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Sample records for statistically significant dose-response

  1. Statistical and low dose response

    The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem

  2. Lack of Statistical Significance

    Kehle, Thomas J.; Bray, Melissa A.; Chafouleas, Sandra M.; Kawano, Takuji

    2007-01-01

    Criticism has been leveled against the use of statistical significance testing (SST) in many disciplines. However, the field of school psychology has been largely devoid of critiques of SST. Inspection of the primary journals in school psychology indicated numerous examples of SST with nonrandom samples and/or samples of convenience. In this…

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

    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

  4. Statistical Estimation of Dose-response Functions of Respiratory Diseases and Societal Costs of Haze-related Air Pollution in Brunei Darussalam

    Anaman, K. A.; Ibrahim, N.

    - The effects on human health resulting from the January to April 1998 haze-related air pollution episode in Brunei Darussalam were analysed for five groups of diseases of the respiratory system. The analysis concentrated on the statistical estimation of dose-response functions which related the number of cases of respiratory diseases to the level of quality of ambient environment as measured by the pollutants standards index (PSI) and other environmental variables. The total number of cases of the five groups of diseases was shown to be significantly related to PSI and temperature. Societal costs were also estimated. The results showed that societal costs were significantly related to PSI, temperature and relative humidity. Societal costs increased with higher PSI and relative humidity but decreased with increasing temperature.

  5. Statistically significant relational data mining :

    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.

  6. Self-play: statistical significance

    Haworth, Guy McCrossan

    2003-01-01

    Heinz recently completed a comprehensive experiment in self-play using the FRITZ chess engine to establish the ‘decreasing returns’ hypothesis with specific levels of statistical confidence. This note revisits the results and recalculates the confidence levels of this and other hypotheses. These appear to be better than Heinz’ initial analysis suggests.

  7. Statistical issues in radiation dose-response analysis of employees of the nuclear industry in Oak Ridge, Tennessee

    Poisson regression methods are used to describe dose-response relations for cancer mortality for a subcohort of 28,347 white male radiation workers. Age specific baseline rates are described using both internal and external (US white male) rates. Regression analyses are based on an analytic data structure (ADS) that consists of a table of observed deaths, expected deaths, and person-years at risk for each combination of levels of seven risk factors. The factors are socioeconomic status, length of employment, birth cohort, age at risk, facility, internal exposure, and external exposure. Each observation in the ADS consists of the index value of each of the stratifying factors, the observed deaths, the expected deaths, the person-years, and the ten year lagged average cumulative dose. Regression diagnostics show that a linear exponential relative risk model is not appropriate for these data. Results are presented using a main effects model for factors other than external radiation, and an excess relative risk term for cumulative external radiation dose

  8. The thresholds for statistical and clinical significance

    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...... 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...

  9. Assessing statistical significance of periodogram peaks

    Baluev, Roman V.

    2007-01-01

    The least-squares (or Lomb-Scargle) periodogram is a powerful tool which is used routinely in many branches of astronomy to search for periodicities in observational data. The problem of assessing statistical significance of candidate periodicities for different periodograms is considered. Based on results in extreme value theory, improved analytic estimations of false alarm probabilities are given. They include an upper limit to the false alarm probability (or a lower limit to the significan...

  10. Assessing statistical significance of periodogram peaks

    Baluev, Roman V

    2007-01-01

    The least-squares (or Lomb-Scargle) periodogram is a powerful tool which is used routinely in many branches of astronomy to search for periodicities in observational data. The problem of assessing statistical significance of candidate periodicities for different periodograms is considered. Based on results in extreme value theory, improved analytic estimations of false alarm probabilities are given. They include an upper limit to the false alarm probability (or a lower limit to the significance). These estimations are tested numerically in order to establish regions of their practical applicability.

  11. Assessing the statistical significance of periodogram peaks

    Baluev, R. V.

    2008-04-01

    The least-squares (or Lomb-Scargle) periodogram is a powerful tool that is routinely used in many branches of astronomy to search for periodicities in observational data. The problem of assessing the statistical significance of candidate periodicities for a number of periodograms is considered. Based on results in extreme value theory, improved analytic estimations of false alarm probabilities are given. These include an upper limit to the false alarm probability (or a lower limit to the significance). The estimations are tested numerically in order to establish regions of their practical applicability.

  12. Dose-response analysis using R

    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...... a flexible and versatile infrastructure for dose-response analyses in general. The present version of the package, reflecting extensions and modifications over the last decade, provides a user-friendly interface to specify the model assumptions about the dose-response relationship and comes with a...

  13. Social significance of community structure: Statistical view

    Li, Hui-Jia

    2015-01-01

    Community structure analysis is a powerful tool for social networks, which can simplify their topological and functional analysis considerably. However, since community detection methods have random factors and real social networks obtained from complex systems always contain error edges, evaluating the significance of community structure partitioned is an urgent and important question. In this paper, integrating the specific characteristics of real society, we present a novel framework analyzing the significance of social community specially. The dynamics of social interactions are modeled by identifying social leaders and corresponding hierarchical structures. Instead of a direct comparison with the average outcome of a random model, we compute the similarity of a given node with the leader by the number of common neighbors. To determine the membership vector, an efficient community detection algorithm is proposed based on the position of nodes and their corresponding leaders. Then, using log-likelihood sco...

  14. Nonlinearity of dose responses in thermoluminescence dosimetry

    All of dose responses in thermoluminescence (TL) dosimetry can be described by a dose response function derived from statistical Poisson distribution. Two characteristic parameters in this function, one hit factor R and characteristic dose D0, can be used to analyze the nonlinearity of TL responses. The one hit factor R indicates whether there is a linear region in the dose responses, and that the responses are linear-sublinear or linear-supralinear-sublinear. The characteristic dose D0 is used to compare the range of linear region in responses and sensitivity of TLD. When coupling with physical mechanisms in the TL process, the dominant features of the TL nonlinear behavior observed in experiments can be explained. (8 refs., 7 figs., 1 tab.)

  15. Effect size as a supplement to statistical significance testing

    Gašper Cankar; Boštjan Bajec

    2003-01-01

    Researchers in the field of psychology often face the situation that the statistical significance depends largely on the sample size and its statistical power. Effect size is a statistical measure that can offer some solutions for constructive research, since it can overcome the problems that are connected to the sample size. This article presents statistical significance testing we meet in psychology and the usage of smaller group of the effect size measures – measures of the standardi...

  16. A Statistical Significance Simulation Study for the General Scientist

    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...

  17. Statistical significance test for transition matrices of atmospheric Markov chains

    Vautard, Robert; Mo, Kingtse C.; Ghil, Michael

    1990-01-01

    Low-frequency variability of large-scale atmospheric dynamics can be represented schematically by a Markov chain of multiple flow regimes. This Markov chain contains useful information for the long-range forecaster, provided that the statistical significance of the associated transition matrix can be reliably tested. Monte Carlo simulation yields a very reliable significance test for the elements of this matrix. The results of this test agree with previously used empirical formulae when each cluster of maps identified as a distinct flow regime is sufficiently large and when they all contain a comparable number of maps. Monte Carlo simulation provides a more reliable way to test the statistical significance of transitions to and from small clusters. It can determine the most likely transitions, as well as the most unlikely ones, with a prescribed level of statistical significance.

  18. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    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

  19. Caveats for using statistical significance tests in research assessments

    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...

  20. Dose response relationship and Alara

    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

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

    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.

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

    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...

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

    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

  4. Mahalanobis distance and variable selection to optimize dose response

    A battery of statistical techniques are combined to improve detection of low-level dose response. First, Mahalanobis distances are used to classify objects as normal or abnormal. Then the proportion classified abnormal is regressed on dose. Finally, a subset of regressor variables is selected which maximizes the slope of the dose response line. Use of the techniques is illustrated by application to mouse sperm damaged by low doses of x-rays

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

    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

  6. A sample size planning approach that considers both statistical significance and clinical significance

    Jia, Bin; Lynn, Henry S

    2015-01-01

    Background The CONSORT statement requires clinical trials to report confidence intervals, which help to assess the precision and clinical importance of the treatment effect. Conventional sample size calculations for clinical trials, however, only consider issues of statistical significance (that is, significance level and power). Method A more consistent approach is proposed whereby sample size planning also incorporates information on clinical significance as indicated by the boundaries of t...

  7. Systematic reviews of anesthesiologic interventions reported as statistically significant

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

    2015-01-01

    nominally statistically significant meta-analyses of anesthesiologic interventions, we used TSA to estimate power and imprecision in the context of sparse data and repeated updates. METHODS: We conducted a search to identify all systematic reviews with meta-analyses that investigated an intervention that...... updates. RESULTS: From 11,870 titles, we found 682 systematic reviews that investigated anesthesiologic interventions. In the 50 sampled meta-analyses, the median number of trials included was 8 (interquartile range [IQR], 5-14), the median number of participants was 964 (IQR, 523-1736), and the median...

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

    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

  9. Implicit dose-response curves.

    Pérez Millán, Mercedes; Dickenstein, Alicia

    2015-06-01

    We develop tools from computational algebraic geometry for the study of steady state features of autonomous polynomial dynamical systems via elimination of variables. In particular, we obtain nontrivial bounds for the steady state concentration of a given species in biochemical reaction networks with mass-action kinetics. This species is understood as the output of the network and we thus bound the maximal response of the system. The improved bounds give smaller starting boxes to launch numerical methods. We apply our results to the sequential enzymatic network studied in Markevich et al. (J Cell Biol 164(3):353-359, 2004) to find nontrivial upper bounds for the different substrate concentrations at steady state. Our approach does not require any simulation, analytical expression to describe the output in terms of the input, or the absence of multistationarity. Instead, we show how to extract information from effectively computable implicit dose-response curves, with the use of resultants and discriminants. We moreover illustrate in the application to an enzymatic network, the relation between the exact implicit dose-response curve we obtain symbolically and the standard hysteresis diagram provided by a numerical ode solver. The setting and tools we propose could yield many other results adapted to any autonomous polynomial dynamical system, beyond those where it is possible to get explicit expressions. PMID:25008963

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

    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

  11. Statistical significance across multiple optimization models for community partition

    Li, Ju; Li, Hui-Jia; Mao, He-Jin; Chen, Junhua

    2016-05-01

    The study of community structure is an important problem in a wide range of applications, which can help us understand the real network system deeply. However, due to the existence of random factors and error edges in real networks, how to measure the significance of community structure efficiently is a crucial question. In this paper, we present a novel statistical framework computing the significance of community structure across multiple optimization methods. Different from the universal approaches, we calculate the similarity between a given node and its leader and employ the distribution of link tightness to derive the significance score, instead of a direct comparison to a randomized model. Based on the distribution of community tightness, a new “p-value” form significance measure is proposed for community structure analysis. Specially, the well-known approaches and their corresponding quality functions are unified to a novel general formulation, which facilitates in providing a detailed comparison across them. To determine the position of leaders and their corresponding followers, an efficient algorithm is proposed based on the spectral theory. Finally, we apply the significance analysis to some famous benchmark networks and the good performance verified the effectiveness and efficiency of our framework.

  12. Large SDSS quasar groups and their statistical significance

    Park, Changbom; Einasto, Maret; Lietzen, Heidi; Heinamaki, Pekka

    2015-01-01

    We use a volume-limited sample of quasars in the Sloan Digital Sky Survey (SDSS) DR7 quasar catalog to identify quasar groups and address their statistical significance. This quasar sample has a uniform selection function on the sky and nearly a maximum possible contiguous volume that can be drawn from the DR7 catalog. Quasar groups are identified by using the Friend-of-Friend algorithm with a set of fixed comoving linking lengths. We find that the richness distribution of the richest 100 quasar groups or the size distribution of the largest 100 groups are statistically equivalent with those of randomly-distributed points with the same number density and sky coverage when groups are identified with the linking length of 70 h-1Mpc. It is shown that the large-scale structures like the huge Large Quasar Group (U1.27) reported by Clowes et al. (2013) can be found with high probability even if quasars have no physical clustering, and does not challenge the initially homogeneous cosmological models. Our results are...

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

    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...

  14. Clinical and practical importance versus statistical significance: limitations of conventional statistical inference.

    Wilkinson, Mick

    2014-01-01

    Decisions about support for therapies in light of data are made using statistical inference. The dominant approach is null-hypothesis-significance-testing. Applied correctly it provides a procedure for making dichotomous decisions about zero-effect null hypotheses with known and controlled error rates. Type I and type II error rates must be specified in advance and the latter controlled by a priori sample size calculation. This approach does not provide the probability of hypotheses or the st...

  15. Distinguishing between statistical significance and practical/clinical meaningfulness using statistical inference.

    Wilkinson, Mick

    2014-01-01

    Decisions about support for predictions of theories in light of data are made using statistical inference. The dominant approach in sport and exercise science is the Neyman-Pearson significance-testing approach. When applied correctly it provides a reliable procedure for making dichotomous decisions for accepting or rejecting zero-effect null hypotheses with known and controlled long-run error rates. Type I and type II error rates must be specified in advance and the latter controlled by cond...

  16. Statistical controversies in clinical research: statistical significance-too much of a good thing ….

    Buyse, M; Hurvitz, S A; Andre, F; Jiang, Z; Burris, H A; Toi, M; Eiermann, W; Lindsay, M-A; Slamon, D

    2016-05-01

    The use and interpretation of P values is a matter of debate in applied research. We argue that P values are useful as a pragmatic guide to interpret the results of a clinical trial, not as a strict binary boundary that separates real treatment effects from lack thereof. We illustrate our point using the result of BOLERO-1, a randomized, double-blind trial evaluating the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line therapy for HER2+ advanced breast cancer. In this trial, the benefit of everolimus was seen only in the predefined subset of patients with hormone receptor-negative breast cancer at baseline (progression-free survival hazard ratio = 0.66, P = 0.0049). A strict interpretation of this finding, based on complex 'alpha splitting' rules to assess statistical significance, led to the conclusion that the benefit of everolimus was not statistically significant either overall or in the subset. We contend that this interpretation does not do justice to the data, and we argue that the benefit of everolimus in hormone receptor-negative breast cancer is both statistically compelling and clinically relevant. PMID:26861602

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

    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.

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

    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

  19. Dose/response relationships and policy formulation

    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

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

    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…

  1. Outcomes of pharmacological management of nocturia with non-antidiuretic agents: does statistically significant equal clinically significant?

    Smith, Ariana L; Wein, Alan J

    2011-05-01

    To evaluate the statistical and clinical efficacy of the pharmacological treatments of nocturia using non-antidiuretic agents. A literature review of treatments of nocturia specifically addressing the impact of alpha blockers, 5-alpha reductase inhibitors (5ARI) and antimuscarinics on reduction in nocturnal voids. Despite commonly reported statistically significant results, nocturia has shown a poor clinical response to traditional therapies for benign prostatic hyperplasia including alpha blockers and 5ARI. Similarly, nocturia has shown a poor clinical response to traditional therapies for overactive bladder including antimuscarinics. Statistical success has been achieved in some groups with a variety of alpha blockers and antimuscarinic agents, but the clinical significance of these changes is doubtful. It is likely that other types of therapy will need to be employed in order to achieve a clinically significant reduction in nocturia. PMID:21518417

  2. Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: Evidence for the prolonged effects of radiation on the thyroid

    The risk of developing thyroid cancer and other thyroid neoplasms after radiation exposure is well known, but specific modifiers of the dose-response relationship are not. The authors have identified 4,296 subjects who received treatment before their sixteenth birthday with orthovoltage radiation for benign conditions in the head and neck area. Individual thyroid dose estimates were calculated for 3,843 subjects. Of the 2,634 subjects who have been found, 1,043 have developed thyroid nodules of all types, and 309 have developed thyroid cancer. The radiation dose-response relationship was consistent with a linear excess relative risk model for thyroid cancer and thyroid nodules within the range of observed doses. Women developed thyroid cancer and thyroid nodules at a higher rate, but the slopes of the dose-response curves were the same for men and women. Age at radiation exposure was a significant factor of the risk, with a lower age at exposure associated with a higher risk. To determine the effect of the wide publicity and the screening program, which began in 1974, the authors compared the dose-response relationship for cases diagnosed before and after 1974. The overall rates increased dramatically after 1974, but the estimates of the slopes of the dose-response curves were not statistically different. The slope of the dose-response curve for thyroid neoplasms appears to have reached a maximum 25-29 yr after radiation exposure, but the dose response continued to be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr

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

    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

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

    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…

  5. Modeling of dose-response relationships.

    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.

  6. Inhalation Anthrax: Dose Response and Risk Analysis

    Coleman, Margaret E.; Thran, Brandolyn; Morse, Stephen S.; Hugh-Jones, Martin; Massulik, Stacey

    2008-01-01

    The notion that inhalation of a single Bacillus anthracis spore is fatal has become entrenched nearly to the point of urban legend, in part because of incomplete articulation of the scientific basis for microbial risk assessment, particularly dose-response assessment. Risk analysis (ie, risk assessment, risk communication, risk management) necessitates transparency: distinguishing scientific facts, hypotheses, judgments, biases in interpretations, and potential misinformation. The difficulty ...

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

    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

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

    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.

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

    Tornetta Paul; Siegel Judith; Sung Jinsil; Bhandari Mohit

    2008-01-01

    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, Cochr...

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

    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. ...

  11. Statistical Significance Does Not Equal Geological Significance: Reply to Comments on “Lies, Damned Lies, and Statistics (in Geology)”

    Vermeesch, Pieter

    2011-02-01

    In my Eos Forum of 24 November 2009 (90(47), 443), I used the chi-square test to reject the null hypothesis that earthquakes occur independent of the weekday to make the point that statistical significance should not be confused with geological significance. Of the five comments on my article, only the one by Sornette and Pisarenko [2011] disputes this conclusion, while the remaining comments take issue with certain aspects of the geophysical case study. In this reply I will address all of these points, after providing some necessary further background about statistical tests. Two types of error can result from a hypothesis test. A Type I error occurs when a true null hypothesis is erroneously rejected by chance. A Type II error occurs when a false null hypothesis is erroneously accepted by chance. By definition, the p value is the probability, under the null hypothesis, of obtaining a test statistic at least as extreme as the one observed. In other words, the smaller the p value, the lower the probability that a Type I error has been made. In light of the exceedingly small p value of the earthquake data set, Tseng and Chen's [2011] assertion that a Type I error has been committed is clearly wrong. How about Type II errors?

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

    Engsted, Tom

    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...... 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...... of how to obtain 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...

  13. The Utility of Statistical Significance Testing in Psychological and Educational Research: A Review of Recent Literature and Proposed Alternatives.

    Sullivan, Jeremy R.

    2001-01-01

    Summarizes the post-1994 literature in psychology and education regarding statistical significance testing, emphasizing limitations and defenses of statistical testing and alternatives or supplements to statistical significance testing. (SLD)

  14. TESS-based dose-response using pediatric clonidine exposures

    Objective: The toxic and lethal doses of clonidine in children are unclear. This study was designed to determine whether data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) could be utilized to determine a dose-response relationship for pediatric clonidine exposure. Methods: 3458 single-substance clonidine exposures in children <6 years of age reported to TESS from January 2000 through December 2003 were examined. Dose ingested, age, and medical outcome were available for 1550 cases. Respiratory arrest cases (n = 8) were classified as the most severe of the medical outcome categories (Arrest, Major, Moderate, Mild, and No effect). Exposures reported as a 'taste or lick' (n = 51) were included as a dose of 1/10 of the dosage form involved. Dose ranged from 0.4 to 1980 (median 13) μg/kg. Weight was imputed based on a quadratic estimate of weight for age. Dose certainty was coded as exact (26% of cases) or not exact (74%). Medical outcome (response) was examined via logistic regression using SAS JMP (release 5.1). Results: The logistic model describing medical outcome (P < 0.0001) included Log dose/kg (P 0.0000) and Certainty (P = 0.045). Conclusion: TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures

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

    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.

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

    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

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

    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

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

    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.

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

    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.

  20. Non-Linear Dose Response Relationships in Biology, Toxicology, and Medicine (June 8-10, 2004). Final Report

    The conference attracts approximately 500 scientists researching in the area of non-linear low dose effects. These scientists represent a wide range of biological/medical fields and technical disciplines. Observations that biphasic dose responses are frequently reported in each of these areas but that the recognition of similar dose response relationships across disciplines is very rarely appreciated and exploited. By bringing scientist of such diverse backgrounds together who are working on the common area of non-linear dose response relationships this will enhance our understanding of the occurrence, origin, mechanism, significance and practical applications of such dose response relationships

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

    FionaFidler

    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.

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

    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...... 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...

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

    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.

  4. Impact of criticism of null-hypothesis significance testing on statistical reporting practices in conservation biology.

