular Lipid Multilayer Microarrays

    Science.gov (United States)

    Kusi-Appiah, A. E.; Lowry, T. W.; Darrow, E. M.; Wilson, K.; Chadwick, B. P.; Davidson, M. W.; Lenhert, S.

    2015-01-01

    The dose-dependent bioactivity of small molecules on cells is a crucial factor in drug discovery and personalized medicine. Although small-molecule microarrays are a promising platform for miniaturized screening, it has been a challenge to use them to obtain quantitative dose-response curves in vitro, especially for lipophilic compounds. Here we establish a small-molecule microarray assay capable of controlling the dosage of small lipophilic molecules delivered to cells by varying the sub-cellular volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. Features with sub-cellular lateral dimensions were found necessary to obtain normal cell adhesion with HeLa cells. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. We used the surface supported lipid volume information to obtain EC-50 values for the response of HeLa cells to three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. No significant toxicity was observed on the control cells surrounding the drug/lipid patterns, indicating lack of interference or leakage from the arrays. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which we explain in terms of cell-adhesion playing a more important role in the surface-based assay. The assay should be scalable to a density of at least 10,000 dose response curves on the area of a standard microtiter plate. PMID:26167949

  1. A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

    Energy Technology Data Exchange (ETDEWEB)

    Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States)

    2013-02-01

    Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  2. Statistical vs. Economic Significance in Economics and Econometrics: Further comments on McCloskey & Ziliak

    DEFF Research Database (Denmark)

    Engsted, Tom

    be eliminated through specification testing, they fail to acknowledge those areas in economics, e.g. rational expectations macroeconomics and asset pricing, where researchers clearly distinguish between statistical and economic significance and where statistical testing plays a relatively minor role in model...... reliable estimates, and I argue that significance tests are useful tools in those cases where a statistical model serves as input in the quantification of an economic model. Finally, I provide a specific example from economics - asset return predictability - where the distinction between statistical......I comment on the controversy between McCloskey & Ziliak and Hoover & Siegler on statistical versus economic significance, in the March 2008 issue of the Journal of Economic Methodology. I argue that while McCloskey & Ziliak are right in emphasizing 'real error', i.e. non-sampling error that cannot...

  3. Measuring individual significant change on the Beck Depression Inventory-II through IRT-based statistics

    NARCIS (Netherlands)

    Brouwer, Danny; Meijer, Rob; Zevalkink, J.

    2013-01-01

    Several researchers have emphasized that item response theory (IRT)-based methods should be preferred over classical approaches in measuring change for individual patients. In the present study we discuss and evaluate the use of IRT-based statistics to measure statistical significant individual chan

  4. Bayesian Dose-Response Modeling in Sparse Data

    Science.gov (United States)

    Kim, Steven B.

    This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a

  5. Using the Bootstrap Method for a Statistical Significance Test of Differences between Summary Histograms

    Science.gov (United States)

    Xu, Kuan-Man

    2006-01-01

    A new method is proposed to compare statistical differences between summary histograms, which are the histograms summed over a large ensemble of individual histograms. It consists of choosing a distance statistic for measuring the difference between summary histograms and using a bootstrap procedure to calculate the statistical significance level. Bootstrapping is an approach to statistical inference that makes few assumptions about the underlying probability distribution that describes the data. Three distance statistics are compared in this study. They are the Euclidean distance, the Jeffries-Matusita distance and the Kuiper distance. The data used in testing the bootstrap method are satellite measurements of cloud systems called cloud objects. Each cloud object is defined as a contiguous region/patch composed of individual footprints or fields of view. A histogram of measured values over footprints is generated for each parameter of each cloud object and then summary histograms are accumulated over all individual histograms in a given cloud-object size category. The results of statistical hypothesis tests using all three distances as test statistics are generally similar, indicating the validity of the proposed method. The Euclidean distance is determined to be most suitable after comparing the statistical tests of several parameters with distinct probability distributions among three cloud-object size categories. Impacts on the statistical significance levels resulting from differences in the total lengths of satellite footprint data between two size categories are also discussed.

  6. Accelerating pairwise statistical significance estimation for local alignment by harvesting GPU's power

    OpenAIRE

    Zhang, Yuhong; Misra, Sanchit; Agrawal, Ankit; Patwary, Md Mostofa Ali; Liao, Wei-keng; Qin, Zhiguang; Choudhary, Alok

    2012-01-01

    Background Pairwise statistical significance has been recognized to be able to accurately identify related sequences, which is a very important cornerstone procedure in numerous bioinformatics applications. However, it is both computationally and data intensive, which poses a big challenge in terms of performance and scalability. Results We present a GPU implementation to accelerate pairwise statistical significance estimation of local sequence alignment using standard substitution matrices. ...

  7. Confidence bounds for nonlinear dose-response relationships.

    Science.gov (United States)

    Baayen, C; Hougaard, P

    2015-11-30

    An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve. It is well known that Wald confidence intervals are based on linear approximations and are often unsatisfactory in nonlinear models. Apart from incorrect coverage rates, they can be unreasonable in the sense that the lower confidence limit of the difference to placebo can be negative, even when an overall test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated using a public dataset and simulations based on the Emax and sigmoid Emax models. PMID:26112765

  8. Statistical significance of task related deep brain EEG dynamic changes in the time-frequency domain.

    Science.gov (United States)

    Chládek, J; Brázdil, M; Halámek, J; Plešinger, F; Jurák, P

    2013-01-01

    We present an off-line analysis procedure for exploring brain activity recorded from intra-cerebral electroencephalographic data (SEEG). The objective is to determine the statistical differences between different types of stimulations in the time-frequency domain. The procedure is based on computing relative signal power change and subsequent statistical analysis. An example of characteristic statistically significant event-related de/synchronization (ERD/ERS) detected across different frequency bands following different oddball stimuli is presented. The method is used for off-line functional classification of different brain areas. PMID:24109865

  9. Codon Deviation Coefficient: a novel measure for estimating codon usage bias and its statistical significance

    Directory of Open Access Journals (Sweden)

    Zhang Zhang

    2012-03-01

    Full Text Available Abstract Background Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB. Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis. Results Here we propose a novel measure--Codon Deviation Coefficient (CDC--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance. Conclusions As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions.

  10. Codon Deviation Coefficient: A novel measure for estimating codon usage bias and its statistical significance

    KAUST Repository

    Zhang, Zhang

    2012-03-22

    Background: Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis.Results: Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance.Conclusions: As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions. 2012 Zhang et al; licensee BioMed Central Ltd.

  11. Confidence intervals permit, but don't guarantee, better inference than statistical significance testing

    Directory of Open Access Journals (Sweden)

    Melissa Coulson

    2010-07-01

    Full Text Available A statistically significant result, and a non-significant result may differ little, although significance status may tempt an interpretation of difference. Two studies are reported that compared interpretation of such results presented using null hypothesis significance testing (NHST, or confidence intervals (CIs. Authors of articles published in psychology, behavioural neuroscience, and medical journals were asked, via email, to interpret two fictitious studies that found similar results, one statistically significant, and the other non-significant. Responses from 330 authors varied greatly, but interpretation was generally poor, whether results were presented as CIs or using NHST. However, when interpreting CIs respondents who mentioned NHST were 60% likely to conclude, unjustifiably, the two results conflicted, whereas those who interpreted CIs without reference to NHST were 95% likely to conclude, justifiably, the two results were consistent. Findings were generally similar for all three disciplines. An email survey of academic psychologists confirmed that CIs elicit better interpretations if NHST is not invoked. Improved statistical inference can result from encouragement of meta-analytic thinking and use of CIs but, for full benefit, such highly desirable statistical reform requires also that researchers interpret CIs without recourse to NHST.

  12. Alcohol and cirrhosis: dose--response or threshold effect?

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Grønbaek, Morten; Tolstrup, Janne;

    2004-01-01

    BACKGROUND/AIMS: General population studies have shown a strong association between alcohol intake and death from alcoholic cirrhosis, but whether this is a dose-response or a threshold effect remains unknown, and the relation among alcohol misusers has not been studied. METHODS: A cohort of 6152...... alcohol misusing men and women aged 15-83 were interviewed about drinking pattern and social issues and followed for 84,257 person-years. Outcome was alcoholic cirrhosis mortality. Data was analyzed by means of Cox-regression models. RESULTS: In this large prospective cohort study of alcohol misusers...... there was a 27 fold increased mortality from alcoholic cirrhosis in men and a 35 fold increased mortality from alcoholic cirrhosis in women compared to the Danish population. Number of drinks per day was not significantly associated with death from alcoholic cirrhosis, since there was no additional risk of death...

  13. Does Statistical Significance Help to Evaluate Predictive Performance of Competing Models?

    Directory of Open Access Journals (Sweden)

    Levent Bulut

    2016-04-01

    Full Text Available In Monte Carlo experiment with simulated data, we show that as a point forecast criterion, the Clark and West's (2006 unconditional test of mean squared prediction errors does not reflect the relative performance of a superior model over a relatively weaker one. The simulation results show that even though the mean squared prediction errors of a constructed superior model is far below a weaker alternative, the Clark- West test does not reflect this in their test statistics. Therefore, studies that use this statistic in testing the predictive accuracy of alternative exchange rate models, stock return predictability, inflation forecasting, and unemployment forecasting should not weight too much on the magnitude of the statistically significant Clark-West tests statistics.

  14. EasyGene – a prokaryotic gene finder that ranks ORFs by statistical significance

    Directory of Open Access Journals (Sweden)

    Larsen Thomas

    2003-06-01

    Full Text Available Abstract Background Contrary to other areas of sequence analysis, a measure of statistical significance of a putative gene has not been devised to help in discriminating real genes from the masses of random Open Reading Frames (ORFs in prokaryotic genomes. Therefore, many genomes have too many short ORFs annotated as genes. Results In this paper, we present a new automated gene-finding method, EasyGene, which estimates the statistical significance of a predicted gene. The gene finder is based on a hidden Markov model (HMM that is automatically estimated for a new genome. Using extensions of similarities in Swiss-Prot, a high quality training set of genes is automatically extracted from the genome and used to estimate the HMM. Putative genes are then scored with the HMM, and based on score and length of an ORF, the statistical significance is calculated. The measure of statistical significance for an ORF is the expected number of ORFs in one megabase of random sequence at the same significance level or better, where the random sequence has the same statistics as the genome in the sense of a third order Markov chain. Conclusions The result is a flexible gene finder whose overall performance matches or exceeds other methods. The entire pipeline of computer processing from the raw input of a genome or set of contigs to a list of putative genes with significance is automated, making it easy to apply EasyGene to newly sequenced organisms. EasyGene with pre-trained models can be accessed at http://www.cbs.dtu.dk/services/EasyGene.

  15. Biological dosimetry in radiological protection: dose response curves elaboration for 60Co and 137Cs

    International Nuclear Information System (INIS)

    Ionizing radiation sources for pacific uses are being extensively utilized by modern society and the applications of these sources have raised the probability of the occurrence of accidents. The accidental exposition to radiation creates a necessity of the development of methods to evaluate dose quantity. This data could be obtained by the measurement of damage caused by radiation in the exposed person. The radiation dose can be estimated in exposed persons through physical methods (physical dosimetry) but the biological methods can't be dispensed, and among them, the cytogenetic one that makes use of chromosome aberrations (dicentric and centric ring) formed in peripheral blood lymphocytes (PBL) exposed to ionizing radiation. This method correlates the frequency of radioinduced aberrations with the estimated absorbed dose, as in vitro as in vivo, which is called cytogenetic dosimetry. By the introduction of improved new techniques in culture, in the interpretation of aberrations in the different analysers of slides and by the adoption of different statistical programs to analyse the data, significant differences are observed among laboratories in dose-response curves (calibration curves). The estimation of absorbed dose utilizing other laboratory calibration curves may introduce some uncertainties, so the International Atomic Energy Agency (IAEA) advises that each laboratory elaborates your own dose-response curve for cytogenetic dosimetry. The results were obtained from peripheral blood lymphocytes of the healthy and no-smoking donors exposed to 60Co and 137Cs radiation, with dose rate of 5 cGy.min.-1. Six points of dose were determined 20,50,100,200,300,400 cGy and the control not irradiated. The analysed aberrations were of chromosomic type, dicentric and centric ring. The dose response curve for dicentrics were obtained by frequencies weighted in liner-quadratic mathematic model and the equation resulted were for 60Co: Y = (3 46 +- 2.14)10-4 cGy-1 + (3.45 +- 0

  16. Statistical significance of trends in monthly heavy precipitation over the US

    KAUST Repository

    Mahajan, Salil

    2011-05-11

    Trends in monthly heavy precipitation, defined by a return period of one year, are assessed for statistical significance in observations and Global Climate Model (GCM) simulations over the contiguous United States using Monte Carlo non-parametric and parametric bootstrapping techniques. The results from the two Monte Carlo approaches are found to be similar to each other, and also to the traditional non-parametric Kendall\\'s τ test, implying the robustness of the approach. Two different observational data-sets are employed to test for trends in monthly heavy precipitation and are found to exhibit consistent results. Both data-sets demonstrate upward trends, one of which is found to be statistically significant at the 95% confidence level. Upward trends similar to observations are observed in some climate model simulations of the twentieth century, but their statistical significance is marginal. For projections of the twenty-first century, a statistically significant upwards trend is observed in most of the climate models analyzed. The change in the simulated precipitation variance appears to be more important in the twenty-first century projections than changes in the mean precipitation. Stochastic fluctuations of the climate-system are found to be dominate monthly heavy precipitation as some GCM simulations show a downwards trend even in the twenty-first century projections when the greenhouse gas forcings are strong. © 2011 Springer-Verlag.

  17. EasyGene – a prokaryotic gene finder that ranks ORFs by statistical significance

    DEFF Research Database (Denmark)

    Larsen, Thomas Schou; Krogh, Anders Stærmose

    2003-01-01

    annotated as genes.Results: In this paper, we present a new automated gene-finding method, EasyGene, which estimates the statistical significance of a predicted gene. The gene finder is based on a hidden Markov model (HMM) that is automatically estimated for a new genome. Using extensions of similarities...

  18. Using the Descriptive Bootstrap to Evaluate Result Replicability (Because Statistical Significance Doesn't)

    Science.gov (United States)

    Spinella, Sarah

    2011-01-01

    As result replicability is essential to science and difficult to achieve through external replicability, the present paper notes the insufficiency of null hypothesis statistical significance testing (NHSST) and explains the bootstrap as a plausible alternative, with a heuristic example to illustrate the bootstrap method. The bootstrap relies on…

  19. Interpreting Statistical Significance Test Results: A Proposed New "What If" Method.

    Science.gov (United States)

    Kieffer, Kevin M.; Thompson, Bruce

    As the 1994 publication manual of the American Psychological Association emphasized, "p" values are affected by sample size. As a result, it can be helpful to interpret the results of statistical significant tests in a sample size context by conducting so-called "what if" analyses. However, these methods can be inaccurate unless "corrected" effect…

  20. Recent Literature on Whether Statistical Significance Tests Should or Should Not Be Banned.

    Science.gov (United States)

    Deegear, James

    This paper summarizes the literature regarding statistical significant testing with an emphasis on recent literature in various discipline and literature exploring why researchers have demonstrably failed to be influenced by the American Psychological Association publication manual's encouragement to report effect sizes. Also considered are…

  1. Statistical significance for hierarchical clustering in genetic association and microarray expression studies

    Directory of Open Access Journals (Sweden)

    Yang Yaning

    2003-12-01

    Full Text Available Abstract Background With the increasing amount of data generated in molecular genetics laboratories, it is often difficult to make sense of results because of the vast number of different outcomes or variables studied. Examples include expression levels for large numbers of genes and haplotypes at large numbers of loci. It is then natural to group observations into smaller numbers of classes that allow for an easier overview and interpretation of the data. This grouping is often carried out in multiple steps with the aid of hierarchical cluster analysis, each step leading to a smaller number of classes by combining similar observations or classes. At each step, either implicitly or explicitly, researchers tend to interpret results and eventually focus on that set of classes providing the "best" (most significant result. While this approach makes sense, the overall statistical significance of the experiment must include the clustering process, which modifies the grouping structure of the data and often removes variation. Results For hierarchically clustered data, we propose considering the strongest result or, equivalently, the smallest p-value as the experiment-wise statistic of interest and evaluating its significance level for a global assessment of statistical significance. We apply our approach to datasets from haplotype association and microarray expression studies where hierarchical clustering has been used. Conclusion In all of the cases we examine, we find that relying on one set of classes in the course of clustering leads to significance levels that are too small when compared with the significance level associated with an overall statistic that incorporates the process of clustering. In other words, relying on one step of clustering may furnish a formally significant result while the overall experiment is not significant.

  2. Historical blunders: how toxicology got the dose-response relationship half right.

    Science.gov (United States)

    Calabrese, E J

    2005-12-14

    Substantial evidence indicates that reliable examples of hormetic dose responses in the toxicological literature are common and generalizable across biological model, endpoint measured and chemical class. Further evaluation revealed that the hormetic dose response model is more common than the threshold dose response model in objective, head-to-head comparisons. Nonetheless, the field of toxicology made a profound error by rejecting the use of the hormetic dose response model in its teaching, research, risk assessment and regulatory activities over nearly the past century. This paper argues that the hormetic dose response model (formerly called the Arndt-Schulz Law) was rejected principally because of its close historical association with the medical practice of homeopathy as a result of the prolonged and bitter feud between traditional medicine and homeopathy. Opponents of the concept of hormesis, making use of strong appeals to authority, were successful in their misrepresentation of the scientific foundations of hormesis and in their unfair association of it with segments of the homeopathic movement with extreme and discreditable views. These misrepresentations became established and integrated within the pharmacology and toxicology communities as a result of their origins in and continuities with traditional medicine and subsequently profoundly impacted a broad range of governmental risk assessment activities further consolidating the rejection of hormesis. This error of judgment was reinforced by toxicological hazard assessment methods using only high and few doses that were unable to assess hormetic responses, statistical modeling processes that were constrained to deny the possibility of hormetic dose response relationships and by the modest nature of the hormetic stimulatory response itself, which required more rigorous study designs to evaluate possible hormetic responses.

  3. A critical discussion of null hypothesis significance testing and statistical power analysis within psychological research

    DEFF Research Database (Denmark)

    Jones, Allan; Sommerlund, Bo

    2007-01-01

    The uses of null hypothesis significance testing (NHST) and statistical power analysis within psychological research are critically discussed. The article looks at the problems of relying solely on NHST when dealing with small and large sample sizes. The use of power-analysis in estimating...... the potential error introduced by small and large samples is advocated. Power analysis is not recommended as a replacement to NHST but as an additional source of information about the phenomena under investigation. Moreover, the importance of conceptual analysis in relation to statistical analysis of hypothesis...

  4. Cognitive Constructivism and the Epistemic Significance of Sharp Statistical Hypotheses in Natural Sciences

    CERN Document Server

    Stern, J M

    2010-01-01

    This book presents our case in defense of a constructivist epistemological framework and the use of compatible statistical theory and inference tools. The basic metaphor of decision theory is the maximization of a gambler's expected fortune, according to his own subjective utility, prior beliefs an learned experiences. This metaphor has proven to be very useful, leading the development of Bayesian statistics since its XX-th century revival, rooted on the work of de Finetti, Savage and others. The basic metaphor presented in this text, as a foundation for cognitive constructivism, is that of an eigen-solution, and the verification of its objective epistemic status. The FBST - Full Bayesian Significance Test - is the cornerstone of a set of statistical tolls conceived to assess the epistemic value of such eigen-solutions, according to their four essential attributes, namely, sharpness, stability, separability and composability. We believe that this alternative perspective, complementary to the one ofered by dec...

  5. The orthopaedic trauma literature: an evaluation of statistically significant findings in orthopaedic trauma randomized trials

    Directory of Open Access Journals (Sweden)

    Tornetta Paul

    2008-01-01

    Full Text Available Abstract Background Evidence-based medicine posits that health care research is founded upon clinically important differences in patient centered outcomes. Statistically significant differences between two treatments may not necessarily reflect a clinically important difference. We aimed to quantify the sample sizes and magnitude of treatment effects in a review of orthopaedic randomized trials with statistically significant findings. Methods We conducted a comprehensive search (PubMed, Cochrane for all randomized controlled trials between 1/1/95 to 12/31/04. Eligible studies include those that focused upon orthopaedic trauma. Baseline characteristics and treatment effects were abstracted by two reviewers. Briefly, for continuous outcome measures (ie functional scores, we calculated effect sizes (mean difference/standard deviation. Dichotomous variables (ie infection, nonunion were summarized as absolute risk differences and relative risk reductions (RRR. Effect sizes >0.80 and RRRs>50% were defined as large effects. Using regression analysis we examined the association between the total number of outcome events and treatment effect (dichotomous outcomes. Results Our search yielded 433 randomized controlled trials (RCTs, of which 76 RCTs with statistically significant findings on 184 outcomes (122 continuous/62 dichotomous outcomes met study eligibility criteria. The mean effect size across studies with continuous outcome variables was 1.7 (95% confidence interval: 1.43–1.97. For dichotomous outcomes, the mean risk difference was 30% (95%confidence interval:24%–36% and the mean relative risk reduction was 61% (95% confidence interval: 55%–66%; range: 0%–97%. Fewer numbers of total outcome events in studies was strongly correlated with increasing magnitude of the treatment effect (Pearson's R = -0.70, p Conclusion Our review suggests that statistically significant results in orthopaedic trials have the following implications-1 On average

  6. The null hypothesis significance test in health sciences research (1995-2006): statistical analysis and interpretation

    OpenAIRE

    Fernández-Somoano Ana; Suárez-Gil Patricio; Silva-Ayçaguer Luis

    2010-01-01

    Abstract Background The null hypothesis significance test (NHST) is the most frequently used statistical method, although its inferential validity has been widely criticized since its introduction. In 1988, the International Committee of Medical Journal Editors (ICMJE) warned against sole reliance on NHST to substantiate study conclusions and suggested supplementary use of confidence intervals (CI). Our objective was to evaluate the extent and quality in the use of NHST and CI, both in Englis...

  7. Testing statistical significance scores of sequence comparison methods with structure similarity

    Directory of Open Access Journals (Sweden)

    Leunissen Jack AM

    2006-10-01

    Full Text Available Abstract Background In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical significance testing for an alignment. The e-value is the most commonly used statistical validation method for sequence database searching. The CluSTr database and the Protein World database have been created using an alternative statistical significance test: a Z-score based on Monte-Carlo statistics. Several papers have described the superiority of the Z-score as compared to the e-value, using simulated data. We were interested if this could be validated when applied to existing, evolutionary related protein sequences. Results All experiments are performed on the ASTRAL SCOP database. The Smith-Waterman sequence comparison algorithm with both e-value and Z-score statistics is evaluated, using ROC, CVE and AP measures. The BLAST and FASTA algorithms are used as reference. We find that two out of three Smith-Waterman implementations with e-value are better at predicting structural similarities between proteins than the Smith-Waterman implementation with Z-score. SSEARCH especially has very high scores. Conclusion The compute intensive Z-score does not have a clear advantage over the e-value. The Smith-Waterman implementations give generally better results than their heuristic counterparts. We recommend using the SSEARCH algorithm combined with e-values for pairwise sequence comparisons.

  8. Identification of Microorganisms by High Resolution Tandem Mass Spectrometry with Accurate Statistical Significance

    Science.gov (United States)

    Alves, Gelio; Wang, Guanghui; Ogurtsov, Aleksey Y.; Drake, Steven K.; Gucek, Marjan; Suffredini, Anthony F.; Sacks, David B.; Yu, Yi-Kuo

    2016-02-01

    Correct and rapid identification of microorganisms is the key to the success of many important applications in health and safety, including, but not limited to, infection treatment, food safety, and biodefense. With the advance of mass spectrometry (MS) technology, the speed of identification can be greatly improved. However, the increasing number of microbes sequenced is challenging correct microbial identification because of the large number of choices present. To properly disentangle candidate microbes, one needs to go beyond apparent morphology or simple `fingerprinting'; to correctly prioritize the candidate microbes, one needs to have accurate statistical significance in microbial identification. We meet these challenges by using peptidome profiles of microbes to better separate them and by designing an analysis method that yields accurate statistical significance. Here, we present an analysis pipeline that uses tandem MS (MS/MS) spectra for microbial identification or classification. We have demonstrated, using MS/MS data of 81 samples, each composed of a single known microorganism, that the proposed pipeline can correctly identify microorganisms at least at the genus and species levels. We have also shown that the proposed pipeline computes accurate statistical significances, i.e., E-values for identified peptides and unified E-values for identified microorganisms. The proposed analysis pipeline has been implemented in MiCId, a freely available software for Microorganism Classification and Identification. MiCId is available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads.html.

  9. On determining the statistical significance of discontinuities within ordered ecological data

    International Nuclear Information System (INIS)

    Current ecological theory hypothesizes that boundaries between adjacent ecosystem units are important in determining ecosystem structure and function across heterogeneous landscapes, and that such boundaries are potentially important sites for early detection of global climate change effects. Yet traditional data analysis methods focus primarily on homogeneous units rather than on the boundaries between them; thus, new methods are being developed for detecting, characterizing and classifying boundaries, e.g., split moving-window boundary analysis (SMW). SMW is a simple yet sensitive method for locating discontinuities that may exist within multivariate, serial data at various scales relative to the length of the data series. However, SMW is subjective and relative, and therefore locates apparent discontinuities even within random, serial data. In this paper they present two nonparametric methods for determining the statistical significance of discontinuities detected by SMW. First, they describe a Monte Carlo method for determining the statistical significance of scale-dependent discontinuities. Second, they propose a nonparametric, scale-independent method that is more appropriate for locating statistically significant discontinuities that separate different, relatively homogeneous groups of varying size along a series. They examine the robustness of these two methods using computer-generated data having varying intensities of imposed discontinuities, and illustrate their application to locating boundaries between vegetation samples collected at systematic intervals across a desert landscape in southern New Mexico

  10. The statistical and practical significance and "effect size" coefficients for the evaluation of physical activity

    Directory of Open Access Journals (Sweden)

    Dagmar Sigmundová

    2012-01-01

    Full Text Available BACKGROUND: An adequate statistical analysis of obtained data is a necessary condition for the right interpretation of results followed by correct formulation of conclusions. The use of appropriate statistical procedures is repeatedly a subject of justified criticism and recommendations in our and other international publications. For example, during the interpretation of results we often "blindly" rely on the statistical significance, and the practical significance of the research is ignored. OBJECTIVE: The main aim of this study is to highlight the formulation of the practical significance of the results and its correct interpretation. We used an analysis of the international studies and own findings from physical activity monitoring. Another aim is to introduce an applicable effect size coefficient as a guide for assessing the practical significance. METHODS: Materials for formulating rules to assess the practical significance and introduction of effect size coefficients was comprised of the 29 international and Czech studies about the level of week and short time (PE lesson, training, exercise lesson physical activity of Czech children and adolescents (1,129 girls and 938 boys, and adults (5,727 females and 5,426 males with use of accelerometers, pedometers and IPAQ questionnaires during 2000-2010. RESULTS: Rules for assessing the practical significance consider measurement error, data variability and the size of position from the beginning on the measurement scale. The formulation of the practical significance should include - a a determination of the minimal values of certain measurement unit that will be limiting for assessing the significancy of the difference; b the determination of a minimal size of mutual relationship between the expected results and findings. The presentation of the "effect size" coefficients (d, r, r2, K2, ω2 comprises of their definition, the conditions for use as well as the calculation and interpretation of

  11. Molecular circuits, biological switches, and nonlinear dose-response relationships.

    OpenAIRE

    Andersen, Melvin E.; Yang, Raymond S.H.; French, C. Tenley; Chubb, Laura S; Dennison, James E

    2002-01-01

    Signaling motifs (nuclear transcriptional receptors, kinase/phosphatase cascades, G-coupled protein receptors, etc.) have composite dose-response behaviors in relation to concentrations of protein receptors and endogenous signaling molecules. "Molecular circuits" include the biological components and their interactions that comprise the workings of these signaling motifs. Many of these molecular circuits have nonlinear dose-response behaviors for endogenous ligands and for exogenous toxicants...

  12. A Multi-Core Parallelization Strategy for Statistical Significance Testing in Learning Classifier Systems.

    Science.gov (United States)

    Rudd, James; Moore, Jason H; Urbanowicz, Ryan J

    2013-11-01

    Permutation-based statistics for evaluating the significance of class prediction, predictive attributes, and patterns of association have only appeared within the learning classifier system (LCS) literature since 2012. While still not widely utilized by the LCS research community, formal evaluations of test statistic confidence are imperative to large and complex real world applications such as genetic epidemiology where it is standard practice to quantify the likelihood that a seemingly meaningful statistic could have been obtained purely by chance. LCS algorithms are relatively computationally expensive on their own. The compounding requirements for generating permutation-based statistics may be a limiting factor for some researchers interested in applying LCS algorithms to real world problems. Technology has made LCS parallelization strategies more accessible and thus more popular in recent years. In the present study we examine the benefits of externally parallelizing a series of independent LCS runs such that permutation testing with cross validation becomes more feasible to complete on a single multi-core workstation. We test our python implementation of this strategy in the context of a simulated complex genetic epidemiological data mining problem. Our evaluations indicate that as long as the number of concurrent processes does not exceed the number of CPU cores, the speedup achieved is approximately linear. PMID:24358057

  13. Pulmonary inflammation and crystalline silica in respirable coal mine dust: dose-response

    Indian Academy of Sciences (India)

    E D Kuempel; M D Attfield; V Vallyathan; N L Lapp; J M Hale; R J Smith; V Castranova

    2003-02-01

    This study describes the quantitative relationships between early pulmonary responses and the estimated lungburden or cumulative exposure of respirable-quartz or coal mine dust. Data from a previous bronchoalveolar lavage (BAL) study in coal miners ( = 20) and nonminers ( = 16) were used including cell counts of alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs), and the antioxidant superoxide dismutase (SOD) levels. Miners’ individual working lifetime particulate exposures were estimated from work histories and mine air sampling data, and quartz lung-burdens were estimated using a lung dosimetry model. Results show that quartz, as either cumulative exposure or estimated lung-burden, was a highly statistically significant predictor of PMN response ( < 0.0001); however cumulative coal dust exposure did not significantly add to the prediction of PMNs ( = 0.2) above that predicted by cumulative quartz exposure ( < 0.0001). Despite the small study size, radiographic category was also significantly related to increasing levels of both PMNs and quartz lung burden (-values < 0.04). SOD in BAL fluid rose linearly with quartz lung burden ( < 0.01), but AM count in BAL fluid did not ( > 0.4). This study demonstrates dose-response relationships between respirable crystalline silica in coal mine dust and pulmonary inflammation, antioxidant production, and radiographic small opacities.

  14. Island method for estimating the statistical significance of profile-profile alignment scores

    Directory of Open Access Journals (Sweden)

    Poleksic Aleksandar

    2009-04-01

    Full Text Available Abstract Background In the last decade, a significant improvement in detecting remote similarity between protein sequences has been made by utilizing alignment profiles in place of amino-acid strings. Unfortunately, no analytical theory is available for estimating the significance of a gapped alignment of two profiles. Many experiments suggest that the distribution of local profile-profile alignment scores is of the Gumbel form. However, estimating distribution parameters by random simulations turns out to be computationally very expensive. Results We demonstrate that the background distribution of profile-profile alignment scores heavily depends on profiles' composition and thus the distribution parameters must be estimated independently, for each pair of profiles of interest. We also show that accurate estimates of statistical parameters can be obtained using the "island statistics" for profile-profile alignments. Conclusion The island statistics can be generalized to profile-profile alignments to provide an efficient method for the alignment score normalization. Since multiple island scores can be extracted from a single comparison of two profiles, the island method has a clear speed advantage over the direct shuffling method for comparable accuracy in parameter estimates.

  15. Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.

    2011-01-01

    Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…

  16. Cumulative lognormal distributions of dose-response vs. dose distributions

    International Nuclear Information System (INIS)

    A review of the author's findings over four decades will show that the lognormal probability density function can be fit to many types of positive-variate radiation measurement and response data. The cumulative lognormal plot on probability vs. logarithmic coordinate graph paper can be shown to be useful in comparing trends in exposure distributions or responses under differing conditions or experimental parameters. For variates that can take on only positive values, such a model is more natural than the 'normal' (Gaussian) model. Such modeling can also be helpful in elucidating underlying mechanisms that cause the observed data distributions. It is important, however, to differentiate between the cumulative plot of a dose distribution, in which successive percentages of data are not statistically independent, and the plots of dose-response data for which independent groups of animals or persons are irradiated or observed for selected doses or dose intervals. While independent response points can often be best fitted by appropriate regression methods, the density functions for cumulative dose or concentration distributions must be fit by particular maximum likelihood estimates from the data. Also, as indicated in the texts by D.J. Finney and by R.O. Gilbert, for example, a simple plot of such data on available probability (or probit) vs. log scale graph paper will quickly show whether an adequate representation of the data is a lognormal function. Processes that naturally generate lognormal variates are sometimes estimated by statistics that follow the lognormal straight line for a cumulative plot on a probability vs. log scale; on the other hand, sometimes the statistics of interpretation follow such a line only over a certain range. Reported examples of lognormal occupational exposure distributions include those in some facilities in which roundoff biases were removed for some years. However, for a number of exposure distributions at licensed facilities in the

  17. Testing statistical significance of trends in learning, ageing and safety indicators

    International Nuclear Information System (INIS)

    A relatively new subject for probabilistic safety methodology is statistical analysis of trends in observed failures and other safety indicators reflecting ageing or learning in operational and maintenance experience at industrial facilities. Random variations of the indicators can mask real changes or cause false alarms. Methodology is proposed for testing statistical significance of apparent trends in safety indicators. Improved methods are developed for detecting both monotonic and non-monotonic trends, some demonstrated by simulation studies and real examples to be more powerful than those known so far. An effective way to use standard trend tests with transformed data for testing exponentiality of data is also demonstrated and found superior to a well-known Lilliefors' goodness-of-fit test

  18. Statistically Non-significant Papers in Environmental Health Studies included more Outcome Variables

    Institute of Scientific and Technical Information of China (English)

    Pentti Nieminen; Khaled Abass; Kirsi Vhkanga; Arja Rautio

    2015-01-01

    Objective The number of analyzed outcome variables is important in the statistical analysis and interpretation of research findings. This study investigated published papers in the field of environmental health studies. We aimed to examine whether differences in the number of reported outcome variables exist between papers with non-significant findings compared to those with significant findings. Articles on the maternal exposure to mercury and child development were used as examples. Methods Articles published between 1995 and 2013 focusing on the relationships between maternal exposure to mercury and child development were collected from Medline and Scopus. Results Of 87 extracted papers, 73 used statistical significance testing and 38 (43.7%) of these reported ‘non-significant’ (P>0.05) findings. The median number of child development outcome variables in papers reporting ‘significant’ (n=35) and ‘non-significant’ (n=38) results was 4 versus 7, respectively (Mann-Whitney test P-value=0.014). An elevated number of outcome variables was especially found in papers reporting non-significant associations between maternal mercury and outcomes when mercury was the only analyzed exposure variable. Conclusion Authors often report analyzed health outcome variables based on their P-values rather than on stated primary research questions. Such a practice probably skews the research evidence.

  19. Population variability in biological adaptive responses to DNA damage and the shapes of carcinogen dose-response curves

    International Nuclear Information System (INIS)

    Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health

  20. Deriving statistical significance maps for SVM based image classification and group comparisons.

    Science.gov (United States)

    Gaonkar, Bilwaj; Davatzikos, Christos

    2012-01-01

    Population based pattern analysis and classification for quantifying structural and functional differences between diverse groups has been shown to be a powerful tool for the study of a number of diseases, and is quite commonly used especially in neuroimaging. The alternative to these pattern analysis methods, namely mass univariate methods such as voxel based analysis and all related methods, cannot detect multivariate patterns associated with group differences, and are not particularly suitable for developing individual-based diagnostic and prognostic biomarkers. A commonly used pattern analysis tool is the support vector machine (SVM). Unlike univariate statistical frameworks for morphometry, analytical tools for statistical inference are unavailable for the SVM. In this paper, we show that null distributions ordinarily obtained by permutation tests using SVMs can be analytically approximated from the data. The analytical computation takes a small fraction of the time it takes to do an actual permutation test, thereby rendering it possible to quickly create statistical significance maps derived from SVMs. Such maps are critical for understanding imaging patterns of group differences and interpreting which anatomical regions are important in determining the classifier's decision.

  1. Performance evaluation of hydrological models: Statistical significance for reducing subjectivity in goodness-of-fit assessments

    Science.gov (United States)

    Ritter, Axel; Muñoz-Carpena, Rafael

    2013-02-01

    SummarySuccess in the use of computer models for simulating environmental variables and processes requires objective model calibration and verification procedures. Several methods for quantifying the goodness-of-fit of observations against model-calculated values have been proposed but none of them is free of limitations and are often ambiguous. When a single indicator is used it may lead to incorrect verification of the model. Instead, a combination of graphical results, absolute value error statistics (i.e. root mean square error), and normalized goodness-of-fit statistics (i.e. Nash-Sutcliffe Efficiency coefficient, NSE) is currently recommended. Interpretation of NSE values is often subjective, and may be biased by the magnitude and number of data points, data outliers and repeated data. The statistical significance of the performance statistics is an aspect generally ignored that helps in reducing subjectivity in the proper interpretation of the model performance. In this work, approximated probability distributions for two common indicators (NSE and root mean square error) are derived with bootstrapping (block bootstrapping when dealing with time series), followed by bias corrected and accelerated calculation of confidence intervals. Hypothesis testing of the indicators exceeding threshold values is proposed in a unified framework for statistically accepting or rejecting the model performance. It is illustrated how model performance is not linearly related with NSE, which is critical for its proper interpretation. Additionally, the sensitivity of the indicators to model bias, outliers and repeated data is evaluated. The potential of the difference between root mean square error and mean absolute error for detecting outliers is explored, showing that this may be considered a necessary but not a sufficient condition of outlier presence. The usefulness of the approach for the evaluation of model performance is illustrated with case studies including those with

  2. Review of dose-response curves for acute antimigraine drugs

    DEFF Research Database (Denmark)

    Hougaard, Anders; Tfelt-Hansen, Peer

    2015-01-01

    INTRODUCTION: Dose-response curves for efficacy and tolerability are the important determinants for the choice of doses of acute migraine drugs. Areas covered: Dose-response curves for the efficacy of seven triptans (5-HT1B/1D receptor agonists), a 5-HT1F receptor agonist (lasmiditan) and four or......, there are many unmet needs. Although upcoming drugs may not be superior to triptans, migraine patients will potentially benefit greatly from these, especially patients who are triptan non-responders and patients with cardiovascular disease.......INTRODUCTION: Dose-response curves for efficacy and tolerability are the important determinants for the choice of doses of acute migraine drugs. Areas covered: Dose-response curves for the efficacy of seven triptans (5-HT1B/1D receptor agonists), a 5-HT1F receptor agonist (lasmiditan) and four oral......, whereas AEs often increase with increasing doses. The two other groups of drugs also have flat dose-response curves for efficacy. Overall, the triptans still have the most favorable efficacy-tolerability profile. Current acute antimigraine drugs do not fulfill the expectations of the patients, and thus...

  3. No difference found in time to publication by statistical significance of trial results: a methodological review

    Science.gov (United States)

    Jefferson, L; Cooper, E; Hewitt, C; Torgerson, T; Cook, L; Tharmanathan, P; Cockayne, S; Torgerson, D

    2016-01-01

    Objective Time-lag from study completion to publication is a potential source of publication bias in randomised controlled trials. This study sought to update the evidence base by identifying the effect of the statistical significance of research findings on time to publication of trial results. Design Literature searches were carried out in four general medical journals from June 2013 to June 2014 inclusive (BMJ, JAMA, the Lancet and the New England Journal of Medicine). Setting Methodological review of four general medical journals. Participants Original research articles presenting the primary analyses from phase 2, 3 and 4 parallel-group randomised controlled trials were included. Main outcome measures Time from trial completion to publication. Results The median time from trial completion to publication was 431 days (n = 208, interquartile range 278–618). A multivariable adjusted Cox model found no statistically significant difference in time to publication for trials reporting positive or negative results (hazard ratio: 0.86, 95% CI 0.64 to 1.16, p = 0.32). Conclusion In contrast to previous studies, this review did not demonstrate the presence of time-lag bias in time to publication. This may be a result of these articles being published in four high-impact general medical journals that may be more inclined to publish rapidly, whatever the findings. Further research is needed to explore the presence of time-lag bias in lower quality studies and lower impact journals. PMID:27757242

  4. Statistically Significant Strings are Related to Regulatory Elements in the Promoter Regions of Saccharomyces cerevisiae

    CERN Document Server

    Hu, R; Hu, Rui; Wang, Bin

    2000-01-01

    Finding out statistically significant words in DNA and protein sequences forms the basis for many genetic studies. By applying the maximal entropy principle, we give one systematic way to study the nonrandom occurrence of words in DNA or protein sequences. Through comparison with experimental results, it was shown that patterns of regulatory binding sites in Saccharomyces cerevisiae(yeast) genomes tend to occur significantly in the promoter regions. We studied two correlated gene family of yeast. The method successfully extracts the binding sites varified by experiments in each family. Many putative regulatory sites in the upstream regions are proposed. The study also suggested that some regulatory sites are a ctive in both directions, while others show directional preference.

  5. Dose-response characteristics of low- and intermediate-risk prostate cancer treated with external beam radiotherapy

    International Nuclear Information System (INIS)

    ASTRO definition, at 5 years after radiotherapy, the dose required for 50% tumor control (TCD50) for low-risk patients was 57.3 Gy (95% confidence interval [CI], 47.6-67.0). The γ50 was 1.4 (95% CI, -0.1 to 2.9) around 57 Gy. A statistically significant dose-response relation was found using the ASTRO definition. However, no dose-response relation was noted using the CN + 2 definition for these low-risk patients. For the intermediate-risk patients, using the ASTRO definition, the TCD50 was 67.5 Gy (95% CI, 65.5-69.5) Gy and the γ50 was 2.2 (95% CI, 1.1-3.2) around TCD50. Using the CN + 2 definition, the TCD50 was 57.8 Gy (95% CI, 49.8-65.9) and the γ50 was 1.4 (95% CI, 0.2-2.5). Recursive partitioning analysis identified two subgroups within the low-risk group, as well as the intermediate-risk group: PSA level 78 Gy for these patients. A dose-response relation was noted for the intermediate-risk patients using either the CN + 2 or ASTRO definition. Most of the benefit from the higher doses also derived from the intermediate-risk patients with higher PSA levels. Some room for improvement appears to exist with additional dose increases in this group

  6. Statistically significant contrasts between EMG waveforms revealed using wavelet-based functional ANOVA.

    Science.gov (United States)

    McKay, J Lucas; Welch, Torrence D J; Vidakovic, Brani; Ting, Lena H

    2013-01-01

    We developed wavelet-based functional ANOVA (wfANOVA) as a novel approach for comparing neurophysiological signals that are functions of time. Temporal resolution is often sacrificed by analyzing such data in large time bins, increasing statistical power by reducing the number of comparisons. We performed ANOVA in the wavelet domain because differences between curves tend to be represented by a few temporally localized wavelets, which we transformed back to the time domain for visualization. We compared wfANOVA and ANOVA performed in the time domain (tANOVA) on both experimental electromyographic (EMG) signals from responses to perturbation during standing balance across changes in peak perturbation acceleration (3 levels) and velocity (4 levels) and on simulated data with known contrasts. In experimental EMG data, wfANOVA revealed the continuous shape and magnitude of significant differences over time without a priori selection of time bins. However, tANOVA revealed only the largest differences at discontinuous time points, resulting in features with later onsets and shorter durations than those identified using wfANOVA (P < 0.02). Furthermore, wfANOVA required significantly fewer (~1/4;×; P < 0.015) significant F tests than tANOVA, resulting in post hoc tests with increased power. In simulated EMG data, wfANOVA identified known contrast curves with a high level of precision (r(2) = 0.94 ± 0.08) and performed better than tANOVA across noise levels (P < <0.01). Therefore, wfANOVA may be useful for revealing differences in the shape and magnitude of neurophysiological signals (e.g., EMG, firing rates) across multiple conditions with both high temporal resolution and high statistical power. PMID:23100136

  7. Scalable detection of statistically significant communities and hierarchies: message-passing for modularity

    CERN Document Server

    Zhang, Pan

    2014-01-01

    Modularity is a popular measure of community structure. However, maximizing the modularity can lead to many competing partitions with almost the same modularity that are poorly correlated to each other; it can also overfit, producing illusory "communities" in random graphs where none exist. We address this problem by using the modularity as a Hamiltonian, and computing the marginals of the resulting Gibbs distribution. If we assign each node to its most-likely community under these marginals, we claim that, unlike the ground state, the resulting partition is a good measure of statistically-significant community structure. We propose an efficient Belief Propagation (BP) algorithm to compute these marginals. In random networks with no true communities, the system has two phases as we vary the temperature: a paramagnetic phase where all marginals are equal, and a spin glass phase where BP fails to converge. In networks with real community structure, there is an additional retrieval phase where BP converges, and ...

  8. Statistical Significance of Non-Reproducibility of Cross Sections in Dissipative Reactions

    Institute of Scientific and Technical Information of China (English)

    王琦; 董玉川; 李松林; 田文栋; 李志常; 路秀琴; 赵葵; 符长波; 刘建成; 姜华; 胡桂青

    2003-01-01

    Two independent excitation function measurements have been performed in the reaction system of 19F+93 Nb using two target foils of the same nominal thickness. We measured the dissipative reaction products at incident energies of 102 through 108 MeV with a step of 250keV. The variance of energy autocorrelation functions of the reaction products was found to be three times of that originated from the randomized counting rates. By analysing the probability distributions of the deviations in the measured cross sections, we found that about 20% of all the deviations exceeds three standard deviations. This indicates that the non-reproducibility of the cross sections in the two independent measurements is of a statistical significance but not originated from randomized fluctuation of counting rates.

  9. Chronic periodontitis and smoking Prevalence and dose-response relationship

    Science.gov (United States)

    Khan, Shahrukh; Khalid, Taimur; Awan, Kamran H.

    2016-01-01

    Objectives: To determine the prevalence and dose-response relationship of chronic periodontitis among smokers in Pakistan. Methods: This is a cross-sectional study among participants seeking dental care in Karachi Medical and Dental College, Karachi, Pakistan. A total of 443 participants with a mean age of 44.3 (±6.5) participated in the study from April 2011 to December 2011. Males comprised 64.7%, and females comprised 35.2%. Participants were interviewed on social demographics and oral habits. Participants with shallow pockets (3.5-5.5 mm) and deep pockets (>5.5 mm) were considered suffering from chronic periodontitis. The characteristics of participants were assessed using frequency distribution for categorical variables and mean (standard deviation) for continuous variables. Results: Among 443 participants, smokers were distributed as 55.1% and non-smokers as 44.9%. Smoking was found to be significantly related to young adults (p<0.007), male gender (p<0.001), and lower education level (p<0.01). Overall prevalence of chronic periodontitis among smokers was estimated at 81.6%. Heavy smoking was found to have significantly high prevalence (p<0.001) and severity (p<0.001) of periodontitis as compared with moderate and light smokers. The multivariate unadjusted model depicted 3.5 times higher risk of chronic periodontitis among smokers (p<0.001). Conclusion: Chronic periodontitis had a high prevalence among smokers. Heavy smoking was found to have a higher risk for having periodontitis. PMID:27464867

  10. Statistics, Probability, Significance, Likelihood: Words Mean What We Define Them to Mean

    Science.gov (United States)

    Drummond, Gordon B.; Tom, Brian D. M.

    2011-01-01

    Statisticians use words deliberately and specifically, but not necessarily in the way they are used colloquially. For example, in general parlance "statistics" can mean numerical information, usually data. In contrast, one large statistics textbook defines the term "statistic" to denote "a characteristic of a "sample", such as the average score",…

  11. Statistical significant changes in ground thermal conditions of alpine Austria during the last decade

    Science.gov (United States)

    Kellerer-Pirklbauer, Andreas

    2016-04-01

    Longer data series (e.g. >10 a) of ground temperatures in alpine regions are helpful to improve the understanding regarding the effects of present climate change on distribution and thermal characteristics of seasonal frost- and permafrost-affected areas. Beginning in 2004 - and more intensively since 2006 - a permafrost and seasonal frost monitoring network was established in Central and Eastern Austria by the University of Graz. This network consists of c.60 ground temperature (surface and near-surface) monitoring sites which are located at 1922-3002 m a.s.l., at latitude 46°55'-47°22'N and at longitude 12°44'-14°41'E. These data allow conclusions about general ground thermal conditions, potential permafrost occurrence, trend during the observation period, and regional pattern of changes. Calculations and analyses of several different temperature-related parameters were accomplished. At an annual scale a region-wide statistical significant warming during the observation period was revealed by e.g. an increase in mean annual temperature values (mean, maximum) or the significant lowering of the surface frost number (F+). At a seasonal scale no significant trend of any temperature-related parameter was in most cases revealed for spring (MAM) and autumn (SON). Winter (DJF) shows only a weak warming. In contrast, the summer (JJA) season reveals in general a significant warming as confirmed by several different temperature-related parameters such as e.g. mean seasonal temperature, number of thawing degree days, number of freezing degree days, or days without night frost. On a monthly basis August shows the statistically most robust and strongest warming of all months, although regional differences occur. Despite the fact that the general ground temperature warming during the last decade is confirmed by the field data in the study region, complications in trend analyses arise by temperature anomalies (e.g. warm winter 2006/07) or substantial variations in the winter

  12. Dose-response relation between physical activity and sick leave

    NARCIS (Netherlands)

    Proper, K.I.; Heuvel, S.G. van den; Vroome, E.M. de; Hildebrandt, V.H.; Beek, A.J. van der

    2006-01-01

    Objective: To investigate the dose-response relation between moderate and vigorous physical activity and sick leave in a working population. Methods: Data were used from three large Dutch databases: two continuous, cross sectional surveys among a representative sample of the Dutch population and one

  13. A Bayesian Semiparametric Model for Radiation Dose-Response Estimation.

    Science.gov (United States)

    Furukawa, Kyoji; Misumi, Munechika; Cologne, John B; Cullings, Harry M

    2016-06-01

    In evaluating the risk of exposure to health hazards, characterizing the dose-response relationship and estimating acceptable exposure levels are the primary goals. In analyses of health risks associated with exposure to ionizing radiation, while there is a clear agreement that moderate to high radiation doses cause harmful effects in humans, little has been known about the possible biological effects at low doses, for example, below 0.1 Gy, which is the dose range relevant to most radiation exposures of concern today. A conventional approach to radiation dose-response estimation based on simple parametric forms, such as the linear nonthreshold model, can be misleading in evaluating the risk and, in particular, its uncertainty at low doses. As an alternative approach, we consider a Bayesian semiparametric model that has a connected piece-wise-linear dose-response function with prior distributions having an autoregressive structure among the random slope coefficients defined over closely spaced dose categories. With a simulation study and application to analysis of cancer incidence data among Japanese atomic bomb survivors, we show that this approach can produce smooth and flexible dose-response estimation while reasonably handling the risk uncertainty at low doses and elsewhere. With relatively few assumptions and modeling options to be made by the analyst, the method can be particularly useful in assessing risks associated with low-dose radiation exposures. PMID:26581473

  14. Dose-response aligned circuits in signaling systems.

    Directory of Open Access Journals (Sweden)

    Long Yan

    Full Text Available Cells use biological signal transduction pathways to respond to environmental stimuli and the behavior of many cell types depends on precise sensing and transmission of external information. A notable property of signal transduction that was characterized in the Saccharomyces cerevisiae yeast cell and many mammalian cells is the alignment of dose-response curves. It was found that the dose response of the receptor matches closely the dose responses of the downstream. This dose-response alignment (DoRA renders equal sensitivities and concordant responses in different parts of signaling system and guarantees a faithful information transmission. The experimental observations raise interesting questions about the nature of the information transmission through DoRA signaling networks and design principles of signaling systems with this function. Here, we performed an exhaustive computational analysis on network architectures that underlie the DoRA function in simple regulatory networks composed of two and three enzymes. The minimal circuits capable of DoRA were examined with Michaelis-Menten kinetics. Several motifs that are essential for the dynamical function of DoRA were identified. Systematic analysis of the topology space of robust DoRA circuits revealed that, rather than fine-tuning the network's parameters, the function is primarily realized by enzymatic regulations on the controlled node that are constrained in limiting regions of saturation or linearity.

  15. On the Statistical Significance of the Bulk Flow Measured by the PLANCK Satellite

    CERN Document Server

    Atrio-Barandela, F

    2013-01-01

    A recent analysis of data collected by the Planck satellite detected a net dipole at the location of X-ray selected galaxy clusters, corresponding to a large-scale bulk flow extending at least to $z\\sim 0.18$, the median redshift of the cluster sample. The amplitude of this flow, as measured with Planck, is consistent with earlier findings based on data from the Wilkinson Microwave Anisotropy Probe (WMAP). However, the uncertainty assigned to the dipole by the Planck team is much larger than that found in the WMAP studies, leading the authors of the Planck study to conclude that the observed bulk flow is not statistical significant. We here show that two of the three implementations of random sampling used in the error analysis of the Planck study lead to systematic overestimates in the uncertainty of the measured dipole. The first method, rotation around the Galactic pole (the Z axis), increases the uncertainty of the X and Y components of the dipole and artificially reduces the significance of the dipole de...

