WorldWideScience
1

Statistical and low dose response  

International Nuclear Information System (INIS)

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

Statistical methods for clinical verification of dose-response parameters related to esophageal stricture and AVM obliteration from radiotherapy  

Energy Technology Data Exchange (ETDEWEB)

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and {chi}{sup 2} test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

Mavroidis, Panayiotis [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University (Sweden); Lind, Bengt K [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University (Sweden); Theodorou, Kyriaki [Department of Medical Physics, Larissa University Hospital, Larissa (Greece); Laurell, Goeran [Department of Otolaryngology, Head and Neck Surgery, Karolinska Hospital, Stockholm (Sweden); Fernberg, Jan-Olof [Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm (Sweden); Lefkopoulos, Dimitrios [Department of Radiation Physics, Tenon Hospital, Paris (France); Kappas, Constantin [Department of Medical Physics, Larissa University Hospital, Larissa (Greece); Brahme, Anders [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University (Sweden)

2004-08-21

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Statistical methods for clinical verification of dose-response parameters related to esophageal stricture and AVM obliteration from radiotherapy  

International Nuclear Information System (INIS)

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and ?2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estmed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use

4

Statistical methods for clinical verification of dose response parameters related to esophageal stricture and AVM obliteration from radiotherapy  

Science.gov (United States)

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and khgr2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

Mavroidis, Panayiotis; Lind, Bengt K.; Theodorou, Kyriaki; Laurell, Göran; Fernberg, Jan-Olof; Lefkopoulos, Dimitrios; Kappas, Constantin; Brahme, Anders

2004-08-01

5

In vivo genotoxicity of EMS: statistical assessment of the dose response curves.  

Science.gov (United States)

EMS induced micronuclei and lacZ mutations in in vivo studies in mice with a clearly sublinear dose dependency. As reported elsewhere in this issue, NOEL dose values of between 25 mg/kg/day and 80 mg/kg/day were observed for the different endpoints and tissues analysed. Here we show that statistical assessment of the data provides solid support that the induction of mutagenic and clastogenic effects after in vivo treatment with the directly DNA damaging mutagen EMS adheres to a thresholded dose response relation. These data corroborate similar evidence obtained in in vitro studies. We conclude that cells are fully capable of repairing large amounts of DNA ethylations induced by EMS without experiencing elevated mutation frequencies. The stochastic, linear risk assessment model generally employed for DNA damaging genotoxins can therefore be refuted for EMS. While presently this conclusion cannot be generalized to other genotoxins a change of paradigm appears to be indicated at least for alkylating agents inducing a comparable type and spectrum of DNA lesions as EMS. PMID:19857797

Gocke, Elmar; Wall, Michael

2009-11-12

6

Some New Aspects of Statistical Inference for Multistage Dose-Response Models with Applications  

Directory of Open Access Journals (Sweden)

Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Applications of the results to dose-response multistage models serve as illustrations. The paper considers various scenarios, and is expected to be of interest to practitioners of risk analysis.

Bimal K. Sinha

2012-07-01

7

Statistical characterization of the random errors in the radioimmunoassay dose--response variable.  

Science.gov (United States)

We have developed practical methods for evaluating the magnitude of the random errors in radioimmunoassay dose--response variables, and the relationship between this error and position on the dose--response curve. This is important: to obtain appropriate weights for each point on the dose--response curve when utilizing least-squares curve-fitting methods; to evaluate whether the standards and the unknowns are subject to error of the same magnitude; for quality-control purposes; and to study the sources of errors in radioimmunoassay. Both standards and unknowns in radioimmunoassays for cAMP and cGMP were analyzed in triplicate. The same mean (Y), sample standard deviation, sy, and variance (2-y) of the response variable were calculated for each dose level. The relationship between s 2-y and y was calculated utilizing several models. Results for standards and unknowns from several assays were pooled, and a curve smoothing procedure was used to minimize random sampling errors. This pooling increased the reliability of the analysis, and confirmed the presence of the theoretically predicted nonuniformity of variance. Thus, the calculation of results from these radioimmunoassays should utilize a weighted least-squares curve-fitting program. These analyses have been computerized, and can be used as a "pre-processor" for programs for routine analysis of results of radioimmunoassay. PMID:175978

Rodbard, D; Lenox, R H; Wray, H L; Ramseth, D

1976-03-01

8

When is statistical significance not significant?  

Directory of Open Access Journals (Sweden)

Full Text Available The article provides a non-technical introduction to the p value statistics. Its main purpose is to help researchers make sense of the appropriate role of the p value statistics in empirical political science research. On methodologica grounds, we use replication, simulations and observational data to show when statistical significance is not significant. We argue that: (1 scholars must always graphically analyze their data before interpreting the p value; (2 it is pointless to estimate the p value for non-random samples; (3 the p value is highly affected by the sample size, and (4 it is pointless to estimate the p value when dealing with data on population.

Dalson Britto Figueiredo Filho

2013-04-01

9

Estimation of dose-response curves and identification of peaks in hormone pulsations: classic marriages of statistics to science  

Science.gov (United States)

Essay on 2 APS Classic Papers by De Léan, Munson, and Rodbard on Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves and by Merriam and Wachter on Algorithms for the study of episodic hormone secretion

PhD Douglas Curran-Everett (National Jewish Medical and Research Center Div. Biostatistics, Depts. Prev. Med./Biometrics, Physiology/Biophys)

2005-09-01

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Dose response in child and adolescent mental health services.  

Science.gov (United States)

This study examines the dose-response relationship, the correlation between the amount of mental health treatment a child receives (dose) and the outcome (response) in a community setting. Participants were 125 children treated in the Stark County Child and Adolescent Mental Health System. Study methods include multiple outcomes, multiple-dose definitions, longitudinal hierarchical analysis of repeated measures, and instrumental variable estimation to control for possible confounding between outcome and treatment dose. Results show no statistically significant dose response. The results do not support the existence of a dose response for children and adolescents consistent enough to guide clinicians, administrators, or policymakers. PMID:12090308

Bickman, Leonard; Andrade, Ana Regina; Lambert, E Warren

2002-06-01

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

International Nuclear Information System (INIS)

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

12

Comments on the Statistical Significance Testing Articles.  

Science.gov (United States)

Expresses a "middle-of-the-road" position on statistical significance testing, suggesting that it has its place but that confidence intervals are generally more useful. Identifies 10 errors of omission or commission in the papers reviewed that weaken the positions taken in their discussions. (SLD)

Knapp, Thomas R.

1998-01-01

13

The Use of Tests of Statistical Significance.  

Science.gov (United States)

Presents an opinion on the appropriate use of significance tests, especially in the context of regression analysis, the most commonly encountered statistical technique in education and related disciplines. Briefly discusses the appropriate use of power analysis. Contains 47 references. (Author/SV)

Knapp, Thomas R.

1999-01-01

14

Fitting and handling dose response data.  

Science.gov (United States)

The half maximal response of any compound in a biological system is a fundamental measure of the compound's potency whether the activity of the compound is beneficial or detrimental. As such, the estimation of this response as an Ec50 or an Ic50 results in a value that has fundamental significance in the determination of the potential of a compound. A collection of these values provide an invaluable data framework for understanding structure-activity relationships and computational method development and benchmarking. Therefore, understanding the errors and reproducibility issues associated with Ic50 determinations is essential for their robust calculation. This paper will discuss the practical approaches to the use of the Levenberg-Marquardt minimization method to fit dose response data and evaluate the resultant data in a statistically rigorous way. PMID:24980646

Jones, Gareth

2015-01-01

15

Social significance of community structure: Statistical view  

Science.gov (United States)

Community structure analysis is a powerful tool for social networks that 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 a partitioned community structure is an urgent and important question. In this paper, integrating the specific characteristics of real society, we present a framework to analyze the significance of a social community. 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 the nodes and their corresponding leaders. Then, using a log-likelihood score, the tightness of the community can be derived. Based on the distribution of community tightness, we establish a connection between p -value theory and network analysis, and then we obtain a significance measure of statistical form . Finally, the framework is applied to both benchmark networks and real social networks. Experimental results show that our work can be used in many fields, such as determining the optimal number of communities, analyzing the social significance of a given community, comparing the performance among various algorithms, etc.

Li, Hui-Jia; Daniels, Jasmine J.

2015-01-01

16

Assessing statistical significance in causal graphs  

Directory of Open Access Journals (Sweden)

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

Chindelevitch Leonid

2012-02-01

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Significant Statistics: Viewed with a Contextual Lens  

Science.gov (United States)

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

Tait-McCutcheon, Sandi

2010-01-01

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Spironolactone dose-response relationships in healthy subjects.  

OpenAIRE

1 The effect of single oral doses of spironolactone 25 mg, 50 mg, 100 mg, 200 mg, 400 mg, and placebo in reversing the urinary electrolyte changes induced by fludrocortisone between 2-10 h and 12-16 h after treatment was examined in healthy subjects. 2 In the two collection periods, there were statistically significant log linear dose-response relationships for sodium excretion (P less than 0.001), potassium excretion (P less than 0.001 and P less than 0.025 respectively) and log10 10 Na/K (P...

Mcinnes, G. T.; Perkins, R. M.; Shelton, J. R.; Harrison, I. R.

1982-01-01

19

Dose response relationship in local radiotherapy for hepatocellular carcinoma  

International Nuclear Information System (INIS)

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 developmon 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-irradiated liver volume

20

The significant digit law in statistical physics  

Science.gov (United States)

The occurrence of the nonzero leftmost digit, i.e., 1,2,…,9, of numbers from many real world sources is not uniformly distributed as one might naively expect, but instead, the nature favors smaller ones according to a logarithmic distribution, named Benford’s law. We investigate three kinds of widely used physical statistics, i.e., the Boltzmann-Gibbs (BG) distribution, the Fermi-Dirac (FD) distribution, and the Bose-Einstein (BE) distribution, and find that the BG and FD distributions both fluctuate slightly in a periodic manner around Benford’s distribution with respect to the temperature of the system, while the BE distribution conforms to it exactly whatever the temperature is. Thus Benford’s law seems to present a general pattern for physical statistics and might be even more fundamental and profound in nature. Furthermore, various elegant properties of Benford’s law, especially the mantissa distribution of data sets, are discussed.

Shao, Lijing; Ma, Bo-Qiang

2010-08-01

21

The Significant Digit Law in Statistical Physics  

CERN Document Server

The occurrence of the nonzero leftmost digit, i.e., 1, 2, ..., 9, of numbers from many real world sources is not uniformly distributed as one might naively expect, but instead, the nature favors smaller ones according to a logarithmic distribution, named Benford's law. We investigate three kinds of widely used physical statistics, i.e., the Boltzmann-Gibbs (BG) distribution, the Fermi-Dirac (FD) distribution, and the Bose-Einstein (BE) distribution, and find that the BG and FD distributions both fluctuate slightly in a periodic manner around the Benford distribution with respect to the temperature of the system, while the BE distribution conforms to it exactly whatever the temperature is. Thus the Benford's law seems to present a general pattern for physical statistics and might be even more fundamental and profound in nature. Furthermore, various elegant properties of Benford's law, especially the mantissa distribution of data sets, are discussed.

Shao, Lijing; 10.1016/j.physa.2010.04.021

2010-01-01

22

Dose response relationship and Alara  

International Nuclear Information System (INIS)

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

23

Mahalanobis distance and variable selection to optimize dose response  

International Nuclear Information System (INIS)

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

24

Caveats for using statistical significance tests in research assessments  

CERN Document Server

This paper raises concerns about the advantages of using statistical significance tests in research assessments as has recently been suggested in the debate about proper normalization procedures for citation indicators. Statistical significance tests are highly 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 is highly problematic and detrimental to critical thinki...

Schneider, Jesper W

2011-01-01

25

A Statistical Significance Simulation Study for the General Scientist  

CERN Document Server

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 that the observed results occurred randomly. This research study visually demonstrates that the commonly used definition for "statistical significance" can erroneously imply a significant finding. This is demonstrated by generating random Gaussian noise data and analyzing that data using statistical testing based on the established two-sample t-test. This study demonstrates that insignificant yet "statistically significant" findings are possible at moderately large sample sizes which are very common in many fields of mode...

Levman, Jacob

2011-01-01

26

Dose--response curve for ethylnitrosourea-induced specific-locus mutations in mouse spermatogonia.  

OpenAIRE

The extreme mutagenic effectiveness of N-ethyl-N-nitrosourea in the mouse has permitted the accumulation of the most extensive dose--response data yet obtained for chemical induction of specific-locus mutations in spermatogonia. In the lower portion of the curve, below a dose of 100 mg/kg, the data fall statistically significantly below a maximum likelihood fit to a straight line. Independent evidence indicates that, over this dose range, ethylnitrosourea reaches the testis in amounts directl...

Russell, W. L.; Hunsicker, P. R.; Raymer, G. D.; Steele, M. H.; Stelzner, K. F.; Thompson, H. M.

1982-01-01

27

A Statistical Significance Simulation Study for the General Scientist  

OpenAIRE

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 th...

Levman, Jacob

2011-01-01

28

Statistical significance test for transition matrices of atmospheric Markov chains  

Science.gov (United States)

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.

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

1990-01-01

29

In vitro human cytogenetic dose-response systems  

International Nuclear Information System (INIS)

To provide dosimetry for radiation accident management, in vitro dose-response models are used for deriving biological estimates of the doses received by individuals involved in accidents. The dose estimates are made by comparing the frequency of specific cytogenetic aberrations in cultured blood lymphocytes of the exposed person with the frequency observed in human lymphocytes irradiated in vitro. Three factors influenced the accuracy of the in vitro dose-response relation determinations. These are the biological aspects of lymphocytes and the culture system, statistical and mathematical aspects of data collection and analysis, and the physical conditions of the in vitro radiation exposure. Each of these factors is discussed and examples of dose-response curves generated for needs of dose-determination in accidents involving americium 241 and iridium 192

30

On detection and assessment of statistical significance of Genomic Islands  

Directory of Open Access Journals (Sweden)

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.

Chaudhuri Probal

2008-04-01

31

Comparable dose-response functions for the effects of glucose and fructose on memory.  

Science.gov (United States)

A passive avoidance-to-active avoidance negative transfer paradigm was used to investigate in rats the effects of glucose and fructose on recently acquired memories. Immediate post-passive avoidance conditioning injections of glucose, fructose, or saline were followed 48 h later by active avoidance conditioning. Equimolar 10, 32, 100, and 2000 mg/kg sc doses of the two sugars significantly impaired acquisition of the reversal task, whereas 3.2 mg/kg doses of both sugars were without significant effect on subsequent performance and 320 mg/kg doses of both sugars significantly enhanced subsequent performance. The cubic trends for both dose-response functions were statistically significant and did not differ from each other. This is the first demonstration that glucose and fructose affect recently acquired memories in accord with comparable cubic dose-response functions, and that there are doses of both sugars that can enhance memory (as indicated by an increase in the number of trials required to reach criterion on the reversal task) and doses of both sugars that can impair memory (as indicated by a decrease in the number of trials required to reach criterion on the reversal task), compared to saline treatment. The similar cubic dose-response functions for glucose and fructose suggest that their mechanisms of action when they are injected peripherally are similar. In addition, because fructose does not readily pass the blood-brain barrier, the results suggest that these two monosaccharides may act through a common peripheral pathway. PMID:8204081

Rodriguez, W A; Horne, C A; Mondragon, A N; Phelps, D D

1994-03-01

32

THE IMPACT OF DOSIMETRY UNCERTAINTIES ON DOSE-RESPONSE ANALYSES  

OpenAIRE

Radiation dose estimates used in epidemiological studies are subject to many sources of uncertainty, and the error structure may be a complicated mixture of different types of error. Increasingly, efforts are being made to evaluate dosimetry uncertainties and to take account of them in statistical analyses. The impact of these uncertainties on dose response analyses depends on the magnitude and type of error. Errors that are independent from subject to subject (random errors) reduce statistic...

Gilbert, Ethel S.

2009-01-01

33

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

International Nuclear Information System (INIS)

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?1 of 0.082 (95% CI 0.031–0.140), and ischemic heart disease, with an excess relative risk Gy?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 0.2). 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 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.

34

Lexical Co-occurrence, Statistical Significance, and Word Association  

OpenAIRE

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 freq...

Chaudhari, Dipak; Damani, Om P.; Laxman, Srivatsan

2010-01-01

35

SIGNIFICANCE OF STATISTICS IN HEALTH SCIENCES IN RURAL AREA  

Directory of Open Access Journals (Sweden)

Full Text Available The present article is aimed at significance ofstatistics in growing health science industries. Health andstatistics are essential tools in demography; health care, medicalprofession and community services. Statistics plays verysignificant role to describe what is normal and healthy inpopulation and to find limits of normality in variables, such asweight and pulse rate, sex and haemoglobin, age andmenstruation cycle etc. Statistics in health sciences willarticulates leading causes of death, sickness, whether particulardiseases is rising or falling in severity and prevalence. Statisticaldata collected from measurements or surveillance that definesthe characteristics of specific population samples. Descriptivestatistics précis the utility, efficacy and expenses of medical goodsand facilities. Progressively, health care organizations employstatistical analysis to measure their performance outcomes. Thistype of study is important in finding the correlation between twovariables, comparison in the action of different drugs, to find anassociation between two attributes, in field of Anatomy &Physiology, Pharmacology, Medicines, and Public health &Community medicines respectively. By collecting the waitingtimes of five different patients chosen at random from Govtdispensary Mallewal, district Patiala, Govt dispensary Dhablan,district Patiala , Govt dispensary Todarpur, district Patiala Govtdispensary Bahadurgarh, district Patiala(treated as out-patientclinics A, B, C, and D to determine if there are differencesbetween the dispensaries using Kruskal-Wallis Application(statistics one can know how statistics is helpful in rural area.

Reetu Malhotra , Vandana Singh , Dr. Rajesh Kumar

2012-05-01

36

Statistical significance of epidemiological data. Seminar: Evaluation of epidemiological studies  

International Nuclear Information System (INIS)

In stochastic damages, the numbers of events, e.g. the persons who are affected by or have died of cancer, and thus the relative frequencies (incidence or mortality) are binomially distributed random variables. Their statistical fluctuations can be characterized by confidence intervals. For epidemiologic questions, especially for the analysis of stochastic damages in the low dose range, the following issues are interesting: - Is a sample (a group of persons) with a definite observed damage frequency part of the whole population? - Is an observed frequency difference between two groups of persons random or statistically significant? - Is an observed increase or decrease of the frequencies with increasing dose random or statistically significant and how large is the regression coefficient (= risk coefficient) in this case? These problems can be solved by sttistical tests. So-called distribution-free tests and tests which are not bound to the supposition of normal distribution are of particular interest, such as: - ?2-independence test (test in contingency tables); - Fisher-Yates-test; - trend test according to Cochran; - rank correlation test given by Spearman. These tests are explained in terms of selected epidemiologic data, e.g. of leukaemia clusters, of the cancer mortality of the Japanese A-bomb survivors especially in the low dose range as well as on the sample of the cancer mortality in the high background area in Yangjiang (China). (orig.) in Yangjiang (China). (orig.)

37

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

International Nuclear Information System (INIS)

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?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 Japatent 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.

38

La (significativa) importancia biológica de la no-significancia estadística / The (significant) biological significance of statistical non-significance  

Scientific Electronic Library Online (English)

Full Text Available SciELO Argentina | Language: Spanish Abstract in spanish El rechazo de hipótesis biológicas incorrectas como consecuencia de resultados estadísticamente no-significativos es comúnmente despreciado como un aporte para el crecimiento del conocimiento científico. Los argumentos previos contra esta creencia se han basado principalmente en las consecuencias ne [...] gativas de la escasa divulgación de resultados estadísticamente no-significativos más que enfocarse sobre el mérito lógico de descartar ideas erróneas. En este ensayo, discutiré cómo los métodos estadísticos clásicos (i.e., estadística frecuentista), y la base epistemológica de la cual derivan, están basados en la eliminación de ideas falsas más que en el descubrimiento de ideas potencialmente verdaderas. El menosprecio de buenas investigaciones y/o su eventual rechazo editorial debido a su no-significancia estadística niega, entonces, la principal ventaja de los métodos estadísticos tradicionales: refutar ideas incorrectas. Rechazar una hipótesis biológica basándose en una investigación de buena calidad y alto poder estadístico es una de las formas más robustas de aprender sobre el funcionamiento de la naturaleza. Abstract in english Rejecting incorrect biological hypotheses as a consequence of statistically non-significant results is commonly undervalued as a step in the growth of our knowledge. Previous arguments against this incorrect belief had been largely based on the negative consequences associated with not publishing pa [...] pers with statistically non-significant results rather than on the intrinsic epistemological merits to discarding erroneous ideas. In this essay, I will discuss how classical statistical methods and the epistemological approach from which these tools are derived are largely based on the elimination of falsehood rather than on the discovery of truth. The rejection of researches with statistically non-significant results denies the main advantage of classical hypothesis-testing methods. In fact, the rejection of an incorrect biological hypothesis based on high-quality research is one of the most powerful ways to understand nature.

Alejandro G, Farji-Brener.

2006-06-01

39

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

Science.gov (United States)

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

Pedersen, Eja; Waye, Kerstin Persson

2004-12-01

40

Hormetic dose-responses in nanotechnology studies.  

Science.gov (United States)

While exposure to nanoparticles is a growing concern, research into their toxicological impact and possible hazard for human health is limited. There remains a lack of information concerning the nature of the dose-response relationship especially at low level exposures. The present paper assesses the occurrence of hormetic-like biphasic dose responses within the nanotoxicology literature. The findings indicate that nanoparticles may induce hormetic-like biphasic dose responses in a wide range of biological cell types, and that these responses can be highly dependent upon the physical and chemical properties of the agent. While the mechanistic foundations of hormetic dose responses induced by chemicals and pharmaceuticals have markedly advanced over the past decade, this remains an important data need for nanotoxicology. PMID:24793332

Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Calabrese, Edward J

2014-07-15

41

Statistical significance of climate sensitivity predictors obtained by data mining  

Science.gov (United States)

Several recent efforts to estimate Earth's equilibrium climate sensitivity (ECS) focus on identifying quantities in the current climate which are skillful predictors of ECS yet can be constrained by observations. This study automates the search for observable predictors using data from phase 5 of the Coupled Model Intercomparison Project. The primary focus of this paper is assessing statistical significance of the resulting predictive relationships. Failure to account for dependence between models, variables, locations, and seasons is shown to yield misleading results. A new technique for testing the field significance of data-mined correlations which avoids these problems is presented. Using this new approach, all 41,741 relationships we tested were found to be explainable by chance. This leads us to conclude that data mining is best used to identify potential relationships which are then validated or discarded using physically based hypothesis testing.