    Fidler, Fiona; Burgman, Mark A; Cumming, Geoff; Buttrose, Robert; Thomason, Neil

    2006-10-01

    Over the last decade, criticisms of null-hypothesis significance testing have grown dramatically, and several alternative practices, such as confidence intervals, information theoretic, and Bayesian methods, have been advocated. Have these calls for change had an impact on the statistical reporting practices in conservation biology? In 2000 and 2001, 92% of sampled articles in Conservation Biology and Biological Conservation reported results of null-hypothesis tests. In 2005 this figure dropped to 78%. There were corresponding increases in the use of confidence intervals, information theoretic, and Bayesian techniques. Of those articles reporting null-hypothesis testing--which still easily constitute the majority--very few report statistical power (8%) and many misinterpret statistical nonsignificance as evidence for no effect (63%). Overall, results of our survey show some improvements in statistical practice, but further efforts are clearly required to move the discipline toward improved practices. PMID:17002771

  5. Bayesian Dose-Response Modeling in Sparse Data

    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

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

    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.

  7. Statistical Significance of the Contribution of Variables to the PCA Solution: An Alternative Permutation Strategy

    Linting, Marielle; van Os, Bart Jan; Meulman, Jacqueline J.

    2011-01-01

    In this paper, the statistical significance of the contribution of variables to the principal components in principal components analysis (PCA) is assessed nonparametrically by the use of permutation tests. We compare a new strategy to a strategy used in previous research consisting of permuting the columns (variables) of a data matrix…

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

    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…

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

    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.

  10. Statistical Significance, Effect Size, and Replication: What Do the Journals Say?

    DeVaney, Thomas A.

    2001-01-01

    Studied the attitudes of representatives of journals in education, sociology, and psychology through an electronic survey completed by 194 journal representatives. Results suggest that the majority of journals do not have written policies concerning the reporting of results from statistical significance testing, and most indicated that statistical…

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

    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...

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

    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…

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

    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…

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

    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.

  15. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  16. Confidence bounds for nonlinear dose-response relationships.

    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

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

    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...

  18. Dose-response in stereotactic irradiation of lung tumors

    The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors (36 NSCLC and 56 metastases) was evaluated. Short course irradiation of 1-8 fractions with different fraction doses was used. After a median follow-up of 14 months (2-85 months) 11 local recurrences were observed with significant advantage for higher doses. When normalization to a biologically effective dose (BED) is used a dose of 94 Gy at the isocenter and 50 Gy at the PTV-margin are demonstrated to give 50% probability of tumor control (TCD50). Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control

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

    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...

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

    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

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

    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

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

    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

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

    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.

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

    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.

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

    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...

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

    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.

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

    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

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

    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.

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

    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

  10. Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose-response

    Purpose: The purpose of this paper is to use the outcome of a dose escalation protocol for three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer to study the dose-response for late rectal toxicity and to identify anatomic, dosimetric, and clinical factors that correlate with late rectal bleeding in multivariate analysis. Methods and Materials: Seven hundred forty-three patients with T1c-T3 prostate cancer were treated with 3D-CRT with prescribed doses of 64.8 to 81.0 Gy. The 5-year actuarial rate of late rectal toxicity was assessed using Kaplan-Meier statistics. A retrospective dosimetric analysis was performed for patients treated to 70.2 Gy (52 patients) or 75.6 Gy (119 patients) who either exhibited late rectal bleeding (RTOG Grade 2/3) within 30 months after treatment (i.e., 70.2 Gy--13 patients, 75.6 Gy--36 patients) or were nonbleeding for at least 30 months (i.e., 70.2 Gy--39 patients, 75.6 Gy--83 patients). Univariate and multivariate logistic regression was performed to correlate late rectal bleeding with several anatomic, dosimetric, and clinical variables. Results: A dose response for ≥ Grade 2 late rectal toxicity was observed. By multivariate analysis, the following factors were significantly correlated with ≥ Grade 2 late rectal bleeding for patients prescribed 70.2 Gy: 1) enclosure of the outer rectal contour by the 50% isodose on the isocenter slice (i.e., Iso50) (p max (p max

  11. Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods

    Jakobsen, Janus Christian; Wetterslev, Jorn; Winkel, Per; Lange, Theis; Gluud, Christian

    2014-01-01

    Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: We propose an eight-step procedure for better validation of meta-analytic results in systematic reviews (1) Obtain the 95% confidence intervals and the P-values from both fixed-effect and random-effects meta-analyses and report the most......BACKGROUND: Thresholds for statistical significance when assessing meta-analysis results are being insufficiently demonstrated by traditional 95% confidence intervals and P-values. Assessment of intervention effects in systematic reviews with meta-analysis deserves greater rigour. METHODS...... proposed eight-step procedure will increase the validity of assessments of intervention effects in systematic reviews of randomised clinical trials....

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

    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

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

    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.

  14. Characterization of a developmental toxicity dose-response model

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

    1989-02-01

    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 developmental evaluations of ethylene glycol, diethylhexyl phthalate, di- and triethylene glycol dimethyl ethers, and nitrofen in rats, mice, or rabbits. Graphic examination and statistical evaluation demonstrate that this model is sensitive to the data when compared to directly measured experimental outcomes. The model was used to interpolate to low-risk dose levels, and comparisons were made between the values obtained and the no-observed-adverse-effect levels (NOAELs) divided by an uncertainty factor. Our investigation suggests that the Rai and Van Ryzin model is sensitive to the developmental toxicity end points, prenatal deaths, and malformations, and appears to model closely their relationship to dose.

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

    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.

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

    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.

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

    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...

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

    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:…

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

    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

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

    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

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

    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

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

    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

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

    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

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

    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 ...

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

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

    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.

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

    Hougaard, Anders; Tfelt-Hansen, Peer

    2015-01-01

    calcitonin-gene related peptide receptor antagonists (telcagepant, MK-3207, BI 44370 TA and BMS-927711) in placebo-controlled trials were reviewed. In addition, dose-response curves for adverse events (AEs) were reviewed. Expert opinion: For most triptans, the dose-response curve for efficacy is flat......, 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....

  8. Evaluation of significantly modified water bodies in Vojvodina by using multivariate statistical techniques

    Vujović Svetlana R.

    2013-01-01

    Full Text Available This paper illustrates the utility of multivariate statistical techniques for analysis and interpretation of water quality data sets and identification of pollution sources/factors with a view to get better information about the water quality and design of monitoring network for effective management of water resources. Multivariate statistical techniques, such as factor analysis (FA/principal component analysis (PCA and cluster analysis (CA, were applied for the evaluation of variations and for the interpretation of a water quality data set of the natural water bodies obtained during 2010 year of monitoring of 13 parameters at 33 different sites. FA/PCA attempts to explain the correlations between the observations in terms of the underlying factors, which are not directly observable. Factor analysis is applied to physico-chemical parameters of natural water bodies with the aim classification and data summation as well as segmentation of heterogeneous data sets into smaller homogeneous subsets. Factor loadings were categorized as strong and moderate corresponding to the absolute loading values of >0.75, 0.75-0.50, respectively. Four principal factors were obtained with Eigenvalues >1 summing more than 78 % of the total variance in the water data sets, which is adequate to give good prior information regarding data structure. Each factor that is significantly related to specific variables represents a different dimension of water quality. The first factor F1 accounting for 28 % of the total variance and represents the hydrochemical dimension of water quality. The second factor F2 accounting for 18% of the total variance and may be taken factor of water eutrophication. The third factor F3 accounting 17 % of the total variance and represents the influence of point sources of pollution on water quality. The fourth factor F4 accounting 13 % of the total variance and may be taken as an ecological dimension of water quality. Cluster analysis (CA is an

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

    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 ...

  10. Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis

    2014-01-01

    Introduction Although previous studies found that cigarette smoking is associated with risk of rheumatoid arthritis (RA), the dose-response relationship remains unclear. This meta-analysis quantitatively summarizes accumulated evidence regarding the association of lifelong exposure to cigarette smoking assessed as pack-years with the risk of RA. Methods Relevant studies were identified by a search of MEDLINE and EMBASE from 1966 to October 2013, with no restrictions. Reference lists from retrieved articles were also reviewed. Studies that reported relative risks (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between pack-years of cigarette smoking and rheumatoid arthritis were included in a dose-response random-effects meta-regression analysis. Results We included 3 prospective cohorts and 7 case-control studies in the meta-analysis. They included a total of 4,552 RA cases. There was no indication of heterogeneity (Pheterogeneity = 0.32) and publication bias did not affect the results. Compared to never smokers, the risk of developing RA increased by 26% (RR = 1.26, 95% CI 1.14 to 1.39) among those who smoked 1 to 10 pack-years and doubled among those with more than 20 pack-years (RR for 21 to 30 pack years = 1.94, 95% CI 1.65 to 2.27). The risk of RA was not increasing further for higher exposure levels (RR for >40 pack-years = 2.07, 95% CI 1.15 to 3.73). The risk of RA was statistically significantly higher among rheumatoid factor (RF)-positive RA cases (RR = 2.47, 95% CI 2.02 to 3.02) compared to RF-negative (RR = 1.58, 95% CI 1.15 to 2.18) when comparing the highest versus lowest category of pack-years for the individual studies. Conclusions Lifelong cigarette smoking was positively associated with the risk of RA even among smokers with a low lifelong exposure. The risk of RA did not further increase with an exposure higher than 20 pack-years. PMID:24594022

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

    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

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

    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

    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. Dose-response aligned circuits in signaling systems.

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

    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

  16. Dose-response relationship with radiotherapy: an evidence?

    The dose-response relationship is a fundamental basis of radiobiology. Despite many clinical data, difficulties remain to demonstrate a relation between dose and local control: relative role of treatment associated with radiation therapy (surgery, chemotherapy, hormonal therapy), tumor heterogeneity, few prospective randomized studies, uncertainty of local control assessment. Three different situations are discussed: tumors with high local control probabilities for which dose effect is demonstrated by randomized studies (breast cancer) or sound retrospective data (soft tissues sarcomas), tumors with intermediate local control probabilities for which dose effect seems to be important according to retrospective studies and ongoing or published phase III trials (prostate cancer), tumors with low local control probabilities for which dose effect appears to be modest beyond standard doses, and inferior to the benefit of concurrent chemotherapy (lung and oesophageal cancer). For head and neck tumors, the dose-response relationship has been explored through hyperfractionation and accelerated radiation therapy and a dose effect has been demonstrated but must be compared to the benefit of concurrent chemotherapy. Last but not least, the development of conformal radiotherapy allow the exploration of the dose response relationship for tumors such as hepatocellular carcinomas traditionally excluded from the field of conventional radiation therapy. In conclusion, the dose-response relationship remains a sound basis of radiation therapy for many tumors and is a parameter to take into account for further randomized studies. (author)

  17. Radiation Dose-Response Relationships and Risk Assessment

    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. Significance and statistical errors in the analysis of DNA microarray data

    Brody, James P.; Williams, Brian A.; Wold, Barbara J.; Quake, Stephen R

    2002-01-01

    DNA microarrays are important devices for high throughput measurements of gene expression, but no rational foundation has been established for understanding the sources of within-chip statistical error. We designed a specialized chip and protocol to investigate the distribution and magnitude of within-chip errors and discovered that, as expected from theoretical expectations, measurement errors follow a Lorentzian-like distribution, which explains the widely observed but unexplained ill-repro...

  19. Dose response curve of 60Co for premature condensed chromosome fragments of human lymphocytes

    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 comparison to the conventional method, the PCC method has many advantages; e.g. it is faster, simpler, more sensitive and accurate. Its significance in the study of radiation damage is also discussed

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

    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.

  1. Similarity criterion analysis of dose-response curves in biological assay and radioimmunoassay of hormones

    The difficulties involved in the control of biological and radioimmunological assay systems, and in the maintenance of standard, as well as, the usual heterogeneity of assayed samples require some evidence of similarity between the dose-response curves obtained with the standard and the sample. Nowadays the parallelism test is used to provide such evidence. However, some indications of non-normal errors distribution, such as the presence of out layers, render the parallelism test both conceptually implausible and statistically inefficient. In such a manner we suggest the non-parametric 'frequencial' test as a more sounding option. (author)

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

    /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

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

    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

  4. Model Averaging Software for Dichotomous Dose Response Risk Estimation

    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.

  5. Statistics

    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

  6. Statistical significance of hair analysis of clenbuterol to discriminate therapeutic use from contamination.

    Krumbholz, Aniko; Anielski, Patricia; Gfrerer, Lena; Graw, Matthias; Geyer, Hans; Schänzer, Wilhelm; Dvorak, Jiri; Thieme, Detlef

    2014-01-01

    Clenbuterol is a well-established β2-agonist, which is prohibited in sports and strictly regulated for use in the livestock industry. During the last few years clenbuterol-positive results in doping controls and in samples from residents or travellers from a high-risk country were suspected to be related the illegal use of clenbuterol for fattening. A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to detect low clenbuterol residues in hair with a detection limit of 0.02 pg/mg. A sub-therapeutic application study and a field study with volunteers, who have a high risk of contamination, were performed. For the application study, a total dosage of 30 µg clenbuterol was applied to 20 healthy volunteers on 5 subsequent days. One month after the beginning of the application, clenbuterol was detected in the proximal hair segment (0-1 cm) in concentrations between 0.43 and 4.76 pg/mg. For the second part, samples of 66 Mexican soccer players were analyzed. In 89% of these volunteers, clenbuterol was detectable in their hair at concentrations between 0.02 and 1.90 pg/mg. A comparison of both parts showed no statistical difference between sub-therapeutic application and contamination. In contrast, discrimination to a typical abuse of clenbuterol is apparently possible. Due to these findings results of real doping control samples can be evaluated. PMID:25388545

  7. A Proposed New "What if Reliability" Analysis for Assessing the Statistical Significance of Bivariate Relationships

    Onwuegbuzie, Anthony J.; Roberts, J. Kyle; Daniel, Larry G.

    2005-01-01

    In this article, the authors (a) illustrate how displaying disattenuated correlation coefficients alongside their unadjusted counterparts will allow researchers to assess the impact of unreliability on bivariate relationships and (b) demonstrate how a proposed new "what if reliability" analysis can complement null hypothesis significance tests of…

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

    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

  9. Dose-response relationship between sleep duration and human psychomotor vigilance and subjective alertness

    Jewett, M. E.; Dijk, D. J.; Kronauer, R. E.; Dinges, D. F.

    1999-01-01

    Although it has been well documented that sleep is required for human performance and alertness to recover from low levels after prolonged periods of wakefulness, it remains unclear whether they increase in a linear or asymptotic manner during sleep. It has been postulated that there is a relation between the rate of improvement in neurobehavioral functioning and rate of decline of slow-wave sleep and/or slow-wave activity (SWS/SWA) during sleep, but this has not been verified. Thus, a cross-study comparison was conducted in which dose-response curves (DRCs) were constructed for Stanford Sleepiness Scale (SSS) and Psychomotor Vigilance Task (PVT) tests taken at 1000 hours by subjects who had been allowed to sleep 0 hours, 2 hours, 5 hours or 8 hours the previous night. We found that the DRCs to each PVT metric improved in a saturating exponential manner, with recovery rates that were similar [time constant (T) approximately 2.14 hours] for all the metrics. This recovery rate was slightly faster than, though not statistically significantly different from, the reported rate of SWS/SWA decline (T approximately 2.7 hours). The DRC to the SSS improved much more slowly than psychomotor vigilance, so that it could be fit equally well by a linear function (slope = -0.26) or a saturating exponential function (T = 9.09 hours). We conclude that although SWS/SWA, subjective alertness, and a wide variety of psychomotor vigilance metrics may all change asymptotically during sleep, it remains to be determined whether the underlying physiologic processes governing their expression are different.

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

    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)

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

    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.

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

    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

  13. Analysis of statistical significance for difference of setup error between staff and new face in radiotherapy

    We verified the setup error (SE) in two persons' radiation therapist's team, which consist of staff and new face. We performed the significance test for SE by the staff group and the new face group. One group consists of four staff therapists with at least 5 to 30 years of experience. The other group consists of new face radiation therapists that have 1 to 1.5 years of experience. Analyzed were 53 patients diagnosed with pelvic cancer (seven patients who underwent 3 dimensional conformal radiation therapy (3DCRT) and 46 patients who underwent intensity modulated radiation therapy (IMRT). Image verification was 1460 times. It was performed through setup verification by cone beam computed tomography (CBCT), and we measured SE of four directions (lateral, long, vertical, 3D). We performed the student's t-test to get the difference of the average error between the staff group and the new face group. The results of significance tests show that there is no difference between SE in the staff group and the new face group in radiotherapy. (author)

  14. Statistics

    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.

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

    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.

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

    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)

  17. Mutans Streptococci Dose Response to Xylitol Chewing Gum

    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...

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

    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

  19. Statistics

    For the year 1999 and 2000, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy Review appear in more detail from the publication Energiatilastot - Energy Statistics issued annually, which also includes historical time series over a longer period (see e.g., Energiatilastot 1998, Statistics Finland, Helsinki 1999, ISSN 0785-3165). The inside of the Review's back cover shows the energy units and the conversion coefficients used for them. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in the volume of GNP and energy consumption, Changes in the volume of GNP and electricity, Coal consumption, Natural gas consumption, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices for heat production, Fuel prices for electricity production, Carbon dioxide emissions, Total energy consumption by source and CO2-emissions, Electricity supply, Energy imports by country of origin in January-March 2000, Energy exports by recipient country in January-March 2000, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Average electricity price by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes and precautionary stock fees on oil products

  20. Maximum likelihood estimation for cytogenetic dose-response curves

    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

  1. Statistics

    For the year 2002, part of the figures shown in the tables of the Energy Review are partly preliminary. The annual statistics of the Energy Review also includes historical time-series over a longer period (see e.g. Energiatilastot 2001, Statistics Finland, Helsinki 2002). The applied energy units and conversion coefficients are shown in the inside back cover of the Review. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in GDP, energy consumption and electricity consumption, Carbon dioxide emissions from fossile fuels use, Coal consumption, Consumption of natural gas, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices in heat production, Fuel prices in electricity production, Price of electricity by type of consumer, Average monthly spot prices at the Nord pool power exchange, Total energy consumption by source and CO2-emissions, Supply and total consumption of electricity GWh, Energy imports by country of origin in January-June 2003, Energy exports by recipient country in January-June 2003, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Price of natural gas by type of consumer, Price of electricity by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Excise taxes, precautionary stock fees on oil pollution fees on energy products

  2. Statistics

    For the year 2003 and 2004, the figures shown in the tables of the Energy Review are partly preliminary. The annual statistics of the Energy Review also includes historical time-series over a longer period (see e.g. Energiatilastot, Statistics Finland, Helsinki 2003, ISSN 0785-3165). The applied energy units and conversion coefficients are shown in the inside back cover of the Review. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in GDP, energy consumption and electricity consumption, Carbon dioxide emissions from fossile fuels use, Coal consumption, Consumption of natural gas, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices in heat production, Fuel prices in electricity production, Price of electricity by type of consumer, Average monthly spot prices at the Nord pool power exchange, Total energy consumption by source and CO2-emissions, Supplies and total consumption of electricity GWh, Energy imports by country of origin in January-March 2004, Energy exports by recipient country in January-March 2004, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Price of natural gas by type of consumer, Price of electricity by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Excise taxes, precautionary stock fees on oil pollution fees

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

    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

  4. Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients

    Coombes Jeff S

    2009-10-01

    Full Text Available Abstract Background Oxidative stress is associated with increased cardiovascular morbidity and mortality particularly in patients with end stage kidney disease. Although observational data from the general population has shown dietary antioxidant intake is associated with reduced cardiovascular morbidity and mortality, most clinical intervention trials have failed to support this relationship. This may be a consequence of not using an effective antioxidant dose and/or not investigating patients with elevated oxidative stress. The SPACE study, conducted in haemodialysis patients, reported that 800 IU/day of alpha tocopherol significantly reduced cardiovascular disease endpoints. A recent time course and dose response study conducted in hypercholesterolaemic patients that found 1600 IU/day of alpha tocopherol was an optimal dose. There is no such dose response data available for haemodialysis patients. Therefore the aim of this study is to investigate the effect of different doses of oral alpha tocopherol on oxidative stress in haemodialysis patients with elevated oxidative stress and the time taken to achieve this effect. Methods The study will consist of a time-course followed by a dose response study. In the time course study 20 haemodialysis patients with elevated oxidative stress will take either 1600 IU/day natural (RRR alpha tocopherol for 20 weeks or placebo. Blood will be collected every two weeks and analysed for a marker of oxidative stress (plasma F2-isoprostanes and alpha tocopherol. The optimum time period to significantly decrease plasma F2-isoprostanes will be determined from this study. In the dose response study 60 patients will be randomised to receive either placebo, 100, 200, 400, 800 or 1600 IU/day of natural (RRR alpha tocopherol for a time period determined from the time course study. Blood will be collected at baseline and every two weeks and analysed for plasma F2-isoprostanes and alpha tocopherol. It is hypothesised that

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

    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)

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

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

    2011-01-01

    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....... 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...... response model developed by J. Hansen and K. Olsen has been implemented in the Monte Carlo code FLUKA, and calculations were compared with experimental results. Results: Calculations of the relative effectiveness deviate less than 5% from the measured values for mono energetic beams. Measured depth...

  7. Proposal of a probabilistic dose-response model

    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)

  8. Detecting multiple periodicities in observational data with the multifrequency periodogram - I. Analytic assessment of the statistical significance

    Baluev, Roman V.