  16. There's more than one way to conduct a replication study: Beyond statistical significance.

    Science.gov (United States)

    Anderson, Samantha F; Maxwell, Scott E

    2016-03-01

    As the field of psychology struggles to trust published findings, replication research has begun to become more of a priority to both scientists and journals. With this increasing emphasis placed on reproducibility, it is essential that replication studies be capable of advancing the field. However, we argue that many researchers have been only narrowly interpreting the meaning of replication, with studies being designed with a simple statistically significant or nonsignificant results framework in mind. Although this interpretation may be desirable in some cases, we develop a variety of additional "replication goals" that researchers could consider when planning studies. Even if researchers are aware of these goals, we show that they are rarely used in practice-as results are typically analyzed in a manner only appropriate to a simple significance test. We discuss each goal conceptually, explain appropriate analysis procedures, and provide 1 or more examples to illustrate these analyses in practice. We hope that these various goals will allow researchers to develop a more nuanced understanding of replication that can be flexible enough to answer the various questions that researchers might seek to understand. PMID:26214497

  17. Radiation Dose-Response Relationships and Risk Assessment

    International Nuclear Information System (INIS)

    The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is also the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of individual risk is presented

  18. Homeopathy: statistical significance versus the sample size in experiments with Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Ana Lúcia Falavigna Guilherme

    2011-09-01

    Full Text Available Introduction: Toxoplasmosis is a zoonosis that represents a serious public health problem, caused by Toxoplasma gondii, which affects 20-90% of the world human population [1,2]. It is a serious problem especially when considering the congenital transmission due to congenital sequels. Treatment with highly diluted substances is one of the alternative/complementary medicines most employed in the world [3,4]. The current ethical rules regarding the number of animals used in animal experimental protocols with the use of more conservative statistical methods [5] can not enhance the biological effects of highly diluted substances observed by the experience of the researcher. Aim: To evaluate the minimum number of animals per group to achieve a significant difference among the groups of animals treated with biotherapic T. gondii and infected with the protozoan regarding the number of cysts observed in the brain. Material and methods: A blind randomized controlled trial was performed using eleven Swiss male mice, aged 57 days, divided into two groups: BIOT-200DH - treated with biotherapic (n=6 and CONTROL - treated with hydroalcoholic solution 7% (n=7.The animals of the group BIOT-200DH were treated for 3 consecutive days in a single dose 0.1ml/dose/day. The animals of BIOT – 200DH group were orally infected with 20 cysts of ME49-T. gondii. The animals of the control group were treated with cereal alcohol 7% (n=7 for 3 consecutive days and then were infected with 20 cysts of ME49 -T. gondii orally. The biotherapic 200DH T. gondii was prepared with homogenized mouse brain, with 20 cysts of T. gondii / 100μL according to the Brazilian Homeopathic Pharmacopoeia [6] in laminar flow. After 60 days post-infection the animals were killed in a chamber saturated with halothane, the brains were homogenized and resuspended in 1 ml of saline solution. Cysts were counted in 25 ml of this suspension, covered with a 24x24 mm coverglass

  19. Statistical Significance of Small Scale Anisotropy in Arrival Directions of Ultra-High Energy Cosmic Rays

    CERN Document Server

    Yoshiguchi, H; Sato, K; Yoshiguchi, Hiroyuki; Nagataki, Shigehiro; Sato, Katsuhiko

    2004-01-01

    Recently, the High Resolution Fly's Eye (HiRes) experiment claims that there is no small scale anisotropy in the arrival distribution of ultra-high energy cosmic rays (UHECRs) above $E>10^{19}$ eV contrary to the Akeno Giant Air Shower Array (AGASA) observation. In this paper, we discuss the statistical significance of this discrepancy between the two experiments. We calculate arrival distribution of UHECRs above $10^{19}$ eV predicted by the source models constructed using the Optical Redshift Survey galaxy sample. We apply the new method developed by us for calculating arrival distribution in the presence of the galactic magnetic field. The great advantage of this method is that it enables us to calculate UHECR arrival distribution with lower energy ($\\sim 10^{19}$ eV) than previous studies within reasonable time by following only the trajectories of UHECRs actually reaching the earth. It has been realized that the small scale anisotropy observed by the AGASA can be explained with the source number density ...

  20. Inorganic Arsenic in Drinking Water and Bladder Cancer: A Meta-Analysis for Dose-Response Assessment

    Directory of Open Access Journals (Sweden)

    Douglas J. Crawford-Brown

    2006-12-01

    Full Text Available Most arsenic cancer risk assessments have been based solely on epidemiological studies to characterize the dose-response relationship for arsenic-associated cancer and to perform risk calculations. However, current epidemiological evidence is too inconsistent and fraught with uncertainty regarding arsenic exposure to provide reliable estimates. This makes it hard to draw a firm conclusion about the shape and slope of the dose-response relationship from individual studies. Meta-analysis is a statistical approach to combining results across studies and offers expanded opportunities for obtaining an improved dose-response relationship. In this study, a meta-analysis of arsenic studies was conducted by combining seven epidemiological studies from different regions to get an overall dose-response relationship between the amount of arsenic intake and the excess probability of bladder cancer. Both the fixed-effect and random-effect models were used to calculate the averaged coefficient of the linear-logistic regression model. A homogeneity test was also conducted. The final product of this research is an aggregated dose-response model in the range of empirical observation of arsenic. Considering the most recent arsenic MCL (maximum contaminant level, i.e. 10μg/L, the associated bladder cancer risk (lifetime excess probability at this MCL is 2.29 10-5.

  1. DOSE RESPONSE CURVE OF 60Co FOR PREMATURE CONDENSED CHROMOSOME FRAGMENTS OF HUMAN LYMPHOCYTES

    Institute of Scientific and Technical Information of China (English)

    高锦声; 郑斯英; 等

    1995-01-01

    The dose-response curves obtained by premature condensed chromosome(PCC) and conventional cellular genetic methods can be represented by two linear equations.The ratio of the slopes,KPCC/KM1,is about 28,In compartison to the conventional method.The PCC method has many advantages;e.g.it is faster,simopler,more sensitive and accurate.Its significance in the study of radiation damage is also discussed.

  2. FES Training in Aging: interim results show statistically significant improvements in mobility and muscle fiber size

    Directory of Open Access Journals (Sweden)

    Helmut Kern

    2012-03-01

    Full Text Available Aging is a multifactorial process that is characterized by decline in muscle mass and performance. Several factors, including reduced exercise, poor nutrition and modified hormonal metabolism, are responsible for changes in the rates of protein synthesis and degradation that drive skeletal muscle mass reduction with a consequent decline of force generation and mobility functional performances. Seniors with normal life style were enrolled: two groups in Vienna (n=32 and two groups in Bratislava: (n=19. All subjects were healthy and declared not to have any specific physical/disease problems. The two Vienna groups of seniors exercised for 10 weeks with two different types of training (leg press at the hospital or home-based functional electrical stimulation, h-b FES. Demografic data (age, height and weight were recorded before and after the training period and before and after the training period the patients were submitted to mobility functional analyses and muscle biopsies. The mobility functional analyses were: 1. gait speed (10m test fastest speed, in m/s; 2. time which the subject needed to rise from a chair for five times (5x Chair-Rise, in s; 3. Timed –Up-Go- Test, in s; 4. Stair-Test, in s; 5. isometric measurement of quadriceps force (Torque/kg, in Nm/kg; and 6. Dynamic Balance in mm. Preliminary analyses of muscle biopsies from quadriceps in some of the Vienna and Bratislava patients present morphometric results consistent with their functional behaviors. The statistically significant improvements in functional testings here reported demonstrates the effectiveness of h-b FES, and strongly support h-b FES, as a safe home-based method to improve contractility and performances of ageing muscles.

  3. Model Averaging Software for Dichotomous Dose Response Risk Estimation

    Directory of Open Access Journals (Sweden)

    Matthew W. Wheeler

    2008-02-01

    Full Text Available Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD, fits the quantal response models, which are also used in the US Environmental Protection Agency benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates. The software fulfills a need for risk assessors, allowing them to go beyond one single model in their risk assessments based on quantal data by focusing on a set of models that describes the experimental data.

  4. Dose-response curve to salbutamol during acute and chronic treatment with formoterol in COPD

    Directory of Open Access Journals (Sweden)

    La Piana GE

    2011-07-01

    Full Text Available Giuseppe Emanuele La Piana¹, Luciano Corda², Enrica Bertella¹, Luigi Taranto Montemurro¹, Laura Pini¹, Claudio Tantucci¹¹Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, ²Prima Divisione di Medicina Interna, Spedali Civili, Brescia, ItalyBackground: Use of short-acting ß2-agonists in chronic obstructive pulmonary disease (COPD during treatment with long-acting ß2-agonists is recommended as needed, but its effectiveness is unclear. The purpose of this study was to assess the additional bronchodilating effect of increasing doses of salbutamol during acute and chronic treatment with formoterol in patients with COPD.Methods: Ten patients with COPD underwent a dose-response curve to salbutamol (until 800 µg of cumulative dose after a 1-week washout (baseline, 8 hours after the first administration of formoterol 12 µg (day 1, and after a 12-week and 24-week period of treatment with formoterol (12 µg twice daily by dry powder inhaler. Peak expiratory flow, forced expiratory volume in one second (FEV1, forced vital capacity, and inspiratory capacity were measured at the different periods of treatment and at different steps of the dose-response curve.Results: Despite acute or chronic administration of formoterol, maximal values of peak expiratory flow, FEV1, and forced vital capacity after 800 µg of salbutamol were unchanged compared with baseline. The baseline FEV1 dose-response curve was steeper than that at day 1, week 12, or week 24 (P < 0.0001. Within each dose-response curve, FEV1 was different only at baseline and at day 1 (P < 0.001, when FEV1 was still greater at 800 µg than at 0 µg (P < 0.02. In contrast, the forced vital capacity dose-response curves were similar at the different periods, while within each dose-response curve, forced vital capacity was different in all instances (P < 0.001, always being higher at 800 µg than at 0 µg (P < 0.05.Conclusion: In patients with stable COPD, the maximal effect

  5. Characterization of a developmental toxicity dose-response model.

    OpenAIRE

    Faustman, E M; Wellington, D G; Smith, W P; Kimmel, C A

    1989-01-01

    The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included ...

  6. Controlled Optimal Design Program for the Logit Dose Response Model

    Directory of Open Access Journals (Sweden)

    Jiaqiao Hu

    2010-10-01

    Full Text Available The assessment of dose-response is an integral component of the drug development process. Parallel dose-response studies are conducted, customarily, in preclinical and phase 1, 2 clinical trials for this purpose. Practical constraints on dose range, dose levels and dose proportions are intrinsic issues in the design of dose response studies because of drug toxicity, efficacy, FDA regulations, protocol requirements, clinical trial logistics, and marketing issues. We provide a free on-line software package called Controlled Optimal Design 2.0 for generating controlled optimal designs that can incorporate prior information and multiple objectives, and meet multiple practical constraints at the same time. Researchers can either run the web-based design program or download its stand-alone version to construct the desired multiple-objective controlled Bayesian optimal designs. Because researchers often adopt ad-hoc design schemes such as the equal allocation rules without knowing how efficient such designs would be for the design problem, the program also evaluates the efficiency of user-supplied designs.

  7. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  8. Dose response in prostate cancer with 8-12 years' follow-up

    International Nuclear Information System (INIS)

    /mL, although large numbers of patients are required to demonstrate a difference. The radiation dose, Gleason score, and palpation T stage were significant predictors for the entire patient set, as well as for those with pretreatment PSA levels between 10 and 20 ng/mL. The FDM rate for all patients included in this series was 89%, 83%, and 83% at 5, 10, and 12 years, respectively. For patients with pretreatment PSA levels 9 years of median follow-up confirm the existence of a dose response for both bNED control and FDM. The dose response in prostate cancer is real, and the absence of biochemical recurrence after 8 years demonstrates the lack of late failure and suggests cure

  9. Accelerator driven reactors, - the significance of the energy distribution of spallation neutrons on the neutron statistics

    International Nuclear Information System (INIS)

    In order to make correct predictions of the second moment of statistical nuclear variables, such as the number of fissions and the number of thermalized neutrons, the dependence of the energy distribution of the source particles on their number should be considered. It has been pointed out recently that neglecting this number dependence in accelerator driven systems might result in bad estimates of the second moment, and this paper contains qualitative and quantitative estimates of the size of these efforts. We walk towards the requested results in two steps. First, models of the number dependent energy distributions of the neutrons that are ejected in the spallation reactions are constructed, both by simple assumptions and by extracting energy distributions of spallation neutrons from a high-energy particle transport code. Then, the second moment of nuclear variables in a sub-critical reactor, into which spallation neutrons are injected, is calculated. The results from second moment calculations using number dependent energy distributions for the source neutrons are compared to those where only the average energy distribution is used. Two physical models are employed to simulate the neutron transport in the reactor. One is analytical, treating only slowing down of neutrons by elastic scattering in the core material. For this model, equations are written down and solved for the second moment of thermalized neutrons that include the distribution of energy of the spallation neutrons. The other model utilizes Monte Carlo methods for tracking the source neutrons as they travel inside the reactor material. Fast and thermal fission reactions are considered, as well as neutron capture and elastic scattering, and the second moment of the number of fissions, the number of neutrons that leaked out of the system, etc. are calculated. Both models use a cylindrical core with a homogenous mixture of core material. Our results indicate that the number dependence of the energy

  10. Using the bootstrap to establish statistical significance for relative validity comparisons among patient-reported outcome measures

    OpenAIRE

    Deng, Nina; Allison, Jeroan J; Fang, Hua Julia; Ash, Arlene S.; Ware, John E.

    2013-01-01

    Background Relative validity (RV), a ratio of ANOVA F-statistics, is often used to compare the validity of patient-reported outcome (PRO) measures. We used the bootstrap to establish the statistical significance of the RV and to identify key factors affecting its significance. Methods Based on responses from 453 chronic kidney disease (CKD) patients to 16 CKD-specific and generic PRO measures, RVs were computed to determine how well each measure discriminated across clinically-defined groups ...

  11. Statistical significance of biomonitoring of marine algae for trace metal levels in a coral environment

    Digital Repository Service at National Institute of Oceanography (India)

    Gopinath, A.; Muraleedharan, N.S.; Chandramohanakumar, N.; Jayalakshmy, K.V.

    Organization (FAO) in seafood for human consumption. None of the species of algae had the tendency to bioconcentrate Pb in their system as the detection level was below 0.1 mg/kg. The metal selectivity index calculated in statistical analysis emphasized...

  12. Testing statistical significance scores of sequence comparison methods with structure similarity

    NARCIS (Netherlands)

    Hulsen, T.; Vlieg, de J.; Leunissen, J.A.M.; Groenen, P.

    2006-01-01

    Background - In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical

  13. Testing statistical significance scores of sequence comparison methods with structure similarity

    NARCIS (Netherlands)

    Hulsen, T.; Vlieg, J. de; Leunissen, J.A.M.; Groenen, P.M.

    2006-01-01

    BACKGROUND: In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical s

  14. Statistics

    CERN Document Server

    Hayslett, H T

    1991-01-01

    Statistics covers the basic principles of Statistics. The book starts by tackling the importance and the two kinds of statistics; the presentation of sample data; the definition, illustration and explanation of several measures of location; and the measures of variation. The text then discusses elementary probability, the normal distribution and the normal approximation to the binomial. Testing of statistical hypotheses and tests of hypotheses about the theoretical proportion of successes in a binomial population and about the theoretical mean of a normal population are explained. The text the

  15. Dose-responses from multi-model inference for the non-cancer disease mortality of atomic bomb survivors.

    Science.gov (United States)

    Schöllnberger, H; Kaiser, J C; Jacob, P; Walsh, L

    2012-05-01

    The non-cancer mortality data for cerebrovascular disease (CVD) and cardiovascular diseases from Report 13 on the atomic bomb survivors published by the Radiation Effects Research Foundation were analysed to investigate the dose-response for the influence of radiation on these detrimental health effects. Various parametric and categorical models (such as linear-no-threshold (LNT) and a number of threshold and step models) were analysed with a statistical selection protocol that rated the model description of the data. Instead of applying the usual approach of identifying one preferred model for each data set, a set of plausible models was applied, and a sub-set of non-nested models was identified that all fitted the data about equally well. Subsequently, this sub-set of non-nested models was used to perform multi-model inference (MMI), an innovative method of mathematically combining different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. This procedure thereby produces more reliable risk estimates based on a more comprehensive appraisal of model uncertainties. For CVD, MMI yielded a weak dose-response (with a risk estimate of about one-third of the LNT model) below a step at 0.6 Gy and a stronger dose-response at higher doses. The calculated risk estimates are consistent with zero risk below this threshold-dose. For mortalities related to cardiovascular diseases, an LNT-type dose-response was found with risk estimates consistent with zero risk below 2.2 Gy based on 90% confidence intervals. The MMI approach described here resolves a dilemma in practical radiation protection when one is forced to select between models with profoundly different dose-responses for risk estimates. PMID:22437350

  16. Diethylene glycol-induced toxicities show marked threshold dose response in rats

    Energy Technology Data Exchange (ETDEWEB)

    Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2015-02-01

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.

  17. Dose-response investigation into glucose facilitation of memory performance and mood in healthy young adults.

    Science.gov (United States)

    Sünram-Lea, Sandra I; Owen, Lauren; Finnegan, Yvonne; Hu, Henglong

    2011-08-01

    It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.

  18. Statistical physics inspired methods to assign statistical significance in bioinformatics and proteomics: From sequence comparison to mass spectrometry based peptide sequencing

    Science.gov (United States)

    Alves, Gelio

    After the sequencing of many complete genomes, we are in a post-genomic era in which the most important task has changed from gathering genetic information to organizing the mass of data as well as under standing how components interact with each other. The former is usually undertaking using bioinformatics methods, while the latter task is generally termed proteomics. Success in both parts demands correct statistical significance assignments for results found. In my dissertation. I study two concrete examples: global sequence alignment statistics and peptide sequencing/identification using mass spectrometry. High-performance liquid chromatography coupled to a mass spectrometer (HPLC/MS/MS), enabling peptide identifications and thus protein identifications, has become the tool of choice in large-scale proteomics experiments. Peptide identification is usually done by database searches methods. The lack of robust statistical significance assignment among current methods motivated the development of a novel de novo algorithm, RAId, whose score statistics then provide statistical significance for high scoring peptides found in our custom, enzyme-digested peptide library. The ease of incorporating post-translation modifications is another important feature of RAId. To organize the massive protein/DNA data accumulated, biologists often cluster proteins according to their similarity via tools such as sequence alignment. Homologous proteins share similar domains. To assess the similarity of two domains usually requires alignment from head to toe, ie. a global alignment. A good alignment score statistics with an appropriate null model enable us to distinguish the biologically meaningful similarity from chance similarity. There has been much progress in local alignment statistics, which characterize score statistics when alignments tend to appear as a short segment of the whole sequence. For global alignment, which is useful in domain alignment, there is still much room for

  19. Mutans Streptococci Dose Response to Xylitol Chewing Gum

    OpenAIRE

    Milgrom, P.; Ly, K.A.; Roberts, M C; Rothen, M; Mueller, G.; Yamaguchi, D.K.

    2006-01-01

    Xylitol is promoted in caries-preventive strategies, yet its effective dose range is unclear. This study determined the dose-response of mutans streptococci in plaque and unstimulated saliva to xylitol gum. Participants (n = 132) were randomized: controls (G1) (sorbitol/maltitol), or combinations giving xylitol 3.44 g/day (G2), 6.88 g/day (G3), or 10.32 g/day (G4). Groups chewed 3 pellets/4 times/d. Samples were taken at baseline, 5 wks, and 6 mos, and were cultured on modified Mitis Salivari...

  20. Dose Response of Alanine Detectors Irradiated with Carbon Ion Beams

    DEFF Research Database (Denmark)

    Herrmann, Rochus; Jäkel, Oliver; Palmans, Hugo;

    2011-01-01

    . Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track-structure based alanine......Purpose: The dose response of the alanine detector shows a dependence on particle energy and type, when irradiated with ion beams. The purpose of this study is to investigate the response behaviour of the alanine detector in clinical carbon ion beams and compare the results with model predictions...... of the detector geometry implemented in the Monte Carlo simulations....

  1. Statistical Analysis and Evaluation of the Depth of the Ruts on Lithuanian State Significance Roads

    Directory of Open Access Journals (Sweden)

    Erinijus Getautis

    2011-04-01

    Full Text Available The aim of this work is to gather information about the national flexible pavement roads ruts depth, to determine its statistical dispersijon index and to determine their validity for needed requirements. Analysis of scientific works of ruts apearance in the asphalt and their influence for driving is presented in this work. Dynamical models of ruts in asphalt are presented in the work as well. Experimental outcome data of rut depth dispersijon in the national highway of Lithuania Vilnius – Kaunas is prepared. Conclusions are formulated and presented. Article in Lithuanian

  2. Statistics

    Science.gov (United States)

    Links to sources of cancer-related statistics, including the Surveillance, Epidemiology and End Results (SEER) Program, SEER-Medicare datasets, cancer survivor prevalence data, and the Cancer Trends Progress Report.

  3. Confidence Intervals: From tests of statistical significance to confidence intervals, range hypotheses and substantial effects

    Directory of Open Access Journals (Sweden)

    Dominic Beaulieu-Prévost

    2006-03-01

    Full Text Available For the last 50 years of research in quantitative social sciences, the empirical evaluation of scientific hypotheses has been based on the rejection or not of the null hypothesis. However, more than 300 articles demonstrated that this method was problematic. In summary, null hypothesis testing (NHT is unfalsifiable, its results depend directly on sample size and the null hypothesis is both improbable and not plausible. Consequently, alternatives to NHT such as confidence intervals (CI and measures of effect size are starting to be used in scientific publications. The purpose of this article is, first, to provide the conceptual tools necessary to implement an approach based on confidence intervals, and second, to briefly demonstrate why such an approach is an interesting alternative to an approach based on NHT. As demonstrated in the article, the proposed CI approach avoids most problems related to a NHT approach and can often improve the scientific and contextual relevance of the statistical interpretations by testing range hypotheses instead of a point hypothesis and by defining the minimal value of a substantial effect. The main advantage of such a CI approach is that it replaces the notion of statistical power by an easily interpretable three-value logic (probable presence of a substantial effect, probable absence of a substantial effect and probabilistic undetermination. The demonstration includes a complete example.

  4. Dose response of selected solid state detectors in applied homogeneous transverse and longitudinal magnetic fields

    International Nuclear Information System (INIS)

    Purpose: MR-Linac devices under development worldwide will require standard calibration, commissioning, and quality assurance. Solid state radiation detectors are often used for dose profiles and percent depth dose measurements. The dose response of selected solid state detectors is therefore evaluated in varying transverse and longitudinal magnetic fields for this purpose. Methods: The Monte Carlo code PENELOPE was used to model irradiation of a PTW 60003 diamond detector and IBA PFD diode detector in the presence of a magnetic field. The field itself was varied in strength, and oriented both transversely and longitudinally with respect to the incident photon beam. The long axis of the detectors was oriented either parallel or perpendicular to the photon beam. The dose to the active volume of each detector in air was scored, and its ratio to dose with zero magnetic field strength was determined as the “dose response” in magnetic field. Measurements at low fields for both detectors in transverse magnetic fields were taken to evaluate the accuracy of the simulations. Additional simulations were performed in a water phantom to obtain few representative points for beam profile and percent depth dose measurements. Results: Simulations show significant dose response as a function of magnetic field in transverse field geometries. This response can be near 20% at 1.5 T, and it is highly dependent on the detectors’ relative orientation to the magnetic field, the energy of the photon beam, and detector composition. Measurements at low transverse magnetic fields verify the simulations for both detectors in their relative orientations to radiation beam. Longitudinal magnetic fields, in contrast, show little dose response, rising slowly with magnetic field, and reaching 0.5%–1% at 1.5 T regardless of detector orientation. Water tank and in air simulation results were the same within simulation uncertainty where lateral electronic equilibrium is present and expectedly

  5. Maximum likelihood estimation for cytogenetic dose-response curves

    International Nuclear Information System (INIS)

    In vitro dose-response curves are used to describe the relation between the yield of dicentric chromosome aberrations and radiation dose for human lymphocytes. The dicentric yields follow the Poisson distribution, and the expected yield depends on both the magnitude and the temporal distribution of the dose for low LET radiation. A general dose-response model that describes this relation has been obtained by Kellerer and Rossi using the theory of dual radiation action. The yield of elementary lesions is kappa[γd + g(t, tau)d2], where t is the time and d is dose. The coefficient of the d2 term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure

  6. Improved Monte Carlo estimation of statistical significance for tests of trend in rates or proportions

    International Nuclear Information System (INIS)

    Asymptotic significance levels of tests for monotone trends in rates or proportions can be profoundly anticonservative when applied to small numbers of events and when distributions of exposure to risk are highly skewed. In such cases Monte Carlo (MC) estimation of observed levels of significance (''p-values'') can be very useful. We describe a simple technique of importance sampling (IS) which can greatly improve the efficiency of MC estimation in this setting. Implementation of the IS technique is described, and the variance of the IS estimator is derived. It is shown that, in many situations likely to occur in practice, the variance is substantially less than that of a simple MC estimator proposed earlier. Generalizations beyond the case of survival data without ties are described, and the use of IS is illustrated with data regarding mortality among atomic bomb survivors. (author)

  7. Dose selection for prostate cancer patients based on dose comparison and dose response studies

    International Nuclear Information System (INIS)

    Purpose: To better define the appropriate dose for individual prostate cancer patients treated with three-dimensional conformal radiation therapy (3D CRT). Methods and Materials: Six hundred eighteen patients treated with 3D CRT between 4/89 and 4/97 with a median follow-up of 53 months are the subject of this study. The bNED outcomes were assessed by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. The patients were grouped into three groups by prostate-specific antigen (PSA) level (<10 ng/ml, 10-19.9 ng/ml, and 20+ ng/ml) and further subgrouped into six subgroups by favorable (T1, 2A and Gleason score ≤6 and no perineural invasion) and unfavorable characteristics (one or more of T2B, T3, Gleason 7-10, perineural invasion). Dose comparisons for bNED studies were made for each of the six subgroups by dividing patients at 76 Gy for all subgroups except the favorable <10 ng/ml subgroup, which was divided at 72.5 Gy. Five-year bNED rates were compared for the median dose of each dose comparison subgroup. Dose response functions were plotted based on 5-year bNED rates for the six patient groupings, with the data from each of the six subgroups divided into three dose groups. The 5-year bNED rate was also estimated using the dose response function and compares 73 Gy with 78 Gy. Results: Dose comparisons show a significant difference in 5-year bNED rates for three of the six subgroups but not for the favorable <10 ng/ml, the favorable 10-19.9 ng/ml, or the unfavorable ≥20 ng/ml subgroups. The significant differences ranged from 22% to 40% improvement in 5-year bNED with higher dose. Dose response functions show significant differences in 5-year bNED rates comparing 73 Gy and 78 Gy for four of the six subgroups. Again, no difference was observed for the favorable <10 ng/ml group or the unfavorable ≥20 ng/ml group. The significant differences observed in 5-year bNED ranged from 15% to 43%. Conclusions: Dose response varies by patient

  8. Dose response curves for effects of low-level radiation

    International Nuclear Information System (INIS)

    The linear dose-response model used by international committees to assess the genetic and carcinogenic hazards of low-level radiation appears to be the most reasonable interpretation of the available scientific data that are relevant to this topic. There are, of course, reasons to believe that this model may overestimate radiation hazards in certain instances, a fact acknowledged in recent reports of these committees. The linear model is now also being utilized to estimate the potential carcinogenic hazards of other agents such as asbestos and polycyclic aromatic hydrocarbons. This model implies that there is no safe dose for any of these agents and that potential health hazards will increase in direct proportion to total accumulated dose. The practical implication is the recommendation that all exposures should be kept 'as low as reasonably achievable, economic and social factors being taken into account'. (auth)

  9. Proposal of a probabilistic dose-response model

    International Nuclear Information System (INIS)

    A biologically updated dose-response model is presented as an alternative to the linear-quadratic model currently in use for cancer risk assessment. The new model is based on the probability functions for misrepair and/or unrepair of DNA lesions, in terms of the radiation damage production rate in the cell (supposedly, a stem cell) and its repair-rate constant. The model makes use, interpreting it on the basis of misrepair probabilities, of the ''dose and dose-rate effectiveness factor'' of ICRP, and provides the way for a continuous extrapolation between the high and low dose-rate regions, ratifying the ''linear non-threshold hypothesis'' as the main option. Anyhow, the model throws some doubts about the additive property of the dose. (author)

  10. Dose-response relationships for radium-induced bone sarcomas

    International Nuclear Information System (INIS)

    The incidence of bone sarcomas among 3055 female radium-dial workers who entered the dial industry before 1950 was used to determine dose-response relationships for the induction of bone sarcomas by radium. Two subpopulations were analyzed: all measured cases who survived at last five years after the start of employment and all cases who survived at least two years after first measurement. The first constituted a group based on year of entry; it contained 1468 women who experienced 42 bone sarcomas; the expected number was 0.4. The second comprised a group based on first measurement; it contained 1257 women who experienced 13 bone sarcomas; the expected number was 0.2. The dose-response function, I = (C + αD + #betta#D2)e/sup -#betta#D/, and simplifications of this general form, were fit to each data set. Two functions, I = (C + αD + #betta#D2)e/sup -#betta#D/ and I = (C + #betta#D2)e/sup -#betta#D/, fit the data for year of entry (p greater than or equal to 0.05); both these functions and I = (C + αD) fit the data for first measurement. The function I = (C + #betta#D2)e/sup -#betta#D/ was used to predict the number of bone sarcomas in all other pre-1950 radium cases (medical, laboratory, and other exposure); fewer were actually observed than the fit of this function to the female dial workers predicted

  11. The dose-response relationship for UV-tumorigenesis

    International Nuclear Information System (INIS)

    The main objective of the investigations was to extend the knowledge on experimental UV-carcinogenesis and to use the experimental results as guidelines for developing a dose-response model for UV-carcinogenesis. The animal experiments carried out were all long-term ones. It was decided that - in anticipation of the data to be obtained - a model for such an assessment should be developed using the experimental results available at the start of the present study (1977). This initial study is presented. The results of two animal experiments are presented, which show that UV radiation is capable of inducing a systemic effect that enhances the de novo formation of UV induced tumors. The results of the main experiment are presented. In this experiment groups of mice were subjected to daily exposure to a certain dose of UV radiation in order to find the dose-response relationship. The relation between the daily dose and the duration of the treatment till the appearance of tumors (for instance, as measured by the yield) was ascertained for tumors of different sizes. It appears that the growth of a tumor is dose-independent, and, therefore, only the initiation of a tumor is dose-dependent. Finally an experiment is presented in which it was measured that, if a mouse is subjected to daily UV exposure, the transmission of the epidermis in the shortwave UV region decreases continuously. This decrease is due to hyperplasia of the epidermis, i.e., thickening of the epidermis by an increase in the number of cells per unit surface area. (Auth.)

  12. Optimal experimental design to estimate statistically significant periods of oscillations in time course data.

    Directory of Open Access Journals (Sweden)

    Márcio Mourão

    Full Text Available We investigated commonly used methods (Autocorrelation, Enright, and Discrete Fourier Transform to estimate the periodicity of oscillatory data and determine which method most accurately estimated periods while being least vulnerable to the presence of noise. Both simulated and experimental data were used in the analysis performed. We determined the significance of calculated periods by applying these methods to several random permutations of the data and then calculating the probability of obtaining the period's peak in the corresponding periodograms. Our analysis suggests that the Enright method is the most accurate for estimating the period of oscillatory data. We further show that to accurately estimate the period of oscillatory data, it is necessary that at least five cycles of data are sampled, using at least four data points per cycle. These results suggest that the Enright method should be more widely applied in order to improve the analysis of oscillatory data.

  13. Myths and Misconceptions Revisited - What are the (Statistically Significant) methods to prevent employee injuries

    International Nuclear Information System (INIS)

    A company's overall safety program becomes an important consideration to continue performing work and for procuring future contract awards. When injuries or accidents occur, the employer ultimately loses on two counts - increased medical costs and employee absences. This paper summarizes the human and organizational components that contributed to successful safety programs implemented by WESKEM, LLC's Environmental, Safety, and Health Departments located in Paducah, Kentucky, and Oak Ridge, Tennessee. The philosophy of 'safety, compliance, and then production' and programmatic components implemented at the start of the contracts were qualitatively identified as contributing factors resulting in a significant accumulation of safe work hours and an Experience Modification Rate (EMR) of <1.0. Furthermore, a study by the Associated General Contractors of America quantitatively validated components, already found in the WESKEM, LLC programs, as contributing factors to prevent employee accidents and injuries. Therefore, an investment in the human and organizational components now can pay dividends later by reducing the EMR, which is the key to reducing Workers' Compensation premiums. Also, knowing your employees' demographics and taking an active approach to evaluate and prevent fatigue may help employees balance work and non-work responsibilities. In turn, this approach can assist employers in maintaining a healthy and productive workforce. For these reasons, it is essential that safety needs be considered as the starting point when performing work. (authors)

  14. Dose-response modeling for the environmental risk assessment in cases of technogenic soil contamination

    Directory of Open Access Journals (Sweden)

    Shitikov Vladimir Kirilloviсh

    2015-09-01

    Full Text Available The review of regression models for the approximation of dependences "dose- response" was performed based on ecotoxicological results. The advantages and deficiencies of different models as well as the problems arising both in modeling and subsequent interpreting results are discussed for the purpose of ecological rationing and estimation of negative influence risk. Search procedures of best dependences based on statistical criteria and the methods of uncertainty estimation of calculated parameters are shown. Construction of models is illustrated in detail using the analysis of toxicity results of soil samples received from uranium mines tailings in Kadzhi-Say province (Kyrgyzstan. Threshold values of activity for U-238 and Ra-226 radionuclides providing the minimum probability of ecological risk were determined.

  15. Dose-response testing with nickel sulphate using the TRUE test in nickel-sensitive individuals. Multiple nickel sulphate patch-test reactions do not cause an 'angry back'

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Lidén, C; Hansen, J;

    1993-01-01

    of the different concentrations. Readings were performed blind. The results were analysed by means of polynomial multiple-regression methods and a logistic dose-response model. Half the patients (38/72) had a threshold patch-test concentration for nickel sulphate in the range of 3-0.3 microgram/cm2. The 'angry...... back' phenomenon was not apparent in this study, as the spill-over effect was not statistically significant. Strong reactions to high concentrations of nickel sulphate did not enhance the response to adjacent lower concentrations of nickel sulphate....

  16. X-ray dose response of calcite-A comprehensive analysis for optimal application in TL dosimetry

    Science.gov (United States)

    Kalita, J. M.; Wary, G.

    2016-09-01

    The effect of various annealing treatments on dosimetric characteristics of orange calcite (CaCO3) mineral has been studied in detail. Quantitative analysis on the dose response shows that the 573 K annealed sample showed sublinear dose response from 10 mGy to 1 Gy. The fading and reproducibility of this sample are also good enough for dosimetric application. However, a specific annealing treatment after irradiation shows some significant improvements in the dosimetric characteristics of the sample. The 773 K pre-annealed sample, after X-ray irradiation post-annealing at 340 K for 6 min provides linear dose response from 10 mGy to 3.60 Gy, very less fading and good reproducibility. Moreover, this sample after post-annealing at 380 K for 6 min shows linear dose response from 10 mGy to 5.40 Gy when analyzed from the ∼408 K thermoluminescence (TL) glow peak. Analysis of TL glow curves confirmed that the 1.30 eV trap center in calcite crystal is the most effective trapping site for dosimetric application.

  17. A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

    Science.gov (United States)

    Wells, Thomas G.; Shahinfar, Shahnaz; Massaad, Rachid; Dankner, Wayne M.; Lam, Chun; Santoro, Emanuela Palumbo; McCrary Sisk, Christine; Blaustein, Robert O.

    2014-01-01

    Background and objectives Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6–16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years. Design, setting, participants, & measurements This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension. Patients were randomized to losartan at the following dosages: 0.1 mg/kg per day (low), 0.3 mg/kg per day (medium), or 0.7 mg/kg per day (high). Losartan was titrated to the next dose level (to a 1.4 mg/kg per day maximum dosage, not exceeding 100 mg/d, which was not one of the three original doses offered at randomization) at weeks 3, 6, and 9 for patients who did not attain their goal BP and were not taking the highest dose. Dose response was evaluated by analyzing the slope of change in sitting systolic BP (SBP; primary end point) and diastolic BP (DBP; secondary end point) after 3 weeks compared with baseline. Adverse events (AEs) were recorded throughout. Results Of the 101 patients randomized, 99 were included in the analysis (low dose, n=32; medium dose, n=34; and high dose, n=33). Mean sitting BP decreased from baseline in the low-, medium-, and high-dose groups by 7.3, 7.6, and 6.7 mmHg, respectively, for SBP and 8.2, 5.1, and 6.7 mmHg, respectively, for DBP after 3 weeks. No dose-response relationship was established by the slope analysis on SBP (P=0.75) or DBP (P=0.64). The BP-lowering effect was observed throughout the 2-year extension. The incidence of AEs was low and comparable between groups. Conclusions Hypertensive children aged 6 months to 6 years treated with losartan 0.1–0.7 mg/kg per day had clinically significant decreases from baseline in SBP and DBP, yet no dose-response relationship was evident. Losartan, at a dosage up to 1.4 mg/kg per day, was well tolerated. PMID:24875194

  18. Methods for Determining the Statistical Significance of Enrichment or Depletion of Gene Ontology Classifications under Weighted Membership

    Directory of Open Access Journals (Sweden)

    Ernesto eIacucci

    2012-02-01

    Full Text Available High-throughput molecular biology studies, such as microarray assays of gene expression, two-hybrid experiments for detecting protein interactions, or ChIP-Seq experiments for transcription factor binding, often result in an interesting set of genes—say, genes that are co-expressed or bound by the same factor. One way of understanding the biological meaning of such a set is to consider what processes or functions, as defined in an ontology, are over-represented (enriched or under-represented (depleted among genes in the set. Usually, the significance of enrichment or depletion scores is based on simple statistical models and on the membership of genes in different classifications. We consider the more general problem of computing p-values for arbitrary integer additive statistics, or weighted membership functions. Such membership functions can be used to represent, for example, prior knowledge on the role of certain genes or classifications, differential importance of different classifications or genes to the experimenter, hierarchical relationships between classifications, or different degrees of interestingness or evidence for specific genes. We describe a generic dynamic programming algorithm that can compute exact p-values for arbitrary integer additive statistics. We also describe several optimizations for important special cases, which can provide orders-of-magnitude speed up in the computations. We apply our methods to datasets describing oxidative phosphorylation and parturition and compare p-values based on computations of several different statistics for measuring enrichment. We find major differences between p-values resulting from these statistics, and that some statistics recover gold standard annotations of the data better than others. Our work establishes a theoretical and algorithmic basis for far richer notions of enrichment or depletion of gene sets with respect to gene ontologies than has previously been available.

  19. Weighted Feature Significance: A Simple, Interpretable Model of Compound Toxicity Based on the Statistical Enrichment of Structural Features

    OpenAIRE

    Huang, Ruili; Southall, Noel; Xia, Menghang; Cho, Ming-Hsuang; Jadhav, Ajit; Nguyen, Dac-Trung; Inglese, James; Tice, Raymond R.; Austin, Christopher P.

    2009-01-01

    In support of the U.S. Tox21 program, we have developed a simple and chemically intuitive model we call weighted feature significance (WFS) to predict the toxicological activity of compounds, based on the statistical enrichment of structural features in toxic compounds. We trained and tested the model on the following: (1) data from quantitative high–throughput screening cytotoxicity and caspase activation assays conducted at the National Institutes of Health Chemical Genomics Center, (2) dat...

  20. Development of a mid-head radiation dose response function

    International Nuclear Information System (INIS)

    Calculations have been made of the incident neutron and gamma-ray absorbed dose response as a function of energy in the mid-head position of a phantom model. The calculations were performed with the DOT discrete ordinates transport code in the adjoint mode using co-axial cylinders to represent the head and torso. Results, given in a coupled 37-neutron-group, 21-gamma-ray-group structure (37/21) and a 22-neutron-group, 18-gamma-ray-group structure (22/18), are compared with previously obtained results. The mid-head response is less than the conventional radiation protection fluence-to-dose factors which are based on maximum phantom values. In the case of a fission source in air the neutron dose is about a factor of 4 less, and the secondary gamma-ray dose is about a factor of 1.5 less. For a fusion source the neutron dose ratio varies from about 1.9 at close range to about 3. The gamma-ray dose ratio is about the same as for the fission source. Tables of the various response functions are presented in the Appendix A

  1. The effect of ongoing exposure dynamics in dose response relationships.

    Directory of Open Access Journals (Sweden)

    Josep M Pujol

    2009-06-01

    Full Text Available Characterizing infectivity as a function of pathogen dose is integral to microbial risk assessment. Dose-response experiments usually administer doses to subjects at one time. Phenomenological models of the resulting data, such as the exponential and the Beta-Poisson models, ignore dose timing and assume independent risks from each pathogen. Real world exposure to pathogens, however, is a sequence of discrete events where concurrent or prior pathogen arrival affects the capacity of immune effectors to engage and kill newly arriving pathogens. We model immune effector and pathogen interactions during the period before infection becomes established in order to capture the dynamics generating dose timing effects. Model analysis reveals an inverse relationship between the time over which exposures accumulate and the risk of infection. Data from one time dose experiments will thus overestimate per pathogen infection risks of real world exposures. For instance, fitting our model to one time dosing data reveals a risk of 0.66 from 313 Cryptosporidium parvum pathogens. When the temporal exposure window is increased 100-fold using the same parameters fitted by our model to the one time dose data, the risk of infection is reduced to 0.09. Confirmation of this risk prediction requires data from experiments administering doses with different timings. Our model demonstrates that dose timing could markedly alter the risks generated by airborne versus fomite transmitted pathogens.

  2. Mutans Streptococci Dose Response to Xylitol Chewing Gum

    Science.gov (United States)

    Milgrom, P.; Ly, K.A.; Roberts, M.C.; Rothen, M.; Mueller, G.; Yamaguchi, D.K.

    2008-01-01

    Xylitol is promoted in caries-preventive strategies, yet its effective dose range is unclear. This study determined the dose-response of mutans streptococci in plaque and unstimulated saliva to xylitol gum. Participants (n = 132) were randomized: controls (G1) (sorbitol/maltitol), or combinations giving xylitol 3.44 g/day (G2), 6.88 g/day (G3), or 10.32 g/day (G4). Groups chewed 3 pellets/4 times/d. Samples were taken at baseline, 5 wks, and 6 mos, and were cultured on modified Mitis Salivarius agar for mutans streptococci and on blood agar for total culturable flora. At 5 wks, mutans streptococci levels in plaque were 10x lower than baseline in G3 and G4 (P = 0.007/0.003). There were no differences in saliva. At 6 mos, mutans streptococci in plaque for G3 and G4 remained 10x lower than baseline (P = 0.007/0.04). Saliva for G3 and G4 was lower than baseline by 8 to 9x (P = 0.011/0.038). Xylitol at 6.44 g/day and 10.32 g/day reduces mutans streptococci in plaque at 5 wks, and in plaque and unstimulated saliva at 6 mos. A plateau effect is suggested between 6.44 g and 10.32 g xylitol/day. PMID:16434738

  3. Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer

    International Nuclear Information System (INIS)

    Background and purpose: We fit phenomenological tumor control probability (TCP) models to biopsy outcome after three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer patients to quantify the local dose-response of prostate cancer. Materials and methods: We analyzed the outcome after photon beam 3D-CRT of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan-Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81 Gy) who had a prostate biopsy performed ≥2.5 years after end of treatment. A univariate logistic regression model based on Dmean (mean dose in the planning target volume of each patient) was fit to the whole data set and separately to subgroups characterized by low and high values of tumor-related prognostic factors T-stage (6), and pre-treatment prostate-specific antigen (PSA) (≤10 ng/ml vs. >10 ng/ml). In addition, we evaluated five different classifications of the patients into three risk groups, based on all possible combinations of two or three prognostic factors, and fit bivariate logistic regression models with Dmean and the risk group category to all patients. Dose-response curves were characterized by TCD50, the dose to control 50% of the tumors, and γ50, the normalized slope of the dose-response curve at TCD50. Results: Dmean correlates significantly with biopsy outcome in all patient subgroups and larger values of TCD50 are observed for patients with unfavorable compared to favorable prognostic factors. For example, TCD50 for high T-stage patients is 7 Gy higher than for low T-stage patients. For all evaluated risk group definitions, Dmean and the risk group category are independent predictors of biopsy outcome in bivariate analysis. The fit values of TCD50 show a clear separation of 9-10.6 Gy between low and high risk patients. The corresponding dose-response curves are steeper (γ50=3.4-5.2) than those obtained when all patients are analyzed together (γ50=2.9). Conclusions: Dose-response

  4. Accounting for Shared and Unshared Dosimetric Uncertainties in the Dose Response for Ultrasound-Detected Thyroid Nodules after Exposure to Radioactive Fallout

    Science.gov (United States)

    Hoffman, F. Owen; Moroz, Brian; Drozdovitch, Vladimir; Bouville, André; Beck, Harold; Luckyanov, Nicholas; Weinstock, Robert M.; Simon, Steven L.

    2015-01-01

    Dosimetic uncertainties, particularly those that are shared among subgroups of a study population, can bias, distort or reduce the slope or significance of a dose response. Exposure estimates in studies of health risks from environmental radiation exposures are generally highly uncertain and thus, susceptible to these methodological limitations. An analysis was published in 2008 concerning radiation-related thyroid nodule prevalence in a study population of 2,994 villagers under the age of 21 years old between August 1949 and September 1962 and who lived downwind from the Semi-palatinsk Nuclear Test Site in Kazakhstan. This dose-response analysis identified a statistically significant association between thyroid nodule prevalence and reconstructed doses of fallout-related internal and external radiation to the thyroid gland; however, the effects of dosimetric uncertainty were not evaluated since the doses were simple point “best estimates”. In this work, we revised the 2008 study by a comprehensive treatment of dosimetric uncertainties. Our present analysis improves upon the previous study, specifically by accounting for shared and unshared uncertainties in dose estimation and risk analysis, and differs from the 2008 analysis in the following ways: 1. The study population size was reduced from 2,994 to 2,376 subjects, removing 618 persons with uncertain residence histories; 2. Simulation of multiple population dose sets (vectors) was performed using a two-dimensional Monte Carlo dose estimation method; and 3. A Bayesian model averaging approach was employed for evaluating the dose response, explicitly accounting for large and complex uncertainty in dose estimation. The results were compared against conventional regression techniques. The Bayesian approach utilizes 5,000 independent realizations of population dose vectors, each of which corresponds to a set of conditional individual median internal and external doses for the 2,376 subjects. These 5

  5. The effect of measurement error on the dose-response curve.

    OpenAIRE

    Yoshimura, I

    1990-01-01

    In epidemiological studies for an environmental risk assessment, doses are often observed with errors. However, they have received little attention in data analysis. This paper studies the effect of measurement errors on the observed dose-response curve. Under the assumptions of the monotone likelihood ratio on errors and a monotone increasing dose-response curve, it is verified that the slope of the observed dose-response curve is likely to be gentler than the true one. The observed variance...

  6. Shared Dosimetry Error in Epidemiological Dose-Response Analyses

    Science.gov (United States)

    Stram, Daniel O.; Preston, Dale L.; Sokolnikov, Mikhail; Napier, Bruce; Kopecky, Kenneth J.; Boice, John; Beck, Harold; Till, John; Bouville, Andre

    2015-01-01

    Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed. PMID:25799311

  7. Shared Dosimetry Error in Epidemiological Dose-Response Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Stram, Daniel; Preston, D. L.; Sokolnkov, Mikhail; Napier, Bruce A.; Kopecky, Kenneth; Boice, John; Beck, Harold L.; Till, John E.; Bouville, A.

    2015-03-23

    Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. Use of these methods for several studies, including the Mayak Worker Cohort and the U.S. Atomic Veterans Study, is discussed.

  8. Shared dosimetry error in epidemiological dose-response analyses

    International Nuclear Information System (INIS)

    Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of 'possible' dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed

  9. Shared dosimetry error in epidemiological dose-response analyses.

    Directory of Open Access Journals (Sweden)

    Daniel O Stram

    Full Text Available Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR model that allows for a linear dose response (risk in relation to radiation and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations as if it was true dose (ignoring both shared and unshared dosimetry errors gives asymptotically unbiased estimates (i.e. the score has expectation zero and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed.

  10. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

    Directory of Open Access Journals (Sweden)

    Sara C Johnston

    Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

  11. Dose response of surfactants to attenuate gas embolism related platelet aggregation

    Science.gov (United States)

    Eckmann, David M.; Eckmann, Yonaton Y.; Tomczyk, Nancy

    2014-03-01

    Intravascular gas embolism promotes blood clot formation, cellular activation, and adhesion events, particularly with platelets. Populating the interface with surfactants is a chemical-based intervention to reduce injury from gas embolism. We studied platelet activation and platelet aggregation, prominent adverse responses to blood contact with bubbles. We examined dose-response relationships for two chemically distinct surfactants to attenuate the rise in platelet function stimulated by exposure to microbubbles. Significant reduction in platelet aggregation and platelet activation occurred with increasing concentration of the surfactants, indicating presence of a saturable system. A population balance model for platelet aggregation in the presence of embolism bubbles and surfactants was developed. Monte Carlo simulations for platelet aggregation were performed. Results agree qualitatively with experimental findings. Surfactant dose-dependent reductions in platelet activation and aggregation indicate inhibition of the gas/liquid interface's ability to stimulate cellular activation mechanically.

  12. Statistically significant dependence of the Xaa-Pro peptide bond conformation on secondary structure and amino acid sequence

    Directory of Open Access Journals (Sweden)

    Leitner Dietmar

    2005-04-01

    Full Text Available Abstract Background A reliable prediction of the Xaa-Pro peptide bond conformation would be a useful tool for many protein structure calculation methods. We have analyzed the Protein Data Bank and show that the combined use of sequential and structural information has a predictive value for the assessment of the cis versus trans peptide bond conformation of Xaa-Pro within proteins. For the analysis of the data sets different statistical methods such as the calculation of the Chou-Fasman parameters and occurrence matrices were used. Furthermore we analyzed the relationship between the relative solvent accessibility and the relative occurrence of prolines in the cis and in the trans conformation. Results One of the main results of the statistical investigations is the ranking of the secondary structure and sequence information with respect to the prediction of the Xaa-Pro peptide bond conformation. We observed a significant impact of secondary structure information on the occurrence of the Xaa-Pro peptide bond conformation, while the sequence information of amino acids neighboring proline is of little predictive value for the conformation of this bond. Conclusion In this work, we present an extensive analysis of the occurrence of the cis and trans proline conformation in proteins. Based on the data set, we derived patterns and rules for a possible prediction of the proline conformation. Upon adoption of the Chou-Fasman parameters, we are able to derive statistically relevant correlations between the secondary structure of amino acid fragments and the Xaa-Pro peptide bond conformation.

  13. Marginal iodide deficiency and thyroid function: Dose-response analysis for quantitative pharmacokinetic modeling

    International Nuclear Information System (INIS)

    Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 μg/kg I to the base diet (∼25 μg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal + added I, Treatment 1: 1000 μg I/kg chow) to deficient (Treatment 5: 25 μg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation.

  14. Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study.