Caldwell, Peter M.; Bretherton, Christopher S.; Zelinka, Mark D.; Klein, Stephen A.; Santer, Benjamin D.; Sanderson, Benjamin M.

2014-03-01

42

A new approach to evaluating statistical significance of spectral identifications.  

Science.gov (United States)

While nonlinear peptide natural products such as Vancomycin and Daptomycin are among the most effective antibiotics, the computational techniques for sequencing such peptides are still in their infancy. Previous methods for sequencing peptide natural products are based on Nuclear Magnetic Resonance spectroscopy and require large amounts (milligrams) of purified materials. Recently, development of mass spectrometry-based methods has enabled accurate sequencing of nonlinear peptide natural products using picograms of material, but the question of evaluating statistical significance of Peptide Spectrum Matches (PSM) for these peptides remains open. Moreover, it is unclear how to decide whether a given spectrum is produced by a linear, cyclic, or branch-cyclic peptide. Surprisingly, all previous mass spectrometry studies overlooked the fact that a very similar problem has been successfully addressed in particle physics in 1951. In this work, we develop a method for estimating statistical significance of PSMs defined by any peptide (including linear and nonlinear). This method enables us to identify whether a peptide is linear, cyclic, or branch-cyclic, an important step toward identification of peptide natural products. PMID:23343606

Mohimani, Hosein; Kim, Sangtae; Pevzner, Pavel A

2013-04-01

43

Large SDSS quasar groups and their statistical significance  

CERN Document Server

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...

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

2015-01-01

44

Lexical Co-occurrence, Statistical Significance, and Word Association  

CERN Document Server

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...

Chaudhari, Dipak; Laxman, Srivatsan

2010-01-01

45

The statistical significance of the superhump signal in U Gem  

CERN Document Server

Although its well determined mass ratio of $q=\\Msec/\\Mwd=0.357\\pm0.007$ should avoid superoutbursts according to the thermal tidal instability model, the prototypical dwarf nova U Gem experienced in 1985 an extraordinary long outburst resembling very much superoutbursts observed in SU UMa systems. Recently, the situation for the model became even worse as superhump detections have been reported for the 1985 outburst of U Gem. The superhump signal is noisy and the evidence provided by simple periodograms seems to be weak. Therefore and because of the importance for our understanding of superoutbursts and superhumps, we determine the statistical significance of the recently published detection of superhumps in the AAVSO light curve of the famous long 1985 outburst of U Gem. Using Lomb-Scargle periodograms, analysis of variance (AoV), and Monte-Carlo methods we analyse the 160 visual magnitudes obtained by the AAVSO during the outburst and relate our analyse to previous superhump detections. The 160 data points ...

Schreiber, M R

2007-01-01

46

A dose response study of oxitropium bromide in chronic bronchitis.  

OpenAIRE

In a dose response study 12 patients with chronic bronchitis and airflow obstruction received inhaled placebo and incremental doses of oxitropium bromide. Significant improvements in peak expiratory flow rate, forced expiratory volume in one second, and forced vital capacity were recorded at all times up to 10 hours after all doses of oxitropium bromide. Oxitropium bromide is an effective bronchodilator in chronic bronchitis with an optimal dose of 400-600 micrograms.

Peel, E. T.; Anderson, G.

1984-01-01

47

Dose-response relationship in clinical oncology  

International Nuclear Information System (INIS)

The relationship of dose (and dose rate) to response and toxicity in clinical oncology is reviewed. The concepts expressed by some authors in dose-response studies in animal and human systems are reviewed briefly. Dose rate and tactics of conducting clinical studies are reviewed for both radiotherapy and various types of chemotherapeutic treatment. Examples are given from clinical studies in Hodgkin's disease, acute leukemia, and breast cancer that may prove useful in planning future clinical studies

48

Dose-response relationship in clinical oncology  

Energy Technology Data Exchange (ETDEWEB)

The relationship of dose (and dose rate) to response and toxicity in clinical oncology is reviewed. The concepts expressed by some authors in dose-response studies in animal and human systems are reviewed briefly. Dose rate and tactics of conducting clinical studies are reviewed for both radiotherapy and various types of chemotherapeutic treatment. Examples are given from clinical studies in Hodgkin's disease, acute leukemia, and breast cancer that may prove useful in planning future clinical studies.

Gehan, E.A.

1984-09-15

49

Inhalation Anthrax: Dose Response and Risk Analysis  

OpenAIRE

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 ...

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

2008-01-01

50

Comparison of the dose-response relationships for chromosome aberration frequencies between the T65D and DS86 dosimetries  

International Nuclear Information System (INIS)

Cytogenetic data, derived from cultured lymphocytes of atomic bomb survivors and controls in the ABCC-RERF Adult Health Study cohort, have been analyzed to determine differences in the dose-response relationships for chromosome aberrations between the T65D and DS86 dose estimates and to assess differences between Hiroshima and Nagasaki. For a linear dose-response model, the average percentage of cells with at least one chromosome aberration increases less rapidly with dose in Nagasaki than in Hiroshima. The magnitude of the intercity difference in the percentage of cells with aberrations per gray is less for DS86 than for T65D, though the difference is statistically significant for both kerma and bone marrow dose with either dosimetry. The percentage of cells with aberrations per gray for DS86 kerma estimates is about 60 % greater than the corresponding T65D slope. Analyses to test nonlinearity in the dose-response function indicate significant departures (p<.001) from linearity, using both dosimetries for both kerma and marrow dose. Therefore, comparative results are presented for a range of RBE relationships under various linear (L) and linearquadratic linear (LQ-L) models. As an illustrative result, if one assumes an LQ-L model similar to models reported in the cytogenetic literature, with a limiting RBE of 20 at zero dose, the DS86 slope (the percentage of cells with aberrations per sievert) is 120 % greater than the corresponding T65D value. (J.P.N.)

51

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

52

Library Statistics and User Satisfaction: No Significant Correlation.  

Science.gov (United States)

Suggests such traditional measures of an academic library's worth as volumes added, numbers of serials, total staff, and materials expenditures have no significant correlation to the effectiveness of a library's services or user satisfaction; also that future success in effectiveness lies with cost effective management of available resources. (RAA)

De Gennaro, Richard

1980-01-01

53

Dose-response of inhaled drugs in asthma. An update.  

Science.gov (United States)

The demographic characteristics of patients used in clinical trials (such as the severity of airway obstruction) can significantly influence the results of dose-response studies, emphasising the need to evaluate effects on the steep part of the dose-response curve. Differences in inhaler devices can also influence study outcomes, as for inhaled drugs both airway efficacy and adverse effect profiles are primarily determined by lung deposition and hence bioavailability. Dose-response studies with short- and long-acting beta 2-agonists show an excellent therapeutic ratio at conventional doses used in everyday clinical practice (i.e. 2 to 4 puffs). Dose-related systemic effects of beta 2-agonist occur at higher doses, for salbutamol (albuterol) > 500 micrograms. Fenoterol is a beta 2-agonists with higher intrinsic activity than salbutamol and produces greater systemic effects at higher than conventional doses on a microgram equivalent basis, although even at 4000 micrograms such differences are unlikely to be clinically relevant. No differences between fenoterol and salbutamol have been shown in terms of bronchodilator potency on a microgram equivalent basis. The long-acting beta 2-agonist salmeterol, as a partial agonist, has the potential to attenuate the acute bronchodilator response to a higher activity beta 2-agonist such as salbutamol or fenoterol, although there is no evidence to date on whether this is relevant in the setting of acute asthma. When comparing inhaled corticosteroids, attention should be focused on their respective risk-benefit ratios for antiasthmatic versus systemic activity. In terms of detecting systemic activity, it is important to use sensitive measures, such as urinary cortisol excretion, rather than insensitive parameters, such as a single morning plasma cortisol measurement between 0800h and 1000h. For fluticasone, a greater in vitro potency results in only marginal differences in antiasthmatic efficacy, particularly on the flatter part of the dose-response curve above 1000 micrograms/day in adults and 400 micrograms/day in children. However, the same enhanced potency translates directly into commensurate differences in systemic adverse effects on the steep part of the systemic dose-response curve above 1000 micrograms/day in adults and 400 micrograms/day in children, respectively. Furthermore, with repeated twice-daily administration, a longer elimination half-life and prolonged systemic tissue retention due to enhanced lipophilicity will result in greater systemic activity observed at steady-state in long term administration studies. This dissociation of airway and systemic dose-response curves results in a J-shaped curve for benefit: risk ratio, with a watershed area above 1000 microgram/day in adults. This fall in the benefit: risk ratio is likely to be greater for fluticasone than for budesonide or beclomethasone. Further studies are needed to clearly define the dose-response relationships of higher potency steroids such as fluticasone, particularly on the steep part of the curve (for clinical efficacy), using the appropriate back-titration design along with sensitive measures of antiasthmatic and systemic activity. PMID:9012556

Clark, D J; Lipworth, B J

1997-01-01

54

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

International Nuclear Information System (INIS)

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

55

Modeling dose response using generalized linear models  

Energy Technology Data Exchange (ETDEWEB)

This paper describes a method to determine and model dose-response relationships from binomial response data using generalized linear models (GLM). The main advantage of this technique is that it allows LC{sub p} or LD{sub p} to be determined without an initial linearizing transformation. (LC{sub p} and LD{sub p} are the lethal concentration or dose that causes p proportion of test animals to die at a specified time period.) Thus, the method of GLM is an appropriate way to analyze a dose-response relationship because it utilizes the inherent S-shaped feature of the toxicologic response and incorporates the sample size of each trial in parameter estimation. This method is also much better behaved when the extremes of the response probability are considered because responses of 0% and 100% are included in the model. Another advantageous feature of this method is that confidence intervals (C.I.s) for both the dose estimate and response probabilities can be computed with GLM, which provides a more complete description of the estimates and their inherent uncertainty. Because C.I.s for both the dose estimate and response probabilities can be constructed, the lowest observed effect concentration (LOEC) can also be determined.

Kerr, D.R. [Univ. of Washington, Seattle, WA (United States). Dept. of Statistics; Meador, J.P. [National Oceanic and Atmospheric Administration, Seattle, WA (United States)

1996-03-01

56

Dose-response relations from epidemiological studies  

International Nuclear Information System (INIS)

The paper discusses dose-response relations by using information about carcinogens in man as examples. Setting aside tobacco, alcoholic drinks and certain drugs, there are only two factors for which quantitative data about personal exposure in industry to incidence of cancer are available over a range wide enough to make it possible to study the shape of the relation: chrysotile asbestos and ionizing radiation. In both cases the relation is considered to be linear. As far as chrysotile is concerned, extrapolation based on the linear model suggests that the risks of lung cancer associated with exposure to the levels of asbestos dust found in buildings not under construction or repair and in ambient urban air are trivial. Contrary to popular opinion, the risk of mesothelioma increases with the dose of asbestos (principally amphiboles), but the exact shape of the relation is not known. The experience of Canadian uranium miners is discussed to contrast the dose-response relations for fatal industrial accidents and industrial lung cancer in this population of workers. (author)

57

Evaluating clinical significance: incorporating robust statistics with normative comparison tests.  

Science.gov (United States)

The purpose of this study was to evaluate a modified test of equivalence for conducting normative comparisons when distribution shapes are non-normal and variances are unequal. A Monte Carlo study was used to compare the empirical Type I error rates and power of the proposed Schuirmann-Yuen test of equivalence, which utilizes trimmed means, with that of the previously recommended Schuirmann and Schuirmann-Welch tests of equivalence when the assumptions of normality and variance homogeneity are satisfied, as well as when they are not satisfied. The empirical Type I error rates of the Schuirmann-Yuen were much closer to the nominal ? level than those of the Schuirmann or Schuirmann-Welch tests, and the power of the Schuirmann-Yuen was substantially greater than that of the Schuirmann or Schuirmann-Welch tests when distributions were skewed or outliers were present. The Schuirmann-Yuen test is recommended for assessing clinical significance with normative comparisons. PMID:23751017

van Wieringen, Katrina; Cribbie, Robert A

2014-05-01

58

Dose response from pharmacological interventions for CBF changes in a baboon model using 99Tcm-HMPAO and SPECT  

International Nuclear Information System (INIS)

This study assesses the sensitivity of the baboon model under anaesthesia to determine by single photon emission computed tomography (SPECT) and 99Tcm-hexamethylpropyleneamine oxime (HMPAO) dose responses from drugs (acetazolamide) with known regional cerebral blood flow (rCBF) effects on humans. Three dosages of acetazolamide were chosen: 250, 500 and 750 mg. The effects of these were studied by conventional SPECT 5 min after intravenous (i.v.) administration and compared to previous studies of rCBF with the baboons under anaesthesia only. An additional study concerned the effect of 500 mg acetazolamide at 15 min after administration. Haemodynamic parameters and blood gases were also monitored. No statistically significant regional effects were noted. The largest increase in CBF (39%) was observed from 500 mg acetazolamide after 5 min. This was statistically significantly different from control values only at a 10% level of confidence; then following a 27% increase above control values after 750 mg (5 min). At 15 min 500 mg yielded values lower by 10% than the high dose. No effects were observed from 250 mg acetazolamide; only pO2 showed changes which largely confirm the CBF findings. The model did not give significant results at a 5% level of confidence but large fluctuations were observed, also in the haemodynamic and blood gas values. At a 10% level a significant dose response was confirmed for acetazolamide. (author) for acetazolamide. (author)

59

Dose response for iodine - 125 prostate implants  

International Nuclear Information System (INIS)

Objective: No dose response study has ever been performed for I-125 prostate implants using modern techniques of implant evaluation and modern treatment outcome endpoints. Using an interactive ultrasound guided technique and post-implant dosimetry, we have increased the amount of activity implanted per volume over time. This has resulted in different delivered dose levels. This study explores the relationship between dose, biochemical failure and biopsy results. Materials and Methods: 121 patients with T1 - T2 prostate cancer were implanted with I-125 radioactive seeds and followed from 6 to 67 months (median - 25) post-implant. No patient received external beam irradiation or hormonal therapy. All patients implanted with I-125 had Gleason scores ? 6. Presenting PSA levels ranged from 1.9 - 189 ng/ml (median - 7.6 ng/ml). One month post-implant, a CT based three dimensional dosimetric evaluation was performed on all patients. Using TG43 guidelines, dose volume histograms were calculated. The dose delivered to the gland was defined as the D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged from 26.8 to 229.8 Gy (median - 136.9 Gy). Biochemical failure was defined as 2 consecutive rises in PSA or a nadir level above 1.0 ng/ml. Post-treatment prostate biopsies (6 core samples) were routinely performed at 2 years post-implant. Results: A dose response was found at a D90 of 140 Gy. Patients receiving a D90 10 ng/ml were seen in (60% vs. 40%) and (68% vs. 32%) for the low dose and high dose groups, respectively. Stages were T1b-T2a vs. T2b-T2c in (48% vs. 52%) and (57% vs. 43%) for the low and high dose groups, respectively. Low grade lesions (score 2-4) were seen in 40% and 23% of low dose and high dose groups, respectively. Moderate grade lesions (score 5-6) were seen in 60% and 77% of low dose and high dose groups, respectively. Patients receiving a D90 10 ng/ml. In these patients, the 4 year FBF rates were 51% and 100% for the low and high dose groups, respectively (p=0.04). In patients with presenting PSA ? 10 ng/ml, the 4 year FBF rates were 66% and 89% for the low and high dose groups, respectively (p=0.29). Conclusion: A dose response was observed at a level of 140 Gy. Adequate I -125 implants should be considered those delivering a minimum of 140 Gy to the D90. Longer follow-up with more patients is needed to assess dose response levels above 140 Gy

60

Dose-response and risk assessment of airborne hexavalent chromium and lung cancer mortality.  

Science.gov (United States)

This study evaluates the dose-response relationship for inhalation exposure to hexavalent chromium [Cr(VI)] and lung cancer mortality for workers of a chromate production facility, and provides estimates of the carcinogenic potency. The data were analyzed using relative risk and additive risk dose-response models implemented with both Poisson and Cox regression. Potential confounding by birth cohort and smoking prevalence were also assessed. Lifetime cumulative exposure and highest monthly exposure were the dose metrics evaluated. The estimated lifetime additional risk of lung cancer mortality associated with 45 years of occupational exposure to 1 microg/m3 Cr(VI) (occupational exposure unit risk) was 0.00205 (90%CI: 0.00134, 0.00291) for the relative risk model and 0.00216 (90%CI: 0.00143, 0.00302) for the additive risk model assuming a linear dose response for cumulative exposure with a five-year lag. Extrapolating these findings to a continuous (e.g., environmental) exposure scenario yielded an environmental unit risk of 0.00978 (90%CI: 0.00640, 0.0138) for the relative risk model [e.g., a cancer slope factor of 34 (mg/kg-day)-1] and 0.0125 (90%CI: 0.00833, 0.0175) for the additive risk model. The relative risk model is preferred because it is more consistent with the expected trend for lung cancer risk with age. Based on statistical tests for exposure-related trend, there was no statistically significant increased lung cancer risk below lifetime cumulative occupational exposures of 1.0 mg-yr/m3, and no excess risk for workers whose highest average monthly exposure did not exceed the current Permissible Exposure Limit (52 microg/m3). It is acknowledged that this study had limited power to detect increases at these low exposure levels. These cancer potency estimates are comparable to those developed by U.S. regulatory agencies and should be useful for assessing the potential cancer hazard associated with inhaled Cr(VI). PMID:14641890

Crump, Casey; Crump, Kenny; Hack, Eric; Luippold, Rose; Mundt, Kenneth; Liebig, Elizabeth; Panko, Julie; Paustenbach, Dennis; Proctor, Deborah

2003-12-01

61

Quantification of Hormesis in Anticancer-Agent Dose-Responses  

OpenAIRE

Quantitative features of dose responses were analyzed for 2,189 candidate anticancer agents in 13 strains of yeast (Saccharomyces cerevisiae). The agents represent a diverse class of chemical compounds including mustards, other alkylating agents, and antimetabolites, inter alia. Previous analyses have shown that the responses below the toxic threshold were stimulatory and poorly predicted by a threshold dose-response model, while better explained by a hormetic dose-response model. We determin...

Nascarella, Marc A.; Stanek, Edward J.; Hoffmann, George R.; Calabrese, Edward J.

2009-01-01

62

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

Science.gov (United States)

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…

Ozturk, Elif

2012-01-01

63

Dose-response analysis for nasopharyngeal carcinoma: an historical perspective  

International Nuclear Information System (INIS)

Historical review of 118 patients with nasopharyngeal cancer treated in our institution from 1950--1978 showed a 20% improvement in tumor control for patients irradiated during the most recent period (1974--1978). This improvement was attributed to prescription of higher doses of radiation as well as improvements in technical accuracy and dose delivery to the tumor during that period. Rates of severe and mild complications were comparable and survival was not significantly altered over time despite improved tumor control. Within the range of doses delivered, there was no improvement in tumor control with increasing doses of radiation for small or large nasopharyngeal carcinomas. The dose-response analysis for tumor control was less than ideal because a number of prerequisites were lacking and because the study extended over a 28-year span during which there were significant changes in technology and physician orientation

64

Dose-response relationship for radiation therapy of subclinical disease  

International Nuclear Information System (INIS)

Purpose: To determine the dose-response relationship for elective treatment of subclinical metastatic deposits and validate a model for metastatic tumor cell burden. Methods and Materials: The incidence of overt metastases in electively irradiated potential sites of spread from carcinomas of the head and neck, breast, cervix, ovary, lung, and testis, and from melanomas and osteosarcomas, was compared with the incidence in patients not receiving elective irradiation. The reduction in incidence of metastases was analyzed as a function of radiation dose. Results: The dose-response curve for control of subclinical metastases is linear and shallow, and extrapolates to a dose intercept not demonstrably different from zero. A small threshold may reflect growth of residual micrometastases between treatment for the primary and elective irradiation. The shallow linear dose response reflects interpatient heterogeneity in metastatic tumor cell burden, ranging from 1 to M cells, where M is the upper limit of clinical undetectability. While a dose of 50 Gy in 2 Gy fractions is necessary to achieve an overall 90% reduction in the incidence of metastases, the metastatic cell burden in a proportion of patients can be eliminated by low doses. Thus, worthwhile rates of control can still be achieved when 'tolerance' dictates lower than optimal doses, evidenced by the linearity and lack of significant threshold in the dose-response curve. This is an important difference from treatment of an important difference from treatment of gross disease. The biological effectiveness of elective treatment is measured directly by the percent reduction in failure rate. Although it depends upon the log cell kill, it relates only to that proportion of patients harboring subclinical disease, and, therefore, is not well described by the increase in the cure rate for the total patient population. The linear dose-response relationship for reduction in failure rate is independent of the 'natural' (untreated) incidence of subclinical metastasis, and, therefore, of site, histology, growth rate, stage, or other characteristics of the tumor. Conversely, the clinical effectiveness of elective treatment is measured by increase in tumor control rate and depends upon the 'natural' incidence of metastasis: the higher it is, the greater the absolute increase in cure rate from a constant biological effect (log cell kill). Conclusions: (a) High control rates for subclinical metastases require doses of about 50 Gy in 2 Gy fractions, but worthwhile benefits can be achieved by lower doses if necessitated by reduced tolerance; (b) elective treatment of subclinical metastases should be instituted close to the time of treatment of the primary; (c) the biological effectiveness of elective radiation (or chemotherapy) should be measured by the percentage decrease in metastasis, not by improvements in the rate of control; and (d) demonstration of success in clinical trials of adjuvant therapy is more likely the higher the incidence of metastases in untreated controls

65

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

International Nuclear Information System (INIS)

Ionizing radiation sources for pacific uses are being extensively utilized by modern society and the applications of these sources have raised the probability of the occurrence of accidents. The accidental exposition to radiation creates a necessity of the development of methods to evaluate dose quantity. This data could be obtained by the measurement of damage caused by radiation in the exposed person. The radiation dose can be estimated in exposed persons through physical methods (physical dosimetry) but the biological methods can't be dispensed, and among them, the cytogenetic one that makes use of chromosome aberrations (dicentric and centric ring) formed in peripheral blood lymphocytes (PBL) exposed to ionizing radiation. This method correlates the frequency of radioinduced aberrations with the estimated absorbed dose, as in vitro as in vivo, which is called cytogenetic dosimetry. By the introduction of improved new techniques in culture, in the interpretation of aberrations in the different analysers of slides and by the adoption of different statistical programs to analyse the data, significant differences are observed among laboratories in dose-response curves (calibration curves). The estimation of absorbed dose utilizing other laboratory calibration curves may introduce some uncertainties, so the International Atomic Energy Agency (IAEA) advises that each laboratory elaborates your own dose-response curve for cytogenetic dosimetry. The results were obtained from peripheral blood lymphocytes of the healthy and no-smoking donors exposed to 60Co and 137Cs radiation, with dose rate of 5 cGy.min.-1. Six points of dose were determined 20,50,100,200,300,400 cGy and the control not irradiated. The analysed aberrations were of chromosomic type, dicentric and centric ring. The dose response curve for dicentrics were obtained by frequencies weighted in liner-quadratic mathematic model and the equation resulted were for 60Co: Y = (3 46 +- 2.14)10-4 cGy-1 + (3.45 +- 0.64)10-6 cGy''-2 and for 137Cs'Cs: Y = (7.69 +- 2.33)10-4 cGy-1 + (l,96 +- 0,58)10-6 cGy-2. (author)

66

Curve fitting toxicity test data: Which comes first, the dose response or the model?  