    2013-11-01

    We consider the `multifrequency' periodogram, in which the putative signal is modelled as a sum of two or more sinusoidal harmonics with independent frequencies. It is useful in cases when the data may contain several periodic components, especially when their interaction with each other and with the data sampling patterns might produce misleading results. Although the multifrequency statistic itself was constructed earlier, for example by G. Foster in his CLEANest algorithm, its probabilistic properties (the detection significance levels) are still poorly known and much of what is deemed known is not rigorous. These detection levels are nonetheless important for data analysis. We argue that to prove the simultaneous existence of all n components revealed in a multiperiodic variation, it is mandatory to apply at least 2n - 1 significance tests, among which most involve various multifrequency statistics, and only n tests are single-frequency ones. The main result of this paper is an analytic estimation of the statistical significance of the frequency tuples that the multifrequency periodogram can reveal. Using the theory of extreme values of random fields (the generalized Rice method), we find a useful approximation to the relevant false alarm probability. For the double-frequency periodogram, this approximation is given by the elementary formula (π/16)W2e- zz2, where W denotes the normalized width of the settled frequency range, and z is the observed periodogram maximum. We carried out intensive Monte Carlo simulations to show that the practical quality of this approximation is satisfactory. A similar analytic expression for the general multifrequency periodogram is also given, although with less numerical verification.

  9. The dose-response relationship for UV-tumorigenesis

    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.)

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

    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. 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'

    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....

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

    L. Østvand

    2014-03-01

    Full Text Available 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 70 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 parameters of the null models are estimated from the instrumental record, but are also checked to be consistent with a Northern Hemisphere temperature reconstruction prior to 1750 for which an anthropogenic trend is negligible. The linear trend in the period 1850–2010 AD is significant in all cases, but the oscillatory trend is insignificant for ocean data and barely significant for land data. However, by using the significance of the linear trend to constrain the null hypothesis, the oscillatory trend in the land record appears to be statistically significant. The results suggest that the global land record may be better suited for detection of the global warming signal than the ocean record.

  13. No statistically significant effect of a short-term decrease in the nucleation rate on atmospheric aerosols

    E. M. Dunne

    2012-06-01

    Full Text Available Observed correlations between short-term decreases in cosmic ray ionisation and cloud and aerosol properties have been attributed to short-term decreases in the ion-induced nucleation rate. We use a global aerosol microphysics model to determine whether a 10-day reduction of 15% in the nucleation rate could generate a statistically significant response in aerosol concentrations and optical properties. As an upper limit to the possible effect of changes in the ion-induced nucleation rate, we perturb the total nucleation rate, which has been shown to generate particle concentrations and nucleation events in reasonable agreement with global observations. When measured against a known aerosol control state, the model predicts a 0.15% decrease in global mean cloud condensation nucleus concentrations at the surface. However, taking into account the variability in aerosol, no statistically significant response can be detected in concentrations of particles with diameters larger than 10 nm, in cloud condensation nuclei with diameters larger than 70 nm, or in the Ångström exponent. The results suggest that the observed correlation between short-term decreases in cosmic ray ionisation and cloud and aerosol properties cannot be explained by associated changes in the large-scale nucleation rate.

  14. Detecting multiple periodicities in observational data with the multi-frequency periodogram. I. Analytic assessment of the statistical significance

    Baluev, Roman V

    2013-01-01

    We consider the "multi-frequency" periodogram, in which the putative signal is modelled as a sum of two or more sinusoidal harmonics with idependent frequencies. It is useful in the cases when the data may contain several periodic components, especially when their interaction with each other and with the data sampling patterns might produce misleading results. Although the multi-frequency statistic itself was already constructed, e.g. by G. Foster in his CLEANest algorithm, its probabilistic properties (the detection significance levels) are still poorly known and much of what is deemed known is unrigourous. These detection levels are nonetheless important for the data analysis. We argue that to prove the simultaneous existence of all $n$ components revealed in a multi-periodic variation, it is mandatory to apply at least $2^n-1$ significance tests, among which the most involves various multi-frequency statistics, and only $n$ tests are single-frequency ones. The main result of the paper is an analytic estima...

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

    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.

  16. Application of Dempster-Shafer theory in dose response outcome analysis

    Chen, Wenzhou; Cui, Yunfeng; He, Yanyan; Yu, Yan; Galvin, James; Hussaini, Yousuff M.; Xiao, Ying

    2012-09-01

    The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) reviews summarize the currently available three-dimensional dose/volume/outcome data from multi-institutions and numerous articles to update and refine the normal tissue dose/volume tolerance guidelines. As pointed out in the review, the data have limitations and even some inconsistency. However, with the help of new physical and statistical techniques, the information in the review could be updated so that patient care can be continually improved. The purpose of this work is to demonstrate the application of a mathematical theory, the Dempster-Shafer theory, in dose/volume/outcome data analysis. We applied this theory to the original data obtained from published clinical studies describing dose response for radiation pneumonitis. Belief and plausibility concepts were introduced for dose response evaluation. We were also able to consider the uncertainty and inconsistency of the data from these studies with Yager's combination rule, a special methodology of Dempster-Shafer theory, to fuse the data at several specific doses. The values of belief and plausibility functions were obtained at the corresponding doses. Then we applied the Lyman-Kutcher-Burman (LKB) model to fit these values and a belief-plausibility range was obtained. This range could be considered as a probability range to assist physicians and treatment planners in determining acceptable dose-volume constraints. Finally, the parameters obtained from the LKB model fitting were compared with those in Emami and Burman's papers and those from other frequentist statistics methods. We found that Emami and Burman's parameters are within the belief-plausibility range we calculated by the Dempster-Shafer theory.

  17. Application of Dempster–Shafer theory in dose response outcome analysis

    The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) reviews summarize the currently available three-dimensional dose/volume/outcome data from multi-institutions and numerous articles to update and refine the normal tissue dose/volume tolerance guidelines. As pointed out in the review, the data have limitations and even some inconsistency. However, with the help of new physical and statistical techniques, the information in the review could be updated so that patient care can be continually improved. The purpose of this work is to demonstrate the application of a mathematical theory, the Dempster–Shafer theory, in dose/volume/outcome data analysis. We applied this theory to the original data obtained from published clinical studies describing dose response for radiation pneumonitis. Belief and plausibility concepts were introduced for dose response evaluation. We were also able to consider the uncertainty and inconsistency of the data from these studies with Yager's combination rule, a special methodology of Dempster–Shafer theory, to fuse the data at several specific doses. The values of belief and plausibility functions were obtained at the corresponding doses. Then we applied the Lyman–Kutcher–Burman (LKB) model to fit these values and a belief–plausibility range was obtained. This range could be considered as a probability range to assist physicians and treatment planners in determining acceptable dose–volume constraints. Finally, the parameters obtained from the LKB model fitting were compared with those in Emami and Burman's papers and those from other frequentist statistics methods. We found that Emami and Burman's parameters are within the belief–plausibility range we calculated by the Dempster–Shafer theory. (paper)

  18. Linear dose response curves in fungi and tradescantia

    Tradescantia Clone 02 data suggests that linear non-threshold dose responses are expected to the lowest doses and dose rates of low linear energy transfer (LET) radiation. This is likely to be true for other living organisms even though Clone 02 is radiation sensitive. It is concluded that Clone 02 is partially defective in the RAD 6 pathway for the repair of DNA interstrand cross-links (ISCL) and other loss of coding damage (LCD), based on its cross sensitivities to EMS and ionizing radiation. Tradescantia Clone 02 data showing linear non-threshold induction of somatic genetic events in part reflects the repair deficiency of this Clone. More DNA damage is repaired by recombinational mechanisms in Clone 02 than would occur in a wild-type strain. Two important classes of DNA lesions are induced by ionizing radiation in DNA - double strand breaks (DSB) which are repaired by recombination mechanisms, and loss of coding information damage (LCD), which is repaired by error prone mechanisms but may also be a substrate for recombinational repair. Based on data from yeast, there are two different repair pathways which deal with these differing lesions with different somatic genetic consequences. From yeast, yield cross sections can be derived and applied to DNA damage and repair in Tradescantia. For Clone 02, per lesion, more visible genetic events are scored than in wild-type strains. In a radiation-derived sub-clone, Clone 0106, which is more variable than Clone 02, even more events occur per lesion. This derivative clone, plus breeding experiments, indicate that Clone 02 is heterozygous, or a 'carrier' for a mutant version of a gene in the Tradescantia RAD 6 repair pathway. Clone 02 is, therefore, much like a Fanconi's anemia carrier in a human population, while the Clone 0106 derivative is much like a homozygous Fanconi's anemia patient, with respect to its response to ionizing radiation damage. Two anomalies in its dose response curves for 'pink' loss of

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

    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

  20. Investigating quartz optically stimulated luminescence dose-response curves at high doses

    Lowick, Sally E., E-mail: lowick@geo.unibe.c [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Preusser, Frank [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Wintle, Ann G. [Institute of Geography and Earth Sciences, Aberystwyth University, AberystwythSY23 3DB (United Kingdom)

    2010-10-15

    Despite the general expectation that optically stimulated luminescence (OSL) growth should be described by a simple saturating exponential function, an additional high dose component is often reported in the dose response of quartz. Although often reported as linear, it appears that this response is the early expression of a second saturating exponential. While some studies using equivalent doses that fall in this high dose region have produced ages that correlate well with independent dating, others report that it results in unreliable age determinations. Two fine grain sedimentary quartz samples that display such a response were used to investigate the origin of this additional high dose component: three experiments were conducted to examine their dose-response up to >1000 Gy. The high dose rates provided by laboratory irradiation were found not to induce a sensitivity change in the response to a subsequent test dose, with the latter not being significantly different from those generated following naturally acquired doses. The relative percentage contributions of the fast and medium OSL components remained fixed throughout the dose-response curve, suggesting that the electron traps that give rise to the initial OSL do not change with dose. An attempt was made to investigate a change in luminescence centre recombination probability by monitoring the depletion of the '325 {sup o}C' thermoluminescence (TL) during the optical stimulation that would result in depletion of the OSL signal. The emissions measured through both the conventional ultraviolet (UV), and a longer wavelength violet/blue (VB) window, displayed similar relative growth with dose, although it was not possible to resolve the origin of the VB emissions. No evidence was found to indicate whether the additional component at high doses occurs naturally or is a product of laboratory treatment. However, it appears that these samples display an increased sensitivity of quartz OSL to high doses

  1. Combined Statistical Analyses of Peptide Intensities and Peptide Occurrences Improves Identification of Significant Peptides from MS-based Proteomics Data

    Webb-Robertson, Bobbie-Jo M.; McCue, Lee Ann; Waters, Katrina M.; Matzke, Melissa M.; Jacobs, Jon M.; Metz, Thomas O.; Varnum, Susan M.; Pounds, Joel G.

    2010-11-01

    Liquid chromatography-mass spectrometry-based (LC-MS) proteomics uses peak intensities of proteolytic peptides to infer the differential abundance of peptides/proteins. However, substantial run-to-run variability in peptide intensities and observations (presence/absence) of peptides makes data analysis quite challenging. The missing abundance values in LC-MS proteomics data are difficult to address with traditional imputation-based approaches because the mechanisms by which data are missing are unknown a priori. Data can be missing due to random mechanisms such as experimental error, or non-random mechanisms such as a true biological effect. We present a statistical approach that uses a test of independence known as a G-test to test the null hypothesis of independence between the number of missing values and the experimental groups. We pair the G-test results evaluating independence of missing data (IMD) with a standard analysis of variance (ANOVA) that uses only means and variances computed from the observed data. Each peptide is therefore represented by two statistical confidence metrics, one for qualitative differential observation and one for quantitative differential intensity. We use two simulated and two real LC-MS datasets to demonstrate the robustness and sensitivity of the ANOVA-IMD approach for assigning confidence to peptides with significant differential abundance among experimental groups.

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

    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

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

    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

  4. Mutans Streptococci Dose Response to Xylitol Chewing Gum

    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

  5. Optimal dose-response relationships in voice therapy.

    Roy, Nelson

    2012-10-01

    Like other areas of speech-language pathology, the behavioural management of voice disorders lacks precision regarding optimal dose-response relationships. In voice therapy, dosing can presumably vary from no measurable effect (i.e., no observable benefit or adverse effect), to ideal dose (maximum benefit with no adverse effects), to doses that produce toxic or harmful effects on voice production. Practicing specific vocal exercises will inevitably increase vocal load. At ideal doses, these exercises may be non-toxic and beneficial, while at intermediate or high doses, the same exercises may actually be toxic or damaging to vocal fold tissues. In pharmacology, toxicity is a critical concept, yet it is rarely considered in voice therapy, with little known regarding "effective" concentrations of specific voice therapies vs "toxic" concentrations. The potential for vocal fold tissue damage related to overdosing on specific vocal exercises has been under-studied. In this commentary, the issue of dosing will be explored within the context of voice therapy, with particular emphasis placed on possible "overdosing". PMID:22574765

  6. Nonlinear dose-response relationships and inducible cellular defence mechanisms

    With the inclusion of inducible radioprotective mechanisms in a radiobiological state-vector model it was possible to explain plateaus in dose-response relationships for neoplastic transformation produced by in vitro irradiation of different cell lines with low-LET irradiation at high dose rates. The current study repeated the simulation of one data set that contains a plateau at mid doses. In contrast to earlier studies, the new one did not model the repair of double-strand breaks (DSBs) located in bulk DNA (likely via non-homologous end joining) as being inducible. Repair of specific DSBs located in actively transcribed genes was assumed to occur via homologous recombination and was considered to be inducible. This reduced the number of parameters that have to be determined by fitting the model to data. In addition, all types of radical scavengers were formerly considered to be inducible by radiation. This was redefined in the current work and the effectiveness of scavengers was implemented in a refined way. The current work investigated whether these and other model adjustments lead to an improved fit of the data set. (author)

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

    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...

  8. Optimal designs for dose-response models with restricted design spaces

    Dette, Holger; Biedermann, Stefanie; Zhu, Wei

    2004-01-01

    In dose-response studies, the dose range is often restricted due to concerns over drug toxicity and/or efficacy. We derive optimal designs for estimating the underlying dose-response curve for a restricted or unrestricted dose range with respect to a broad class of optimality criteria. The underlying curve belongs to a diversified set of link functions suitable for the dose response studies and having a common canonical form. These include the fundamental binary response models -- t...

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

    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.

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

    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

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

    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...

  12. Dose-response behavior of the bacterium Vibrio fischeri exposed to pharmaceuticals and personal care products.

    Ortiz de García, Sheyla; García-Encina, Pedro A; Irusta-Mata, Rubén

    2016-01-01

    The presence of pharmaceuticals and personal care products (PPCPs) in the environment has become a real and widespread concern in recent years. Therefore, the primary goal of this study was to investigate 20 common and widely used PPCPs to assess their individual and combined effect on an important species in one trophic level, i.e., bacteria. The ecotoxicological effects of PPCPs at two different concentration ranges were determined in the bacterium Vibrio fischeri using Microtox(®) and were statistically analyzed using three models in the GraphPad Prism 6 program for Windows, v.6.03. A four-parameter model best fit the majority of the compounds. The half maximal effective concentration (EC50) of each PPCP was estimated using the best-fitting model and was compared with the results from a recent study. Comparative analysis indicated that most compounds showed the same level of toxicity. Moreover, the stimulatory effects of PPCPs at environmental concentrations (low doses) were assessed. These results indicated that certain compounds have traditional inverted U- or J-shaped dose-response curves, and 55% of them presented a stimulatory effect below the zero effect-concentration point. Effective concentrations of 0 (EC0), 5 (EC5) and 50% (EC50) were calculated for each PPCP as the ecotoxicological points. All compounds that presented narcosis as a mode of toxic action at high doses also exhibited stimulation at low concentrations. The maximum stimulatory effect of a mixture was higher than the highest stimulatory effect of each individually tested compound. Moreover, when the exposure time was increased, the hormetic effect decreased. Hormesis is being increasingly included in dose-response studies because this may have a harmful, beneficial or indifferent effect in an environment. Despite the results obtained in this research, further investigations need to be conducted to elucidate the behavior of PPCPs in aquatic environments. PMID:26518677

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

    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.

  14. Shared Dosimetry Error in Epidemiological Dose-Response Analyses

    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

  15. Shared Dosimetry Error in Epidemiological Dose-Response Analyses

    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.

  16. Shared dosimetry error in epidemiological dose-response analyses

    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

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

    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.

  18. Development of free statistical software enabling researchers to calculate confidence levels, clinical significance curves and risk-benefit contours

    Confidence levels, clinical significance curves, and risk-benefit contours are tools improving analysis of clinical studies and minimizing misinterpretation of published results, however no software has been available for their calculation. The objective was to develop software to help clinicians utilize these tools. Excel 2000 spreadsheets were designed using only built-in functions, without macros. The workbook was protected and encrypted so that users can modify only input cells. The workbook has 4 spreadsheets for use in studies comparing two patient groups. Sheet 1 comprises instructions and graphic examples for use. Sheet 2 allows the user to input the main study results (e.g. survival rates) into a 2-by-2 table. Confidence intervals (95%), p-value and the confidence level for Treatment A being better than Treatment B are automatically generated. An additional input cell allows the user to determine the confidence associated with a specified level of benefit. For example if the user wishes to know the confidence that Treatment A is at least 10% better than B, 10% is entered. Sheet 2 automatically displays clinical significance curves, graphically illustrating confidence levels for all possible benefits of one treatment over the other. Sheet 3 allows input of toxicity data, and calculates the confidence that one treatment is more toxic than the other. It also determines the confidence that the relative toxicity of the most effective arm does not exceed user-defined tolerability. Sheet 4 automatically calculates risk-benefit contours, displaying the confidence associated with a specified scenario of minimum benefit and maximum risk of one treatment arm over the other. The spreadsheet is freely downloadable at www.ontumor.com/professional/statistics.htm A simple, self-explanatory, freely available spreadsheet calculator was developed using Excel 2000. The incorporated decision-making tools can be used for data analysis and improve the reporting of results of any

  19. Volume and heterogeneity dependence of the dose response relationship for head and neck tumours

    Based on the Poisson statistics of cell kill a model for the response of heterogeneous tumours to non-uniform dose delivery have been developed. The five parameters required to characterize the response are the 50% response dose, D50, the normalized dose-response gradient, γ, the tumour heterogeneity factor, h, the relative volume, y and the extra daily dose required to counteract the tumour cell proliferation, δ. The model has been fitted to data from a number of clinical investigations to allow the derivation of clinically relevant radiation response parameters for head and neck tumours. The D50 value for T2 larynx cancers is 59.9 Gy in 41 days with a relative standard deviation of 2.1 Gy and the γ value is 2.9 with a relative standard deviation of 0.3. The value of δ, which is most consistent with the clinical data for laryngeal tumours, is 0.35 Gy/day and this value should be used if the treatment time is changed from the 41 days normalization. The heterogeneity factor, h, is close to zero for laryngeal tumours which indicates that their response is basically governed by Poisson statistics. Nasopharyngeal tumours, on the other hand, exhibit h values around 0.2 which indicates that these tumours are more heterogeneous in their internal organization and so are their responses to radiation. (orig.)

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

    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.

  1. 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

    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...

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

    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.

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

    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.

  4. Dose-response relationship of neutrons and γ rays to leukemia incidence among atomic bomb survivors in Hiroshima and Nagasaki by type of leukemia, 1950--1971

    The incidence of leukemia during 1950 to 1971 in a fixed mortality sample of atomic bomb survivors in Hiroshima and Nagasaki was analyzed as a function of neutron and γ kerma and marrow doses. Two dose-response models were tested for acute leukemia, chronic granulocytic leukemia, and all types of leukemia, respectively. Each model postulates that the leukemia incidence depends upon the sum of separate risks imposed by γ and neutron doses. In Model I the risk from both types of radiation is assumed to be directly proportional to the respective doses, while Model II assumes that whereas the risk from neutrons is directly proportional to the dose, the risk from γ rays is proportional to dose-squared. The analysis demonstrated that the dose-response of the two types of leukemia differed by type of radiation. The data suggested that the response of acute leukemia was best explained by Model II, while the response of chronic granulocytic leukemia depended almost linearly upon neutron dose alone, because the regression coefficients associated with γ radiation for both Models I and II were not significant. The relative biological effectiveness (RBE) of neutrons in relation to γ rays for incidence of acute leukemia was estimated to be approximately 30/(Dn)/sup 1/2/ [95% confidence limits; 17/(Dn)/sup 1/2/ approx. 54/(Dn)/sup 1/2/] for kerma and 32/(Dn)/sup 1/2/ [95% confidence limits; 18/(Dn)/sup 1/2/ approx. 58/(Dn)/sup 1/2/] for marrow dose (Dn = neutron dose). If acute and chronic granulocytic leukemias are considered together as all types of leukemia, Model II appears to fit the data slightly better than Model I, but neither model is statistically rejected by the data

  5. 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

    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

  6. 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.

    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

  7. 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

    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/.