    Science.gov (United States)

    Wali, Bushra; Ishrat, Tauheed; Won, Soonmi; Stein, Donald G; Sayeed, Iqbal

    2014-02-01

    Currently, the only approved treatment for ischaemic stroke is tissue plasminogen activator, a clot-buster. This treatment can have dangerous consequences if not given within the first 4 h after stroke. Our group and others have shown progesterone to be beneficial in preclinical studies of stroke, but a progesterone dose-response and time-window study is lacking. We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance. For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion, and subcutaneous injections at 6 h and then once every 24 h for 7 days. For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke. Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume. Both 8 and 16 mg/kg doses of progesterone produced attenuation of infarct volume compared with the placebo, and improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests. In the time-window study, the progesterone group exhibited substantial neuroprotection as late as 6 h after stroke onset. Compared with placebo, progesterone showed a significant reduction in infarct size with 3- and 6-h delays. Moderate doses (8 and 16 mg/kg) of progesterone reduced infarct size and improved functional deficits in our clinically relevant model of stroke. The 8 mg/kg dose was optimal in improving motor, sensory and memory function, and this effect was observed over a large therapeutic time window. Progesterone shows promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischaemic stroke. PMID:24374329

  15. The Shape of the Dose-Response Relationship between Sugars and Caries in Adults.

    Science.gov (United States)

    Bernabé, E; Vehkalahti, M M; Sheiham, A; Lundqvist, A; Suominen, A L

    2016-02-01

    Dental caries is considered a diet-mediated disease, as sugars are essential in the caries process. However, some gaps in knowledge about the sugars-caries relationship still need addressing. This longitudinal study aimed to explore 1) the shape of the dose-response association between sugars intake and caries in adults, 2) the relative contribution of frequency and amount of sugars intake to caries levels, and 3) whether the association between sugars intake and caries varies by exposure to fluoride toothpaste. We used data from 1,702 dentate adults who participated in at least 2 of 3 surveys in Finland (Health 2000, 2004/05 Follow-up Study of Adults' Oral Health, and Health 2011). Frequency and amount of sugars intake were measured with a validated food frequency questionnaire. The DMFT index was the repeated outcome measure. Data were analyzed with fractional polynomials and linear mixed effects models. None of the 43 fractional polynomials tested provided a better fit to the data than the simpler linear model. In a mutually adjusted linear mixed effects model, the amount of, but not the frequency of, sugars intake was significantly associated with DMFT throughout the follow-up period. Furthermore, the longitudinal association between amount of sugars intake and DMFT was weaker in adults who used fluoride toothpaste daily than in those using it less often than daily. The findings of this longitudinal study among Finnish adults suggest a linear dose-response relationship between sugars and caries, with amount of intake being more important than frequency of ingestion. Also, daily use of fluoride toothpaste reduced but did not eliminate the association between amount of sugars intake and dental caries. PMID:26553884

  16. The Shape of the Dose-Response Relationship between Sugars and Caries in Adults.

    Science.gov (United States)

    Bernabé, E; Vehkalahti, M M; Sheiham, A; Lundqvist, A; Suominen, A L

    2016-02-01

    Dental caries is considered a diet-mediated disease, as sugars are essential in the caries process. However, some gaps in knowledge about the sugars-caries relationship still need addressing. This longitudinal study aimed to explore 1) the shape of the dose-response association between sugars intake and caries in adults, 2) the relative contribution of frequency and amount of sugars intake to caries levels, and 3) whether the association between sugars intake and caries varies by exposure to fluoride toothpaste. We used data from 1,702 dentate adults who participated in at least 2 of 3 surveys in Finland (Health 2000, 2004/05 Follow-up Study of Adults' Oral Health, and Health 2011). Frequency and amount of sugars intake were measured with a validated food frequency questionnaire. The DMFT index was the repeated outcome measure. Data were analyzed with fractional polynomials and linear mixed effects models. None of the 43 fractional polynomials tested provided a better fit to the data than the simpler linear model. In a mutually adjusted linear mixed effects model, the amount of, but not the frequency of, sugars intake was significantly associated with DMFT throughout the follow-up period. Furthermore, the longitudinal association between amount of sugars intake and DMFT was weaker in adults who used fluoride toothpaste daily than in those using it less often than daily. The findings of this longitudinal study among Finnish adults suggest a linear dose-response relationship between sugars and caries, with amount of intake being more important than frequency of ingestion. Also, daily use of fluoride toothpaste reduced but did not eliminate the association between amount of sugars intake and dental caries.

  17. Bayesian dose-response analysis for epidemiological studies with complex uncertainty in dose estimation.

    Science.gov (United States)

    Kwon, Deukwoo; Hoffman, F Owen; Moroz, Brian E; Simon, Steven L

    2016-02-10

    Most conventional risk analysis methods rely on a single best estimate of exposure per person, which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2376 subjects who were exposed to fallout from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulations and comparisons against conventional regression risk analysis methods. When the estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple a priori plausible draws of dose vectors gave similar results to the conventional regression-based methods of dose-response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods and better coverage, that is, a markedly increased capability to include the true risk coefficient within the 95% credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure.

  18. Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study.

    Science.gov (United States)

    Ouwehand, Arthur C; DongLian, Cai; Weijian, Xu; Stewart, Morgan; Ni, Jiayi; Stewart, Tad; Miller, Larry E

    2014-01-16

    Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU(®) Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n=503) were randomized among three study groups: HOWARU(®) Restore probiotic 1.70×10(10) CFU (high-dose, n=168), HOWARU(®) Restore probiotic 4.17×10(9) CFU (low-dose, n=168), or placebo (n=167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p=0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p=0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients.

  19. Dose-Response Relationship between Cumulative Occupational Lead Exposure and the Associated Health Damages: A 20-Year Cohort Study of a Smelter in China

    Directory of Open Access Journals (Sweden)

    Yue Wu

    2016-03-01

    Full Text Available Long-term airborne lead exposure, even below official occupational limits, has been found to cause lead poisoning at higher frequencies than expected, which suggests that China’s existing occupational exposure limits should be reexamined. A retrospective cohort study was conducted on 1832 smelting workers from 1988 to 2008 in China. These were individuals who entered the plant and came into continuous contact with lead at work for longer than 3 months. The dose-response relationship between occupational cumulative lead exposure and lead poisoning, abnormal blood lead, urinary lead and erythrocyte zinc protoporphyrin (ZPP were analyzed and the benchmark dose lower bound confidence limits (BMDLs were calculated. Statistically significant positive correlations were found between cumulative lead dust and lead fumes exposures and workplace seniority, blood lead, urinary lead and ZPP values. A dose-response relationship was observed between cumulative lead dust or lead fumes exposure and lead poisoning (p < 0.01. The BMDLs of the cumulative occupational lead dust and fumes doses were 0.68 mg-year/m3 and 0.30 mg-year/m3 for lead poisoning, respectively. The BMDLs of workplace airborne lead concentrations associated with lead poisoning were 0.02 mg/m3 and 0.01 mg/m3 for occupational exposure lead dust and lead fume, respectively. In conclusion, BMDLs for airborne lead were lower than occupational exposure limits, suggesting that the occupational lead exposure limits need re-examination and adjustment. Occupational cumulative exposure limits (OCELs should be established to better prevent occupational lead poisoning.

  20. Light exposure at night, sleep duration, melatonin, and breast cancer: a dose-response analysis of observational studies.

    Science.gov (United States)

    Yang, Wan-Shui; Deng, Qin; Fan, Wen-Yan; Wang, Wei-Ye; Wang, Xin

    2014-07-01

    Evidence from observational studies on light at night (LAN) exposure, sleep duration, endogenous melatonin levels, and risk for breast cancer in women is conflicting. This led us to conduct a dose-response analysis of published observational data. Pertinent studies were identified by searching Medline, Web of Science, and EMBASE through April 2013. The dose-response relationship between sleep duration, urinary 6-sulphatoxymelatonin levels, and breast cancer was assessed using the restricted cubic spline model and by multivariate random-effects metaregression. A separate meta-analysis was also carried out to calculate the relative risks (RRs) with 95% confidence intervals (CIs) for breast cancer for the comparable categories or highest levels of exposure versus the lowest levels. Twelve case-control and four cohort studies were included in the analysis. High artificial LAN exposure is associated with an increased risk for breast cancer (RR=1.17, 95% CI: 1.11-1.23), but not ambient LAN exposure (RR=0.91, 95% CI: 0.78-1.07). The summary RR for breast cancer is 1.00 (95% CI: 0.995-1.01) for an increment of 1 h of sleep per night. No significant dose-response relationship between sleep duration and breast cancer was found either for the linearity test (Ptrend=0.725) or for the nonlinearity (Ptrend=0.091) test. An increasein of 15 ng/mg creatinine in urinary 6-sulphatoxymelatonin is associated with a 14% reduced risk for breast cancer (RR=0.86, 95% CI: 0.78-0.95), with a linear dose-response trend (Ptrend=0.003). There was no evidence of substantial heterogeneity or publication bias in the analysis. Our study adds to the evidence of LAN breast cancer theory. Further research in this area is warranted. PMID:24858716

  1. The Statistical Significance Test of Regional Climate Change Caused by Land Use and Land Cover Variation in West China

    Institute of Scientific and Technical Information of China (English)

    WANG Hanjie; SHI Weilai; CHEN Xiaohong

    2006-01-01

    The West Development Policy being implemented in China is causing significant land use and land cover (LULC) changes in West China. With the up-to-date satellite database of the Global Land Cover Characteristics Database (GLCCD) that characterizes the lower boundary conditions, the regional climate model RIEMS-TEA is used to simulate possible impacts of the significant LULC variation. The model was run for five continuous three-month periods from 1 June to 1 September of 1993, 1994, 1995, 1996, and 1997, and the results of the five groups are examined by means of a student t-test to identify the statistical significance of regional climate variation. The main results are: (1) The regional climate is affected by the LULC variation because the equilibrium of water and heat transfer in the air-vegetation interface is changed. (2) The integrated impact of the LULC variation on regional climate is not only limited to West China where the LULC varies, but also to some areas in the model domain where the LULC does not vary at all. (3) The East Asian monsoon system and its vertical structure are adjusted by the large scale LULC variation in western China, where the consequences are the enhancement of the westward water vapor transfer from the east oast and the relevant increase of wet-hydrostatic energy in the middle-upper atmospheric layers. (4) The ecological engineering in West China affects significantly the regional climate in Northwest China, North China and the middle-lower reaches of the Yangtze River; there are obvious effects in South, Northeast, and Southwest China, but minor effects in Tibet.

  2. In situ protocol for the determination of dose-response effect of low-fluoride dentifrices on enamel remineralization

    Directory of Open Access Journals (Sweden)

    Rebeca Lima AFONSO

    2013-12-01

    Full Text Available No in situ protocol has assessed the dose-response effects of fluoride dentifrices involving low-fluoride formulations. Objective: To assess the ability of an in situ remineralization model in determining dose-response effects of dentifrices containing low fluoride concentrations ([F] on bovine enamel. Material and Methods: Volunteers wore palatal appliances containing demineralized enamel blocks and brushed their teeth and devices with the dentifrices supplied (double-blind, crossover protocol separately for 3 and 7 days. Surface hardness (SH, integrated subsurface hardness (ΔKHN and [F] in enamel were determined. Data were analyzed by ANOVA, Tukey's test and Pearson's correlation (p<0.05. Results: Dose-response relationships were verified between [F] in dentifrices and SH, ΔKHN and enamel [F]. Higher correlation coefficients between enamel [F] and SH and ΔKHN were obtained for the 3-day period. Significant differences in SH and ΔKHN were observed among all groups for the 3-day period, but not between 0-275, 275-550, and 550-1,100 µg F/g dentifrices for the 7-day period, nor between 3- and 7-day periods for the 1,100 µg F/g groups. Conclusions: Considering that the peak remineralization capacity of the conventional dentifrice (1,100 µg F/g was achieved in 3 days, this experimental period could be used in future studies assessing new dentifrice formulations, especially at low-fluoride concentrations.

  3. Testing earthquake prediction algorithms: Statistically significant advance prediction of the largest earthquakes in the Circum-Pacific, 1992-1997

    Science.gov (United States)

    Kossobokov, V.G.; Romashkova, L.L.; Keilis-Borok, V. I.; Healy, J.H.

    1999-01-01

    Algorithms M8 and MSc (i.e., the Mendocino Scenario) were used in a real-time intermediate-term research prediction of the strongest earthquakes in the Circum-Pacific seismic belt. Predictions are made by M8 first. Then, the areas of alarm are reduced by MSc at the cost that some earthquakes are missed in the second approximation of prediction. In 1992-1997, five earthquakes of magnitude 8 and above occurred in the test area: all of them were predicted by M8 and MSc identified correctly the locations of four of them. The space-time volume of the alarms is 36% and 18%, correspondingly, when estimated with a normalized product measure of empirical distribution of epicenters and uniform time. The statistical significance of the achieved results is beyond 99% both for M8 and MSc. For magnitude 7.5 + , 10 out of 19 earthquakes were predicted by M8 in 40% and five were predicted by M8-MSc in 13% of the total volume considered. This implies a significance level of 81% for M8 and 92% for M8-MSc. The lower significance levels might result from a global change in seismic regime in 1993-1996, when the rate of the largest events has doubled and all of them become exclusively normal or reversed faults. The predictions are fully reproducible; the algorithms M8 and MSc in complete formal definitions were published before we started our experiment [Keilis-Borok, V.I., Kossobokov, V.G., 1990. Premonitory activation of seismic flow: Algorithm M8, Phys. Earth and Planet. Inter. 61, 73-83; Kossobokov, V.G., Keilis-Borok, V.I., Smith, S.W., 1990. Localization of intermediate-term earthquake prediction, J. Geophys. Res., 95, 19763-19772; Healy, J.H., Kossobokov, V.G., Dewey, J.W., 1992. A test to evaluate the earthquake prediction algorithm, M8. U.S. Geol. Surv. OFR 92-401]. M8 is available from the IASPEI Software Library [Healy, J.H., Keilis-Borok, V.I., Lee, W.H.K. (Eds.), 1997. Algorithms for Earthquake Statistics and Prediction, Vol. 6. IASPEI Software Library]. ?? 1999 Elsevier

  4. Statistical significance of rising and oscillatory trends in global ocean and land temperature in the past 160 years

    CERN Document Server

    Østvand, Lene; Rypdal, Martin

    2013-01-01

    Various interpretations of the notion of a trend in the context of global warming are discussed, contrasting the difference between viewing a trend as the deterministic response to an external forcing and viewing it as a slow variation which can be separated from the background spectral continuum of long-range persistent climate noise. The emphasis in this paper is on the latter notion, and a general scheme is presented for testing a multi-parameter trend model against a null hypothesis which models the observed climate record as an autocorrelated noise. The scheme is employed to the instrumental global sea-surface temperature record and the global land-temperature record. A trend model comprising a linear plus an oscillatory trend with period of approximately 60 yr, and the statistical significance of the trends, are tested against three different null models: first-order autoregressive process, fractional Gaussian noise, and fractional Brownian motion. The linear trend is significant in all cases, but the o...

  5. Threshold estimation based on a p-value framework in dose-response and regression settings

    CERN Document Server

    Mallik, Atul; Banerjee, Moulinath; Michailidis, George

    2011-01-01

    We use p-values to identify the threshold level at which a regression function takes off from its baseline value, a problem motivated by applications in toxicological and pharmacological dose-response studies and environmental statistics. We study the problem in two sampling settings: one where multiple responses can be obtained at a number of different covariate-levels and the other the standard regression setting involving limited number of response values at each covariate. Our procedure involves testing the hypothesis that the regression function is at its baseline at each covariate value and then computing the potentially approximate p-value of the test. An estimate of the threshold is obtained by fitting a piecewise constant function with a single jump discontinuity, otherwise known as a stump, to these observed p-values, as they behave in markedly different ways on the two sides of the threshold. The estimate is shown to be consistent and its finite sample properties are studied through simulations. Ou...

  6. Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

    Energy Technology Data Exchange (ETDEWEB)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis, E-mail: panayiotis.mavroidis@ki.se; Lind, Bengt K.; Brahme, Anders [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm S-17176 (Sweden)

    2011-05-18

    Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ{sup 2}-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.

  7. Time and total dose response of non-volatile UVPROMs

    International Nuclear Information System (INIS)

    While survivability testing of floating gate non-volatile UVPROM memory devices has been documented in numerous journals, this paper reports on the total dose radiation response and intrinsic charge loss as a function of operating time in a system. Five groups of Intel and Signetics 27C256 devices were aged from one to five years through accelerated bake to simulate system use. Characterizations of the groups with five years of simulated use will be presented in detail in this paper. Device margin voltage was characterized before and after aging and after exposure to five total dose radiation levels (1K - 5K rads (Si)). A statistical model based upon the characterization data was developed to establish re-programming intervals for these devices when used in airborne electronic systems

  8. A randomized trial in a massive online open course shows people don't know what a statistically significant relationship looks like, but they can learn

    OpenAIRE

    Aaron Fisher; G. Brooke Anderson; Roger Peng; Jeff Leek

    2014-01-01

    Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online cour...

  9. Inhalation of racemic epinephrine in children with asthma. Dose-response relation and comparison with salbutamol.

    Science.gov (United States)

    Kjellman, B; Tollig, H; Wettrell, G

    1980-10-01

    In this study the effects of nebulized racemic epinephrine (Micronephrine) were investigated in children with asthma. The drug was inhaled by a compressor nebulizer with a plastic mask. In the first part of the study it is shown that nebulized Micronephrine has a dose-dependent bronchodilatory effect. In the second part the effect is compared with that of nebulized salbutamol in 10 children (7-16 years of age) with bronchial asthma. The highest dose used in the dose-response trials (=0.9 mg Micronephrine/kg body-weight) was compared with 0.15 mg salbutamol/kg body-weight, which is the dose commonly used in Sweden. There was no significant difference between the drugs as regards increase of forced expiratory volume in 1 sec or duration of the increase. There was a small but significant increase in systolic blood pressure, measured 5 min after the inhalation of Micronephrine but no significant change in diastolic pressure or heart rate. Four children complained of temporary sore throat after the inhalation. PMID:7468946

  10. Statistical analysis and significance testing of serial analysis of gene expression data using a Poisson mixture model

    Directory of Open Access Journals (Sweden)

    Zuyderduyn Scott D

    2007-08-01

    Full Text Available Abstract Background Serial analysis of gene expression (SAGE is used to obtain quantitative snapshots of the transcriptome. These profiles are count-based and are assumed to follow a Binomial or Poisson distribution. However, tag counts observed across multiple libraries (for example, one or more groups of biological replicates have additional variance that cannot be accommodated by this assumption alone. Several models have been proposed to account for this effect, all of which utilize a continuous prior distribution to explain the excess variance. Here, a Poisson mixture model, which assumes excess variability arises from sampling a mixture of distinct components, is proposed and the merits of this model are discussed and evaluated. Results The goodness of fit of the Poisson mixture model on 15 sets of biological SAGE replicates is compared to the previously proposed hierarchical gamma-Poisson (negative binomial model, and a substantial improvement is seen. In further support of the mixture model, there is observed: 1 an increase in the number of mixture components needed to fit the expression of tags representing more than one transcript; and 2 a tendency for components to cluster libraries into the same groups. A confidence score is presented that can identify tags that are differentially expressed between groups of SAGE libraries. Several examples where this test outperforms those previously proposed are highlighted. Conclusion The Poisson mixture model performs well as a a method to represent SAGE data from biological replicates, and b a basis to assign significance when testing for differential expression between multiple groups of replicates. Code for the R statistical software package is included to assist investigators in applying this model to their own data.

  11. A randomized trial in a massive online open course shows people don’t know what a statistically significant relationship looks like, but they can learn

    Directory of Open Access Journals (Sweden)

    Aaron Fisher

    2014-10-01

    Full Text Available Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC. Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%–49.7%] of statistically significant relationships, and 74.6% (95% CI [72.5%–76.6%] of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1 that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2 data analysts can be trained to improve detection of statistically significant results with practice, but (3 data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/.

  12. A randomized trial in a massive online open course shows people don’t know what a statistically significant relationship looks like, but they can learn

    Science.gov (United States)

    Fisher, Aaron; Anderson, G. Brooke; Peng, Roger

    2014-01-01

    Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC). Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%–49.7%]) of statistically significant relationships, and 74.6% (95% CI [72.5%–76.6%]) of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1) that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2) data analysts can be trained to improve detection of statistically significant results with practice, but (3) data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/. PMID:25337457

  13. A randomized trial in a massive online open course shows people don't know what a statistically significant relationship looks like, but they can learn.

    Science.gov (United States)

    Fisher, Aaron; Anderson, G Brooke; Peng, Roger; Leek, Jeff

    2014-01-01

    Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC). Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%-49.7%]) of statistically significant relationships, and 74.6% (95% CI [72.5%-76.6%]) of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1) that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2) data analysts can be trained to improve detection of statistically significant results with practice, but (3) data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/. PMID:25337457

  14. Folate intake and the risk of breast cancer: a dose-response meta-analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Yu-Fei Zhang

    Full Text Available BACKGROUND: Previous observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: We performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that reported breast cancer effect estimates with 95% confidence intervals (CIs for more than 2 folate intake categories were included. We excluded traditional case-control studies because of possible bias from various confounding factors. Overall, we included 14 prospective studies that reported data on 677,858 individuals. Folate intake had little effect on the breast cancer risk (relative risk (RR for highest versus lowest category = 0.97; 95% CI, 0.90-1.05; P = 0.451. Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of breast cancer (RR = 0.99; 95% CI, 0.98-1.01; P = 0.361. Furthermore, we used restricted cubic splines to evaluate the nonlinear relationship between folate intake and the risk of breast cancer, and discovered a potential J-shaped correlation between folate intake and breast cancer risk (P = 0.007 and revealed that a daily folate intake of 200-320 µg was associated with a lower breast cancer risk; however, the breast cancer risk increased significantly with a daily folate intake >400 µg. CONCLUSION/SIGNIFICANCE: Our study revealed that folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested a J-shaped association between folate intake and breast cancer.

  15. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

    Science.gov (United States)

    Urbain, Paul; Jakobsen, Jette

    2015-09-23

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon. PMID:26314311

  16. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms

    DEFF Research Database (Denmark)

    Urbain, Paul; Jakobsen, Jette

    2015-01-01

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour...... of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered...... a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P mushrooms and comparable to levels found...

  17. Dose - response relationship between noise exposure and the risk of occupational injury

    Directory of Open Access Journals (Sweden)

    Jin-Ha Yoon

    2015-01-01

    Full Text Available Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers′ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively. Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals derived from a logistic regression model were 1.68 (1.27-2.24 and 3.42 (2.26-5.17 at 80-89 dB and ≥90 dB versus <80 dB. These associations remained significant when in a separate analysis according to high or low dust exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

  18. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis.

    Science.gov (United States)

    Bo, Yacong; Lu, Yan; Zhao, Yan; Zhao, Erjiang; Yuan, Ling; Lu, Weiquan; Cui, Lingling; Lu, Quanjun

    2016-04-15

    While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.

  19. Youth suicide attempts and the dose-response relationship to parental risk factors: a population-based study

    DEFF Research Database (Denmark)

    Christiansen, E; Goldney, R D; Beautrai, A L;

    2011-01-01

    for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 (0.8%) were registered as having had a suicide attempt. Twenty controls were matched...... illness and low level of income were all significant independent risk factors for offspring's suicide attempts. CONCLUSIONS: Knowledge of the effect of multiple risk factors on the likelihood of suicide attempts in children and adolescents is important for risk assessment. Dose-response effects...

  20. The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, T., E-mail: schmito@uni-mainz.de [Institute for nuclear chemistry, Johannes Gutenberg-University, Mainz D-55128 (Germany); Bassler, N. [Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, Aarhus C, Aarhus 8000 (Denmark); Blaickner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220 (Austria); Ziegner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220, Austria and TU Wien, Vienna University of Technology, Vienna A-1020 (Austria); Hsiao, M. C. [Insitute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Liu, Y. H. [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Koivunoro, H. [Department of Physics, University of Helsinki, POB 64, FI-00014, Finland and HUS Medical Imaging Center, Helsinki University Central Hospital, FI-00029 HUS (Finland); Auterinen, I.; Serén, T.; Kotiluoto, P. [VTT Technical Research Centre of Finland, Espoo (Finland); Palmans, H. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW, United Kingdom and Medical Physics Group, EBG MedAustron GmbH, Wiener Neustadt A-2700 (Austria); Sharpe, P. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW (United Kingdom); Langguth, P. [Department of Pharmacy and Toxicology, University of Mainz, Mainz D-55128 (Germany); Hampel, G. [Institut für Kernchemie, Johannes Gutenberg-Universität, Mainz D-55128 (Germany)

    2015-01-15

    Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The

  1. Dose-response relationships using brain-computer interface technology impact stroke rehabilitation.

    Science.gov (United States)

    Young, Brittany M; Nigogosyan, Zack; Walton, Léo M; Remsik, Alexander; Song, Jie; Nair, Veena A; Tyler, Mitchell E; Edwards, Dorothy F; Caldera, Kristin; Sattin, Justin A; Williams, Justin C; Prabhakaran, Vivek

    2015-01-01

    Brain-computer interfaces (BCIs) are an emerging novel technology for stroke rehabilitation. Little is known about how dose-response relationships for BCI therapies affect brain and behavior changes. We report preliminary results on stroke patients (n = 16, 11 M) with persistent upper extremity motor impairment who received therapy using a BCI system with functional electrical stimulation of the hand and tongue stimulation. We collected MRI scans and behavioral data using the Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) before, during, and after the therapy period. Using anatomical and functional MRI, we computed Laterality Index (LI) for brain activity in the motor network during impaired hand finger tapping. Changes from baseline LI and behavioral scores were assessed for relationships with dose, intensity, and frequency of BCI therapy. We found that gains in SIS Strength were directly responsive to BCI therapy: therapy dose and intensity correlated positively with increased SIS Strength (p ≤ 0.05), although no direct relationships were identified with ARAT or 9-HPT scores. We found behavioral measures that were not directly sensitive to differences in BCI therapy administration but were associated with concurrent brain changes correlated with BCI therapy administration parameters: therapy dose and intensity showed significant (p ≤ 0.05) or trending (0.05 stroke rehabilitation, therapy frequency may be less important than dose and intensity.

  2. Gamma- and electron dose response of the electrical conductivity of polyaniline based polymer blends

    International Nuclear Information System (INIS)

    Complete text of publication follows. Conducting polymers, also known as 'synthetic metals' have been the subject of widespread investigations over the past decade due to their very promising characteristics. Polyaniline (PANI) holds a special position among conducting polymers in that its most highly conducting doped form can be reached by protonic acid doping or oxidative doping. It was published earlier, that the electrical conductivity of some polyaniline based polymer composites increases to a significant extent when irradiated to gamma, electron or UV radiation. The aim of the present study was to measure the high frequency conductivity of blended films of PANI with poly(vinylchloride), PVC, and chlorinated poly(propylene) irradiated in air to different doses. In order to find the most suitable composition od these composites the mass percentage of PANI within the PPCl and PVC matrix was changed between 5 - 30%. These samples were then gamma irradiated and the induced electrical conductivity was measured in the 1 kHz - 1 MHz frequency range to determine the most sensitive evaluation conditions. After selecting both the most suitable measuring conditions as well as the blend compositions the dose response of the chosen samples was determined in the dose range of 10 - 250 kGy. With respect to potential dosimetry application the effect of electron irradiation, the effect of irradiation temperature and the stability of the irradiated samples have also been investigated

  3. Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry

    International Nuclear Information System (INIS)

    The aim of this thesis is to contribute to a better understanding of the health effects of chronic external low doses of ionising radiation. This work is based on the French cohort of CEA-AREVA NC nuclear workers. The mains stages of this thesis were (1) conducting a review of epidemiological studies on nuclear workers, (2) completing the database and performing a descriptive analysis of the cohort, (3) quantifying risk by different statistical methods and (4) modelling the exposure-time-risk relationship. The cohort includes monitored workers employed more than one year between 1950 and 1994 at CEA or AREVA NC companies. Individual annual external exposure, history of work, vital status and causes of death were reconstructed for each worker. Standardized mortality ratios using French national mortality rates as external reference were computed. Exposure-risk analysis was conducted in the cohort using the linear excess relative risk model, based on both Poisson regression and Cox model. Time dependent modifying factors were investigated by adding an interaction term in the model or by using exposure time windows. The cohort includes 36, 769 workers, followed-up until age 60 in average. During the 1968- 2004 period, 5, 443 deaths, 2, 213 cancers, 62 leukemia and 1, 314 cardiovascular diseases were recorded. Among the 57% exposed workers, the mean cumulative dose was 21.5 milli-sieverts (mSv). A strong Healthy Worker Effect is observed in the cohort. Significant elevated risks of pleura cancer and melanoma deaths were observed in the cohort but not associated with dose. No significant association was observed with solid cancers, lung cancer and cardiovascular diseases. A significant dose-response relationship was observed for leukemia excluding chronic lymphatic leukemia, mainly for doses received less than 15 years before and for yearly dose rates higher than 10 mSv. This PhD work contributes to the evaluation of risks associated to chronic external radiation

  4. Radiation dose-response relationship of micronucleus occurrence in pollen mother cells of tradescantia

    International Nuclear Information System (INIS)

    This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronucleus showed a good dose-response relationship in the range of dose 0∼50 cGy. On the basis of the relationship, a dose of 1 cGy resulted in two additional micronuclei in 100 tetrads. The radiation dose-response relationship of micronucleus occurrence is prerequisite to biological monitoring of radiation and can be modified for biological risk assessment of toxicants, and to safety test of water or soil integrity

  5. Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Torekov, Signe Sørensen; Kipnes, M S; Harley, R E;

    2011-01-01

    To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles.......To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles....

  6. Dose response and fading characteristics of an alanine-agarose gel

    International Nuclear Information System (INIS)

    The dose response of an alanine-agarose gel, analyzed by ESR spectrometry, and the stability of the radiation-induced free radicals have been investigated. The stability of the ESR signal is higher for dosimeter samples analyzed at 77 K than for dried samples, analyzed at room-temperature. The dose response is linear to within ±2% in the absorbed dose interval 2-100 Gy. The variations in spectral line shape were analyzed at temperatures between 77 and 270 K. The experimental ESR spectrum at 77 K was compared with a simulated spectrum of polycrystals of L-α-alanine. (Author)

  7. Dietary magnesium intake and metabolic syndrome in the adult population: dose-response meta-analysis and meta-regression.

    Science.gov (United States)

    Ju, Sang-Yhun; Choi, Whan-Seok; Ock, Sun-Myeong; Kim, Chul-Min; Kim, Do-Hoon

    2014-12-22

    ncreasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational studies reporting risk ratios with 95% confidence intervals (CIs) for metabolic syndrome in ≥ 3 categories of dietary magnesium intake levels were selected. The data extraction was performed independently by two authors, and the quality of the studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Based on eight cross-sectional studies and two prospective cohort studies, the pooled relative risks of metabolic syndrome per 150 mg/day increment in magnesium intake was 0.88 (95% CI, 0.84-0.93; I(2) = 36.3%). The meta-regression model showed a generally linear, inverse relationship between magnesium intake (mg/day) and metabolic syndrome. This dose-response meta-analysis indicates that dietary magnesium intake is significantly and inversely associated with the risk of metabolic syndrome. However, randomized clinical trials will be necessary to address the issue of causality and to determine whether magnesium supplementation is effective for the prevention of metabolic syndrome.

  8. Limitations in dose-response and surrogate species methodologies for risk assessment of Cry toxins on arthropod natural enemies.

    Science.gov (United States)

    Paula, Débora P; Andow, David A; Bellinati, André; Timbó, Renata Velozo; Souza, Lucas M; Pires, Carmen S S; Sujii, Edison R

    2016-04-01

    Dose-response assays and surrogate species are standard methods for risk analysis for environmental chemicals. These assume that individuals within a species have unimodal responses and that a surrogate species can predict responses of other related taxa. We exposed immature individuals of closely related aphidophagous coccinellid predators, Cycloneda sanguinea and Harmonia axyridis, to Cry1Ac and Cry1F toxins through uniform and constant artificial tritrophic exposure through Myzus persicae aphids. Both toxins were detected in coccinellid pupae, with individual and interspecific variation. Uptake was significantly higher in H. axyridis than in C. sanguinea, both in the proportion of individuals and the concentrations per individual. We also observed bimodal uptake of the Cry toxins by H. axyridis, which indicated that some individuals had low bioaccumulation and some had high bioaccumulation. This suggests that standard dose-response assays need to be interpreted with caution and future assays should examine the modality of the responses. In addition, the similarity in the biological effects of the Cry toxins in the two predators was due to different biological exposure mechanisms. The majority of H. axyridis were exposed both internally and in the gut, while C. sanguinea was exposed primarily in the gut. Thus, despite their close phylogenetic relatedness, these species would not be good surrogates for each other and the surrogate species methodology should be tested more rigorously. PMID:26846212

  9. Statistic characteristics and weather significance of infrared TBB during May―August in Beijing and its vicinity

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In order to meet the demand of nowcasting convective storms in Beijing, the climatological characteristics of convective storms in Beijing and its vicinity were analyzed based on the infrared (IR) temperature of black body (TBB) data during May―August of 1997―2004. The climatological probabilities, the diurnal cycle and the spatial distribution of convective storms are given respectively in this paper. The results show that the climatological characteristics of convective storms denoted by TBB≤-52℃ are consistent with those statistic studies based on the surface and lightning observations. Furthermore, the climatological characteristics of May and June are very different from those of July and August, showing that there are two types of convective storms in this region. One occurs in the transient polar air mass on the midlatitude continent during the late spring and early summer. This type of convection arises with thunder, strong wind gust and hail over the mountainous area in the northern part of this region from afternoon to nightfall, the other occurs with heavy rainfall in the warm and moist air mass over the North China Plain and vicinity of Bohai Sea. This study also shows that the long-term data of IR TBB observed by geostationary satellite can complement the temporal and spatial limitation of the weather radar and surface observations.

  10. Dose-response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity

    NARCIS (Netherlands)

    Imre, G; Fokkema, DS; Den Boer, JA; Ter Horst, GJ

    2006-01-01

    The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PP1), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined

  11. Dose response of a new phytse on dry matter, calcium, and phosphorus digestibility in weaned piglets

    NARCIS (Netherlands)

    Bento, M.H.L.; Pedersen, C.; Plumstead, P.W.; Salmon, L.; Nyachoti, C.M.; Bikker, P.

    2012-01-01

    The present study evaluated the dose response of Buttiauxella phytase on apparent total tract digestibility (ATTD) of DM, Ca, and P in weaned pigs at 2 locations. Experimental diets fed to weaned pigs were a positive control (PC), a negative control (NC), and NC supplemented with increasing levels o

  12. The Dose-Response Relationship of Adolescent Religious Activity and Substance Use: Variation across Demographic Groups

    Science.gov (United States)

    Steinman, Kenneth J.; Ferketich, Amy K.; Sahr, Timothy

    2008-01-01

    This article addresses two inconsistent findings in the literature on adolescent religious activity (RA) and substance use: whether a dose-response relationship characterizes the association of these variables, and whether the association varies by grade, gender, ethnicity, family structure, school type, and type of substance. Multinomial logistic…

  13. Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity

    NARCIS (Netherlands)

    G. Koshy; A. Delpisheh; B.J. Brabin

    2011-01-01

    The combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported. A community based cross-sectional survey of 3038 children aged 5-11 years from 15 primary schools in Merseyside, UK. Self-completed parental questionnai

  14. Development of the dose-response relationship for human toxoplasma gondii infection associated with meat consumption

    Science.gov (United States)

    Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States.A substantial portion of human T. gondii infections may be acquired through the consumption of meats. The dose-response relationship for human exposure...

  15. Cytogenetics dosimetry: dose-response curve for low doses of X-ray

    International Nuclear Information System (INIS)

    The purpose of this study was to conduct a preliminary study for the standardization in the future, the dose-response curve for low doses of X-rays, through the analysis of in vitro cultures of peripheral blood samples of 3 men and 3 women occupationally not exposed to artificial sources of ionizing radiation, age 18-40 years, where possible nonsmokers

  16. Dose-Response Issues Concerning the Relations between Regular Physical Activity and Health.

    Science.gov (United States)

    Rankinen, Tuomo; Bouchard, Claude

    2002-01-01

    This paper categorizes the many benefits of physical activity, offering information concerning the type of dose necessary to get that benefit. In 2000, Health Canada and the United States Centers for Disease Control and Prevention, along with other agencies, sponsored a symposium to determine whether there was a dose-response relationship between…

  17. Analysis/plot generation code with significance levels computed using Kolmogorov-Smirnov statistics valid for both large and small samples

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, S.E.; Fields, D.E.

    1983-10-01

    This report describes a version of the TERPED/P computer code that is very useful for small data sets. A new algorithm for determining the Kolmogorov-Smirnov (KS) statistics is used to extend program applicability. The TERPED/P code facilitates the analysis of experimental data and assists the user in determining its probability distribution function. Graphical and numerical tests are performed interactively in accordance with the user's assumption of normally or log-normally distributed data. Statistical analysis options include computation of the chi-square statistic and the KS one-sample test statistic and the corresponding significance levels. Cumulative probability plots of the user's data are generated either via a local graphics terminal, a local line printer or character-oriented terminal, or a remote high-resolution graphics device such as the FR80 film plotter or the Calcomp paper plotter. Several useful computer methodologies suffer from limitations of their implementations of the KS nonparametric test. This test is one of the more powerful analysis tools for examining the validity of an assumption about the probability distribution of a set of data. KS algorithms are found in other analysis codes, including the Statistical Analysis Subroutine (SAS) package and earlier versions of TERPED. The inability of these algorithms to generate significance levels for sample sizes less than 50 has limited their usefulness. The release of the TERPED code described herein contains algorithms to allow computation of the KS statistic and significance level for data sets of, if the user wishes, as few as three points. Values computed for the KS statistic are within 3% of the correct value for all data set sizes.

  18. Dose-response effects of atropine and HI-6 treatment of organophosphorus poisoning in guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Koplovitz, I.; Menton, R.; Matthews, C.; Shutz, M.; Nalls, C.

    1995-12-31

    H1-6 (1-2-hydrnxyiminomethyl-1 pyridino-3-(4-carbameyl- 1--pyddino)-2- oxaprnpane dichioride) has been evaluated as an oxime alternative to pralidoxime, and toxogonin in the treatment of organophosphorus (OP) poisoning. The dose response effects of atropine (ATR) and HI-6 were investigated to more fully explore the interaction of these compounds in the treatment of OP poisoning. ATR, HI-6 and various combinations of the two drugs were evaluated against lethal poisoning by soman (GD) and tabun (GA) in guinea pigs. The effect of adjunctive diazepam treatment on the efficacy of atropine and HI-6 against soman was also investigated. Animals of either sex were challenged s.c. with OP and treated i.m. 1 min later with ATR and/or HI-6. When used, diazepam was injected immediately after ATR+HI6. LD50s of each treatment were calculated from probit models based on 24-hour survival against 5 levels of nerve agent and 6 animals per challenge level. A protective index (PI) was calculated by dividing the nerve agent LD50 in the presence of treatment by the LD50 in the absence of treatment. Treatment with HI-6 alone had little effect on the toxicity of either OP. Treatment with ATR alone was more effective than HI-6 alone and was significantly more effective against soman than against tabun. When used in combination atropine and HI-6 had a strong synergistic effect against both agents. The dose of atropine used with HI-6 was critical in determining the efficacy of HI-6 against either agent. The slopes of the dose-lethality curves were minimally affected by the dose of ATR or HI-6. Adjunctive treatment with diazepam enhanced the efficacy of HI-6 and atropine against soman.

  19. Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships

    International Nuclear Information System (INIS)

    Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback

  20. Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose volume outcome relationships

    Science.gov (United States)

    El Naqa, I.; Suneja, G.; Lindsay, P. E.; Hope, A. J.; Alaly, J. R.; Vicic, M.; Bradley, J. D.; Apte, A.; Deasy, J. O.

    2006-11-01

    Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

  1. Test the Overall Significance of p-values by Using Joint Tail Probability of Ordered p-values as Test Statistic

    NARCIS (Netherlands)

    Fang, Yongxiang; Wit, Ernst

    2008-01-01

    Fisher’s combined probability test is the most commonly used method to test the overall significance of a set independent p-values. However, it is very obviously that Fisher’s statistic is more sensitive to smaller p-values than to larger p-value and a small p-value may overrule the other p-values a

  2. Dairy products consumption and risk of type 2 diabetes: systematic review and dose-response meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dengfeng Gao

    Full Text Available BACKGROUND: The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM, but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies, low-fat dairy products (8 studies, cheese (7 studies and yogurt (7 studies and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97 and 0.88 (0.84-0.93 for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93 and 0.91 (0.82-1.00 for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. CONCLUSION: A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

  3. Genotoxicity testing: moving beyond qualitative "screen and bin" approach towards characterization of dose-response and thresholds.

    Science.gov (United States)

    Pottenger, Lynn H; Gollapudi, B Bhaskar

    2010-01-01

    For more than 40+ years, genotoxicity data have been interpreted in a qualitative, binary mode; a chemical is considered either positive or negative for a response in the test system. Although dose-response information is sometimes used in this decision, it is not routine to obtain the amount of information needed to inform risk assessment, for example to determine no-observed-genotoxic-effect-levels, primarily due to the historical view of genotoxic responses as "linear, no-threshold." Only recently have researchers begun to address this issue through robust experimental designs and application of statistical models. A growing body-of-evidence supports the existence of response thresholds for a number of mutagenic agents, in vitro and in vivo. Clearly, simple observation of a "hockey-stick" dose-response curve is not sufficient to establish a threshold. Collection of robust empirical data must be supported with an analysis of biological plausibility for the observed threshold. In this context, a chemical-specific mode-of-action (MOA) approach, which identifies key events responsible for the observed mutagenic effect, is extremely valuable. Biomarkers of key events, providing qualitative and quantitative information, can be integrated in a weight-of-evidence-based assessment of genotoxicity data from multiple test systems and used to identify data gaps to resolve/reduce uncertainties during the risk assessment process. To this end, specific recommendations on study design and data analysis are proposed. As the Environmental Mutagen Society celebrates its 40th anniversary, the field of genetic toxicology is marking a milestone on the path to a new paradigm, using a MOA, data-driven approach to answer questions about thresholds for genotoxic agents. PMID:20806283

  4. Tenuous dose-response correlations for common disease states: case study of cholesterol and perfluorooctanoate/sulfonate (PFOA/PFOS) in the C8 Health Project.

    Science.gov (United States)

    Kerger, Brent D; Copeland, Teri L; DeCaprio, Anthony P

    2011-10-01

    Persistent organic chemicals, such as perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), dioxins, and polychlorinated biphenyls, pose investigative challenges because they are found in virtually everyone (there is no unexposed control group). To overcome this problem, outcome data in some studies are sorted by chemical dose level and findings in low-end dose groups are compared to sequential higher dose groups. An example is the C8 Health Project that evaluated serum PFOA/PFOS (C8) and total cholesterol among 46,294 West Virginia residents who lived, worked, or went to school for at least 1 year in a C8 contaminated drinking-water district and were over age 18 in 2005-2006. The risk for high total cholesterol (>240 mg/dL) measured via odds ratios (ORs) in logistic regression models showed sequential OR increases with PFOA quartile, in comparison to the lowest quartile (OR = 1.00), that were each significantly elevated (OR = 1.21, 1.33, and 1.40, respectively), but age, sex, and body mass index were stronger correlates. Importantly, the magnitude of cholesterol increase was small (12 mg/dL from lowest to highest exposure deciles) and comparison to similar statistics for the general U.S. population showed the C8 cohort had lower rates of high cholesterol. This suggests that inadvertent selection bias may have affected the lowest exposure quartile (control group), making tenuous the dose-response relationship between PFOA/PFOS and risk of high cholesterol. This case illustrates the substantial difficulties in assigning toxicological importance to statistical comparisons for common disease states that utilize subgroups with low exposures as an effective control group. PMID:21770727

  5. The Role of Baryons in Creating Statistically Significant Planes of Satellites around Milky Way-Mass Galaxies

    CERN Document Server

    Ahmed, Sheehan H; Christensen, Charlotte R

    2016-01-01

    We investigate whether the inclusion of baryonic physics influences the formation of thin, coherently rotating planes of satellites such as those seen around the Milky Way and Andromeda. For four Milky Way-mass simulations, each run both as dark matter-only and with baryons included, we are able to identify a planar configuration that significantly maximizes the number of plane satellite members. The maximum plane member satellites are consistently different between the dark matter-only and baryonic versions of the same run due to the fact that satellites are both more likely to be destroyed and to infall later in the baryonic runs. Hence, studying satellite planes in dark matter-only simulations is misleading, because they will be composed of different satellite members than those that would exist if baryons were included. Additionally, the destruction of satellites in the baryonic runs leads to less radially concentrated satellite distributions, a result that is critical to making planes that are statistica...

  6. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y [University of Michigan, Ann Arbor, MI (United States)

    2014-06-15

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  7. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 Diabetics

    NARCIS (Netherlands)

    Nesse, Willem; Linde, Annemiek; Abbas, Frank; Spijkervet, Frederik Karst Lucien; Dijkstra, Pieter Ubele; de Brabander, Eric Carl; Gerstenbluth, Izzy; Vissink, Arjan

    2009-01-01

    Nesse W, Linde A, Abbas F, Spijkervet FKL, Dijkstra PU, de Brabander EC, Gerstenbluth I, Vissink A. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 diabetics. J Clin Periodontol 2009; 36: 295-300. doi: 10.1111/j.1600-051X.2009.01377.x. A dose-response relatio

  8. Influence of Relative Humidity, Dose Rate and Dose Fractionation on Gamma Dose Response of Glycine Dosimetric System

    OpenAIRE

    Santosh H. Shinde; T. Mukherjee

    2011-01-01

    Glycine dosimeter based on spectrophotometric read-out method has great potential for gamma dosimetry in low dose applications of radiation processing. However, external factors such as relative humidity, dose rate, and dose fractionation, may have a profound effect on its gamma dose response Influence of these factors on the gamma dose response of glycine dosimeter was studied in the present work.

  9. The impact of different dose response parameters on biologically optimized IMRT in breast cancer

    Science.gov (United States)

    Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.

    2008-05-01

    The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients

  10. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  11. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    International Nuclear Information System (INIS)

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF

  12. Dose-response association between leisure time physical activity and work ability

    DEFF Research Database (Denmark)

    Calatayud, Joaquin; Jakobsen, Markus D.; Sundstrup, Emil;

    2015-01-01

    INTRODUCTION: Regular physical activity is important for longevity and health, but knowledge about the optimal dose of physical activity for maintaining good work ability is unknown. This study investigates the association between intensity and duration of physical activity during leisure time......, lifestyle and chronic disease showed that the duration of high-intensity physical activity during leisure was positively associated with work ability, in a dose-response fashion (p physical activity per week had on average 8 points higher work ability...... than those not performing such activities. The duration of low-intensity leisure-time physical activity was not associated with work ability (p = 0.5668). CONCLUSIONS: The duration of high-intensity physical activity during leisure time is associated in a dose-response fashion with work ability...

  13. Aspartame tablets-gamma dose response and usability for routine radiation processing dosimetry using spectrophotometry

    Energy Technology Data Exchange (ETDEWEB)

    Shinde, S.H. [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: shs_barc@yahoo.com; Mukherjee, T. [Radiation Safety Systems Division, Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2007-02-15

    Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10{sup -4}moldm{sup -3} and xylenol orange with 2.5x10{sup -1}moldm{sup -3} of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%.

  14. Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis

    DEFF Research Database (Denmark)

    Trauelsen, Anne Marie; Bendall, Sarah; Jansen, Jens Einar;

    2015-01-01

    BACKGROUND: Reviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk...... of psychosis have not been consistently found. The current study aimed to explore adversity specificity and dose-response effects of adversities on risk of psychosis. METHOD: Participants were 101 persons with first-episode psychosis (FEP) diagnosed with ICD-10 F20 - F29 (except F21) and 101 non......% of the control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all ppsychosis increased two and a half times for each additional adversity. All...

  15. Dose Effects of Ion Beam Exposure on Deinococcus Radiodurans: Survival and Dose Response

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To explore the survival and dose response of organism for different radiation sources is of great importance in the research of radiobiology. In this study, the survival-dose response of Deinococcus radiodurans (E.coli, as the control) for ultra-violet (UV), γ-rays radiation and ion beam exposure was investigated. The shoulder type of survival curves were found for both UV and γ-ray ionizing radiation, but the saddle type of survival curves were shown for H+ 、 N+( 20keV and 30keV) and Ar+ beam exposure. This dose effect of the survival initially decreased withthe increase in dose and then increased in the high dose range and finally decreased again in thehigher dose range. Our experimental results suggest that D. radiodurans, which is considerablyradio-resistant to UV and x-ray and γ-ray ionizing radiation, do not resist ion beam exposure.

  16. Dose Effects of Ion Beam Exposure on Deinococcus Radiodurans: Survival and Dose Response

    Science.gov (United States)

    Song, Dao-jun; Wu, Li-fang; Wu, Li-jun; Yu, Zeng-liang

    2001-02-01

    To explore the survival and dose response of organism for different radiation sources is of great importance in the research of radiobiology. In this study, the survival-dose response of Deinococcus radiodurans (E.coli, as the control) for ultra-violet (UV), γ-rays radiation and ion beam exposure was investigated. The shoulder type of survival curves were found for both UV and γ-ray ionizing radiation, but the saddle type of survival curves were shown for H+, N+(20keV and 30keV) and Ar+ beam exposure. This dose effect of the survival initially decreased with the increase in dose and then increased in the high dose range and finally decreased again in the higher dose range. Our experimental results suggest that D. radiodurans, which is considerably radio-resistant to UV and x-ray and γ-ray ionizing radiation, do not resist ion beam exposure.

  17. Dose-response relationships of polycyclic aromatic hydrocarbons exposure and oxidative damage to DNA and lipid in coke oven workers.

    Science.gov (United States)

    Kuang, Dan; Zhang, Wangzhen; Deng, Qifei; Zhang, Xiao; Huang, Kun; Guan, Lei; Hu, Die; Wu, Tangchun; Guo, Huan

    2013-07-01

    Polycyclic aromatic hydrocarbons (PAHs) are known to induce reactive oxygen species and oxidative stress, but the dose-response relationships between exposure to PAHs and oxidative stress levels have not been established. In this study, we recruited 1333 male coke oven workers, monitored the levels of environmental PAHs, and measured internal PAH exposure biomarkers including 12 urinary PAH metabolites and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, as well as the two oxidative biomarkers urinary 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α). We found that the total concentration of urinary PAH metabolites and plasma BPDE-Alb adducts were both significantly associated with increased 8-OHdG and 8-iso-PGF2α in both smokers and nonsmokers (all p coke oven workers. PMID:23745771

  18. Separation of Points and Interval Estimation in Mixed Dose-Response Curves with Selective Component Labeling

    OpenAIRE

    Flake, Darl D.

    2016-01-01

    This dissertation develops, applies, and investigates new methods to improve the analysis of logistic regression mixture models. An interesting dose-response experiment was previously carried out on a mixed population, in which the class membership of only a subset of subjects (survivors) were subsequently labeled. In early analyses of the dataset, challenges with separation of points and asymmetric confidence intervals were encountered. This dissertation extends the previous analyses by char...

  19. Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Yuece, Ulkue Rabia, E-mail: ulkuyuce@hotmail.co [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Meric, Niyazi, E-mail: meric@ankara.edu.t [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Atakol, Orhan, E-mail: atakol@science.ankara.edu.t [Ankara University, Science Faculty, Department of Chemistry, 06100, Tandogan - Ankara (Turkey); Yasar, Fusun, E-mail: ab121310@adalet.gov.t [Council of Forensic Medicine, Ankara Branch, Ankara (Turkey)

    2010-08-15

    The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.

  20. Dose-response effects of gamma irradiation on colour and antioxidant activity of wild Malva neglecta

    OpenAIRE

    Pinela, José; Antonio, Amilcar L.; Barros, Lillian; Carvalho, Ana Maria; Oliveira, M.B.P.P.; Ferreira, Isabel C. F. R.

    2014-01-01

    Radiation processing technology has been used to improve food security, safety and quality. However there are a few reports in the literature on the effect of irradiation on bioactivity of herbs and medicinal plants [1]. Hence, the present work was undertaken to investigate the dose-response effects of gamma irradiation on the colour and antioxidant activity of wild Malva neglecta Wallr. In the north-eastern of Portugal, this annual herbaceous plant is traditionally eaten raw as leafy vegetab...

  1. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

    OpenAIRE

    Johnston, Sara C.; Lin, Kenny L.; Twenhafel, Nancy A.; Raymond, Jo Lynne W.; Shamblin, Joshua D.; Wollen, Suzanne E.; Wlazlowski, Carly B.; Wilkinson, Eric R.; Botto, Miriam A.; Goff, Arthur J.

    2015-01-01

    Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-ex...

  2. A comparison of dose-response models for death from hematological depression

    International Nuclear Information System (INIS)

    Many radiation-induced lethality experiments that have been published for various mammalian species have been compiled into a database suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behavior within each experiment, etc. The data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Also, photon source energy, exposure geometry, and body weight considerations were used to select studies where the dose to hematopoietic marrow was nearly uniform, i.e., < +- 20%. The data base reflects 13 mammalian test species ranging from mouse to cattle. Some 211 studies were compiled but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to practical human exposures. Of the 105 studies, 70 were for various rodent species, and 35 were for nonrodent groups ranging from standard laboratory primates (body weight ∼5 kg) to cattle (body weight 375 kg). This paper considers seven different dose-response models which are tested for validity against those 105 studies. The dose-response models included: a right-skewed extreme value, a left-skewed extreme value model, log-logistic, log-probit, logistic, probit, and Weibull models. In general, the log transformed models did not improve model performance and the extreme value models did not seem consistent with the preponderance of the data. Overall, the probit and the logistic models seemed preferable over the Weibull model. 30 refs., 8 tabs

  3. ANTIOXIDANT VITAMINS AND THE RISK OF ENDOMETRIAL CANCER: A DOSE-RESPONSE META-ANALYSIS

    OpenAIRE

    Elisa V Bandera; Gifkins, Dina M.; Moore, Dirk F.; McCullough, Marjorie L; Lawrence H Kushi

    2008-01-01

    Antioxidant vitamins may reduce cancer risk by limiting oxidative DNA damage. To summarize and quantify the current epidemiologic evidence of an association between antioxidant vitamin intake and endometrial cancer we conducted a systematic literature review and meta-analysis. One cohort and 12 case-control studies presenting relevant risk estimates were identified by conducting bibliographical searches through June 2008. Dose-response meta-analyses were conducted for beta-carotene, vitamin C...