Energy Technology Data Exchange (ETDEWEB)

The probit model frequently does not fit the concentration-response curve of NPDES toxicity test data and non-parametric models must be used instead. The non-parametric models, trimmed Spearman-Karber, IC{sub p}, and linear interpolation, all require a monotonic concentration-response. Any deviation from a monotonic response is smoothed to obtain the desired concentration-response characteristics. Inaccurate point estimates may result from such procedures and can contribute to imprecision in replicate tests. The following study analyzed reference toxicant and effluent data from giant kelp (Macrocystis pyrifera), purple sea urchin (Strongylocentrotus purpuratus), red abalone (Haliotis rufescens), and fathead minnow (Pimephales promelas) bioassays using commercially available curve fitting software. The purpose was to search for alternative parametric models which would reduce the use of non-parametric models for point estimate analysis of toxicity data. Two non-linear models, power and logistic dose-response, were selected as possible alternatives to the probit model based upon their toxicological plausibility and ability to model most data sets examined. Unlike non-parametric procedures, these and all parametric models can be statistically evaluated for fit and significance. The use of the power or logistic dose response models increased the percentage of parametric model fits for each protocol and toxicant combination examined. The precision of the selected non-linear models was also compared with the EPA recommended point estimation models at several effect.levels. In general, precision of the alternative models was equal to or better than the traditional methods. Finally, use of the alternative models usually produced more plausible point estimates in data sets where the effects of smoothing and non-parametric modeling made the point estimate results suspect.

Gully, J.; Baird, R.; Bottomley, J.

1995-12-31

67

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

International Nuclear Information System (INIS)

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

68

Strategies for Testing Statistical and Practical Significance in Detecting DIF with Logistic Regression Models  

Science.gov (United States)

This study examines three controversial aspects in differential item functioning (DIF) detection by logistic regression (LR) models: first, the relative effectiveness of different analytical strategies for detecting DIF; second, the suitability of the Wald statistic for determining the statistical significance of the parameters of interest; and…

Fidalgo, Angel M.; Alavi, Seyed Mohammad; Amirian, Seyed Mohammad Reza

2014-01-01

69

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

OpenAIRE

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 predicte...

Larsen Thomas; Krogh Anders

2003-01-01

70

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

Science.gov (United States)

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.

Xu, Kuan-Man

2006-01-01

71

Dose-response curves for chromosome aberrations induced by 60Co ?-rays and analysed by dual-colour fluorescence in situ hybridization  

International Nuclear Information System (INIS)

Objective: To explore the feasibility of using fluorescence in situ hybridization (FISH) to detect stable chromosome translocation as a biological dosimeter. Methods: Translocation and dicentric frequencies in peripheral blood lymphocytes induced by 60Co ?-rays at different doses were analysed by conventional staining and dual-colour FISH with composite whole chromosome-specific probes for human chromosomes 1 and 4, and their dose-response curves were fitted. Results: All dose response curves for translocation and dicentrics from FISH analysis, as well as dicentrics from conventional staining could be described by linear-quadratic equations Y = c + ?D + ?D2. The difference between dicentric frequencies analysed by FISH and conventional staining were not statistically significant (P>0.05). for radiation-induced translocation and dicentrics in chromosomes 1 and 4, no significant differences were found between the observed frequencies and expected frequencies based on DNA content. Conclusion: Chromosome translocation can be quickly and accurately analysed by FISH and has a good dose-response relationship; thus, it is hopeful to use translocation frequencies measured by FISH as a long-term or accumulative biological dosimeter

72

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

DEFF Research Database (Denmark)

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 in model evaluation. In these areas models are treated as inherently misspecified and, consequently, are evaluated empirically by other methods than statistical tests. I also criticise McCloskey & Ziliak for their strong focus on the size of parameter estimates while neglecting the important question 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 between statistical and economic significance is well appreciated, but which also shows how statistical tests have contributed to our substantive economic understanding.

Engsted, Tom

2009-01-01

73

Determining sexual dimorphism in frog measurement data: integration of statistical significance, measurement error, effect size and biological significance  

Directory of Open Access Journals (Sweden)

Full Text Available Several analytic techniques have been used to determine sexual dimorphism in vertebrate morphological measurement data with no emergent consensus on which technique is superior. A further confounding problem for frog data is the existence of considerable measurement error. To determine dimorphism, we examine a single hypothesis (Ho = equal means for two groups (females and males. We demonstrate that frog measurement data meet assumptions for clearly defined statistical hypothesis testing with statistical linear models rather than those of exploratory multivariate techniques such as principal components, correlation or correspondence analysis. In order to distinguish biological from statistical significance of hypotheses, we propose a new protocol that incorporates measurement error and effect size. Measurement error is evaluated with a novel measurement error index. Effect size, widely used in the behavioral sciences and in meta-analysis studies in biology, proves to be the most useful single metric to evaluate whether statistically significant results are biologically meaningful. Definitions for a range of small, medium, and large effect sizes specifically for frog measurement data are provided. Examples with measurement data for species of the frog genus Leptodactylus are presented. The new protocol is recommended not only to evaluate sexual dimorphism for frog data but for any animal measurement data for which the measurement error index and observed or a priori effect sizes can be calculated.Técnicas analíticas variadas têm sido usadas para avaliar o dimorfismo sexual em medidas de vertebrados, mas não há consenso sobre o melhor procedimento. Um problema adicional, no caso dos anfíbios, é a presença de ponderável erro de medida. Para analisar dimorfismo sexual examinamos uma única hipótese (Ho = médias iguais para dois grupos (fêmeas e machos. Demonstramos que dados de anfíbios preenchem as premissas para hipóteses estatísticas claramente definidas, usando modelos lineares em vez de técnicas exploratórias multivaraiadas, tais como components principais, correlação ou análise de correspondências. Para distinguir significância biológica de significância estatística nas hipóteses, propomos um protocolo incorporando erro de medida e "effect size". O erro de medida é avaliado por meio de um novo índice específico. Demonstramos que "effect size", amplamente usado nas ciências do comportamento e em meta-análises biológicas, é a medida mais útil na discriminação entre significância biológica e significância estatística. São dadas definições de uma ampla gama de "effect sizes" para dados anfibiológicos. São apresentados exemplos com medidas do gênero Leptodactylus. O novo protocolo é recomenadado não apenas no caso de anfíbios, mas em todos os casos de vertebrados em que possam ser calculados erros de medida e "effect sizes" observados ou determinados a priori.

Lee-Ann C. Hayek

2005-03-01

74

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

KAUST Repository

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.

Zhang, Zhang

2012-03-22

75

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

OpenAIRE

Permutation-based statistics for evaluating the significance of class prediction, predictive attributes, and patterns of association have only appeared within the learning classifier system (LCS) literature since 2012. While still not widely utilized by the LCS research community, formal evaluations of test statistic confidence are imperative to large and complex real world applications such as genetic epidemiology where it is standard practice to quantify the likelihood that a seemingly mean...

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

2013-01-01

76

Computer program for fitting dose-response curves  

International Nuclear Information System (INIS)

A BASIC language microcomputer program is described for analysis of the dose-response curves. The mathematical consideration is based on the single hit-multi target model by using the least square method

77

Estimating Dose-Response Relationships Between Noise Exposure ...  

SCPinfonet

20081 the IGCB(N) established a framework to achieving this task and identified \\further ... Where a robust evidence base exists, to develop robust dose-response \\functions ... general application to inform policy on adverse health effects.

78

Characterization of Statin Dose-response within Electronic Medical Records  

OpenAIRE

Efforts to define the genetic architecture underlying variable statin response have met with limited success possibly because previous studies were limited to effect based on one-single-dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 pre-selected variants. Two large biobanks were used to construct dose-response curves for 2,026 (simvastatin) and 2,252 subjects (atorvastat...

Wei, Wei-qi; Feng, Qiping; Jiang, Lan; Waitara, Magarya S.; Iwuchukwu, Otito F.; Roden, Dan M.; Jiang, Min; Xu, Hua; Krauss, Ronald M.; Rotter, Jerome I.; Nickerson, Deborah A.; Davis, Robert L.; Berg, Richard L.; Peissig, Peggy L.; Mccarty, Catherine A.

2013-01-01

79

Cardiac dose-response relationships of oral and intravenous pindolol  

OpenAIRE

1 The dose-response curve of pindolol on exercise heart rate has been constructed from observations in healthy male subjects studied 2 h after oral doses of pindolol 0.25 mg, 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg and 20 mg. This dose-response curve has been compared with historical controls who received atenolol, oxprenolol, practolol, propranolol and sotalol.

Carruthers, S. George

1982-01-01

80

A Bayesian Approach to Dose-Response Assessment and Synergy and Its Application to In Vitro Dose-Response Studies  

OpenAIRE

In this article, we propose a Bayesian approach to dose-response assessment and the assessment of synergy between two combined agents. We consider the case of an in vitro ovarian cancer research study aimed at investigating the antiproliferative activities of four agents, alone and paired, in two human ovarian cancer cell lines. In this study, independent dose-response experiments were repeated three times. Each experiment included replicates at investigated dose levels including control (no ...

Hennessey, Violeta G.; Rosner, Gary L.; Bast, Robert C.; Chen, Min-yu

2010-01-01

81

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

DEFF Research Database (Denmark)

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D-50,D-TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), gamma(50,TRG1) = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D-50,D-TRG1&2 = 72.1 Gy (CI 65.3-94.0 Gy), gamma(50,TRG1&2) = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered. (C) 2013 Elsevier Inc.

Appelt, A. L.; Ploen, J.

2013-01-01

82

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

Directory of Open Access Journals (Sweden)

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.

Yang Yaning

2003-12-01

83

Lymphocyte-dose response relationship in spontaneous lymphocyte mediated cytotoxicity (SLMC) measured by microcytotoxicity assay.  

Science.gov (United States)

Titrations of spontaneous lymphocyte-mediated cytotoxicity (SLMC) in a 44-hour microcytotoxicity assay (MA) by serial dilutions of effector lymphocytes were performed to characterize the lymphocyte-dose response relationship, and to investigate the methodological basis for comparative cytotoxicity studies. The following lymphocyte fractions were used: unseparated, E rosetting, non-E rosetting, EA rosetting, and non-EA rosetting. Assays were performed against target cell lines from normal and malignant urothelium with high or low sensitivity to SLMC in allogeneic and autologous combinations, and against an osteosarcoma cell line. Analysis of SLMC titration curves showed that two different mathematical models could be used to describe the relationship between lymphocyte concentration and SLMC, I: linear relationship (log lymphocytes, CI) with exclusion of both high and low CI values, and II: sigmoid relationship (log lymphocytes, CI) which was transformed to linear relationship (log lymphocytes, log CI/100 - CI), including also high and low values. It is pointed out that perfect quantitative comparisons of SLMC in different combinations were complicated by statistically significant differences between the curve slopes. However, estimations based on experimental results in a range close to 50% cytotoxicity index (CI) may be acceptable, as the differences between slopes were small. PMID:7170957

Vilien, M; Schultz, K; Wolf, H; Rasmussen, F

1982-12-01

84

Bounding the total-dose response of modern bipolar transistors  

International Nuclear Information System (INIS)

The excess base current in an irradiated BJT increases super-linearly with total dose at low-total-dose levels. In this regime, the excess base current depends on the particular charge-trapping properties of the oxide that covers the emitter-base junction. The device response is dose-rate-, irradiation-bias-, and technology-dependent in this regime. However, once a critical amount of charge has accumulated in the oxide, the excess base current saturates at a value that is independent of how the charge accumulated. This saturated excess base current depends on the device layout, bulk lifetime in the base region, and the measurement bias. In addition to providing important insight into the physics of bipolar-transistor total-dose response, these results have significant circuit-level implications. For example, in some circuits, the transistor gain that corresponds to the saturated excess base current is sufficient to allow reliable circuit operation. For cases in which the saturated value of current gain is acceptable, and where other circuit elements permit such over-testing, this can greatly simplify hardness assurance for space applications

85

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

CERN Document Server

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...

Stern, J M

2010-01-01

86

Computer simulation of a clinical trial as an aid to teaching the concept of statistical significance.  

Science.gov (United States)

The advent of cheap and powerful microcomputers provides opportunities for improving the teaching of statistics in medicine. This paper describes a practical exercise in which students study the concept of statistical significance using a simple computer program which simulates a clinical trial. The students are required to make decisions about patients with incomplete data and form contingency tables for analysis. This includes analysing contingency tables with several cells having small expected frequencies. The results from 25 groups of students are collected together and presented to the class. Two null hypotheses are tested, one of which is true. For the true null hypothesis the group is likely to produce, by chance, at least one significant result at the 0.05 level. For the false null hypothesis only a minority of results will be significant, because the sample size is small. This leads to a discussion of the concept of statistical significance. The simulation model is described and the advantages and potential of this type of teaching are discussed. PMID:3520739

Bland, J M

1986-01-01

87

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

DEFF Research Database (Denmark)

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: Methodologies for assessing statistical and clinical significance of intervention effects in systematic reviews were considered. Balancing simplicity and comprehensiveness, an operational procedure was developed, based mainly on The Cochrane Collaboration methodology and the Grading of Recommendations 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 conservative results as the main results. (2) Explore the reasons behind substantial statistical heterogeneity using subgroup and sensitivity analyses (see step 6). (3) To take account of problems with multiplicity adjust the thresholds for significance according to the number of primary outcomes. (4) Calculate required information sizes (? the a priori required number of participants for a meta-analysis to be conclusive) for all outcomes and analyse each outcome with trial sequential analysis. Report whether the trial sequential monitoring boundaries for benefit, harm, or futility are crossed. (5) Calculate Bayes factors for all primary outcomes. (6) Use subgroup analyses and sensitivity analyses to assess the potential impact of bias on the review results. (7) Assess the risk of publication bias. (8) Assess the clinical significance of the statistically significant review results. CONCLUSIONS: If followed, the proposed eight-step procedure will increase the validity of assessments of intervention effects in systematic reviews of randomised clinical trials.

Jakobsen, Janus Christian; Wetterslev, JØrn

2014-01-01

88

Determination of tolerance dose uncertainties and optimal design of dose response experiments with small animal numbers  

International Nuclear Information System (INIS)

Background: Dose response experiments aim to determine the complication probability as a function of dose. Adjusting the parameters of the frequently used dose response model P(D)=1/[1+(D50/D)k] to the experimental data, 2 intuitive quantities are obtained: The tolerance dose D50 and the slope parameter k. For mathematical reasons, however, standard statistic software uses a different set of parameters. Therefore, the resulting fit parameters of the statistic software as well as their standard errors have to be transformed to obtain D50 and k as well as their standard errors. Material and Methods: The influence of the number of dose levels on the uncertainty of the fit parameters is studied by a simulation for a fixed number of animals. For experiments with small animal numbers, statistical artifacts may prevent the determination of the standard errors of the fit parameters. Consequences on the design of dose response experiments are investigated. Results: Explicit formulas are presented, which allow to calculate the parameters D50 and k as well as their standard errors from the output of standard statistic software. The simulation shows, that the standard errors of the resulting parameters are independent of the number of dose levels, as long as the total number of animals involved in the experiment, remains constant. Conclusion: Statistical artifacts in experiments containing small animal numbers may be preventeining small animal numbers may be prevented by an adequate design of the experiment. For this, it is suggested to select a higher number of dose levels, rather than using a higher number of animals per dose level. (orig.)

89

Dose-response curves for stochastic radiation intensity  

International Nuclear Information System (INIS)

Dose-response curves of the lesions yield and cell survival rate are obtained for radiation intensity stochastic in time. It was shown that, by analogy with the microdosimetric description, the quadratic dependence, that presents the lesions yield as a function of radiation intensity within the high dose range, is to produce a linear-quadratic dose response. The appearance of a linear component is conditioned by the correlativeness of radiation. The asymptotic values are obtained for a single-hit scheme survival rate in the cases of prolonged and pulse irradiation

90

Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves.  

Science.gov (United States)

Physiological and pharmacological studies of hormones, drugs, and neurotransmitters often generate families of sigmoidal dose-response curves. Optimally efficient data analysis should involve simultaneous description of all curves, rather than fitting each one individually. We have developed a general computerized method to describe the dose-response curves in terms of basal and maximal responses, ED50, and curve shape or steepness. This facile method permits rigorous statistical analysis, provides a basis for pooling of information from separate experiments, and allows one to test which characteristics are shared by various curves. PMID:686171

DeLean, A; Munson, P J; Rodbard, D

1978-08-01

91

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

Directory of Open Access Journals (Sweden)

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 large risk reductions are reported 2 Large treatment effects (>50% relative risk reduction are correlated with few number of total outcome events. Readers should interpret the results of such small trials with these issues in mind.

Tornetta Paul

2008-01-01

92

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

Directory of Open Access Journals (Sweden)

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

Douglas J. Crawford-Brown

2006-12-01

93

Assessing the Uncertainty in QUANTEC's Dose–Response Relation of Lung and Spinal Cord With a Bootstrap Analysis  

International Nuclear Information System (INIS)

Purpose: To apply a statistical bootstrap analysis to assess the uncertainty in the dose–response relation for the endpoints pneumonitis and myelopathy reported in the QUANTEC review. Methods and Materials: The bootstrap method assesses the uncertainty of the estimated population-based dose-response relation due to sample variability, which reflects the uncertainty due to limited numbers of patients in the studies. A large number of bootstrap replicates of the original incidence data were produced by random sampling with replacement. The analysis requires only the dose, the number of patients, and the number of occurrences of the studied endpoint, for each study. Two dose–response models, a Poisson-based model and the Lyman model, were fitted to each bootstrap replicate using maximum likelihood. Results: The bootstrap analysis generates a family of curves representing the range of plausible dose–response relations, and the 95% bootstrap confidence intervals give an estimated upper and lower toxicity risk. The curve families for the 2 dose–response models overlap for doses included in the studies at hand but diverge beyond that, with the Lyman model suggesting a steeper slope. The resulting distributions of the model parameters indicate correlation and non-Gaussian distribution. For both data sets, the likelihood of the observed data was higher for the Lyman model in >90% of the bootstrap replicates. Conclusions: The bootstrap method provides a statistical analysis of the uncertainty in the estimated dose–response relation for myelopathy and pneumonitis. It suggests likely values of model parameter values, their confidence intervals, and how they interrelate for each model. Finally, it can be used to evaluate to what extent data supports one model over another. For both data sets considered here, the Lyman model was preferred over the Poisson-based model

94

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

International Nuclear Information System (INIS)

Purpose: This communication reports the long-term results of the original group of prostate cancer patients who participated in the first prospective Fox Chase Cancer Center radiation dose escalation study for which 8-12 years of follow-up is now available. Methods and Materials: Between March 1, 1989 and October 31, 1992, 232 patients with clinically localized prostate cancer received three-dimensional conformal radiotherapy only at Fox Chase Cancer Center in a prospective dose-escalation study. Of these patients, 229 were assessable. The 8-, 10-, and 12-year actuarial rates of biochemical control (biochemically no evidence of disease [bNED]), freedom from distant metastasis (FDM), and morbidity were calculated. The Cox proportional hazards model was used to assess multivariately the predictors of bNED control and FDM, including pretreatment prostate-specific antigen (PSA) level (continuous), tumor stage (T1/T2a vs. T2b/T3), Gleason score (2-6 vs. 7-10), and radiation dose (continuous). The median total dose for all patients was 74 Gy (range 67-81). The median follow-up for living patients was 110 months (range 89-147). bNED control was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Results: The actuarial bNED control for all patients included in this series was 55% at 5 years, 48% at 10 years, and 48% at 12 years. Patients with pretreatment PSA levels of 10-20 ng/mL had statistically significant differences (19% vs. 3tically significant differences (19% vs. 31% vs. 84%, p=0.0003) in bNED control when stratified by dose (75.6 Gy, respectively) on univariate analysis. For the 229 patients with follow-up, 124 (54%) were clinically and biochemically without evidence of disease. Sixty-nine patients were alive at the time of last follow-up, and 55 patients were dead of intercurrent disease. On multivariate analysis, radiation dose was a statistically significant predictor of bNED control for all patients and for unfavorable patients with a pretreatment PSA 20 ng/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

95

Generalized multi-hit dose response model for low-dose extrapolation  

International Nuclear Information System (INIS)

Man is exposed to a variety of natural and synthetic substances that are known to be harmful to experimental animals at high dose levels and consequently are under suspicion of being harmful to humans. The large number of animals required to obtain any positive response at low-dose levels makes it prohibitive to directly estimate the risk at the required dose levels. Thus, the most common method for establishing safe dose levels is to estimate a dose-response curve based on laboratory tests on a limited number of animals at exposure levels well beyond the human usage levels. Then, using such a dose-response curve, one attempts to establish a safe dose based on a statistical low-dose extrapolation procedure. This thesis introduces a generalized multi-hit dose-response model. A biological interpretation of the model in terms of the occurrence of k hits to cause the toxic response, and a statistical interpretation in terms of a gamma tolerance distribution are given. Other dose-response models in the literature are reviewed, with the one-hit or linear model being seen as a special case of the proposed model. The method of maximum likelihood for estimating the parameters of the model, their large sample properties, and their use in risk assessment through extrapolation to low-doses is presented. A method of point estimation of the virtual safe dose, along with its lower 100(1 - ?)% confidence limit is treated. The resulting procedures are then applied to twelve sets of tures are then applied to twelve sets of toxic response data from the literature. Based on these applications, it is seen that the peformance of the model for risk assessment is similar to that of the one-hit model under evidence of near linearity of the dose-response curve in the low-dose range. However, under evidence of concavity (convexity) in the low-dose range, the model is more (less) stringent in its risk assessment

96

Using sparse dose-response data for wildlife risk assessment.  