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

    Bosch, Ernesto; Nyboe Andersen, Anders; Barri, Pedro; García-Velasco, Juan Antonio; de Sutter, Petra; Fernández-Sánchez, Manuel; Visnova, Hana; Klein, Bjarke M; Mannaerts, Bernadette; Arce, Joan-Carles

    2015-01-01

    : Follicular development and endocrine parameters during controlled ovarian stimulation (COS) with rhFSH. RESULTS: Serum FSH levels increased with increasing rhFSH doses and steady-state levels for each dose were similar in both AMH strata. In the whole study population, significant (P < 0·001) positive dose...... responses were observed for the number of follicles ≥12 mm, and serum levels of oestradiol, inhibin B, inhibin A and progesterone at end of stimulation. In comparison with the higher AMH stratum, patients in the lower AMH stratum had significantly different slopes of the dose-response curves for these...

  9. Critical evaluation of a study trying to prove a supralinear dose response relationship for low doses of the Hiroshima- and Nagasaki-data

    In a reappraisal of the data of the Hiroshima and Nagasaki A-bomb survivors, the cancer risk is calculated based on the five lowest dose groups. It is concluded that a linear extrapolation underestimates the cancer risk. Therefore, a supralinear dose response curve is fitted for the lowest dose groups (< 0.6 Sv). This reappraisal has been evaluated by the Ministry of social affairs, health and energy. The evaluation shows that a supralinear dose response relationship is not significant for the lowest dose groups. By restriction to the lowest dose groups, part of the information on the dose response relation is discarded. Including all dose groups, however, does not yield significant supralinearity. (orig.)

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

    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

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

    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

  12. Reproducibilty test of ferrous xylenol orange gel dose response with optical cone beam CT scanning

    Jordan, K.; Battista, J.

    2004-01-01

    Our previous studies of ferrous xylenol orange gelatin gel have revealed a spatial dependence to the dose response of samples contained in 10 cm diameter cylinders. Dose response is defined as change in optical attenuation coefficient divided by the dose (units cm-1 Gy-1). This set of experiments was conducted to determine the reproducibility of our preparation, irradiation and full 3D optical cone beam CT scanning. The data provided an internal check of a larger storage time-dose response dependence study.

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

    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...

  14. Detecting multiple periodicities in observational data with the multi-frequency periodogram. I. Analytic assessment of the statistical significance

    Baluev, Roman V.

    2013-01-01

    We consider the "multi-frequency" periodogram, in which the putative signal is modelled as a sum of two or more sinusoidal harmonics with idependent frequencies. It is useful in the cases when the data may contain several periodic components, especially when their interaction with each other and with the data sampling patterns might produce misleading results. Although the multi-frequency statistic itself was already constructed, e.g. by G. Foster in his CLEANest algorithm, its probabilistic ...

  15. PCBS: CANCER DOSE-RESPONSE ASSESSMENT AND APPLICATION TO ENVIRONMENTAL MIXTURES (1996)

    This report updates the cancer dose-response assessment for polychlorinated biphenyls (PCBs) and shows how information on toxicity, disposition, and environmental processes can be considered together to evaluate health risks from PCB mixtures in the environment. Processes that ch...

  16. CorSig: A General Framework for Estimating Statistical Significance of Correlation and Its Application to Gene Co-Expression Analysis

    Wang, Hong-Qiang; Tsai, Chung-Jui

    2013-01-01

    With the rapid increase of omics data, correlation analysis has become an indispensable tool for inferring meaningful associations from a large number of observations. Pearson correlation coefficient (PCC) and its variants are widely used for such purposes. However, it remains challenging to test whether an observed association is reliable both statistically and biologically. We present here a new method, CorSig, for statistical inference of correlation significance. CorSig is based on a biol...

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

    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

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

    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

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

    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.

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

    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.

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

    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

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

    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...

  3. DNA vaccination of rainbow trout against viral hemorrhagic septicemia virus: A dose-response and time-course study

    Lorenzen, Ellen; Einer-Jensen, Katja; Martinussen, T.; LaPatra, S.E.; Lorenzen, Niels

    2000-01-01

    investigate the potential for protecting fish against VHS by DNA vaccination, experiments were conducted to determine the amount of plasmid DNA needed for induction of protective immunity. The time to onset of immunity and the duration of protection following administration of a protective vaccine dose were...... also analyzed. The dose-response analysis revealed that significant protection of rainbow trout fingerlings was obtained following intramuscular injection of only 0.01 mug of plasmid DNA encoding the VHSV glycoprotein gene. In addition, higher doses of DNA induced immunity to a virus isolate...

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

    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

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

    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.

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

    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

  7. X-Ray energy dependence of the dose response of SIRAD radiation dosimeters

    Cheung, Tsang [City University of Hong Kong, Department of Physics and Materials Science, Kowloon Tong, Hong Kong (China); Butson, Martin J. [City University of Hong Kong, Department of Physics and Materials Science, Kowloon Tong, Hong Kong (China); Illawarra Cancer Care Centre, Department of Medical Physics, Crown St, Wollongong, NSW 2500 (Australia); Centre for Medical Radiation Physics, University of Wollongong, Northfields Ave, Gwyneville 2518, NSW (Australia); E-mail: martin.Butson@sesiahs.health.nsw.gov.au; Yu, Peter K.N. [City University of Hong Kong, Department of Physics and Materials Science, Kowloon Tong, Hong Kong (China)

    2007-07-15

    SIRADs (self-indicating instant radiation alert dosimeters) are designed to measure accident radiation doses. As the energy of radiation is usually unknown in such situations, a detector with a weak energy dependence of its response to dose would be ideal. We have studied the energy dependence of the dose response of SIRADs in the range from 50kVp to 10MV, which corresponds to photon equivalent energies from 25.5keV to 2.2MeV. The response to the same dose at 25.5keV is (29+/-4)%(+/-1s) lower than the response at 1.4MeV. The response to a dose slowly increases with radiation energy. This energy dependence is relatively weak in comparison with the dependence for radiographic films and similar in magnitude to the dependence for lithium fluoride thermoluminescence dosimeters. This energy dependence of the response diminishes the accuracy of dose assessments in radiation fields of unknown energy, but does not significantly compromise the core ability of the devices to provide visual estimates of radiation doses.

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

    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

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

    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

  10. The Importance of Integrating Clinical Relevance and Statistical Significance in the Assessment of Quality of Care –Illustrated Using the Swedish Stroke Register

    Lindmark, Anita; van Rompaye, Bart; Goetghebeur, Els; Glader, Eva-Lotta; Eriksson, Marie

    2016-01-01

    Background When profiling hospital performance, quality inicators are commonly evaluated through hospital-specific adjusted means with confidence intervals. When identifying deviations from a norm, large hospitals can have statistically significant results even for clinically irrelevant deviations while important deviations in small hospitals can remain undiscovered. We have used data from the Swedish Stroke Register (Riksstroke) to illustrate the properties of a benchmarking method that integrates considerations of both clinical relevance and level of statistical significance. Methods The performance measure used was case-mix adjusted risk of death or dependency in activities of daily living within 3 months after stroke. A hospital was labeled as having outlying performance if its case-mix adjusted risk exceeded a benchmark value with a specified statistical confidence level. The benchmark was expressed relative to the population risk and should reflect the clinically relevant deviation that is to be detected. A simulation study based on Riksstroke patient data from 2008–2009 was performed to investigate the effect of the choice of the statistical confidence level and benchmark value on the diagnostic properties of the method. Results Simulations were based on 18,309 patients in 76 hospitals. The widely used setting, comparing 95% confidence intervals to the national average, resulted in low sensitivity (0.252) and high specificity (0.991). There were large variations in sensitivity and specificity for different requirements of statistical confidence. Lowering statistical confidence improved sensitivity with a relatively smaller loss of specificity. Variations due to different benchmark values were smaller, especially for sensitivity. This allows the choice of a clinically relevant benchmark to be driven by clinical factors without major concerns about sufficiently reliable evidence. Conclusions The study emphasizes the importance of combining clinical relevance

  11. Dose-response relationships for female radium dial workers

    Among 1474 women employed in the United States radium dial-painting industry before 1930, there are 61 known cases of bone sarcoma and 21 cases of carcinoma of the paranasal sinuses or the mastoid air cells (''head carcinomas''). The relative effectiveness of 226Ra and 228Ra and dose-incidence relationships were examined for the 759 of these women whose radium body burden has been determined; there are 38 cases of bone sarcoma and 17 cases of head carcinoma in this group. Incidence (I) was expressed as tumor cases per person-year and the dose parameter (D) was the quantity (microcuries) of radium that entered the blood during the period of exposure. To the observed data for each type of tumor were fitted equations that can be formulated from the general form I = (C + alpha dD+ βD2)e-γ/sup D/, where C, the natural incidence for this population, was about 10-5 per person-year. For each equation, the best values of the dose coefficients were found by a least-squares fitting procedure. An equation of the form I = (C + BD2)e-/sup γD/ provided the best fit for the bone sarcomas, when the dose was expressed as microcuries of 226Ra plus 2.5 times microcuries of 228Ra. An acceptable fit to the head carcinoma data was provided by the linear equation I = C + d alpha γ with D equal to microcuries of 226Ra. As a test of bias due to selection of cases with known symptoms of malignancy, the analyses were repeated after removal of all cases for whom radium was determined only after exhumation, and no significant changes in the fitted coefficients were found. The dose-incidence equations obtained when the dose was expressed as average skeletal dose in rad are also given

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

    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

  13. Application of Monte Carlo-based statistical significance determinations to the Beta Cephei stars V400 Car, V401 Car, V403 Car and V405 Car

    Engelbrecht, C. A.; Frescura, F. A. M.; Frank, B. S.

    2009-01-01

    We have used Lomb-Scargle periodogram analysis and Monte Carlo significance tests to detect periodicities above the 3-sigma level in the Beta Cephei stars V400 Car, V401 Car, V403 Car and V405 Car. These methods produce six previously unreported periodicities in the expected frequency range of excited pulsations: one in V400 Car, three in V401 Car, one in V403 Car and one in V405 Car. One of these six frequencies is significant above the 4-sigma level. We provide statistical significances for...

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

    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)

  15. Surgical Results of Symmetric and Asymmetric Surgeries and Dose-Response in Patients with Infantile Esotropia

    Nazife Sefi Yurdakul

    2015-10-01

    Full Text Available Objectives: To evaluate the results of symmetric and asymmetric surgery and responses to surgical amounts in patients with infantile esotropia. Materials and Methods: The records of patients with infantile esotropia who underwent bilateral medial rectus recession (symmetric surgery and unilateral medial rectus recession with lateral rectus resection (asymmetric surgery were analyzed. The results of the cases with symmetric (group 1 and asymmetric (group 2, successful (group 3 and failed (group 4 surgeries were compared, and responses to the amount of surgery were investigated. Results: There were no significant differences between group 1 (n=71 and group 2 (n=13 cases in terms of gender, refraction, preoperative distance deviation, anisometropia and postoperative deviation angles, binocular vision, surgical success or follow-up period (p>0.05. The rate of amblyopia, near deviation and amount of surgery were higher in group 2 cases (p0.05. The average postoperative follow-up period was 15.41±19.93 months (range, 6-98 months in group 3 cases and 40.45±40.06 months (range, 6-143 months in group 4 cases (p=0.000. No significant difference was detected in the amount of deviation corrected per 1 mm of surgical procedure between the successful cases in the symmetric and asymmetric groups (p>0.05. Conclusion: Symmetric or asymmetric surgery may be preferable in patients with infantile esotropia according to the clinical features. It is necessary for every clinic to review its own dose-response results. (Turk J Ophthalmol 2015; 45: 197-202

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

    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

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

    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

  18. Multi-spectral detection of statistically significant components in pre-seismic electromagnetic emissions related with Athens 1999, M = 5.9 earthquake

    Kalimeris, A.; Potirakis, S. M.; Eftaxias, K.; Antonopoulos, G.; Kopanas, J.; Nomikos, C.

    2016-05-01

    A multi-spectral analysis of the kHz electromagnetic time series associated with Athens' earthquake (M = 5.9, 7 September 1999) is presented here, that results to the reliable discrimination of the fracto-electromagnetic emissions from the natural geo-electromagnetic field background. Five spectral analysis methods are utilized in order to resolve the statistically significant variability modes of the studied dynamical system out of a red noise background (the revised Multi-Taper Method, the Singular Spectrum Analysis, and the Wavelet Analysis among them). The performed analysis reveals the existence of three distinct epochs in the time series for the period before the earthquake, a "quiet", a "transitional" and an "active" epoch. Towards the end of the active epoch, during a sub-period which is approximately starting two days before the earthquake, the dynamical system passes into a high activity state, where electromagnetic signal emissions become powerful and statistically significant almost in all time-scales. The temporal behavior of the studied system in each one of these epochs is further searched through mathematical reconstruction in the time domain of those spectral features that were found to be statistically significant. The transition of the system from the quiet to the active state proved to be detectable first in the long time-scales and afterwards in the short scales. Finally, a Hurst exponent analysis revealed persistent characteristics embedded in the two strong EM bursts observed during the "active" epoch.

  19. Longitudinal evaluation of dose-response relationships for environmental exposures and pulmonary function in swine production workers.

    Reynolds, S J; Donham, K J; Whitten, P; Merchant, J A; Burmeister, L F; Popendorf, W J

    1996-01-01

    Studies describing respiratory health hazards for workers in swine production facilities have been published in the United States, Sweden, Canada, the Netherlands, and Denmark. Up to 50% of these workers experience bronchitis, organic dust toxic syndrome, hyper-reactive airways disease, chronic mucous membrane irritation, and other respiratory effects. These studies clearly point to the fact that this occupational environment poses a significant health risk hazard, and that control methods are needed to protect the worker. Before precise control strategies can be developed, implemented, and evaluated, dose-response studies are required to determine acceptable target levels for exposure. A previous manuscript described the development of multiple regression equations characterizing the relationships between environmental exposures and pulmonary response in a cohort of 207 swine producers. Baseline pulmonary function was included as a significant predictor of cross-shift decrements in pulmonary function in addition to personal measurements of dust, endotoxin, and ammonia concentrations. These equations were then used to predict specific exposure levels of dust and ammonia that could be expected to elicit significant decrements in cross-shift pulmonary function. This paper presents the results from analysis of follow-up data obtained on this same cohort 2 years after the initial measurements. At the second measurement period of the study (time-2), swine workers were found to have a mean cross-shift decrease in FEV1 of 2%. Cross-shift change in FEV1 was significantly correlated with personal exposures to total dust, total endotoxin, respirable endotoxin, and ammonia. The magnitude of the decrease in FEV1 was associated with increasing airborne concentrations of these environmental parameters thus confirming the dose-response relationship observed in the initial study (time-1). The correlation of dust with FEV1 changes in workers with more than 6 years of exposure (time

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

    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

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

    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…

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

    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

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

    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

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

    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…

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

    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...

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

    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

  7. Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

    Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

    2016-07-01

    Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration. PMID:26717881

  8. Dose-response relationship between sports activity and musculoskeletal pain in adolescents.

    Kamada, Masamitsu; Abe, Takafumi; Kitayuguchi, Jun; Imamura, Fumiaki; Lee, I-Min; Kadowaki, Masaru; Sawada, Susumu S; Miyachi, Motohiko; Matsui, Yuzuru; Uchio, Yuji

    2016-06-01

    Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose-response relationship between sports activity and MSP among adolescents. Two school-based serial surveys were conducted 1 year apart in adolescents aged 12 to 18 years in Unnan, Japan. Self-administered questionnaires were completed by 2403 students. Associations between time spent in organized sports activity and MSP were analyzed cross-sectionally (n = 2403) and longitudinally (n = 374, students free of pain and in seventh or 10th grade at baseline) with repeated-measures Poisson regression and restricted cubic splines, with adjustment for potential confounders. The prevalence of overall pain, defined as having pain recently at least several times a week in at least one part of the body, was 27.4%. In the cross-sectional analysis, sports activity was significantly associated with pain prevalence. Each additional 1 h/wk of sports activity was associated with a 3% higher probability of having pain (prevalence ratio = 1.03, 95% confidence interval = 1.02-1.04). Similar trends were found across causes (traumatic and nontraumatic pain) and anatomic locations (upper limbs, lower back, and lower limbs). In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P adolescents played sports, the more likely they were to have and develop pain. PMID:26894915

  9. Intracoronary irradiation: dose response for the prevention of restenosis in swine

    Purpose: Restenosis after percutaneous transluminal coronary angioplasty represents, in part, a proliferative response of vascular smooth muscle at the site of injury. We have previously shown that high-dose radiation (20 Gy), delivered via an intracoronary 192Ir source, causes focal medial fibrosis and markedly impairs the restenosis process after balloon angioplasty in swine. This study sought to delineate the dose-response characteristics of this effect. Methods and Materials: Forty juvenile swine underwent coronary angiography; a segment of the left coronary artery was chosen as a target for balloon injury. In 30 swine, a 2 cm ribbon of 192Ir was positioned at the target segment and 20, 15, or 10 Gy were delivered to the vessel wall (10 animals/dose). Subsequently, overdilatation balloon angioplasty was performed at the irradiated segment. In 10 control swine, overdilatation balloon angioplasty was performed without previous irradiation. Thirty-eight animals survived until sacrifice at 30 ± 3 days. Histopathological analysis was performed by a pathologist in a blinded manner. The area of maximal luminal compromise within the target segment was analyzed via computer-assisted planimetry. Results: Neointimal area was decreased by 71.4% at 20 Gy and by 58.3% at 15 Gy compared with control animals (p < 0.05 for both). A stimulatory effect on smooth muscle cell proliferation was noted at 10 Gy, with a 123% increase in neointimal area compared with controls (p < 0.05). Mean percent area stenosis was also reduced by 63% at 20 Gy and by 74.8% at 15 Gy compared with controls (p < 0.05 for both). Conclusions: Intracoronary irradiation prior to overstretch balloon angioplasty markedly reduces neointima formation; this effect is dose dependent, with evidence of a significant stimulatory effect at 10 Gy. The effective therapeutic dose range for the prevention of restenosis in this model begins at approximately 15 Gy delivered to the vessel wall

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

    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

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

    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.

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

    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.

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

    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

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

    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

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

    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

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

    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.

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

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

    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

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

    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, 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. However, the jump

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

    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

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

    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

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

    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.

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

    Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10-4moldm-3 and xylenol orange with 2.5x10-1moldm-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%

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

    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......-4-(trifluoromethyl)phenoxy-phenol) with ranges of representative slopes at 50% response (0.54-2.62) and EC50s (2.20-357 mg/L) were selected. Reference EC50s and EC10s with 95% confidence limits using probit or Weibull models are calculated by nonlinear regression on the whole dataset using a dose - response...

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

    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%.

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

    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

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

    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

  8. STATISTICAL ESTIMATION OF CONTINUITY OF FORMATION OF SOCIALLY SIGNIFICANT HIERARCHY OF MOTIVES OF THE LEARNING OF SENIOR PUPILS BY MEANS OF MULTIMEDIA TECHNOLOGY OF TRAINING

    Marina Yepifanova

    2012-01-01

    Full Text Available It is theoretically proved and experimentally possibility of maintenance of continuity of formation of socially significant hierarchy of motives of the learning of senior pupils by means of multimedia technology proves to be true at training to the physicist.The pedagogical category of continuity as one of important didactic principles is discussed. On the basis of the wide pedagogical experiment which has captured a number of educational institutions, efficiency of multimedia technology is shown at formation of hierarchy of motives of the learning of the schoolboys, having socially significant orientation.Introduction possibility in pedagogical researches of modern statistical measures of estimation is discussed and their efficiency with reference to a problem of continuity of formation of motives of the learning of senior pupils is shown.

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

    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)

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

    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.

  11. Dose-response data for X-ray induced translocations in spermatogonia of rhesus monkeys

    The yields of translocations in spermatocytes after irradiation of spermatogonia of Rhesus monkeys with doses of 100, 220, or 300 rad X-rays were low and consistent with a humped dose-response curve with a peak at about 200 rad. Such a curve would agree well with earlier results on the marmoset and man, but the yields at any dose in the Rhesus monkey were lower

  12. Dose response severity functions for acoustic disturbance in cetaceans using recurrent event survival analysis

    Harris, C. M.; Sadykova, D.; DeRuiter, S.L.; Tyack, P. L.; Miller, P.J.O.; Kvadsheim, P. H.; Lam, F.P.A.; L. Thomas

    2015-01-01

    Behavioral response studies (BRSs) aim to enhance our understanding of the behavior changes made by animals in response to specific exposure levels of different stimuli, often presented in an increasing dosage. Here, we focus on BRSs that aim to understand behavioral responses of free-ranging whales and dolphins to manmade acoustic signals (although the methods are applicable more generally). One desired outcome of these studies is dose-response functions relevant to different species, signal...

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

    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...

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

    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...

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

    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

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

    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...

  17. Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses

    Liu, Li; An, Min; Johnson, Ian R.; Lovett, John V.

    2003-01-01

    Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the alleloc...

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

    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...

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

    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...