  4. Vitamin D dose response is underestimated by Endocrine Society's Clinical Practice Guideline

    OpenAIRE

    McKenna, Malachi J; Murray, Barbara F

    2013-01-01

    Objective The recommended daily intakes of vitamin D according to the recent Clinical Practice Guideline (CPG) of the Endocrine Society are three- to fivefold higher than the Institute of Medicine (IOM) report. We speculated that these differences could be explained by different mathematical approaches to the vitamin D dose response. Methods Studies were selected if the daily dose was ≤2000 IU/day, the duration exceeded 3 months, and 25-hydroxyvitamin D (25OHD) concentrations were measured at...

  5. Repetitive TASER X26 discharge resulted in adverse physiologic events with a dose-response relationship related to the duration of discharge in anesthetized swine model.

    Science.gov (United States)

    Park, Eun-Jung; Choi, Sang-Cheon; Ahn, Jung-Hwan; Min, Young-Gi

    2013-01-01

    The objectives of our study were to investigate the dose-response relationship of the TASER X26 discharge duration in an anesthetized swine model. Fourteen swines were anesthetized and then exposed to TASER X26 discharge for 5 sec (n = 5) or for 10 sec (n = 6). The sham control group (n = 3) was anesthetized and studied using the same protocol except TASER X26 discharges during the experiments. Hemodynamic parameters were obtained. Blood pressure and total peripheral resistance decreased significantly after TASER discharge and returned to baseline value at 15 min after 5 sec of TASER discharge but did not return to baseline values during the 30-min observation period after 10 sec of TASER discharge. Repetitive TASER X26 discharge resulted in adverse physiologic events with a dose-response relationship related to the duration of TASER X26 discharge in an anesthetized swine model. PMID:23066880

  6. Comparison of US and FRG post-irradiation examination procedures to measure statistically significant failure fractions of irradiated coated-particle fuels. [HTGR

    Energy Technology Data Exchange (ETDEWEB)

    Kania, M.J.; Homan, F.J.; Mehner, A.W.

    1982-08-01

    Two methods for measuring failure fraction on irradiated coated-particle fuels have been developed, one in the United States (the IMGA system - Irradiated-Microsphere Gamma Analyzer) and one in the Federal Republic of Germany (FRG) (the PIAA procedure - Postirradiation Annealing and Beta Autoradiography). A comparison of the two methods on two standardized sets of irradiated particles was undertaken to evaluate the accuracy, operational procedures, and expense of each method in obtaining statistically significant results. From the comparison, the postirradiation examination method employing the IMGA system was found to be superior to the PIAA procedure for measuring statistically significant failure fractions. Both methods require that the irradiated fuel be in the form of loose particles, each requires extensive remote hot-cell facilities, and each is capable of physically separating failed particles from unfailed particles. Important differences noted in the comparison are described.

  7. Comparison of US and FRG post-irradiation examination procedures to measure statistically significant failure fractions of irradiated coated-particle fuels

    International Nuclear Information System (INIS)

    Two methods for measuring failure fraction on irradiated coated-particle fuels have been developed, one in the United States (the IMGA system - Irradiated-Microsphere Gamma Analyzer) and one in the Federal Republic of Germany (FRG) (the PIAA procedure - Postirradiation Annealing and Beta Autoradiography). A comparison of the two methods on two standardized sets of irradiated particles was undertaken to evaluate the accuracy, operational procedures, and expense of each method in obtaining statistically significant results. From the comparison, the postirradiation examination method employing the IMGA system was found to be superior to the PIAA procedure for measuring statistically significant failure fractions. Both methods require that the irradiated fuel be in the form of loose particles, each requires extensive remote hot-cell facilities, and each is capable of physically separating failed particles from unfailed particles. Important differences noted in the comparison are described

  8. Quantitative structure-activity relationships of selected phenols with non-monotonic dose-response curves

    Institute of Scientific and Technical Information of China (English)

    GAO ChangAn; ZHANG AiQian; LIN Yuan; YIN DaQiang; WANG LianSheng

    2009-01-01

    Particular non-monotonic dose-response curves of many endocrine disrupting chemicals (EDCs) suggest the existence of diverse toxicity mechanisms at different dose levels. As a result, the biologi-cal activities of EDCs cannot be simply exhibited by unique EC/LD<,50. values, and the quantitative structure-activity relationship (QSAR) analysis for non-monotonic dose-response relationship be-comes an unknown field in the environmental science. In this paper, nine phenols with inverted U-shaped dose-response curves in lymphocyte proliferation test of Carassius auratus were selected. The binding interactions between the phenols and several typical EDCs-related receptors were then explored in a molecular simulation study. The estrogen receptor (ER), androgen receptor (AR), thyroid hormone receptor (TR), bacterial O2 sensing FixL protein (FixL), aryl hydrocarbon receptor (AhR), and the peroxisome proliferator-activated receptor (PPAR) were the target receptors in the study. Linear regression QSAR models for the low and high exposure levels of the compounds were developed separately. The results indicated that the lymphocyte proliferation in the low-dose range might involve ER-mediated process, while the proliferation inhibition in the high dose range was dominated by the acute toxicity of phenols due to receptor occupancy and cell damage.

  9. Human evidence on the shape of the dose-response curves for radiation carcinogenesis

    International Nuclear Information System (INIS)

    The carcinogenic effects of high levels of ionizing radiation are better understood than those of any other environmental agent. However, the somatic risk from low doses is highly disputed. The uncertainties stem from the fact that a direct estimation of small risks requires impracticably large samples. Therefore, risk estimates for low doses have to be derived indirectly by extrapolation from high exposure data and are heavily dependent on assumptions about the form of the dose-response curve. Although radiobiological theories tested on in vitro systems predict a quadratic term in the dose-response equation which should, at least for sparsely ionizing radiation, dominate the shape of the curve, the epidemiological data available cannot exclude the possibility of a pure linear relationship. In some cases, apparent thresholds may result from latent periods inversely related to dose. Besides depending on the quality of the radiation, the shape seems also to differ with the type of cancer induced. Studies on uranium miners, atomic bomb survivors and on irradiated patients are reviewed with emphasis on the shape of the dose-response. The credibility of the most publicized reports claiming a large cancer risk from low levels of radiation is assessed. The feasibility of a new study in an area of high natural background is explored. Finally, the influence of the uncertainties concerning the effect of low level radiation on future exposure limits set by regulatory bodies is discussed. (Auth.)

  10. A comparison of dose-response models for death from hematological depression in different species

    International Nuclear Information System (INIS)

    A database has been completed suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behaviour within each experiment, etc. Data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Photon source energy, exposure geometry, and body weight considerations were used to select studies where dose to hematopoietic tissue was approximately uniform. The database reflects 13 mammalian species ranging in size from mouse to cattle. Some 211 studies were compiled, but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to human exposures. Of the 105 studies, 70 were for rodent species, 35 for non-rodent groups ranging from standard laboratory primates (body weight ∼ 5 kg) to cattle (body weight ∼ 375 kg). Seven different dose-response models are tested for validity against the 105 studies. In general, log transformation models did not improve model performance and extreme value models did not seem consistent with the preponderance of the data. Probit and the logistic models seemed preferable over the Weibull model. (author)

  11. Variation through the cell cycle in the dose-response of DNA neutral filter elution in X-irradiated synchronous CHO-cells

    International Nuclear Information System (INIS)

    Dose-response curves for DNA neutral (pH 9.6) filter elution were obtained with synchronized CHO cells exposed to X-rays at various phases of cell cycle. The dose response was similar in synchronized and plateau-phase G1 cells, as well as in cells arrested at the G1/S border using aphidicolin; it flattened as cells progressed into S phase and reached a minimum in the middle of this phase. An increase in DNA elution dose response, to values only slightly lower than those obtained with G1 cells, was observed as cells entered G2 phase. Significant alterations in the sedimentation properties of the DNA during S phase were also observed in Ehrlich ascites tumor cells using the neutral sucrose gradient centrifugation technique. A significant proportion of the DNA from S cells irradiated with 10 Gy sedimented at speeds (350S-700S) well above the maximum sedimentation speed expected for free sedimenting DNA molecules (ssub(max) = 350S), indicating the formation of a DNA complex. DNA from G1, G1/S, or G2 + M cells sedimented as expected for free sedimenting molecules. (author)

  12. The effect of manipulating root mean square window length and overlap on reliability, inter-individual variability, statistical significance and clinical relevance of electromyograms.

    Science.gov (United States)

    Mark Burden, Adrian; Lewis, Sandra Elizabeth; Willcox, Emma

    2014-12-01

    Numerous ways exist to process raw electromyograms (EMGs). However, the effect of altering processing methods on peak and mean EMG has seldom been investigated. The aim of this study was to investigate the effect of using different root mean square (RMS) window lengths and overlaps on the amplitude, reliability and inter-individual variability of gluteus maximus EMGs recorded during the clam exercise, and on the statistical significance and clinical relevance of amplitude differences between two exercise conditions. Mean and peak RMS of 10 repetitions from 17 participants were obtained using processing window lengths of 0.01, 0.15, 0.2, 0.25 and 1 s, with no overlap and overlaps of 25, 50 and 75% of window length. The effect of manipulating window length on reliability and inter-individual variability was greater for peak EMG (coefficient of variation [CV] mean EMG (CV mean EMG was affected by manipulation of window length. Statistical significance of peak EMG was more sensitive to changes in window length, with lower p-values generally being recorded for the 1 s window. As use of different window lengths has a greater effect on variability and statistical significance of the peak EMG, then clinicians should use the mean EMG. They should also be aware that use of different numbers of exercise repetitions and participants can have a greater effect on EMG parameters than length of processing window.

  13. Dose-response effects of atropine and HI-6 treatment of organophosphorus poisoning in guinea pigs.

    Science.gov (United States)

    Koplovitz, I; Menton, R; Matthews, C; Shutz, M; Nalls, C; Kelly, S

    1995-01-01

    HI-6 (1-2-hydroxyiminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino -2- oxapropane dichloride) has been evaluated as an oxime alternative to pralidoxime, and toxogonin in the treatment of organophosphorus (OP) poisoning. The dose response effects of atropine (ATR) and HI-6 were investigated to more fully explore the interaction of these compounds in the treatment of OP poisoning. ATR, HI-6 and various combinations of the two drugs were evaluated against lethal poisoning by soman (GD) and tabun (GA) in guinea pigs. The effect of adjunctive diazepam treatment on the efficacy of atropine and HI-6 against soman was also investigated. Animals of either sex were challenged s.c. with OP and treated i.m. 1 min later with ATR and/or HI-6. When used, diazepam was injected immediately after ATR+HI6. LD50s of each treatment were calculated from probit models based on 24-hour survival against 5 levels of nerve agent and 6 animals per challenge level. A protective index (PI) was calculated by dividing the nerve agent LD50 in the presence of treatment by the LD50 in the absence of treatment. Treatment with HI6 alone had little effect on the toxicity of either OP. Treatment with ATR alone was more effective than HI-6 alone and was significantly more effective against soman than against tabun. When used in combination atropine and HI-6 had a strong synergistic effect against both agents. The dose of atropine used with HI-6 was critical in determining the efficacy of HI-6 against either agent. The slopes of the dose-lethality curves were minimally affected by the dose of ATR or HI-6. Adjunctive treatment with diazepam enhanced the efficacy of HI-6 and atropine against soman. It is concluded that 1) ATR has a large effect on the efficacy of HI-6 against OP poisoning, 2) the dose of ATR must be carefully selected in studies investigating the efficacy of HI-6 against OP poisoning, 3) the effective dose of ATR in the guinea pig is approximately 16 mg/kg, and 4) diazepam is a useful

  14. INFLUENCE OF SUCCINYLCHOLINE ON THE DOSE-RESPONSE RELATIONSHIP OF SUBSEQUENTLY ADMINISTERED ROCURONIUN

    Institute of Scientific and Technical Information of China (English)

    陈锡明; 闻大翔; 杭燕南; 孙大金

    2005-01-01

    Objective To investigate the effect of succinylcholine on the dose-response relationship of subsequently administered rocuronium in healthy patients. Methods Forty-eight ASA physical status Ⅰ-Ⅱ patients,aged 17 -65 years, scheduled for elective general surgery, were randomly assigned to either the rocuronium treatment group (R) or succinylcholine-rocuronium treatment group (SR). General anesthesia was induced with thiopental 4 to 6mg/kg and fentanyl 2 to 5μg/kg intravenously and maintained with 60% nitrous oxide in oxygen. Additional doses of thiopental or fentanyl were administered as required. The dose-response relationship of rocuronium was determined by the single dose-response technique. In R group ( n =24) , rocuronium was given after induction of anesthesia. In SR group (n =24 ) , patients were intubated after 1.5mg/kg of succinylcholine and rocuronium was given after the complete recovery of neuromuscular blockade from succinylcholine. Patients were further randomly divided into 4 subgroups receiving 150, 200, 250 or 300μg/kg of rocuronium respectively in both groups. Neuromuscular function was assessed accelographically with train-of-four (TOF) stimulation at the wrist every 12s (using the TOF Guard(R) accelerometer). The relationship between probit-tranformed percentage depression of first twitch height (Th) of train-of-four stimulation and logarithm dose of rocuronium was analyzed using linear regression.Results The dose-response curve of rocuronium after succinylcholine was shifted to the left in a parallel fashion compared with that of rocuronium given alone. ED50 and ED95 of rocuronium were 193 ±69 and 367 ± 73μg/kg respectively in R group, and 158 ± 35 and 317 ± 80μg/kg respectively in SR group ( P < 0. 05 ). Conclusion Succinylcholine shifts the dose-response curve of rocuronium to the left and potentiates the effects of the neuromuscular blockade by about 15% of subsequently administered rocuronium. Lower doses of rocuronium are

  15. Dose-response relationship analysis for cancer and circulatory system disease mortality risks among uranium miners

    International Nuclear Information System (INIS)

    The relation between lung cancer risk and radon exposure has been clearly established, especially from the studies on uranium miner cohorts. But the association between radon exposure and extrapulmonary cancers and non-cancer diseases remains not well known. Moreover, the health risks associated with the other mining-related ionizing radiation exposures are still under consideration. The aim of this thesis is to contribute to the estimation of the radio-induced health risks at low-doses through the analysis of the kidney cancer and Circulatory System Disease (CSD) mortality risks among uranium miners. Kidney cancer mortality risk analyses were performed from the French cohort of uranium miners (n=5086; follow-up period: 1946-2007), the post-55 cohort (n=3,377; follow-up period: 1957-2007) and the German cohort of the Wismut (n=58,986; follow-up period: 1946-2003) which included 24, 11 and 174 deaths from kidney cancer, respectively. The exposures to radon and its short-lived progeny (expressed in Working Level Month WLM), to uranium ore dust (kBqh.m-3) and to external gamma rays (mSv) were estimated for each miners and the equivalent kidney dose was calculated. The dose-response relation was refined considering two responses: the instantaneous risk of kidney cancer mortality (corresponding to the classical analysis, Cause specific Hazard Ratio (CSHR) estimated with the Cox model) and its occurrence probability during the followup (Sub-distribution Hazard Ratio (SHR) estimated with the Fine and Gray model). An excess of kidney cancer mortality was observed only in the French cohort (SMR = 1.62 CI95%[1.04; 2.41]). In the Wismut cohort, a decrease of the kidney cancer mortality was observed (0.89 [0.78; 0.99]). For these three cohorts, the occupational radiological exposures (or the equivalent kidney dose) were significantly associated neither with the risk of kidney cancer mortality (e.g. CSHRWismut-radon/100 WLM=1.023 [0.993; 1.053]), nor with its occurrence

  16. The influence of tube voltage and phantom size in computed tomography on the dose-response relationship of dicentrics in human blood samples

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the dose response relationship of dicentrics in human lymphocytes after CT scans at tube voltages of 80 and 140 kV. Blood samples from a healthy donor placed in tissue equivalent abdomen phantoms of standard, pediatric and adipose sizes were exposed at dose levels up to 0.1 Gy using a 64-slice CT scanner. It was found that both the tube voltage and the phantom size significantly influenced the CT scan-induced linear dose-response relationship of dicentrics in human lymphocytes. Using the same phantom (standard abdomen), 80 kV CT x-rays were biologically more effective than 140 kV CT x-rays. However, it could also be determined that the applied phantom size had much more influence on the biological effectiveness. Obviously, the increasing slopes of the CT scan-induced dose response relationships of dicentrics in human lymphocytes obtained in a pediatric, a standard and an adipose abdomen have been induced by scattering effects of photons, which strongly increase with increasing phantom size.

  17. Comparison of the dose-response relationship of radiation-induced apoptosis in the hippocampal dentate gyrus and intestinal crypt of adult mice

    International Nuclear Information System (INIS)

    The present study compared the dose-response curves for the frequency of apoptosis in mouse hippocampal dentate gyrus (DG) and intestinal crypt using whole-body gamma irradiation. The incidence of gamma-ray-induced apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labelling (TUNEL) method. TUNEL-positive apoptotic nuclei in the DG and intestinal crypt were increased in a dose-dependent pattern (0-2 Gy). The dose-response curves were linear-quadratic, with a significant relationship between the appearance of apoptosis and irradiation dose. The slopes of the dose-response curves in the DG were much steeper (∼5-6-fold) than those in the intestinal crypt within the range of 0-1 Gy exposure. Hippocampal DG might be a more effective and sensitive evaluation structure than the intestinal crypt to estimate the degree of radiation exposure in damaged organs of adult mice exposed to low irradiation dose. copy; The Author 2011. Published by Oxford Univ. Press. All rights reserved. (authors)

  18. Meta-analysis for deriving age- and gender-specific dose-response relationships between urinary cadmium concentration and β 2-microglobulinuria under environmental exposure

    International Nuclear Information System (INIS)

    A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and β 2-microglobulinuria (β2MG-uria) under environmental exposure. β2MG-uria was defined by a cutoff point of 1000 μg β 2-microglobulin/g creatinine. We proposed a model for describing the relationships among the interindividual variabilities in urinary Cd concentration, the ratio of Cd concentrations in the target organ and in urine, and the threshold Cd concentration in the target organ. The parameters in the model were determined so that good agreement might be achieved between the prevalence rates of β2MG-uria reported in the literature and those estimated by the model. In this analysis, only the data from the literature on populations environmentally exposed to Cd were used. Using the model and estimated parameters, the prevalence rate of β2MG-uria can be estimated for an age- and gender-specific subpopulation for which the distribution of urinary Cd concentrations is known. The maximum permissible level of urinary Cd concentration was defined as the maximum geometric mean of the urinary Cd concentration in an age- and gender-specific subpopulation that would not result in a statistically significant increase in the prevalence rate of β2MG-uria. This was estimated to be approximately 3 μg/g creatinine for a population in a small geographical area and approximately 2 μg/g creatinine for a nationwide population

  19. On the significance of contaminant plume-scale and dose-response models in defining hydrogeological characterization needs

    Science.gov (United States)

    de Barros, F.; Rubin, Y.; Maxwell, R.; Bai, H.

    2007-12-01

    Defining rational and effective hydrogeological data acquisition strategies is of crucial importance since financial resources available for such efforts are always limited. Usually such strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of the impacts of uncertainty. This paper presents an approach for determining site characterization needs based on human health risk factors. The main challenge is in striking a balance between improved definition of hydrogeological, behavioral and physiological parameters. Striking this balance can provide clear guidance on setting priorities for data acquisition and for better estimating adverse health effects in humans. This paper addresses this challenge through theoretical developments and numerical testing. We will report on a wide range of factors that affect the site characterization needs including contaminant plume's dimensions, travel distances and other length scales that characterize the transport problem, as well as health risk models. We introduce a new graphical tool that allows one to investigate the relative impact of hydrogeological and physiological parameters in risk. Results show that the impact of uncertainty reduction in the risk-related parameters decreases with increasing distances from the contaminant source. Also, results indicate that human health risk becomes less sensitive to hydrogeological measurements when dealing with ergodic plumes. This indicates that under ergodic conditions, uncertainty reduction in human health risk may benefit from better understanding of the physiological component as opposed to a detailed hydrogeological characterization

  20. QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models.

    Science.gov (United States)

    Nilsen, Vegard; Wyller, John

    2016-01-01

    Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed. PMID:26812257

  1. QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models.

    Science.gov (United States)

    Nilsen, Vegard; Wyller, John

    2016-01-01

    Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed.

  2. Statistics Related Self-Efficacy A Confirmatory Factor Analysis Demonstrating a Significant Link to Prior Mathematics Experiences for Graduate Level Students

    Directory of Open Access Journals (Sweden)

    Karen Larwin

    2014-02-01

    Full Text Available The present study examined students' statistics-related self-efficacy, as measured with the current statistics self-efficacy (CSSE inventory developed by Finney and Schraw (2003. Structural equation modeling was used to check the confirmatory factor analysis of the one-dimensional factor of CSSE. Once confirmed, this factor was used to test whether a significant link to prior mathematics experiences exists. Additionally a new post-structural equation modeling (SEM application was employed to compute error-free latent variable score for CSSE in an effort to examine the ancillary effects of gender, age, ethnicity, department, degree level, hours completed, expected course grade, number of college-level math classes, current GPA on students' CSSE scores. Results support the one-dimensional construct and as expected, the model demonstrated a significant link between CSSE scores and prior mathematics experiences to CSSE. Additionally the students' department, expected grade, and number of prior math classes were found to have a significant effect on student's CSSE scores.

  3. Alanine aminotransferase and risk of the metabolic syndrome: a linear dose-response relationship.

    Directory of Open Access Journals (Sweden)

    Setor K Kunutsor

    Full Text Available BACKGROUND: Elevated baseline circulating alanine aminotransferase (ALT level has been demonstrated to be associated with an increased risk of the metabolic syndrome (MetS, but the nature of the dose-response relationship is uncertain. METHODS: We performed a systematic review and meta-analysis of published prospective cohort studies to characterize in detail the nature of the dose-response relationship between baseline ALT level and risk of incident MetS in the general population. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to December 2013. Prospective studies in which investigators reported relative risks (RRs of MetS for 3 or more categories of ALT levels were eligible. A potential nonlinear relationship between ALT levels and MetS was examined using restricted cubic splines. RESULTS: Of the 489 studies reviewed, relevant data were available on 29,815 non-overlapping participants comprising 2,125 incident MetS events from five prospective cohort studies. There was evidence of a linear association (P for nonlinearity=0.38 between ALT level and risk of MetS, characterised by a graded increase in MetS risk at ALT levels 6-40 U/L. The risk of MetS increased by 14% for every 5 U/L increment in circulating ALT level (95% CI: 12-17%. Evidence was lacking of heterogeneity and publication bias among the contributing studies. CONCLUSIONS: Baseline ALT level is associated with risk of the MetS in a linear dose-response manner. Studies are needed to determine whether the association represents a causal relationship.

  4. Environmental standards for ionizing radiation: theoretical basis for dose-response curves.

    Science.gov (United States)

    Upton, A C

    1983-10-01

    The types of injury attributable to ionizing radiation are subdivided, for purposes of risk assessment and radiological protection, into two broad categories: stochastic effects and nonstochastic effects. Stochastic effects are viewed as probablistic phenomena, varying in frequency but not severity as a function of the dose, without any threshold; nonstochastic effects are viewed as deterministic phenomena, varying in both frequency and severity as a function of the dose, with clinical thresholds. Included among stochastic effects are heritable effects (mutations and chromosome aberrations) and carcinogenic effects. Both types of effects are envisioned as unicellular phenomena which can result from nonlethal injury of individual cells, without the necessity of damage to other cells. For the induction of mutations and chromosome aberrations in the low-to-intermediate dose range, the dose-response curve with high-linear energy transfer (LET) radiation generally conforms to a linear nonthreshold relationship and varies relatively little with the dose rate. In contrast, the curve with low-LET radiation generally conforms to a linear-quadratic relationship, rising less steeply than the curve with high-LET radiation and increasing in slope with increasing dose and dose rate. The dose-response curve for carcinogenic effects varies widely from one type of neoplasm to another in the intermediate-to-high dose range, in part because of differences in the way large doses of radiation can affect the promotion and progression of different neoplasms. Information about dose-response relations for low-level irradiation is fragmentary but consistent, in general, with the hypothesis that the neoplastic transformation may result from mutation, chromosome aberration or genetic recombination in a single susceptible cell.

  5. An assessment of non-linear dose response in chemiluminescence dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Jun, J.S. [Department of Physics, Chungnam National University, Taejon (Korea); Dalheimer, A.; Guggenberger, R. [Institute of Applied Radiation Protection, Federal Office of Radiation Protection, Oberschleissheim (Germany)

    2000-05-01

    Sugar and sorbite are well known to be convenient and suitable materials for chemiluminescence (CL) as well as electron spin resonance (ESR) dosimetry, in particular for retrospective dose assessment in an emergency and/or accident situation, mainly because of their close tissue-equivalence. In practice, however, the dose-CL response of those materials are not always shown to be satisfactorily linear. An attempt was made in this study to evaluate and correct the early supralinear dose-CL relationship appeared in the sugar and sorbite samples irradiated to gamma-ray doses of 0.5 to 10 Gy. In consideration of a similarity of the non-linear CL-dose relationship with the initial supralinearity shown in TL-dose response as depicted by Aitken, several recently proposed methods of expressing non-linear dose responses of TL, ESR or CL outputs were examined and investigated in order to look for a fittest means for the assessment of our supralinear dose-CL response of sugar and sorbite. As a result of an extensive study, merits and demerits of each method of representing non-linear dose response could be figured out in the light of our particular dose-CL relationship appeared in the sugar and sorbite samples. It is concluded that the 'supralinearity index', f(D), defined as a function of dose by Chen and McKeever is the most suitable function for expressing and correcting the non-linear dose-CL response shown in the initial low dose range of our irradiated sugar sorbite samples. The CL outputs corrected by use of f(D) are compared with those uncorrected, and the resultant CL sensitivities of the samples are numerically given together with re-evaluated dispersion of the sensitivities in terms of standard deviation. (author)

  6. Dose-response curves for fish MFO induction: How do we interpret different maxima and slopes?

    International Nuclear Information System (INIS)

    Induction of hepatic mixed function oxygenase (MFO) activity has been useful for screening effluents from pulp mills and oil refineries. Effluents and pure compounds can be assessed by direct fish exposure or by concentration with semipermeable membrane devices (SPMDs) and by measuring MFO in fish liver cell lines exposed to SPMD extracts. In these experiments, both fish and fish cells showed differences in slopes of dose-response curves, and in the maximal ethoxyresorufin-O-deethylase (EROD) activity. For example, TCDD elicits an EROD maxima of over 500 pmol/mg/min in PLHC-1 (Poeciliopsis lucida hepatocellular carcinoma cell line), while pulp mill and oil refinery effluent extracts showed maxima of 40 to 200 pmol/mg/min. Substituted phenanthrenes caused induction maxima of 100 pmol/mg/min. Similarly, in rainbow trout in vivo, TCDD and other chlorinated dioxins and furans induced up to 500 pmol/mg/min, whereas pulp mill and refinery effluents and substituted phenanthrenes produced EROD maxima of up to 100 pmol/mg/min. Differences in the slopes of dose-response curves were also common. In the current assessment of potencies, these diverse response curves are boiled-down to one number, the EC50 or other threshold-type of concentration. Comparisons of EC50s cannot express these differences and instead, ignore them. However, the authors realize there must be a better approach that takes into account these large differences in dose-response curve shape, slope and maxima. Interaction and discussions with modelers in the session will allow them to discuss various approaches to expressing the potencies of MFO inducers in fish

  7. Negative dose-response relationship for radiation-induced micronuclei in polychromatic erythrocytes of mice

    International Nuclear Information System (INIS)

    Micronuclei were assessed among the bone marrow PCEs of mice 28 hr after exposures to 1 to 8 Gy of X-rays and at 6-hr intervals from 12-60 hr after exposures to 2 or 6 Gy. At 28 hr, the frequency of micronuclei declined as the exposure level increased from 1 to 8 Gy. The peak proportion of micronucleated PCEs appeared much later following 6 Gy than after 2 Gy exposures, implicating cell cycle delay as the cause of the negative dose-response relationship. 11 refs., 1 fig., 2 tabs

  8. Dose-response regressions for algal growth and similar continuous endpoints: Calculation of effective concentrations

    DEFF Research Database (Denmark)

    Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels

    2009-01-01

    We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50......% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4...

  9. Biphasic Dose Response in Low Level Light Therapy – An Update

    OpenAIRE

    Huang, Ying-Ying; Sharma, Sulbha K.; Carroll, James; Hamblin, Michael R.

    2011-01-01

    Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenos...

  10. Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.

    OpenAIRE

    Burns, Fredric J.; Uddin, Ahmed N.; Wu, Feng; Nádas, Arthur; Rossman, Toby G.

    2004-01-01

    The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experi...

  11. Study on the dose-response relationships between the drinking water fluoride and bone mineral density, and serum osteocalcin%水氟与骨密度和骨钙素的剂量效应关系研究

    Institute of Scientific and Technical Information of China (English)

    黄九宁; 周新亚; 凌莉; 向全永; 张正东

    2009-01-01

    levels of drinking water fluoride in males' and females' families in fluoride exposed group were [(2.38±0.68), (2.62±0.91 )mg/L] significant higher than that in control group [(0.35±0.08), (0.36±0.07)mg/L], the difference being statistically significant(t values were 14.27 and 11.08,and P<0.01, respectively). BMD in males in fluoride exposed group [(0.78±0.07)g/cm2] was significant lower than that in control group[(0.83±0.08)g/cm2], the difference being statistically significant (t=2.37,P<0.05). Serum BGP in males and females in fluoride exposed group [(4.17±0.67), (4.11±0.57) μg/L] were significant higher than that in control group [(1.48±0.40), (1.44±0.39)μg/L], the difference being statistically significant (t values were 17.64 and 19.40, and P<0.01, respectively]. BMD in the group with drinking water fluoride≥2.92 mg/L[(0.66±0.15 )g/cm2] was significant lower than that in the group with drinking water fluoride<0.42 mg/L [(0.76±0.12)g/cm2], the difference being statistically significant (P<0.01). The levels of serum BGP in the groups with the drinking water 0.42-,2.05-, ≥.92 mg/L[(3.83±1.07), (4.22±0.72), (3.99±0.63) μg/L] were significant higher than that in the group with the drinking water<0.42 mg/L [(1.44±0.37) μg/L], the difference being statistically significant (P<0.01). The equation for the dose-response relationship between the drinking water fluoride and the rate of abnormal BMD was y=(0.284-0.058x)-1.260, r=0.999 94; and y=100.05/(1+78.62e-4.5x), r=0.999 99 for the drinking water fluoride and the rate of abnormal serum BGP. Conclusions There were significant dose-response relationships between drinking water fluoride and BMD and serum BGP. It indicated that BMD and BGP might be considered as early screening biomarkers for endemic fluorosis, especially for the bone damage.

  12. Hazard identification and characterisation, and dose response assessment of spore forming pathogens in cooked chilled food containing vegetables

    NARCIS (Netherlands)

    Leusden FM van; MGB

    2001-01-01

    A hazard identification and characterisation, including a preliminary dose response assessment, of sporeforming pathogens in cooked chilled food containing vegetables was performed according to the structure and principles for a quantitative microbiological risk assessment as described by the Codex

  13. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    DEFF Research Database (Denmark)

    Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M

    2010-01-01

    A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high)....

  14. SU-F-BRD-05: Dosimetric Comparison of Protocol-Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed- Beam IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Best, R; Harrell, A; Geesey, C; Libby, B; Wijesooriya, K [University of Virginia, Charlottesville, VA (United States)

    2014-06-15

    Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parameters of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference

  15. SU-F-BRD-05: Dosimetric Comparison of Protocol-Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed- Beam IMRT

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parameters of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference

  16. Influence of Relative Humidity, Dose Rate and Dose Fractionation on Gamma Dose Response of Glycine Dosimetric System

    Directory of Open Access Journals (Sweden)

    Santosh H. Shinde

    2011-07-01

    Full Text Available Glycine dosimeter based on spectrophotometric read-out method has great potential for gamma dosimetry in low dose applications of radiation processing. However, external factors such as relative humidity, dose rate, and dose fractionation, may have a profound effect on its gamma dose response Influence of these factors on the gamma dose response of glycine dosimeter was studied in the present work.

  17. Dose Response Association between Physical Activity and Biological, Demographic, and Perceptions of Health Variables

    Directory of Open Access Journals (Sweden)

    Paul D. Loprinzi

    2013-08-01

    Full Text Available Background: Few population-based studies have examined the association between physical activity (PA and cardiovascular disease risk factors, demographic variables, and perceptions of health status, and we do not have a clear understanding of the dose-response relationship among these variables. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey was used to examine the dose-response relationship between objectively measured PA and metabolic syndrome (and its individual cardiovascular disease risk factors, demographic variables, and perceptions of health. After exclusions, 5,538 participants 18 years or older were included in the present study, with 2,538 participants providing fasting glucose and 2,527 providing fasting triglyceride data. PA was categorized into deciles. Results: Overall, the health benefits showed a general pattern of increase with each increasing levels of PA. Of the ten PA classifications examined, participants in the highest moderate-to-vigorous physical activity (MVPA category (at least 71 min/day had the lowest odds of developing metabolic syndrome. Conclusion: At a minimum, sedentary adults should strive to meet current PA guidelines (i.e., 150 min/week of MVPA, with additional positive benefits associated with engaging in three times this level of PA.

  18. Dose-response study on thyrotoxic patients undergoing positron emission tomography and radioiodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Flower, M.A. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom)); Al-Saadi, A. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom)); Harmer, C.L. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom)); McCready, V.R. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom)); Ott, R.J. (Thyroid Unit, Royal Marsden Hospital, Sutton (United Kingdom))

    1994-06-01

    Our policy had been to give 75 MBq iodine-131 at 6-monthly intervals to patients with Graves' disease until they became euthyroid. Since PET has been available at this hospital, the radiation dose to the thyroid has been calculated with an accuracy of -20%, the thyroid mass being determined from an iodine-124 PET scan. A dose-response study has been carried out on 65 patients who have received single or cumulative radiation doses of < 80 Gy. The results show that patients who receive a low radiation dose (< 20 Gy) at their first treatment have a high probability of remaining toxic at 12 months. In contrast, patients who receive higher radiation doses (> 40 Gy) at their first treatment have a high probability of control. The probability of becoming euthyroid increases more rapidly with increasing radiation dose than the probability of becoming hypothyroid. Following this dose-response study, a new treatment protocol has been introduced. A [sup 124]I PET tracer study prior to [sup 131]I therapy will be performed to enable a prescribed thyroid dose of 50 Gy to be delivered to patients with Graves' disease. Further [sup 131]I therapy will be considered if patients are still toxic at 12 months. (orig./MG)

  19. Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

    Science.gov (United States)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    2004-01-01

    Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

  20. A dose-response analysis of skin cancer from inorganic arsenic in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K.G.; Boyle, K.E.; Chen, C.W.; Gibb, H.J. (Research Triangle Institute, Research Triangle Park, NC (USA))

    1989-12-01

    A study of the prevalence of skin cancer among 40,421 persons consuming arsenic-contaminated drinking water in Taiwan was used for a cancer dose-response assessment of ingested arsenic. The numbers of persons at risk over three dose intervals and four exposure durations were estimated from the data in order to apply the method of maximum likelihood to a multistage-Weibull time/dose-response model. A constant exposure level since birth for each of the exposure categories was assumed. It was found that the cumulative hazard increases as a power of three in age, and is linear or quadratic (with a linear coefficient) in dose. Observations from a smaller epidemiologic survey in Mexico were similar to what would be predicted from the model of the Taiwan data. Assuming that the skin cancer risk from ingested arsenic in the American population would also be similar to the Taiwan population, an American male would have a lifetime risk of developing skin cancer of 1.3 x 10(-3) (3.0 x 10(-3)) if exposed to 1 microgram/kg/day for a 76-year lifespan (median lifespan in the U.S.).

  1. Dose-response relationship for lung cancer induction at radiotherapy dose

    International Nuclear Information System (INIS)

    Cancer induction after radiation therapy is a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the treated patient. Currently there is large uncertainty about the shape of the dose-response relationship for carcinogenesis for most cancer types at high dose levels. In this work a dose-response relationship for lung cancer is derived based on (i) the analysis of lung cancer induction after Hodgkin's disease, (ii) a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii) the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy. The fitted model parameters for an α/β = 3 Gy were α = 0.061Gy-1 and R = 0.84. The value for α is in agreement with analysis of normal tissue complications of the lung after radiation therapy. The repopulation/repair parameter R is large, but seems to be characteristic for lung tissue which is sensitive with regard to fractionation. Lung cancer risk is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 15 Gy and drops off only slightly at larger doses. The predicted EAR for lung after radiotherapy of Hodgkin's disease is 18.4/10000PY which can be compared to the findings of several epidemiological studies were EAR for lung varies between 9.7 and 21.5/10000PY. (orig.)

  2. Does a dose-response relation exist between spinal pain and temporomandibular disorders?

    Directory of Open Access Journals (Sweden)

    Englund Erling

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to test whether a reciprocal dose-response relation exists between frequency/severity of spinal pain and temporomandibular disorders (TMD. Methods A total of 616 subjects with varying severity of spinal pain or no spinal pain completed a questionnaire focusing on symptoms in the jaw, head and spinal region. A subset of the population (n = 266 were sampled regardless of presence or absence of spinal pain. We used two different designs, one with frequency/severity of spinal pain, and the other, with frequency/severity of TMD symptoms as independent variable. All 616 participants were allocated to four groups, one control group without spinal pain and three spinal pain groups. The subjects in the subset were allocated to one control group without TMD symptoms and three TMD groups. Odds ratios (ORs were calculated for presence of frequent TMD symptoms in the separate spinal pain groups as well as for frequent spinal pain in the separate TMD groups. Results The analysis showed increasing ORs for TMD with increasing frequency/severity of spinal pain. We also found increasing ORs for spinal pain with increasing frequency/severity of TMD symptoms. Conclusion This study shows a reciprocal dose-response-like relationship between spinal pain and TMD. The results indicate that these two conditions may share common risk factors or that they may influence each other. Studies on the temporal sequence between spinal pain and TMD are warranted.

  3. Non-linear dose response of a few plant taxa to acute gamma radiation

    International Nuclear Information System (INIS)

    Micronuclei induction serves as an essential biomarker of radiation stress in a living system, and the simplicity of its detection technique has made it a widely used indicator of radiation damage. The present study was conducted to reveal the cytological dose-response of a few plant taxa, viz., Allium cepa var. aggregatum Linn., Allium sativum Linn., Chlorophytum comosum (Thunb.) Jacques and Eichhornia crassipes (Mart.) Solms, to low LET gamma radiation with special emphasis on the pattern of micronuclei induced across low and high dose regimes. A tri-phasic non-linear dose-response pattern was observed in the four taxa studied, characterized by a low dose linear segment, a plateau and a high dose linear segment. Despite a similar response trend, the critical doses where the phase transitions occurred varied amongst the plant taxa, giving an indication to their relative radiosensitivities. E. crassipes and A. sativum, with their lower critical doses for slope modifications of phase transitions, were concluded as being more radiosensitive as compared to C. comosum and A. cepa, which had relatively higher critical doses. (author)

  4. Evaluating statistical and clinical significance of intervention effects in single-case experimental designs: an SPSS method to analyze univariate data.

    Science.gov (United States)

    Maric, Marija; de Haan, Else; Hogendoorn, Sanne M; Wolters, Lidewij H; Huizenga, Hilde M

    2015-03-01

    Single-case experimental designs are useful methods in clinical research practice to investigate individual client progress. Their proliferation might have been hampered by methodological challenges such as the difficulty applying existing statistical procedures. In this article, we describe a data-analytic method to analyze univariate (i.e., one symptom) single-case data using the common package SPSS. This method can help the clinical researcher to investigate whether an intervention works as compared with a baseline period or another intervention type, and to determine whether symptom improvement is clinically significant. First, we describe the statistical method in a conceptual way and show how it can be implemented in SPSS. Simulation studies were performed to determine the number of observation points required per intervention phase. Second, to illustrate this method and its implications, we present a case study of an adolescent with anxiety disorders treated with cognitive-behavioral therapy techniques in an outpatient psychotherapy clinic, whose symptoms were regularly assessed before each session. We provide a description of the data analyses and results of this case study. Finally, we discuss the advantages and shortcomings of the proposed method.

  5. Dose response of selected ion chambers in applied homogeneous transverse and longitudinal magnetic fields

    International Nuclear Information System (INIS)

    Purpose: The magnetic fields of an integrated MR-Linac system will alter the paths of electrons that produce ions in the ionization chambers. The dose response of selected ion chambers is evaluated in the presence of varying transverse and longitudinal magnetic fields. The investigation is useful in calibration of therapeutic x-ray beams associated with MR-Linac systems. Methods: The Monte Carlo code PENELOPE was used to model the irradiation of NE2571, and PR06C ionization chambers in the presence of a transverse and longitudinal (with respect to the photon beam) magnetic fields of varying magnitude. The long axis of each chamber was simulated both parallel and perpendicular to the incident photon beam for each magnetic field case. The dose deposited in each chamber for each case was compared to the case with zero magnetic field by means of a ratio. The PR06C chamber's response was measured in the presence of a transverse magnetic field with field strengths ranging from 0.0 to 0.2 T to compare to simulated results. Results: The simulations and measured data show that in the presence of a transverse magnetic field there is a considerable dose response (maximum of 11% near 1.0 T in the ion chambers investigated, which depends on the magnitude of magnetic field, and relative orientation of the magnetic field, radiation beam, and ion chamber. Measurements made with the PR06C chamber verify these results in the region of measurement. In contrast, a longitudinal magnetic field produces only a slight increase in dose response (2% at 1.5 T) that rises slowly with increasing magnetic field and is seemingly independent of chamber orientation. Response trends were similar for the two ion chambers and relative orientations considered, but slight variations are present from chamber to chamber. Conclusions: Care must be taken when making ion chamber measurements in a transverse magnetic field. Ion chamber responses vary not only with transverse field strength, but with chamber

  6. Positioning and number of nutritional levels in dose-response trials to estimate the optimal-level and the adjustment of the models

    Directory of Open Access Journals (Sweden)

    Fernando Augusto de Souza

    2014-07-01

    Full Text Available The aim of this research was to evaluate the influence of the number and position of nutrient levels used in dose-response trials in the estimation of the optimal-level (OL and the goodness of fit on the models: quadratic polynomial (QP, exponential (EXP, linear response plateau (LRP and quadratic response plateau (QRP. It was used data from dose-response trials realized in FCAV-Unesp Jaboticabal considering the homogeneity of variances and normal distribution. The fit of the models were evaluated considered the following statistics: adjusted coefficient of determination (R²adj, coefficient of variation (CV and the sum of the squares of deviations (SSD.It was verified in QP and EXP models that small changes on the placement and distribution of the levels caused great changes in the estimation of the OL. The LRP model was deeply influenced by the absence or presence of the level between the response and stabilization phases (change in the straight to plateau. The QRP needed more levels on the response phase and the last level on stabilization phase to estimate correctly the plateau. It was concluded that the OL and the adjust of the models are dependent on the positioning and the number of the levels and the specific characteristics of each model, but levels defined near to the true requirement and not so spaced are better to estimate the OL.

  7. Airborne trichloramine (NCl(3)) levels and self-reported health symptoms in indoor swimming pool workers: dose-response relationships.

    Science.gov (United States)

    Fantuzzi, Guglielmina; Righi, Elena; Predieri, Guerrino; Giacobazzi, Pierluigi; Petra, Berchotd; Aggazzotti, Gabriella

    2013-01-01

    The hypothesis that attendance at indoor chlorinated swimming pool is a risk factor for irritative ocular and respiratory symptoms and bronchial asthma is well known in literature, although epidemiological evidence is still inconclusive. The aim of this study was to evaluate the association between airborne trichloramine (NCl(3)) levels and irritative symptoms in swimming pool employees in order to obtain detailed data regarding dose-response relationships and to identify the airborne NCl(3) exposure level, if any, without health effects. A total of 20 indoor swimming pools in the Emilia Romagna region of Italy were included in the study. Information about the health status of 128 employees was collected using a self-administered questionnaire. Exposure to airborne NCl(3) was evaluated in indoor swimming pools by a modified DPD/KI method. The results of the study evidenced a mean value of airborne NCl(3) of 0.65±0.20 mg/m(3) (ranging from 0.20 to 1.02 mg/m(3)). Both ocular and upper respiratory symptoms, in particular red eyes, runny nose, voice loss and cold symptoms, were declared more frequently by lifeguards and trainers when compared with employees working in other areas of the facility (office, cafe, and so on). Pool attendants exposed to airborne NCl(3) levels of >0.5 mg/m(3) experienced higher risks for runny nose (OR: 2.91; 95% CI: 1.22-6.93) red eyes (OR: 3.16; 95% CI: 1.46-6.82), voice loss (OR: 3.56; 95% CI: 1.60-7.95) and itchy eyes (OR: 2.23; 95% CI: 1.04-4.78) than other employees. Moreover, red eyes, itchy eyes, runny nose and voice loss are related to airborne NCl(3) levels, with strong dose-response relationships. In conclusion, this study shows that lifeguards and trainers experience ocular and respiratory irritative symptoms more frequently than employees not exposed. Irritative symptoms become significant starting from airborne NCl(3) levels of >0.5 mg/m(3), confirming that the WHO-recommended value can be considered protective in

  8. Dose response of xylitol and sorbitol for EPR retrospective dosimetry with applications to chewing gum.

    Science.gov (United States)

    Israelsson, A; Gustafsson, H; Lund, E

    2013-04-01

    The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1-84 d after irradiation with minimal changes after 4-8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0-20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD).

  9. Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Ellegaard-Jensen, Lea; Jensen, Keld Alstrup; Johansen, Anders

    2012-01-01

    Toxicity of nano-formulated silver to eukaryotes was assessed by exposing nematodes (Caenorhabditis elegans) to two types of silver nanoparticles (AgNPs): with average primary particle diameters of 1 nm (AgNP1) and 28 nm (AgNP28, PVP coated), respectively. Tests were performed with and without...... adverse dose-response effects and mortality on C. elegans. LC50 for AgNP28 was lower than for AgNP1 and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic than AgNP1. Including E. coil in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when...

  10. Dose-response relationships between four pesticides and phosphorus uptake by hyphae of arbuscular mycorrhizas

    DEFF Research Database (Denmark)

    Schweiger, P.F.; Jakobsen, I.

    1998-01-01

    was separated from the main root compartment by nylon mesh. After 5 weeks of plant growth external hyphae of the AM fungi had spread throughout the hyphal compartment. At this time aqueous solutions of both P-32 and pesticide were added to the hyphal compartment. Resulting soil pesticide concentrations covered...... a wide range with the aim of describing the dose-response relationships between pesticide concentration and hyphal P uptake. Plants were harvested 6d after pesticide application. The amount of P-32 taken up into the plant was measured as was hyphal length in the hyphal compartment. Carbendazim had...... effects on hyphal P uptake even when applied at concentrations of 125 or 46 mu g g(-1) respectively. These concentrations are equivalent to expected field concentrations following pesticide applications at 100 times the recommended field rate. (C) 1998 Elsevier Science Ltd. All rights reserved....

  11. New flux based dose-response relationships for ozone for European forest tree species.

    Science.gov (United States)

    Büker, P; Feng, Z; Uddling, J; Briolat, A; Alonso, R; Braun, S; Elvira, S; Gerosa, G; Karlsson, P E; Le Thiec, D; Marzuoli, R; Mills, G; Oksanen, E; Wieser, G; Wilkinson, M; Emberson, L D

    2015-11-01

    To derive O3 dose-response relationships (DRR) for five European forest trees species and broadleaf deciduous and needleleaf tree plant functional types (PFTs), phytotoxic O3 doses (PODy) were related to biomass reductions. PODy was calculated using a stomatal flux model with a range of cut-off thresholds (y) indicative of varying detoxification capacities. Linear regression analysis showed that DRR for PFT and individual tree species differed in their robustness. A simplified parameterisation of the flux model was tested and showed that for most non-Mediterranean tree species, this simplified model led to similarly robust DRR as compared to a species- and climate region-specific parameterisation. Experimentally induced soil water stress was not found to substantially reduce PODy, mainly due to the short duration of soil water stress periods. This study validates the stomatal O3 flux concept and represents a step forward in predicting O3 damage to forests in a spatially and temporally varying climate.

  12. Dose-response of strengthening exercise for treatment of severe neck pain in women

    DEFF Research Database (Denmark)

    Andersen, C. H.; Andersen, Lars L.; Pedersen, Mogens T.;

    2013-01-01

    Specific strength training is shown to relieve neck pain in office workers. The purpose of this study is to evaluate the effectiveness of specific strength training in women with severe neck pain and to analyze the dose-response relationship between training adherence and pain reduction. One...... hundred eighteen untrained women with severe neck pain (>30 mm VAS pain) were included from a larger study, in which the subjects were randomized to 20-week specific strength training for the neck/shoulders or to a control group. In the intention-to-treat analysis, the training group experienced greater...... better pain relief than the control group and those with low adherence (p <0.0001). The decrease from baseline in the medium and high adherence groups was 37 mm VAS (28-46 mm) and 33 mm VAS (24-43 mm), respectively. Specific strength training reduces pain intensity in women with severe neck pain, and 1...

  13. Dose response of xylitol and sorbitol for epr retrospective dosimetry with applications to chewing gum

    International Nuclear Information System (INIS)

    The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1-84 d after irradiation with minimal changes after 4-8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0-20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD). (authors)

  14. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    DEFF Research Database (Denmark)

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.;

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we...... estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...... of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect...

  15. SO/sub 2/ dose-response sensitivity classification data for crops and natural vegetation species

    Energy Technology Data Exchange (ETDEWEB)

    Irving, P.M.; Ballou, S.W.

    1980-09-01

    Over the past several years studies have been made on the interaction of sulfur dioxide (SO/sub 2/) and vegetation by performing field research and by developing analytical procedures for applying field observation data to energy impact assessments. As a result of this work, numerous reports have been prepared on crop-pollutant interactions, such as dose-response data; on the applications of such data to screening approaches for identifying crops at risk; and on models that predict crop yield reductions from point source emissions of SO/sub 2/. Data that were used for these studies, such as the crop-at-risk screening procedure, are presented in this report. Maps are also presented that show the national distribution of SO/sub 2/-sensitive crops and natural vegetation.

  16. Severity of killer whale behavioral responses to ship noise: a dose-response study.

    Science.gov (United States)

    Williams, Rob; Erbe, Christine; Ashe, Erin; Beerman, Amber; Smith, Jodi

    2014-02-15

    Critical habitats of at-risk populations of northeast Pacific "resident" killer whales can be heavily trafficked by large ships, with transits occurring on average once every hour in busy shipping lanes. We modeled behavioral responses of killer whales to ship transits during 35 "natural experiments" as a dose-response function of estimated received noise levels in both broadband and audiogram-weighted terms. Interpreting effects is contingent on a subjective and seemingly arbitrary decision about severity threshold indicating a response. Subtle responses were observed around broadband received levels of 130 dB re 1 μPa (rms); more severe responses are hypothesized to occur at received levels beyond 150 dB re 1 μPa, where our study lacked data. Avoidance responses are expected to carry minor energetic costs in terms of increased energy expenditure, but future research must assess the potential for reduced prey acquisition, and potential population consequences, under these noise levels. PMID:24373666

  17. Radiation dose response correlation between thermoluminescence and optically stimulated luminescence in quartz

    Energy Technology Data Exchange (ETDEWEB)

    Oniya, E.O. [Archaeometry Laboratory, Cultural and Educational Technology Institute (C.E.T.I.), R.C. ' Athena' , Tsimiski 58, GR-67100 Xanthi (Greece); Physics and Electronics Department, Adekunle Ajasin University, PMB 01, Akungba Akoko (Nigeria); Polymeris, G.S.; Tsirliganis, N.C. [Archaeometry Laboratory, Cultural and Educational Technology Institute (C.E.T.I.), R.C. ' Athena' , Tsimiski 58, GR-67100 Xanthi (Greece); Kitis, G., E-mail: gkitis@auth.gr [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124 Thessaloniki (Greece)

    2012-07-15

    The fast, linearly modulated optically stimulated luminescence (LM-OSL) component in quartz is the main dosimetric signal used for the dating applications of this material. Since the blue light stimulation (470 nm, 40 mW cm {sup -2}) time needed to obtain the fast LM-OSL component is less than 50 s the electron trapping levels responsible for it are still highly populated. In this way an active radiation history is created which could play an important role in the dosimetric characteristics of the fast OSL signal. In the present work the dose response behavior of the fast OSL signal is investigated in quartz samples with an annealed radiation history and quartz samples possessing an artificial radiation history. A computerized curve de-convolution analysis of the LM-OSL curves for 50 s stimulation time showed that it consists of three individual OSL components. The faster component C{sub 1} with peak maximum time around 5 s has a linear dose response in virgin samples, which turns to a slight superlinearity as a function of the artificial radiation history. On the other hand the component C{sub 2} with peak maximum time at 12 s is slightly superlinear which turns into strong superlinearity as a function of artificial radiation history. Finally, component C{sub 3} with peak maximum time at about 45 s is strongly superlinear for both virgin samples and as a function of artificial radiation history. The implications to practical application are discussed. - Highlights: Black-Right-Pointing-Pointer The fast OSL component consists of three components. Black-Right-Pointing-Pointer The linearity of first fast component does not depend on radiation history. Black-Right-Pointing-Pointer The linearity of second and third components depend on radiation history. Black-Right-Pointing-Pointer The TL between 180 and 300 Degree-Sign C is the major source of OSL.