Science.gov (United States)

Hazard quotients based on a point-estimate comparison of exposure to a toxicity reference value (TRV) are commonly used to characterize risks for wildlife. Quotients may be appropriate for screening-level assessments but should be avoided in detailed assessments, because they provide little insight regarding the likely magnitude of effects and associated uncertainty. To better characterize risks to wildlife and support more informed decision making, practitioners should make full use of available dose-response data. First, relevant studies should be compiled and data extracted. Data extractions are not trivial--practitioners must evaluate the potential use of each study or its components, extract numerous variables, and in some cases, calculate variables of interest. Second, plots should be used to thoroughly explore the data, especially in the range of doses relevant to a given risk assessment. Plots should be used to understand variation in dose-response among studies, species, and other factors. Finally, quantitative dose-response models should be considered if they are likely to provide an improved basis for decision making. The most common dose-response models are simple models for data from a particular study for a particular species, using generalized linear models or other models appropriate for a given endpoint. Although simple models work well in some instances, they generally do not reflect the full breadth of information in a dose-response data set, because they apply only for particular studies, species, and endpoints. More advanced models are available that explicitly account for variation among studies and species, or that standardize multiple endpoints to a common response variable. Application of these models may be useful in some cases when data are abundant, but there are challenges to implementing and interpreting such models when data are sparse. PMID:23913468

Hill, Ryan A; Pyper, Brian J; Lawrence, Gary S; Mann, Gary S; Allard, Patrick; Mackintosh, Cheryl E; Healey, Norm; Dwyer, James; Trowell, Jennifer

2014-01-01

97

Effect of specific resistance training on musculoskeletal pain symptoms : dose-response relationship  

DEFF Research Database (Denmark)

ABSTRACT: Pedersen, MT, Andersen, LL, Jørgensen, MB, Søgaard, K, and Sjøgaard, G. Effect of specific resistance training on musculoskeletal pain symptoms: Dose-response relationship. J Strength Cond Res 27(1): 229-235, 2013-The purpose of this study was to investigate the dose-response of strength training for relieving musculoskeletal pain in female office workers. The relation between the dose of training in terms of total training volume (sets × repetitions × load reported in training diaries) during a 16-week strength training program and changes in pain (calculated as pain index, 0-100%, from self-reported intensities and durations of pain in the upper body and low back) was determined by regression analysis. The women were part of a randomized controlled trial with specific strength training (SRT), all-round physical exercise (APE), and a reference group (REF). Results showed that pain index in SRT and APE decreased significantly from baseline to follow-up (-25%/-22%) compared with changes in REF (-15%). In the dose-response analysis within the SRT group (n = 125), the total volume of training (mean 18.056 kg, SD = 13.798) was negatively correlated with changes in pain index (ß = -0.16, p = 0.045), and there was a significant dose-response relationship between training volume per session and change in pain index (ß = -0.20, p = 0.034). In contrast, training attendance (mean 1.69 sessions per week, SD = 0.8) was not significantly related to the change in pain index. In conclusion, achieving higher accumulated training volumes was important for reducing musculoskeletal pain in female office workers. The training volume per session should be optimized by securing a load at 10-15 repetition maximum and adhering to principles of progressive overload.

Pedersen, Mogens Theisen; Andersen, Lars Louis

2013-01-01

98

Statistically comparing EEG/MEG waveforms through successive significant univariate tests: How bad can it be?  

Science.gov (United States)

When making statistical comparisons, the temporal dimension of the EEG signal introduces problems. Guthrie and Buchwald (1991) proposed a formally correct statistical approach that deals with these problems: comparing waveforms by counting the number of successive significant univariate tests and then contrasting this number to a well-chosen critical value. However, in the literature, this method is often used inappropriately. Using real EEG data and Monte Carlo simulations, we examined the problems associated with the incorrect use of this approach under circumstances often encountered in the literature. Our results show inflated false-positive or false-negative rates depending on parameters of the data, including filtering. Our findings suggest that most applications of this method result in an inappropriate familywise error rate control. Solutions and alternative methods are discussed. PMID:25244108

Piai, Vitória; Dahlslätt, Kristoffer; Maris, Eric

2014-09-22

99

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

Directory of Open Access Journals (Sweden)

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 of salbutamol on peak expiratory flow, FEV1, and forced vital capacity was unchanged after either acute or chronic treatment with formoterol. With increasing doses of salbutamol, FEV1 increased only after acute administration of formoterol. Forced vital capacity also significantly improved during long-term treatment with formoterol.Keywords: chronic obstructive pulmonary disease, salbutamol, formoterol, long-acting ß2-agonists

La Piana GE

2011-07-01

100

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

International Nuclear Information System (INIS)

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)

101

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

Science.gov (United States)

Population based pattern analysis and classification for quantifying structural and functional differences between diverse groups has been shown to be a powerful tool for the study of a number of diseases, and is quite commonly used especially in neuroimaging. The alternative to these pattern analysis methods, namely mass univariate methods such as voxel based analysis and all related methods, cannot detect multivariate patterns associated with group differences, and are not particularly suitable for developing individual-based diagnostic and prognostic biomarkers. A commonly used pattern analysis tool is the support vector machine (SVM). Unlike univariate statistical frameworks for morphometry, analytical tools for statistical inference are unavailable for the SVM. In this paper, we show that null distributions ordinarily obtained by permutation tests using SVMs can be analytically approximated from the data. The analytical computation takes a small fraction of the time it takes to do an actual permutation test, thereby rendering it possible to quickly create statistical significance maps derived from SVMs. Such maps are critical for understanding imaging patterns of group differences and interpreting which anatomical regions are important in determining the classifier's decision. PMID:23285616

Gaonkar, Bilwaj; Davatzikos, Christos

2012-01-01

102

Volcanic activity before and after large tectonic earthquakes: Observations and statistical significance  

Science.gov (United States)

The study of volcanic triggering and coupling to the tectonic surroundings has received special attention in recent years, using both direct field observations and historical descriptions of eruptions and earthquake activity. Repeated reports of volcano-earthquake interactions in, e.g., Europe and Japan, may imply that clustered occurrence is important in some regions. However, the regions likely to suffer clustered eruption-earthquake activity have not been systematically identified, and the processes responsible for the observed interaction are debated. We first review previous works about the correlation of volcanic eruptions and earthquakes, and describe selected local clustered events. Following an overview of previous statistical studies, we further elaborate the databases of correlated eruptions and earthquakes from a global perspective. Since we can confirm a relationship between volcanic eruptions and earthquakes on the global scale, we then perform a statistical study on the regional level, showing that time and distance between events follow a linear relationship. In the time before an earthquake, a period of volcanic silence often occurs, whereas in the time after, an increase in volcanic activity is evident. Our statistical tests imply that certain regions are especially predisposed to concurrent eruption-earthquake pairs, e.g., Japan, whereas such pairing is statistically less significant in other regions, such as Europe. Based on this study, we argue that individual and selected observations may bias the perceptible weight of coupling. Volcanoes located in the predisposed regions (e.g., Japan, Indonesia, Melanesia), however, indeed often have unexpectedly changed in association with either an imminent or a past earthquake.

Eggert, S.; Walter, T. R.

2009-04-01

103

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

CERN Document Server

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.

Hu, R; Hu, Rui; Wang, Bin

2000-01-01

104

A suggested statistical approach for dealing with the non-significant interactions between treatments  

Directory of Open Access Journals (Sweden)

Full Text Available A field experiment was conducted to study the effect of nitrogen (N fertilizer and foliar appli-cation of potassium (K and Mepiquat Chloride (MC on yield of cotton. Seed cotton yield per plant and seed cotton and lint yield per hectare; have been increased due to the higher N rate and use of foliar application of K and MC. No significant interactions were found among the variables in the present study (N, K and MC with respect to characters under investigation. Generally, interactions indicated that, the fa-vorable effects ascribed to the application of N; spraying cotton plants with K combined with MC on cotton productivity, were more obvious by applying N at 143 kg per hectare, and combined with spraying cotton plants with K at 957 g per hectare and also with MC at 48 + 24 g active ingredient per hectare. Sensible increases were found in seed cotton yield per hectare (about 40% as a result of applying the same combination. However, this interaction did not reach the level of significance, so, statistical approach for dealing with the non-significant interactions between treatments, depending on the Least Significant Difference values has been suggested, to provide an opportunity to disclosure of the interaction effects regardless of their insignificance. As a matter of fact the original formula used in calculating the significance of interactions suffers a possible shortage, which can be eliminated through applying the new suggested formula.

Zakaria M. Sawan

2011-05-01

105

Aspects of radiation beam quality and their effect on the dose response of polymer gels: Photons, electrons and fast neutrons  

International Nuclear Information System (INIS)

Polymer gels are generally assumed to exhibit no significant dependence of the dose response on the energy or type of irradiation for clinically used beam qualities. Based on reports on differences in dose response for low energy photons and particle beams with high linear energy transfer (LET) we here investigate the dose response and energy dependence for a normoxic methacrylic acid polymer gel (MAGAT) for X-rays (100 kV), high energy photon beams (E = 1.2 MeV (60Co), 6 MV and 15 MV) and for three different electron energies (4, 12 and 20 MeV). Due to the possible impact also the sensitivity of the dose response to the dose rate is reported. A reduction in polymer gel relaxation rate has been observed for proton and carbon beams due to the high Linear Energy Transfer (LET) of these types of radiations. We here report on the dose response of an acryl-amide polymer gel (PAG) in a fast neutron field along with collimation as proposed for Boron neutron capture therapy (BNCT).

106

Cancer dose-response analysis of the radium dial workers  

International Nuclear Information System (INIS)

Bone (46 deaths) and head (19 deaths) cancers have been analyzed using Cox proportional hazard models with cumulative dose treated as a time dependent covariate. For bone cancers, the best models separate the 226Ra and 228Ra isotopes and use a single linear dose-response function with a threshold dose at about 9Gy. Covariates for age-at-first exposure and a tumour latency of 5 years were also important. Head carcinomas depend only on 226Ra, and the best-fitted dose-response function is linear with a threshold at about 5 Gy. For head carcinomas, the inclusion of covariates for age-at-first exposure and tumour latency into the model was not necessary. (orig.)

107

Model Averaging Software for Dichotomous Dose Response Risk Estimation  

Directory of Open Access Journals (Sweden)

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, ?ts 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 ful?lls 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.

Matthew W. Wheeler

2008-02-01

108

Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake.  

Science.gov (United States)

Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C-lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to describe the dose-response curve. The overall pooled absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were also assessed with a random effects model. The pooled LDL-C reduction was 0.34 mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose of 2.15 g phytosterols. The impacts of subject baseline characteristics, food formats, type of phytosterols, and study quality on the continuous dose-response curve were determined by regression or subgroup analyses. Higher baseline LDL-C concentrations resulted in greater absolute LDL-C reductions. No significant differences were found between dose-response curves established for plant sterols vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy foods. A larger effect was observed with solid foods than with liquid foods only at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054) towards a slightly lower efficacy of single vs. multiple daily intakes of phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of phytosterols incorporated in various food formats was confirmed and equations of the continuous relationship were established to predict the effect of a given phytosterol dose. Further investigations are warranted to investigate the impact of solid vs. liquid food formats and frequency of intake on phytosterol efficacy. PMID:19091798

Demonty, Isabelle; Ras, Rouyanne T; van der Knaap, Henk C M; Duchateau, Guus S M J E; Meijer, Linsie; Zock, Peter L; Geleijnse, Johanna M; Trautwein, Elke A

2009-02-01

109

Mesothelioma dose response following intraperitoneal injection of mineral fibres.  

OpenAIRE

The relationship between injected dose and the development of peritoneal mesotheliomas has been examined in rats using the UTCC standard reference samples of chrysotile, crocidolite and amosite as well as a sample of fibrous erionite from Oregon. Doses injected into the peritoneal cavity ranged from 0.005 to 25 mg and with each dust a clear dose response was found. The proportion of animals developing tumours increased with the amount of dust injected while the tumour induction period was red...

Davis, J. M.; Bolton, R. E.; Miller, B. G.; Niven, K.

1991-01-01

110

Characterization of a developmental toxicity dose-response model.  

OpenAIRE

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 ...

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

1989-01-01

111

Dose-response studies with pancuronium, vecuronium and their combination.  

OpenAIRE

Pancuronium, vecuronium and a combination of these were administered in an incremental fashion to study any potentiation of effect with the combination of the two relaxants. The ED95 (dose producing a 95% block) of the combination was 29 micrograms kg-1 for each component in comparison to 57 micrograms kg-1 for vecuronium and 59 micrograms kg-1 for pancuronium. The dose-response curves for the three groups did not differ from each other and no potentiation was demonstrated.

Ferres, C. J.; Mirakhur, R. K.; Pandit, S. K.; Clarke, R. S.; Gibson, F. M.

1984-01-01

112

Dose-response relationship in radioiodine therapy of hyperthyroidism  

International Nuclear Information System (INIS)

For the analysis of the dose-response relationship during radioiodine therapy, the effective dose was calculated based on measurements in 1,171 patients. Early results of the radioiodine therapy of these cases were checked up from 6 to 9 months afterwards. The dose-response curve for the probability of residual hyperthyreoses shows an exponential shape, whereas the curve of induced hypothyroidism is sigmoidally shaped. The results of experimental biophysics concerning dose-response curves allow the statement that there is no reactivity of the thyroid gland in cases of residual hyperthyroidism, whereas distinct compensation mechanisms are counteracting the induction of hypothyroidism. Thus, the conception of fractionated radioiodine therapy is supported by the shape of dose-response curves. The fractionation of the dose leads to accumulated inactivation effects on the hyperthyroidism, while the compensational mechanisms against hypothyroidism are strengthening by intermittent recovery and the rate of induced hypothyroidism is decreasing. The favorable effect of multiple treatment on the number of induced hypothyreoses could be verified. A defined interrelation is found between the effective dose, the thyroid mass and the effect of the dose. A formula of the isoeffective dose in dependence on the thyroid mass is derived. The deviation of the effective dose from the dose previously calculated is represented as a distribution function. The mean value of this distribution tion. The mean value of this distribution function can be regarded as an expectation of the effective dose. Hence, a previous calculation of the dose is considered useful also in future. The isoeffective dose is proposed to be chosen in dependence on the thyroid mass according to a 50% probability of residual hyperthyroidism. Relative to the intensity of residual hyperthyroidism, a second treatment considering the same standards should be performed after 4 to 9 months. The number of reiterated treatments needed depends on individual radiation sensitivity resulting from biological factors. (orig./MG)

113

Model Averaging Software for Dichotomous Dose Response Risk Estimation  

OpenAIRE

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), ?ts the quantal response mod...

Wheeler, Matthew W.

2008-01-01

114

Dose response to inhaled salbutamol in chronic obstructive airways disease.  

OpenAIRE

High dose inhaled salbutamol is increasingly used in the management of chronic obstructive airways disease. To determine the range of doses to achieve optimal bronchodilatation and the proportion of patients requiring high dose therapy we have studied 23 patients with chronic obstructive airways disease. Cumulative dose responses were measured to six incremental doses of salbutamol (0.2 to 1.2 mg) delivered by metered dose inhaler. Results were analysed by polynomial regression to calculate t...

Teale, C.; Morrison, J. F.; Page, R. L.; Pearson, S. B.

1991-01-01

115

Henry Eyring: Statistical Mechanics, Significant Structure Theory, and the Inductive-Deductive Method  

CERN Document Server

Henry Eyring was, and still is, a towering figure in science. Some aspects of his life and science, beginning in Mexico and continuing in Arizona, California, Wisconsin, Germany, Princeton, and finally Utah, are reviewed here. Eyring moved gradually from quantum theory toward statistical mechanics and the theory of liquids, motivated in part by his desire to understand reactions in condensed matter. Significant structure theory, while not as successful as Eyring thought, is better than his critics realize. Eyring won many awards. However, most chemists are surprised, if not shocked, that he was never awarded a Nobel Prize. He joined Lise Meitner, Rosalind Franklin, John Slater, and others, in an even more select group, those who should have received a Nobel Prize but did not.

Henderson, Douglas

2010-01-01

116

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

CERN Document Server

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

Zhang, Pan

2014-01-01

117

In vitro dose response studies on bone marrow fibroblasts (CFU-F) obtained from chronically irradiated dogs  

International Nuclear Information System (INIS)

In vitro dose response studies were performed on bone marrow fibroblastic colony forming units (CFU-F). The bone marrow was obtained from dogs that had been chronically irradiated beginning at 21 days of gestation or at 150 days of age. Fibroblasts from irradiated dogs were significantly more radioresistant than those from age-matched controls

118

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

OpenAIRE

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximu...

Magdalena Adamus-Górka; Panayiotis Mavroidis; Lind, Bengt K.; Anders Brahme

2011-01-01

119

Biphasic Dose Response in Low Level Light Therapy – An Update  

OpenAIRE

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...

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

2011-01-01

120

Prediction of the mortality dose-response relationship in man  

International Nuclear Information System (INIS)

Based upon an extensive data base including 100 separate animal studies, an estimate of the mortality dose-response relationship due to continuous photon radiation is predicted for 70 kg man. The model used in this prediction exercise includes fixed terms accounting for effects of body weight and dose rate, and random terms accounting for inter- and intra-species variation and experimental error. Point predictions and 95% prediction intervals are given for the LD05, LD10, LD25, LD50, LD75, LD90, and LD95, for dose rates ranging from 1 to 50 R/min. 6 refs., 5 tabs

121

Regression analysis of ESR/TL dose-response data  

International Nuclear Information System (INIS)

Methods are described for the analysis of ESR (electron spin resonance) or TL (thermoluminescence) dose-response data. When fitting data to a straight line, an expression is derived which allows the error in the accumulated dose, AD, to be estimated. For fitting data to a saturating exponential, the simplex algorithm with quadratic convergence is proposed. This allows the errors in the parameters, including the AD, to be estimated. An alternative method for estimating the parameter errors, using analytical expressions for the required partial derivatives, is also described. These techniques are more satisfactory than jackknifing for estimating uncertainties in ADs. (author)

122

Mutans Streptococci Dose Response to Xylitol Chewing Gum  

OpenAIRE

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...

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

2006-01-01

123

Dose-response curves of gamma-irradiated purine and pyrimidine powders  

International Nuclear Information System (INIS)

E.s.r. spectra have been obtained of gamma-irradiated dry purine and pyrimidine powders. Relative radical yields have been calculated and dose-response curves obtained. Relative recombination rates and formation rates of the radicals have been derived from the dose-response curves. The effect of crystalline structure on the dose-response curves is discussed. (author)

124

The Statistical Significance Controversy Is Definitely Not Over: A Rejoinder to Responses by Thompson, Knapp, and Levin.  

Science.gov (United States)

Considers reviews of L. Daniels's article on editorial policy regarding statistical significance testing and concludes that the controversy is not over, although the gradual movement toward requiring additional information in the reporting of statistical results is viewed as a positive trend. (SLD)

Daniel, Larry G.