  20. Polymer gel dosimetry. The dose response for X-ray irradiation

    Polymer gel dosimetry has been considered a promising technique for clinical use, but this potential has not yet been fully realized in Japan. One reason may be because the commercialized gel detector, BANGTM gel, is expensive and it is only produced abroad. A second reason is the difficulty of controlling dose sensitivity of the gel so that it is stable under ordinary clinical conditions. In this work we introduce two types of gel detectors (MAG and PAG) which we produced in-house. First the method of fabrication of gel is presented in detail, then the dose responses of MAG and PAG for X-ray irradiation are evaluating for MRI and X-ray CT scanning. The MAG-type gel is useful in low contrast dosimetry because of the high sensitivity in its dose response (R2). The PAG-type gel is effective for dosimetry in multiple field irradiations because its dose response (CT value) has reproducibility independent of the different irradiation conditions. Finally, we summarize the potential for clinical use of polymer gel dosimetry with these gel detectors. (author)

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

    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.)

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

    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)

  3. CorSig: a general framework for estimating statistical significance of correlation and its application to gene co-expression analysis.

    Hong-Qiang Wang

    Full Text Available With the rapid increase of omics data, correlation analysis has become an indispensable tool for inferring meaningful associations from a large number of observations. Pearson correlation coefficient (PCC and its variants are widely used for such purposes. However, it remains challenging to test whether an observed association is reliable both statistically and biologically. We present here a new method, CorSig, for statistical inference of correlation significance. CorSig is based on a biology-informed null hypothesis, i.e., testing whether the true PCC (ρ between two variables is statistically larger than a user-specified PCC cutoff (τ, as opposed to the simple null hypothesis of ρ = 0 in existing methods, i.e., testing whether an association can be declared without a threshold. CorSig incorporates Fisher's Z transformation of the observed PCC (r, which facilitates use of standard techniques for p-value computation and multiple testing corrections. We compared CorSig against two methods: one uses a minimum PCC cutoff while the other (Zhu's procedure controls correlation strength and statistical significance in two discrete steps. CorSig consistently outperformed these methods in various simulation data scenarios by balancing between false positives and false negatives. When tested on real-world Populus microarray data, CorSig effectively identified co-expressed genes in the flavonoid pathway, and discriminated between closely related gene family members for their differential association with flavonoid and lignin pathways. The p-values obtained by CorSig can be used as a stand-alone parameter for stratification of co-expressed genes according to their correlation strength in lieu of an arbitrary cutoff. CorSig requires one single tunable parameter, and can be readily extended to other correlation measures. Thus, CorSig should be useful for a wide range of applications, particularly for network analysis of high-dimensional genomic data.A web

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

    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

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

    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

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

    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

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

    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.

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

    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)

  9. 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

    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.

  10. Dose response of ferrous-xylenol orange gels: the effects of gel substrate, gelation time and dose fractionation

    Jordan, K.; Battista, J.

    2004-01-01

    Investigations of the dose dependent change in optical transmission, dose response, for radiochromic ferrous-xylenol orange-gelatin gels (FXG) 3D optical CT scanning has revealed that gelation time, temperature, and dose fractionation affect the dose response (Δμ/Δdose). Correction for these factors is important for developing a reproducible dosimeter that can be reliably calibrated and used clinically. The purpose of this report is to examine trends in dose response changes for the following parameters: gelation time-temperature, concentrations of ferrous ion and xylenol orange (XO), dose range and dose fractionation.

  11. Dose-response curve of a microfluidic magnetic bead-based surface coverage sandwich assay.

    Cornaglia, Matteo; Trouillon, Raphaël; Tekin, H Cumhur; Lehnert, Thomas; Gijs, Martin A M

    2015-09-25

    Magnetic micro- and nanoparticles ('magnetic beads') have been used to advantage in many microfluidic devices for sensitive antigen (Ag) detection. Today, assays that use as read-out of the signal the number count of immobilized beads on a surface for quantification of a sample's analyte concentration have been among the most sensitive and have allowed protein detection lower than the fgmL(-1) concentration range. Recently, we have proposed in this category a magnetic bead surface coverage assay (Tekin et al., 2013 [1]), in which 'large' (2.8μm) antibody (Ab)-functionalized magnetic beads captured their Ag from a serum and these Ag-carrying beads were subsequently exposed to a surface pattern of fixed 'small' (1.0μm) Ab-coated magnetic beads. When the system was exposed to a magnetic induction field, the magnet dipole attractive interactions between the two bead types were used as a handle to approach both bead surfaces and assist with Ag-Ab immunocomplex formation, while unspecific binding (in absence of an Ag) of a large bead was reduced by exploiting viscous drag flow. The dose-response curve of this type of assay had two remarkable features: (i) its ability to detect an output signal (i.e. bead number count) for very low Ag concentrations, and (ii) an output signal of the assay that was non-linear with respect to Ag concentration. We explain here the observed dose-response curves and show that the type of interactions and the concept of our assay are in favour of detecting the lowest analyte concentrations (where typically either zero or one Ag is carried per large bead), while higher concentrations are less efficiently detected. We propose a random walk process for the Ag-carrying bead over the magnetic landscape of small beads and this model description explains the enhanced overall capture probability of this assay and its particular non-linear dose response curves. PMID:25817550

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

    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)

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

    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

  14. Dose response curve of the unsterilized products and the survival on the products

    Using the microbial radiation resistance distribution given by AAMI, the unsterilized fraction of the products was calculated at various bioburden levels, and the results obtained were shown in the dose response curves. With increasing microbical bioburden, the shoulder of the curves is becoming more remarkable. The appearance of the curves is resembled to that of multi-targets survival curves, and this fact can be realized from the analogy that the microbes on the products are to be the targets and the products are to be the cells in the target theory. (author)

  15. Dose response curve of the unsterilized products and the survival on the products

    Oka, Mitsuru; Hosobuchi, Kazunari.

    1988-11-01

    Using the microbial radiation resistance distribution given by AAMI, the unsterilized fraction of the products was calculated at various bioburden levels, and the results obtained were shown in the dose response curves. With increasing microbical bioburden, the shoulder of the curves is becoming more remarkable. The appearance of the curves is resembled to that of multi-targets survival curves, and this fact can be realized from the analogy that the microbes on the products are to be the targets and the products are to be the cells in the target theory.

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

    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...

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

    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...

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

    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

  19. Dose-response approaches for nuclear receptor-mediated modes of action for liver carcinogenicity: Results of a workshop

    A public workshop, organized by a Steering Committee of scientists from government, industry, universities, and research organizations, was held at the National Institute of Environmental Health Sciences (NIEHS) in September, 2010. The workshop explored the dose-response implicat...

  20. Dose response of F center optical absorption in LiF:Mg,Ti (TLD-100)

    Optical absorption (OA) of nominally pure single crystal LiF following beta irradiation was measured in order to estimate, the energy and width of the dominant F-band with minimum interference from dopant-related bands. The OA dose response of LiF:Mg,Ti was measured to 30,000 Gy, a level of dose sufficiently high to observe total saturation of the F band, which, we believe, reduces uncertainty in the estimation of the dose filling constant. The dose filling constants for the OA bands associated with the trapping center (4 eV) and competitive center (5.45 eV) responsible for the major dosimetric TL glow peak 5 were also determined. The results of these studies will be used in the framework of a kinetic model which includes the effects of radiation created defects and which will aid in the investigation of the capability of Track Structure Theory to predict OA heavy charged particle (HCP) relative efficiencies. - Highlights: • The energy and width of the F-band in LiF are estimated. • OA dose response was extended to high levels of dose including deconvolution. • Dose filling constants of the major OA bands were determined

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

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

    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)

  3. Thermoluminescence from igneous and natural hydrothermal vein quartz: dose response after optical bleaching

    We studied optical bleaching and gamma dose response of primary quartz isolated from volcanic and granitic host rocks as well as from pegmatites and hydrothermal veins using thermoluminescence (TL). We attempted to isolate the TL signature of these individual types of quartz so that improved analysis of the TL behaviour of composite sedimentary quartz mixtures is possible. We have identified the following aspects of quartz TL in these samples: (1) large variation in TL residuals after extensive bleaching; (2) shifts in glow curve peak temperatures during bleaching and gamma dose apparently related to 2nd order TL kinetics; (3) differences in TL sensitivity to gamma dose among samples; (4) supralinear dose response of both a 230oC TL peak and a germanium EPR signal only in the pegmatitic quartz samples; and (5) the volcanic and pegmatitic samples had generally higher TL sensitivity to gamma dose than did the granitic or hydrothermal samples. We concluded that (1), (2) and (3) could contribute to enhanced scatter in routine TL dating of sediments composed of mixed fractions of different quartz types, but that none of the effects observed appear to introduce any unforeseen sources of error into ED determinations using any of the standard sediment dating methods. (author)

  4. Dose - Response Curves for Dicentrics and PCC Rings: Preparedness for Radiological Emergency in Thailand

    Establishing in-vitro dose calibration curves is important for reconstruction of radiation dose in the exposed individuals. The aim of this pioneering work in Thailand was to generate dose-response curves using conventional biological dosimetry: dicentric chromosome assay (DCA) and premature chromosome condensation (PCC) assay. The peripheral blood lymphocytes were irradiated with 137Cs at a dose rate of 0.652 Gy/min to doses of 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy for DCA technique, and 5, 10, 15, 20 and 25 Gy for PCC technique. The blood samples were cultured and processed following the standard procedure given by the IAEA with slight modifications. At least 500-1,000 metaphases or 100 dicentrics/ PCC rings were analyzed using an automated metaphase finder system. The yield of dicentrics with dose was fitted to a linear quadratic model using Chromosome Aberration Calculation Software (CABAS, version 2.0), whereas the dose-response curve of PCC rings was fitted to a linear relationship. These curves will be useful for in-vitro dose reconstruction and can support the preparedness for radiological emergency in the country.

  5. Dose response in radiation-induced human carcinogenesis: accumulated data do not yet solve the enigma

    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 due to a multitude of confounding factors 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 shape of the dose-response curve. Although radiobiological theories tested mostly on in vitro systems predict a quadratic term in the dose-response equation, which should dominate the shape of the curve at least for sparsely ionizing radiation, the epidemiological data available are not yet sufficient to exclude the possibility of a purely 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 also seems to differ with the type of cancer induced. The huge epidemiological data base on atomic bomb survivors, irradiated patients, miners, and other exposed groups can most consistently be fitted to a linear quadratic model. For lung cancer in miners resulting from high linear energy transfer alpha radiation and for female breast cancer, the linear component seems to be dominant

  6. Application of the Key Events Dose-response Framework to Folate Metabolism.

    Hu, Jing; Wang, Bing; Sahyoun, Nadine R

    2016-06-10

    Folate is a vitamin that plays a role as a cofactor and coenzyme in many essential reactions. These reactions are interrelated and any change in folate homeostasis could affect other reactions. With food fortified with folic acid, and use of multivitamin, unmetabolized folic acid (UMFA) has been detected in blood circulation, particularly among older adults. This has raised concern about the potential harmful effect of high folic acid intake and UMFA on health conditions such as cognitive dysfunction and cancer. To examine what is known about folate metabolism and the release of circulating UMFA, the Key Events Dose-Response Framework (KEDRF) was used to review each of the major key events, dose-response characteristics and homeostatic mechanisms of folate metabolism. The intestine, liver and kidneys each play essential roles in regulating body folate homeostasis. But the determining event in folate metabolism leading to the release of UMFA in circulation appears to be the saturation of dihydrofolate reductase in the liver. However, at each of the key events in folate metabolism, limited information is available on threshold, homeostatic regulation and intracellular effects of folic acid. More studies are needed to fill in the knowledge gaps for quantitatively characterizing the dose-effect relationship especially in light of the call for extending folate fortification to other foods. PMID:25674817

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

    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.

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

    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)

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

    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

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

    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

  11. The Enigma of Linear/Supralinear Thermoluminescence Dose Response Mixed Localized/Delocalized Recombination describes a Solution

    Kinetic models of thermoluminescence (TL) dose response have recently been proposed which propose to solve the long-standing conundrumconcerning the dependence of the TL dose response on ionization density. Many TL materials exhibit an initially linear dose response over several decades of dose which then turns supralinear before entering into saturation. LiF:Mg,Ti is perhaps the most outstanding and widely studied example. The dose response of the major dosimetric glow peak is strictly linear from the lowest level of dose measurable of ~10-4 Gy to ~ 1 Gy and then turns supralinear reaching maximum values of the normalized TL dose response f(D) of 3-5 at levels of dose between 300 -500 Gy .This behaviour coupled with the dependence of the supralinearity on particle type and energy (i.e., on ionization density) has presented a formidable challenge to conventional kinetic theories of dose response. It has been gradually recognized over the past decade that this behaviour in LiF:Mg,Ti requires both nanodosimetric input coupled with a mixture of both localized and delocalized recombination mechanisms. This due to the complex nature of the trapping structure giving rise to the TL. Following irradiation the trapping center (TC)- luminescent center (LC) can be populated by a locally trapped electron-hole (e-h) or an electron (e) only. The former giving rise to geminate (localized) recombination the latter to mainly delocalized recombination via charge transfer migration in the conduction band. The relative concentrations of these configurations are dependent on ionization density. In this paper we present the latest developments in which we attempt to simulate the linear/supralinear dose response, the dependence of the supralinearity on electron energy and the shape of composite glow peak 5 as a function of electron energy. In order to predict all three characteristics the simulations require the incorporation of band tail states allowing semi-localized recombination from

  12. The influence of parameters of A-type carbonated apatites synthesis on radiation dose response

    The aim of this work is the investigation of dose response of A-type carbonated apatites prepared in different conditions. Irradiated samples prepared with carbonate content of 1.45 to 4.84% are studied by using electron paramagnetic resonance (EPR). The EPR spectra are mainly constituted of lines associated to axial CO2- species (gperp = 2.0028 and g// = 1.9973) and CO3- species (g1 = 2,0170, g2 = 2,0090 e g3 = 2,0041). The production of CO2- species on gamma irradiation depends on the carbonate concentration and the hydroxyapatite stoichiometry. The lowest dose detection limit was achieved with stoichiometric samples and carbonate content around of 3.7%. (author)

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

    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. Summary of dosimetry, pathology, and dose response for bone sarcomas in beagles injected with radium-226

    In the completed 226Ra portion of a 30-year-long experiment to determine the relative radiotoxicity of injected 226Ra and 239Pu, 42 of 116 animals injected with 226Ra developed 63 bone sarcomas; none were observed in 44 controls. Average alpha plus beta dose to the skeleton to death was calculated on the basis of mathematical functions developed from sequential measurements of radium and radon retention in each dog. Bone sarcomas were identified radiographically or clinically, with subsequent histopathological confirmation and classification. Most primary bone tumors were classified as osteosarcomas if osteoid arose from a malignant stroma. The dose-response curve over the six lowest injected dose levels fits well to a linear, no-threshold, least squares fit, through a control incidence of 0.8%, and with a slope of 0.042% incidence per rad. 19 refs., 5 figs., 2 tabs

  15. Dose response characteristics of polymethacrylic acid gel (PMAAG) for a polymerization-based dosimeter using NMR.

    Iskandar, S M; Elias, S; Jumiah, H; Asri, M T M; Masrianis, A; Ab Rahman, M Z; Taiman, K; Abdul Rashid, M Y

    2004-05-01

    The radiation-response characteristics of polymetharylic acid gel dosimeter prepared with different concentrations of monomer and cross-linker is described in these studies. The dosimeters were prepared under the hypoxic condition in a glove box and were then irradiated with gamma-rays produced by Co-60 radionuclide that was generated at 1.25MeV energy. The irradiation took place at different doses ranged from 0Gy to 19Gy. Due to the radiation activities, chain-reaction polymerisation processes had taken place in the formation of polymethacrylic acid (PMAA) gel, which cause the dose response mechanism increased in the NMR relaxation rates of protons. It has been observed that for higher concentration of monomer and cross-linker, the polymerization rate was increased. PMID:15468893

  16. Study on the dose-response relation of premature chromosome condensation induced by Okadaic acid

    In order to study the effect-dosage relationship between the PCC induced by Okadaic acid and the IR dosages, human peripheral blood in vitro was irradiated by X-rays at different doses (0, 0.5, 1.0, 2.0, 3.0, 5.0Gy) cultivated for 48 hours and added with Okadaic acid two hours before the end of culture. Chromosome aberrations frequencies was analyzed and compared with that induced by the conventional chromosome assay and their dose-response curves were fitted. The results show that the mitotic index of the PCC induced by Okadaic acid is higher than that of the conventional chromosome assay. And the fragment rate of chromosome condensation induced by Okadaic acid has a favorable linearity relationship with external radiation doses. (authors)

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

    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...

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

    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

  19. Relative radiation sensitivity of the integumentary system: Dose response of the epidermal, microvascular, and dermal populations

    This presentation lists gross and histologic changes produced by irradiation of the skin that have been quantified. It examines available cell kinetic radiobiological and morphological variables to identify interactions that occur between component populations. The dose response data of the hair and epidermal, fibrocytic, and endothelial cell populations are examined and a rank ordering is attempted. The contribution of the radiosensitivity of these populations to defining the dose tolerance of the skin is discussed. Future clinical needs are considered. The intent is to quantify or define tissue population changes in the irradiated skin so that the data may serve as guidelines to aid the radiation therapist to select therapy schedules that preserve skin function while improving cancer control

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

    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.

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

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

    2013-01-01

    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 of......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...

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

    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...... 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 p<0.01). The risk of psychosis increased two and a half times for each additional adversity. All......-clinical control persons matched by gender, age and parents' socio-economic status. Assessment included the Childhood Trauma Questionnaire and parts of the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Eighty-nine percent of the FEP group reported one or more adversities compared to 37% of the...

  3. Dose-response relationships after incorporation of β-active radionuclides by mycobacteria

    Experimental and theoretical studies have been carried out to overcome the problems encountered in the dosimetry of the intracellular β-decay of different radionuclides in mycobacteria (BCG). The absorbed dose can be calculated theoretically if the activity is homogeneously distributed in spherical-symmetrical sections. The radiobiologic criteria determined were on the one hand the radioactivity content, and on the other hand the inactivation and the radiation-induced resistance of the bacteria to Isoniazid. On the basis of the dose-response curves the following conclusions have been drawn: The absorbed dose concept is applicable to the intracellular 3H-decay. It is the nucleus dose which determines the mutagenic effect, while inactivation is also caused by the energy deposit in the cell plasma. However, no clear correlation has been found between dose and response with regard to the local effects (transmutation, recoil energy) resulting from intracellular 35S- and 32P-decay. (orig.)

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

    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. 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. 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. The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients

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

    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.

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

    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.

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

    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.

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

    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.

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

    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

  10. A dose-response study on opening of imidazole ring of adenine in DNA by ionizing radiation

    A dose-response relationship between γ-irradiation and the cleavage of the imidazole ring of adenine in DNA to form formamidopyrimidine has been demonstrated. When the DNA aqueous solution was irradiated with 0.1 Gy under N2O there is little evidence of imidazole ring cleavage. A significant increase in cleavage begins to be noticed above 1 Gy reaching a plateau at 1000 Gy. No formamidopyrimidine was formed when 2'-deoxyadenosine was irradiated with up to 1000 Gy. A dose of 100 Gy converts 18 per cent of adenine in DNA to formamidopyrimidine. In irradiated DNA aqueous solution 1000 Gy convert 25 per cent of adenine to formamidopyrimidine under N2O. Some of the adenine was converted to 7,8-dihydro-8-oxoadenine but in amount that is 20 per cent of that converted to formamidopyrimidine under N2O. There was more adenine in DNA converted to formamidopyrimidine under N2O than under N2. (author)

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

    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

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

    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

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

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

    2011-01-01

    BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... 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...... to each case and a link to the offspring's biological parents was established. RESULTS: There was a dose-response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric...

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

    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.

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

    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

  16. Consequences of dose response curves for tumor control and normal tissue injury on the precision necessary in patient management

    This paper is concerned with an analysis of the relationship between dose response curves, treatment precision, and treatment outcome. The approach that is taken is first to define the term ''treatment precision'' as it is used in this paper and then to compare the expected treatment outcomes for two treatment systems with different levels of precision. The treatment outcomes will be calculated using assumed dose response curves for tumor control and for severe normal tissue injury. This approach is admittedly theoretical and is not intended to provide any quantitative conclusions concerning the treatment of patients. The approach will, however, provide valuable insight into the relationship between treatment precision and outcome

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

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

    2009-01-01

    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 for...

  18. Fundamental investigations of natural and laboratory generated SAR dose response curves for quartz OSL in the high dose range

    Timar-Gabor, Alida; Constantin, Daniela; Buylaert, Jan-Pieter; Jain, Mayank; Murray, Andrew; Wintle, A.G.

    2015-01-01

    SAR-OSL investigations on quartz from Romanian loess resulted in non concordant fine and coarse-grain ages for equivalent doses higher than ~100 Gy. The laboratory dose response for both grain sizes is well represented by a sum of two saturating exponential functions, fine and coarse grains chara...... equivalent dose of 2000e2500 Gy were found to be below the saturation level of the laboratory dose response curve for both grain sizes; this also applied to the luminescence signals measured after >5000 Gy given on top of natural doses. © 2015 Elsevier Ltd. All rights reserved....