  18. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  19. Radiation dose response correlation between thermoluminescence and optically stimulated luminescence in quartz

    International Nuclear Information System (INIS)

    The fast, linearly modulated optically stimulated luminescence (LM-OSL) component in quartz is the main dosimetric signal used for the dating applications of this material. Since the blue light stimulation (470 nm, 40 mW cm −2) time needed to obtain the fast LM-OSL component is less than 50 s the electron trapping levels responsible for it are still highly populated. In this way an active radiation history is created which could play an important role in the dosimetric characteristics of the fast OSL signal. In the present work the dose response behavior of the fast OSL signal is investigated in quartz samples with an annealed radiation history and quartz samples possessing an artificial radiation history. A computerized curve de-convolution analysis of the LM-OSL curves for 50 s stimulation time showed that it consists of three individual OSL components. The faster component C1 with peak maximum time around 5 s has a linear dose response in virgin samples, which turns to a slight superlinearity as a function of the artificial radiation history. On the other hand the component C2 with peak maximum time at 12 s is slightly superlinear which turns into strong superlinearity as a function of artificial radiation history. Finally, component C3 with peak maximum time at about 45 s is strongly superlinear for both virgin samples and as a function of artificial radiation history. The implications to practical application are discussed. - Highlights: ► The fast OSL component consists of three components. ► The linearity of first fast component does not depend on radiation history. ► The linearity of second and third components depend on radiation history. ► The TL between 180 and 300 °C is the major source of OSL.

  20. Dose-response relationship for breast cancer induction at radiotherapy dose

    Directory of Open Access Journals (Sweden)

    Gruber Günther

    2011-06-01

    Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

  1. Use of three-dimensional lognormal dose-response surfaces in lifetime studies of radiation-induced cancer

    International Nuclear Information System (INIS)

    The three-dimensional lognormal cumulative probability power function was used to provide a unifying dose-response description of the lifetime cancer risk for chronic exposure of experimental animals and people, for risk evaluation, and for scaling between species. Bone tumor fatilities, primarily from alpha irradiation of the skeleton in lifetime studies of beagles injected with 226Ra, were shown to be well described by this function. This function described cancer risk in lifetime studies as a curved smooth surface depending on radiation exposure rate and elapsed time, such that the principal risk at low dose rates occurred near the end of the normal life span without significant life shortening. Essentially identical functions with the median value of the power function displaced with respect to appropriate RBE values were shown to describe bone-cancer induction primarily from alpha irradiation of the skeleton in lifetime beagle studies with injected 226Ra, 228Th, 239Pu and 241Am, and with inhaled 238Pu. Application of this model to human exposures to 226Ra yielded a response ratio of 3.6; that is, the time required for development of bone cancer in people was 3.6 times longer than for beagles at the same average skeletal dose rate. It was suggested that similar techniques were appropriate to other carcinogens and other critical organs. 20 refs., 8 figs., 3 tabs

  2. Coffee consumption and risk of endometrial cancer: a dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Zhou, Quan; Luo, Mei-Ling; Li, Hui; Li, Min; Zhou, Jian-Guo

    2015-08-25

    This is a dose-response (DR) meta-analysis to evaluate the association of coffee consumption on endometrial cancer (EC) risk. A total 1,534,039 participants from 13 published articles were added in this meta-analysis. The RR of total coffee consumption and EC were 0.80 (95% CI: 0.74-0.86). A stronger association between coffee intake and EC incidence was found in patients who were never treated with hormones, 0.60 (95% CI: 0.50-0.72), and subjects with a BMI ≥25 kg/m(2), 0.57 (95% CI: 0.46-0.71). The overall RRs for caffeinated and decaffeinated coffee were 0.66 (95% CI: 0.52-0.84) and 0.77 (95% CI: 0.63-0.94), respectively. A linear DR relationship was seen in coffee, caffeinated coffee, decaffeinated coffee and caffeine intake. The EC risk decreased by 5% for every 1 cup per day of coffee intake, 7% for every 1 cup per day of caffeinated coffee intake, 4% for every 1 cup per day of decaffeinated intake of coffee, and 4% for every 100 mg of caffeine intake per day. In conclusion, coffee and intake of caffeine might significantly reduce the incidence of EC, and these effects may be modified by BMI and history of hormone therapy.

  3. Dose-response effects of Elephantopus scaber methanolic extract on N-nitrosodiethylamine-induced hepatotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    A.Linza; P.J.Wills; P.N.Ansil; S.P.Prabha; A.Nitha; B.Latha; K.O.Sheeba; M.S.Latha

    2013-01-01

    AIM:A decoction of Elephantopus scaber (Asteraceae) root is used to treat liver disorders in Indian and Chinese traditional medicine.The study was designed to examine the dose response effects of E.scaber methanolic extract on rats exposed to N-nitrosodiethylamine (NDEA) induced hepatotoxicity (0.02% NDEA in water five days per week,per oral) in preventive and curative models.METHODS:In preventive groups,NDEA was administered for six weeks.Daily doses of E.scaber methanolic extract (200 and 100mg·kg-1) started one week before the onset of NDEA intoxication and continued for six weeks.In curative animals,NDEA was administered for six weeks followed by treatment with the methanolic n-hexane extract of E.scaber (200 and 100mg·kg-1) for ten days.RESULTS:E.scaber extract treatment significantly (P≤0.05) reduced the levels of AST,ALT,and MDA in both experimental groups.The extract also enhanced the antioxidant enzyme and protein levels in rats intoxicated with NDEA.Treatment with the extract dose dependently protected the liver from NDEA-induced hepatotoxicity with normal hepatocytes and uniform sinusoids,but in some areas showed degenerating hepatic cells in both treatment groups.CONCLUSION:E.scaber methanolic extract dose dependently prevented and reversed the hepatotoxicity induced by NDEA in both experimental models.

  4. Generation of dose-response relationships to assess the effects of acidity in precipitation on growth and productivity of vegetation

    International Nuclear Information System (INIS)

    Experiments were performed with several plant species in natural environments as well in a greenhouse and/or tissue culture facilities to establish dose-response functions of plant responses to simulated acidic rain in order to determine environmental risk assessments to ambient levels of acidic rain. Response functions of foliar injury, biomass of leaves and seed of soybean and pinto beans, root yields of radishes and garden beets, and reproduction of bracken fern are considered. The dose-response function of soybean seed yields with the hydrogen ion concentration of simulated acidic rainfalls was expressed by the equation y = 21.06-1.01 log x where y = seed yield in grams per plant and x = the hydrogen concentration if μeq l-1. The correlation coefficient of this relationship was -0.90. A similar dose-response function was generated for percent fertilization of ferns in a forest understory. When percent fertilization is plotted on logarithmic scale with hydrogen ion concentration of the simulated rain solution, the Y intercept is 51.18, slope -0.041 with a correlation coefficient of -0.98. Other dose-response functions were generated that assist in a general knowledge as to which plant species and which physiological processes are most impacted by acidic precipitation. Some responses did not produce convenient dose-response relationships. In such cases the responses may be altered by other environmental factors or there may be no differences among treatment means

  5. Generation of dose-response relationships to assess the effects of acidity in precipitation on growth and productivity of vegetation

    Energy Technology Data Exchange (ETDEWEB)

    Evans, L.S.

    1981-01-01

    Experiments were performed with several plant species in natural environments as well in a greenhouse and/or tissue culture facilities to establish dose-response functions of plant responses to simulated acidic rain in order to determine environmental risk assessments to ambient levels of acidic rain. Response functions of foliar injury, biomass of leaves and seed of soybean and pinto beans, root yields of radishes and garden beets, and reproduction of bracken fern are considered. The dose-response function of soybean seed yields with the hydrogen ion concentration of simulated acidic rainfalls was expressed by the equation y = 21.06-1.01 log x where y = seed yield in grams per plant and x = the hydrogen concentration if ..mu..eq l/sup -1/. The correlation coefficient of this relationship was -0.90. A similar dose-response function was generated for percent fertilization of ferns in a forest understory. When percent fertilization is plotted on logarithmic scale with hydrogen ion concentration of the simulated rain solution, the Y intercept is 51.18, slope -0.041 with a correlation coefficient of -0.98. Other dose-response functions were generated that assist in a general knowledge as to which plant species and which physiological processes are most impacted by acidic precipitation. Some responses did not produce convenient dose-response relationships. In such cases the responses may be altered by other environmental factors or there may be no differences among treatment means.

  6. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

    Science.gov (United States)

    Calabrese, Edward J; Bachmann, Kenneth A; Bailer, A John; Bolger, P Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M George; Chiueh, Chuang C; Clarkson, Thomas W; Cook, Ralph R; Diamond, David M; Doolittle, David J; Dorato, Michael A; Duke, Stephen O; Feinendegen, Ludwig; Gardner, Donald E; Hart, Ronald W; Hastings, Kenneth L; Hayes, A Wallace; Hoffmann, George R; Ives, John A; Jaworowski, Zbigniew; Johnson, Thomas E; Jonas, Wayne B; Kaminski, Norbert E; Keller, John G; Klaunig, James E; Knudsen, Thomas B; Kozumbo, Walter J; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I; Masoro, Edward J; McClellan, Roger O; Mehendale, Harihara M; Mothersill, Carmel; Newlin, David B; Nigg, Herbert N; Oehme, Frederick W; Phalen, Robert F; Philbert, Martin A; Rattan, Suresh I S; Riviere, Jim E; Rodricks, Joseph; Sapolsky, Robert M; Scott, Bobby R; Seymour, Colin; Sinclair, David A; Smith-Sonneborn, Joan; Snow, Elizabeth T; Spear, Linda; Stevenson, Donald E; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M; Mattson, Mark P

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  7. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu

    2005-12-15

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology.

  8. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

    International Nuclear Information System (INIS)

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology

  9. Patch test dose-response study: polysensitized individuals do not express lower elicitation thresholds than single/double-sensitized individuals

    DEFF Research Database (Denmark)

    Carlsen, B C; Fischer, Louise Arup; Sosted, H;

    2009-01-01

    and compare elicitation dose-response curves and elicitation thresholds in a polysensitized vs. a single/double-sensitized group for allergens to which the test subjects were already sensitized. PATIENTS/METHODS: Fifty-one patients (13 polysensitized and 38 single/double-sensitized) were patch tested...... with nickel sulphate, methyldibromo glutaronitrile (MDBGN) and p-phenylenediamine (PPD) in dilution series. The ratio between the doses eliciting a response in 50% of patients in the two groups was used as the measure for relative sensitivity. RESULTS: The dose-response curves of the polysensitized group...

  10. Linearization of dose-response curve of the radiochromic film dosimetry system

    Energy Technology Data Exchange (ETDEWEB)

    Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad; DeBlois, Francois; Seuntjens, Jan; Chan, Maria F.; Lewis, Dave [Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Executive Administration for Radiation Protection and Safety Medical Devices Sector, Saudi Food and Drug Authority, Riyadh, Kingdom of Saudi Arabia 13312 (Saudi Arabia); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center Basking Ridge, New Jersey 07920 (United States); Ashland Inc., Wayne, New Jersey 07470 (United States)

    2012-08-15

    Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also

  11. Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships

    Directory of Open Access Journals (Sweden)

    Thompson Sally

    2010-11-01

    Full Text Available Abstract Background To compare the efficacy of pregabalin and gabapentin at comparable effective dose levels in patients with refractory partial epilepsy. Methods Eight randomized placebo controlled trials investigating the efficacy of pregabalin (4 studies and gabapentin (4 studies over 12 weeks were identified with a systematic literature search. The endpoints of interest were "responder rate" (where response was defined as at least a 50% reduction from baseline in the number of seizures and "change from baseline in seizure-free days over the last 28 days (SFD". Results of all trials were analyzed using an indirect comparison approach with placebo as the common comparator. The base-case analysis used the intention-to-treat last observation carried forward method. Two sensitivity analyses were conducted among completer and responder populations. Results The base-case analysis revealed statistically significant differences in response rate in favor of pregabalin 300 mg versus gabapentin 1200 mg (odds ratio, 1.82; 95% confidence interval, 1.02, 3.25 and pregabalin 600 mg versus gabapentin 1800 mg (odds ratio, 2.52; 95% confidence interval, 1.21, 5.27. Both sensitivity analyses supported the findings of the base-case analysis, although statistical significance was not demonstrated. All dose levels of pregabalin (150 mg to 600 mg were more efficacious than corresponding dosages of gabapentin (900 mg to 2400 mg in terms of SFD over the last 28 days. Conclusion In patients with refractory partial epilepsy, pregabalin is likely to be more effective than gabapentin at comparable effective doses, based on clinical response and the number of SFD.

  12. Dose-response effect of exercise frequency on bone mineral density in post-menopausal, osteopenic women.

    Science.gov (United States)

    Kemmler, W; von Stengel, S

    2014-06-01

    The purpose of this study was to determine the long-term dose-response relationship of exercise frequency on areal bone mineral density (aBMD) in early post-menopausal women with osteopenia. Based on the 12-year results of the consequently supervised exercise group (EG) of the Erlangen Fitness and Osteoporosis Prevention Study, we retrospectively structured two exercise groups according to the overall exercise frequency. Changes in aBMD at lumbar spine and proximal femur as assessed by dual-energy x-ray absorptiometry technique were compared between a low-frequency exercise group (LEF-EG, n = 16) with 1.5-exercise group (HEF-EG, n = 25) with ≥ 2-3.5 sessions/week. Changes in aBMD at the lumbar spine and proximal femur were significantly more favorable in the HEF-EG compared with the LEF-EG; lumbar spine: (mean value ± standard deviation) 1.1 ± 4.7% vs -4.1 ± 3.0%; P = 0.001, ES: d' = 1.26; total hip: -4.4 ± 3.9% vs -6.7 ± 3.5%, P = 0.045, ES: d' = 0.70). BMD results of the LEF-EG did not significantly differ from the data of the non-training control group (lumbar spine: -4.4 ± 5.2%, total hip: -6.9 ± 5.0%). Although this result might not be generalizable across all exercise types and cohorts, it indicates that to impact bone, an overall exercise frequency of at least 2 sessions/week may be crucial, even if exercise is applied with high intensity/impact.

  13. Component resolved OSL dose response and sensitization of various sedimentary quartz samples

    Energy Technology Data Exchange (ETDEWEB)

    Kiyak, N.G. [Faculty of Science and Arts, ISIK University, Istanbul (Turkey)]. E-mail: kiyak@isikun.edu.tr; Polymeris, G.S. [Cultural and Educational Technology Institute, Archaeometry Laboratory, Tsimiski 58, 67100-Xanthi (Greece); Nuclear Physics Laboratory, Aristotle University of Thessaloniki, 54124-Thessaloniki (Greece); Kitis, G. [Nuclear Physics Laboratory, Aristotle University of Thessaloniki, 54124-Thessaloniki (Greece)

    2007-02-15

    The structure of the linearly modulated optically stimulated luminescence (LM-OSL) signal was studied for four sedimentary quartz samples, collected from different sites around Istanbul, Turkey. Applying a computerized deconvolution analysis to the LM-OSL curves, at least six individual components of first-order kinetics were identified and photoionization cross-section of each component was evaluated. The OSL dose-response curve of each component for each quartz sample was obtained, showing a remarkable differentiation from component to component. The behavior of a highly dosed sample to successive LM-OSL measurements was also studied showing a stable recuperation signal in the position of the 'slow' and 'medium' components and high resistance to OSL bleaching of the 'slow' component. The individual sensitivity of each component as a function of the activation temperature was obtained. The sensitivity of each component was normalized over the respective sensitivity of the glow-peak at 110 deg. C of quartz in order to investigate the ability of the 110 deg. C glow-peak to act as a correction factor for all components of the LM-OSL curves examined.

  14. Dose-response relationships for female radium dial workers: A new look

    International Nuclear Information System (INIS)

    The values of initial systemic intake and of skeletal dose for all of the U.S. radium cases have recently been revised. This revision was required following the demonstrations by Rundo and by Keane that humans who were exposed to radium as adults lost radium at a rate that depended on the quantity of radium originally deposited within their bodies. These new values have been used to define new dose-response relationships for both the bone sarcomas and the carcinomas arising in the paranasal sinuses and mastoid air cells induced by internally deposited radium. The population examined was employed in the U.S. dial painting industry prior to 1950 and consisted of 1530 female dial workers for whom radium body burden measurements were available. By the end of 1990, 46 cases of bone sarcomas and 19 cases of head carcinomas had been diagnosed in this cohort. The head carcinoma incidence can be adequately fitted by a simple linear function, as was found in previous analyses. The bone sarcoma cases were previously fitted by a dose-squared-exponential function. With the revised values of systemic intake, the sarcoma results could not be satisfactorily fitted with this expression. When the exponent on D was increased to larger values, excellent fits were obtained

  15. Three-dimensional dose-response models of risk for radiation injury carcinogenesis

    International Nuclear Information System (INIS)

    The use of computer graphics in conjunction with three-dimensional models of dose-response relationships for chronic exposure to ionizing radiation dramaticly clarifies the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. As an example, the functionally injurious and carcinogenic responses after systemic uptake of Ra-226 by beagles, mice and people with consequent alpha particle irradiation of the bone are represented by three-dimensional dose-rate/time/response surfaces that demonstrate the contributions with the passage of time of the competing deleterious responses. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each effect. Radiation bone injury predominates at high dose rates and bone cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for bone cancer induction. Risk assessment is benefited by the insights that become apparent with these three-dimensional models. The improved conceptualization afforded by them contributes to planning and evaluating epidemiological analyses and experimental studies

  16. Dose response effect of Paracoccidioides brasiliensis in an experimental model of arthritis.

    Science.gov (United States)

    Loth, Eduardo Alexandre; Biazim, Samia Khalil; Dos Santos, José Henrique Fermino Ferreira; Puccia, Rosana; Brancalhão, Rosimeire Costa; Chasco, Lucinéia de Fátima; Gandra, Rinaldo Ferreira; Simão, Rita de Cássia Garcia; de Franco, Marcello Fabiano

    2014-01-01

    Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

  17. DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Eduardo Alexandre Loth

    2014-06-01

    Full Text Available Paracoccidioidomycosis (PCM is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18 cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

  18. Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations.

    Science.gov (United States)

    Calabrese, Edward J

    2016-08-01

    This article provides the first extensive documentation of the dose response features of pre- and postconditioning. Pre- and postconditioning studies with rigorous study designs, using multiple doses/concentrations along with refined dose/concentration spacing strategies, often display hormetic dose/concentration response relationships with considerable generality across biological model, inducing (i.e., conditioning) agent, challenging dose treatment, endpoint, and mechanism. Pre- and postconditioning hormesis dose/concentration-response relationships are reported for 154 diverse conditioning agents, affecting more than 550 dose/concentration responses, across a broad range of biological models and endpoints. The quantitative features of the pre- and postconditioning-induced protective responses are modest, typically being 30-60% greater than control values at maximum, findings that are consistent with a large body (>10,000) of hormetic dose/concentration responses not related to pre- and postconditioning. Regardless of the biological model, inducing agent, endpoint or mechanism, the quantitative features of hormetic dose/concentration responses are similar, suggesting that the magnitude of response is a measure of biological plasticity. This paper also provides the first documentation that hormetic effects account for preconditioning induced early (1-3h) and delayed (12-72h) windows of protection. These findings indicate that pre- and postconditioning are specific types of hormesis. PMID:26757428

  19. Dose response curve of induction of MN in lymphocytes for energies Cs-137

    International Nuclear Information System (INIS)

    The determination of the dose-response curve is a crucial step to use the Micronucleus assay in Lymphocytes as a biological dosimeters. The most widely used fitting function is the linear-quadratic function. The coefficients are fitted by calibration data provided by irradiations of blood from healthy donors. In our case we performed the calibration curve corresponding to gamma radiation from Cesium-137 (660 keV). Doses ranged from 0 to 16 Gy. The fitting procedure used was the iteratively re weighted least square algorithm implemented in a Matlab routine. The results of the analysis of our data show that the dose-effect curve does not follow a linear-quadratic curve at high radiation doses, diminishing the quadratic parameters as dose increases. This can be interpreted as a micronucleus saturation effect beyond a certain dose level. We conclude that the MN assay with lymphocytes can be well characterized as a biological dosimeters up to a maximum dose of 4.5 Gy. (Author)

  20. New flux based dose-response relationships for ozone for European forest tree species.

    Science.gov (United States)

    Büker, P; Feng, Z; Uddling, J; Briolat, A; Alonso, R; Braun, S; Elvira, S; Gerosa, G; Karlsson, P E; Le Thiec, D; Marzuoli, R; Mills, G; Oksanen, E; Wieser, G; Wilkinson, M; Emberson, L D

    2015-11-01

    To derive O3 dose-response relationships (DRR) for five European forest trees species and broadleaf deciduous and needleleaf tree plant functional types (PFTs), phytotoxic O3 doses (PODy) were related to biomass reductions. PODy was calculated using a stomatal flux model with a range of cut-off thresholds (y) indicative of varying detoxification capacities. Linear regression analysis showed that DRR for PFT and individual tree species differed in their robustness. A simplified parameterisation of the flux model was tested and showed that for most non-Mediterranean tree species, this simplified model led to similarly robust DRR as compared to a species- and climate region-specific parameterisation. Experimentally induced soil water stress was not found to substantially reduce PODy, mainly due to the short duration of soil water stress periods. This study validates the stomatal O3 flux concept and represents a step forward in predicting O3 damage to forests in a spatially and temporally varying climate. PMID:26164201

  1. High-LET dose-response characteristics by track structure theory of heavy charged particles

    International Nuclear Information System (INIS)

    The track structure theory developed by Katz and co-workers ascribes the effect of high-LET radiation to the highly inhomogeneous dose distribution due to low energy Δ-rays ejected from the particle track. The theory predicts the effectiveness of high-LET radiation by using the ion parameters zsub(eff') effective charge of the ion, and β = v/c, the relative ion velocity, together with the characteristic dose D37 derived from low-LET dose-response characteristic of the detector and the approximate size asub(0) of the sensitive element of the detector. 60Co gamma-irradiation is used as a reference low-LET radiation, while high-LET radiation ranging from 16 MeV protons to 4 MeV/amu 160-ions covering an initial LET range of 30-5500 MeVcm2/g is obtained from a tandem Van de Graaff accelerator. A thin film (5mg/cm2) radiochromic dye cyanide plastic dosemeter was used as detector with the characteristic dose of 16.8 Mrad and a sensitive element size of 10-7 cm. Theoretical and experimental effectiveness, RBE, agreed within 10 to 25% depending on LET. (author)

  2. Estimation and uncertainty analysis of dose response in an inter-laboratory experiment

    Science.gov (United States)

    Toman, Blaza; Rösslein, Matthias; Elliott, John T.; Petersen, Elijah J.

    2016-02-01

    An inter-laboratory experiment for the evaluation of toxic effects of NH2-polystyrene nanoparticles on living human cancer cells was performed with five participating laboratories. Previously published results from nanocytoxicity assays are often contradictory, mostly due to challenges related to producing a reliable cytotoxicity assay protocol for use with nanomaterials. Specific challenges include reproducibility preparing nanoparticle dispersions, biological variability from testing living cell lines, and the potential for nano-related interference effects. In this experiment, such challenges were addressed by developing a detailed experimental protocol and using a specially designed 96-well plate layout which incorporated a range of control measurements to assess multiple factors such as nanomaterial interference, pipetting accuracy, cell seeding density, and instrument performance. Detailed data analysis of these control measurements showed that good control of the experiments was attained by all participants in most cases. The main measurement objective of the study was the estimation of a dose response relationship between concentration of the nanoparticles and metabolic activity of the living cells, under several experimental conditions. The dose curve estimation was achieved by imbedding a three parameter logistic curve in a three level Bayesian hierarchical model, accounting for uncertainty due to all known experimental conditions as well as between laboratory variability in a top-down manner. Computation was performed using Markov Chain Monte Carlo methods. The fit of the model was evaluated using Bayesian posterior predictive probabilities and found to be satisfactory.

  3. Maternal Caffeine Consumption during Pregnancy and Risk of Low Birth Weight: A Dose-Response Meta-Analysis of Observational Studies.

    Directory of Open Access Journals (Sweden)

    Jongeun Rhee

    Full Text Available Epidemiologic studies have shown inconsistent conclusions about the effect of caffeine intake during pregnancy on the risk of low birth weight (LBW. We performed a meta-analysis and linear-dose response analysis examining the association between caffeine consumption during pregnancy and risk of LBW. PubMed and EMBASE were searched for relevant articles published up to March 2014. Eight cohort and four case-control studies met all inclusion criteria. Using a random-effects model of the twelve studies, the pooled odds ratio (OR for the risk of LBW comparing the highest versus lowest level of caffeine intake during pregnancy was 1.38 (95% CI: 1.10, 1.73. Linear dose-response analysis showed that every additional 100 mg of caffeine intake (1 cup of coffee or 2 cups of tea per day during pregnancy was associated with a 3.0% increase in OR for LBW. There was a moderate level of overall heterogeneity with an I-squared value of 55% (95% CI: 13, 76%, and no evidence of publication bias based on Egger's test (P = 0.20 and the funnel plot. Thus, high caffeine intake during pregnancy is associated with a significant increase in the risk of LBW, and this risk appears to increase linearly as caffeine intake increases.

  4. European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'

    DEFF Research Database (Denmark)

    Calderón, M A; Larenas, D; Kleine-Tebbe, J;

    2011-01-01

    For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen prod...

  5. Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-fixed paraffin-embedded (FFPE) Samples

    Science.gov (United States)

    Formalin-fixed paraffin-embedded (FFPE) samples provide a vast untapped resource for chemical safety and translational science. To date, genomic profiling of FFPE samples has been limited by poor RNA quality and inconsistent results with limited utility in dose-response assessmen...

  6. Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? ###SETAC

    Science.gov (United States)

    The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. Recently, claims have arisen tha...

  7. Continuous Dose-Response Response Relationship of the LDL-Cholesterol-Lowering Effect of Phytosterol Intake 1,2

    NARCIS (Netherlands)

    Demonty, I.; Ras, R.T.; Knaap, van der H.C.M.; Duchateau, G.S.M.J.E.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A.

    2009-01-01

    Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)¿lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C¿lowering efficacy of different

  8. Influence of lung parenchymal destruction on the different indexes of the methacholine dose-response curve in COPD patients

    NARCIS (Netherlands)

    G.T. Verhoeven; A.F.M. Verbraak (Anton); S. Boere-van der Straat; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan)

    2000-01-01

    textabstractSTUDY OBJECTIVES: The interpretation of nonspecific bronchial provocation dose-response curves in COPD is still a matter of debate. Bronchial hyperresponsiveness (BHR) in patients with COPD could be influenced by the destruction of the parenchyma and the aug

  9. Dose response on the 110 °C thermoluminescence peak of un-heated, synthetic Merck quartz

    Science.gov (United States)

    Kaya Keleş, Şule; Meriç, Niyazi; Polymeris, George S.

    2016-07-01

    Studies on 110 °C TL peak have been carried out using natural quartz from different origins and synthetic quartz produced by different suppliers. The interest in quartz is due to its usage in dating and retrospective dosimetry as a main material; both synthetic and natural types of quartz yield the 110 °C TL peak in their glow curve. In most studies to understand the physical mechanism behind the TL system, synthetic quartz samples are used and there are many investigations about dose response, in both low and high radiation dose region. In these studies generally synthetic quartz samples produced by Sawyer Research Products are used and the studies showed that both heated and un-heated synthetic quartz samples have intense supra-linear responses. Supra-linearity was enhanced by applying a pre-irradiation while several models have been developed towards an explanation to these supra-linearity effects. In this study commercially available synthetic Merck quartz was used. Different combinations of optical filters were used to obtain dose response curves upto 266 Gy and the effect of pre-dose to these dose response curves was studied. Un-pre-dosed Merck quartz samples dose supra-linearity index is below 1 independently on the optical filters; so Merck quartz showed linear or sub-linear dose response.

  10. EFFECTS OF PRENATAL TESTOSTERONE PROPIONATE ON THE SEXUAL DEVELOPMENT OF MALE AND FEMALE RATS: A DOSE-RESPONSE STUDY

    Science.gov (United States)

    Effects of Prenatal Testosterone Propionate on the Sexual Development of Male and Female Rats: A Dose-Response Study Cynthia J. Wolf1,2, Andrew Hotchkiss3, Joseph S. Ostby1, Gerald A. LeBlanc2 and L. Earl Gray1,4, Jr.ABSTRACTTestosterone plays a major role in ...

  11. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  12. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  13. Dairy Consumption and Incidence of Hypertension : A Dose-Response Meta-Analysis of Prospective Cohort Studies

    NARCIS (Netherlands)

    Soedamah-Muthu, S.S.; Verberne, L.D.M.; Ding, E.L.; Engberink, M.F.; Geleijnse, J.M.

    2012-01-01

    Dairy Consumption and Incidence of Hypertension : A Dose-Response Meta-Analysis Prospective Cohort Studies Sabita S. Soedamah-Muthu, Lisa D.M. Verberne, Eric L. Ding, Mariëlle F. Engberink and Johanna M. Geleijnse Hypertension. published online September 17, 2012; Hypertension is published by the Am

  14. Revised assessment of cancer risk to dichloromethane: part I Bayesian PBPK and dose-response modeling in mice.

    OpenAIRE

    Marino, Dale J.; Clewell, Harvey J.; Gentry, P. Robinan; Covington, Tammie R.; Hack, C. Eric; David, Raymond M.; Morgott, David A.

    2006-01-01

    KEYWORDS - CLASSIFICATION: analysis;Animals;Bayes Theorem;chemically induced;Carcinogens;Dose-Response Relationship,Drug;Environment;Inhalation Exposure;metabolism;methods;Markov Chains;mechanisms of carcinogenesis;Methylene Chloride;Mice;Models,Biological;Monte Carlo Method;Neoplasms;pharmacokinetics;Risk Assessment;Safety.

  15. [Exercise-induced asthma in children and oral terbutaline. A dose-response relationship study].

    Science.gov (United States)

    Hertz, B; Fuglsang, G; Holm, E B

    1994-09-26

    We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate in 17 asthmatic children aged 6-12 years (mean 9 years). Placebo, 2, 4, and 6 mg terbutaline were given b.i.d. for 14 days in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline/day, respectively. A small but statistically significant dose-related increase was seen in morning and evening peak expiratory flow (PEF) recordings. It is concluded that continuous treatment, even with high doses or oral terbutaline, does not offer clinically useful protection against exercise-induced asthma. PMID:7985255

  16. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    Science.gov (United States)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  17. A dose-response relationship between maternal smoking during late pregnancy and adult intelligence in male offspring.

    Science.gov (United States)

    Mortensen, Erik Lykke; Michaelsen, Kim Fleischer; Sanders, Stephanie A; Reinisch, June Machover

    2005-01-01

    An association between maternal smoking during pregnancy and cognitive and behavioural development has been observed in several studies, but potential effects of maternal smoking on offspring adult intelligence have not been investigated. The objective of the present study was to investigate a potential association between maternal smoking during pregnancy and offspring intelligence in young adulthood. Adult intelligence was assessed at the mean age of 18.7 years by a military draft board intelligence test (Borge Priens Prove) for 3044 singleton males from the Copenhagen Perinatal Cohort with information regarding maternal smoking during the third trimester coded into five categories (about 50% of the mothers were smokers). The following potential confounders were included as covariates in multivariable analyses: parental social status and education, single mother status, mother's height and age, number of pregnancies, and gestational age. In separate analyses, birthweight and length were also included as covariates. Maternal cigarette smoking during the third trimester, adjusted for the seven covariates, showed a negative association with offspring adult intelligence (P=0.0001). The mean difference between the no-smoking and the heaviest smoking category amounted to 0.41 standard deviation, corresponding to an IQ difference of 6.2 points [95% confidence interval 0.14, 0.68]. The association remained significant when further adjusted for birthweight and length (P=0.007). Both unadjusted and adjusted means suggested a dose-response relationship between maternal smoking during pregnancy and offspring adult intelligence. When subjects with missing data were excluded, essentially the same results were obtained in the reduced sample (n=1829). These results suggest that smoking during pregnancy may have long-term negative consequences on offspring adult intelligence. PMID:15670102

  18. Isoflavone consumption and risk of breast cancer: a dose-response meta-analysis of observational studies.

    Science.gov (United States)

    Xie, Qi; Chen, Ming-Liang; Qin, Yu; Zhang, Qian-Yong; Xu, Hong-Xia; Zhou, Yong; Mi, Man-Tian; Zhu, Jun-Dong

    2013-01-01

    Epidemiologic studies that examine whether isoflavone consumption protects against breast cancer have yielded inconsistent results. The controversy focuses on the effects of the menopausal status and exposure dose of isoflavone. We aim to conduct a meta-analysis on the association between isoflavone intake and breast cancer risk by comprehensively assessing isoflavone exposure in the targeted populations. We searched PUBMED and EMBASE databases for case-control and cohort studies that assess the association between isoflavone intake and breast cancer risk. We extracted relative risks (RR) and odds ratios (OR) of different reported categories of isoflavone intake from each study. Fixed- or random-effects models were used to summarize dose-response data. Twenty-two studies were selected for the meta-analysis. Overall, the results showed that isoflavone reduced the breast cancer risk (a combined RR/OR of 0.68, 95% CI: 0.52-0.89) in Asian populations rather than Western populations (a combined RR/OR of 0.98, 95% CI: 0.87, 1.11) for the high-dose category. Further analysis showed that the intake of isoflavone in postmenopausal Asian women 0.46 (95% CI: 0.28-0.78) was better than premenopausal 0.63 (95% CI: 0.50-0.80) but similar in postmenopausal Western women 1.00 (95% CI: 0.98-1.02) and premenopausal 0.99 (95% CI: 0.87-1.12). Exposure to high isoflavone may be associated with a reduced breast cancer risk in Asian populations, especially in postmenopausal women. However, no significant difference in the studies of Western populations may be due to the low intake of isoflavone levels. PMID:23353619

  19. Henry S. Kaplan Distinguished Scientist Award 2003. The crooked shall be made straight; dose-response relationships for carcinogenesis.

    Science.gov (United States)

    Hall, E J

    2004-05-01

    Estimates of radiation-induced malignancies come principally from the atomic (A)-bomb survivors and show an excess incidence of carcinomas that is linearly related to dose from about 5 cGy to 2.5 Gy. Above and below this dose range there is considerable uncertainty about the shape of the dose-response relationship. Both the International Commission of Radiation Protected (ICRP) and the National Council of Radiation Protection (NCRP) suggest that cancer risks at doses lower than those at which direct epidemiological observations are possible should be obtained by a linear extrapolation from higher doses. The demonstrated bystander effect for irradiation exaggerates the consequences of small doses of radiation and implies that a linear extrapolation from high doses would underestimate low dose risks. It is possible to make estimates of the cancer risk of diagnostic radiological procedures. Helical computed tomography in children is of particular interest since it is rapidly increasing in use and the doses involved are close to the lower limit of significance in the A-bomb survivors. For example, an abdominal computed tomographic scan in a 1-year-old child can be estimated to result in a lifetime cancer risk of about 1:1000. In the context of radiotherapy, some normal tissues receive 70 Gy, while a larger volume receives a lower dose, but still far higher than the range for which data are available from the A-bomb survivors. Data are available for the risk of radiation-induced malignancies for patients who received radiotherapy, e.g. for prostate or cervical cancer. New technologies such as intensity modulated radiation therapy could result in a doubling of radiation-induced second cancers since the technique involves a larger total-body dose due to leakage radiation and the dose distribution obtained involves a larger volume of normal tissue exposed to lower radiation doses. PMID:15223765

  20. Dose-response model of murine typhus (Rickettsia typhi: time post inoculation and host age dependency analysis

    Directory of Open Access Journals (Sweden)

    Tamrakar Sushil B

    2012-03-01

    Full Text Available Abstract Background Rickettsia typhi (R. mooseri is the causative agent of murine typhus. It is one of the most widely distributed flea-borne diseases with a relatively mild febrile initial illness with six to 14 days of incubation period. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through fleabites or via contact with infected feces. This paper develops dose-response models of different routes of exposure for typhus in rodents. Methods Data from published articles were analyzed using parametric dose-response relationship models. Dose-response relationships were fit to data using the method of maximum likelihood estimation (MLE. Results Dose-response models quantifying the effects of different ages of rats and time post inoculation in BALB/c mice were analyzed in the study. Both the adult rats (inoculated intradermally and newborn rats (inoculated subcutaneously were best fit by exponential models and both distributions could be described by a single dose-response relationship. The BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The time post inoculation analysis showed that there was a definite time and response relationship existed in this case. Conclusions Intradermally or subcutaneously inoculated rats (adult and newborn models suggest that less than 1 plaque-forming unit (PFU (1.33 to 0.38 in 95% confidence limits of the pathogen is enough to seroconvert 50% of the exposed population on average. For the BALB/c mouse time post inoculation model, an average dose of 0.28 plaque-forming units (PFU (0.75 to 0.11 in 95% confidence limits will seroconvert 50% of the exposed mice.

  1. Energy crop (Sida hermaphrodita) fertilization using digestate under marginal soil conditions: A dose-response experiment

    Science.gov (United States)

    Nabel, Moritz; Bueno Piaz Barbosa, Daniela; Horsch, David; Jablonowski, Nicolai David

    2014-05-01

    The global demand for energy security and the mitigation of climate change are the main drivers pushing energy-plant production in Germany. However, the cultivation of these plants can cause land use conflicts since agricultural soil is mostly used for plant production. A sustainable alternative to the conventional cultivation of food-based energy-crops is the cultivation of special adopted energy-plants on marginal lands. To further increase the sustainability of energy-plant cultivation systems the dependency on synthetic fertilizers needs to be reduced via closed nutrient loops. In the presented study the energy-plant Sida hermaphrodita (Malvaceae) will be used to evaluate the potential to grow this high potential energy-crop on a marginal sandy soil in combination with fertilization via digestate from biogas production. With this dose-response experiment we will further identify an optimum dose, which will be compared to equivalent doses of NPK-fertilizer. Further, lethal doses and deficiency doses will be observed. Two weeks old Sida seedlings were transplanted to 1L pots and fertilized with six doses of digestate (equivalent to a field application of 5, 10, 20, 40, 80, 160t/ha) and three equivalent doses of NPK-fertilizer. Control plants were left untreated. Sida plants will grow for 45 days under greenhouse conditions. We hypothesize that the nutrient status of the marginal soil can be increased and maintained by defined digestate applications, compared to control plants suffering of nutrient deficiency due to the low nutrient status in the marginal substrate. The dose of 40t/ha is expected to give a maximum biomass yield without causing toxicity symptoms. Results shall be used as basis for further experiments on the field scale in a field trial that was set up to investigate sustainable production systems for energy crop production under marginal soil conditions.

  2. Dose-response relationship of octylphenol and radiation evaluated by tradescantia-micronucleus assay

    International Nuclear Information System (INIS)

    Many kinds of synthetic chemicals have been being used for various purposes. Some of them are called 'Endocrine Disruptor's because they can disturb the endocrine system of organisms. Presently no technique is established for the quantitative assessment of biological risk of the environmental hormones. The pollen mother cells (PMC) of Tradescantia are very sensitive to chemical toxicants or ionizing radiation, and thus can be used as a biological end-point assessing their effect. Micronucleus frequencies in PMC showed a good dose- and concentration-response relationship for radiation, bisphenol A and octylphenol. A parallel series of experiment using five increasing doses of gamma-ray at 10, 20, 30, 40 and 50 cGy was conducted. The MCN frequencies of 12.0, 25.2, 41.7, 76 and 83 MCN/100 tetrads were observed from each of the increasing gamma-ray dosage groups, respectively. Lenear regression analysis of the gamma-ray data MCN frequencies yielded a correlation coefficient of 0.95. the MCN frequencies in pollen mother cells treated with bisphenol a and octylphenol showed dose-response relationship in a concentration of 0, 1, 2, 4 μM and 0, 4, 10, 20 μM. the MCN frequency for the bisphenol a and octylphenol group yields 2.33, 8.06, 12.7 and 19.6 MCN/100 tetrads for the bisphenol a and 2.33, 2.33, 11.47, 17.6 MCN/100 tetrads for the octylphenol. The MCN frequency of the control was 2.33 MCN/100 tetrads. It is known from the result that Trad-MCN assay can be an excellent tool for detection of biological risk due to environmental toxicants or synthetic chemicals

  3. Digitoxin medication and cancer; case control and internal dose-response studies

    Directory of Open Access Journals (Sweden)

    Spigset Olav

    2001-08-01

    Full Text Available Abstract Background Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. Methods Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. Results The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. Conclusion Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease.These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents.

  4. Effect of Relative Humidity on Dose Response of Effervescent Glycine Pellet Dosimeters

    Directory of Open Access Journals (Sweden)

    Santosh H Shinde

    2013-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Glycine pellet dosimeter based on spectrophotometric read-out method has a useful dose range of 100 to 1000 Gy and is apt for routine dosimetry in low dose applications of radiation processing. The read-out method requires dissolution of these pellets in acidified solution of ferrous ammonium sulphate and xylenol orange, but due to appreciable hardness of these pellets it is required to stir the solution for complete dissolution which is generally not preferable. Hence fast dissolving pellets were fabricated using sodium bicarbonate as an effervescent agent. As sodium bicarbonate is hygroscopic, study of effect of relative humidity on dose response of these pellets was carried out in the present work.  

  5. Ondansetron: A newer aspect of dose response relationship on ileal smooth muscles of rabbit.

    Science.gov (United States)

    Afzal, Ayesha; Khan, Bushra Tayyaba; Bakhtiar, Salman

    2016-01-01

    There are several life threatening deadly diseases in our world but ‘Cancer’ out powers them all in recent years. Chemotherapy may be used on its own or an adjunct to other forms of therapy. Despite the advancement in cytotoxic drug therapy and supportive treatment almost 70% of patient suffer from chemotherapy induced nausea and vomiting (CINV). Ondansetron, a 5-HT(3) receptor antagonist has now become a gold standard in the treatment of chemotherapy induced nausea and vomiting. The central actions of ondansetron are well established but its peripheral actions are not well recognized. The aim of our study was to explore the peripheral actions of ondansetron. Experiments were performed in five groups (n=6) and ileal smooth muscles activity was recorded on power lab (USA). The effects of increasing concentrations of acetylcholine, serotonin & ondansetron alone was observed in first three groups. In the next two groups effects of acetylcholine and serotonin pretreated with fixed concentration (1ml) of ondansetron (10¯ϖ M)were studied. The maximum response obtained by acetylcholine served as a control for our study. Maximum response with acetylcholine was taken as 100% and with serotonin was 177 percent of control. Cumulative dose response curve with ondansetron was triphasic. At 10¯ψM it was 28.8%, whereas with 10¯ξM the amplitude decreased to 16.87%, it reached to plateau at 10¯ϖ M. Response of acetylcholine & serotonin was decreased to 57% and 78% respectively in the presence of fixed concentration of ondansetron (10¯ϖ M). Ondansetron reduces the acetylcholine and serotonin induced gastrointestinal motility. Our study has indicated that ondansetron apart from having central action also has marked peripheral actions that play an important role in CINV and may act as a partial agonist. PMID:26826825

  6. Differences in Radiation Dose Response between Small and Large Intestinal Crypts.

    Science.gov (United States)

    Otsuka, Kensuke; Suzuki, Keiji

    2016-09-01

    The protection of intestinal epithelial cells from the lethal effects induced by high-dose radiation is an important issue in radiotherapy and in the treatment of acute radiation syndrome. However, the effects of middle- and low-dose radiation on intestinal epithelial cells remain unclear. Because the accumulation of DNA damage in intestinal stem cells may be crucial for the development of cancer-initiating cells, it is important to understand the kinetics of DNA repair and tissue response (which are involved in the elimination of damaged cells and tissue injury repair) to middle- to low-dose irradiation. In this study, mice were X-ray irradiated with 0.1, 1 or 4 Gy, after which the small intestine (duodenum and ileum) and colon were harvested from the animals. DNA damage repair and the elimination of damaged cells were quantified by measuring the number of foci of 53BP1, a surrogate marker for DNA double-strand breaks. Tissue-proliferative response was evaluated by determining the number of Ki-67(+) and mitotic cells. Intra-crypt response differed considerably between the small intestine and the colon. In the small intestine, 53BP1 foci were detected immediately after irradiation, but rapidly disappeared thereafter, especially noticeable in Lgr5(+) stem cells. Cellular growth was temporally arrested; however, cell numbers and mitotic cell numbers in the crypt did not change. The kinetics of DNA damage repair in Lgr5(+) stem cells were similar to those in the small intestines, while the colon was more susceptible to radiation-induced damage. Preferential cell loss in the lower crypt was clearly observed in the colon; and after low-dose X-ray irradiation, only the colon exhibited considerably reduced cell numbers and dramatic induction of mitosis. These results suggest that differences in radiation dose response between the small and the large intestine may depend on the growth activity of stem cells after DNA repair. PMID:27556352

  7. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    Science.gov (United States)

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  8. Which cities produce more excellent papers than can be expected? A new mapping approach, using Google Maps, based on statistical significance testing

    NARCIS (Netherlands)

    L. Bornmann; L. Leydesdorff

    2011-01-01

    The methods presented in this paper allow for a statistical analysis revealing centers of excellence around the world using programs that are freely available. Based on Web of Science data (a fee-based database), field-specific excellence can be identified in cities where highly cited papers were pu

  9. Evaluating statistical and clinical significance of intervention effects in single-case experimental designs: An SPSS method to analyze univariate data

    NARCIS (Netherlands)

    M. Maric; M. de Haan; S.M. Hogendoorn; L.H. Wolters; H.M. Huizenga

    2015-01-01

    Single-case experimental designs are useful methods in clinical research practice to investigate individual client progress. Their proliferation might have been hampered by methodological challenges such as the difficulty applying existing statistical procedures. In this article, we describe a data-

  10. The Existence of Health statistics in Hospital management Significance%卫生统计在医院管理中存在的意义

    Institute of Scientific and Technical Information of China (English)

    余松玲

    2014-01-01

    医院统计工作是医院管理的一项重要内容,它可以帮助了解医院管理的宏观水平,并为改进医院管理提供可靠的依据。全面提高医院卫生统计工作的质量,高效利用卫生统计信息的综合效能,目前已经变成医院管理者关注的课题。%Hospital statistical work is an important part of hospital management,it can help us to understand the macro level of the hospital management,and provide the reliable basis for the improvement of hospital management.Improve the quality of hospital health statistical work,the efficient use of the comprehensive effectiveness of health statistics information,has become the topic of hospital management.

  11. Experimental determination of the lateral dose response functions of detectors to be applied in the measurement of narrow photon-beam dose profiles

    Science.gov (United States)

    Poppinga, D.; Meyners, J.; Delfs, B.; Muru, A.; Harder, D.; Poppe, B.; Looe, HK

    2015-12-01

    This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585-607). In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x)  =  K(x)  ∗  D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation. The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585-607). They are typical for the perturbation of the secondary electron field by a detector with

  12. Experimental determination of the lateral dose response functions of detectors to be applied in the measurement of narrow photon-beam dose profiles

    International Nuclear Information System (INIS)

    This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585–607).In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x)  =  K(x)  ∗  D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation.The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585–607). They are typical for the perturbation of the secondary electron field by a detector

  13. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA. PMID

  14. Tea consumption and risk of stroke: a dose-response meta-analysis of prospective studies

    Institute of Scientific and Technical Information of China (English)

    Li SHEN; Liu-guang SONG; Hong MA; Chun-na JIN; Jian-an WANG; Mei-xiang XIANG

    2012-01-01

    Objective:To determine the association between tea consumption and the risk of stroke.Methods:We searched the PubMed database from January 1966 to March 2012 and reviewed reference lists of retrieved articles to identify relevant studies.Studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of stroke with respect to three or more categories of tea consumption.A random-effects model was used to combine the study-specific risk estimates.Results:Fourteen studies,consisting of 513 804 participants with a median follow-up of 11.5 years,were included in this meta-analysis.We observed a modest but statistically significant inverse association between tea consumption and risk of stroke.An increase of three cups/d in tea consumption was associated with a 13% decreased risk of stroke (RR 0.87; 95% CI,0.81-0.94).The decreased risk of stroke with tea consumption was consistent among most subgroups.Based on the three studies that provided results for stroke subtypes,tea consumption was also inversely associated with the risk of ischemic stroke (RR 0.76; 95% CI,0.69-0.84),but not cerebral hemorrhage (RR 0.96; 95% CI,0.82-1.11 ) or subarachnoid hemorrhage (RR 0.81 ; 95% CI,0.57-1.16).Conclusions:Tea consumption is associated with a decreased risk of stroke,particularly ischemic stroke.More well-designed,rigorously conducted studies are needed in order to make confident conclusions about the association between tea consumption and stroke subtypes.

  15. Gamma dose response of synthetic A-type carbonated apatite in comparison with the response of tooth enamel

    International Nuclear Information System (INIS)

    Synthetic A-type carbonated apatite samples were irradiated at room temperature with 60Co γ rays. Their ESR spectra consist of the lines of CO2- and CO3- radicals of orthorhombic and axial symmetry. The measurements carried out immediately after sample irradiation showed that CO2- species are produced by decomposition of CO3- radicals. Intensity of the CO2- lines in the synthetic and enamel samples increases during the first 400 and 200 h after irradiation, respectively. The dependence of the EPR signal on the dose varies with carbonate content of the sample. The dose response curve for tooth enamel is steeper for the synthetic material. Nonuniformity in the radical site structure in the synthetic samples may arise in the process of sample preparation; this nonuniformity affects the shape of the dose-response curve

  16. The effects of heating rate on the dose response characteristics of CaF2 :Dy (TLD-200)

    International Nuclear Information System (INIS)

    In this study; the effects of heating rates (1 degree C/s and 10 degree C/s) on the dose response characteristics of low temperature peaks, LTPs, (30 degree C - 250 degree C) and high temperature peaks, HTPs, (260 degree C- 600 degree C) of CaF2:Dy (TLD-200) crystal has been investigated using the dose dependence curve and dose response function f(D). The samples were obtained from Harshaw Chemical Company, Ohio, USA. All irradiations were performed immediately after the standard annealing at 500 degree C for 1 hour at room temperature with β rays from a 90Sr- 90Y source (∼0.04 Gy/s). Glow curves were obtained using a Harshaw QS 3500 Manuel type reader. The results of the experiments have shown that the linearity and behavior of the TL glow peaks of TLD-200 are affected from the heating rate.

  17. Follicular and endocrine dose responses according to anti-Müllerian hormone levels in IVF patients treated with a novel human recombinant FSH (FE 999049)

    DEFF Research Database (Denmark)

    Bosch, Ernesto; Nyboe Andersen, Anders; Barri, Pedro;

    2015-01-01

    OBJECTIVE: To study the association between serum anti-Müllerian hormone (AMH) levels and follicular development and endocrine responses induced by increasing doses (5·2-12·1 μg/day) of a novel recombinant human FSH (rhFSH, FE 999049) in patients undergoing in vitro fertilization (IVF)/intracytop......OBJECTIVE: To study the association between serum anti-Müllerian hormone (AMH) levels and follicular development and endocrine responses induced by increasing doses (5·2-12·1 μg/day) of a novel recombinant human FSH (rhFSH, FE 999049) in patients undergoing in vitro fertilization (IVF...... for these hormones, and no clear dose-related increase was observed for the number of follicles in these patients. CONCLUSIONS: Dose-response relationships between rhFSH and follicular development and endocrine parameters are significantly different for IVF/ICSI patients with lower and higher serum AMH levels...

  18. Statistical behavior and geological significance of the geochemical distribution of trace elements in the Cretaceous volcanics Cordoba and San Luis, Argentina

    International Nuclear Information System (INIS)

    Statistical analysis of trace elements in volcanics research s, allowed to distinguish two independent populations with the same geochemical environment. For each component they have variable index of homogeneity resulting in dissimilar average values that reveal geochemical intra telluric phenomena. On the other hand the inhomogeneities observed in these rocks - as reflected in its petrochemical characters - could be exacerbated especially at so remote and dispersed location of their pitches, their relations with the enclosing rocks for the ranges of compositional variation, due differences relative ages

  19. Dose-response studies on the spermatogonial stem cells of the rhesus monkey (Macaca mulatta) after X irradiation

    International Nuclear Information System (INIS)

    Studies of the dose response of the spermatogonial stem cells in the rhesus monkey were performed at intervals of 130 and 160 days after graded doses of X irradiation. The D0 of the spermatogonial stem cells was established using the total numbers of the type A spermatogonia that were present at 130 and 160 days after irradiation and was found to be 1.07 Gy; the 95% confidence interval was 0.90-1.34 Gy

  20. Developing guidelines for economic evaluation of environmental impacts in EIAs. Part II: Case studies and dose-response literature

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6.

  1. Folate Intake and the Risk of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Studies

    OpenAIRE

    Yu-Fei Zhang; Wei-Wu Shi; Hong-Fang Gao; Li Zhou; An-Ji Hou; Yu-Hao Zhou

    2014-01-01

    BACKGROUND: Previous observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: We performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that rep...