1998-01-01

125

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

Directory of Open Access Journals (Sweden)

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 doses ? 800 IU of vitamin E will be required to significantly decrease plasma F2-isoprostanes. Discussion This study will determine the time and dose required for alpha tocopherol to significantly decrease oxidative stress in haemodialysis patients. Data will be used to plan a large randomised controlled trial to assess the effects of alpha tocopherol on cardiovascular outcomes in haemodialysis patients. Trial Registration ACTRN12609000608268

Coombes Jeff S

2009-10-01

126

Body Mass Index and Risk of Breast Cancer: A Nonlinear Dose-Response Meta-Analysis of Prospective Studies  

Science.gov (United States)

The role of Body Mass Index (BMI) for Breast Cancer (BC) remains to be great interest for a long time. However, the precise effect of nonlinear dose-response for BMI and BC risk is still unclear. We conducted a dose-response meta-analysis to quantitatively assess the effect of BMI on BC risk. Twelve prospective studies with 4,699 cases identified among 426,199 participants and 25 studies of 22,809 cases identified among 1,155,110 participants in premenopausal and postmenopausal groups, respectively, were included in this meta-analysis. Significant non-linear dose-response (P < 0.001) association was identified between BMI and BC risk in postmenopausal women. Individuals with BMI of 25, 30, and 35?kg/m2 yielded relative risks (RRs) of 1.02 [95% confidence interval (CI): 0.98–1.06], 1.12 (95% CI: 1.01–1.24), and 1.26 (95% CI: 1.07–1.50), respectively, when compared to the mean level of the normal BMI range. However, inverse result though not significant was observed in premenopausal women. In conclusion, the results of this meta-analysis highlighted that obesity contributed to increased BC risk in a nonlinear dose-response manner in postmenopausal women, and it is important to realize that body weight control may be a crucial process to reduce BC susceptibility. PMID:25504309

Xia, Xiaoping; Chen, Wei; Li, Jiaoyuan; Chen, Xueqin; Rui, Rui; Liu, Cheng; Sun, Yu; Liu, Li; Gong, Jing; Yuan, Peng

2014-01-01

127

Dose-response relationships for radium-induced bone sarcomas  

International Nuclear Information System (INIS)

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

128

Maximum likelihood estimation for cytogenetic dose-response curves  

International Nuclear Information System (INIS)

In vitro dose-response curves are used to describe the relation between chromosome aberrations and radiation dose for human lymphocytes. The lymphocytes are exposed to low-LET radiation, and the resulting dicentric chromosome aberrations follow the Poisson distribution. The expected yield depends on both the magnitude and the temporal distribution of the dose. A general dose-response model that describes this relation has been presented by Kellerer and Rossi (1972, Current Topics on Radiation Research Quarterly 8, 85-158; 1978, Radiation Research 75, 471-488) using the theory of dual radiation action. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting dose-time-response models are intrinsically nonlinear in the parameters. A general-purpose maximum likelihood estimation procedure is described, and estimation for the nonlinear models is 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

129

Characterization of Statin Dose-response within Electronic Medical Records  

Science.gov (United States)

Efforts to define the genetic architecture underlying variable statin response have met with limited success possibly because previous studies were limited to effect based on one-single-dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 pre-selected variants. Two large biobanks were used to construct dose-response curves for 2,026 (simvastatin) and 2,252 subjects (atorvastatin). Atorvastatin was more efficacious, more potent, and demonstrated less inter-individual variability than simvastatin. A pharmacodynamic variant emerging from randomized trials (PRDM16) was associated with Emax for both. For atorvastatin, Emax was 51.7 mg/dl in homozygous for the minor allele versus 75.0 mg/dl for those homozygous for the major allele. We also identified several loci associated with ED50. The extraction of rigorously defined traits from EMRs for pharmacogenetic studies represents a promising approach to further understand of genetic factors contributing to drug response. PMID:24096969

Wei, Wei-Qi; Feng, Qiping; Jiang, Lan; Waitara, Magarya S.; Iwuchukwu, Otito F.; Roden, Dan M.; Jiang, Min; Xu, Hua; Krauss, Ronald M.; Rotter, Jerome I.; Nickerson, Deborah A.; Davis, Robert L.; Berg, Richard L.; Peissig, Peggy L.; McCarty, Catherine A.; Wilke, Russell A.; Denny, Joshua C.

2013-01-01

130

Retrieval accuracy, statistical significance and compositional similarity in protein sequence database searches  

OpenAIRE

Protein sequence database search programs may be evaluated both for their retrieval accuracy—the ability to separate meaningful from chance similarities—and for the accuracy of their statistical assessments of reported alignments. However, methods for improving statistical accuracy can degrade retrieval accuracy by discarding compositional evidence of sequence relatedness. This evidence may be preserved by combining essentially independent measures of alignment and compositional similarit...

Yu, Yi-kuo; Gertz, E. Michael; Agarwala, Richa; Scha?ffer, Alejandro A.; Altschul, Stephen F.

2006-01-01

131

Indirectional statistics and the significance of an asymmetry discovered by Birch  

International Nuclear Information System (INIS)

Birch (1982, Nature, 298, 451) reported an apparent 'statistical asymmetry of the Universe'. The authors here develop 'indirectional analysis' as a technique for investigating statistical effects of this kind and conclude that the reported effect (whatever may be its origin) is strongly supported by the observations. The estimated pole of the asymmetry is at RA 13h 30m, Dec. -37deg. The angular error in its estimation is unlikely to exceed 20-30deg. (author)

132

Dose-response studies of indenolol, a beta adrenoceptor blocker.  

Science.gov (United States)

Two studies were conducted on indenolol, a new beta-adrenoceptor blocker. In the first, nine healthy men received indenolol 40, 80, 160, and 320 mg and placebo orally. Two hours later a standard exercise test was performed, and systolic blood pressure, heart rate, and peak expiratory flow rate were recorded. Indenolol induced attenuation of exercise-induced rise in systolic blood pressure and tachycardia. In the second study, seven healthy men received indenolol 40, 80, 160, and 320 mg and propranolol 40, 80, 160, and 320 mg in randomized order. Dose-response curves for both drugs revealed that maximum attenuation of exercise tachycardia and systolic blood pressure were in the same range but suggested that indenolol induced a greater response in the lower doses. Neither drug had any effect on the exercise-induced rise in peak expiratory flow rate. Indenolol was well tolerated. PMID:6110504

Okupa, F E; Daneshmend, T K; Shrosbree, E; Roberts, C J

1981-04-01

133

Total dose response of transconductance in MOSFETs at low temperature  

International Nuclear Information System (INIS)

N and p channel MOSFETs from four bulk CMOS technologies and two CMOS/SIMOX technologies were characterized for total dose response up to 1 Mrad (SiO2) at temperatures from 10K to 120K. The peak transconductance in the linear region increased in n channel devices and decreased in p channel devices for devices with lightly doped drain (LDD) implants. These changes were much larger as the temperature was decreased and were as much as a factor of 50 in p MOSFETs at 10K. The one technology without LDD showed only a minor change in gm with dose even at 10K. The changes in transconductance are most likely a result of hole trapping in the spacer oxide affecting the series resistance

134

Proposal of a probabilistic dose-response model  

International Nuclear Information System (INIS)

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

135

The dose-response relationship for UV-tumorigenesis  

International Nuclear Information System (INIS)

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

136

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

International Nuclear Information System (INIS)

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 oC' thermoluminescence (TL) during the optical stimulation that would result in depletal 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 that is not recorded by the sensitivity to a subsequent test dose, and which results in a change in the sensitivity-corrected dose-response curve.

137

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

Energy Technology Data Exchange (ETDEWEB)

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 distribution of the spallation neutrons leads to second moments that differ significantly from the ones calculated with the average energy distribution only. With the most realistic model of the energy distributions, the second moment of the number of fissions was underestimated with 12-16%.

Fhager, V

2000-01-01

138

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

International Nuclear Information System (INIS)

Background and purpose: We fit phenomenological tumor control probability (TCP) models to biopsy outcome after three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer patients to quantify the local dose-response of prostate cancer. Materials and methods: We analyzed the outcome after photon beam 3D-CRT of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan-Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81 Gy) who had a prostate biopsy performed ?2.5 years after end of treatment. A univariate logistic regression model based on Dmean (mean dose in the planning target volume of each patient) was fit to the whole data set and separately to subgroups characterized by low and high values of tumor-related prognostic factors T-stage (6), and pre-treatment prostate-specific antigen (PSA) (?10 ng/ml vs. >10 ng/ml). In addition, we evaluated five different classifications of the patients into three risk groups, based on all possible combinations of two or three prognostic factors, and fit bivariate logistic regression models with Dmean and the risk group category to all patients. Dose-response curves were characterized by TCD50, the dose to control 50% of the tumors, and ?50, the normalized slope of the dose-response curve at TCD50. Results: Dmean correlates significantly with biopsy outcome in all patly 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 (?50=3.4-5.2) than those obtained when all patients are analyzed together (?50=2.9). Conclusions: Dose-response of prostate cancer, quantified by TCD50 and ?50, varies by prognostic subgroup. Our observations are consistent with the hypothesis that the shallow nature of clinically observed dose-response curves for local control result from a patient population that is a heterogeneous mixture of sub-populations with steeper dose-response curves and varying values of TCD50. Such results may eventually help to identify patients, based on their individual pre-treatment prognostic factors, that would benefit most from dose-escalation, and to guide dose prescription

139

Blood glucose concentration and risk of pancreatic cancer: systematic review and dose-response meta-analysis  

Science.gov (United States)

Objective To evaluate potential linear and non-linear dose-response relations between blood glucose and risk of pancreatic cancer. Design Systematic review and dose-response meta-analysis of prospective observational studies. Data sources Search of PubMed, Scopus, and related reviews before 30 November 2013 without language restriction. Eligibility criteria Prospective studies evaluating the association between blood glucose concentration and pancreatic cancer. Retrospective and cross sectional studies excluded to avoid reverse causality. Data extraction and synthesis Two reviewers independently extracted relevant information and assessed study quality with the Newcastle-Ottawa scale. Random effects dose-response meta-analysis was conducted to assess potential linear and non-linear dose-response relations. Results Nine studies were included for analysis, with a total of 2408 patients with pancreatic cancer. There was a strong linear dose-response association between fasting blood glucose concentration and the rate of pancreatic cancer across the range of prediabetes and diabetes. No non-linear association was detected. The pooled rate ratio of pancreatic cancer per 0.56 mmol/L (10 mg/dL) increase in fasting blood glucose was 1.14 (95% confidence interval 1.06 to 1.22; P<0.001) without significant heterogeneity. Sensitivity analysis excluding blood glucose categories in the range of diabetes showed similar results (pooled rate ratio per 0.56 mmol/L increase in fasting blood glucose was 1.15, 95% confidence interval 1.05 to 1.27; P=0.003), strengthening the association between prediabetes and pancreatic cancer. Conclusions Every 0.56 mmol/L increase in fasting blood glucose is associated with a 14% increase in the rate of pancreatic cancer. As prediabetes can be improved or even reversed through lifestyle changes, early detection of prediabetes coupled with lifestyle changes could represent a viable strategy to curb the increasing incidence of pancreatic cancer. PMID:25556126

Liao, Wei-Chih; Wu, Ming-Shiang; Lin, Jaw-Town; Wang, Hsiu-Po

2015-01-01

140

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

Science.gov (United States)

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 10g/kg DEG and blood, kidney and liver tissues were collected at 48h. Both rat strains treated with 10g/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 5g/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 10g/kg DEG, but no DGA was present at 2 or 5g/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. PMID:25545985

Landry, Greg M; Dunning, Cody L; Abreo, Fleurette; Latimer, Brian; Orchard, Elysse; McMartin, Kenneth E

2015-02-01

141

Gamma and electron dose response of the electrical conductivity of polyaniline based polymer composites  

International Nuclear Information System (INIS)

Conducting polymers, also known as 'synthetic metals', have been the subject of wide-spread investigations over the past decade due to their very promising characteristics. It was published earlier that the electrical conductivity of polyaniline (PANI) based polymer composites increases to a significant extent when irradiated to gamma, electron or UV radiation. The aim of the present study was to determine the dose response of PANI samples blended with poly(vinyl chloride) (PVC) and chlorinated poly(propylene) (PPCl) by measuring the high frequency conductance of these blends irradiated to different doses. In order to find the most suitable composition of these blends the concentration of both the PPCl and PVC, and the PANI base were changed, respectively. These samples were then gamma irradiated and the induced electrical conductivity was measured in the frequency range of 1 kHz-1 MHz in order to find the most sensitive evaluation conditions. After selecting both, the most suitable measuring conditions as well as the blend compositions, the dose response of the samples was determined in the dose range of 10-250 kGy. With respect to potential dosimetry application the effects of electron irradiation, irradiation temperature and the stability of the irradiated samples have also been investigated

142

Gamma and electron dose response of the electrical conductivity of polyaniline based polymer composites  

Science.gov (United States)

Conducting polymers, also known as "synthetic metals", have been the subject of wide-spread investigations over the past decade due to their very promising characteristics. It was published earlier that the electrical conductivity of polyaniline (PANI) based polymer composites increases to a significant extent when irradiated to gamma, electron or UV radiation. The aim of the present study was to determine the dose response of PANI samples blended with poly(vinyl chloride) (PVC) and chlorinated poly(propylene) (PPCl) by measuring the high frequency conductance of these blends irradiated to different doses. In order to find the most suitable composition of these blends the concentration of both the PPCl and PVC, and the PANI base were changed, respectively. These samples were then gamma irradiated and the induced electrical conductivity was measured in the frequency range of 1 kHz-1 MHz in order to find the most sensitive evaluation conditions. After selecting both, the most suitable measuring conditions as well as the blend compositions, the dose response of the samples was determined in the dose range of 10-250 kGy. With respect to potential dosimetry application the effects of electron irradiation, irradiation temperature and the stability of the irradiated samples have also been investigated.

Sevil, U. A.; Güven, O.; Kovács, A.; Slezsák, I.

2003-06-01

143

Linear dose response curves in fungi and tradescantia  

International Nuclear Information System (INIS)

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 moch 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 heterozygosity (LOH) events occur because Clone 02 repairs both DSB and LCD by recombination. Clone 02 has a linear dose response for high LET radiation. Starting from the same initial yieId frequency, wild-types have a sublinear response. The sublinear response reflects a smoothly decreasing probability that 'pinks' are generated as a function of increasing high LET dose for wild-type but not Clone 02. This smoothly decreasing response would be expected for LOH in 'wild-type' humans. It reflects an increasing proportion of DNA damage being repaired by non-recombinational pathways and/or an increasing probability of cell death with increasing dose. Clone 02 at low doses and low dose rates of low LET radiation has a linear dose response, reflecting a 1/16 probability of a lesion leading to LOH, relative to high LET lesions. This differential is held to reflect: microdosimetric differences in energy deposition and, therefore, DNA damage by low and high LET radiations; the effects of lesion clustering after high LET on the probability of generating the end wild-types. While no observations have been made at very low doses and dose rates in wild-types, there is no reason to suppose that the low LET linear non-threshold dose response of Clone 02 is abnormal. The importance of the LOH somatic genetic end-point is that it reflects cancer risk in humans. The linear non-threshold low dose low LET response curves reflects either the probability that recombinational Holliday junctions are occasionally cleaved in a rare orientation to generate LOH, or the probability that low LET lesions include a small proportion of clustered events similar to high LET ionization or both. Calculations of the Poisson probability that two or more low LET lesions will be induced in the same target suggest that dose rate effects depend upon the coincidence of DNA lesions in the same target, and that the probability of LOH depends upon lesion and repair factors. But the slope of LOH in Clone 02 and all other strains never approaches the expected slope of predicted

144

A methodology for testing for statistically significant differences between fully 3D PET reconstruction algorithms  

International Nuclear Information System (INIS)

We present a practical methodology for evaluating 3D PET reconstruction methods. It includes generation of random samples from a statistically described ensemble of 3D images resembling those to which PET would be applied in a medical situation, generation of corresponding projection data with noise and detector point spread function simulating those of a 3D PET scanner, assignment of figures of merit appropriate for the intended medical applications, optimization of the reconstruction algorithms on a training set of data, and statistical testing of the validity of hypotheses that say that two reconstruction algorithms perform equally well (from the point of view of a particular figure of merit) as compared to the alternative hypotheses that say that one of the algorithms outperforms the other. Although the methodology was developed with the 3D PET in mind, it can be used, with minor changes, for other 3D data collection methods, such as fully 3D CT or SPECT. (Author)

145

Significance and statistical errors in the analysis of DNA microarray data  

OpenAIRE

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...

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

2002-01-01

146

A dose-response study for I-125 prostate implants  

International Nuclear Information System (INIS)

Purpose: No dose-response study has ever been performed for I-125 prostate implants using modern techniques of implant evaluation and modern treatment outcome end points. The amount of activity per volume implanted was increased over time based on review of postimplant dosimetry. This resulted in different delivered dose levels. This study explores the relationship between dose, biochemical failure, and biopsy results. Materials and Methods: 134 patients with T1-T2 prostate cancer were implanted with I-125 radioactive seeds and followed from 12 to 74 months (median: 32) postimplant. No patient received external beam irradiation or hormonal therapy. All patients implanted with I-125 had Gleason scores ?6. One month postimplant, a CT-based three-dimensional dosimetric evaluation was performed on all patients. Using TG43 guidelines, dose-volume histograms were calculated. The dose delivered to the gland was defined as the D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged from 26.8 to 256.3 Gy (median: 140.8 Gy). Biochemical failure was defined as two consecutive rises in prostate specific antigen (PSA) or a nadir level above 1.0 ng/ml. Posttreatment prostate biopsies (six to eight core samples) were routinely performed at 2 years postimplant. Results: Improvements in freedom from biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year FFBF rates for patients with D90 values 10 ng/ml. In these patients, the 4-year FFBF rates were 51 and 100% for the low and high dose groups, respectively (p = 0.009) and the negative biopsy rates were 64% (14 of 22) and 100% (8 of 8), respectively (p = 0.05). In patients with presenting PSA <10 ng/ml, the 4-year FFBF rates were 82 and 88% for the low and high dose groups, respectively (p = 0.29). Conclusion: A dose response was observed at a level of 140 Gy. Adequate I -125 implants should deliver a dose of 140-160 Gy using TG43 guidelines

147

Exposure-dose-response of Anadara trapezia to metal contaminated estuarine sediments. 1. Cadmium spiked sediments  

Energy Technology Data Exchange (ETDEWEB)

Highlights: Black-Right-Pointing-Pointer We describe an exposure-dose-response approach for assessing cadmium exposure in Anadara trapezia. Black-Right-Pointing-Pointer Accumulated cadmium was detoxified in metallothionein like proteins or as active metal in mitochondria. Black-Right-Pointing-Pointer Increased cadmium dose resulted in a reduction in total antioxidant capacity, decreased lysosomal stability and genotoxic damage. Black-Right-Pointing-Pointer Elevated sediment cadmium concentrations can lead to increased biologically active cadmium and cellular impairment of A. trapezia. - Abstract: The relationship between cadmium exposure dose and response was investigated in Anadara trapezia exposed to cadmium spiked sediment (10 {mu}g/g and 50 {mu}g/g dry mass) for 56 days. A. trapezia reached an equilibrium cadmium tissue concentration (13 {mu}g/g and 25 {mu}g/g, respectively) by day 42. Gills accumulated significantly more cadmium than the hepatopancreas and haemolymph. After 56 days exposure between 46 and 73% of accumulated gill and hepatopancreas cadmium was detoxified and in the metallothionein like protein fraction. Approximately half of the biologically active cadmium in both tissues was in the mitochondrial fraction which has the potential to cause dysfunction in mitochondrial activity. Cadmium exposed A. trapezia generally had reduced GPx activity with an associated increase in total glutathione concentrations and reduced GSH:GSSG ratios due to a build up of oxidised glutathione. The changes in the glutathione pathway were reflected in the total antioxidant capacity of cadmium exposed A. trapezia which were significantly reduced compared to control organisms. There was a trend of increased lipid peroxidation with increased cadmium exposure but this was not significant. Increased cadmium exposure resulted in significant lysosomal destabilisation and increased frequency of micronuclei. The significant exposure-dose-response relationship for A. trapezia exposed to cadmium enriched sediments indicates that elevated sediment cadmium concentrations have the potential to lead to increased biologically active cadmium burdens and impairment of individual A. trapezia at cellular and subcellular levels.

Taylor, Anne M., E-mail: anne.taylor@canberra.edu.au [Ecochemistry Laboratory, Institute for Applied Ecology, Faculty of Applied Science, University of Canberra, ACT 2601 (Australia); Maher, William A. [Ecochemistry Laboratory, Institute for Applied Ecology, Faculty of Applied Science, University of Canberra, ACT 2601 (Australia)

2012-03-15

148

Nickel-sulphate-induced contact dermatitis in the guinea pig maximization test : a dose-response study  

DEFF Research Database (Denmark)

Nickel sulphate is a sensitizer in guinea pigs, but the frequency of sensitization varies from study to study. The dose-response relationship for NiSO4.6H2O was evaluated in the guinea pig maximization test in this study. 6 intradermal (0.01%-3.0% aq.) and 6 topical (0.25%-10.0% pet.) concentrations were chosen for induction and NiSO4.6H2O 1% pet. was used for challenge, based on the absence of skin irritation in a pilot study. Blind reading was performed. A logistic dose-response model was applied to the challenge results. At 48 h, a linear relationship was obtained between the intradermal induction dose (but not topical dose) and the response, resulting in a maximum sensitization rate of 40% after 3% i.d. The reactivity disappeared at re-challenge 1 week later. Following a booster closed patch on day 35, using NiSO4 10% pet., the animals were challenged with NiSO4 2% pet. and statistical analyses of 72-h readings revealed a non-linear dose-response relationship, giving a maximum response frequency of 40% after initial induction with NiSO4 3% i.d. and 2% topical.

Rohold, A E; Nielsen, G D

1991-01-01

149

Dose Response of Alanine Detectors Irradiated with Carbon Ion Beams  

DEFF Research Database (Denmark)

Purpose: The amino acid alanine is used for dosimetry for several decades. For proton and ion radiation the detector dose response depends on the particle energy and particle type. Based on the track structure theory by Butts and Katz, a model developed by J. Hansen and K. Olsen describes this dependence. Methods: This paper presents experiments to verify the model for carbon ions in MeV an energy range of 89-400. The relative effectiveness of alanine is measured in this regime. Using the Monte Carlo code FLUKA the response of the detector is simulated and compared with the experimental results. Results: Calculations of the relative effectiveness deviate less than 4% from the measured values for mono energetic beams. Deviations in the peak area of 12.9 % and up to 9.6 % in the tail area in term of peak response have been found for depth dose-curves. Conclusions: The used model and its implementation show a very good overall agreement, deviations are attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.

Herrmann, Rochus; Jäkel, Oliver

2011-01-01

150

Fast neutron dose response of a commercial polycarbonate  

Science.gov (United States)

A commercial polycarbonate produced in Brazil is being studied to be used as neutron detector material using Solid State Nuclear Track Detection (SSNTD) method replacing the well-known detector materials Makrofol and CR-39. This technique is based on the damage (tracks) registration of charged particles produced by the interaction of neutrons with carbon and oxygen atoms of some dielectric materials. The IPEN dosimeter prototype is composed by 30×10×1.5 mm 3 polycarbonate piece inserted between two Polymethyl Methacralate (PMMA) plates 2 mm thick. The prototypes were irradiated placed on an ISO slab phantom using an isotropic 241AmBe source at LN/LNMRI (Neutrons Laboratory of the National Laboratory of Ionizing Radiation Metrology). To study the dose response groups of five prototypes were irradiated with Hp(10) from 0.5 to 20 mSv with normal incidence and to investigate the angular incidence effect with Hp(10) = 5 mSv with incidence angles of 15°, 45°, 60°, 75°, 85° and 90°. The detectors were revealed by chemical etching with the solution PEW-40 during 3 h. The track density of the detector surface was determined by the average of track counting of five fields ( 20×0.1 mm 2). The track response to equivalent dose Hp(10) showed a good agreement with linear fit in the studied interval. The track density strongly decreases for incidence angles higher than 45°.