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

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

    2012-06-01

    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 28nm (AgNP28, PVP coated), respectively. Tests were performed with and without presence of Escherichia coli to evaluate how the presence of a food bacterium affects the AgNP toxicity. A pre-exposure experiment was also conducted with nematodes pre-exposed to 0 and 1mgAgNPL(-1), respectively, for 20 h prior to exposure at higher concentrations of AgNP. Both AgNP1 and AgNP28 showed adverse dose-response effects and mortality on C. elegans. LC(50) 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. coli in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when bacteria were not present. Pre-exposure to a low-level AgNP1 concentration made the nematodes slightly more sensitive to further exposure at higher concentrations compared to no pre-exposure, indicating that nematodes have no efficient physiological ability to counteract nano-silver toxicity by acclimation. The amount of dissolved Ag(+) was 0.18 to 0.21 mg L(-1) after 20 h at the highest AgNP1 (10 mg L(-1)) and AgNP28 (3 mg L(-1)) doses in the exposure medium, respectively. The upper limit of Ag(+) solubility cannot immediately explain the dose-response-related toxic effects of the AgNP nor the difference between AgNP1 and AgNP28. Higher toxicity of AgNP28 than AgNP1 may be explained by a combination of effects of coating, Ag-solubility and higher uptake rates due to agglomeration into μm-size agglomerates in the exposure medium. PMID:22475389

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

    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

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

    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.

  2. Kinetic modeling of Fluorine vacancy/F center creation in LiF:Mg,Ti including vacancy-interstitial recombination: Evaluating the factors leading to the lack of supralinearity in the optical absorption F center concentration dose response

    Kinetic model simulations of charge carrier transport following irradiation of LiF:Mg,Ti (TLD-100) including Fluorine vacancy/F center creation by the radiation and dose-dependent vacancy-interstitial recombination are presented which describe the experimentally measured linear/exponentially saturating optical absorption dose response of the electron trapping centers at 4.0 eV, 4.77 eV, 5.08 eV (F band) and 5.45 eV. Linear/exponentially saturating dose response is commonly observed for centers which are not created by the radiation. The creation of Fluorine vacancies by the radiation could therefore be expected to lead to a supralinear dose response of the F center before the onset of saturation. Nonetheless, the dose response is linear from 10 Gy to 500 Gy and can be fitted with a dose-filling constant β = 6.1 · 10−5 Gy−1 corresponding to a 5% and 25% decrease from linearity at 103 Gy and 5 · 103 Gy respectively. The model attempts to resolve a central question concerning the mechanisms leading to the linear/exponentially saturating dose response of the F band even though Fluorine vacancies are being continuously created during the irradiation. The electron-trapping characteristics of the created vacancies are assumed to differ somewhat from the vacancies originally present in un-irradiated samples due to differences in their immediate environment. Vacancy-interstitial recombination for separation distances less than a critical distance, dc is demonstrated to be significant for D > 500 Gy (dc = 36 Å) and is an important mechanism contributing to the F center saturation at high dose-levels. The kinetic model accurately simulates the experimentally observed F center dose response over the entire investigated dose range of 10–105 Gy under the following conditions: (i) The concentration of vacancies initially present is unexpectedly high at ∼1023 m−3, possibly due to the highly doped, non-crystalline and hot-pressed nature of the LiF:Mg,Ti samples. (ii

  3. Low-dose neutron dose response of zebrafish embryos obtained from the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility

    The dose response of embryos of the zebrafish, Danio rerio, irradiated at 5 h post fertilization (hpf) by 2-MeV neutrons with ≤100 mGy was determined. The neutron irradiations were made at the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility in the National Institute of Radiological Sciences (NIRS), Chiba, Japan. A total of 10 neutron doses ranging from 0.6 to 100 mGy were employed (with a gamma-ray contribution of 14% to the total dose), and the biological effects were studied through quantification of apoptosis at 25 hpf. The responses for neutron doses of 10, 20, 25, and 50 mGy approximately fitted on a straight line, while those for neutron doses of 0.6, 1 and 2.5 mGy exhibited neutron hormetic effects. As such, hormetic responses were generically developed by different kinds of ionizing radiations with different linear energy transfer (LET) values. The responses for neutron doses of 70 and 100 mGy were significantly below the lower 95% confidence band of the best-fit line, which strongly suggested the presence of gamma-ray hormesis. - Highlights: • Neutron dose response was determined for embryos of the zebrafish, Danio rerio. • Neutron doses of 0.6, 1 and 2.5 mGy led to neutron hormetic effects. • Neutron doses of 70 and 100 mGy accompanied by gamma rays led to gamma-ray hormesis

  4. Magnetization transfer proportion: a simplified measure of dose response for polymer gel dosimetry

    The response to radiation of polymer gel dosimeters has most often been described by measuring the nuclear magnetic resonance transverse relaxation rate as a function of dose. This approach is highly dependent upon the choice of experimental parameters, such as the echo spacing time for Carr-Purcell-Meiboom-Gill-type pulse sequences, and is difficult to optimize in imaging applications where a range of doses are applied to a single gel, as is typical for practical uses of polymer gel dosimetry. Moreover, errors in computing dose can arise when there are substantial variations in the radiofrequency (B1) field or resonant frequency, as may occur for large samples. Here we consider the advantages of using magnetization transfer imaging as an alternative approach and propose the use of a simplified quantity, the magnetization transfer proportion (MTP), to assess doses. This measure can be estimated through two simple acquisitions and is more robust in the presence of some sources of system imperfections. It also has a dependence upon experimental parameters that is independent of dose, allowing simultaneous optimization at all dose levels. The MTP is shown to be less susceptible to B1 errors than are CPMG measurements of R2. The dose response can be optimized through appropriate choices of the power and offset frequency of the pulses used in magnetization transfer imaging.

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

    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

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

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

    2012-01-01

    presence of Escherichia coil to evaluate how the presence of a food bacterium affects the AgNP toxicity. A pre-exposure experiment was also conducted with nematodes pre-exposed to 0 and 1 mg AgNP L-1, respectively, for 20 h prior to exposure at higher concentrations of AgNP. Both AgNP1 and AgNP28 showed...... 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...... AgNP1 and AgNP28. Higher toxicity of AgNP28 than AgNP1 may be explained by a combination of effects of coating, Ag-solubility and higher uptake rates due to agglomeration into mu m-size agglomerates in the exposure medium. (C) 2012 Elsevier Inc. All rights reserved....

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

    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

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

    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

  9. Dose-response for bone regeneration after single doses of 60Co irradiation

    The Bone Growth Chamber (BGC) methodology was used to establish a dose-response relationship for regeneration of mature bone tissue after irradiation of 5, 8, 11, 15 and 25 Gy single dose 60Co. The BGC, which is a titanium implant, was inserted in the proximal tibial metaphyses, bilaterally, of a rabbit immediately following local irradiation to one tibia. Each animal thus served as its own control. During a healing period of 4 weeks, the two canals penetrating the implant became filled with more or less newly formed bone. At the end of the healing period, the implants were removed and taken apart and the newly formed bone was collected and its volume measured by microradiography and microdensitometry. It was found that in the dose range of 5 to 8 Gy bone regeneration was reduced by about 20% as compared to non-irradiated controls. Between 8 and 11 Gy, there was a critical range in that a small increase in dose resulted in a greatly reduced bone formation. At 11 Gy and above, the depression in bone formation, as compared to non-irradiated controls, was about 65 to 75%

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

    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)

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

    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)

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

    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

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

    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.

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

    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

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

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

    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...

  17. Biological Stress Response Terminology: Integrating the Concepts of Adaptive Response and Preconditioning Stress Within a Hormetic Dose-Response Framework

    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 stres...

  18. Glyphosate resistant and susceptible soybean (Glycine max) and canola (Brassica napus) dose response and metabolism relationships with glyphosate

    Experiments were conducted to determine 1) dose response of glyphosate-resistant (GR) and –susceptible (non-GR) soybean [Glycine max (L.) Merr.] and canola (Brassica napus L.) to glyphosate, 2) if differential metabolism of glyphosate to aminomethylphosphonic acid (AMPA) is the underlying mechanism ...

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

    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...

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

    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...

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

    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...

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

    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.

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

    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

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

    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.

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

    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

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

    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

  7. Effects of the pre-irradiation storage procedure on the dose response of a Fricke xylenol orange gel dosimeter

    Liosi Giulia Maria

    2015-09-01

    Full Text Available The Fricke xylenol orange (FX gel system is a chemical dosimeter characterized by good sensitivity, linear dose response, tissue equivalence, no toxicity, easy preparation, reproducibility and low cost. Thanks to the presence of the gelatinous matrix, the system is particularly suitable to perform reliable 3D mapping of the absorbed dose spatial distribution via magnetic resonance imaging (MRI or optical techniques. The aim of this work is to study in a systematic way the influence of the pre-irradiation storage procedure upon sensitivity, dose response stability and lifetime of use of a FX gel system made with gelatin from porcine skin subjected to homogeneous irradiation. For this purpose, different pre-irradiation storage procedures, in terms of temperature and duration of each storage step, were investigated. In order to evaluate the dose response stability, the optical analyses of the samples were performed up to 6 hours after irradiation. Moreover, the samples were irradiated at time intervals of 24 hours for up to 7 days after preparation in order to evaluate the system lifetime of use. Regardless of their thermal and temporal life, the samples show linear dose responses in the investigated dose range (3-24 Gy and an increase of sensitivity with the time elapsed between preparation and irradiation. Among the three pre-irradiation storage procedures considered here, a procedure that provides the best dose response stability and lifetime of use was identified and recommended for further use. The analyzed dosimetric system possesses good properties that make it promising for medical application, particularly concerning the evaluation of pre-treatment plan quality assurance within the conformational external beam radiotherapy

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

    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.

  9. Development of Dose-Response Models to Predict the Relationship for Human Toxoplasma gondii Infection Associated with Meat Consumption.

    Guo, Miao; Mishra, Abhinav; Buchanan, Robert L; Dubey, Jitender P; Hill, Dolores E; Gamble, H Ray; Jones, Jeffrey L; Du, Xianzhi; Pradhan, Abani K

    2016-05-01

    Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States. It is thought that a substantial portion of human T. gondii infections is acquired through the consumption of meats. The dose-response relationship for human exposures to T. gondii-infected meat is unknown because no human data are available. The goal of this study was to develop and validate dose-response models based on animal studies, and to compute scaling factors so that animal-derived models can predict T. gondii infection in humans. Relevant studies in literature were collected and appropriate studies were selected based on animal species, stage, genotype of T. gondii, and route of infection. Data were pooled and fitted to four sigmoidal-shaped mathematical models, and model parameters were estimated using maximum likelihood estimation. Data from a mouse study were selected to develop the dose-response relationship. Exponential and beta-Poisson models, which predicted similar responses, were selected as reasonable dose-response models based on their simplicity, biological plausibility, and goodness fit. A confidence interval of the parameter was determined by constructing 10,000 bootstrap samples. Scaling factors were computed by matching the predicted infection cases with the epidemiological data. Mouse-derived models were validated against data for the dose-infection relationship in rats. A human dose-response model was developed as P (d) = 1-exp (-0.0015 × 0.005 × d) or P (d) = 1-(1 + d × 0.003 / 582.414)(-1.479) . Both models predict the human response after consuming T. gondii-infected meats, and provide an enhanced risk characterization in a quantitative microbial risk assessment model for this pathogen. PMID:26477997

  10. Teratogenic radiation effects: Phenomena, dose-response relationships and risk levels

    The report in hand informs about a study performed within the framework of the research project 'Animal experiments with albino mice for establishing a model for the detection and assessment of radiation-induced, developmental risks in man due to low-dose irradiation'. The subjects investigated in this study are: (1) Dose-response relationships for postnatal developmental disturbances of the brain as a result of prenatal X-ray treatment. (2) Biokinetics, distribution patterns and effects of inorganically and organically bonded radioiodine (I-125) during the phase of development of the brain. For investigation of the first-mentioned subject, computerized microphotograph analysis was applied for detecting and assessing disturbances of the alignment of axons, as well as deviations from normal cross-sectional data of the Cortex layer, and cerebral commissures as final locations of neurogenetic damage. With all parameters studied, the slope of the relevant curves was found to decrease as a function of age of the fetus at the time of exposure. In addition, time factor effects were investigated. For the parameter cross-sectional area of the Cortex, a clear decrease of effect was found, but for all other parameters, reactions were ambiguous. The study into the second subject was done with cell cultures, showing that the I-125 bonded to the cell nucleus has a much stronger radiotoxic effect than I-125 bonded to the cytoplasma. This difference in effect was studied in mice after incorporation of equal doses administered by way of (I-125)-sodium iodide or (I-125)-iododesoxyuridine. Long-term effects on Cortex cross-sectional areas, cerebral commissures or the texture of axons were quantified by microphotograph analysis. Acute cell death and initial disturbances of the neuronal cell growth were evident after incorporation of (I-125)-IdUR, but not detectable after administration of (I-125)-NaI. (orig./MG)

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

    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

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

    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.

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

    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.  

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

    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

  15. Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme

    Purpose: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125I implant boost after external beam radiotherapy. Methods and Materials: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analyses of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. Results: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm3 of normal brain. Conclusion: Although higher minimum brachytherapy tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy boost

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

    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

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

    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

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

    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

  19. Weak energy dependence of EBT gafchromic film dose response in the 50 kVp-10 MVp X-ray range

    Butson, Martin J [Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong (China) and Department of Medical Physics, Illawarra Cancer Care Centre, Crown St, Wollongong, N.S.W 2500 (Australia)]. E-mail: butsonm@iahs.nsw.gov.au; Cheung Tsang [Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong (China); Yu, Peter K.N. [Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong (China)

    2006-01-01

    The energy dependence of the dose response of EBT Gafchromic film is assessed over a broad energy range, from superficial to megavoltage X-rays. The film is auto-developing and sensitive, it provides accurate dose assessment of low doses (about 1-2 Gy) used in radiotherapy. The energy dependence of the response of EBT film was found to be very weak: the variations do not exceed 10% over the range from 50 kVp to 10 MVp X-rays. By contrast, variations of the response of Gafchromic HS film are as big as 30% over the same range, and variations of the response of Radiographic film exceed one order of magnitude. This weak dependence provides significantly higher accuracy of dose measurements under conditions of varying spectral quality of X-ray beams, which are common in radiation therapy.

  20. Critical dose threshold for TL dose response non-linearity: Dependence on the method of analysis: It’s not only the data

    It is demonstrated that the method of data analysis, i.e., the method of the phenomenological/theoretical interpretation of dose response data, can greatly influence the estimation of the onset of deviation from dose response linearity of the high temperature thermoluminescence in LiF:Mg,Ti (TLD-100).

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

    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

  2. Dose response of commercially available optically stimulated luminescent detector, Al2O3:C for megavoltage photons and electrons.

    Kim, Dong Wook; Chung, Weon Kuu; Shin, Dong Oh; Yoon, Myonggeun; Hwang, Ui-Jung; Rah, Jeong-Eun; Jeong, Hojin; Lee, Sang Yeob; Shin, Dongho; Lee, Se Byeong; Park, Sung Yong

    2012-04-01

    This study examined the dose response of an optically stimulated luminescence dosemeter (OSLD) to megavoltage photon and electron beams. A nanoDot™ dosemeter was used to measure the dose response of the OSLD. Photons of 6-15 MV and electrons of 9-20 MeV were delivered by a Varian 21iX machine (Varian Medical System, Inc. Milpitas, CA, USA). The energy dependency was tool that is independent of the energy, has dose linearity and a rapid response compared with normal in vivo dosimetric tools, such as thermoluminescence detectors. However, the OSLD must be treated very carefully due to the high angular dependency of the photon beam. PMID:21636557

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

    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.

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

    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.

  5. Dose-response relationships and risk estimates for the induction of cancer due to low doses of low-LET radiation

    Risk estimates for radiation-induced cancer at low doses can be obtained only by extrapolation from the known effects at high doses and high dose rates, using a suitable dose-response model. The applicability of three different models, linear, sublinear and supralinear, are discussed in this paper. Several experimental studies tend to favour a sublinear dose-response model (linear-quadratic model) for low-LET radiation. However, human epidemiological studies do not exclude any of the dose-response relationships. The risk estimates based on linear and linear quadratic dose-response models are compared and it is concluded that, for low-LET radiation, the linear dose-response model would probably over-estimate the actual risk of cancer by a factor of two or more. (author)

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

    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

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

    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

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

    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

  9. Red and processed meat consumption and risk of ovarian cancer: a dose-response meta-analysis of prospective studies

    Wallin, A.; Orsini, N.; Wolk, A

    2011-01-01

    Background: During the last decade, the epidemiological evidence on consumption of meat and risk of ovarian cancer has accumulated. Methods: We assessed the relationship between red and processed meat consumption and risk of ovarian cancer with a dose-response meta-analysis. Relevant prospective cohort studies were identified by searching the PubMed and EMBASE databases through 21 January 2011, and by reviewing the reference lists of retrieved articles. Study-specific relative risk (RR) estim...

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

    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.

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

    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...

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

    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...

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

    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.

  14. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

    Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

    2003-01-01

    OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness

  15. Dose-response of x-ray-induced anaphase aberrations in the mitotic root tip chromosomes of allium

    A simplified Allium root mitotic chromosome aberration assay by using only the aberrant anaphases (fragments, laggards and bridges) as the end-points were developed by Rank and Nielsen (1993) for screening water soluble chemicals and complex mixtures. A dose-response curve was established by Meir et al., (1994) using a known clastogen, 4-nitroquinolene-N-oxide between the dose range of 0.1-0.5 ug/ml. In order to further validate this assay for clastogen detection, a series of X-ray dose response experiments was carried out. Allium roots were germinated in tapwater for 48 h and treated with a series of 10, 20, 30, 40, 50, 60 R (80 Kvp, 5 ma, dose rate 60 R/min) dosages. After an 18 hr recovery time, the root tips were hydrolyzed in 45% acetic and 1 N HC1 acid (9:1 ratio) solution under 50 degrees C for 5 min and stained with aceto-carmine. Each of the data points were derived from scoring 7-10 slides (15-50 anaphases/slide). The corrrelation coefficient, slope and intercept values of the dose-response curve are: 0.954, 0.515 and 1.155 respectively

  16. Comparison of effects of six tritiated compounds on chromosomal aberrations in human lymphocytes in vitro and dose-response relationships

    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

  17. An Estimation of the Likelihood of Significant Eruptions During 2000-2009 Using Poisson Statistics on Two-Point Moving Averages of the Volcanic Time Series

    Wilson, Robert M.

    2001-01-01

    Since 1750, the number of cataclysmic volcanic eruptions (volcanic explosivity index (VEI)>=4) per decade spans 2-11, with 96 percent located in the tropics and extra-tropical Northern Hemisphere. A two-point moving average of the volcanic time series has higher values since the 1860's than before, being 8.00 in the 1910's (the highest value) and 6.50 in the 1980's, the highest since the 1910's peak. Because of the usual behavior of the first difference of the two-point moving averages, one infers that its value for the 1990's will measure approximately 6.50 +/- 1, implying that approximately 7 +/- 4 cataclysmic volcanic eruptions should be expected during the present decade (2000-2009). Because cataclysmic volcanic eruptions (especially those having VEI>=5) nearly always have been associated with short-term episodes of global cooling, the occurrence of even one might confuse our ability to assess the effects of global warming. Poisson probability distributions reveal that the probability of one or more events with a VEI>=4 within the next ten years is >99 percent. It is approximately 49 percent for an event with a VEI>=5, and 18 percent for an event with a VEI>=6. Hence, the likelihood that a climatically significant volcanic eruption will occur within the next ten years appears reasonably high.

  18. 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

    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

  19. Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women.

    Yang, Yang; Gao, Jing; Li, Hong-Lan; Zheng, Wei; Yang, Gong; Zhang, Wei; Ma, Xiao; Tan, Yu-Ting; Rothman, Nathaniel; Gao, Yu-Tang; Chow, Wong-Ho; Shu, Xiao-Ou; Xiang, Yong-Bing

    2016-07-15

    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), 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

  20. Validity of bioeffect dose response models for normal tissue early and late complications of the skin

    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)

  1. PSOD: an interactive Fortran program to simulate the radiation dose response of membrane populations

    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

  2. Derivation of the critical effect size/benchmark response for the dose-response analysis of the uptake of radioactive iodine in the human thyroid.

    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

  3. Dose-response relationship of γ-H2AX foci induction in human lymphocytes after X-rays exposure

    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.

  4. Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review

    Chronic arsenic (As) poisoning has become a worldwide public health issue. Most human As exposure occurs from consumption of drinking water containing high amounts of inorganic As (iAs). In this paper, epidemiological studies conducted on the dose-response relationships between iAs exposure via the drinking water and related adverse health effects are reviewed. Before the review, the methods for evaluation of the individual As exposure are summarized and classified into two types, that is, the methods depending on As concentration of the drinking water and the methods depending on biological monitoring for As exposure; certain methods may be applied as optimum As exposure indexes to study dose-response relationship based on various As exposure situation. Chronic effects of iAs exposure via drinking water include skin lesions, neurological effects, hypertension, peripheral vascular disease, cardiovascular disease, respiratory disease, diabetes mellitus, and malignancies including skin cancer. The skin is quite sensitive to arsenic, and skin lesions are some of the most common and earliest nonmalignant effects related to chronic As exposure. The increase of prevalence in the skin lesions has been observed even at the exposure levels in the range of 0.005-0.01 mg/l As in drinking waters. Skin, lung, bladder, kidney, liver, and uterus are considered as sites As-induced malignancies, and the skin is though to be perhaps the most sensitive site. Prospective studies in large area of endemic As poisoning, like Bangladesh or China, where the rate of malignancies is expected to increase within the next several decades, will help to clarify the dose-response relationship between As exposure levels and adverse health effects with enhanced accuracy

  5. Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

    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.