  2. QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

    Science.gov (United States)

    Nilsen, Vegard; Wyller, John

    2016-01-01

    Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. PMID:26812258

  3. Developing guidelines for economic evaluation of environmental impacts in EIAs. Part II: Case studies and dose-response literature

    International Nuclear Information System (INIS)

    This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6

  4. Predictive testing for contact allergy : comparison of some guinea pig and mouse protocols including dose-response designs

    OpenAIRE

    Wahlkvist, Helen

    2000-01-01

    Contact allergy (delayed hypersensitivity) may develop as a result of skin exposure to contact allergens (haptens) and can lead to allergic contact dermatitis. The purpose of this study was to evaluate some predictive animal test methods for contact allergens. It was done with the aim that the test methods giving the clinically most relevant results should be used in risk assessment of chemicals and in research. A slightly modified multi-dose-response induction protocol was...

  5. Superlinear dose response of thermoluminescence (TL) and optically stimulated luminescence (OSL) signals in luminescence materials: An analytical approach

    Energy Technology Data Exchange (ETDEWEB)

    Pagonis, Vasilis, E-mail: vpagonis@mcdaniel.edu [Physics Department, McDaniel College, Westminster, MD 21158 (United States); Chen, Reuven [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel); Lawless, John L. [Redwood Scientific Incorporated, Pacifica, CA 94044-4300 (United States)

    2012-06-15

    The phenomenon of superlinear dose response of thermoluminescence (TL) and optically stimulated luminescence (OSL) signals has been reported for several important dosimetric materials. We develop new analytical equations for the filling of traps and centers during irradiation and for the read-out stage of annealed luminescence materials, within the context of a two-trap and two-center model. The equations are applicable for both TL and OSL signals in annealed dosimetric materials, and are derived under the assumptions of low irradiation doses and dominant strong retrapping (weak recombination) processes. For low doses all traps and centers display linear dose response, which leads to quadratic dose response of the integrated TL/OSL signals. A new analytical expression is presented for this well-known quadratic dose dependence, in terms of the kinetic parameters in the model. The effect of elevated irradiation temperature on the integrated TL/OSL signals is also considered, and analytical expressions are obtained for this situation as well. A new type of dose-rate effect is reported based on the modeling results, which is due to irradiation during elevated temperatures. The accuracy of the analytical expressions is verified by comparing with the results of numerical simulations. - Highlights: Black-Right-Pointing-Pointer New analytical equations for the filling of traps and centers during irradiation. Black-Right-Pointing-Pointer Equations are applicable for TL and OSL signals in annealed dosimetric materials. Black-Right-Pointing-Pointer New analytical expression for the quadratic dose dependence of TL and OSL. Black-Right-Pointing-Pointer Analytical expressions for dose response at elevated irradiation temperatures. Black-Right-Pointing-Pointer A new type of dose-rate effect is reported based on the modeling results.

  6. Comparison of effects of six tritiated compounds on chromosomal aberrations in human lymphocytes in vitro and dose-response relationships

    International Nuclear Information System (INIS)

    The effects of six tritiated compounds on chromosomal aberrations were compared in cultured human lymphocytes, and dose-response relationships were analysed. According to the efficiency of inducing aberrations, these compounds could be arranged in decreasing order as follows: 3H-TdR > 3H-UdR > 3H-lysine > 3H-thymine > 3H-leucine > HTO, when the dose-response relationship was expressed in radioactivity/ml of the medium. This order is determined mainly by the radioactivities incorporated into the nuclei or the cells. However, when compared in terms of the dose absorbed by the nuclei or the cells, the differences among various compounds would be much more reduced. The data of aberration yields for different tritium activities (or absorbed dsoes) were fitted satisfactorily to the linear-quadratic dose-response equation Y = A + BX + CX2. The yields of chromatid-type and chromosometype aberrations induced by various tritiated compounds were quite different. These differences are related to the metabolism of the compounds

  7. Influence of the Culture Medium in Dose-Response Effect of the Chlorhexidine on Streptococcus mutans Biofilms.

    Science.gov (United States)

    de Queiroz, Vanessa Salvadego; Ccahuana-Vásquez, Renzo Alberto; Tedesco, Alcides Fabiano; Lyra, Luzia; Cury, Jaime Aparecido; Schreiber, Angélica Zaninelli

    2016-01-01

    The aim of this study was to evaluate the influence of culture medium on dose-response effect of chlorhexidine (CHX) on Streptococcus mutans UA159 biofilm and validate the use of the cation-adjusted-Müller-Hinton broth (MH) for the evaluation of antibacterial activity. Ultrafiltered Tryptone-Yeast Extract Broth (UTYEB) was compared against MH and MH with blood supplementation (MHS). For each medium, six groups (n = 4) were assessed: two negative control groups (baseline 48 and 120 h) and four experimental groups (0.0001, 0.001, 0.012, and 0.12% CHX). S. mutans biofilm grew on glass slides of each media containing 1% sucrose. After 48 h of growth, biofilms of baseline 48 h were collected and the other groups were treated for 1 min, twice a day, for 3 days, with their respective treatments. The media were changed daily and pH was measured. After 120 h, biofilms were collected and dry weight and viable microorganisms were determined. Results showed CHX dose-response effect being observed in all media for all the variables. However, MH and MHS showed higher sensitivity than UTYEB (p culture medium does influence dose-response effect of CHX on Streptococcus mutans biofilm and that MH can be used for antibacterial activity.

  8. Influence of the Culture Medium in Dose-Response Effect of the Chlorhexidine on Streptococcus mutans Biofilms

    Science.gov (United States)

    de Queiroz, Vanessa Salvadego; Ccahuana-Vásquez, Renzo Alberto; Tedesco, Alcides Fabiano; Lyra, Luzia; Cury, Jaime Aparecido; Schreiber, Angélica Zaninelli

    2016-01-01

    The aim of this study was to evaluate the influence of culture medium on dose-response effect of chlorhexidine (CHX) on Streptococcus mutans UA159 biofilm and validate the use of the cation-adjusted-Müller-Hinton broth (MH) for the evaluation of antibacterial activity. Ultrafiltered Tryptone-Yeast Extract Broth (UTYEB) was compared against MH and MH with blood supplementation (MHS). For each medium, six groups (n = 4) were assessed: two negative control groups (baseline 48 and 120 h) and four experimental groups (0.0001, 0.001, 0.012, and 0.12% CHX). S. mutans biofilm grew on glass slides of each media containing 1% sucrose. After 48 h of growth, biofilms of baseline 48 h were collected and the other groups were treated for 1 min, twice a day, for 3 days, with their respective treatments. The media were changed daily and pH was measured. After 120 h, biofilms were collected and dry weight and viable microorganisms were determined. Results showed CHX dose-response effect being observed in all media for all the variables. However, MH and MHS showed higher sensitivity than UTYEB (p < 0.05). We can conclude that the culture medium does influence dose-response effect of CHX on Streptococcus mutans biofilm and that MH can be used for antibacterial activity. PMID:27293967

  9. QSAR study on the non-monotonic dose-response curve of PCBs in chicken embryo hepatocyte bioassay

    Institute of Scientific and Technical Information of China (English)

    MU YunSong; ZHANG AiQian; GAO ChangAn; PENG SuFen; WANG LianSheng

    2009-01-01

    Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls con-geners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might he related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.

  10. QSAR study on the non-monotonic dose-response curve of PCBs in chicken embryo hepatocyte bioassay

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls congeners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might be related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.

  11. Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women

    Science.gov (United States)

    Yang, Yang; Gao, Jing; Li, Hong-Lan; Zheng, Wei; Yang, Gong; Zhang, Wei; Ma, Xiao; Tan, Yu-Ting; Rothman, Nat; Gao, Yu-Tang; Chow, Wong-Ho; Shu, Xiao-Ou; Xiang, Yong-Bing

    2016-01-01

    We aimed at evaluating the risk of liver cancer in different levels of HBsAg among Chinese men and women. We carried out a nested case-control study including 363 cases and 3,511 controls in two population-based cohorts in Shanghai. Plasma samples collected at enrollment were quantified for HBsAg levels using the Architect QT assay. Conditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95%CIs) for liver cancer, with adjustment for potential confounders. HBsAg was detected in 6.29% of control subjects overall (7.02% in men and 4.98% in women). HBsAg levels were positively associated with liver cancer risk in a dose-response manner (Ptrend<0.001). Such association showed a significant gender disparity. With increasing levels of HBsAg, liver cancer risks rose more steeply in men than in women. In men, the adjusted ORs increased from 7.27 (95%CI: 3.49–15.15) at the lowest detectable level of HBsAg (5–9 IU/ml) to 7.16 (95%CI: 3.21–15.96), 34.30 (95%CI: 16.94–69.44), and 47.33 (95%CI: 23.50–95.34) at the highest level of HBsAg (≥1,000 IU/ml) compared to those negative for HBsAg. The corresponding ORs were much lower for women, from 1.37 (95%CI: 0.25–7.47) to 3.81 (95%CI: 1.09–13.28), 7.36 (95%CI: 2.41–22.46), and 16.86 (95%CI: 7.24–39.27), respectively. HBsAg quantification has potential to distinguish individuals at different risks of liver cancer. Men with the lowest detectable level of HBsAg should still pay attention to their liver cancer risks, but those with a higher level may be given a higher priority in future liver cancer surveillance program. PMID:26990915

  12. Validity of bioeffect dose response models for normal tissue early and late complications of the skin

    International Nuclear Information System (INIS)

    Background: The bioeffect of a physical dose depends on the nature of the tissue, fractionation scheme, dose rate and treatment time. Certainly, experienced radiotherapists are convinced of the existence of patient-to-patient variability in normal tissue response to radiotherapy for malignant tumours. The absorbed dose needs to be translated into a bioeffect dose, which takes into account treatment variables and the radiobiological characteristics of the relevant tissue. Various bioeffect models such as NSD, CRE, TDF and BED have been proposed to predict the biological effect of radiotherapy treatments. Aim: This study was aimed at deriving tolerance bioeffect dose values for normal tissue complication rate. Materials/Methods: Compiled clinical data of time dose fractionation schedules and incidence of erythema, desquamation and telangiectasia were used for the present analysis. Results: For erythema and desquamation the radiation dose varied from 23.9 to 55.1 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 40 days. For telangiectasia (score .1 at 3 years) the radiation dose varied from 25.8 to 55.1 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 40 days. For telangiectasia (score .2 at 5 years) the radiation dose varied from 25.8 to 63.0 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 68 days. For telangiectasia (score .1, .2, .3, .4 at 10 years) the radiation dose varied from 25.8 to 63.0 Gy in 04 to 35 fractions (dose per fraction 1.7 to 7.3 Gy) in 22 to 68 days. TDF and LQF values for erythema, desquamation and telangiectasia were evaluated with a/b values of 7.5 Gy, 11.2 Gy and 2.8 Gy respectively. TDF and LQF had a statistically significant correlation with probability of erythema, desquamation and telangiectasia (p<0.001). Conclusions: TDF and LQF values should be limited to 60 and 86 Gy in order to limit the probability of telangiectasia. (authors)

  13. PSOD: an interactive Fortran program to simulate the radiation dose response of membrane populations

    International Nuclear Information System (INIS)

    Program PSOD was written to simulate the distribution in responses of membrane populations subjected to random radiation doses and dose rates. It computes the response (damage) according to one of three formulas selected by the user, and outputs statistical results to the terminal. It will plot simulated dose- and response-frequency distributions in two or three dimensions. Doses and dose rates are selected from the log normal distribution; other distributions can be incorporated as the need arises. A true log normal curve with defined mean and standard deviation can also be generated. The purpose of this documentation is to provide a complete operating manual for the program. A user guide is available on-line after initiating a session of PSOD. Detailed examinations of the statistical validity of various steps have been included to aid future modifications and updating

  14. Derivation of the critical effect size/benchmark response for the dose-response analysis of the uptake of radioactive iodine in the human thyroid.

    Science.gov (United States)

    Weterings, Peter J J M; Loftus, Christine; Lewandowski, Thomas A

    2016-08-22

    Potential adverse effects of chemical substances on thyroid function are usually examined by measuring serum levels of thyroid-related hormones. Instead, recent risk assessments for thyroid-active chemicals have focussed on iodine uptake inhibition, an upstream event that by itself is not necessarily adverse. Establishing the extent of uptake inhibition that can be considered de minimis, the chosen benchmark response (BMR), is therefore critical. The BMR values selected by two international advisory bodies were 5% and 50%, a difference that had correspondingly large impacts on the estimated risks and health-based guidance values that were established. Potential treatment-related inhibition of thyroidal iodine uptake is usually determined by comparing thyroidal uptake of radioactive iodine (RAIU) during treatment with a single pre-treatment RAIU value. In the present study it is demonstrated that the physiological intra-individual variation in iodine uptake is much larger than 5%. Consequently, in-treatment RAIU values, expressed as a percentage of the pre-treatment value, have an inherent variation, that needs to be considered when conducting dose-response analyses. Based on statistical and biological considerations, a BMR of 20% is proposed for benchmark dose analysis of human thyroidal iodine uptake data, to take the inherent variation in relative RAIU data into account. Implications for the tolerated daily intakes for perchlorate and chlorate, recently established by the European Food Safety Authority (EFSA), are discussed. PMID:27268963

  15. Dose-response relationship of γ-H2AX foci induction in human lymphocytes after X-rays exposure

    International Nuclear Information System (INIS)

    Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of γ-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and γ-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y(0.5h) = 11.66D + 0.15 (R2 = 0.99), Y(5h) = 2.44D + 0.15 (R2 = 0.99), Y(8h) = 1.57D + 0.22 (R2 = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using γ-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in γ-H2AX foci kinetics after gamma- and X-irradiation in vitro.

  16. Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

    Energy Technology Data Exchange (ETDEWEB)

    Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Gilbert, Ethel; Curtis, Rochelle; Inskip, Peter; Kleinerman, Ruth; Morton, Lindsay; Rajaraman, Preetha; Little, Mark P. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-06-01

    Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.

  17. Evaluation of the Comet Assay for Assessing the Dose-Response Relationship of DNA Damage Induced by Ionizing Radiation

    OpenAIRE

    Qiang Liu; Bing Wang; Takanori Katsube; Sai Jun Fan; Fei-Yue Fan; Hui Zhao; Xu Su; Jian Xiang Liu; Jia Cao; Li Qing Du; Chang Xu; Yan Wang

    2013-01-01

    Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by γ-ray irradiation. A clear dose-response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p < 0.001). A time-response relationship was also found within 72 h after irradiation (p < 0.001). The curves for DNA double-strand bre...

  18. Pancreatic beta cell function increases in a linear dose-response manner following exercise training in adults with prediabetes

    DEFF Research Database (Denmark)

    Malin, Steven K; Solomon, Thomas; Blaszczak, Alecia;

    2013-01-01

    composition (dual-energy x-ray absorptiometry and computed tomography) were also measured before and after the intervention. Exercise dose was computed using VO2-heart rate derived linear-regression equations. Subjects expended 474.5±8.8 kcal/session (2372.5±44.1 kcal/week) during the intervention, and lost......While some studies suggest that a linear dose-response relationship exists between exercise and insulin sensitivity, the exercise dose required to enhance pancreatic beta-cell function is unknown. Thirty-five older, obese adults with prediabetes underwent a progressive 12-week supervised exercise...

  19. Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

    DEFF Research Database (Denmark)

    Beausoleil, Claire; Ormsby, Jean-Nicolas; Gies, Andreas;

    2013-01-01

    A workshop was held in Berlin September 12–14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses (“low dose hypothesis”) for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted...... no consensus was reached the robust discussions were helpful to inform both basic scientists and risk assessors on all the issues. There were a number of important ideas developed to help continue the discussion and improve communication over the next few years....

  20. Which cities produce worldwide more excellent papers than can be expected? A new mapping approach--using Google Maps--based on statistical significance testing

    CERN Document Server

    Bornmann, Lutz

    2011-01-01

    The methods presented in this paper allow for a spatial analysis revealing centers of excellence around the world using programs that are freely available. Based on Web of Science data, field-specific excellence can be identified in cities where highly-cited papers were published. Compared to the mapping approaches published hitherto, our approach is more analytically oriented by allowing the assessment of an observed number of excellent papers for a city against the expected number. With this feature, this approach can not only identify the top performers in output but the "true jewels." These are cities locating authors who publish significantly more top cited papers than can be expected. As the examples in this paper show for physics, chemistry, and psychology, these cities do not necessarily have a high output of excellent papers.

  1. Evaluation of three methods for calculating statistical significance when incorporating a systematic uncertainty into a test of the background-only hypothesis for a Poisson process

    International Nuclear Information System (INIS)

    Hypothesis tests for the presence of new sources of Poisson counts amidst background processes are frequently performed in high energy physics (HEP), gamma ray astronomy (GRA), and other branches of science. While there are conceptual issues already when the mean rate of background is precisely known, the issues are even more difficult when the mean background rate has non-negligible uncertainty. After describing a variety of methods to be found in the HEP and GRA literature, we consider in detail three classes of algorithms and evaluate them over a wide range of parameter space, by the criterion of how close the ensemble-average Type I error rate (rejection of the background-only hypothesis when it is true) compares with the nominal significance level given by the algorithm. We recommend wider use of an algorithm firmly grounded in frequentist tests of the ratio of Poisson means, although for very low counts the overcoverage can be severe due to the effect of discreteness. We extend the studies of Cranmer, who found that a popular Bayesian-frequentist hybrid can undercover severely when taken to high Z-values. We also examine the profile likelihood method, which has long been used in GRA and HEP; it provides an excellent approximation in much of the parameter space, as previously studied by Rolke and collaborators

  2. Low dose radiation induced adaptive response upon salt stress and vacuum stress: a possible mechanism for the effect of saddle-like dose response curve

    International Nuclear Information System (INIS)

    To explore mechanism for the effect of saddle-like dose-response curve, the relationship of irradiation-vacuum stress, and irradiation-salt stress, was investigated with rice seeds irradiated to 60-560 Gy by 60Co γ-rays. The dose-response curve was simulated based on seedling height data, which showed obedient to linear-quadratic model. During germination,the irradiated rice seeds were stressed by 10-3 Pa vacuum, or by NaCl in different concentrations. After that, the dose-response curve manifested a saddle-like shape. The results indicate that while low dose irradiation could retard seedling growth synergistically with vacuum stress and salt stress, it could also induce adaptive response upon vacuum stress and salt stress. Low dose irradiation induced adaptive response upon environmental adverse factors could contribute to the mechanism for the effect of saddle-like dose-response curve. (authors)

  3. Biphasic and triphasic dose responses in zebrafish embryos to low-dose 150 kV X-rays with different levels of hardness.

    Science.gov (United States)

    Kong, Eva Yi; Cheng, Shuk Han; Yu, Kwan Ngok

    2016-07-01

    The in vivo low-dose responses of zebrafish (Danio rerio) embryos to 150 kV X-rays with different levels of hardness were examined through the number of apoptotic events revealed at 24 h post fertilization by vital dye acridine orange staining. Our results suggested that a triphasic dose response was likely a common phenomenon in living organisms irradiated by X-rays, which comprised an ultra-low-dose inhibition, low-dose stimulation and high-dose inhibition. Our results also suggested that the hormetic zone (or the stimulation zone) was shifted towards lower doses with application of filters. The non-detection of a triphasic dose response in previous experiments could likely be attributed to the use of hard X-rays, which shifted the hormetic zone into an unmonitored ultra-low-dose region. In such cases where the subhormetic zone was missed, a biphasic dose response would be reported instead.

  4. Dose-response modeling : Evaluation, application, and development of procedures for benchmark dose analysis in health risk assessment of chemical substances

    OpenAIRE

    Sand, Salomon

    2005-01-01

    In this thesis, dose-response modeling and procedures for benchmark dose (BMD) analysis in health risk assessment of chemical substances have been investigated. The BMD method has been proposed as an alternative to the NOAEL (no-observedadverse- effect-level) approach in health risk assessment of non-genotoxic agents. According to the BMD concept, a dose-response model is fitted to data and the BMD is defined as the dose causing a predetermined change in response. A lowe...

  5. Stage sensitivity and dose response of meiotic chromosomes of pollen mother cells of Tradescantia to X-rays

    International Nuclear Information System (INIS)

    Chromosome damage induced by physical and chemical mutagens can be quantitated by the frequencies of micronuclei (MCN) produced in tetrads of the meiotic pollen mother cells of Tradescantia, i.e. the 'MCN-in-Tetrad' test. The stage sensitivity and dose response of these meiocytes to low exposures of X-rays was studied to improve the efficiency and reliability of this test. Stage sensitivity was determined by observing, at 3 hr intervals, the frequencies of X-ray (35 rads)-induced MCN in tetrads from a series of 16 fixations of tetrad-containing inflorescences. Late stages of meiosis (3-9 hr post-irradiation fixation groups) were insensitive (5-14 MCN/100 tetrads). Relatively high sensitivity was exhibited in the early stages of meiosis. The first and second sensitive peaks (62 and 61 MCN/100 tetrads) centered around the 21 and 39 hr post-irradiation fixation groups respectively. Control groups yielded around 3-4 MCN/100 tetrads. A dose-response relation for MCN was determined by treating early stages of meiotic pollen mother cells with X-ray exposures ranging from 9.5 to 57.5 rads. A linear regression line was established with about 20 MCN/100 tetrads per 10 rad increment. (author)

  6. DNA repair processes and the shape of dose-response curves for induced genetic changes in yeast

    International Nuclear Information System (INIS)

    Gene conversion is a genetic change which requires a functional recombinational repair system. Dose-response curves for induced gene conversion in D7 strains of diploid S. cerevisiae appear to be one-hit (effect proportional to dose) for ionizing radiation or mitomycin C, but are closer to two-hit characteristics (effect proportional to square of dose) for 254 nm UV radiation or nitrous acid at sublethal doses of these agents. These data are suggest that recombinational repair in normal cells is stimulated by coincident or double-strand damage in the DNA: for example, a double-strand break produced by ionizing radiation, an interstrand cross-link produced by mitomycin C, or a double strand break produced by ''overlapping'' excision repair of two pyrimidine dimers located on opposite DNA strands within about 100 base pairs of each other. Other initiating mechanisms for UV-induced conversion may predominate when the excision repair pathway is not available (as in rad 3 mutants). It is of interest that the shapes of the dose-response curves for back mutations affecting the iIvl locus in repair - proficient D7 strains are similar to those observed for gene conversions induced by γ-rays, UV light and nitrous acid, even though the relative yields of convertants and back mutations vary considerably from one agent to another

  7. Study on the dose response characteristics of a scanning liquid ion-chamber electronic portal imaging device

    CERN Document Server

    Ma Shao Gang; Song Yi Xin

    2002-01-01

    Objective: To study the dose response characteristics and the influence factors such as gantry angle, field size and acquisition mode on the dosimetric response curves, when using a scanning liquid ion-chamber electronic portal imaging device (EPID) for dose verification. Methods: All experiments were carried out on a Varian 600 C/D accelerator (6 MV X-ray) equipped with a Varian PortalVision sup T sup M MK2 type EPID. To obtain the dose response curve, the relationship between the incident radiation intensity to the detector and the pixel value output from the EPID were established. Firstly, the different dose rates of 6 MV X-rays were obtained by varying SSD. Secondly, three digital portal images were acquired for each dose rate using the EPID and averaged to avoid the influence of the dose rate fluctuations of the accelerator. The pixel values of all images were read using self-designed image analysis software, and and average for a region consisting of 11 x 11 pixels around the center was taken as the res...

  8. Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice.

    Science.gov (United States)

    Cai, Hong; Scott, Edwina; Kholghi, Abeer; Andreadi, Catherine; Rufini, Alessandro; Karmokar, Ankur; Britton, Robert G; Horner-Glister, Emma; Greaves, Peter; Jawad, Dhafer; James, Mark; Howells, Lynne; Ognibene, Ted; Malfatti, Michael; Goldring, Christopher; Kitteringham, Neil; Walsh, Joanne; Viskaduraki, Maria; West, Kevin; Miller, Andrew; Hemingway, David; Steward, William P; Gescher, Andreas J; Brown, Karen

    2015-07-29

    Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a lack of information on the optimal dose prohibits rationally designed trials to assess efficacy. To challenge the assumption that "more is better," we compared the pharmacokinetics and activity of a dietary dose with an intake 200 times higher. The dose-response relationship for concentrations generated and the metabolite profile of [(14)C]-resveratrol in colorectal tissue of cancer patients helped us to define clinically achievable levels. In Apc(Min) mice (a model of colorectal carcinogenesis) that received a high-fat diet, the low resveratrol dose suppressed intestinal adenoma development more potently than did the higher dose. Efficacy correlated with activation of adenosine monophosphate-activated protein kinase (AMPK) and increased expression of the senescence marker p21. Nonlinear dose responses were observed for AMPK and mechanistic target of rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and senescence. In human colorectal tissues exposed to low dietary concentrations of resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The expression of the cytoprotective NAD(P)H dehydrogenase, quinone 1 (NQO1) enzyme was also increased in tissues from cancer patients participating in our [(14)C]-resveratrol trial. These findings warrant a revision of developmental strategies for diet-derived agents designed to achieve cancer chemoprevention. PMID:26223300

  9. An in vitro dynamic microcosm biofilm model for caries lesion development and antimicrobial dose-response studies.

    Science.gov (United States)

    Maske, T T; Brauner, K V; Nakanishi, L; Arthur, R A; van de Sande, F H; Cenci, M S

    2016-01-01

    Some dynamic biofilm models for dental caries development are limited as they require multiple experiments and do not allow independent biofilm growth units, making them expensive and time-consuming. This study aimed to develop and test an in vitro dynamic microcosm biofilm model for caries lesion development and for dose-response to chlorhexidine. Microcosm biofilms were grown under two different protocols from saliva on bovine enamel discs for up to 21 days. The study outcomes were as follows: the percentage of enamel surface hardness change, integrated hardness loss, and the CFU counts from the biofilms formed. The measured outcomes, mineral loss and CFU counts showed dose-response effects as a result of the treatment with chlorhexidine. Overall, the findings suggest that biofilm growth for seven days with 0.06 ml min(-1) salivary flow under exposure to 5% sucrose (3 × daily, 0.25 ml min(-1), 6 min) was suitable as a pre-clinical model for enamel demineralization and antimicrobial studies. PMID:26905384

  10. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis.

    Science.gov (United States)

    Crippa, Alessio; Discacciati, Andrea; Larsson, Susanna C; Wolk, Alicja; Orsini, Nicola

    2014-10-15

    Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality.

  11. Radiation dose response simulation for biomechanical-based deformable image registration of head and neck cancer treatment

    International Nuclear Information System (INIS)

    Biomechanical-based deformable image registration is conducted on the head and neck region. Patient specific 3D finite element models consisting of parotid glands (PG), submandibular glands (SG), tumor, vertebrae (VB), mandible, and external body are used to register pre-treatment MRI to post-treatment MR images to model the dose response using image data of five patients. The images are registered using combinations of vertebrae and mandible alignments, and surface projection of the external body as boundary conditions. In addition, the dose response is simulated by applying a new loading technique in the form of a dose-induced shrinkage using the dose-volume relationship. The dose-induced load is applied as dose-induced shrinkage of the tumor and four salivary glands. The Dice Similarity Coefficient (DSC) is calculated for the four salivary glands, and tumor to calculate the volume overlap of the structures after deformable registration. A substantial improvement in the registration is found by including the dose-induced shrinkage. The greatest registration improvement is found in the four glands where the average DSC increases from 0.53, 0.55, 0.32, and 0.37 to 0.68, 0.68, 0.51, and 0.49 in the left PG, right PG, left SG, and right SG, respectively by using bony alignment of vertebrae and mandible (M), body (B) surface projection and dose (D) (VB+M+B+D). (paper)

  12. Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.

    Science.gov (United States)

    Miller, Patrick J O; Antunes, Ricardo N; Wensveen, Paul J; Samarra, Filipa I P; Alves, Ana Catarina; Tyack, Peter L; Kvadsheim, Petter H; Kleivane, Lars; Lam, Frans-Peter A; Ainslie, Michael A; Thomas, Len

    2014-02-01

    Eight experimentally controlled exposures to 1-2 kHz or 6-7 kHz sonar signals were conducted with four killer whale groups. The source level and proximity of the source were increased during each exposure in order to reveal response thresholds. Detailed inspection of movements during each exposure session revealed sustained changes in speed and travel direction judged to be avoidance responses during six of eight sessions. Following methods developed for Phase-I clinical trials in human medicine, response thresholds ranging from 94 to 164 dB re 1 μPa received sound pressure level (SPL) were fitted to Bayesian dose-response functions. Thresholds did not consistently differ by sonar frequency or whether a group had previously been exposed, with a mean SPL response threshold of 142 ± 15 dB (mean ± s.d.). High levels of between- and within-individual variability were identified, indicating that thresholds depended upon other undefined contextual variables. The dose-response functions indicate that some killer whales started to avoid sonar at received SPL below thresholds assumed by the U.S. Navy. The predicted extent of habitat over which avoidance reactions occur depends upon whether whales responded to proximity or received SPL of the sonar or both, but was large enough to raise concerns about biological consequences to the whales.

  13. An in vitro dynamic microcosm biofilm model for caries lesion development and antimicrobial dose-response studies.

    Science.gov (United States)

    Maske, T T; Brauner, K V; Nakanishi, L; Arthur, R A; van de Sande, F H; Cenci, M S

    2016-01-01

    Some dynamic biofilm models for dental caries development are limited as they require multiple experiments and do not allow independent biofilm growth units, making them expensive and time-consuming. This study aimed to develop and test an in vitro dynamic microcosm biofilm model for caries lesion development and for dose-response to chlorhexidine. Microcosm biofilms were grown under two different protocols from saliva on bovine enamel discs for up to 21 days. The study outcomes were as follows: the percentage of enamel surface hardness change, integrated hardness loss, and the CFU counts from the biofilms formed. The measured outcomes, mineral loss and CFU counts showed dose-response effects as a result of the treatment with chlorhexidine. Overall, the findings suggest that biofilm growth for seven days with 0.06 ml min(-1) salivary flow under exposure to 5% sucrose (3 × daily, 0.25 ml min(-1), 6 min) was suitable as a pre-clinical model for enamel demineralization and antimicrobial studies.

  14. Injury Statistics

    Science.gov (United States)

    ... Data Consumer Opinion Surveys Home / Research & Statistics Injury Statistics This is the statistic reports page for scientific ... Home Appliances, Maintenance and Construction Injury Statistics Injury Statistics September 30, 2012 Submersions Related to Non-Pool ...

  15. Dose response to chlorthalidone in patients with mild hypertension. Efficacy of a lower dose.

    Science.gov (United States)

    Materson, B J; Oster, J R; Michael, U F; Bolton, S M; Burton, Z C; Stambaugh, J E; Morledge, J

    1978-08-01

    A multicenter study of chlorthalidone was performed to determine the relative antihypertensive efficacy and side effects of doses lower than those usually recommended for therapy. After a 4-wk placebo control period 100 patients with mild hypertension were randomly assigned doubleblind to 12.5-, 25-, 50-, or 75-mg regimens of chlorthalidone or to placebo for 12 wk. The groups of patients taking 25, 50, and 75 mg had declines in blood pressure which were not significantly different from each other. Serum potassium decreased in the 50- and 75-mg groups but not significantly in the 25-mg group. We conclude that chlorthalidone, 25 mg daily, was at least as effective for hypertension as 50 and 75 mg with less perturbation of potassium. Use of smaller initial diuretic doses may provide equal efficacy with fewer side effects for many patients. PMID:354839

  16. Prenatal irradiation and spatial memory in mice: investigation of dose-response relationship

    Energy Technology Data Exchange (ETDEWEB)

    Sienkiewicz, Z.J.; Haylock, R.G.E.; Saunders, R.D. (National Radiological Protection Board, Chilton (United Kingdom))

    1994-05-01

    Pregnant CD1 mice were exposed on gestational day 18 to 250 kV X-rays at 0.1, 0.25, 0.35 and 0.5 Gy. The performances of 10 adult male offspring from each exposure condition were investigated on a spatial discrimination learning task in a radial arm maze. An impairment in the performance of this task was found which showed a correlation with dose. Compared with sham exposed control mice, performance was not significantly affected with irradiation at 0.1 Gy and was slightly but non-significantly reduced at 0.25 Gy. Irradiation at 0.35 Gy caused a significant impairment in performance, and exposure at 0.5 Gy resulted in a still larger impairment. The overall association between dose and behavioural impairment was best described by a linear relationship without a threshold, although at doses lower than about 0.25 Gy any impairment would appear to be too small to be detectable. (Author).

  17. Data mining-based statistical analysis of biological data uncovers hidden significance: clustering Hashimoto's thyroiditis patients based on the response of their PBMC with IL-2 and IFN-γ secretion to stimulation with Hsp60.

    Science.gov (United States)

    Tonello, Lucio; Conway de Macario, Everly; Marino Gammazza, Antonella; Cocchi, Massimo; Gabrielli, Fabio; Zummo, Giovanni; Cappello, Francesco; Macario, Alberto J L

    2015-03-01

    The pathogenesis of Hashimoto's thyroiditis includes autoimmunity involving thyroid antigens, autoantibodies, and possibly cytokines. It is unclear what role plays Hsp60, but our recent data indicate that it may contribute to pathogenesis as an autoantigen. Its role in the induction of cytokine production, pro- or anti-inflammatory, was not elucidated, except that we found that peripheral blood mononucleated cells (PBMC) from patients or from healthy controls did not respond with cytokine production upon stimulation by Hsp60 in vitro with patterns that would differentiate patients from controls with statistical significance. This "negative" outcome appeared when the data were pooled and analyzed with conventional statistical methods. We re-analyzed our data with non-conventional statistical methods based on data mining using the classification and regression tree learning algorithm and clustering methodology. The results indicate that by focusing on IFN-γ and IL-2 levels before and after Hsp60 stimulation of PBMC in each patient, it is possible to differentiate patients from controls. A major general conclusion is that when trying to identify disease markers such as levels of cytokines and Hsp60, reference to standards obtained from pooled data from many patients may be misleading. The chosen biomarker, e.g., production of IFN-γ and IL-2 by PBMC upon stimulation with Hsp60, must be assessed before and after stimulation and the results compared within each patient and analyzed with conventional and data mining statistical methods.

  18. Dose-response effects of Lepidium meyenii (Maca) aqueous extract on testicular function and weight of different organs in adult rats.

    Science.gov (United States)

    Chung, Francisco; Rubio, Julio; Gonzales, Carla; Gasco, Manuel; Gonzales, Gustavo F

    2005-04-01

    Lepidium meyenii (Brassicaceae) known as Maca grows exclusively between 4000 and 4500 m over the sea level in the Peruvian central Andes. The dried hypocotyls of Maca are traditionally used as food and for its supposed fertility-enhancing properties. A dose-response study was performed to determine the effect of 7 days oral administration of an aqueous lyophilized extract of Maca at 0.01-5 g/kg (corresponding to 0.022-11 g dry hypocotyls of Maca/kg) on body and different organ weights, stages of the seminiferous tubules, epididymal sperm count and motility, and serum testosterone and estradiol levels in rats. In doses up to 5 g extract/kg, no toxicity was observed. Almost all organ weights were similar in controls and in the Maca extract-treated groups. Seminal vesicles weight was significantly reduced at 0.01 and 0.10 g extract/kg. Maca increased in length of stages VII-VIII of the seminiferous tubules in a dose-response fashion, with highest response at 1.0 g/kg, while caput/corpus epididymal sperm count increased at the 1.0 g dose. Cauda epididymal sperm count, sperm motility, and serum estradiol level were not affected at any of the doses studied. Serum testosterone was lower at 0.10 g extract/kg. Low-seminal vesicle weights correlated with low-serum testosterone levels (R2=0.33; P<0.0001) and low-testosterone/estradiol ratio (R2=0.35; P<0.0001). Increase in epididymal sperm count was related to lengths of stages VII-VIII. Highest effect on stages VII-VIII of the seminiferous tubules was observed at 1.0 g Maca aqueous extract/kg. The present study demonstrated that Maca extract in doses up to 5 g/kg (equivalent to the intake of 770 g hypocotyls in a man of 70 kg) was safe and that higher effect on reproductive parameters was elicited with a dose of 1 g extract/kg corresponding to 2.2 g dry Maca hypocotyls/kg. PMID:15763375

  19. Evaluation of the Comet Assay for Assessing the Dose-Response Relationship of DNA Damage Induced by Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2013-11-01

    Full Text Available Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by γ-ray irradiation. A clear dose-response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p < 0.001. A time-response relationship was also found within 72 h after irradiation (p < 0.001. The curves for DNA double-strand breaks and DNA repair in vitro of human lymphocytes presented a nice model, and a smooth, three-dimensional plane model was obtained when the two curves were combined.

  20. Is the dose-response relationship for local control of Hodgkin disease obscured by lung inhomogeneity corrections

    International Nuclear Information System (INIS)

    Absence of dose response has been reported for local control of Hodgkin disease between 30 Gy and 42 Gy delivered to the mantle field in definitive irradiation. These dose ranges were determined at the central ray by using irregular field calculations without benefit of dosimetric correction for lung inhomogeneity. The authors have performed a detailed analysis of dose delivered to the hilar and mediastinal regions with mantle field irradiation incorporating lung inhomogeneity corrections for the dose ranges indicated for both cobalt-60 and 6 MVX linear accelerator. For a prescribed dose of 36 Gy to midline with 6 MVX, the hila and mediastinum would receive 40-42 Gy with irregular field and lung inhomogeneity corrections. Similar increases in hilar and lateral mediastinal doses were observed with cobalt-60

  1. Non-invasive plant growth measurements for detection of blue-light dose response of stem elongation in Chrysanthemum morifolium

    DEFF Research Database (Denmark)

    Kjær, Katrine Heinsvig

    2012-01-01

    . In the present study a non-invasive plant growth sensor (PlantEye, Phenospex B.V, Heerlen, NL) was tested in analysing changes in diurnal stem elongation patterns and plant height in response to the spectral quality of the light environment. Plants were grown in four different LED supplemental lighting...... treatments with 0%, 12.5%, 18.5% and 22.5% blue light under greenhouse conditions in winter (18 h day/4 h night). The non-invasive measurements were carried out automatically every four hour with three repetitions, and supported by manual measurements of plant height every third day. A strong linear relation...... between the non-invasive measurements and manual measurements of plant height was achieved, and a blue-light dose-response showing a decrease in plant height in relation to an increase in blue light was demonstrated. However, the non-invasive plant growth sensor was not able to distinguish between diurnal...

  2. CurveP Method for Rendering High-Throughput Screening Dose-Response Data into Digital Fingerprints.

    Science.gov (United States)

    Sedykh, Alexander

    2016-01-01

    The nature of high-throughput screening (HTS) puts certain limits on optimal test conditions for each particular sample, therefore, on top of usual data normalization, additional parsing is often needed to account for incomplete read outs or various artifacts that arise from signal interferences.CurveP is a heuristic, user-tunable, curve-cleaning algorithm that attempts to find a minimum set of corrections, which would give a monotonic dose-response curve. After applying the corrections, the algorithm proceeds to calculate a set of numeric features, which can be used as a fingerprint characterizing the sample, or as a vector of independent variables (e.g., molecular descriptors in case of chemical substances testing). The resulting output can be a part of HTS data analysis or can be used as input for a broad spectrum of computational applications, such as Quantitative Structure-Activity Relationship (QSAR) modeling, computational toxicology, bio- and cheminformatics. PMID:27518631

  3. Comment on the treatment of dose-response relationship for the epidemiological data of atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Tatsuo [Radiation Education Forum, Tokyo (Japan)

    2000-05-01

    As for the dose-response relationship for solid cancer incidence rate at low dose radiation, the epidemiological study of atomic bomb survivors by RERF have been regarded to be the most important and authentic, and ICRP has its conceptual basis in the policy of radiation protection on this data for adopting the linear, non-threshold (LNT) model. However, we have found that there are two fundamental problems in the way of treatment of the data, and we believe it may bring an important modification on the validity of the LNT model for the interpretation of the radiation effect at low dose. The first point is that in estimating the exposure dose of the survivors, the chronic dose received by them should be considered in addition to the acute dose calculated by T65D or DS86, which only estimates the dose at the instant of explosion of the bomb. It seems there are ample evidences that the survivors received additional chronic dose due to the radioactivity contained both in the fallout and in the induced radioactivity by the neutron bombardment of the environmental materials. For example, it is a well-known fact that there was a heavy temporary shower (so to speak ''black rain'') in a wide region of the city after the bomb explosion, which contained much radioactivity due to the fission products. According to a literature, in the case of residents at Nishiyama District in Nagasaki, which is located 3 km from the explosion center but is shielded by a mountain from the instantaneous bomb explosion, the cumulative dose received by 280 residents there was estimated to be as much as 0.2 Gy, which caused an abnormal increase in the number of leukocytes for most of the residents. For the case of Hiroshima, a literature reports that the dose due to the black rain was about 0.03-0.04 Gy. In both cities, a substantial percentage of the survivors had stayed for considerable time in the contaminated area in the city after bombing, such as for the purpose of

  4. Exposure dose response relationships of the freshwater bivalve Hyridella australis to cadmium spiked sediments

    Energy Technology Data Exchange (ETDEWEB)

    Marasinghe Wadige, Chamani P.M., E-mail: chamani.marasinghe.wadige@canberra.edu.au; Maher, William A.; Taylor, Anne M.; Krikowa, Frank

    2014-07-01

    Highlights: • The exposure–dose–response approach was used to assess cadmium exposure and toxicity. • Accumulated cadmium in H. australis reflected the sediment cadmium exposure. • Spill over of cadmium into the biologically active pool was observed. • Increased cadmium resulted in measurable biological effects. • H. australis has the potential to be a cadmium biomonitor in freshwater environments. - Abstract: To understand how benthic biota may respond to the additive or antagonistic effects of metal mixtures in the environment it is first necessary to examine their responses to the individual metals. In this context, laboratory controlled single metal-spiked sediment toxicity tests are useful to assess this. The exposure–dose–response relationships of Hyridella australis to cadmium-spiked sediments were, therefore, investigated in laboratory microcosms. H. australis was exposed to individual cadmium spiked sediments (<0.05 (control), 4 ± 0.3 (low) and 15 ± 1 (high) μg/g dry mass) for 28 days. Dose was measured as cadmium accumulation in whole soft body and individual tissues at weekly intervals over the exposure period. Dose was further examined as sub-cellular localisation of cadmium in hepatopancreas tissues. The biological responses in terms of enzymatic and cellular biomarkers were measured in hepatopancreas tissues at day 28. H. australis accumulated cadmium from spiked sediments with an 8-fold (low exposure organisms) and 16-fold (high exposure organisms) increase at day 28 compared to control organisms. The accumulated tissue cadmium concentrations reflected the sediment cadmium exposure at day 28. Cadmium accumulation in high exposure organisms was inversely related to the tissue calcium concentrations. Gills of H. australis showed significantly higher cadmium accumulation than the other tissues. Accumulated cadmium in biologically active and biologically detoxified metal pools was not significantly different in cadmium exposed

  5. Association between physical activity and all cancer mortality: Dose-response meta-analysis of cohort studies.

    Science.gov (United States)

    Li, Yingjun; Gu, Mengjia; Jing, Fangyuan; Cai, Shaofang; Bao, Chengzhen; Wang, Jianbing; Jin, Mingjuan; Chen, Kun

    2016-02-15

    The relationship between physical activity (PA) before cancer diagnosis and all cancer mortality among the general population is not well defined because of inconsistent results from published studies. Thus, the lack of a meta-analysis that addresses that issue prompted the current report. We conducted a literature search of PubMed and Web of Science to identify all relevant epidemiological studies published before February 28, 2015. We performed categorical and dose-response meta-analyses to evaluate and quantify the association between pre-diagnosis PA and all cancer mortality. A total of 32 prospective cohort studies involving 59,362 cancer deaths were included in this meta-analysis. The pooled relative risks (RRs) of all cancer mortality were 0.80 [95% confidence interval (CI) = 0.76-0.85)] for highest versus lowest PA group and 0.85 (95% CI = 0.82-0.88) for PA versus non/occasional PA group. Dose-response analysis showed that the increment in pre-diagnosis PA level was associated with a decreased risk of cancer death continuously. Moreover, an increment of 10 MET-h/week was related to a 7% lower risk for all cancer mortality (RR = 0.93, 95% CI = 0.91-0.95). In conclusion, the present meta-analysis provides evidence of an inverse association between pre-diagnosis PA and all cancer mortality among the general population. High-quality epidemiological studies that employ standardized PA assessments and unified definitions of PA levels should be developed in future.

  6. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Ruiping; He, Mingyuan; Dong, Chen; Xie, Yuexia; Ye, Shuang; Yuan, Dexiao [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2013-01-15

    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles.

  7. Dose-response curve for blood exposed to gamma-neutron mixed field by conventional cytogenetic method

    Energy Technology Data Exchange (ETDEWEB)

    Brandao, Jose Odinilson de C.; Souza, Priscilla L.G.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F., E-mail: jodinilson@cnen.gov.b, E-mail: fflima@cnen.gov.b, E-mail: jasantos@cnen.gov.b [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Calixto, Merilane S.; Santos, Neide, E-mail: santos_neide@yahoo.com.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Genetica

    2009-07-01

    There is increasing concern about airline crew members (about one million worldwide) are exposed to measurable neutrons doses. Historically, cytogenetic biodosimetry assays have been based on quantifying asymmetrical chromosome alterations (dicentrics, centric rings and acentric fragments) in mytogen-stimulated T-lymphocytes in their first mitosis after radiation exposure. Increased levels of chromosome damage in peripheral blood lymphocytes are a sensitive indicator of radiation exposure and they are routinely exploited for assessing radiation absorbed dose after accidental or occupational exposure. Since radiological accidents are not common, not all nations feel that it is economically justified to maintain biodosimetry competence. However, dependable access to biological dosimetry capabilities is completely critical in event of an accident. In this paper the dose-response curve was measured for the induction of chromosomal alterations in peripheral blood lymphocytes after chronic exposure in vitro to neutron-gamma mixes field. Blood was obtained from one healthy donor and exposed to two neutron-gamma mixed field from sources {sup 241}AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The evaluated absorbed doses were 0.2 Gy; 1.0 Gy and 2.5 Gy. The dicentric chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphase figures were analyzed for the presence of dicentrics by two experienced scorers after painted by giemsa 5%. Our preliminary results showed a linear dependence between radiations absorbed dose and dicentric chromosomes frequencies. Dose-response curve described in this paper will contribute to the construction of calibration curve that will be used in our laboratory for biological dosimetry. (author)

  8. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    International Nuclear Information System (INIS)

    Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles

  9. Dose response of red imported fire ant colonies to Solenopsis invicta virus 3.

    Science.gov (United States)

    Valles, Steven M; Porter, Sanford D

    2015-10-01

    Baiting tests were conducted to evaluate the effect of increasing Solenopsis invicta virus 3 (SINV-3) dose on fire ant colonies. Actively growing early-stage fire ant (Solenopsis invicta Buren) laboratory colonies were pulse-exposed for 24 hours to six concentrations of SINV-3 (10(1), 10(3), 10(5), 10(7), 10(9) genome equivalents/μl) in 1 ml of a 10 % sucrose bait and monitored regularly for two months. SINV-3 concentration had a significant effect on colony health. Brood rating (proportion of brood to worker ants) began to depart from the control group at 19 days for the 10(9) concentration and 26 days for the 10(7) concentration. At 60 days, brood rating was significantly lower among colonies treated with 10(9), 10(7), and 10(5) SINV-3 concentrations. The intermediate concentration, 10(5), appeared to cause a chronic, low-level infection with one colony (n = 9) supporting virus replication. Newly synthesized virus was not detected in any fire ant colonies treated at the 10(1) concentration, indicating that active infections failed to be established at this level of exposure. The highest bait concentration chosen, 10(9), appeared most effective from a control aspect; mean colony brood rating at this concentration (1.1 ± 0.9 at the 60 day time point) indicated poor colony health with minimal brood production. No clear relationship was observed between the quantity of plus genome strand detected and brood rating. Conversely, there was a strong relationship between the presence of the replicative genome strand and declining brood rating, which may serve as a predictor of disease severity. Recommendations for field treatment levels to control fire ants with SINV-3 are discussed. PMID:26162304

  10. Detector dose response in megavoltage small photon beams. I. Theoretical concepts

    Energy Technology Data Exchange (ETDEWEB)

    Bouchard, Hugo, E-mail: hugo.bouchard@npl.co.uk; Duane, Simon [Acoustics and Ionising Radiation Team, National Physical Laboratory, Hampton Road, Teddington TW11 0LW (United Kingdom); Seuntjens, Jan [Medical Physics Unit, McGill University, Montréal, Québec H3G 1A4 (Canada); Kamio, Yuji [Centre hospitalier de l’Université de Montréal (CHUM), 1560 Sherbrooke est, Montréal, Québec H2L 4M1 (Canada); Palmans, Hugo [Acoustics and Ionising Radiation Team, National Physical Laboratory, Hampton Road, Teddington TW11 0LW (United Kingdom); Medical Physics, EBG MedAustron GmbH, A-2700 Wiener Neustadt (Austria)

    2015-10-15

    Purpose: To explain the reasons for significant quality correction factors in megavoltage small photon fields and clarify the underlying concepts relevant to dosimetry under such conditions. Methods: The validity of cavity theory and the requirement of charged particle equilibrium (CPE) are addressed from a theoretical point of view in the context of nonstandard beams. Perturbation effects are described into four main subeffects, explaining their nature and pointing out their relative importance in small photon fields. Results: It is demonstrated that the failure to meet classical cavity theory requirements, such as CPE, is not the reason for significant quality correction factors. On the contrary, it is shown that the lack of CPE alone cannot explain these corrections and that what matters most, apart from volume averaging effects, is the relationship between the lack of CPE in the small field itself and the density of the detector cavity. The density perturbation effect is explained based on Fano’s theorem, describing the compensating effect of two main contributions to cavity absorbed dose. Using the same approach, perturbation effects arising from the difference in atomic properties of the cavity medium and the presence of extracameral components are explained. Volume averaging effects are also discussed in detail. Conclusions: Quality correction factors of small megavoltage photon fields are mainly due to differences in electron density between water and the detector medium and to volume averaging over the detector cavity. Other effects, such as the presence of extracameral components and differences in atomic properties of the detection medium with respect to water, can also play an accentuated role in small photon fields compared to standard beams.

  11. DOSE-RESPONSE OF PORCINE OVARIAN GRANULOSA CELLS TO AMYGDALIN TREATMENT COMBINED WITH DEOXYNIVALENOL

    Directory of Open Access Journals (Sweden)

    Marek Halenár

    2014-02-01

    Full Text Available Amygdalin is one of many nitrilosides, which are natural cyanide-containing substances abundant in the seeds of apricots, almond, peaches, apples, and other rosaceous plants. It is a controversial anti-tumor natural product that has been used as an alternative cancer drug for many years. On the other hand, one of the most widely distributed mycotoxin contaminating food and animal feed is deoxynivalenol (DON. Deoxynivalenol has adverse effects on humans, animals, and crops that result in illnesses. The aim of the in vitro study was to investigated the effect of natural substance amygdalin at the selected doses (1, 10, 100, 1000, 10 000 µg/mL in combination with deoxynivalenol (1000 ng/mL on secretion of steroid hormones (progesterone and estradiol by ovarian granulosa cells (GCs from cyclic pigs. Our results showed that the releasing of progesterone and estradiol by ovarian granulosa cells was affected by amygdalin plus DON addition. The secretion of progesterone by ovarian GCs was significantly (P≤0.05 affected by administration of both compounds in all experimental groups. Similarly, estradiol releasing by GCs was significantly (P≤0.05 increased in experimental groups with amygdalin (10, 100 and 10 000 µg/mL plus DON (1000 ng/mL addition. Amygdalin treatment combined with DON caused increase of steroid hormones release by ovarian granulosa cells. Our findings suggest possible involvement of these natural substances (amygdalin and deoxynivalenol in the regulation process of steroidogenesis. In conclusion, results from this experiment contribute to knowledge about interaction between two different natural compounds and their positive or negative interferences with ovarian functions.

  12. Dose-response relationship of cadmium or radiation-induced embryotoxicity in mouse whole embryo culture

    Energy Technology Data Exchange (ETDEWEB)

    Nakashima, Kiyohito; Kawamata, Akitoshi; Matsuoka, Masato; Wakisaka, Takashi; Fujiki, Yoshishige (Asahi University School of Dentistry, Gifu (Japan))

    1988-12-01

    Mouse embryos of B6C3F/sub 1/ strain were exposed in vitro to 1.2 to 2.2 {mu}M cadmium chloride (Cd) or to 100 to 320 R x-rays, and the effects of the exposure on development were examined after 39 h of culture. Development of embryos was assessed from lethality, formation of the neural tube defect, diameter and protein of yolk sac, crown-rump and head lengths, embryonic protein, and number of somites. Incidence of the neural tube defect increased from 3.4 to 100% by 1.2 to 2.0 {mu}M Cd, while embryo deaths increased from 13.8 to 93.3% by 2.0 to 2.2 {mu}M Cd. Embryonic protein was significantly reduced at the teratogenic range, but the number of somites was only affected by 1.6 to 2.0 {mu}M Cd. X-irradiation at 100 to 320 R induced the neural tube defect in 2.9 to 72.7% of the embryos. An embryolethal effect was observed only at the 320 R dose. Crown-rump and head lengths and embryonic protein were significantly affected at the teratogenic range, but the diameter and protein of yolk sac and number of somites were hardly affected. Cadmium- or radiation-induced response data of both teratogenicity and endpoints indicating inhibition of embryonic development were acceptably fitted to a linear log-probit regression. These regressions suggest that as an estimation of interference in development of embryos, embryonic protein and head length are sensitive endpoints while the number of somites is an insensitive criterion. (author).