Souto, E. B.; Campos, L. L.

2007-09-01

151

Dose response characteristics in polymer gel for the composition ratio  

Energy Technology Data Exchange (ETDEWEB)

Although a gel dosimeter is not widely used, it has many potential merits for 3D dosimetry in the development of radiotherapy techniques. Because conventional gel dosimeters tend to sensitively polymerize with oxygen. A new polymer gel that solves these problems was introduced recently. The gel dosimeter contains anti-oxidants that eliminate oxygen chemically instead of using complicated facilities. The type and the concentration of the monomer affect the polymerization of the polymer gel dosimeter. Therefore, the polymerization of the normoxic polymer gel dosimeter is affected by anti-oxidant, the monomer, the constituent ratio, and the condition of the monomer, so many researchers have concentrated on the anti-oxidant, the type of monomer, and the constituent ratio. In this study, a normoxic polymer gel dosimeter was composed using anti-oxidants in a laboratory, and the dose response and sensitivity were measured. The results of this study are as follow the threshold R2 values were reduced, and the radio sensitivity was reduced with the increasing MAA ratio. Otherwise, the increase in the gelatin represented an increase and decrease in the threshold value of R2 values and the radio sensitivity, respectively. Therefore, in this study, 6 - 8 % MAA ratios and an 8 % gelatin ratio, considering the aging effect of the gel, were the optimal values.

Cho, Sam Ju; Shim, Su Jung [Eulji University, Seongnam (Korea, Republic of); Kim, Chul Yong; Sim, Jang Bo; Lee, Suk [Korea University, Seoul (Korea, Republic of); Lee, Sang Hoon [Kwandong University College of Medicine, Seoul (Korea, Republic of); Huh, Hyun Do [Inha University Hospital, Incheon (Korea, Republic of); Shin, Dong Oh [Kyung Hee University, Suwon (Korea, Republic of); Lee, Rena [Ewha Woman' s University, Seoul (Korea, Republic of)

2010-01-15

152

Fast neutron dose response of a commercial polycarbonate  

International Nuclear Information System (INIS)

A commercial polycarbonate produced in Brazil is being studied to be used as neutron detector material using Solid State Nuclear Track Detection (SSNTD) method replacing the well-known detector materials Makrofol and CR-39. This technique is based on the damage (tracks) registration of charged particles produced by the interaction of neutrons with carbon and oxygen atoms of some dielectric materials. The IPEN dosimeter prototype is composed by 30x10x1.5 mm3 polycarbonate piece inserted between two Polymethyl Methacralate (PMMA) plates 2 mm thick. The prototypes were irradiated placed on an ISO slab phantom using an isotropic 241AmBe source at LN/LNMRI (Neutrons Laboratory of the National Laboratory of Ionizing Radiation Metrology). To study the dose response groups of five prototypes were irradiated with Hp(10) from 0.5 to 20 mSv with normal incidence and to investigate the angular incidence effect with Hp(10) = 5 mSv with incidence angles of 15o, 45o, 60o, 75o, 85o and 90o. The detectors were revealed by chemical etching with the solution PEW-40 during 3 h. The track density of the detector surface was determined by the average of track counting of five fields (20x0.1 mm2). The track response to equivalent dose Hp(10) showed a good agreement with linear fit in the studied interval. The track density strongly decreases for incidence angles higher than 45 degnce angles higher than 45 deg

153

Dose response of alanine detectors irradiated with carbon ion beams  

Energy Technology Data Exchange (ETDEWEB)

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 behavior of the alanine detector in clinical carbon ion beams and compare the results to 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 Hansen and Olsen has been implemented in the Monte Carlo code FLUKA and calculations were compared to experimental results. Results: Calculations of the relative effectiveness deviate less than 5% from the measured values for monoenergetic beams. Measured depth-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. Conclusions: The used model and its implementation show a good overall agreement for quasimonoenergetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.

Herrmann, Rochus; Jaekel, Oliver; Palmans, Hugo; Sharpe, Peter; Bassler, Niels [Department of Physics and Astronomy, Aarhus University, 8000 Aarhus (Denmark); Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg (Germany) and Department of Experimental Clinical Oncology, Aarhus University Hospital, 8000 Aarhus (Denmark); Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg (Germany) and Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg (Germany); National Physical Laboratory, Teddington, Middlesex, TW 11 OLW (United Kingdom); Department of Physics and Astronomy, Aarhus University, 8000 Aarhus (Denmark); Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg (Germany) and Department of Experimental Clinical Oncology, Aarhus University Hospital, 8000 Aarhus (Denmark)

2011-04-15

154

Dose response of alanine detectors irradiated with carbon ion beams  

International Nuclear Information System (INIS)

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 behavior of the alanine detector in clinical carbon ion beams and compare the results to 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 Hansen and Olsen has been implemented in the Monte Carlo code FLUKA and calculations were compared to experimental results. Results: Calculations of the relative effectiveness deviate less than 5% from the measured values for monoenergetic beams. Measured depth-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. Conclusions: The used model and its implementation show a good overall agreement for quasimonoenergetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.

155

Dose-response patterns of Radix Glycyrrhizae in Shanghan Lun  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract: In order to explore the dose-response patterns of Gancao (Radix Glycyrrhizae in Shanghan Lun (Treatise on Febrile Diseases, all prescriptions containing Gancao in Shanghan Lun were analyzed by frequency and hierarchical clustering analysis. The doses of Gancao used in Shanghan Lun ranged from six zhu (Chinese unit, and one zhu is equal to 0.65 g to four liang (Chinese unit, and one liang is equal to 15.625 g. Doses of one, two, three or four liang were commonly used. One liang Gancao as juvantia was usually matched with Mahuang (Herba Ephedrae, Xingren (Semen Armeniacae and Guizhi (Ramulus Cinnamomi for restricting the excessive diaphoresis of Mahuang. Two liang Gancao was often matched with some couple drugs, such as Guizhi and Shaoyao (Radix Paeoniae, Shigao (Gypsum Fibrosum and Zhimu (Rhizoma Anemarrhenae, Fuzi (Radix Aconiti Lateralis and Ganjiang (Rhizoma Zingiberis, for warming yang to supplement qi, nourishing yin, detoxifying Fuzi, and preventing qi impairment from heat evil. Three liang Gancao was mainly matched with Banxia (Rhizoma Pinelliae or Renshen (Radix Ginseng for treating middle energizer emesis. Four liang Gancao was matched with Ganjiang or tonifying herbs for invigorating vital qi and relieving spasm in deficiency syndromes with contraction, palpitation or diarrhea. Gancao is used for treating many syndromes in Shanghan Lun. It is frequently used to treat excess or heat syndromes with one or two liang in a dose and deficiency or cold syndromes with three or four liang in a dose.

Xue YANG

2009-03-01

156

Aged garlic extract reduces blood pressure in hypertensives: a dose–response trial  

Science.gov (United States)

Background/objectives: Hypertension affects about 30% of adults worldwide. Garlic has blood pressure-lowering properties and the mechanism of action is biologically plausible. Our trial assessed the effect, dose–response, tolerability and acceptability of different doses of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with uncontrolled hypertension. Subjects/methods: A total of 79 general practice patients with uncontrolled systolic hypertension participated in a double-blind randomised placebo-controlled dose–response trial of 12 weeks. Participants were allocated to one of three garlic groups with either of one, two or four capsules daily of aged garlic extract (240/480/960?mg containing 0.6/1.2/2.4?mg of S-allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and compared with baseline using a mixed-model approach. Tolerability was monitored throughout the trial and acceptability was assessed at 12 weeks by questionnaire. Results: Mean systolic blood pressure was significantly reduced by 11.8±5.4?mm?Hg in the garlic-2-capsule group over 12 weeks compared with placebo (P=0.006), and reached borderline significant reduction in the garlic-4-capsule group at 8 weeks (?7.4±4.1?mm?Hg, P=0.07). Changes in systolic blood pressure in the garlic-1-capsule group and diastolic blood pressure were not significantly different to placebo. Tolerability, compliance and acceptability were high in all garlic groups (93%) and highest in the groups taking one or two capsules daily. Conclusions: Our trial suggests aged garlic extract to be an effective and tolerable treatment in uncontrolled hypertension, and may be considered as a safe adjunct treatment to conventional antihypertensive therapy. PMID:23169470

Ried, K; Frank, O R; Stocks, N P

2013-01-01

157

Isometric exercise and cognitive function: an investigation of acute dose-response effects during submaximal fatiguing contractions.  

Science.gov (United States)

Abstract The purpose of this study was to explore the dose-response relationship between exercise and cognitive performance using an acute bout of isometric exercise. University students (N = 55) were randomly assigned to control, 30%, 50% and 70% of maximum voluntary handgrip contraction groups. Participants performed a modified Stroop task before and after completion of an isometric handgrip endurance trial at their assigned exercise intensity. Ratings of perceived exertion (RPE) and forearm muscle activation (EMG) showed linear trends of progressively greater RPE and muscle activation at greater exercise intensity levels. Regression analysis showed significant (P task with increasing exercise intensity. We conclude that performing isometric exercise until exhaustion is associated with reduced cognitive performance and that higher intensity isometric exercise leads to greater performance impairments in a linear dose-response manner. PMID:25260112

Brown, Denver M Y; Bray, Steven R

2015-03-01

158

What is the meaning of non-linear dose-response relationships between blood lead concentrations and IQ?  

Science.gov (United States)

Recent literature [e.g. Canfield RL, Henderson CR, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP. Intellectual impairment in children with blood lead concentrations below 10mg per deciliter. New Engl J Med 2003;348(16):1517-1526; Lanphear BP, Hornung R, Khoury J, Yolton K, Baghurst P, Bellinger DC, Canfield RL, Dietrich KN, Bornschein R, Greene T, Rothenberg SJ, Needleman HL, Schnaas L, Wasserman G, Graziano J, Roberts R. Low-level environmental lead exposure and children's intellectual function: an international pooled analysis. Environ Health Perspect 2005;113(7):894-899] has suggested the existence of a supra-linear dose-response relationship between environmental measures such as blood lead concentrations and IQ. This communication explores the mathematical requirements placed on such dose-response relationships when the environmental measure, or independent variable, is lognormally distributed and the effect, or dependent variable, is normally distributed. Results of the analyses show that a supra-linear slope is a required outcome of correlations between data distributions where one is lognormally distributed and the other is normally distributed. The analysis shows that caution should be taken in assigning biological significance to supra-linear dose-response relationships in these instances. Detailed analyses of such data sets should be conducted to determine if the magnitude of supra-linear slopes are more or less than mathematically required, and from there to consider biological significance. PMID:16551479

Bowers, Teresa S; Beck, Barbara D

2006-07-01

159

Methods for extracting dose response curves from radiation therapy data. I. A unified approach  

International Nuclear Information System (INIS)

This paper discusses an approach to fitting models to radiation therapy data in order to extract dose response curves for tumor local control and normal tissue damage. The approach is based on the method of maximum likelihood and is illustrated by several examples. A general linear logistic equation which leads to the Ellis nominal standard dose (NSD) equation is discussed; the fit of this equation to experimental data for mouse foot skin reactions produced by fractionated irradiation is described. A logistic equation based on the concept that normal tissue reactions are associated with the surviving fraction of cells is also discussed, and the fit of this equation to the same set of mouse foot skin reaction data is also described. These two examples illustrate the importance of choosing a model based on underlying mechanisms when one seeks to attach biological significance to a model's parameters

160

Dose response of surfactants to attenuate gas embolism related platelet aggregation  

Science.gov (United States)

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.

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

2014-03-01

161

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

Science.gov (United States)

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 ?g/kg I to the base diet (~25 ?g I/kg chow) to produce 5 nominal I levels, ranging from excess (basal+added I, Treatment 1: 1000 ?g I/kg chow) to deficient (Treatment 5: 25 ?g 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. PMID:21315791

Gilbert, M E; McLanahan, E D; Hedge, J; Crofton, K M; Fisher, J W; Valentín-Blasini, L; Blount, B C

2011-04-28

162

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

International Nuclear Information System (INIS)

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

163

A method to adjust radiation dose–response relationships for clinical risk factors  

International Nuclear Information System (INIS)

Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose–response curves and apply the method to adjust the dose–response for radiation pneumonitis for patients with/without pre-existing pulmonary co-morbidities.

164

NEUROTOXIC EFFECTS OF ENVIRONMENTAL AGENTS: DATA GAPS THAT CHALLENGE DOSE-RESPONSE ESTIMATION  

Science.gov (United States)

Neurotoxic effects of environmental agents: Data gaps that challenge dose-response estimation S Gutter*, P Mendola+, SG Selevan**, D Rice** (*UNC Chapel Hill; +US EPA, NHEERL; **US EPA, NCEA) Dose-response estimation is a critical feature of risk assessment. It can be...

165

A suggested statistical approach for dealing with the non-significant interactions between treatments  

OpenAIRE

A field experiment was conducted to study the effect of nitrogen (N) fertilizer and foliar appli-cation of potassium (K) and Mepiquat Chloride (MC) on yield of cotton. Seed cotton yield per plant and seed cotton and lint yield per hectare; have been increased due to the higher N rate and use of foliar application of K and MC. No significant interactions were found among the variables in the present study (N, K and MC) with respect to characters under investigation. Generally, interactions ind...

Sawan, Zakaria M.

2011-01-01

166

Characterizing dose-responses of catalase to nitrofurazone exposure in model ciliated protozoan Euplotes vannus for ecotoxicity assessment: enzyme activity and mRNA expression.  

Science.gov (United States)

In environmental studies, some biological responses, known as biomarkers, have been used as a powerful bioassay tool for more than four decades. Disparity between enzyme activity and mRNA abundance leads to correlation equivocality, which makes the application of biomarkers for environmental risk assessment more complicated. This study investigates this disparity in the case of catalase when used as a biomarker for detecting ecotoxicity induced by antibiotics in aquatic ecosystems. In particular, dose-responses for catalase activity and mRNA expression abundance were investigated in Euplotes vannus which were exposed to graded doses of nitrofurazone for several discrete durations, and dose-response models were developed to characterize the dose-response dynamics. Significant differences were found in both catalase activity and mRNA expression abundance among the E. vannus treated with nitrofurazone. Catalase activity showed a hormetic-like effect in terms of dose-response, characterized by a biphasic relationship which was more clearly evident after a longer exposure period, while mRNA expression abundance increased linearly with the exposure duration. Additionally, the correlation between catalase activity and mRNA expression abundance reversed along with the duration of exposure to nitrofurazone. Taken together, our results demonstrate that catalase mRNA expression offers a more straightforward dose-response model than enzyme activity. Our findings suggest that both catalase enzyme activity and mRNA expression abundance can be used jointly as bioassay tools for detecting ecotoxicity induced by nitrofurazone in aquatic ecosystems. PMID:24075098

Li, Jiqiu; Zhou, Liang; Lin, Xiaofeng; Yi, Zhenzhen; Al-Rasheid, Khaled A S

2014-02-01

167

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

OpenAIRE

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

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

2009-01-01

168

On the use of resampling tests for evaluating statistical significance of binding-site co-occurrence  

OpenAIRE

Abstract Background In eukaryotes, most DNA-binding proteins exert their action as members of large effector complexes. The presence of these complexes are revealed in high-throughput genome-wide assays by the co-occurrence of the binding sites of different complex components. Resampling tests are one route by which the statistical significance of apparent co-occurrence can be assessed. Results We have investigated two resampling approaches for evaluating the st...

Russell Steven; Huen David S

2010-01-01

169

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose-response using different monomers  

International Nuclear Information System (INIS)

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential forolymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies

170

Dose-response effects of inactivated Newcastle disease vaccines: influence of serologic assay, time after vaccination, and type of chickens.  

Science.gov (United States)

Knowledge of the dose-response relation of inactivated vaccines and of the factors that influence this relation is essential for the evaluation of existing vaccine potency assays and the development of new potency assays that are based on the antigen content of the inactivated vaccines. We quantified the relation between vaccine dose, serologic response, and clinical protection after vaccination for three different inactivated Newcastle disease (ND) vaccines. Qualitatively, similar dose-response curves were obtained for the three vaccines when either the serologic response or the clinical protection of specific-pathogen-free (SPF) chickens was plotted against the different vaccine doses applied. However, the vaccines differed quantitatively: doses of vaccines that induced similar antibody titers or clinical protection differed 2-8-fold. In contrast with the narrow range of antibody titers induced by a full vaccine dose, a very broad range of titers was obtained after dilution of the vaccines. At least 95% of the SPF chickens with detectable antibody in the serum were protected against a challenge with virulent Herts ND virus. The relation between the dosage of two different ND vaccines and the serum antibody titers remained markedly constant between 3 and 18 wk after vaccination. Vaccination of broilers instead of layers with a dilution series of inactivated ND vaccine resulted in significantly lower antibody levels and less clinical protection against virulent challenge. In conclusion, despite quantitative differences, we found comparable dose-response relations for the three inactivated ND vaccines studied. PMID:10611983

Maas, R A; Oei, H L; Venema-Kemper, S; Koch, G; Bongers, J

1999-01-01

171

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose-response using different monomers  

Energy Technology Data Exchange (ETDEWEB)

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R{sub 2}) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R{sub 2}) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R{sub 2} response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

Senden, R J [Department of Chemical Engineering, Queen' s University, Kingston, Ont. K7L 3N6 (Canada); Jean, P de [Cancer Centre of Southeastern Ontario, Kingston, Ont. K7L 5P9 (Canada); McAuley, K B [Department of Chemical Engineering, Queen' s University, Kingston, Ont. K7L 3N6 (Canada); Schreiner, L J [Cancer Centre of Southeastern Ontario, Kingston, Ont. K7L 5P9 (Canada)

2006-07-21

172

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

Science.gov (United States)

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

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

2014-07-01

173

Meta-analysis on occupational exposure to pesticides - Neurobehavioral impact and dose-response relationships.  

Science.gov (United States)

While the health impact of high exposures to pesticides is acknowledged, the impact of chronic exposures in the absence of acute poisonings is controversial. A systematic analysis of dose-response relationships is still missing. Its absence may provoke alternative explanations for altered performances. Consequently, opportunities for health prevention in the occupational and environmental field may be missed. Objectives were (1) quantification of the neurotoxic impact of pesticides by an analysis of functional alterations in workers measured by neuropsychological performance tests, (2) estimates of dose-response relationships on the basis of exposure duration, and (3) exploration of susceptible subgroups. The meta-analysis employed a random effects model to obtain overall effects for individual performance tests. Twenty-two studies with a total of 1758 exposed and 1260 reference individuals met the inclusion criteria. At least three independent outcomes were available for twenty-six performance variables. Significant performance effects were shown in adults and referred to both cognitive and motor performances. Effect sizes ranging from dRE=-0.14 to dRE=-0.67 showed consistent outcomes for memory and attention. Relationships between effect sizes and exposure duration were indicated for individual performance variables and the total of measured performances. Studies on adolescents had to be analyzed separately due to numerous outliers. The large variation among outcomes hampered the analysis of the susceptibility in this group, while data on female workers was too scant for the analysis. Relationships exist between the impact of pesticides on performances and exposure duration. A change in test paradigms would help to decipher the impact more specifically. The use of biomarkers appropriate for lower exposures would allow a better prevention of neurotoxic effects due to occupational and environmental exposure. Intervention studies in adolescents seem warranted to specify their risk. PMID:25460642

Meyer-Baron, Monika; Knapp, Guido; Schäper, Michael; van Thriel, Christoph

2015-01-01

174

Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity  

International Nuclear Information System (INIS)

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due tval time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time

175

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

International Nuclear Information System (INIS)

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

176

On the use of resampling tests for evaluating statistical significance of binding-site co-occurrence  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background In eukaryotes, most DNA-binding proteins exert their action as members of large effector complexes. The presence of these complexes are revealed in high-throughput genome-wide assays by the co-occurrence of the binding sites of different complex components. Resampling tests are one route by which the statistical significance of apparent co-occurrence can be assessed. Results We have investigated two resampling approaches for evaluating the statistical significance of binding-site co-occurrence. The permutation test approach was found to yield overly favourable p-values while the independent resampling approach had the opposite effect and is of little use in practical terms. We have developed a new, pragmatically-devised hybrid approach that, when applied to the experimental results of an Polycomb/Trithorax study, yielded p-values consistent with the findings of that study. We extended our investigations to the FL method developed by Haiminen et al, which derives its null distribution from all binding sites within a dataset, and show that the p-value computed for a pair of factors by this method can depend on which other factors are included in that dataset. Both our hybrid method and the FL method appeared to yield plausible estimates of the statistical significance of co-occurrences although our hybrid method was more conservative when applied to the Polycomb/Trithorax dataset. A high-performance parallelized implementation of the hybrid method is available. Conclusions We propose a new resampling-based co-occurrence significance test and demonstrate that it performs as well as or better than existing methods on a large experimentally-derived dataset. We believe it can be usefully applied to data from high-throughput genome-wide techniques such as ChIP-chip or DamID. The Cooccur package, which implements our approach, accompanies this paper.

Russell Steven

2010-06-01

177

A statistically significant signature of multi-decadal solar activity changes in atmospheric temperatures at three European stations  

Science.gov (United States)

We study the effect of solar variability on temperatures recorded in three European stations with the longest gapless series available (Prague, Bologna and Uccle). Following a pattern recognition approach, we partition daily temperature “indices” (minimum, maximum and range) in two separate classes with respect to the level of solar activity (high H vs low L 11 year cycles). Using the two-sample Kolmogorov-Smirnov statistics, multiple shuffles of data, and other partitions, we demonstrate that the separation between the probability distribution functions of H and L temperatures is statistically significant and robust. We find that average annual variations for the H and L classes display common and site-specific patterns. For practically all series considered, differences between graphs of annual change for the two classes H and L are large (˜1 °C). Solar activity accounts, at least in part, for the multi-decadal variations in temperature observed at these European sites in the past two centuries.