  6. Evaluation of the Comet Assay for Assessing the Dose-Response Relationship of DNA Damage Induced by Ionizing Radiation

    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...

  7. Pancreatic beta cell function increases in a linear dose-response manner following exercise training in adults with prediabetes

    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...

  8. Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

    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 of lectu...... 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....

  9. Low dose radiation induced adaptive response upon salt stress and vacuum stress: a possible mechanism for the effect of saddle-like dose response curve

    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)

  10. SU-D-16A-02: A Novel Methodology for Accurate, Semi-Automated Delineation of Oral Mucosa for Radiation Therapy Dose-Response Studies

    Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in

  11. SU-D-16A-02: A Novel Methodology for Accurate, Semi-Automated Delineation of Oral Mucosa for Radiation Therapy Dose-Response Studies

    Dean, J; Welsh, L; Gulliford, S; Harrington, K; Nutting, C [The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London (United Kingdom)

    2014-06-01

    Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in

  12. Injury Statistics

    ... 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 ...

  13. Stage sensitivity and dose response of meiotic chromosomes of pollen mother cells of Tradescantia to X-rays

    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)

  14. The dose-response-relation of erythema of the domestic pig induced by UVC-radiation (254 nm)

    For domestic pigs the time-course and the dose-response-relationship of erythemal effective UVC-radiation was investigated. By the chromameter CR 300 (Minolta) the redness of the skin was measured, using the international L*a*b*-system. As UVC-source a germicidal lamp (TUV, Philips) was housed in a tube. The irradiance of the 10 zylindric holes were attenuated by a wire mash, changing the intensity along a logarithmic decrement. For the experiment 10 pigs were used. Each pig could be irradiated with 40 dose-steps. The redness of the marked skin-areas was not only determined once before the irradiation but also several times within 36 hours. The reaction of the skin of the pigs to UVC-radiation was different to human's. The time-course of the UVC-erythema was biphasical. The second erythema-maximum could not be explained by the pigmentation, which had just begun, but by an new increase of the reddening of the skin. No dose-response-correlation like the human's UVC-erythema could be detected. Therefore, the domestic pig can not be used as a human's photo-biological model for UVC. (author)

  15. Radiation dose response simulation for biomechanical-based deformable image registration of head and neck cancer treatment

    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)

  16. Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice.

    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

  17. DNA repair processes and the shape of dose-response curves for induced genetic changes in yeast

    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

  18. Study on the dose response characteristics of a scanning liquid ion-chamber electronic portal imaging device

    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...

  19. An in vitro dynamic microcosm biofilm model for caries lesion development and antimicrobial dose-response studies.

    Maske, T T; Brauner, K V; Nakanishi, L; Arthur, R A; van de Sande, F H; Cenci, M S

    2016-03-01

    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

  20. Absorbed dose response of Al2O3 dosimeter irradiated by 60Co γ spectrum source capture and collimators

    Objective: To investigated the absorbed dose response of Al2O3 dosimeter in water phantom irradiated by 60Co γ spectrum source. Methods: The EGSnrc simulation program code DOSRZnrc was used to calculate the absorbed dose of the Al2O3 dosimeter and that of the equivalent volume of water in the corresponding position, as well as the absorbed dose conversion factor, irradiated by 60Co photon beams in a water phantom. Simulations were done for a cylindrical geometry dosimeter (diameter 0.4 cm and height 0.1 cm) and the dosimeter was placed at the centre of the water phantom at different depths. Results: The average absorbed dose conversion factor is 1.143±0.006 and changes little with the depth of the dosimeter in the water phantom, and the deviation is less than 1.0%. Conclusion: The absorbed dose response of Al2O3 dosimeter irradiated by 60Co γ spectrum source is steady and is independent on the depth of the dosimeter in water phantom in this research. (authors)

  1. Thyroid nodules in the population living around semipalatinsk nuclear test site. Possible implications for dose-response relationships study

    The risk of radiation-induced nodules is higher than the risk for radiation-induced cancer. Risk factors and specific modifiers of the dose-response relationship may vary among different populations and not be well recognized. Many thyroid studies have considered thyroid nodularity itself, but not specific morphological types of thyroid nodules. There are many specific types of thyroid nodules which follow a morphological classification of thyroid lesions, including some congenital and tumor-like conditions. Modern equipment and technique can help us to identify particular specific types of thyroid nodules. In this study we report some results of a clinically applicable approach to materials derived from three studies. From 1999 through 2002, we have screened 571 current residents from 4 exposed and 1 control village near the Semipalatinsk Nuclear Test Site area, who were of similar ages (<20) at the time of major radiation fallout events at the Semipalatinsk Nuclear Test Site (SNTS). Prevalent nodules were identified by ultrasound and fine-needle aspiration biopsy, cytopathology results. Analysis of ultrasound images and cytopathology of thyroid lesions among exposed and non-exposed population allowed us to distinguish some interesting ultrasound features for specific types of thyroid nodules. We believe that it would be interesting and possibly more informative for thyroid dosimetry studies to consider specific morphological types of thyroid nodules. We need more detailed research to clarify the feasibility of applying these findings for study of the dose-response relationship. (author)

  2. Ingestion risks of metals in groundwater based on TIN model and dose-response assessment - A case study in the Xiangjiang watershed, central-south China

    Groundwater samples were collected in the Xiangjiang watershed in China from 2002 to 2008 to analyze concentrations of arsenic, cadmium, chromium, copper, iron, lead, mercury, manganese, and zinc. Spatial and seasonal trends of metal concentrations were then discussed. Combined with geostatistics, an ingestion risk assessment of metals in groundwater was performed using the dose-response assessment method and the triangulated irregular network (TIN) model. Arsenic concentration in groundwater had a larger variation from year to year, while the variations of other metal concentrations were minor. Meanwhile, As concentrations in groundwater over the period of 2002-2004 were significantly higher than that over the period of 2005-2007, indicating the improvement of groundwater quality within the later year. The hazard index (HI) in 2002 was also significantly higher than that in 2005, 2006, 2007 and 2008. Moreover, more than 80% of the study area recorded an HI of more than 1.0 for children, suggesting that some people will experience deleterious health effects from drinking groundwater in the Xiangjiang watershed. Arsenic and manganese were the largest contributors to human health risks (HHRs). This study highlights the value of long-term health risk evaluation and the importance of geographic information system (GIS) technologies in the assessment of watershed-scale human health risk.

  3. Chloroatranol, an extremely potent allergen hidden in perfumes: a dose-response elicitation study

    Johansen, Jeanne Duus; Andersen, Klaus Ejner; Svedman, Cecilia;

    2003-01-01

    Oak moss absolute is a long-known, popular natural extract widely used in perfumes. It is reported as the cause of allergic reactions in a significant number of those with perfume allergy. Oak moss absolute has been the target of recent research to identify its allergenic components. Recently, ch...

  4. Dose response to chlorthalidone in patients with mild hypertension. Efficacy of a lower dose.

    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

  5. Dose response behaviour of water scarcity towards genetical and morphological traits in spring wheat

    Combining ability was studied in a Line * Tester mating fashion in wheat (Tricticum aestivum L.). Significant differences were observed for all the yield and yield contributing traits. GCA and SCA components of variation were found significant for most of the traits. Under water stressed conditions among lines the genotype Kohistan-97 revealed significant GCA effects for all the traits except spike length. Among testers, the genotype V08172 showed significant effects for the traits spike length, 1000-grain weight and flag leaf area. Based on desirable SCA effects and mean performance the cross combinations Kohistan-97 * V08172, Chakwal-86 * Punjab-81, Fsd-2008 * Punjab-81, Sehar-2006 * V08172 and Chakwal-86 * V08172 behaved best combiner to tolerate the water stress. Results of genetic analysis offered over dominance type of gene action that remained unchanged with the change in water provision for the traits like 1000 grain weight and economic yield. Similarly additive gene action was observed for the trait plant height under both normal irrigation and water stress conditions. However the cumulative genetic effects to control the expression of yield and yield components was shifted due to the changed environments. The study was concluded that due to presence of additive variance, selection could be practiced in early generation whereas in the presence of recessiveness the selection may be delayed up to the later generations. Plant traits associated with water stress tolerance having high heritability and with additive gene action may be used as indirect selection criteria for early selection of water stress tolerant genotypes. The information generated as a result of this study on genetic analysis of important economic traits of wheat under contrasting water availability positions will be of great value to the wheat breeders to design future breeding programmes. (author)

  6. Dose-response evaluation after Yttrium-90 resin microsphere radio-embolization of breast cancer liver metastases

    Full text of publication follows. Aim: Yttrium-90 resin microsphere radio-embolization is a valuable therapeutic option in metastatic breast cancer patients with progressive disease refractory to chemotherapy. The goal of this study was to evaluate the dose-response relationship of liver metastasis based on a 3D voxelized 90Y PET dosimetry. Materials and methods: we studied the dose-response relationship of twelve hepatic lesions in four selected patients with metastatic breast cancer who underwent 90Y radio-embolization (Sirtex SIR-Spheres Pty Ltd.). The administered activity ranged from 1 to 1.3 GBq. Ten days before treatment, patients underwent a baseline 18F-FDG PET/CT. The determination of the 90Y-microsphere activity to administer for treatment was based on the BSA method refined with the partition model derived from a 99mTc-MAA SPECT/CT performed a week prior to radio-embolization. Within 24 hours after treatment, 90Y TOF PET/CT imaging was performed. A follow-up 18F-FDG PET/CT was performed 1 month after the treatment to evaluate the response to radio-embolization. For each patient, 3D voxelized dose-maps were obtained from the post-treatment 90Y TOF PET/CT. A volume of interest (VOI) was drawn for each selected hepatic lesion using the baseline 18F-FDG PET/CT. To obtain dose-volume histogram (DVH) for each lesion, image co-registration and VOI masks were generated using the PMOD 3.4 software and then exported in Matlab for dose calculation. Furthermore, the average absorbed dose in lesions was corrected for PVE effects by multiplication for appropriate (phantom-based) recovery coefficients according to the lesion size. Early metabolic lesion response was assessed in terms of variation in the maximum standard uptake value (ΔSUVmax) between baseline and follow-up 18F-FDG PET/CT. The average absorbed dose for each lesion was associated with the respective metabolic response. Results: for the 12 selected lesions, the average volume was 35 cm3 (range 8-147 cm3

  7. Evaluation of the Comet Assay for Assessing the Dose-Response Relationship of DNA Damage Induced by Ionizing Radiation

    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.

  8. Comment on the treatment of dose-response relationship for the epidemiological data of atomic bomb survivors

    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 searching their families

  9. Comment on the treatment of dose-response relationship for the epidemiological data of atomic bomb survivors

    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

  10. Mutations induced in Tradescantia by small doses of X-rays and neutrons - Analysis of dose-response curves.

    Sparrow, A. H.; Underbrink, A. G.; Rossi, H. H.

    1972-01-01

    Dose-response curves for pink somatic mutations in Tradescantia stamen hairs were analyzed after neutron and X-ray irradiation with doses ranging from a fraction of a rad to the region of saturation. The dose-effect relation for neutrons indicates a linear dependence from 0.01 to 8 rads; between 0.25 and 5 rads, a linear dependence is indicated for X-rays also. As a consequence the relative biological effectiveness reaches a constant value (about 50) at low doses. The observations are in good agreement with the predictions of the theory of dual radiation action and support its interpretation of the effects of radiation on higher organisms. The doubling dose of X-rays was found to be nearly 1 rad.

  11. CurveP Method for Rendering High-Throughput Screening Dose-Response Data into Digital Fingerprints.

    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

  12. Is the dose-response relationship for local control of Hodgkin disease obscured by lung inhomogeneity corrections

    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

  13. High-Throughput Dose-Response Measurement Using a Label-Free Microarray-in-Microplate Assay Platform.

    Landry, J P; Malovichko, G; Zhu, X D

    2015-06-01

    Microarray-based binding assays facilitate the discovery of protein ligands from large collections of small molecules. Hundreds of ligands can be identified, yet only a small portion of them have interfering effects (competitive or noncompetitive) on a specific protein-receptor binding reaction. Further efficient screening of ligands for those with specific modifying effect is needed in order to take the full advantage of throughputs of microarray-based assays for drug discovery. We report a label-free "microarray-in-microplate" assay platform for simultaneous acquisition of at least 32 dose-response curves in a single experiment, each curve having 12 concentration points. When combined with ligand discovery, this makes the microarray-based platform a true high-throughout means of finding inhibitors to specific protein-receptor reactions starting from a large collection of small-molecule libraries. PMID:25921700

  14. Exposure dose response relationships of the freshwater bivalve Hyridella australis to cadmium spiked sediments

    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

  15. 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

    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

  16. In search of a statistical probability model for petroleum-resource assessment : a critique of the probabilistic significance of certain concepts and methods used in petroleum-resource assessment : to that end, a probabilistic model is sketched

    Grossling, Bernardo F.

    1975-01-01

    Exploratory drilling is still in incipient or youthful stages in those areas of the world where the bulk of the potential petroleum resources is yet to be discovered. Methods of assessing resources from projections based on historical production and reserve data are limited to mature areas. For most of the world's petroleum-prospective areas, a more speculative situation calls for a critical review of resource-assessment methodology. The language of mathematical statistics is required to define more rigorously the appraisal of petroleum resources. Basically, two approaches have been used to appraise the amounts of undiscovered mineral resources in a geologic province: (1) projection models, which use statistical data on the past outcome of exploration and development in the province; and (2) estimation models of the overall resources of the province, which use certain known parameters of the province together with the outcome of exploration and development in analogous provinces. These two approaches often lead to widely different estimates. Some of the controversy that arises results from a confusion of the probabilistic significance of the quantities yielded by each of the two approaches. Also, inherent limitations of analytic projection models-such as those using the logistic and Gomperts functions --have often been ignored. The resource-assessment problem should be recast in terms that provide for consideration of the probability of existence of the resource and of the probability of discovery of a deposit. Then the two above-mentioned models occupy the two ends of the probability range. The new approach accounts for (1) what can be expected with reasonably high certainty by mere projections of what has been accomplished in the past; (2) the inherent biases of decision-makers and resource estimators; (3) upper bounds that can be set up as goals for exploration; and (4) the uncertainties in geologic conditions in a search for minerals. Actual outcomes can then

  17. A comparison of natural- and laboratory-generated dose response curves for quartz optically stimulated luminescence signals from Chinese Loess

    It has previously been observed that laboratory-generated quartz optically stimulated luminescence (OSL) signals from different samples have similar dose response curves (DRCs) after they are normalized using a test dose. It therefore seems likely that growth of the normalized signal due to natural irradiation of quartz may also follow a general dose response curve. The existence of such a curve is investigated by constructing a natural DRC from the test dose-normalized natural OSL signals of seven samples from the Luochuan section of the Chinese Loess Plateau. The same aliquots are then used to build single aliquot regenerative (SAR) DRCs, making it possible to compare the natural and laboratory constructed curves. Two main differences are observed. Firstly, the laboratory-generated DRCs are best fitted with double saturating exponential functions whereas the natural DRC is equally well fitted with a single saturating function. Secondly, in the laboratory-generated DRCs the normalized OSL signal continues to increase at high laboratory doses (>500 Gy), whereas no growth is seen at these doses in the equivalent natural DRC. These differences between natural- and laboratory-generated DRCs are still apparent even if data are manipulated to isolate the fast component, or if a sensitivity corrected multiple aliquot regenerative (SC-MAR) dose procedure is used. This suggests that the observed differences are not due to the influence of different components or inter-regenerative dose cycle sensitivity changes. The divergence between the natural- and laboratory-generated DRC means that the current maximum limit of quartz OSL dating at the Luochuan section is 150 Gy, as De estimates above this value are likely to be underestimations.

  18. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    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.

  19. Dose-response curve for blood exposed to gamma-neutron mixed field by conventional cytogenetic method

    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 241AmBe (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)

  20. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

    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

  1. Dose-response characteristics of a monoclonal antibody based two-si immunoradiometric assay for hepatitis B surface antigen (HBsAg)

    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

  2. DOSE-RESPONSE OF PORCINE OVARIAN GRANULOSA CELLS TO AMYGDALIN TREATMENT COMBINED WITH DEOXYNIVALENOL

    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.

  3. Detector dose response in megavoltage small photon beams. I. Theoretical concepts

    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

  4. Dose response of red imported fire ant colonies to Solenopsis invicta virus 3.

    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

  5. Dose-response relationship of cadmium or radiation-induced embryotoxicity in mouse whole embryo culture

    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).

  6. Detector dose response in megavoltage small photon beams. I. Theoretical concepts

    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.

  7. Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

    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

  8. Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

    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

  9. Analysis of bias effects on the total ionizing dose response in a 180 nm technology

    Liu Zhangli, E-mail: liuzhangli@mail.sim.ac.cn [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100039 (China); Hu Zhiyuan [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100039 (China); Zhang, Zhengxuan; Shao Hua [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Chen Ming [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100039 (China); Bi Dawei [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Ning Bingxu [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100039 (China); Zou Shichang [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050 (China)

    2011-07-11

    The effects of gamma ray irradiation on the shallow trench isolation (STI) leakage current in a 180 nm technology are investigated. The radiation response is strongly influenced by the bias modes, gate bias during irradiation, substrate bias during irradiation and operating substrate bias after irradiation. We found that the worst case occurs under the ON bias condition for the ON, OFF and PASS bias mode. A positive gate bias during irradiation significantly enhances the STI leakage current, indicating the electric field influence on the charge buildup process during radiation. Also, a negative substrate bias during irradiation enhances the STI leakage current. However a negative operating substrate bias effectively suppresses the STI leakage current, and can be used to eliminate the leakage current produced by the charge trapped in the deep STI oxide. Appropriate substrate bias should be introduced to alleviate the total ionizing dose (TID) response, and lead to acceptable threshold voltage shift and subthreshold hump effect. Depending on the simulation results, we believe that the electric field distribution in the STI oxide is the key parameter influencing bias effects on the radiation response of transistor. - Highlights: > ON bias is the worst bias condition for the ON, PASS and OFF bias modes. > Larger gate bias during irradiation leads to more pronounced characteristic degradation. > TID induced STI leakage can be suppressed by negative operating substrate bias voltage. > Negative substrate bias during irradiation leads to larger increase of off-state leakage. > Electric field in the STI oxide greatly influences the device's radiation effect.

  10. The high dose response and functional capability of the DT-702/Pd lithium fluoride thermoluminescent dosimeter.

    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

  11. Analysis of bias effects on the total ionizing dose response in a 180 nm technology

    Liu, Zhangli; Hu, Zhiyuan; Zhang, Zhengxuan; Shao, Hua; Chen, Ming; Bi, Dawei; Ning, Bingxu; Zou, Shichang

    2011-07-01

    The effects of gamma ray irradiation on the shallow trench isolation (STI) leakage current in a 180 nm technology are investigated. The radiation response is strongly influenced by the bias modes, gate bias during irradiation, substrate bias during irradiation and operating substrate bias after irradiation. We found that the worst case occurs under the ON bias condition for the ON, OFF and PASS bias mode. A positive gate bias during irradiation significantly enhances the STI leakage current, indicating the electric field influence on the charge buildup process during radiation. Also, a negative substrate bias during irradiation enhances the STI leakage current. However a negative operating substrate bias effectively suppresses the STI leakage current, and can be used to eliminate the leakage current produced by the charge trapped in the deep STI oxide. Appropriate substrate bias should be introduced to alleviate the total ionizing dose (TID) response, and lead to acceptable threshold voltage shift and subthreshold hump effect. Depending on the simulation results, we believe that the electric field distribution in the STI oxide is the key parameter influencing bias effects on the radiation response of transistor.

  12. Arc Statistics

    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...

  13. Trial sequential analysis may be insufficient to draw firm conclusions regarding statistically significant treatment differences using observed intervention effects: a case study of meta-analyses of multiple myeloma trials.