  13. Detector dose response in megavoltage small photon beams. I. Theoretical concepts

    International Nuclear Information System (INIS)

    Purpose: To explain the reasons for significant quality correction factors in megavoltage small photon fields and clarify the underlying concepts relevant to dosimetry under such conditions. Methods: The validity of cavity theory and the requirement of charged particle equilibrium (CPE) are addressed from a theoretical point of view in the context of nonstandard beams. Perturbation effects are described into four main subeffects, explaining their nature and pointing out their relative importance in small photon fields. Results: It is demonstrated that the failure to meet classical cavity theory requirements, such as CPE, is not the reason for significant quality correction factors. On the contrary, it is shown that the lack of CPE alone cannot explain these corrections and that what matters most, apart from volume averaging effects, is the relationship between the lack of CPE in the small field itself and the density of the detector cavity. The density perturbation effect is explained based on Fano’s theorem, describing the compensating effect of two main contributions to cavity absorbed dose. Using the same approach, perturbation effects arising from the difference in atomic properties of the cavity medium and the presence of extracameral components are explained. Volume averaging effects are also discussed in detail. Conclusions: Quality correction factors of small megavoltage photon fields are mainly due to differences in electron density between water and the detector medium and to volume averaging over the detector cavity. Other effects, such as the presence of extracameral components and differences in atomic properties of the detection medium with respect to water, can also play an accentuated role in small photon fields compared to standard beams

  14. Dose-response effect between cannabis use and psychosis liability in a non-clinical population: evidence from a snowball sample.

    Science.gov (United States)

    Ruiz-Veguilla, Miguel; Barrigón, María Luisa; Hernández, Laureano; Rubio, José Luis; Gurpegui, Manuel; Sarramea, Fernando; Cervilla, Jorge; Gutiérrez, Blanca; James, Anthony; Ferrin, Maite

    2013-08-01

    This study aimed to explore the associations between daily cannabis use and the specific profiles of subclinical symptoms in a non-clinical population obtained through snowball sampling, taking into account alcohol use, other drug use, social exclusion and age at onset of cannabis use. We included 85 daily cannabis users and 100 non-daily cannabis users. Both the case and the control populations were identified by snowball sampling. Daily cannabis use was associated with more alcohol intake and other drug use, as well as with early onset in the use of cannabis. Daily cannabis use appeared to exert a dose-response effect on first-rank symptoms, mania symptoms and auditory hallucinations, even after adjusting for sex, age, other drug use, social exclusion and age at onset of cannabis use. The paranoid dimension was only associated with the heaviest consumption of cannabis. Initial age of cannabis use modified the effects of daily cannabis use on the first-rank and voices experiences. Daily cannabis use was associated with significantly more first-rank and voices experiences among those subjects who started to use cannabis before 17 years of age. Our study supports the association of psychotic experiences with cannabis use even among non-psychotic subjects.

  15. Dose-response characteristics of a monoclonal antibody based two-si immunoradiometric assay for hepatitis B surface antigen (HBsAg)

    International Nuclear Information System (INIS)

    Since the correlation between HBV infectivity and circulating HBsAG was established, increasingly sensitive tests for HBsAg have been developed. Of these, two-site immunoradiometric assays (2S-IRMA) employing polyclonal antibodies of diverse animal origins have proven to be the most sensitive. A number of 2S-IRMA based on mouse monoclonal antibodies have been developed and in 1983 one was released commercially by NML(R). The present study has compared the performance of this assay with that of the polyclonal antibody based HBsAg-assay, AUSRIA(R) II-125, and has looked particularly at dose responsiveness, sensitivity and specificity. The NML(R) monoclonal antibody based assay was found to have the capacity to detect HBsAg at concentrations of 0.31 ng/mL ad and 0.22 ng/mL ay respectively, whereas the polyclonal-based assay (AUSRIA(R) II-125) detected HBsAg as low as 0.09 ng/mL ad and 0.17 ng/mL ay. These findings are contrary to the expectations raised by the claim of significantly improved assay sensitivity with research prototype of the NML(R) assay published by the workers who developed the anti-HBs producing mouse hybridomas

  16. DOSE-RESPONSE Relationships Between Whole-Body Vibration and Lumbar Disk DISEASE—A Field Study on 388 Drivers of Different Vehicles

    Science.gov (United States)

    Schwarze, S.; Notbohm, G.; Dupuis, H.; Hartung, E.

    1998-08-01

    In a longitudinal study, the dose-response relationships between long term occupational exposure to whole-body vibration and degenerative processes in the lumbar spine caused by the lumbar disks were examined. From 1990 to 1992, 388 vibration-exposed workers from different driving jobs were examined medically and by lumbar X-ray. For each individual, a history of all exposure conditions was recorded, and a cumulative vibration dose was calculated allowing comparisons between groups of low, middle, and high intensity of exposure. 310 subjects were selected for a follow-up four years later, of whom 90·6% (n=281) agreed to participate. In comparing the exposure groups, the results indicate that the limit value ofazw(8h)=0·8 m/s2should be reviewed. The best fit between the lifelong vibration dose and the occurrence of a lumbar syndrome was obtained by applying a daily reference ofazw(8h)=0·6 ms2as a limit value. The results became more distinct still when only those subjects were included in the statistical analysis who had had no lumbar symptoms up to the end of the first year of exposure. The prevalence of lumbar syndrome is 1·55 times higher in the highly exposed group when compared to the reference group with low exposure (CI95%=1·24/1·95). Calculating the cumulative incidence of new cases of lumbar syndrome in the follow-up period yields a relative risk ofRRMH=1·37 (CI95%=0·86/2·17) for the highly exposed group. It is concluded that the limit value for the calculation of an individual lifelong vibration dose should be based on a daily reference exposure ofazw(8h)=0·6 m/s2. With increasing dose it is more and more probable that cases of lumbar syndrome are caused by exposure to vibration.

  17. Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Matthew D. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E., E-mail: schultheiss@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Smith, David D. [Division of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Nguyen, Khanh H. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Department of Radiation Oncology, Bayhealth Cancer Center, Dover, Delaware (United States); Wong, Jeffrey Y.C. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

    2015-01-01

    Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the

  18. Dose-response relationships for resetting of human circadian clock by light

    Science.gov (United States)

    Boivin, D. B.; Duffy, J. F.; Kronauer, R. E.; Czeisler, C. A.

    1996-01-01

    Since the first report in unicells, studies across diverse species have demonstrated that light is a powerful synchronizer which resets, in an intensity-dependent manner, endogenous circadian pacemakers. Although it is recognized that bright light (approximately 7,000 to 13,000 lux) is an effective circadian synchronizer in humans, it is widely believed that the human circadian pacemaker is insensitive to ordinary indoor illumination (approximately 50-300 lux). It has been proposed that the relationship between the resetting effect of light and its intensity follows a compressive nonlinear function, such that exposure to lower illuminances still exerts a robust effect. We therefore undertook a series of experiments which support this hypothesis and report here that light of even relatively low intensity (approximately 180 lux) significantly phase-shifts the human circadian pacemaker. Our results clearly demonstrate that humans are much more sensitive to light than initially suspected and support the conclusion that they are not qualitatively different from other mammals in their mechanism of circadian entrainment.

  19. The high dose response and functional capability of the DT-702/Pd lithium fluoride thermoluminescent dosimeter.

    Science.gov (United States)

    Lawlor, Tyler M; Talmadge, Molly D; Murray, Mark M; Nelson, Martin E; Mueller, Andrew C; Romanyukha, Alexander A; Fairchild, Gregory R; Grypp, Matthew D; Williams, Anthony S

    2015-05-01

    The United States Navy monitors the dose its radiation workers receive using the DT-702/PD thermoluminescent dosimeter, which consists of the Harshaw 8840 holder and the four-element Harshaw 8841 card. There were two main objectives of this research. In the first objective, the dosimeters were exposed to 100 Gy using electron and x-ray beams and found to respond approximately 30-40% lower than the delivered dose. No significant effect on the under-response was found when dose rate, radiation type, dosimeter position on the phantom, and dosimeter material were varied or when the card was irradiated while enclosed in its holder. Since the current naval policy is to remove from occupational use any thermoluminescent dosimeter with an accumulated deep dose equivalent of 0.05 Sv or greater, the functionality of the dosimeter was also investigated at deep dose equivalents of 0.05, 0.15, and 0.25 Sv using 60Co and 137Cs sources as the second main objective. All dosimeters were annealed following exposure and then exposed to 5.0 mSv from a 90Sr source. In all cases, the dosimeters responded within 3% of the delivered dose, indicating that the dosimeters remained functional as defined by naval dosimetry requirements. However, the anneal time required to clear the thermoluminescent dosimeter's reading was found to increase approximately as the cube root with the delivered dose. PMID:25811149

  20. Dose response of dexmedetomidine‑induced resistance to hypoxia in mice.

    Science.gov (United States)

    Pan, Wanying; Hua, Xiaoxiao; Wang, Yueting; Guo, Ruixian; Chen, Jingfu; Mo, Liqiu

    2016-10-01

    Tolerance to hypoxia can be induced by reducing oxygen consumption. Dexmedetomidine (DEX) decreases locomotor activity and induces bradycardia and hypothermia in mice. The present study examined the hypothesis that DEX improves hypoxia tolerance in mice. Adult mice received an intraperitoneal injection of 1, 5, 10, 20, 40, 80, 160 or 320 µg/kg DEX, 20 mg/kg propranolol or saline. Acute hypoxic conditions were induced by placing the mice in a limited enclosed container with soda lime. Core body temperature (CBT) and heart rate (HR) were measured prior to and 30 min after drug administration. Survival time was monitored in the sealed container. Survival times (mean ± standard deviation) of mice in the saline, 1, 5, 10, 20, 40, 80, 160 and 320 µg/kg DEX, and the 20 mg/kg propranolol groups were 22.4±1.1, 23.4±1.1, 26.0±0.9, 36.9±5.2, 42.4±2.9, 43.2±2.3, 58.2±4.2, 80.5±4.0, 79.2±6.0, and 38.2±2.8 min, respectively. Pretreatment with propranolol and 10, 20, 40, 80, 160 or 320 µg/kg DEX, but not 1 or 5 µg/kg, significantly prolonged survival time compared with saline‑injected mice (PHR decreased in a similar manner. The correlation coefficients between survival time and CBT, and survival time and HR were ‑0.802 and ‑0.726, respectively. Thus, DEX dose‑dependently enhances hypoxia tolerance in mice. In conclusion, it is suggested that DEX may be used in clinical practice as a novel protective agent for organs and tissues during hypoxic injury. PMID:27498747

  1. Ozone dose-response relationships for spring oilseed rape and broccoli

    Science.gov (United States)

    De Bock, Maarten; Op de Beeck, Maarten; De Temmerman, Ludwig; Guisez, Yves; Ceulemans, Reinhart; Vandermeiren, Karine

    2011-03-01

    Tropospheric ozone is an important air pollutant with known detrimental effects for several crops. Ozone effects on seed yield, oil percentage, oil yield and 1000 seed weight were examined for spring oilseed rape ( Brassica napus cv. Ability). For broccoli ( Brassica oleracea L. cv. Italica cv. Monaco) the effects on fresh marketable weight and total dry weight were studied. Current ozone levels were compared with an increase of 20 and 40 ppb during 8 h per day, over the entire growing season. Oilseed rape seed yield was negatively correlated with ozone dose indices calculated from emergence until harvest. This resulted in an R2 of 0.24 and 0.26 ( p crops (UNECE, Mills, 2004), can indeed be applied for spring oilseed rape. The reduction of oilseed rape yield showed the highest correlation with the ozone uptake during the vegetative growth stage: when only the first 47 days after emergence were used to calculate POD 6, R2 values increased up to 0.476 or even 0.545 when the first 23 days were excluded. The highest ozone treatments, corresponding to the future ambient level by 2100 (IPCC, Meehl et al., 2007), led to a reduction of approximately 30% in oilseed rape seed yield in comparison to the current ozone concentrations. Oil percentage was also significantly reduced in response to ozone ( p oil yield was even more severely affected by elevated ozone exposure compared to seed yield: critical levels for oil yield dropped to 3.2 ppm h and 3.9 mmol m -2. For broccoli the applied ozone doses had no effect on yield.

  2. Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry; Effets sanitaires des faibles doses a faibles debits de dose: modelisation de la relation dose-reponse dans une cohorte de travailleurs du nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Metz-Flamant, Camille

    2011-09-19

    The aim of this thesis is to contribute to a better understanding of the health effects of chronic external low doses of ionising radiation. This work is based on the French cohort of CEA-AREVA NC nuclear workers. The mains stages of this thesis were (1) conducting a review of epidemiological studies on nuclear workers, (2) completing the database and performing a descriptive analysis of the cohort, (3) quantifying risk by different statistical methods and (4) modelling the exposure-time-risk relationship. The cohort includes monitored workers employed more than one year between 1950 and 1994 at CEA or AREVA NC companies. Individual annual external exposure, history of work, vital status and causes of death were reconstructed for each worker. Standardized mortality ratios using French national mortality rates as external reference were computed. Exposure-risk analysis was conducted in the cohort using the linear excess relative risk model, based on both Poisson regression and Cox model. Time dependent modifying factors were investigated by adding an interaction term in the model or by using exposure time windows. The cohort includes 36, 769 workers, followed-up until age 60 in average. During the 1968- 2004 period, 5, 443 deaths, 2, 213 cancers, 62 leukemia and 1, 314 cardiovascular diseases were recorded. Among the 57% exposed workers, the mean cumulative dose was 21.5 milli-sieverts (mSv). A strong Healthy Worker Effect is observed in the cohort. Significant elevated risks of pleura cancer and melanoma deaths were observed in the cohort but not associated with dose. No significant association was observed with solid cancers, lung cancer and cardiovascular diseases. A significant dose-response relationship was observed for leukemia excluding chronic lymphatic leukemia, mainly for doses received less than 15 years before and for yearly dose rates higher than 10 mSv. This PhD work contributes to the evaluation of risks associated to chronic external radiation

  3. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

    Science.gov (United States)

    MacVittie, Thomas J; Farese, Ann M; Jackson, William

    2015-11-01

    Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

  4. Arc Statistics

    CERN Document Server

    Meneghetti, M; Dahle, H; Limousin, M

    2013-01-01

    The existence of an arc statistics problem was at the center of a strong debate in the last fifteen years. With the aim to clarify if the optical depth for giant gravitational arcs by galaxy clusters in the so called concordance model is compatible with observations, several studies were carried out which helped to significantly improve our knowledge of strong lensing clusters, unveiling their extremely complex internal structure. In particular, the abundance and the frequency of strong lensing events like gravitational arcs turned out to be a potentially very powerful tool to trace the structure formation. However, given the limited size of observational and theoretical data-sets, the power of arc statistics as a cosmological tool has been only minimally exploited so far. On the other hand, the last years were characterized by significant advancements in the field, and several cluster surveys that are ongoing or planned for the near future seem to have the potential to make arc statistics a competitive cosmo...

  5. The dose-response decrease in heart rate variability: any association with the metabolites of polycyclic aromatic hydrocarbons in coke oven workers?

    Directory of Open Access Journals (Sweden)

    Xiaohai Li

    Full Text Available BACKGROUND: Air pollution has been associated with an increased risk of cardiopulmonary mortality and decreased heart rate variability (HRV. However, it is unclear whether coke oven emissions (COEs and polycyclic aromatic hydrocarbons (PAHs are associated with HRV. OBJECTIVES: Our goal in the present study was to investigate the association of exposure to COEs and the urinary metabolite profiles of PAHs with HRV of coke oven workers. METHODS: We measured benzene soluble matter, carbon monoxide, sulfur dioxide, particulate matters, and PAHs at different workplaces of a coke oven plant. We determined 10 urinary PAH metabolites and HRV indices of 1333 workers using gas chromatography-mass spectrometry and a 3-channel digital Holter monitor, respectively. RESULTS: Our results showed that there was a significant COEs-related dose-dependent decrease in HRV, and an inverse relationship between the quartiles of urinary 2-hydroxynaphthalene and five HRV indices (p(trend<0.01 for all. After adjustment for potential confounders, elevation per interquartile range (IQR (1.81 µg/mmol creatinine of urinary 2-hydroxynaphthalene was associated with a 5.46% (95% CI, 2.50-8.32 decrease in standard deviation of NN intervals (SDNN. As workers worked more years, SDNN gradually declined in the same quartiles of 2-hydroxynaphthalene levels (p(trend = 1.40×10(-4, especially in workers with the highest levels of 2-hydroxynaphthalene. CONCLUSIONS: Occupational exposure to COEs is associated with a dose-response decrease in HRV. In particular, increased exposure to 2-hydroxynaphthalene is associated with significantly decreased HRV. Increase of working years and exposure levels has resulted in a gradual decline of HRV.

  6. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  7. Identification of low-dose responsive metabolites in X-irradiated human B lymphoblastoid cells and fibroblasts

    International Nuclear Information System (INIS)

    Ionizing radiation (IR) induces cellular stress responses, such as signal transduction, gene expression, protein modification, and metabolite change that affect cellular behavior. We analyzed X-irradiated human Epstein-Barr virus-transformed B lymphoblastoid cells and normal fibroblasts to search for metabolites that would be suitable IR-responsive markers by Liquid Chromotography–Mass spectrometry (LC–MS). Mass spectra, as analyzed with principal component analysis, showed that the proportion of peaks with IR-induced change was relatively small compared with the influence of culture time. Dozens of peaks that had either been upregulated or downregulated by IR were extracted as candidate IR markers. The IR-changed peaks were identified by comparing mock-treated groups to 100 mGy-irradiated groups that had recovered after 10 h, and the results indicated that the metabolites involved in nucleoside synthesis increased and that some acylcarnitine levels decreased in B lymphoblastoids. Some peaks changed by as much as 20 mGy, indicating the presence of an IR-sensitive signal transduction/metabolism control mechanism in these cells. On the other hand, we could not find common IR-changed peaks in fibroblasts of different origin. These data suggest that cell phenotype-specific pathways exist, even in low-dose responses, and could determine cell behavior. (author)

  8. Dose response and time course of manganese-enhanced magnetic resonance imaging for visual pathway tracing in vivo

    Institute of Scientific and Technical Information of China (English)

    Wei-ling Wang; Hui Xu; Ying Li; Zhi-zhong Ma; Xiao-dong Sun; Yun-tao Hu

    2016-01-01

    Axonal tracing is useful for detecting optic nerve injury and regeneration, but many commonly used methods cannot be used to observe axoplasmic lfow and synaptic transmission in vivo. Manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) can be used for in vivo longitudinal tracing of the visual pathway. Here, we explored the dose response and time course of an intravitreal injection of MnCl2 for tracing the visual pathway in rabbits in vivo using MEMRI. We found that 2 mM MnCl2 enhanced images of the optic nerve but not the lateral geniculate body or superior colliculus, whereas at all other doses tested (5–40 mM), images of the visual pathway from the retina to the contralateral superior colliculus were signiifcantly enhanced. The images were brightest at 24 hours, and then decreased in brightness until the end of the experiment (7 days). No signal enhancement was observed in the visual cortex at any concentration of MnCl2. These results suggest that MEMRI is a viable method for temporospatial tracing of the visual pathway in vivo. Signal enhancement in MEMRI de-pends on the dose of MnCl2, and the strongest signals appear 24 hours after intravitreal injection.

  9. A novel method of estimating dose responses for polymer gels using texture analysis of scanning electron microscopy images.

    Directory of Open Access Journals (Sweden)

    Cheng-Ting Shih

    Full Text Available Polymer gels are regarded as a potential dosimeter for independent validation of absorbed doses in clinical radiotherapy. Several imaging modalities have been used to convert radiation-induced polymerization to absorbed doses from a macro-scale viewpoint. This study developed a novel dose conversion mechanism by texture analysis of scanning electron microscopy (SEM images. The modified N-isopropyl-acrylamide (NIPAM gels were prepared under normoxic conditions, and were administered radiation doses from 5 to 20 Gy. After freeze drying, the gel samples were sliced for SEM scanning with 50×, 500×, and 3500× magnifications. Four texture indices were calculated based on the gray level co-occurrence matrix (GLCM. The results showed that entropy and homogeneity were more suitable than contrast and energy as dose indices for higher linearity and sensitivity of the dose response curves. After parameter optimization, an R (2 value of 0.993 can be achieved for homogeneity using 500× magnified SEM images with 27 pixel offsets and no outlier exclusion. For dose verification, the percentage errors between the prescribed dose and the measured dose for 5, 10, 15, and 20 Gy were -7.60%, 5.80%, 2.53%, and -0.95%, respectively. We conclude that texture analysis can be applied to the SEM images of gel dosimeters to accurately convert micro-scale structural features to absorbed doses. The proposed method may extend the feasibility of applying gel dosimeters in the fields of diagnostic radiology and radiation protection.

  10. EMS in Viracept--initial ('traditional') assessment of risk to patients based on linear dose response relations.

    Science.gov (United States)

    Gocke, Elmar; Müller, Lutz; Pfister, Thomas

    2009-11-12

    Prior to having performed in depth toxicological, genotoxicological and DMPK studies on ethyl methanesulfonate (EMS) providing solid evidence for a thresholded dose response relationship, we had prepared and shared with regulatory authorities a preliminary risk estimate based on standard linear dose-effect projections. We estimated that maximal lifetime cancer risk was in the order of 10(-3) (for lifetime ingestion of the maximally contaminated tablets) or 10(-4) for the exposure lasting for 3 months. This estimate was based on a lifetime cancer study with methyl methanesulfonate (MMS; as insufficient data were available for EMS) in rodents and default linear back extrapolation. Analogous estimates were made specifically for breast cancer based on short term tumorigenicity studies with EMS in rats, for the induction of heritable mutations based on specific locus and dominant lethal tests in mice and for the induction of birth defects based on teratogenicity studies in mice. We concluded that even under worst case assumptions of linear dose relations the chance of experiencing these adverse effects would be very small, comprising at most a minute additional burden among the background incidence of the patients.

  11. Impact of dose-response calorie reduction or supplementation of a covertly manipulated lunchtime meal on energy compensation.

    Science.gov (United States)

    Tey, Siew Ling; Chia, Edwin Ming En; Forde, Ciarán G

    2016-10-15

    Numerous studies have examined energy compensation following overfeeding regimes whereas much less is known about the impact of acute underfeeding on energy compensation and fewer still have compared energy reduction and addition in the same group of individuals. This study compared the effects of consuming lunches with varying energy content (7.2-fold difference) on subsequent energy intake. A total of 27 healthy males took part in this randomized, crossover study with five treatments: 163kcal (very low energy meal, VLEM), 302kcal (low energy meal, LEM), 605kcal (control), 889kcal (high energy meal, HEM), and 1176kcal (very high energy meal, VHEM) served as a noodle soup. Participants were instructed to consume a standardized breakfast in the morning and they were provided with one of the five treatments for lunch on non-consecutive test day. Test lunches were matched for palatability, sensory properties, and volume. Participants were provided with an afternoon snack and ad libitum dinner on each test day and recorded food intake for the rest of the day. Appetite ratings were measured at regular intervals. As the energy content of treatments increased, participants' hunger, desire to eat, and prospective consumption decreased significantly whereas fullness increased significantly. However, no significant difference in subsequent meal intake was found between the treatments (P=0.458): 1003kcal VLEM, 1010kcal LEM, 1011kcal control, 940kcal HEM, and 919kcal VHEM. Total daily energy intake was statistically significantly different between the treatments (Penergy content of the lunchtime meal. Despite the large difference in energy content between the treatments, participants did not compensate for the "missing calories" or "additional calories" at subsequent meals. These results suggest that covertly manipulated, equally palatable, sensory and volume matched meals have the potential to promote either positive or negative energy balance if the effects seen in this

  12. Health risks from arsenic-contaminated soil in Flin Flon-Creighton, Canada: Integrating geostatistical simulation and dose-response model

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Hua [Environmental Systems Engineering Program, Faculty of Engineering, University of Regina, Regina, Saskatchewan, S4S 0A2 (Canada); Huang Guohe, E-mail: huang@iseis.or [Environmental Systems Engineering Program, Faculty of Engineering, University of Regina, Regina, Saskatchewan, S4S 0A2 (Canada); Zeng Guangming [College of Environmental Science and Engineering, Hunan University, Changsha, Hunan 410082 (China)

    2009-08-15

    Elevated concentrations of arsenic were detected in surface soils adjacent to a smelting complex in northern Canada. We evaluated the cancer risks caused by exposure to arsenic in two communities through combining geostatistical simulation with demographic data and dose-response models in a framework. Distribution of arsenic was first estimated using geostatistical circulant-embedding simulation method. We then evaluated the exposures from inadvertent ingestion, inhalation and dermal contact. Risks of skin caner and three internal cancers were estimated at both grid scale and census-unit scale using parametric dose-response models. Results indicated that local residents could face non-negligible cancer risks (skin cancer and liver cancer mainly). Uncertainties of risk estimates were discussed from the aspects of arsenic concentrations, exposed population and dose-response model. Reducing uncertainties would require additional soil sampling, epidemic records as well as complementary studies on land use, demographic variation, outdoor activities and bioavailability of arsenic. - Cancer risks induced by arsenic in soil were evaluated using geostatistical simulation and dose-response model.

  13. A dose-response of consuming high fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults

    Science.gov (United States)

    National Health and Nutrition Examination Survey data show increased risk of cardiovascular disease (CVD) mortality with increased intake of added sugar across quintiles. Objective: To determine the dose response effects of consuming beverages sweetened with high fructose corn syrup (HFCS) at zero, ...

  14. The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

    International Nuclear Information System (INIS)

    Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type (Trp53+/+) and heterozygous (Trp53+/-) mice. The dose response for Trp53+/+ mice showed higher initial levels of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation

  15. Cytogenetics dosimetry: dose-response curve for low doses of X-ray; Dosimetria citogenetica: curva dosis-respuesta para bajas dosis de rayos-X

    Energy Technology Data Exchange (ETDEWEB)

    Lara, Virginia E. Noval; Pineda Bolivar, William R.; Riano, Victor M. Pabon, E-mail: venovall.15@hotmail.com, E-mail: wrpineda@misena.edu.co, E-mail: vmpabonr@udistrital.edu.co [Universidad Distrital Francisco Jose de Caldas (UD), Bogota (Colombia). Grupo de Investigacion en Ciencia y Tecnologia Nuclear; Ureana, Cecilia Crane, E-mail: cecicrane@yahoo.com [Instituto Nacional de Salud (INS), Bogota (Colombia). Laboratorio de Genetica

    2013-07-01

    The purpose of this study was to conduct a preliminary study for the standardization in the future, the dose-response curve for low doses of X-rays, through the analysis of in vitro cultures of peripheral blood samples of 3 men and 3 women occupationally not exposed to artificial sources of ionizing radiation, age 18-40 years, where possible nonsmokers.

  16. Dose-response and time-course of neurotoxicity and tissue concentrations of carbaryl in Brown Norway rats from preweaning to senescence.

    Science.gov (United States)

    Factors impacting sensitivity to chemicals across life stages include toxicokinetic and toxicodynamic changes. We systematically compared the dose-response (3, 7.5, 15,22.5 mg/kg) and time-course (3 or 15 mg/kg at 30, 60, 120, 240 min) of acute effects of carbaryl (oral gavage) i...

  17. No protection by oral terbutaline against exercise-induced asthma in children: a dose-response study.

    Science.gov (United States)

    Fuglsang, G; Hertz, B; Holm, E B

    1993-04-01

    We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate, in 17 asthmatic children aged 6-12 yrs (mean 9 yrs). Placebo, 2, 4 and 6 mg terbutaline were given b.i.d. for 14 days, in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline.day-1, respectively. There was no correlation between plasma terbutaline and dose of terbutaline. A small but statistically significant dose-related increase in morning and evening peak expiratory flow (PEF) recordings occurred, but the incidence of side-effects also increased with the dose given. There was a trend towards more side-effects when the high doses were used, and two patients withdrew from the study because of side-effects at this dose. It is concluded that continuous treatment, even with high doses of oral terbutaline, does not offer clinically useful protection against exercise-induced asthma. PMID:8491302

  18. Cancer Statistics

    Science.gov (United States)

    ... What Is Cancer? Cancer Statistics Cancer Disparities Cancer Statistics Cancer has a major impact on society in ... success of efforts to control and manage cancer. Statistics at a Glance: The Burden of Cancer in ...

  19. Dose-response relationship in cyclophosphamide-treated B-cell lymphoma xenografts monitored with [{sup 18}F]FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Brepoels, Lieselot; Saint-Hubert, Marijke de; Mortelmans, Luc [University Hospital Gasthuisberg Leuven, Department of Nuclear Medicine, Leuven (Belgium); Stroobants, Sigrid [University Hospital Antwerpen, Department of Nuclear Medicine, Edegem (Belgium); Verhoef, Gregor [University Hospital Gasthuisberg Leuven, Department of Hematology, Leuven (Belgium); Balzarini, Jan [KU Leuven, Department of Microbiology and Immunology, Leuven (Belgium); Mottaghy, Felix M. [University Hospital Gasthuisberg Leuven, Department of Nuclear Medicine, Leuven (Belgium); Universitaetsklinikum der RWTH Aachen, Klinik fuer Nuklearmedizin, Aachen (Germany)

    2010-09-15

    Although [{sup 18}F]FDG PET can measure therapy response sooner and more accurately than morphological imaging techniques, there is still some debate as to whether [{sup 18}F]FDG uptake really reflects changes in the viable cell fraction. In this study changes in [{sup 18}F]FDG uptake were investigated in a lymphoma model at several time-points after treatment and with different doses of chemotherapy. Data were analysed in terms of several parameters. SCID mice were subcutaneously inoculated with 5 x 10{sup 6} Daudi cells in the right thigh. One group was not treated (control group). The other groups received cyclophosphamide 75 mg/kg (low-dose group), 125 mg/kg (medium-dose group) and 175 mg/kg (high-dose group) on day 0. Sequential [{sup 18}F]FDG small-animal PET ({mu}PET) scans were performed on days 0, 2, 6, 9, 13 and 16 after treatment. The mean and maximum standardized uptake value (SUV{sub mean} and SUV{sub max}), metabolic tumour volume (Vol{sub metab}) and total lesion glycolysis (TLG) were calculated. A significant decrease in [{sup 18}F]FDG uptake was observed on day 2 in the medium-dose and high-dose groups and on day 6 in the low-dose group, all preceding morphological changes. SUV{sub mean} and SUV{sub max} formed a plateau from day 6 to day 9, corresponding to the known influx of inflammatory cells. No obvious plateau was observed with TLG which was found to be the most sensitive parameter clearly differentiating the low-dose group from the medium- and high-dose groups early after therapy. [{sup 18}F]FDG uptake was able to reflect the dose-response relationship for cyclophosphamide. TLG was the best parameter for dose-related response assessment in this tumour model. (orig.)

  20. A randomized comparative trial of first-dose response to Angiotensin- Converting Enzyme Perindopril and Captopril in Indonesian heart failure patients

    Directory of Open Access Journals (Sweden)

    Lukman H. Makmun

    2002-03-01

    Full Text Available Several large placebo-controlled trials have confirmed that angiotensin converting enzyme (ACE inhibitors significantly reduce mortality aid morbidity in all functional grades of congestive heart failure (CHF, nevertheless only a proportion of patients who may benefit from treatment are priscribed an ACE inhibitor. One of the perceived difficulties is the occurrence of first-dose hypotension in susceptible patients. A double-blind, randomised, single-dose therapy, parallel-group study was conducted with the aim to compare the first-dose responses to low dose ACE inhibitors captopril and perindopril in patients with stable chronic heart failure. Seventy patients (New York Heart Association class I-IV were included. Blood pressure was recorded every 15 minutes 2 hours before starting treatment. The mean of these readings was taken as the baseline blood pressure. Patients were randomised to receive a single-dose of captopril 6.25 mg or perindopril 2 mg. After taking the drug, blood pressure was monitored every 15 minutes for 2 hours, every 30 minutes during 5 hours then hourly after 2 hours. The maximum mean arterial pressure fall from baseline of perindopril was 0.85 mmHg compared to captopril 4.60 mmHg. The maximum mean systolic fall from baseline of perindopril was 3 '31 'mmHg compared to captopril 6.76 mmHg while the maximum mean diastolic fall from baseline of perindopril was 1.08 mmHg compared to captopril 2.63 mmHg. The hypotensive effect of the captopril group started soon after dosing and reached its maximum after 1 to 2 hours while perindopril showed slight reduction of systolic after 1 hour and slight reduction of diastolic after 4 hours. Compared to captopril, perindopril seemed to be less likely to cause first-dose hypotension in patients with heart failure. (Med J Indones 2002; 11: 19-23Keywords: first dose hypotension, perindopril, captopril, chronic heart failure

  1. Has the sensitivity of soybean cultivars to ozone pollution increased with time? An analysis of published dose-response data.

    Science.gov (United States)

    Osborne, Stephanie A; Mills, Gina; Hayes, Felicity; Ainsworth, Elizabeth A; Büker, Patrick; Emberson, Lisa

    2016-09-01

    The rising trend in concentrations of ground-level ozone (O3 ) - a common air pollutant and phytotoxin - currently being experienced in some world regions represents a threat to agricultural yield. Soybean (Glycine max (L.) Merr.) is an O3 -sensitive crop species and is experiencing increasing global demand as a dietary protein source and constituent of livestock feed. In this study, we collate O3 exposure-yield data for 49 soybean cultivars, from 28 experimental studies published between 1982 and 2014, to produce an updated dose-response function for soybean. Different cultivars were seen to vary considerably in their sensitivity to O3 , with estimated yield loss due to O3 ranging from 13.3% for the least sensitive cultivar to 37.9% for the most sensitive, at a 7-h mean O3 concentration (M7) of 55 ppb - a level frequently observed in regions of the USA, India and China in recent years. The year of cultivar release, country of data collection and type of O3 exposure used were all important explanatory variables in a multivariate regression model describing soybean yield response to O3 . The data show that the O3 sensitivity of soybean cultivars increased by an average of 32.5% between 1960 and 2000, suggesting that selective breeding strategies targeting high yield and high stomatal conductance may have inadvertently selected for greater O3 sensitivity over time. Higher sensitivity was observed in data from India and China compared to the USA, although it is difficult to determine whether this effect is the result of differential cultivar physiology, or related to local environmental factors such as co-occurring pollutants. Gaining further understanding of the underlying mechanisms that govern the sensitivity of soybean cultivars to O3 will be important in shaping future strategies for breeding O3 -tolerant cultivars. PMID:27082950

  2. Biological effects in lymphocytes irradiated with 99mTc: determination of the curve dose-response

    International Nuclear Information System (INIS)

    Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with 99m Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with 99m Tc were used, allowing the irradiation of blood with different administered activities of 99m Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with 99m Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with 99m Tc was best fitted by the curve Y=(8,99 ±2,06) x 1--4 + (1,24 ±0,62) x 10-2 D + (5,67 ± 0,64) x 10-2 D2. (author)

  3. Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis.

    Science.gov (United States)

    Greenwood, Darren C; Thatcher, Natalie J; Ye, Jin; Garrard, Lucy; Keogh, Georgina; King, Laura G; Cade, Janet E

    2014-10-01

    Caffeine is commonly consumed during pregnancy, crosses the placenta, with fetal serum concentrations similar to the mother's, but studies of birth outcome show conflicting findings. We systematically searched Medline and Embase for relevant publications. We conducted meta-analysis of dose-response curves for associations between caffeine intake and spontaneous abortion, stillbirth, preterm delivery, low birth weight and small for gestational age (SGA) infants. Meta-analyses included 60 unique publications from 53 cohort and case-control studies. An increment of 100 g caffeine was associated with a 14 % (95 % CI 10-19 %) increase in risk of spontaneous abortion, 19 % (5-35 %) stillbirth, 2 % (-2 to 6 %) preterm delivery, 7 % (1-12 %) low birth weight, and 10 % (95 % CI 6-14 %) SGA. There was substantial heterogeneity in all models, partly explained by adjustment for smoking and previous obstetric history, but not by prospective assessment of caffeine intake. There was evidence of small-study effects such as publication bias. Greater caffeine intake is associated with an increase in spontaneous abortion, stillbirth, low birth weight, and SGA, but not preterm delivery. There is no identifiable threshold below which the associations are not apparent, but the size of the associations are generally modest within the range of usual intake and are potentially explained by bias in study design or publication. There is therefore insufficient evidence to support further reductions in the maximum recommended intake of caffeine, but maintenance of current recommendations is a wise precaution.

  4. Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung

    Energy Technology Data Exchange (ETDEWEB)

    Izzotti, Alberto; Larghero, Patrizia; Longobardi, Mariagrazia; Cartiglia, Cristina; Camoirano, Anna [Department of Health Sciences, University of Genoa, Genoa (Italy); Steele, Vernon E. [National Cancer Institute (NCI), Rockville, MD (United States); De Flora, Silvio, E-mail: sdf@unige.it [Department of Health Sciences, University of Genoa, Genoa (Italy)

    2011-12-01

    Our previous studies demonstrated that exposure to cigarette smoke (CS), either mainstream or environmental, results in a remarkable downregulation of microRNA expression in the lung of both mice and rats. The goals of the present study were to evaluate the dose responsiveness to CS and the persistence of microRNA alterations after smoking cessation. ICR (CD-1) neonatal mice were exposed whole-body to mainstream CS, at the doses of 119, 292, 438, and 631 mg/m{sup 3} of total particulate matter. Exposure started within 12 h after birth and continued daily for 4 weeks. The levels of bulky DNA adducts and 8-oxo-7,8-dihydro-2 Prime -deoxyguanosine (8-oxodGuo) were measured by {sup 32}P postlabeling procedures, and the expression of 697 mouse microRNAs was analyzed by microarray. The highest CS dose was lethal. Exposure to CS caused a dose-dependent increase of DNA alterations. DNA adducts and, even more sharply, 8-oxodGuo were reverted 1 and 4 weeks after smoking cessation. Exposure to CS resulted in an evident dysregulation of microRNA expression profiles, mainly in the sense of downregulation. The two lowest doses were not particularly effective, while the highest nonlethal dose produced extensive microRNA alterations. The expression of most downregulated microRNAs, including among others 7 members of the let-7 family, was restored one week after smoking cessation. However, the recovery was incomplete for a limited array of microRNAs, including mir-34b, mir-345, mir-421, mir-450b, mir-466, and mir-469. Thus, it appears that microRNAs mainly behave as biomarkers of effect and that exposure to high-dose, lasting for an adequate period of time, is needed to trigger the CS-related carcinogenesis process in the experimental animal model used.

  5. Dairy foods intake and risk of Parkinson's disease: a dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Jiang, Wenjie; Ju, Chuanxia; Jiang, Hong; Zhang, Dongfeng

    2014-09-01

    Dairy foods have been linked to Parkinson's disease (PD), and a meta-analysis of prospective cohort studies on dairy foods intake and PD risk was conducted. Eligible studies were identified in a literature search of EMBASE and PubMed up to April 2014. Seven results from prospective studies were included, including 1,083 PD cases among 304,193 subjects. The combined risk of PD for highest vs. lowest level of dairy foods intake was 1.40 (1.20-1.63) overall, 1.66 (1.29-2.14) for men and 1.15 (0.85-1.56) for women. For highest vs. lowest level, the PD risk was 1.45 (1.23-1.73) for milk, 1.26 (0.99-1.60) for cheese, 0.95 (0.76-1.20) for yogurt and 0.76 (0.51-1.13) for butter. The linear dose-response relationship showed that PD risk increased by 17% [1.17 (1.06-1.30)] for every 200 g/day increment in milk intake (Pfor non-linearity = 0.22), and 13% [1.13 (0.91-1.40)] for every 10 g/day increment in cheese intake (Pfor non-linearity = 0.39). The absolute risk differences were estimated to be 2-4 PD cases per 100,000 person-years for every 200 g/day increment in milk intake, and 1-3 PD cases per 100,000 person-years for every 10 g/day increment in cheese intake. Dairy foods (milk, cheese) might be positively associated with increased risk of PD, especially for men. PMID:24894826

  6. A dose-response study of consuming high-fructose corn syrup–sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults123456

    Science.gov (United States)

    Medici, Valentina; Bremer, Andrew A; Lee, Vivien; Lam, Hazel D; Nunez, Marinelle V; Chen, Guoxia X; Keim, Nancy L; Havel, Peter J

    2015-01-01

    Background: National Health and Nutrition Examination Survey data show an increased risk of cardiovascular disease (CVD) mortality with an increased intake of added sugar. Objective: We determined the dose-response effects of consuming beverages sweetened with high-fructose corn syrup (HFCS) at zero, low, medium, and high proportions of energy requirements (Ereq) on circulating lipid/lipoprotein risk factors for CVD and uric acid in adults [age: 18–40 y; body mass index (in kg/m2): 18–35]. Design: We conducted a parallel-arm, nonrandomized, double-blinded intervention study in which adults participated in 3.5 inpatient days of baseline testing at the University of California Davis Clinical and Translational Science Center’s Clinical Research Center. Participants then consumed beverages sweetened with HFCS at 0% (aspartame sweetened, n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) of Ereq during 13 outpatient days and during 3.5 inpatient days of intervention testing at the research center. We conducted 24-h serial blood collections during the baseline and intervention testing periods. Results: Consuming beverages containing 10%, 17.5%, or 25% Ereq from HFCS produced significant linear dose-response increases of lipid/lipoprotein risk factors for CVD and uric acid: postprandial triglyceride (0%: 0 ± 4; 10%: 22 ± 8; 17.5%: 25 ± 5: 25%: 37 ± 5 mg/dL, mean of Δ ± SE, P < 0.0001 effect of HFCS-dose), fasting LDL cholesterol (0%: −1.0 ± 3.1; 10%: 7.4 ± 3.2; 17.5%: 8.2 ± 3.1; 25%: 15.9 ± 3.1 mg/dL, P < 0.0001), and 24-h mean uric acid concentrations (0%: −0.13 ± 0.07; 10%: 0.15 ± 0.06; 17.5%: 0.30 ± 0.07; 25%: 0.59 ± 0.09 mg/dL, P < 0.0001). Compared with beverages containing 0% HFCS, all 3 doses of HFCS-containing beverages increased concentrations of postprandial triglyceride, and the 2 higher doses increased fasting and/or postprandial concentrations of non–HDL cholesterol, LDL cholesterol, apolipoprotein B, apolipoprotein CIII, and

  7. An update on modeling dose-response relationships: Accounting for correlated data structure and heterogeneous error variance in linear and nonlinear mixed models.

    Science.gov (United States)

    Gonçalves, M A D; Bello, N M; Dritz, S S; Tokach, M D; DeRouchey, J M; Woodworth, J C; Goodband, R D

    2016-05-01

    Advanced methods for dose-response assessments are used to estimate the minimum concentrations of a nutrient that maximizes a given outcome of interest, thereby determining nutritional requirements for optimal performance. Contrary to standard modeling assumptions, experimental data often present a design structure that includes correlations between observations (i.e., blocking, nesting, etc.) as well as heterogeneity of error variances; either can mislead inference if disregarded. Our objective is to demonstrate practical implementation of linear and nonlinear mixed models for dose-response relationships accounting for correlated data structure and heterogeneous error variances. To illustrate, we modeled data from a randomized complete block design study to evaluate the standardized ileal digestible (SID) Trp:Lys ratio dose-response on G:F of nursery pigs. A base linear mixed model was fitted to explore the functional form of G:F relative to Trp:Lys ratios and assess model assumptions. Next, we fitted 3 competing dose-response mixed models to G:F, namely a quadratic polynomial (QP) model, a broken-line linear (BLL) ascending model, and a broken-line quadratic (BLQ) ascending model, all of which included heteroskedastic specifications, as dictated by the base model. The GLIMMIX procedure of SAS (version 9.4) was used to fit the base and QP models and the NLMIXED procedure was used to fit the BLL and BLQ models. We further illustrated the use of a grid search of initial parameter values to facilitate convergence and parameter estimation in nonlinear mixed models. Fit between competing dose-response models was compared using a maximum likelihood-based Bayesian information criterion (BIC). The QP, BLL, and BLQ models fitted on G:F of nursery pigs yielded BIC values of 353.7, 343.4, and 345.2, respectively, thus indicating a better fit of the BLL model. The BLL breakpoint estimate of the SID Trp:Lys ratio was 16.5% (95% confidence interval [16.1, 17.0]). Problems with

  8. A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects.

    Directory of Open Access Journals (Sweden)

    Luciana Cadore Stefani

    Full Text Available Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation.The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects.Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT and the pressure pain tolerance (PPTo. Quantitative sensory testing (QST was used to measure the heat pain threshold (HPT and the heat pain tolerance (HPTo. Sedation was assessed with a visual analogue scale and bispectral analysis.Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg and the highest (0.25 mg/kg melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R(2  = 0.492 for HPT, R(2  = 0.538 for PPT, R(2  = 0.558 for HPTo and R(2  = 0.584 for PPTo.The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec: (U1111

  9. Dose-response relationship of nasopharyngeal carcinoma above conventional tumoricidal level: A study by the Hong Kong nasopharyngeal carcinoma study group (HKNPCSG)

    International Nuclear Information System (INIS)

    Background and purpose: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique. Patients and methods: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n=2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (≤40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. Results: On multivariate analysis, T-stage (P< 0.01; hazard ratio [HR], 1.58) and optimal boost (P=0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P=0.01; HR, 0.33); use of a boost (P<0.01; HR, 0.60) and age (P=0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications. Conclusions: Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity

  10. 生物多样性和均匀度显著性的随机化检验及计算软件%Randomization tests and computational software on statistic significance of community biodiversity and evenness

    Institute of Scientific and Technical Information of China (English)

    张文军; 齐艳红; 等

    2002-01-01

    Diversity and evenness indices were widely used in community ecology and biodiversity researches. However, shortage of statistic tests on these indices restricted their reliability. To develop statistic test methods on diversity is one of the focuses in biodiversity researches. In present study, some randomization tests on statistic significance of diversity and evenness indices, confidence interval of diversity and evenness, and randomization test on statistic significance of between-community differences were presented. Shannon-Wiener diversity index, Simpson diversity index, McIntosh diversity index, Berger-Parker diversity index, Hurlbert diversity index, Brillouin diversity index, and corresponding evenness indices are included in the randomization test procedure. The web-based computational software for the statistic tests, BiodiversityTest, which is comprised of seven Java classes and an HTML file, is developed. It can be run on various operational systems and java-enabled web browsers and, may read ODBC linked databases such as MS Access, Excel, FoxPro, dBASE, etc. Rice arthropod diversity (15 sampling sites, 125 arthropod species, 17 functional groups) was recorded on September,1996 in IRRI rice farm using RiceVac apparatus and bucket enclosure. The data were analysed using BiodiversityTest with Shannon-Wiener index and Berger-Parker index respectively, and the results showed that the changes of diversity and evenness can be effectively detected by these tests. The randomization tests will correct the possible wrong conclusions aroused in direct comparison of arthropod diversity which was used in most of the researches up to now. The development of randomization tests on biodiversity will provide a quantitative tool for stricter statistic comparison of biodiversity between communities and present an absolute criterion fordiversity measuring. BiodiversityTest will make the computation realistic and accessible on Internet.%多样性指数和均匀

  11. Fat Intake Is Not Linked to Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Chang Xu

    Full Text Available Since the late 1960s, the average global supply of fat has increased by 20 g per capita per day. While fat intake has been considered a potential risk factor for prostate cancer (Pca, the hypothesis from previous epidemiologic studies remained equivocal.Relevant cohort studies were identified through a literature search in PubMed, ScienceDirect and Wiley Online Library up to March 1, 2015. A systematic review and dose-response meta-analysis were used to assess the relationship between fat intake and the risk for Pca.We identified 14 cohort studies, which included 37,349 cases and a total of 751,030 participants. We found no evidence of a non-linear association between fat intake and the risk for Pca. Overall, the summarized relative risks for every 28.35 g increment a day was 0.99 (95%CI: 0.98, 1.01; P=0.94; n=13 for total fat intake, 1.00 (95%CI: 1.00, 1.00; P=0.72; n=9 for saturated fat, 0.99 (95%CI: 0.95, 1.03; P=0.55; n=7 for polyunsaturated fat, and 1.00 (95%CI: 0.95, 1.04; P=0.85; n=8 for monounsaturated fat. Additionally, there was no link to the risk for advanced stage Pca regarding total fat intake (RR=1.02, 95%CI: 0.96, 1.08; P=0.63; n=5, saturated fat (RR=0.96, 95%CI: 0.84, 1.11; P=0.61; n=6, polyunsaturated fat (RR=0.96, 95%CI: 0.79, 1.17; P=0.68; n=6, or monounsaturated fat (RR=0.96, 95%CI: 0.86, 1.07; P=0.42; n=6. Subgroup and sensitively analyses showed consistent results.Little evidence from published cohort studies supports the statement that total fat, saturated fat or unsaturated fat intake increases the risk for Pca or advanced stage Pca.

  12. Establishment of in vitro 192Ir γ-ray dose-response relationship for dose assessment by the lymphocyte dicentric assay

    Science.gov (United States)

    Kowalska, Maria; Meronka, Katarzyna; Szewczak, Kamil

    2012-03-01

    In vitro dose-response relationships are used to describe the relation between dicentric chromosomes and radiation dose for human peripheral blood lymphocytes. The dicentric yield depends on both the dose and the radiation quality. Thus, for reliable dose estimation in vitro dose responses must be determined for different radiation qualities. This paper reports the work for setting up the relationship for the dicentric production in the lymphocytes exposed in vitro to 192Ir g-rays at Central Laboratory for Radiological Protection (CLOR). In a case of a radiation accident in industrial radiography using 192Ir sealed sources, this will be the basis for the indirect evaluation of the g-ray dose to which an accidental victim was exposed.

  13. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

    DEFF Research Database (Denmark)

    Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera;

    2010-01-01

    Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...... blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium.......Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...

  14. Fundamental studies on the radiation chemical dose-response with use of thymine. Is activation of the surface between radiation biology and radiation chemistry possible?

    International Nuclear Information System (INIS)

    The review described the importance and difficulty of radiation chemical assessment of dose-response. The assessment has the tasks of the unit, low dose region evaluation and direct/indirect effects in biology. The authors' vacuum evaporated thymine for G-value determination is appropriate for XANES (X-ray absorption near edge structures) measurement with monochromic ultrasoft X-rays (-550 eV photon) generated by SPring-8. However, the data of yielded thymine derivatives as well as those yielded after 60Co γ-ray (1.5 MeV photon) irradiation are not suitable for direct application in DNA damage evaluation of living cells due to trans-scientific uncertainty. Efforts are required for reducing the uncertainty present in dose-response assessment. (K.H.)

  15. The six year report: Acidification of surface water in Europe and North America. Dose/response relationships and long-term trends

    Energy Technology Data Exchange (ETDEWEB)

    Skjelkvaale, B.L.; Newell, A.D.; Raddum, G.; Johannessen, M.; Hovind, H.; Tjomsland, T.; Wathne, B.M.

    1994-12-31

    This report discusses The International Cooperative Programme on Assessment and Monitoring of Acidification of Rivers and Lakes, which is designed to (1) establish degree and extent of acidification of surface waters, (2) evaluate dose/response relationships and (3) define long-term trends and variations in aquatic chemistry and biota attributable to atmospheric pollution. Data from 200 sites in 14 countries of Europe and North America are available. Dose/response relationships show that the fauna is adapted to different water qualities in different regions, and that critical limits for the fauna must be calculated according to data for the specific region. Long-term trends of water chemistry show decreases in SO{sub 4}{sup 2-} and Ca{sup 2+} at many sites. Nitrate shows no consistent trends. 66 refs., 26 figs., 16 tabs.

  16. Dissolution and subsequent re-crystallization as zeroing mechanism, thermal properties and component resolved dose response of salt (NaCl) for retrospective dosimetry

    International Nuclear Information System (INIS)

    In the present study we report dosimetric properties of iodized salt aiming at using it as an accidental luminescent dosimeter. It was found that the very good sensitivity of its main dosimetric peak is strongly affected by thermal treatments. This is also the case for OSL emission. The sensitivity loss due to heating implies that caution should be exercised while applying single aliquot protocols for dose evaluation. The sequence of dissolution and subsequent re-crystallization was established to be an extremely effective zeroing mechanism for the TL signal. The linearity in the dose response was also monitored in the case of dissolved and subsequently re-crystallized salt. In the case of naturally occurring salt, zeroing of the TL signal due to dissolution as well as the linearity of dose response up to doses as large as 100 Gy were found to be very promising features for dating applications.

  17. Dissolution and subsequent re-crystallization as zeroing mechanism, thermal properties and component resolved dose response of salt (NaCl) for retrospective dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Polymeris, George S., E-mail: polymers@auth.gr [Faculty of Science and Arts, Physics Department, ISIK University, 34980-Sile, Istanbul (Turkey); Kitis, George [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124-Thessaloniki (Greece); Kiyak, Nafiye G. [Faculty of Science and Arts, Physics Department, ISIK University, 34980-Sile, Istanbul (Turkey); Sfamba, Ioanna; Subedi, Bhagawan [Aristotle University of Thessaloniki, Nuclear Physics Laboratory, 54124-Thessaloniki (Greece); Pagonis, Vasilis [Physics Department, McDaniel College, Westminster, MD 21157 (United States)

    2011-09-15

    In the present study we report dosimetric properties of iodized salt aiming at using it as an accidental luminescent dosimeter. It was found that the very good sensitivity of its main dosimetric peak is strongly affected by thermal treatments. This is also the case for OSL emission. The sensitivity loss due to heating implies that caution should be exercised while applying single aliquot protocols for dose evaluation. The sequence of dissolution and subsequent re-crystallization was established to be an extremely effective zeroing mechanism for the TL signal. The linearity in the dose response was also monitored in the case of dissolved and subsequently re-crystallized salt. In the case of naturally occurring salt, zeroing of the TL signal due to dissolution as well as the linearity of dose response up to doses as large as 100 Gy were found to be very promising features for dating applications.