Kossobokov, Vladimir; Le Mouël, Jean-Louis; Courtillot, Vincent

2010-05-01

178

Tests of the linear, no-threshold dose-response relationship for high-LET radiation  

Energy Technology Data Exchange (ETDEWEB)

It is pointed out that induction of lung cancer by exposure to Rn daughters, applied at high doses to miners and at low doses to exposures in homes, provides a very stringent and sensitive test of the linear, no-threshold dose-response relationship for high-LET radiation, because this relationship predicts that a substantial fraction of lung cancer among non-smokers is due to average Rn levels. Therefore, it predicts an easily observable elevation of lung cancer rates in areas where Rn levels are many times greater than the average, especially at times before cigarette smoking began to have important effects on lung cancer statistics. While more data are needed (and will be forthcoming), some of the early indications of these studies are reviewed here. Several cases are now known where average Rn levels are very high, and in all of these cases lung cancer rates are well below average. Methods for analyzing these data are discussed, and it is concluded that, based on current evidence, they indicate at least a factor of 4 disagreement with linear, no-threshold predictions.

Cohen, B.L.

1987-05-01

179

Tests of the linear, no-threshold dose-response relationship for high-LET radiation  

International Nuclear Information System (INIS)

It is pointed out that induction of lung cancer by exposure to Rn daughters, applied at high doses to miners and at low doses to exposures in homes, provides a very stringent and sensitive test of the linear, no-threshold dose-response relationship for high-LET radiation, because this relationship predicts that a substantial fraction of lung cancer among non-smokers is due to average Rn levels. Therefore, it predicts an easily observable elevation of lung cancer rates in areas where Rn levels are many times greater than the average, especially at times before cigarette smoking began to have important effects on lung cancer statistics. While more data are needed (and will be forthcoming), some of the early indications of these studies are reviewed here. Several cases are now known where average Rn levels are very high, and in all of these cases lung cancer rates are well below average. Methods for analyzing these data are discussed, and it is concluded that, based on current evidence, they indicate at least a factor of 4 disagreement with linear, no-threshold predictions

180

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

CERN Document Server

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...

Mallik, Atul; Banerjee, Moulinath; Michailidis, George

2011-01-01

181

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

Directory of Open Access Journals (Sweden)

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

Magdalena Adamus-Górka

2011-05-01

182

Application of re-establishing dose-response curves by fluorescence in situ hybridization (FISH)  

International Nuclear Information System (INIS)

To establish a dose-response relationship between stable chromosome aberration and radiation dose by fluorescence in situ hybridization (FISH). Translocation frequencies in peripheral blood lymphocytes induced by 60Co ?-ray at different doses were analyzed by FISH with WCP whole chromosome specific probes for human chromosomes No. 1, No. 2 and No. 4, and its dose-response curve was fitted. The dose-response formula fitted with translocation frequencies is Y=0.01316 + 0.07569D + 0.01583D2. After checked by unknown samples. The formula is certified that it could be used to reestablish dose. Chromosome translocation can be quickly analyzed by FISH and it is hopeful to use translocation frequencies measured by FISH as a dose-response curve reestablished biological dosimeter. (authors)

183

Equivalent dose determination in foraminifera: analytical description of the CO2--signal dose-response curve  

International Nuclear Information System (INIS)

The dose-response of the CO2-signal (g=2.0006) in foraminifera with ages between 19 and 300 ka is investigated. The sum of two exponential saturation functions is an adequate function to describe the dose-response curve up to an additional dose of 8000 Gy. It yields excellent dating results but requires an artificial doses of at least 5000 Gy. For small additional doses of about 500 Gy the single exponential saturation function can be used to calculate a reliable equivalent dose DE, although it does not describ the dose-response for higher doses. The CO2--signal dose-response indicates that the signal has two components of which one is less stable than the other

184

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

CERN Document Server

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...

Baluev, Roman V

2013-01-01

185

Dose–Response Relationship of Prenatal Mercury Exposure and IQ: An Integrative Analysis of Epidemiologic Data  

OpenAIRE

Background: Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives: We estimated a dose–response relationship between maternal mercury body burden and subsequent childhood decrements in intelligence quotient (IQ), using a Bayesian hierarchical model to integrate data from three epidemiologic studies. Method...

Axelrad, Daniel A.; Woodruff, Tracey J.; Bellinger, David C.; Ryan, Louise Marie

2007-01-01

186

Transcriptional Profiling of the Dose Response: A More Powerful Approach for Characterizing Drug Activities  

OpenAIRE

The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmac...

Ji, Rui-ru; Silva, Heshani; Jin, Yisheng; Bruccoleri, Robert E.; Cao, Jian; He, Aiqing; Huang, Wenjun; Kayne, Paul S.; Neuhaus, Isaac M.; Ott, Karl-heinz; Penhallow, Becky; Cockett, Mark I.; Neubauer, Michael G.; Siemers, Nathan O.; Ross-macdonald, Petra

2009-01-01

187

Dose-response models incorporating aerosol size dependency for Francisella tularensis.  

Science.gov (United States)

The effect of bioaerosol size was incorporated into predictive dose-response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 ?m. Aerosol-size-dependent models were formulated as modification of the exponential and ?-Poisson dose-response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose-response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose-response data was best fit by an exponential dose-response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol-size-dependence equation and models that better represent the observed dose-response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure. PMID:24382336

Teske, Sondra S; Weir, Mark H; Bartrand, Timothy A; Huang, Yin; Tamrakar, Sushil B; Haas, Charles N

2014-05-01

188

Bronchial and cardiovascular responses to inhaled reproterol in asthmatics: a double-blind placebo controlled dose-response study.  

OpenAIRE

Reproterol is a synthetic selective beta-adrenoceptor agonist with a xanthine side chain. The bronchial and cardiovascular responses to inhaled reproterol were studied in 14 asthmatics. The study was placebo controlled and double-blind, comparing doubling doses of reproterol from 500 micrograms-8 mg. The peak improvement in FEV1 showed a non-linear dose-response, with an initial plateau at the 1 mg dose producing a mean increase in FEV1 of 17%, but significant further improvement at the 8 mg ...

Patchett, P.; Patchett, S. M.; Burge, P. S.

1985-01-01

189

Dose response and factors related to interstitial pneumonitis after bone marrow transplant  

International Nuclear Information System (INIS)

Purpose: Total body irradiation (TBI) and chemotherapy are common components of conditioning regimens for bone marrow transplantation. Interstitial pneumonitis (IP) is a known regimen-related complication. Using published data of IP in a multivariate logistic regression, this study sought to identify the parameters in the bone marrow transplantation conditioning regimen that were significantly associated with IP and to establish a radiation dose-response function. Methods and Materials: A retrospective review was conducted of articles that reported IP incidence along with lung dose, fractionation, dose rate, and chemotherapy regimen. In the final analysis, 20 articles (n = 1090 patients), consisting of 26 distinct TBI/chemotherapy regimens, were included in the analysis. Multivariate logistic regression was performed to determine dosimetric and chemotherapeutic factors that influenced the incidence of IP. Results: A logistic model was generated from patients receiving daily fractions of radiation. In this model, lung dose, cyclophosphamide dose, and the addition of busulfan were significantly associated with IP. An incidence of 3%-4% with chemotherapy-only conditioning regimens is estimated from the models. The ?/? value of the linear-quadratic model was estimated to be 2.8 Gy. The dose eliciting a 50% incidence, D 50, for IP after 120 mg/kg of cyclophosphamide was 8.8 Gy; in the absence of chemotherapy, the estimated D 50 is 10.6 Gy. No dose red D 50 is 10.6 Gy. No dose rate effect was observed. The use of busulfan as a substitute for radiation is equivalent to treating with 14.8 Gy in 4 fractions with 50% transmission blocks shielding the lung. The logistic regression failed to find a model that adequately fit the multiple-fraction-per-day data. Conclusions: Dose responses for both lung radiation dose and cyclophosphamide dose were identified. A conditioning regimen of 12 Gy TBI in 6 daily fractions induces an IP incidence of about 11% in the absence of lung shielding. Shielding the lung to receive 50% of this dose lowers the estimated incidence to about 2.3%. Because the lungs can be adequately shielded, we recommend against using busulfan as a substitute for fractionated TBI with cyclophosphamide

190

Exposure-dose-response of Tellina deltoidalis to contaminated estuarine sediments 3. Selenium spiked sediments.  

Science.gov (United States)

The metalloid selenium is an essential element which at slightly elevated concentrations is toxic and mutagenic. In Australia the burning of coal for power generation releases selenium into estuarine environments where it accumulates in sediments. The relationship between selenium exposure, dose and response was investigated in the deposit feeding, benthic, marine bivalve Tellina deltoidalis. Bivalves were exposed in microcosms for 28 days to individual selenium spiked sediments, 0, 5 and 20 ?g/g dry mass. T. deltoidalis accumulated selenium from spiked sediment but not in proportion to the sediment selenium concentrations. The majority of recovered subcellular selenium was associated with the nuclei and cellular debris fraction, probably as protein bound selenium associated with plasma and selenium bound directly to cell walls. Selenium exposed organisms had increased biologically detoxified selenium burdens which were associated with both granule and metallothionein like protein fractions, indicating selenium detoxification. Half of the biologically active selenium was associated with the mitochondrial fraction with up to 4 fold increases in selenium in exposed organisms. Selenium exposed T. deltoidalis had significantly reduced GSH:GSSG ratios indicating a build-up of oxidised glutathione. Total antioxidant capacity of selenium exposed T. deltoidalis was significantly reduced which corresponded with increased lipid peroxidation, lysosomal destabilisation and micronuclei frequency. Clear exposure-dose-response relationships have been demonstrated for T. deltoidalis exposed to selenium spiked sediments, supporting its suitability for use in selenium toxicity tests using sub-lethal endpoints. PMID:25008056

Taylor, Anne M; Maher, William A

2014-11-01

191

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

Directory of Open Access Journals (Sweden)

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

Leitner Dietmar

2005-04-01

192

Low dose responses of different glyphosate formulations on plants  

OpenAIRE

Although glyphosate clearly has real and potential commercial uses as a growth regulator at low doses, its main commercial significance has been as an herbicide. An important prerequisite for low dose applications gaining significance is a high efficiency and reliability of effects. This, however, seems to be a major constraint, especially regarding the approach of increasing yield by glyphosate hormesis. Glyphosate is marketed in various formulations, but potential disparities in low dose re...

Belz, Regina G.; Leberle, Claudia

2012-01-01

193

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

194

Habitual Chocolate Consumption May Increase Body Weight in a Dose-Response Manner  

Science.gov (United States)

Objective Habitual chocolate intake was recently found to be associated with lower body weight in three cross-sectional epidemiological studies. Our objective was to assess whether these cross-sectional results hold up in a more rigorous prospective analysis. Methods We used data from the Atherosclerosis Risk in Communities cohort. Usual dietary intake was assessed by questionnaire at baseline (1987–98), and after six years. Participants reported usual chocolate intake as the frequency of eating a 1-oz (?28 g) serving. Body weight and height were measured at the two visits. Missing data were replaced by multiple imputation. Linear mixed-effects models were used to evaluate cross-sectional and prospective associations between chocolate intake and adiposity. Results Data were from 15,732 and 12,830 participants at the first and second visit, respectively. More frequent chocolate consumption was associated with a significantly greater prospective weight gain over time, in a dose-response manner. For instance, compared to participants who ate a chocolate serving less often than monthly, those who ate it 1–4 times a month and at least weekly experienced an increase in Body Mass Index (kg/m2) of 0.26 (95% CI 0.08, 0.44) and 0.39 (0.23, 0.55), respectively, during the six-year study period. In cross-sectional analyses the frequency of chocolate consumption was inversely associated with body weight. This inverse association was attenuated after excluding participants with preexisting obesity-related illness. Compared to participants without such illness, those with it had higher BMI and reported less frequent chocolate intake, lower caloric intake, and diets richer in fruits and vegetables. They tended to make these dietary changes after becoming ill. Conclusions Our prospective analysis found that a chocolate habit was associated with long-term weight gain, in a dose-response manner. Our cross-sectional finding that chocolate intake was associated with lower body weight did not apply to participants without preexisting serious illness. PMID:23950919

Greenberg, James A.; Buijsse, Brian

2013-01-01

195

Statistical significance of hierarchical multi-body potentials based on Delaunay tessellation and their application in sequence-structure alignment.  

Science.gov (United States)

Statistical potentials based on pairwise interactions between C alpha atoms are commonly used in protein threading/fold-recognition attempts. Inclusion of higher order interaction is a possible means of improving the specificity of these potentials. Delaunay tessellation of the C alpha-atom representation of protein structure has been suggested as a means of defining multi-body interactions. A large number of parameters are required to define all four-body interactions of 20 amino acid types (20(4) = 160,000). Assuming that residue order within a four-body contact is irrelevant reduces this to a manageable 8,855 parameters, using a nonredundant dataset of 608 protein structures. Three lines of evidence support the significance and utility of the four-body potential for sequence-structure matching. First, compared to the four-body model, all lower-order interaction models (three-body, two-body, one-body) are found statistically inadequate to explain the frequency distribution of residue contacts. Second, coherent patterns of interaction are seen in a graphic presentation of the four-body potential. Many patterns have plausible biophysical explanations and are consistent across sets of residues sharing certain properties (e.g., size, hydrophobicity, or charge). Third, the utility of the multi-body potential is tested on a test set of 12 same-length pairs of proteins of known structure for two protocols: Sequence-recognizes-structure, where a query sequence is threaded (without gap) through the native and a non-native structure; and structure-recognizes-sequence, where a query structure is threaded by its native and another non-native sequence. Using cross-validated training, protein sequences correctly recognized their native structure in all 24 cases. Conversely, structures recognized the native sequence in 23 of 24 cases. Further, the score differences between correct and decoy structures increased significantly using the three- or four-body potential compared to potentials of lower order. PMID:9232648

Munson, P J; Singh, R K

1997-07-01

196

Quantitative dose-response analysis of ethyl methanesulfonate genotoxicity in adult gpt-delta transgenic mice.  

Science.gov (United States)

The assumption that mutagens have linear dose-responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA-reactive mutagen and carcinogen, exhibited sublinear or thresholded dose-responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Müller L [2009]: Mutat Res 678:101-107). In order to explore variables in establishing genotoxicity dose-responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta™Mouse. Male gpt-delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig-a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no-observed-genotoxic-effect-levels (NOGELs), lower confidence limits of threshold effect levels (Td-LCIs), and lower confidence limits of 10% benchmark response rates (BMDL10 s). Similar PoDs were calculated from the published EMS dose-responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig-a MFs were 13-40-fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose-responses in gpt-delta mice had lower PoDs than those calculated from the Muta™Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds. PMID:24535894

Cao, Xuefei; Mittelstaedt, Roberta A; Pearce, Mason G; Allen, Bruce C; Soeteman-Hernández, Lya G; Johnson, George E; Bigger, C Anita H; Heflich, Robert H

2014-06-01

197

Non-linear least squares curve fitting of a simple theoretical model to radioimmunoassay dose-response data using a mini-computer  

International Nuclear Information System (INIS)

Using the simple univalent antigen univalent-antibody equilibrium model the dose-response curve of a radioimmunoassay (RIA) may be expressed as a function of Y, X and the four physical parameters of the idealised system. A compact but powerful mini-computer program has been written in BASIC for rapid iterative non-linear least squares curve fitting and dose interpolation with this function. In its simplest form the program can be operated in an 8K byte mini-computer. The program has been extensively tested with data from 10 different assay systems (RIA and CPBA) for measurement of drugs and hormones ranging in molecular size from thyroxine to insulin. For each assay system the results have been analysed in terms of (a) curve fitting biases and (b) direct comparison with manual fitting. In all cases the quality of fitting was remarkably good in spite of the fact that the chemistry of each system departed significantly from one or more of the assumptions implicit in the model used. A mathematical analysis of departures from the model's principal assumption has provided an explanation for this somewhat unexpected observation. The essential features of this analysis are presented in this paper together with the statistical analyses of the performance of the program. From these and the results obtained to date in the routine quality control of these 10 assays, it is concluded that the method of curve fitting and dose interpolation presented in this paper is likely to be of general applicability. (orig.)

198

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

International Nuclear Information System (INIS)

A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and ? 2-microglobulinuria (?2MG-uria) under environmental exposure. ?2MG-uria was defined by a cutoff point of 1000 ?g ? 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 ?2MG-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 ?2MG-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 ?2MG-uria. This was estimated to be approximately 3 ?g/g creatinine for a population in a small geographical area and approximately 2 ?g/g creatinine for a nationwid ?g/g creatinine for a nationwide population

199

Campylobacteriosis outbreak associated with consumption of undercooked chicken liver pâté in the East of England, September 2011: identification of a dose-response risk.  

Science.gov (United States)

A foodborne outbreak with 49 cases (22 culture positive for Campylobacter sp.) following a wedding party in the East of England was investigated. A retrospective cohort study identified an association between consumption of chicken liver pâté and infection with Campylobacter jejuni/coli. There was a statistically significant association between dose (amount of chicken liver pâté eaten) and the risk of disease ['tasted': odds ratio (OR) 1·5, 95% confidence interval (CI) 0·04-?; 'partly eaten': OR 8·4, 95% CI 1·4-87·5; 'most or all eaten': OR 36·1, 95% CI 3·3-2119). The local authority found evidence that the preparation of chicken livers breached Food Standards Agency's guidelines. This epidemiological investigation established a clear dose-response relationship between consumption of chicken liver pâté and the risk of infection with Campylobacter. The continuing need to raise public awareness of the risk to human health posed by undercooked chicken liver is evident. PMID:23711104

Edwards, D S; Milne, L M; Morrow, K; Sheridan, P; Verlander, N Q; Mulla, R; Richardson, J F; Pender, A; Lilley, M; Reacher, M

2014-02-01

200

Bell-shaped and ultrasensitive dose-response in phosphorylation-dephosphorylation cycles: the role of kinase-phosphatase complex formation  

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Full Text Available Abstract Background Phosphorylation-dephosphorylation cycles (PDCs mediated by kinases and phosphatases are common in cellular signalling. Kinetic modelling of PDCs has shown that these systems can exhibit a variety of input-output (dose-response behaviors including graded response, ultrasensitivity and bistability. In addition to proteins, there are a class of lipids known as phosphoinositides (PIs that can be phosphorylated. Experimental studies have revealed the formation of an antagonistic kinase-phosphatase complex in regulation of phosphorylation of PIs. However, the functional significance of this type of complex formation is not clear. Results We first revisit the basic PDC and show that partial asymptotic phosphorylation of substrate limits ultrasensitivity. Also, substrate levels are changed one can obtain non-monotonic bell-shaped dose-response curves over a narrow range of parameters. Then we extend the PDC to include kinase-phosphatase complex formation. We report the possibility of robust bell-shaped dose-response for a specific class of the model with complex formation. Also, we show that complex formation can produce ultrasensitivity outside the Goldbeter-Koshland zero-order ultrasensitivity regime through a mechanism similar to competitive inhibition between an enzyme and its inhibitor. Conclusions We conclude that the novel PDC module studied here exhibits new dose-response behaviour. In particular, we show that the bell-shaped response could result in transient phosphorylation of substrate. We discuss the relevance of this result in the context of experimental observations on PI regulation in endosomal trafficking.

Szomolay Barbara

2012-04-01

201

Antioxidant Dose Response in Human Blood Cells Exposed to Different Types of Irradiation  

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Full Text Available The research work was conducted to investigate the changes of superoxide dismutases (SODs activity in human blood cells irradiated with 22.6 MeV protons, and to compare the results with examinations performed with x- and ?- rays. The activity of SOD was significantly lowered after 1 Gy of proton beam and increase of dose further decreases total SOD activity. The effect of proton beam is same in the cases of cytosol SOD (CuZnSOD and mitochondrial SOD (MnSOD, which means that both defense lines are disturbed already after 1Gy proton beam irradiation, which is very important in the radio therapy of tumor cells. This dose response is compared to dose of x- or ? - irradiation, the difference is obvious. The increased MnSOD activity is induced by in vitro irradiation with 2 Gy of x - rays and after 4 Gy of MnSOD activity is on the control level again. The measured activity of mitochondrial SOD shows that the most striking fall after irradiation with 3 Gy or 4 Gy of ?-rays.

S.B. Pajovi

2001-01-01

202

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

CERN Document Server

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...

Østvand, Lene; Rypdal, Martin

2013-01-01

203

A simple dose-response relationship for modeling secondary cancer incidence after radiotherapy  

International Nuclear Information System (INIS)

Estimates of secondary cancer risk after radiotherapy are becoming more important for comparative treatment planning. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at doses higher than 4 Gy. The purpose of this report is to determine a simple dose-response relationship for secondary cancer incidence after radiotherapy treatment which can be used for comparative treatment planning. In this report a simple one-parameter model to estimate the complication probability of secondary cancer was fitted to literature data on secondary cancer incidence after radiotherapy. The results showed a linear dose-response relationship in the low-dose part and an exponentially decreasing one after a maximum at around 10 Gy. The observed dose-response relationship and the literature data used to fit the dose-response indicate that cell death effects are important for the explanation of secondary cancer incidence. Even using a dose and dose-rate effectiveness factor (DDREF) of two (instead of one), a cancer incidence maximum is observed at around 10 Gy, with decreasing incidence at higher doses. (orig.)