    Miladinovic, Branko; Kumar, Ambuj; Hozo, Iztok; Mahony, Helen; Djulbegovic, Benjamin

    2013-03-01

    Trial sequential analysis (TSA) has been proposed as a method to assess the risk of random error in cumulative meta-analysis (MA), which increases due to repeated significance testing. The aim of TSA is to assist researchers from wrongly concluding treatment differences in the absence of a benefit (i.e. true versus false positive). Similar to monitoring boundaries applied in individual randomized controlled trials, recent literature has advocated the use of TSA for assessing the conclusiveness of results from MAs to determine the requirement for future studies in case of true positive results. While this may be desirable, we present empirical evidence from a recent systematic review to demonstrate that the use of TSA may lead to a premature declaration of statistically significant treatment difference, when further accumulated evidence suggested otherwise. Using all apparently conclusive MAs in multiple-myeloma, we empirically studied under what thresholds for the risk ratio reduction and power a true positive result becomes false positive. We recommend that the conclusion of significant treatment differences in cumulative MA should be weighed against acceptable thresholds regarding the type I error, power and apriori specified clinically meaningful treatment difference. PMID:23274403

  14. Ozone dose-response relationships for spring oilseed rape and broccoli

    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 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 < 0.001). As a consequence 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.

  15. The dose-response relationship of T-cell receptor gene mutation of rat peripheral blood lymphocytes induced by X-ray

    Objective: To investigate the does-response relationship of T-cell receptor from rat peripheral blood lymphocyte induced by X-ray. Methods: Freshly isolated peripheral lymphocytes from rat were irradiated with X-ray ranged from 0 Gy to 3 Gy and cultured with phytohemagglutinin Concanavalin A and interleukin-27 days, The mutant frequencies of TCR gene were detected by flow cytometry. Results: TCR genes mutation increases with the dose incense in the cultured the rat lymphocytes 7 days and it exists favourable dose-response relationship. Data were found to be fitted out optimal by a quadratic polynomial dose-response model, which could be described by regression equation: TCRMF= TCRMF=1.615 +9.979D + 1.712D2 (F=146.781, P2adj=0.867). Conclusion: The favourable dose-response relationship between TCRMF induced by X ray and dose can be found from this study. (authors)

  16. The scientific basis for the establishment of threshold levels and dose response relationships of carcinogenesis

    -sterilized medical supplies have increasingly been introduced in the markets of the countrie s beyond their national boundary of manufacturing. An early acceptance of such products of public health significance continue to rely on the international standardization of the partices concerned. Agency's document on the Recommended Practice for Radiation Sterilization of Medical Products was discussed and reviewed by the participants in order to revise and up-date in the light of the current experiences. The Recommendations continue to serve as a guide in the formulation of the national standards and specifications by the Member States. (author)

  17. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

    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

  18. Dose-response study of probiotic bacteria Bifidobacterium animalis subsp lactis BB-12 and Lactobacillus paracasei subsp paracasei CRL-341 in healthy young adults

    Larsen, C.N.; Nielsen, S.; Kaestel, P.;

    2006-01-01

    Objective: This study was performed to investigate the dose-response effects of supplementation with Bifidobacterium animalis subsp lactis (BB-12) and Lactobacillus paracasei subsp paracasei (CRL-431) on blood lipids, recovery from feces and bowel habits. Changes of the fecal microflora 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...

  19. Cancer Statistics

    ... 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 ...

  20. The dose-response decrease in heart rate variability: any association with the metabolites of polycyclic aromatic hydrocarbons in coke oven workers?

    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.

  1. Dietary flavonoid intake and the risk of stroke: a dose-response meta-analysis of prospective cohort studies

    Tang, Zhenyu; Li, Min; Zhang, Xiaowei; Hou, Wenshang

    2016-01-01

    Objective To clarify and quantify the potential association between intake of flavonoids and risk of stroke. Design Meta-analysis of prospective cohort studies. Data source Studies published before January 2016 identified through electronic searches using PubMed, Embase and the Cochrane Library. Eligibility criteria for selecting studies Prospective cohort studies with relative risks and 95% CIs for stroke according to intake of flavonoids (assessed as dietary intake). Results The meta-analysis yielded 11 prospective cohort studies involving 356 627 participants and more than 5154 stroke cases. The pooled estimate of the multivariate relative risk of stroke for the highest compared with the lowest dietary flavonoid intake was 0.89 (95% CI 0.82 to 0.97; p=0.006). Dose-response analysis indicated that the summary relative risk of stroke for an increase of 100 mg flavonoids consumed per day was 0.91 (95% CI 0.77 to 1.08) without heterogeneity among studies (I2=0%). Stratifying by follow-up duration, the relative risk of stroke for flavonoid intake was 0.89 (95% CI 0.81 to 0.99) in studies with more than 10 years of follow-up. Conclusions Results from this meta-analysis suggest that higher dietary flavonoid intake may moderately lower the risk of stroke. PMID:27279473

  2. Identification of low-dose responsive metabolites in X-irradiated human B lymphoblastoid cells and fibroblasts

    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)

  3. ESTIMATING A DOSE-RESPONSE RELATIONSHIP BETWEEN LENGTH OF STAY AND FUTURE RECIDIVISM IN SERIOUS JUVENILE OFFENDERS.

    Loughran, Thomas A; Mulvey, Edward P; Schubert, Carol A; Fagan, Jeffrey; Piquero, Alex R; Losoya, Sandra H

    2009-01-01

    The effect of sanctions on subsequent criminal activity is of central theoretical importance in criminology. A key question for juvenile justice policy is the degree to which serious juvenile offenders respond to sanctions and/or treatment administered by the juvenile court. The policy question germane to this debate is finding the level of confinement within the juvenile justice system that maximizes the public safety and therapeutic benefits of institutional confinement. Unfortunately, research on this issue has been limited with regard to serious juvenile offenders. We use longitudinal data from a large sample of serious juvenile offenders from two large cities to 1) estimate a causal treatment effect of institutional placement, as opposed to probation, on future rate of rearrest and 2) investigate the existence of a marginal effect (i.e., benefit) for longer length of stay once the institutional placement decision had been made. We accomplish the latter by determining a dose-response relationship between the length of stay and future rates of rearrest and self-reported offending. The results suggest that an overall null effect of placement exists on future rates of rearrest or self-reported offending for serious juvenile offenders. We also find that, for the group placed out of the community, it is apparent that little or no marginal benefit exists for longer lengths of stay. Theoretical, empirical, and policy issues are outlined. PMID:20052309

  4. ESTIMATING A DOSE-RESPONSE RELATIONSHIP BETWEEN LENGTH OF STAY AND FUTURE RECIDIVISM IN SERIOUS JUVENILE OFFENDERS*

    Loughran, Thomas A.; Mulvey, Edward P.; Schubert, Carol A.; Fagan, Jeffrey; Piquero, Alex R.; Losoya, Sandra H.

    2009-01-01

    The effect of sanctions on subsequent criminal activity is of central theoretical importance in criminology. A key question for juvenile justice policy is the degree to which serious juvenile offenders respond to sanctions and/or treatment administered by the juvenile court. The policy question germane to this debate is finding the level of confinement within the juvenile justice system that maximizes the public safety and therapeutic benefits of institutional confinement. Unfortunately, research on this issue has been limited with regard to serious juvenile offenders. We use longitudinal data from a large sample of serious juvenile offenders from two large cities to 1) estimate a causal treatment effect of institutional placement, as opposed to probation, on future rate of rearrest and 2) investigate the existence of a marginal effect (i.e., benefit) for longer length of stay once the institutional placement decision had been made. We accomplish the latter by determining a dose-response relationship between the length of stay and future rates of rearrest and self-reported offending. The results suggest that an overall null effect of placement exists on future rates of rearrest or self-reported offending for serious juvenile offenders. We also find that, for the group placed out of the community, it is apparent that little or no marginal benefit exists for longer lengths of stay. Theoretical, empirical, and policy issues are outlined. PMID:20052309

  5. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    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.

  6. Study of the dose response of the system ferrous ammonium sulfate–sucrose–xylenol orange in acid aqueous solution

    An aqueous solution of ammonium ferrous sulfate–sucrose–xylenol orange in sulfuric acid (FSX) is proposed as a dosimetric system for the processes of gamma irradiation in a range between 0.3 and 6 Gy. This system is based on the indirect oxidation of ferrous ion by an organic compound (sucrose) to ferric ion and on the formation of a color complex of Fe3+ in an acidic medium with xylenol orange (a dye). After gamma radiation, an observable change occurs in the color of the system. Irradiation was executed at three different temperatures (13 °C, 22 °C, and 40 °C). A spectrometric readout method at 585 nm was employed to evaluate the system's dose response. In all of the cases analyzed, the responses had a linear behavior, and a slight effect of irradiation temperature was observed. Post-irradiation response was also evaluated and showed the stability of the solutions 24 h after the irradiation. The results obtained suggest that FSX might be used as a dosimeter for low doses of gamma irradiation because it provides a stable signal, good reproducibility, and an accessible technique for analysis. - Highlights: • The system ferrous-sucrose-xylenol is reproducibility with less than 5% error. • The dosimeter has low cost and easy readout using UV-vis spectrometry, and the response is stable for several days. • The system proposed is suitable for low irradiation doses

  7. No protection by oral terbutaline against exercise-induced asthma in children: a dose-response study.

    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

  8. NITRO MUSK ADDUCTS OF RAINBOW TROUT HEMOGLOBIN: DOSE-RESPONSE AND TOXICOKINETICS DETERMINATION BY GC-NICI-MS FOR A SENTINEL SPECIES

    Rainbow trout and other fish species can serve as 'sentinel' species for the assessment of ecological status and the presence of certain environmental contaminants. As such they act as bioindicators of exposure. Here we present seminal data regarding dose-response and toxicokinet...

  9. Health risks from arsenic-contaminated soil in Flin Flon-Creighton, Canada: Integrating geostatistical simulation and dose-response model

    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.

  10. The influence of TRP53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells

    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

  11. Low-Level Laser Therapy Attenuates the Myeloperoxidase Activity and Inflammatory Mediator Generation in Lung Inflammation Induced By Gut Ischemia and Reperfusion: A Dose-Response Study

    de Lima, Flávia Mafra; Aimbire, Flávio; Miranda, Humberto; Vieira, Rodolfo Paula; de Oliveira, Ana Paula Ligeiro; Albertini, Regiane

    2014-01-01

    Introduction: Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). Herein we evaluate the dose-response effect of low-level laser therapy (LLLT) on lung inflammation induced by i-I/R.

  12. A dose-response of consuming high fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults

    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, ...

  13. Cytogenetics dosimetry: dose-response curve for low doses of X-ray; Dosimetria citogenetica: curva dosis-respuesta para bajas dosis de rayos-X

    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.

  14. Dose-response and time-course of neurotoxicity and tissue concentrations of carbaryl in Brown Norway rats from preweaning to senescence.

    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...

  15. Dose-response relationship in cyclophosphamide-treated B-cell lymphoma xenografts monitored with [{sup 18}F]FDG PET

    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.)

  16. A randomized comparative trial of first-dose response to Angiotensin- Converting Enzyme Perindopril and Captopril in Indonesian heart failure patients

    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

  17. Tissue differences, dose-response relationship and persistence of DNA adducts in blue mussels (Mytilus edulis L.) exposed to benzo[a]pyrene

    Baltic Sea blue mussels (Mytilus edulis) were experimentally exposed to the genotoxic model substance benzo[a]pyrene (B[a]P) to study DNA adduct formation. The specific aims were (a) to examine where in the mussels the DNA adducts were formed, in gills or digestive gland; (b) to study the dose-response relationship between B[a]P exposure and DNA adduct formation; and (c) to examine the persistence of the formed adducts. A Scope for growth (SFG) study was also run to compare physiological responses of the mussels with the degree of DNA adduct formation. In an initial dose-response experiment, the mussels were exposed to 0, 5, 50, and 100 μg/l of tritium labelled B[a]P under semi-static conditions for 4 days, and thereafter the bioaccumulation of B[a]P and DNA adduct formation in different tissues was determined using liquid scintillation counting and 32P-postlabelling analysis, respectively. In a following exposure-depuration experiment, mussels were exposed to 17 μg/l of radiolabelled B[a]P under semi-static conditions for 6 days. B[a]P accumulation and DNA adduct formation were determined during the exposure, and B[a]P elimination and persistence of DNA adducts were studied during 28 days of depuration in uncontaminated water. The results revealed large tissue differences in DNA adduct formation. DNA adduct levels were not elevated in the digestive gland of the mussels at any exposure concentration (0-100 μg/l), even though the highest B[a]P tissue concentrations were found in the digestive gland (1.0±0.1 mg B[a]P/g tissue dry wt at 100 μg/l, mean±SE, n=12). DNA adducts were on the other hand formed in the gills, with the highest levels found in mussels exposed to 50 and 100 μg B[a]P/l, and a dose dependent increase in adduct levels (from 1.6 to 5.9 nmol adducts/mol nucleotides) from 0 to 50 μg B[a]P/l. In gills, DNA adduct levels increased with time during the 6-day exposure period in the exposure-depuration experiment, and then persisted for at least 2

  18. Are atomic-bomb dose-response data from ABCC/RERF reasonable for assessment of radiation risk?

    Ever since ABCC was established in 1948, the Unified Program, conceived in 1955 and a fixed population sample (Life Span Study extended) was selected from the A-Bomb survivors Supplementary Schedules of 1950 National Census, originally consisted of approximately 110,000 persons in Hiroshima and Nagasaki. Since 1958, the AHS, a fixed sub-sample of LSS-extend sample, originally consisting of nearly 20,000 persons, has been followed for long-term clinical examinations for any late ionizing radiation effects of the A-bombs. AHS participants are thus provided complete physical examinations and laboratory tests during their biennial ''cycle'' visits to the ABCC/RERF clinics. The AHS sample includes persons NIC as the control groups. On the basis of the survey of the fixed population sample, ABCC/RERF have published many papers upto the present. Those data became the basis for reports of ICRP (1979, 1990), UNSCEAR (1977, 1933), and BEIR (1990). The author would like to raise a question whether the use of ABCC/RERF data was reasonable or not. Based on the cancer incidence in Hiroshima and Nagasaki A-bomb survivors, LNT model that radiation risk is always proportional to dose, no matter how small, was adopted by ICRP, UNSCEAR, and BEIR for the assessment of risk at low doses and for recommendation of dose limits. RERF reported the cancer incidence in A-bomb survivors, 1958-1987 (1994). A linear dose-response relationship was expressed for all solid cancers. In the ABCC/RERF study, however, abscissa of dose-response curves is done from A-bomb with no consideration of dose-rate in spite that the dose-rate is a great factor for the incidence. Incidence is affected not only with radiation dose but also with radiation dose-rate both of which are in inverse proportion to distance from the A-bomb explosion center. The patients were exposed to the radiation at the different dose-rate depending on the distance. Real animal experimental data from HTO administration by Yamamoto et al

  19. Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung

    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/m3 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′-deoxyguanosine (8-oxodGuo) were measured by 32P 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.

  20. Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung

    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.

  1. Has the sensitivity of soybean cultivars to ozone pollution increased with time? An analysis of published dose-response data.

    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. Chronic exposure to odorous chemicals in residential areas and effects on human psychosocial health: dose-response relationships.

    Blanes-Vidal, Victoria; Bælum, Jesper; Nadimi, Esmaeil S; Løfstrøm, Per; Christensen, Lars P

    2014-08-15

    Perceived air pollution, including environmental odor pollution, is known to be an environmental stressor that affects individuals' psychosocial health and well-being. However, very few studies have been able to quantify exposure-response associations based on individual-specific residential exposures to a proxy gas and to examine the mechanisms underlying these associations. In this study, individual-specific exposures in non-urban residential environments during 2005-2010 on a gas released from animal biodegradable wastes (ammonia, NH3) were calculated by the Danish Eulerian long-range transport model and the local-scale transport deposition model. We used binomial and multinomial logistic regression and mediation analyses to examine the associations between average exposures and questionnaire-based data on psychosocial responses, after controlling for person-specific covariates. About 45% of the respondents were annoyed by residential odor pollution. Exposures were associated with annoyance (adjusted odds ratio [ORadj]=3.54, 95% confidence interval [CI]=2.33-5.39), health risk perception (ORadj=4.94; 95% CI=1.95-12.5) and behavioral interference (ORadj=3.28; 95% CI=1.77-6.11), for each unit increase in loge(NH3 exposure). Annoyance was a strong mediator in exposure-behavior interference and exposure-health risk perception relationships (81% and 44% mediation, respectively). Health risk perception did not play a mediating role in exposure-annoyance or exposure-behavioral interference relationships. This is the first study to provide a quantitative estimation of the dose-response associations between ambient NH3 exposures and psychosocial effects caused by odor pollution in non-urban residential outdoor environments. It further shows that these effects are both direct and mediated by other psychosocial responses. The results support the use of NH3 as a proxy gas of air pollution from animal biodegradable wastes in epidemiologic studies. PMID:24880544

  3. Biological effects in lymphocytes irradiated with 99mTc: determination of the curve dose-response

    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)

  4. Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

    Purpose: We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. Methods and Materials: Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. Results: Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade ≤ 1) and short duration (≤1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. Conclusions: In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction

  5. Dose-response relationship of nasopharyngeal carcinoma above conventional tumoricidal level: A study by the Hong Kong nasopharyngeal carcinoma study group (HKNPCSG)

    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

  6. A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects.

    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

  7. Bayesian statistics

    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

  8. Usage Statistics

    ... 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 ...

  9. Fat Intake Is Not Linked to Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis.

    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.

  10. Statistical Inference

    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...

  11. The six year report: Acidification of surface water in Europe and North America. Dose/response relationships and long-term trends

    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.

  12. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

    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...

  13. Fundamental studies on the radiation chemical dose-response with use of thymine. Is activation of the surface between radiation biology and radiation chemistry possible?

    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.)

  14. Establishment of in vitro 192Ir γ-ray dose-response relationship for dose assessment by the lymphocyte dicentric assay

    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.

  15. Dissolution and subsequent re-crystallization as zeroing mechanism, thermal properties and component resolved dose response of salt (NaCl) for retrospective dosimetry

    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.

  16. Dissolution and subsequent re-crystallization as zeroing mechanism, thermal properties and component resolved dose response of salt (NaCl) for retrospective dosimetry

    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.

  17. Antidepressant treatments: effects in rodents on dose-response curves of 5-hydroxytryptamine- and dopamine-mediated behaviours and 5-HT2 receptor number in frontal cortex.

    Green, A. R.; Heal, D. J.; Johnson, P.; Laurence, B. E.; Nimgaonkar, V. L.

    1983-01-01

    The effects of repeated electroconvulsive shock (ECS) administration, repeated desmethylimipramine injection (5 mg kg-1, twice daily for 14 days) and acute administration of the beta-adrenoceptor, clenbuterol, on 5-hydroxytryptamine (5-HT)- and dopamine-mediated behaviours in mice have been examined. All three treatments enhanced the carbidopa/5-hydroxytryptophan (5-HTP)-induced head-twitch response at all doses of 5-HTP examined, producing a parallel shift in the dose-response curve. A singl...

  18. Dose-response curve of EBT, EBT2, and EBT3 radiochromic films to synchrotron-produced monochromatic x-ray beams

    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...

  19. Dose-response analysis of infants prenatally exposed to methyl mercury: An application of a single compartment model to single-strand hair analysis

    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

  20. Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study.

    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...

  1. 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

    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

  2. Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

    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.

  3. Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: a dose-response study.

    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

  4. Statistical methods

    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

  5. Statistical optics

    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

  6. A kinetic model incorporating both localized and delocalized recombination: Application to the dependence of the TL dose response on photon energy

    Eliyahu, I. [Ben Gurion University of the Negev, Beersheva 84105 (Israel); Soreq Nuclear Research Center, Yavne 81800 (Israel); Horowitz, Y.S., E-mail: yigalho@gmail.com [Soreq Nuclear Research Center, Yavne 81800 (Israel); Oster, L. [Sami Shamoon College of Engineering, Beersheva 84100 (Israel); Mardor, I. [Soreq Nuclear Research Center, Yavne 81800 (Israel)

    2014-01-15

    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, n{sub e–h} and e-only concentration, n{sub e}, 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 n{sub e–h} and n{sub e} as a function of photon energy. Specifically, for low dose-levels below ∼1–10 Gy, n{sub e–h}/n{sub e} 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 n{sub e–h}/n{sub e} corresponds to the approximate onset of supralinearity observed for composite peak 5 in LiF:Mg,Ti. This assumed behaviour for n{sub e–h}/n{sub e} is consistent with the structure/size of

  7. A kinetic model incorporating both localized and delocalized recombination: Application to the dependence of the TL dose response on photon energy

    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

  8. Dose-response relationship of physical activity to premature and total all-cause and cardiovascular disease mortality in walkers.

    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. Scan Statistics

    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.

  10. 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

    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.

  11. Introductory statistics

    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

  12. Introductory statistics

    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

  13. Statistics Clinic

    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.

  14. Statistical physics

    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

  15. Reversible Statistics

    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 by...

  16. Multiparametric statistics

    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. ...

  17. SEER Statistics

    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.

  18. CMS Statistics

    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...

  19. Accident Statistics

    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...

  20. Citation Statistics

    Adler, Robert; Ewing, John; Taylor, Peter

    2009-01-01

    This is a report about the use and misuse of citation data in the assessment of scientific research. The idea that research assessment must be done using ``simple and objective'' methods is increasingly prevalent today. The ``simple and objective'' methods are broadly interpreted as bibliometrics, that is, citation data and the statistics derived from them. There is a belief that citation statistics are inherently more accurate because they substitute simple numbers for complex judgments, and...