  18. Bayesian statistics

    OpenAIRE

    Draper, D.

    2001-01-01

    © 2012 Springer Science+Business Media, LLC. All rights reserved. Article Outline: Glossary Definition of the Subject and Introduction The Bayesian Statistical Paradigm Three Examples Comparison with the Frequentist Statistical Paradigm Future Directions Bibliography

  19. Usage Statistics

    Science.gov (United States)

    ... www.nlm.nih.gov/medlineplus/usestatistics.html MedlinePlus Statistics To use the sharing features on this page, ... By Quarter View image full size Quarterly User Statistics Quarter Page Views Unique Visitors Oct-Dec-98 ...

  20. The incidence of radioepidermitis and the dose-response relationship in parotid gland cancer patients treated with 125I seed brachytherapy. Incidence of radioepidermitis and the dose-response relationship

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Ming-Hui; Zheng, Lei; Gao, Hong; Zhang, Jie; Liu, Shu-ming; Huang, Ming-wei; Shi, Yan [Peking University School and Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Beijing (China); Zhang, Jian-Guo [Peking University School and Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Beijing (China); Fujian Provincial Hospital, Fujian (China)

    2014-09-09

    We studied the incidence and dose-response relationship of radioepidermitis in parotid gland carcinoma patients treated with [{sup 125}I] seed brachytherapy in the hopes of designing an optimized pre-implant treatment plan that would reduce the incidence and severity of radioepidermitis in patients receiving this therapy. Between January 2007 and May 2010, 100 parotid gland cancer patients were treated postoperatively with [{sup 125}I] seed brachytherapy. The matched peripheral dose (MPD) was 80-140 Gy, and [{sup 125}I] seed activity was 0.7-0.8 mCi. The mean dose delivered to the skin was calculated in the post-implant CT on day 0 following implantation. Grades of acute and late dermatitis were evaluated at 2, 6, 12, and 18 months post-implantation. Most patients experienced grade 0-2 acute and late skin side effects (86 and 97 %, respectively), though a small subset developed severe complications. Most grade 1-3 effects resolved within 6 months of implantation, though some grade 1-3 effects and all grade 4 effects remained unchanged throughout the 18-month follow-up period. Grade 3 and 4 effects were most prominent (75 and 25 %, respectively) with doses of 110-140 Gy; doses higher than 140 Gy produced only grade 4 effects. [{sup 125}I] seed brachytherapy produced acceptable levels of acute and late radioepidermitis with a good clinical outcome. A mean dose under 100 Gy delivered to the skin was safe, though doses of 110-140 Gy should be given with caution and extra monitoring; doses greater than 140 Gy are dangerous and likely to produce grade 4-5 effects. (orig.) [German] Wir untersuchten die Inzidenz und die Dosis-Wirkung-Beziehung bei Patienten mit Ohrspeicheldruesenkrebs, die mit [{sup 125}I]-Seed-Brachytherapie behandelt wurden, in der Hoffnung, eine optimierte praeimplantologische Behandlung zu entwickeln, welche die Inzidenz und Schwere der Radioepidermitis bei Patienten, die diese Therapie erhalten haben, reduziert. Zwischen Januar 2007 und Mai 2010

  1. Library statistics.

    OpenAIRE

    Melita Ambrožič

    1991-01-01

    The contribution deals with the purpose, beginnings and development of library statistics and the strivings for international standardization in this field. International recommendations are presented, as well as the ISO standard for library statistics. An overview is given of the theoretical contributions and statistical practice in Slovenian librarianship. Cautionary notice on the limitations of the applicability of library statistics in determining library performance is given and the inte...

  2. Mathematical statistics

    CERN Document Server

    Pestman, Wiebe R

    2009-01-01

    This textbook provides a broad and solid introduction to mathematical statistics, including the classical subjects hypothesis testing, normal regression analysis, and normal analysis of variance. In addition, non-parametric statistics and vectorial statistics are considered, as well as applications of stochastic analysis in modern statistics, e.g., Kolmogorov-Smirnov testing, smoothing techniques, robustness and density estimation. For students with some elementary mathematical background. With many exercises. Prerequisites from measure theory and linear algebra are presented.

  3. Dose-response curve of EBT, EBT2, and EBT3 radiochromic films to synchrotron-produced monochromatic x-ray beams

    OpenAIRE

    Brown, Thomas A. D.; Hogstrom, Kenneth R; Alvarez, Diane; Matthews II, Kenneth L.; Ham, Kyungmin; Dugas, Joseph P.

    2012-01-01

    This work investigates the dose-response curves of GAFCHROMIC EBT, EBT2, and EBT3 radiochromic films using synchrotron-produced monochromatic x-ray beams. EBT2 film is being utilized for dose verification in photoactivated Auger electron therapy at the Louisiana State University CAMD synchrotron facility. Monochromatic beams of 25, 30, and 35 keV were generated on the tomography beamline at CAMD. Ion chamber depth-dose measurements were used to determine the dose delivered to films irradiated...

  4. Dose-response analysis of infants prenatally exposed to methyl mercury: An application of a single compartment model to single-strand hair analysis

    International Nuclear Information System (INIS)

    A new method of estimating fetal exposure is used in a dose-response analysis of data from the 1971 outbreak of methyl mercury poisoning in rural Iraq. An X-ray fluorescence instrument for the measurement of single strands of human hair was employed to obtain longitudinal profiles recapitulating fetal exposure. Logit and hockey-stick models as well as nonparametric smoothing are used to describe data on delayed development and central nervous system abnormality

  5. Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study.

    OpenAIRE

    Zuckerman, J N; Sabin, C.; Craig, F. M.; Williams, A.; Zuckerman, A J

    1997-01-01

    OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response. DESIGN: Single centre, randomised, double blind, dose-response study. SETTING: Research vaccine evaluation centre at a teaching hospital. SUBJECTS: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a...

  6. Statistical Inference

    CERN Document Server

    Casella, George

    2002-01-01

    "Statistical Inference is a delightfully modern text on statistical theory and deserves serious consideration from every teacher of a graduate- or advanced undergraduate-level first course in statistical theory. . . Chapters 1-5 provide plenty of interesting examples illustrating either the basic concepts of probability or the basic techniques of finding distribution. . . The book has unique features [throughout Chapters 6-12] for example, I have never seen in any comparable text such extensive discussion of ancillary statistics [Ch. 6], including Basu's theorem, dealing with the independence of complete sufficient statistics and ancillary statistics. Basu's theorem is such a useful tool that it should be available to every graduate student of statistics. . . The derivation of the analysis of variance (ANOVA)F test in Chapter 11 via the union-intersection principle is very nice. . . Chapter 12 contains, in addition to the standard regression model, errors-in-variables models. This topic will be of considerabl...

  7. Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

    Directory of Open Access Journals (Sweden)

    Owain Thomas

    Full Text Available Low molecular weight heparins (LMWH's are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa, activated partial thromboplastin time (aPTT and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.To examine the effects of two different LMWH's on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests' concordance.Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR and Hemochron Jr (HCJ and an optical plasma method using two different reagents (ActinFSL and PTT-Automat. Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.Methods' mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11 and 69s (SD 14 for enoxaparin and between 101s (SD 21 and 140s (SD 28 for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62-0.87, whereas the other aPTT methods had similar correlation coefficients (Rs0.80-0.92.aPTT displays a linear dose-response to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa's present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH's.

  8. Dose-response relationship of physical activity to premature and total all-cause and cardiovascular disease mortality in walkers.

    Directory of Open Access Journals (Sweden)

    Paul T Williams

    Full Text Available PURPOSE: To assess the dose-response relationships between cause-specific mortality and exercise energy expenditure in a prospective epidemiological cohort of walkers. METHODS: The sample consisted of the 8,436 male and 33,586 female participants of the National Walkers' Health Study. Walking energy expenditure was calculated in metabolic equivalents (METs, 1 MET = 3.5 ml O2/kg/min, which were used to divide the cohort into four exercise categories: category 1 (≤ 1.07 MET-hours/d, category 2 (1.07 to 1.8 MET-hours/d, category 3 (1.8 to 3.6 MET-hours/d, and category 4 (≥ 3.6 MET-hours/d. Competing risk regression analyses were use to calculate the risk of mortality for categories 2, 3 and 4 relative to category 1. RESULTS: 22.9% of the subjects were in category 1, 16.1% in category 2, 33.3% in category 3, and 27.7% in category 4. There were 2,448 deaths during the 9.6 average years of follow-up. Total mortality was 11.2% lower in category 2 (P = 0.04, 32.4% lower in category 3 (P<10(-12 and 32.9% lower in category 4 (P = 10(-11 than in category 1. For underlying causes of death, the respective risk reductions for categories 2, 3 and 4 were 23.6% (P = 0.008, 35.2% (P<10(-5, and 34.9% (P = 0.0001 for cardiovascular disease mortality; 27.8% (P = 0.18, 20.6% (P = 0.07, and 31.4% (P = 0.009 for ischemic heart disease mortality; and 39.4% (P = 0.18, 63.8% (P = 0.005, and 90.6% (P = 0.002 for diabetes mortality when compared to category 1. For all related mortality (i.e., underlying and contributing causes of death combined, the respective risk reductions for categories 2, 3 and 4 were 18.7% (P = 0.22, 42.5% (P = 0.001, and 57.5% (P = 0.0001 for heart failure; 9.4% (P = 0.56, 44.3% (P = 0.0004, and 33.5% (P = 0.02 for hypertensive diseases; 11.5% (P = 0.38, 41.0% (P<10(-4, and 35.5% (P = 0.001 for dysrhythmias: and 23.2% (P = 0.13, 45.8% (P = 0.0002, and 41.1% (P

  9. A kinetic model incorporating both localized and delocalized recombination: Application to the dependence of the TL dose response on photon energy

    International Nuclear Information System (INIS)

    A conduction band/valence band kinetic model for thermoluminescence (TL) dose response is described which incorporates both localized and delocalized recombination mechanisms. The model is capable of simulating the linear/supralinear behaviour of TL dose response and, as well, the experimentally observed decrease of the supralinearity with decreasing photon energy. These characteristics are observed in the dose response of the various peaks in the glow curve of LiF:Mg,Ti and in other TL materials. In the irradiation stage, the model uses nanodosimetric considerations to describe the electron–hole concentration, ne–h and e-only concentration, ne, filling rates with dose of a spatially correlated trapping center/luminescent center (TC/LC) complex. The linear dose response arises from the dominant role of the geminate/localized recombination at low dose. The supralinearity arises due to the increased relative intensity of delocalized recombination at high dose coupled with a decrease in the efficiency of the competitive processes with increasing dose. The dependence of the supralinearity on photon energy is obtained by adopting different dose-filling-rates of ne–h and ne as a function of photon energy. Specifically, for low dose-levels below ∼1–10 Gy, ne–h/ne is assumed to increase slowly/linearly with dose and to increase slightly with decreasing photon energy below ∼100 keV due to the increasing average ionization density of the electron tracks. For levels of dose above ∼10 Gy, the ratio increases more rapidly in an exponential manner with later entry to maximum values with decreasing photon energy. The demarcation dose of ∼1–10 Gy separating the linear from the exponentially increasing behaviour of ne–h/ne corresponds to the approximate onset of supralinearity observed for composite peak 5 in LiF:Mg,Ti. This assumed behaviour for ne–h/ne is consistent with the structure/size of electron tracks and the onset and relative importance of intra

  10. Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy

    Directory of Open Access Journals (Sweden)

    Sumila Marcin

    2011-07-01

    Full Text Available Abstract Background and Purpose Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors. Since, for radiation protection purposes, the dose span of main interest is between zero and one Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses larger than one Gy are becoming more important for radiotherapy patients. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation induced solid cancer. Materials and methods For various organs and tissues the analysis of cancer induction was extended by an attempted combination of the linear-no-threshold model from the A-bomb survivors in the low dose range and the cancer risk data of patients receiving radiotherapy for Hodgkin's disease in the high dose range. The data were fitted using organ equivalent dose (OED calculated for a group of different dose-response models including a linear model, a model including fractionation, a bell-shaped model and a plateau-dose-response relationship. Results The quality of the applied fits shows that the linear model fits best colon, cervix and skin. All other organs are best fitted by the model including fractionation indicating that the repopulation/repair ability of tissue is neither 0 nor 100% but somewhere in between. Bone and soft tissue sarcoma were fitted well by all the models. In the low dose range beyond 1 Gy sarcoma risk is negligible. For increasing dose, sarcoma risk increases rapidly and reaches a plateau at around 30 Gy. Conclusions In this work OED for various organs was calculated for a linear, a bell-shaped, a plateau and a mixture between a bell-shaped and plateau dose-response relationship for typical treatment plans of Hodgkin's disease patients. The model parameters (α and R were obtained by a fit of the dose-response relationships to these OED data and to the A-bomb survivors. For

  11. Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: a dose-response study.

    Science.gov (United States)

    Pasquali, Renato; Ambrosi, Bruno; Armanini, Decio; Cavagnini, Francesco; Uberti, Ettore Degli; Del Rio, Graziano; de Pergola, Giovanni; Maccario, Mauro; Mantero, Franco; Marugo, Mario; Rotella, Carlo Maria; Vettor, Roberto

    2002-01-01

    There is increasing evidence that the abdominal obesity phenotype may be associated with multiple alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis activity in both sexes. Our hypothesis is that the lack of adequate cortisol suppression after the dexamethasone test may constitute an indirect marker of HPA axis hyperactivity in the presence of the abdominal obesity phenotype. A total of 34 normal-weight (13 men and 21 women) and 87 obese (36 men and 51 women), healthy, nondepressed subjects therefore underwent four different dexamethasone suppression tests randomly performed at varying intervals of at least 1 wk between each test. After a standard overnight 1-mg dexamethasone test, which served as a reference, three other tests were randomly performed at 1-wk intervals by administering 0.0035, 0.0070, and 0.015 mg oral dexamethasone per kilogram of body weight overnight. Blood samples were obtained for cortisol, ACTH, and dexamethasone. Results were analyzed separately in men and women as well as in normal-weight [body mass index (BMI) 25 kg/m(2)) subjects. The waist circumference and the waist to hip ratio (WHR) were used as markers of body fat distribution. After the standard 1-mg test, cortisol suppression was greater than 90% in all subjects. However, after each test, obese women had significantly higher values of percent cortisol and percent ACTH suppression than normal-weight women without any difference between obese and normal-weight men. Considering the response to the three variable-dose tests, a clear dose- response pattern (P < 0.001 for trend analysis) in percent cortisol and percent ACTH suppression was found in all subjects. After each test men had significantly higher dexamethasone levels than women, regardless of BMI. However, obese women, but not men, had significantly higher dexamethasone levels after each test than their normal-weight counterpart. Plasma dexamethasone concentrations were dose related (P < 0.001 for trend

  12. Statistical optics

    CERN Document Server

    Goodman, Joseph W

    2015-01-01

    This book discusses statistical methods that are useful for treating problems in modern optics, and the application of these methods to solving a variety of such problems This book covers a variety of statistical problems in optics, including both theory and applications.  The text covers the necessary background in statistics, statistical properties of light waves of various types, the theory of partial coherence and its applications, imaging with partially coherent light, atmospheric degradations of images, and noise limitations in the detection of light. New topics have been introduced i

  13. Statistical distributions

    CERN Document Server

    Forbes, Catherine; Hastings, Nicholas; Peacock, Brian J.

    2010-01-01

    A new edition of the trusted guide on commonly used statistical distributions Fully updated to reflect the latest developments on the topic, Statistical Distributions, Fourth Edition continues to serve as an authoritative guide on the application of statistical methods to research across various disciplines. The book provides a concise presentation of popular statistical distributions along with the necessary knowledge for their successful use in data modeling and analysis. Following a basic introduction, forty popular distributions are outlined in individual chapters that are complete with re

  14. Statistical methods

    CERN Document Server

    Szulc, Stefan

    1965-01-01

    Statistical Methods provides a discussion of the principles of the organization and technique of research, with emphasis on its application to the problems in social statistics. This book discusses branch statistics, which aims to develop practical ways of collecting and processing numerical data and to adapt general statistical methods to the objectives in a given field.Organized into five parts encompassing 22 chapters, this book begins with an overview of how to organize the collection of such information on individual units, primarily as accomplished by government agencies. This text then

  15. [Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

    Science.gov (United States)

    Koterov, A N; Ushenkova, L N; Biryukov, A P

    2016-01-01

    reduce the strength of associations for RET/PTC in total. On the basis of ordinal scale doses (background, "low" (0.1 Gy), "middle" (0.1-1 Gy) and "large" (1-10 Gy) dose) also found was a significant correlation (Spearman) with the dose for the frequency RET/PTC in total (r = 0.736; p = 0.0098), but for certain types of rearrangements the results were reverse to the previous analysis (the effect was significant only for the RET/PTC3: r = 0.731; p = 0.024). The linear dose-response trends of the Cochrane-Armitage-test for the frequency of RET/PTC in total, RET/PTC1 and RET/PTC3 depending on the dose to the thyroid in the ordinal scale were registered (p, respectively: thyroid radiogenic carcinomas the comprehensive evidence of the dose-effect dependence existence indicating a real relationship between the studied parameters and a radiation factor was obtained for the first time.

  16. Scan Statistics

    CERN Document Server

    Glaz, Joseph

    2009-01-01

    Suitable for graduate students and researchers in applied probability and statistics, as well as for scientists in biology, computer science, pharmaceutical science and medicine, this title brings together a collection of chapters illustrating the depth and diversity of theory, methods and applications in the area of scan statistics.

  17. Modeling the low-LET dose-response of BCR-ABL formation: predicting stem cell numbers from A-bomb data.

    Science.gov (United States)

    Radivoyevitch, T; Hoel, D G

    1999-01-01

    Formation of the BCR-ABL chromosomal translocation t(9;22)(q34;q11) is essential to the genesis of chronic myeloid leukemia (CML). An interest in the dose-response of radiation induced CML therefore leads naturally to an interest in the dose-response of BCR-ABL formation. To predict the BCR-ABL dose-response to low-linear energy transfer (LET) ionizing radiation, three models valid over three different dose ranges are examined: the first for doses greater than 80 Gy, the second for doses less than 5 Gy and the third for doses greater than 2 Gy. The first of the models, due to Holley and Chatterjee, ignores the accidental binary eurejoining of DNA double-strand break (DSB) free ends ('eurejoining' refers to the accidental restitution of DSB free ends with their own proper mates). As a result, the model is valid only in the limit of high doses. The second model is derived directly from cytogenetic data. This model has the attractive feature that it implicitly accounts for single-track effects at low doses. The third model, based on the Sax-Markov binary eurejoining/misrejoining (SMBE) algorithm, does not account for single-track effects and is therefore limited to moderate doses greater than approximately 2 Gy. Comparing the second model to lifetime excess CML risks expected after 1 Gy, estimates of the number of hematopoietic stem cells capable of causing CML were obtained for male and female atomic bomb survivors in Hiroshima and Nagasaki. The stem cell number estimates lie in the range of 5 x 10(7)-3 x 10(8) cells. PMID:10616282

  18. Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

    Directory of Open Access Journals (Sweden)

    A. Ribeiro

    2009-06-01

    Full Text Available The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor® (18:1:1 and administered ip (0.1 mL/10 g body weight; control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg increased (P < 0.05 the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05 after exposing the animals to the open field test.

  19. Dose response and time course studies on superoxide dismutase as a urinary biomarker of carbon tetrachloride-induced hepatic injury in the Hanover Wistar rat.

    Science.gov (United States)

    Smyth, Rosemary; Munday, Michael R; York, Malcolm J; Clarke, Christopher J; Dare, Theo; Turton, John A

    2009-10-01

    Previous studies have shown that the enzyme copper/zinc superoxide dismutase (SOD-1) is increased in the urine of rats with carbon tetrachloride (CCl(4))-induced hepatotoxicity. The present experiments aimed to investigate further the usefulness of urinary SOD-1 as a non-invasive biomarker of liver injury. Two investigations were carried out, a dose response study and a time course study. In the dose response study, rats were given a single dose of CCl(4) at 0 (control), 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 and 0.80 ml/kg and urine samples collected from 12 to 36 h postdosing. In the time course study, rats were dosed at 0.80 ml/kg CCl(4) and urine sampled at 4, 12, 24 and 36 h postdosing. In both studies, the presence of SOD-1 in the urine was confirmed by Western blotting with an SOD-1 antibody. In the dose response study, serum SOD activity was elevated in all CCl(4)-treated animals and urinary SOD-1 activity was increased 2.2 times at the lowest dose (0.10 ml/kg) and 60.4 times at the highest CCl(4) dose level (0.80 ml/kg). In the time course study, urinary SOD-1 was first detected in samples collected from 4 to 12 h postdosing. We conclude that urinary SOD-1 has potential as a sensitive non-invasive biomarker of CCl(4)-induced hepatocellular injury.

  20. SU-D-16A-03: A Radiation Pneumonitis Dose-Response Model Incorporating Non- Local Radiation-Induced Bystander Effect

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J; Snyder, K; Zhong, H; Chetty, I [Henry Ford Health System, Dept. Radiation Oncology, Detroit, MI (United States)

    2014-06-01

    Purpose: Dose-response models that can reliably predict radiation pneumonitis (RP) to guide radiation therapy (RT) for lung cancer presently do not exist. A model is proposed that incorporates non-local radiationinduced bystander effect (RIBE). Methods: A single sigmoid response function, derived from published data for whole lung irradiation, relates RP probability to cumulative lung damage, regardless of fractionation scheme. Lung damage is assumed to be caused by direct local radiation damage, quantified via the linear-quadratic (LQ) model, and RIBE. Based on published data, RIBE is assumed to be activated when per-fraction dose rises above ∼0.6 Gy, but is constant with dose above that threshold. Integral RIBE damage is assumed proportional to lung volume irradiated above ∼0.6 Gy per fraction. Key model parameters include LQ α and β, and two RIBE parameters: the single-fraction probability δ of damage, and a proportionality parameter κ that relates the potential for RIBE damage to irradiated lung volume. All parameters are tentatively fitted from published data, the RIBE parameters from published RP rates for conventionally fractionated RT (CFRT) and stereotactic body RT (SBRT). Results: The model predicts dose-response curves that are consistent with clinical experience. It provides a tentative explanation for why V20 (33 fractions), V13 (20 fractions) and V5 (<10 fractions) are observed to be correlated with RP. It also provides a plausible explanation for the success of SBRT — RIBE damage increases with the number of fractions, so penalizes CFRT relative to SBRT. Conclusion: The proposed model is relatively simple, extrapolates from published data, plausibly explains several clinical observations, and produces dose-response curves that are consistent with clinical experience. While capable of elaboration, its ability to explain doseresponse experience with different fractionation schemes using a small number of assumptions and parameters is an

  1. Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests.

    Science.gov (United States)

    Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Palermo-Neto, J

    2009-06-01

    The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P open field test.

  2. Dose-response relationship of induction kinetics of In vivo DNA damage and repair in mouse leukocytes exposed to gamma radiation

    International Nuclear Information System (INIS)

    The Unicellular electrophoresis in gel technique is a useful tool in the determination of simple ruptures and labile sites to the alkali in DNA of eucariontes cells. The determination of the induction kinetics of damage and repair of DNA can give more information. The objective of this work was to determine whether the analysis of the area under the damage/repair induction kinetics curve in comets percent or the comets frequency in the two peaks of maximum induction is adequate for determining the dose-response relationship. The mice were exposed at the doses of 0.5, 1.0, 2.0 Gy. (Author)

  3. Semiconductor statistics

    CERN Document Server

    Blakemore, J S

    1962-01-01

    Semiconductor Statistics presents statistics aimed at complementing existing books on the relationships between carrier densities and transport effects. The book is divided into two parts. Part I provides introductory material on the electron theory of solids, and then discusses carrier statistics for semiconductors in thermal equilibrium. Of course a solid cannot be in true thermodynamic equilibrium if any electrical current is passed; but when currents are reasonably small the distribution function is but little perturbed, and the carrier distribution for such a """"quasi-equilibrium"""" co

  4. Introductory statistics

    CERN Document Server

    Ross, Sheldon M

    2005-01-01

    In this revised text, master expositor Sheldon Ross has produced a unique work in introductory statistics. The text's main merits are the clarity of presentation, contemporary examples and applications from diverse areas, and an explanation of intuition and ideas behind the statistical methods. To quote from the preface, ""It is only when a student develops a feel or intuition for statistics that she or he is really on the path toward making sense of data."" Ross achieves this goal through a coherent mix of mathematical analysis, intuitive discussions and examples.* Ross's clear writin

  5. Introductory statistics

    CERN Document Server

    Ross, Sheldon M

    2010-01-01

    In this 3rd edition revised text, master expositor Sheldon Ross has produced a unique work in introductory statistics. The text's main merits are the clarity of presentation, contemporary examples and applications from diverse areas, and an explanation of intuition and ideas behind the statistical methods. Concepts are motivated, illustrated and explained in a way that attempts to increase one's intuition. To quote from the preface, ""It is only when a student develops a feel or intuition for statistics that she or he is really on the path toward making sense of data."" Ross achieves this

  6. Statistics Clinic

    Science.gov (United States)

    Feiveson, Alan H.; Foy, Millennia; Ploutz-Snyder, Robert; Fiedler, James

    2014-01-01

    Do you have elevated p-values? Is the data analysis process getting you down? Do you experience anxiety when you need to respond to criticism of statistical methods in your manuscript? You may be suffering from Insufficient Statistical Support Syndrome (ISSS). For symptomatic relief of ISSS, come for a free consultation with JSC biostatisticians at our help desk during the poster sessions at the HRP Investigators Workshop. Get answers to common questions about sample size, missing data, multiple testing, when to trust the results of your analyses and more. Side effects may include sudden loss of statistics anxiety, improved interpretation of your data, and increased confidence in your results.

  7. Statistical physics

    CERN Document Server

    Wannier, Gregory H

    2010-01-01

    Until recently, the field of statistical physics was traditionally taught as three separate subjects: thermodynamics, statistical mechanics, and kinetic theory. This text, a forerunner in its field and now a classic, was the first to recognize the outdated reasons for their separation and to combine the essentials of the three subjects into one unified presentation of thermal physics. It has been widely adopted in graduate and advanced undergraduate courses, and is recommended throughout the field as an indispensable aid to the independent study and research of statistical physics.Designed for

  8. SEER Statistics

    Science.gov (United States)

    The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute works to provide information on cancer statistics in an effort to reduce the burden of cancer among the U.S. population.

  9. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  10. Accident Statistics

    Data.gov (United States)

    Department of Homeland Security — Accident statistics available on the Coast Guard’s website by state, year, and one variable to obtain tables and/or graphs. Data from reports has been loaded for...

  11. CMS Statistics

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Center for Strategic Planning produces an annual CMS Statistics reference booklet that provides a quick reference for summary information about health...

  12. Multiparametric statistics

    CERN Document Server

    Serdobolskii, Vadim Ivanovich

    2007-01-01

    This monograph presents mathematical theory of statistical models described by the essentially large number of unknown parameters, comparable with sample size but can also be much larger. In this meaning, the proposed theory can be called "essentially multiparametric". It is developed on the basis of the Kolmogorov asymptotic approach in which sample size increases along with the number of unknown parameters.This theory opens a way for solution of central problems of multivariate statistics, which up until now have not been solved. Traditional statistical methods based on the idea of an infinite sampling often break down in the solution of real problems, and, dependent on data, can be inefficient, unstable and even not applicable. In this situation, practical statisticians are forced to use various heuristic methods in the hope the will find a satisfactory solution.Mathematical theory developed in this book presents a regular technique for implementing new, more efficient versions of statistical procedures. ...

  13. Statistical Microeconomics

    OpenAIRE

    Baaquie, Belal E.

    2012-01-01

    A statistical generalization is made of microeconomics in the spirit of going from classical to statistical mechanics. The price and quantity of every commodity1 traded in the market, at each instant of time, is considered to be an independent random variable: all prices and quantities are considered to be stochastic processes, with the observed market prices being a random sample of the stochastic prices. The dynamics of market prices is determined by an action functional and, for concretene...

  14. Dose-response curve of EBT, EBT2, and EBT3 radiochromic films to synchrotron-produced monochromatic x-ray beams

    CERN Document Server

    Brown, Thomas A D; Alvarez, Diane; Matthews, Kenneth L; Ham, Kyungmin; Dugas, Joseph P; 10.1118/1.4767770

    2012-01-01

    This work investigates the dose-response curves of GAFCHROMIC EBT, EBT2, and EBT3 radiochromic films using synchrotron-produced monochromatic x-ray beams. EBT2 film is being utilized for dose verification in photoactivated Auger electron therapy at the Louisiana State University CAMD synchrotron facility. Monochromatic beams of 25, 30, and 35 keV were generated on the tomography beamline at CAMD. Ion chamber depth-dose measurements were used to determine the dose delivered to films irradiated at depths from 0.7 to 8.5 cm in a 10x10x10-cm3 PMMA phantom. AAPM TG-61 protocol was applied to convert measured ionization into dose. Films were digitized using an Epson 1680 Professional flatbed scanner and analyzed using the net optical density (NOD) derived from the red channel. A dose-response curve was obtained at 35 keV for EBT film, and at 25, 30, and 35 keV for EBT2 and EBT3 films. Calibrations of films for 4 MV x-rays were obtained for comparison using a radiotherapy accelerator at Mary Bird Perkins Cancer Cent...

  15. Comparison of skin stripping, in vitro release, and skin blanching response methods to measure dose response and similarity of triamcinolone acetonide cream strengths from two manufactured sources.

    Science.gov (United States)

    Pershing, Lynn K; Bakhtian, Shahrzad; Poncelet, Craig E; Corlett, Judy L; Shah, Vinod P

    2002-05-01

    The collective studies compare in vitro drug release, in vivo skin stripping, and skin blanching response methods for dose responsiveness and bioequivalence assessment of triamcinolone acetonide cream products, as a function of application duration, drug concentration, and manufacturer source. Commercially available triamcinolone acetonide creams (0.025%, 0.1%, and 0.5%) from two manufacturers were evaluated in vitro for rate and extent of drug release across synthetic membranes and in vivo for rate, extent, and variability of drug uptake into human stratum corneum and skin blanching response in human forearm skin. Data demonstrate that increasing triamcinolone acetonide cream concentration applied increased the rate and extent of drug released in vitro as well as the extent of drug uptake and skin blanching response in human skin in vivo. No difference (p blanching response methods. Dermatopharmacokinetic analysis of triamcinonide acetonide in vivo is therefore dose responsive to drug concentration applied and application duration and agrees with in vivo skin blanching results. Data support the use of dermatopharmacokinetic methods for bioequivalence and bioavailability assessment of topical drug products.

  16. No evident dose-response relationship between cellular ROS level and its cytotoxicity--a paradoxical issue in ROS-based cancer therapy.

    Science.gov (United States)

    Zhu, Chunpeng; Hu, Wei; Wu, Hao; Hu, Xun

    2014-01-01

    Targeting cancer via ROS-based mechanism has been proposed as a radical therapeutic approach. Cancer cells exhibit higher endogenous oxidative stress than normal cells and pharmacological ROS insults via either enhancing ROS production or inhibiting ROS-scavenging activity can selectively kill cancer cells. In this study, we randomly chose 4 cancer cell lines and primary colon or rectal cancer cells from 4 patients to test the hypothesis and obtained following paradoxical results: while piperlongumin (PL) and β-phenylethyl isothiocyanate (PEITC), 2 well-defined ROS-based anticancer agents, induced an increase of cellular ROS and killed effectively the tested cells, lactic acidosis (LA), a common tumor environmental factor that plays multifaceted roles in promoting cancer progression, induced a much higher ROS level in the tested cancer cells than PL and PEITC, but spared them; L-buthionine sulfoximine (L-BSO, 20 μM) depleted cellular GSH more effectively and increased higher ROS level than PL or PEITC but permitted progressive growth of the tested cancer cells. No evident dose-response relationship between cellular ROS level and cytotoxicity was observed. If ROS is the effecter, it should obey the fundamental therapeutic principle - the dose-response relationship. This is a major concern. PMID:24848642

  17. Summarizing EC50 estimates from multiple dose-response experiments: a comparison of a meta-analysis strategy to a mixed-effects model approach.

    Science.gov (United States)

    Jiang, Xiaoqi; Kopp-Schneider, Annette

    2014-05-01

    Dose-response studies are performed to investigate the potency of a compound. EC50 is the concentration of the compound that gives half-maximal response. Dose-response data are typically evaluated by using a log-logistic model that includes EC50 as one of the model parameters. Often, more than one experiment is carried out to determine the EC50 value for a compound, requiring summarization of EC50 estimates from a series of experiments. In this context, mixed-effects models are designed to estimate the average behavior of EC50 values over all experiments by considering the variabilities within and among experiments simultaneously. However, fitting nonlinear mixed-effects models is more complicated than in a linear situation, and convergence problems are often encountered. An alternative strategy is the application of a meta-analysis approach, which combines EC50 estimates obtained from separate log-logistic model fitting. These two proposed strategies to summarize EC50 estimates from multiple experiments are compared in a simulation study and real data example. We conclude that the meta-analysis strategy is a simple and robust method to summarize EC50 estimates from multiple experiments, especially suited in the case of a small number of experiments.

  18. Statistical mechanics

    CERN Document Server

    Jana, Madhusudan

    2015-01-01

    Statistical mechanics is self sufficient, written in a lucid manner, keeping in mind the exam system of the universities. Need of study this subject and its relation to Thermodynamics is discussed in detail. Starting from Liouville theorem gradually, the Statistical Mechanics is developed thoroughly. All three types of Statistical distribution functions are derived separately with their periphery of applications and limitations. Non-interacting ideal Bose gas and Fermi gas are discussed thoroughly. Properties of Liquid He-II and the corresponding models have been depicted. White dwarfs and condensed matter physics, transport phenomenon - thermal and electrical conductivity, Hall effect, Magneto resistance, viscosity, diffusion, etc. are discussed. Basic understanding of Ising model is given to explain the phase transition. The book ends with a detailed coverage to the method of ensembles (namely Microcanonical, canonical and grand canonical) and their applications. Various numerical and conceptual problems ar...

  19. Statistical mechanics

    CERN Document Server

    Schwabl, Franz

    2006-01-01

    The completely revised new edition of the classical book on Statistical Mechanics covers the basic concepts of equilibrium and non-equilibrium statistical physics. In addition to a deductive approach to equilibrium statistics and thermodynamics based on a single hypothesis - the form of the microcanonical density matrix - this book treats the most important elements of non-equilibrium phenomena. Intermediate calculations are presented in complete detail. Problems at the end of each chapter help students to consolidate their understanding of the material. Beyond the fundamentals, this text demonstrates the breadth of the field and its great variety of applications. Modern areas such as renormalization group theory, percolation, stochastic equations of motion and their applications to critical dynamics, kinetic theories, as well as fundamental considerations of irreversibility, are discussed. The text will be useful for advanced students of physics and other natural sciences; a basic knowledge of quantum mechan...

  20. Statistical mechanics

    CERN Document Server

    Davidson, Norman

    2003-01-01

    Clear and readable, this fine text assists students in achieving a grasp of the techniques and limitations of statistical mechanics. The treatment follows a logical progression from elementary to advanced theories, with careful attention to detail and mathematical development, and is sufficiently rigorous for introductory or intermediate graduate courses.Beginning with a study of the statistical mechanics of ideal gases and other systems of non-interacting particles, the text develops the theory in detail and applies it to the study of chemical equilibrium and the calculation of the thermody

  1. Statistical Physics

    CERN Document Server

    Mandl, Franz

    1988-01-01

    The Manchester Physics Series General Editors: D. J. Sandiford; F. Mandl; A. C. Phillips Department of Physics and Astronomy, University of Manchester Properties of Matter B. H. Flowers and E. Mendoza Optics Second Edition F. G. Smith and J. H. Thomson Statistical Physics Second Edition E. Mandl Electromagnetism Second Edition I. S. Grant and W. R. Phillips Statistics R. J. Barlow Solid State Physics Second Edition J. R. Hook and H. E. Hall Quantum Mechanics F. Mandl Particle Physics Second Edition B. R. Martin and G. Shaw The Physics of Stars Second Edition A. C. Phillips Computing for Scient

  2. Statistical methods

    CERN Document Server

    Freund, Rudolf J; Wilson, William J

    2010-01-01

    Statistical Methods, 3e provides students with a working introduction to statistical methods offering a wide range of applications that emphasize the quantitative skills useful across many academic disciplines. This text takes a classic approach emphasizing concepts and techniques for working out problems and intepreting results. The book includes research projects, real-world case studies, numerous examples and data exercises organized by level of difficulty. This text requires that a student be familiar with algebra. New to this edition: NEW expansion of exercises a

  3. AP statistics

    CERN Document Server

    Levine-Wissing, Robin

    2012-01-01

    All Access for the AP® Statistics Exam Book + Web + Mobile Everything you need to prepare for the Advanced Placement® exam, in a study system built around you! There are many different ways to prepare for an Advanced Placement® exam. What's best for you depends on how much time you have to study and how comfortable you are with the subject matter. To score your highest, you need a system that can be customized to fit you: your schedule, your learning style, and your current level of knowledge. This book, and the online tools that come with it, will help you personalize your AP® Statistics prep

  4. Statistical inference

    CERN Document Server

    Rohatgi, Vijay K

    2003-01-01

    Unified treatment of probability and statistics examines and analyzes the relationship between the two fields, exploring inferential issues. Numerous problems, examples, and diagrams--some with solutions--plus clear-cut, highlighted summaries of results. Advanced undergraduate to graduate level. Contents: 1. Introduction. 2. Probability Model. 3. Probability Distributions. 4. Introduction to Statistical Inference. 5. More on Mathematical Expectation. 6. Some Discrete Models. 7. Some Continuous Models. 8. Functions of Random Variables and Random Vectors. 9. Large-Sample Theory. 10. General Meth

  5. Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study [v2; ref status: indexed, http://f1000r.es/5bj

    Directory of Open Access Journals (Sweden)

    Sreeram V Ramagopalan

    2015-04-01

    Full Text Available Background: We and others have shown a significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. The objectives of this study were to investigate whether changes made to primary outcomes are associated with the likelihood of reporting a statistically significant primary outcome on ClinicalTrials.gov. Methods: A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 20 November 2014 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Findings: 13,238 completed interventional trials were registered with ClinicalTrials.gov that also had study results posted on the website. 2555 (19.3% had one or more statistically significant primary outcomes. Statistical analysis showed that registration year, funding source and primary outcome change after trial completion were associated with reporting a statistically significant primary outcome. Conclusions: Funding source and primary outcome change after trial completion are associated with a statistically significant primary outcome report on clinicaltrials.gov.

  6. Fractional statistic

    OpenAIRE

    Bergère, M. C.

    1999-01-01

    We improve Haldane's formula which gives the number of configurations for $N$ particles on $d$ states in a fractional statistic defined by the coupling $g=l/m$. Although nothing is changed in the thermodynamic limit, the new formula makes sense for finite $N=pm+r$ with $p$ integer and $0

  7. Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose-response curves in mice.

    Science.gov (United States)

    Salama, Raghda A M; El Gayar, Nesreen H; Georgy, Sonia S; Hamza, May

    2016-01-01

    Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose-response curves. This study aims at identifying the equivalent intraperitoneal (i.p.) doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose-response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.). The dose-response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents), the area under the 'change in mechanical threshold'-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations.

  8. A Dose-Response Relationship between Organic Mercury Exposure from Thimerosal-Containing Vaccines and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    David A. Geier

    2014-09-01

    Full Text Available A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg exposure from thimerosal-containing (49.55% Hg by weight vaccines on the risk of neurodevelopmental disorders (NDs. Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991–2000 in the Vaccine Safety Datalink (VSD project. ND cases were diagnosed with pervasive developmental disorder (PDD, specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR = 1.054, specific developmental delay (OR = 1.035, tic disorder (OR = 1.034 and hyperkinetic syndrome of childhood (OR = 1.05 cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis.

  9. Dose response effect of rutin a dietary antioxidant on alcohol-induced prooxidant and antioxidant imbalance - a histopathologic study.

    Science.gov (United States)

    Shenbagam, Madhavan; Nalini, Namasivayam

    2011-08-01

    The present study was designed to investigate the effect of rutin on ethanol-induced hepatotoxicity in a dose-dependent manner in rats. Male albino rats were divided into six groups. Group 1 rats served as control and group 2 rats received rutin 100 mg/kg body weight. Hepatotoxicity was induced in groups 3-6 rats (20% ethanol) for 60 days. In addition, groups 4-6 rats received rutin at doses of 25, 50, 100 mg/kg body weight, respectively for the last 30 days of the experiment. We observed a significant increase in the activities of liver marker enzymes, serum amino transferases, alkaline phosphatase, γ-glutamyl transpeptidase the levels of thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides, and a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione and its related enzymes, vitamins C and E when compared to ethanol-fed rats. Rutin supplementation along with ethanol significantly decreased the levels of liver marker enzymes, lipid peroxidation and significantly elevated the activities of liver SOD, CAT, GSH, glutathione peroxidase, vitamins C and E when compared to untreated ethanol supplemented rats. Among the three doses, 100 mg/kg body weight of rutin was found to exert a more pronounced hepatoprotective effect against ethanol-induced toxicity. Our results were also confirmed by the histopathologic observations. PMID:20727014

  10. Quantifying murine bone marrow and blood radiation dose response following 18F-FDG PET with DNA damage biomarkers

    International Nuclear Information System (INIS)

    Highlights: • Mice received either a range of 18F-FDG activities or whole body X-ray doses. • Blood samples were collected at 24 and 43 h for MN-RET and QPCR analysis. • Regression analysis showed that both types of exposure produced a linear response. • BM doses of 33 mGy (18F-FDG) and 25 mGy X-rays were significantly higher than controls. • No significant difference between internal (18F-FDG) and external (X-ray) was found. - Abstract: The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3–5 mice were randomly assigned to 10 groups, each receiving either a different activity of 18F-FDG: 0–37 MBq or whole body irradiated with corresponding doses of 0–300 mGy X-rays. Blood samples were collected at 24 h and at 43 h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of 18F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43 mGy and above for internal 18F-FDG exposure and to 25 mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P < 0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R2 of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose–responses at 24 h for Bbc3 and Cdkn1 were similar for 18F-FDG and X-ray exposures, with significant modifications occurring for doses over 300 mGy for Bbc3 and at the lower dose of 150 mGy for Cdkn1a. Both

  11. Quantifying murine bone marrow and blood radiation dose response following {sup 18}F-FDG PET with DNA damage biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Manning, Grainne [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom); Taylor, Kristina [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON (Canada); Finnon, Paul [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom); Lemon, Jennifer A.; Boreham, Douglas R. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON (Canada); Badie, Christophe, E-mail: christophe.badie@phe.gov.uk [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom)

    2014-12-15

    Highlights: • Mice received either a range of {sup 18}F-FDG activities or whole body X-ray doses. • Blood samples were collected at 24 and 43 h for MN-RET and QPCR analysis. • Regression analysis showed that both types of exposure produced a linear response. • BM doses of 33 mGy ({sup 18}F-FDG) and 25 mGy X-rays were significantly higher than controls. • No significant difference between internal ({sup 18}F-FDG) and external (X-ray) was found. - Abstract: The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 ({sup 18}F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3–5 mice were randomly assigned to 10 groups, each receiving either a different activity of {sup 18}F-FDG: 0–37 MBq or whole body irradiated with corresponding doses of 0–300 mGy X-rays. Blood samples were collected at 24 h and at 43 h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of {sup 18}F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43 mGy and above for internal {sup 18}F-FDG exposure and to 25 mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P < 0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R{sup 2} of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose–responses at 24 h for Bbc3 and Cdkn1 were similar for {sup 18}F-FDG and X-ray exposures, with significant modifications occurring for doses over 300 mGy for Bbc3

  12. 癫痫患者顺式阿曲库铵的剂量反应曲线测定%The measurement of dose-response curve of cisatracurium in epilepsy patients

    Institute of Scientific and Technical Information of China (English)

    刘中杰; 徐世元; 张庆国; 梁启波; 曾繁荣

    2011-01-01

    Objective To determine the dose-response curve and the ED95 of cisatracurium in epilepsy patients. Methods Forty ASA grade Ⅰ or Ⅱ epilepsy patients were randomly divided into four groups. The dose-response curve was determined by single bolus injection of cisatracurium under midazolam-fentanyl intravenous anesthesia. For each group, the dose of cisatracurium were 20,30, 40 and 50 μg/kg respectively. The neuromuscular block was measured by Neuromuscular Transmission Monitor, and the responses were defined in terms of the percentages of maximum suppression in T1 of TOF of the adductor pollicis muscle. After logprobit transformation of the data of dose and response, the dose-response curve of cisatracurium was then established by linear regression. The onset time of cisatracurium was also recorded. Results The ED50, ED75, ED90 and ED95 of cisatracurium in epilepsy patients were 36.3, 46.1, 57.4 and 65.4 μg/kg. There was no significant change in onset time among 4 groups. Conclusion The ED95 of cisatracurium in epilepsy patients is 65.4 μg/kg, which is about 30.8% higher than that in normal human.%目的 采用单次剂量注射法建立癫痫患者顺式阿曲库铵的剂量反应曲线,确定其量效关系及ED95,为癫痫患者合理应用顺式阿曲库铵提供依据.方法 选取择期癫痫手术患者40例,ASA Ⅰ~Ⅱ级,年龄16岁~42岁,病史3年~26年,均具有服用抗癫痫药物史,术前无酸碱平衡及水电解质紊乱,心肺、肝肾功能正常.患者按随机数字法分为20μg/kg组、30μg/kg组、40 μg/kg组、50μg/kg组共4个剂量组,每组10例.记录拇内收肌四个成串刺激反应中第1次反应最大抑制的百分率,并进行概率单位转换,将顺式阿曲库铵的首次剂量进行对数转换,用直线回归方法建立顺式阿曲库铵的剂量-反应曲线,并记录起效时间.结果 癫痫患者顺式阿曲库铵ED50、ED75、ED90、ED95值分别为36.3、46.1、57.4、65.4μg/kg,起效时间在4个剂

  13. Dose-response study of probiotic bacteria Bifidobacterium animalis subsp lactis BB-12 and Lactobacillus paracasei subsp paracasei CRL-341 in healthy young adults

    DEFF Research Database (Denmark)

    Larsen, C.N.; Nielsen, S.; Kaestel, P.;

    2006-01-01

    was analyzed in the 10(10) CFU/day probiotic and placebo group. Design: The study was designed as a randomized, placebo-controlled, double-blinded, parallel dose-response study. Subjects: Healthy young adults (18 - 40 years) were recruited by advertising in local newspapers. Of the 75 persons enrolled, 71 ( 46...... women, 25 men, mean age 25.6 years ( range 18 - 40 years)) completed the study. Intervention: The volunteers were randomly assigned into five groups receiving either placebo or a mixture of the two probiotics in the concentration of 10(8), 10(9), 10(10) or 10(11) CFU/day in 2 weeks run-in period, 3...

  14. Surveys of radon levels in homes in the United States: A test of the linear-no-threshold dose-response relationship for radiation carcinogenesis

    International Nuclear Information System (INIS)

    The University of Pittsburgh Radon Project for large scale measurements of radon concentrations in homes is described. Its principal research is to test the linear-no threshold dose-response relationship for radiation carcinogenesis by determining average radon levels in the 25 U.S. counties (within certain population ranges) with highest and lowest lung cancer rates. The theory predicts that the former should have about 3 times higher average radon levels than the latter, under the assumption that any correlation between exposure to radon and exposure to other causes of lung cancer is weak. The validity of this assumption is tested with data on average radon level vs replies to items on questionnaires; there is little correlation between radon levels in houses and smoking habits, educational attainment, or economic status of the occupants, or with urban vs rural environs which is an indicator of exposure to air pollution

  15. Efeito dose-resposta de fatores de risco para a doença isquêmica do coração Dose-response effect of risk factors to ischaemic heart disease

    Directory of Open Access Journals (Sweden)

    Suzana Alves de Moraes

    1996-10-01

    factors to ischaemic heart disease (IHD. However few of them have investigated the existence of a linear gradient related to the levels of these exposures and IHD. The effect of different levels of these exposures and IHD after adjusting for known confounders of effect, is assessed. The project was designed as a case-control study and the data were collected over one year from March/93 to February/94. The sample was composed of a total of 833 individuals of both genders aged 30-69 living in the city of S. Paulo, SP (Brazil, 280 of whom were compared with 553 controls (285 neighbourhood controls and 268 hospital controls. Logistic regression was the statistical method wold for the analysis of the data. The results showed a linear gradient for known duration of hypertension and daily number of cigarettes consumed. Although the variables duration of hypercholesterolemia and duration of the habit smoking presented statistically significant odds ratio in the respective strata there was no indication of a linear gradient. Some methodological issues are presented to explain this absence of a linear gradient for known duration of hypercholesterolemia and duration of the smoking habit. It is concluded that the dose response effect detected for known duration of hypertension and daily number of cigarettes consumed were independent of the presence of major risk factors ischaemic heart disease.

  16. Statistical Optics

    Science.gov (United States)

    Goodman, Joseph W.

    2000-07-01

    The Wiley Classics Library consists of selected books that have become recognized classics in their respective fields. With these new unabridged and inexpensive editions, Wiley hopes to extend the life of these important works by making them available to future generations of mathematicians and scientists. Currently available in the Series: T. W. Anderson The Statistical Analysis of Time Series T. S. Arthanari & Yadolah Dodge Mathematical Programming in Statistics Emil Artin Geometric Algebra Norman T. J. Bailey The Elements of Stochastic Processes with Applications to the Natural Sciences Robert G. Bartle The Elements of Integration and Lebesgue Measure George E. P. Box & Norman R. Draper Evolutionary Operation: A Statistical Method for Process Improvement George E. P. Box & George C. Tiao Bayesian Inference in Statistical Analysis R. W. Carter Finite Groups of Lie Type: Conjugacy Classes and Complex Characters R. W. Carter Simple Groups of Lie Type William G. Cochran & Gertrude M. Cox Experimental Designs, Second Edition Richard Courant Differential and Integral Calculus, Volume I RIchard Courant Differential and Integral Calculus, Volume II Richard Courant & D. Hilbert Methods of Mathematical Physics, Volume I Richard Courant & D. Hilbert Methods of Mathematical Physics, Volume II D. R. Cox Planning of Experiments Harold S. M. Coxeter Introduction to Geometry, Second Edition Charles W. Curtis & Irving Reiner Representation Theory of Finite Groups and Associative Algebras Charles W. Curtis & Irving Reiner Methods of Representation Theory with Applications to Finite Groups and Orders, Volume I Charles W. Curtis & Irving Reiner Methods of Representation Theory with Applications to Finite Groups and Orders, Volume II Cuthbert Daniel Fitting Equations to Data: Computer Analysis of Multifactor Data, Second Edition Bruno de Finetti Theory of Probability, Volume I Bruno de Finetti Theory of Probability, Volume 2 W. Edwards Deming Sample Design in Business Research

  17. Experimental statistics

    CERN Document Server

    Natrella, Mary Gibbons

    2005-01-01

    Formulated to assist scientists and engineers engaged in army ordnance research and development programs, this well-known and highly regarded handbook is a ready reference for advanced undergraduate and graduate students as well as for professionals seeking engineering information and quantitative data for designing, developing, constructing, and testing equipment. Topics include characterizing and comparing the measured performance of a material, product, or process; general considerations in planning experiments; statistical techniques for analyzing extreme-value data; use of transformations

  18. Fractal Statistics

    OpenAIRE

    B. G. Sidharth

    2000-01-01

    We consider the recent description of elementary particles in terms of Quantum Mechanical Kerr-Newman Black Holes, a description which provides a rationale for and at the same time reconciles the Bohm-hydrodynamical formulation on the one hand and the Nelsonian stochastiic formulation on the other. The Boson-Fermion divide is discussed, and it is pointed out that in special situations, anomalous statistics, rather than Bose-Einstein or Fermi-Dirac states, can be encountered.

  19. Engineering Statistics

    OpenAIRE

    Vardeman, Stephen B.

    2003-01-01

    In this entry we seek to put into perspective some of the ways in which statistical methods contribute to modern engineering practice. Engineers design and oversee the production, operation, and maintenance of the products and systems that under-gird modern technological society. Their work is built on the foundation of physical (and increasingly biological) science. However, it is of necessity often highly empirical, because there simply isn’t scientific theory complete and simple enough to ...

  20. Cardiovascular effects of indapamide in hypertensive patients with or without renal failure. A dose-response curve.

    Science.gov (United States)

    Leenen, F H; Smith, D L; Farkas, R M; Boer, W H; Reeves, R A; Marquez-Julio, A

    1988-01-29

    Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients--five with normal renal function--were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular end-diastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate the antihypertensive effect of indapamide.