204

Biphasic dose responses in biology, toxicology and medicine: Accounting for their generalizability and quantitative features  

International Nuclear Information System (INIS)

The most common quantitative feature of the hormetic-biphasic dose response is its modest stimulatory response which at maximum is only 30–60% greater than control values, an observation that is consistently independent of biological model, level of organization (i.e., cell, organ or individual), endpoint measured, chemical/physical agent studied, or mechanism. This quantitative feature suggests an underlying “upstream” mechanism common across biological systems, therefore basic and general. Hormetic dose response relationships represent an estimate of the peak performance of integrative biological processes that are allometrically based. Hormetic responses reflect both direct stimulatory or overcompensation responses to damage induced by relatively low doses of chemical or physical agents. The integration of the hormetic dose response within an allometric framework provides, for the first time, an explanation for both the generality and the quantitative features of the hormetic dose response. -- Highlights: •The hormetic stimulation is at maximum 30–60% greater than control responses. •Hormesis is a measure of biological performance and plasticity. •The hormetic response is evolutionary based and highly generalizable. -- This paper provides a biologically based explanation for the generalizability/quantitative features of the hormetic dose response, representing a fundamental contribution to the field

205

Regression and error analysis applied to the dose-response curves in thermoluminescence dating  

International Nuclear Information System (INIS)

In the dating of Quaternary geological materials by thermoluminescence (TL), one frequently encounters sublinear TL vs applied dose curves for which accurate extrapolation is required. For dating the last exposure to sunlight of unheated Quaternary sediments, the intersection of two sublinear dose-response curves is usually sought. Adequate methods for estimating the uncertainty in this intersection have not been previously described. Here we outline an iteratively reweighted least-squares procedure for calculating the coefficients of second-order polynomials as well as saturating exponentials, and a variance-covariance method of error analysis appropriate for the intersection of two dose-response curves. Applications to several data sets are presented. The procedures described here are equally applicable, with trivial changes, to extrapolations of single sublinear dose-response curves (the additive dose technique). (author)

206

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

Science.gov (United States)

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

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

2014-01-01

207

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

Science.gov (United States)

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

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

2014-01-01

208

Dose response of micronuclei induced by combination radiation of ?-particles and ?-rays in human lymphoblast cells  

International Nuclear Information System (INIS)

Highlights: ? ?-Particle induced MN had a biphasic dose–response followed by a bystander model. ? MN dose–response of ?- and ?-combination IR was similar to that of ?-particle. ? ?-Particles followed by ?-rays yielded a synergistic effect on MN induction. ? Low dose ?-rays triggered antagonistic and adaptive responses against ?-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 ?-particles, ?-rays, and their combinations. Results showed that the dose–response of MN induced by ?-rays was well-fitted with the linear-quadratic model. But for ?-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 ?-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with ?-particles at first and then ?-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with ?-rays followed by ?-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 ?-rays but not ?-particles

209

Dose response of micronuclei induced by combination radiation of ?-particles and ?-rays in human lymphoblast cells  

Energy Technology Data Exchange (ETDEWEB)

Highlights: ? ?-Particle induced MN had a biphasic dose–response followed by a bystander model. ? MN dose–response of ?- and ?-combination IR was similar to that of ?-particle. ? ?-Particles followed by ?-rays yielded a synergistic effect on MN induction. ? Low dose ?-rays triggered antagonistic and adaptive responses against ?-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 ?-particles, ?-rays, and their combinations. Results showed that the dose–response of MN induced by ?-rays was well-fitted with the linear-quadratic model. But for ?-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 ?-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with ?-particles at first and then ?-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with ?-rays followed by ?-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 ?-rays but not ?-particles.

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

210

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

Science.gov (United States)

ncreasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational studies reporting risk ratios with 95% confidence intervals (CIs) for metabolic syndrome in ?3 categories of dietary magnesium intake levels were selected. The data extraction was performed independently by two authors, and the quality of the studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Based on eight cross-sectional studies and two prospective cohort studies, the pooled relative risks of metabolic syndrome per 150 mg/day increment in magnesium intake was 0.88 (95% CI, 0.84-0.93; I2 = 36.3%). The meta-regression model showed a generally linear, inverse relationship between magnesium intake (mg/day) and metabolic syndrome. This dose-response meta-analysis indicates that dietary magnesium intake is significantly and inversely associated with the risk of metabolic syndrome. However, randomized clinical trials will be necessary to address the issue of causality and to determine whether magnesium supplementation is effective for the prevention of metabolic syndrome. PMID:25533010

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

2014-01-01

211

Dietary Magnesium Intake and Metabolic Syndrome in the Adult Population: Dose-Response Meta-Analysis and Meta-Regression  

Directory of Open Access Journals (Sweden)

Full Text Available ncreasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational studies reporting risk ratios with 95% confidence intervals (CIs for metabolic syndrome in ?3 categories of dietary magnesium intake levels were selected. The data extraction was performed independently by two authors, and the quality of the studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS. Based on eight cross-sectional studies and two prospective cohort studies, the pooled relative risks of metabolic syndrome per 150 mg/day increment in magnesium intake was 0.88 (95% CI, 0.84–0.93; I2 = 36.3%. The meta-regression model showed a generally linear, inverse relationship between magnesium intake (mg/day and metabolic syndrome. This dose-response meta-analysis indicates that dietary magnesium intake is significantly and inversely associated with the risk of metabolic syndrome. However, randomized clinical trials will be necessary to address the issue of causality and to determine whether magnesium supplementation is effective for the prevention of metabolic syndrome.

Sang-Yhun Ju

2014-12-01

212

Dose-Response Relationship of Phototherapy for Hyperbilirubinemia  

DEFF Research Database (Denmark)

BACKGROUND AND OBJECTIVE:Using light-emitting diodes during conventional phototherapy, it is possible to reduce the distance from light source to infant, thus increasing light irradiance. The objective of this study was to search for a "saturation point" (ie, an irradiation level above which there is no further decrease in total serum bilirubin [TsB]). This was a prospective randomized study performed in the NICU of Aalborg Hospital, Denmark.METHODS:One hundred fifty-one infants (gestational age ?33 weeks) with uncomplicated hyperbilirubinemia were randomized to 1 of 4 distances from the phototherapy device to the mattress (20, 29, 38, and 47 cm). TsB was measured before and after 24 hours of phototherapy and irradiance every eighth hour. Main outcome was 24-hour decrease of TsB expressed in percent, ( TsB(0-24), difference between TsB(0) and TsB(24) [%]).RESULTS:A highly significant linear relation was seen between light irradiance and TsB(0-24) (%) (P <.001): when the irradiance increased from 20 to 55 ?W/cm(2)/nm, TsB(0-24) (%) increased from approximately 30% to 50%. In addition, smooth regression showed no tendency for TsB(0-24) (%) to level off as irradiance increased. TsB(0-24) (%) was negatively correlated to birth weight and positively to formula volume. Average weight gain during phototherapy was 1%, independent of light irradiance.CONCLUSIONS:By using light-emitting diodes, we found a linear relation between light irradiance in the range of 20 to 55 ?W/cm(2)/nm and a decrease in TsB after 24 hours of therapy, with no evidence of a saturation point.

Vandborg, Pernille Kure; Hansen, Bo Moelholm

2012-01-01

213

Dose–response relationship of ultrasound contrast agent in an in vivo murine melanoma model  

Science.gov (United States)

Abstract Many factors affect the sensitivity and reliability of tumor vasculature assessment at the small doses of contrast agent necessary for imaging mice. In this study we investigate the dose–response relationship of ultrasound contrast agent for a minimal exposure power Doppler technique (minexPD) in a murine melanoma model. K1735 murine melanomas grown in 25 C3H/HeN mice were imaged by power Doppler ultrasound using different doses of contrast agents, Optison® and Definity®. Six mice were treated with an antivascular agent, combretastatin A4-phosphate (CA4P), and imaged before and after treatment. The color-weighted fractional area (CWFA) of the peak-enhanced image was measured to assess tumor perfusion on a relative scale of 0 to 100. CWFA increased logarithmically with dose (R2=0.97). Treatment with CA4P resulted in pronounced reduction in tumor perfusion 2?h after contrast injection, but perfusion recovered in the tumor periphery after 2 days. CWFA was significantly different between pre- and post-treatment for all doses at 2?h and 2 days (p < 0.05, respectively). There was no significant difference detectable between the two contrast agents, Optison® and Definity® (p = 0.46). In vivo tumor enhancement in mice increases as logarithmic function with dose. Although the extent of enhancement is dose dependent, the difference between pre- and post-therapy enhancement is relatively unchanged and uniform at varying doses. The two contrast agents tested in this study performed equally well. These results suggest that quantitative contrast-enhanced power Doppler imaging is an effective method for monitoring therapy response of tumors in mice. PMID:18083651

Ziemer, Lisa S; Schultz, Susan; Lee, William M.F; Sehgal, Chandra M

2007-01-01

214

BowStrap v1.0: Assigning statistical significance to expressed genes using short-read transcriptome data  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Background: Deep RNA sequencing, the application of Next Generation sequencing technology to generate a comprehensive profile of the message RNA present in a set of biological samples, provides unprecedented resolution into the molecular foundations of biological processes. By aligning short read RNA sequence data to a set of gene models, expression patterns for all of the genes and gene variants in a biological sample can be calculated. However, accurate determination of gene model expression from deep RNA sequencing is hindered by the presence of ambiguously aligning short read sequences. Findings BowStrap, a program for implementing the sequence alignment tool ‘Bowtie’ in a bootstrap-style approach, accommodates multiply-aligning short read sequences and reports gene model expression as an averaged aligned reads per Kb of gene model sequence per million aligned deep RNA sequence reads with a confidence interval, suitable for calculating statistical significance of presence/absence of detected gene model expression. BowStrap v1.0 was validated against a simulated metatranscriptome. Results were compared with two alternate ‘Bowtie’-based calculations of gene model expression. BowStrap is better at accurately identifying expressed gene models in a dataset and provides a more accurate estimate of gene model expression level than methods that do not incorporate a boot-strap style approach. Conclusions BowStrap v1.0 is superior in ability to detect significant gene model expression and calculate accurate determination of gene model expression levels compared to other alignment-based methods of determining patterns of gene expression. BowStrap v1.0 also can utilize multiple processors as has decreased run time compared to the previous version, BowStrap 0.5. We anticipate that BowStrap will be a highly useful addition to the available set of Next Generation RNA sequence analysis tools.

Larsen Peter E

2012-06-01

215

Mechanistic interpretation of radiation dose-response relationship for subclinical metastasis  

International Nuclear Information System (INIS)

To use a biophysical model based on the kinetics of metastatic formation to interpret radiation dose-response relationship for subclinical metastasis, and compare with what is predicted by the empirical model of Withers et al.. Methods: The metastases control probability (MCP) was formulated as a function of radiation dose and metastatic cell burden (MCB). The MCB was expressed to be log-uniformly distributed, as suggested by Withers et al.. In the mechanistic model, it was derived from the kinetics of primary tumor growth and subsequent metastatic colony formation and growth. A limiting resolution for clinical detection of metastasis (e.g. 109 cells) was assumed, and heterogeneous distributions for various biological parameters were considered. Mathematical expressions for both empirical and mechanistic models were solved analytically, and numerical simulations were performed using Mathcad software. Results: Withers et al. had presented clinical data to support a sigmoid-shaped MCP curve with a slope that is flatter than the control probability for gross tumor. This was verified by assuming the MCB to be log-uniformly distributed from 1 to 109 cells, provided that patients without subclinical metastasis are excluded. However, for patients diagnosed to have localized primary tumor, whether or not subclinical metastases are present remains unknown. This difficulty is alleviated in the mechanistic model, as an explicit expression for the metastasis an explicit expression for the metastasis-free cohort was obtained by subjecting all patients to undergo the Poisson process of metastatic establishment. Numerical simulations confirmed that the sigmoid MCP curve has a shallower slope if heterogeneity in metastatic rate is considered using log-normal distribution. Heterogeneity in metastatic growth rate with Gaussian distribution also resulted in significant flattening from an otherwise sharply-rising deterministic MCP curve. Conclusion: The mechanistic model of metastatogenesis appears to be more versatile for clinical application than the empirical model. It may help in formulating appropriate therapeutic strategy for subclinical metastases

216

Assessment of dose-response relationship in carcinogenesis following low radiation dosage  

International Nuclear Information System (INIS)

The quantitative experimental study of low-level radiation carcinogenesis entails numerous complex problems. Observation of large animal samples over the entire life span is required for definition of the basic (naturally occurring) and modulated (following irradiation) tumour spectrum. As a consequence, a detailed study of the spontaneous tumour incidence in the control population is essential. The data presented are based on a total of 8229 C57 Black/6M mice, of both sexes, observed over their whole life span which, under pathogen-free conditions, extended to about 1200 days. The basic tumour spectrum was defined and subsequently used as a reference system for the comparative evaluaton of the tumour yield following small doses of neutrons or gamma radiation or tritiated thymidine. The experiment was aimed at providing dose-response relationships from external versus internal iradiation. The following conclusions can be tentatively drawn: (1) In control mice, a very high incidence of tumour was observed, namely 84.4% in females versus 66.7% in males. As a consequence, it would seem that the whole concept of tumour induction versus natural tumour incidence should be re-evaluated. (2) Modulation of the basic tumour spectrum incidence following irradiaton appeared to be, in some instances, not only quantitative but also qualitative in nature, as evidenced by an observed shift from type A to type B reticulum cell lymphoma in irradiated mice at all dose levels. (3)In age-diated mice at all dose levels. (3)In age-specific incidence rates for lymphocytic lymphomas, the time shift of observed values was twofold, towards relatively higher incidence earlier in life and towards relatively lower incidence in late survivors. These observtions suggest an in-depth re-evaluation of some current concepts on the modulation of tumour incidence by carcinogenic agents, from the point of view of their qualitative significance and quantitative assessment

217

Test of significant toxicity: a statistical application for assessing whether an effluent or site water is truly toxic.  

Science.gov (United States)

The U.S. Environmental Protection Agency (U.S. EPA) and state agencies implement the Clean Water Act, in part, by evaluating the toxicity of effluent and surface water samples. A common goal for both regulatory authorities and permittees is confidence in an individual test result (e.g., no-observed-effect concentration [NOEC], pass/fail, 25% effective concentration [EC25]), which is used to make regulatory decisions, such as reasonable potential determinations, permit compliance, and watershed assessments. This paper discusses an additional statistical approach (test of significant toxicity [TST]), based on bioequivalence hypothesis testing, or, more appropriately, test of noninferiority, which examines whether there is a nontoxic effect at a single concentration of concern compared with a control. Unlike the traditional hypothesis testing approach in whole effluent toxicity (WET) testing, TST is designed to incorporate explicitly both ? and ? error rates at levels of toxicity that are unacceptable and acceptable, given routine laboratory test performance for a given test method. Regulatory management decisions are used to identify unacceptable toxicity levels for acute and chronic tests, and the null hypothesis is constructed such that test power is associated with the ability to declare correctly a truly nontoxic sample as acceptable. This approach provides a positive incentive to generate high-quality WET data to make informed decisions regarding regulatory decisions. This paper illustrates how ? and ? error rates were established for specific test method designs and tests the TST approach using both simulation analyses and actual WET data. In general, those WET test endpoints having higher routine (e.g., 50th percentile) within-test control variation, on average, have higher method-specific ? values (type I error rate), to maintain a desired type II error rate. This paper delineates the technical underpinnings of this approach and demonstrates the benefits to both regulatory authorities and permitted entities. PMID:21305584

Denton, Debra L; Diamond, Jerry; Zheng, Lei

2011-05-01

218

New scanning technique using Adaptive Statistical lterative Reconstruction (ASIR) significantly reduced the radiation dose of cardiac CT  

International Nuclear Information System (INIS)

The aims of our study were to evaluate the effect of application of Adaptive Statistical Iterative Reconstruction (ASIR) algorithm on the radiation dose of coronary computed tomography angiography (CCTA) and its effects on image quality of CCTA and to evaluate the effects of various patient and CT scanning factors on the radiation dose of CCTA. This was a retrospective study that included 347 consecutive patients who underwent CCTA at a tertiary university teaching hospital between 1 July 2009 and 20 September 2011. Analysis was performed comparing patient demographics, scan characteristics, radiation dose and image quality in two groups of patients in whom conventional Filtered Back Projection (FBP) or ASIR was used for image reconstruction. There were 238 patients in the FBP group and 109 patients in the ASIR group. There was no difference between the groups in the use of prospective gating, scan length or tube voltage. In ASIR group, significantly lower tube current was used compared with FBP group, 550mA (450–600) vs. 650mA (500–711.25) (median (interquartile range)), respectively, P<0.001. There was 27% effective radiation dose reduction in the ASIR group compared with FBP group, 4.29mSv (2.84–6.02) vs. 5.84mSv (3.88–8.39) (median (interquartile range)), respectively, P<0.001. Although ASIR was associated with increased image noise compared with FBP (39.93±10.22 vs. 37.63±18.79 (mean ±standard deviation), respectively, P<001), it did not affect the signal intensity, signal-to-noise ratio, contrast-to-noise ratio or the diagnostic quality of CCTA. Application of ASIR reduces the radiation dose of CCTA without affecting the image quality.

219

Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors  

Science.gov (United States)

Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

220

EXPERIMENTAL DESIGN STRATEGY FOR THE WEIBULL DOSE RESPONSE MODEL (JOURNAL VERSION)  

Science.gov (United States)

The objective of the research was to determine optimum design point allocation for estimation of relative yield losses from ozone pollution when the true and fitted yield-ozone dose response relationship follows the Weibull. The optimum design is dependent on the values of the We...

221

Generalized Estimating Equations for Repeated Measures Logistic Regression in Mosquito Dose-Response  

OpenAIRE

Dose-response studies in arthropod research usually involve observing and collecting successive information at different times on the same group of insects exposed to different concentrations of stimulus. When the same measure is collected repeatedly over time, the data become correlated and Probit Analysis technique which is the standard method in analyzing bioassay experiments dat...

Gabriel Otieno; Waititu, Gichihu A.; Daisy Salifu

2013-01-01

222

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

DEFF Research Database (Denmark)

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

Torekov, Signe SØrensen; Kipnes, M S

2011-01-01

223

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

International Nuclear Information System (INIS)

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

224

Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays  

International Nuclear Information System (INIS)

Chromosome aberration is a bio marker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard bio dosimetry of individuals over exposed to ionizing radiation. In radiation accident the dicentric assays has been applied as biological dosimetry to estimate radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric) in human lymphocyte induced by gamma radiation. Peripheral blood samples from three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0 Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + ?D + ?D2. The result showed that ? and ? values of the curve obtained were 0.018 ± 0.006 and 0.013 ± 0.002, respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration dicentric for bio dosimetry, this standard curve still need to be validated. (author)

225

Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays  

Directory of Open Access Journals (Sweden)

Full Text Available Chromosome aberration is a biomarker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard biodosimetry of individuals over exposed to ionizing radiation. In radiation accident the dicentric assays has been applied as biological dosimetry to estimate radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric in human lymphocyte induced by gamma radiation. Peripheral blood samples from three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0 Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + ?D + ?D2. The result showed that ? and ? values of the curve obtained were 0.018 ± 0.006 and 0.013 ± 0.002, respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration disentric for biodosimetry, this standar curve still need to be validated.

Y. Lusiyanti

2013-12-01

226

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

Science.gov (United States)

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.

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

227

Dairy Products Consumption and Risk of Type 2 Diabetes: Systematic Review and Dose-Response Meta-Analysis  

Science.gov (United States)

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. PMID:24086304

Gao, Dengfeng; Ning, Ning; Wang, Congxia; Wang, Yuhuan; Li, Qing; Meng, Zhe; Liu, Yang; Li, Qiang

2013-01-01

228

Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial  

International Nuclear Information System (INIS)

Purpose: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. Methods and Materials: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. Results: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p=0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p=0.01). For patients with a pretreatment PSA ?10 ng/mL, no significant dose response was found, with an average 6-year FFF rate of about 75%. Although no difference occurred in overall survival, the freedom from distant metastasis rate was higher for those with PSA levelsate was higher for those with PSA levels >10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p=0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p=0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. Conclusion: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives ?70 Gy to <25% should be used

229

Dose-response of acute urinary toxicity of long-course preoperative chemoradiotherapy for rectal cancer.  

Science.gov (United States)

Abstract Background. Long-course preoperative chemoradiotherapy (chemo-RT) improves outcomes for rectal cancer patients, but acute side effects during treatment may cause considerable patient discomfort and may compromise treatment compliance. We developed a dose-response model for acute urinary toxicity based on a large, single-institution series. Material and methods. In total 345 patients were treated with (chemo-)RT for primary rectal cancer from January 2007 to May 2012. Urinary toxicity during RT was scored prospectively using the CTCAE v 3.0 cystitis score (grade 0-5). Clinical variables and radiation dose to the bladder were related to graded toxicity using multivariate ordinal logistic regression. Three models were optimized, each containing all available clinical variables and one of three dose metrics: Mean dose (Dmean), equivalent uniform dose (EUD), or relative volume given x Gy or above (dose cut-off model, Vx). The optimal dose metric was chosen using the Akaike Information Criterion (AIC). Results. Grade 1 cystitis was experienced by 138 (40%), grade 2 by 39 (11%) and grade 3 by two (1%) patients, respectively. Dose metrics were significantly correlated with toxicity in all models, but the dose cut-off model provided the best AIC value. The only significant clinical risk factors in the Vx model were male gender (p = 0.006) and brachytherapy boost (p = 0.02). Reducing the model to include gender, brachytherapy boost and Vx yielded odds ratios ORmale = 1.82 (1.17-2.80), ORbrachy = 1.36 (1.02-1.80 for each 5 Gy), x = 35.1 Gy (28.6-41.5 Gy). The predicted risk of grade 2 and above cystitis ranged from 2% to 26%. Conclusion. Acute cystitis correlated significantly with radiation dose to the bladder; the dose-cut-off model (V35Gy) was superior to Dmean and EUD models. Male gender and brachytherapy boost increased the risk of toxicity. Wide variation in predicted risks suggests room for treatment optimization using individual dose constraints. PMID:24975373

Appelt, Ane L; Bentzen, Søren M; Jakobsen, Anders; Vogelius, Ivan R

2015-02-01

230

A mass action model of the dose-response curve of immunoradiometric assay and its curve fitting  

International Nuclear Information System (INIS)

In view of no satisfactory mathematical model is presently available for the dose-response curve of immunoradiometric assay, a three parameter model based on single binding site mass action law has been derived. A curve fitting method based on similar principle of linear robust regression was designed and a software was prepared for use on IBM personal computers. Experiments revealed that the model is applicable to a variety of IRMA systems as well as to time-resolved immunofluorometric assay of hAFP. When there was outlier(s) of the calibration curve, the average bias of unknown samples obtained with this method is significantly smaller than methods using four parameter logistic model or four parameter single site mass action model

231

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

International Nuclear Information System (INIS)

A dose-response relationship between ?-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)

232

Calculating the statistical significance of physical clusters of co-regulated genes in the genome: the role of chromatin in domain-wide gene regulation  

OpenAIRE

Physical clusters of co-regulated, but apparently functionally unrelated, genes are present in many genomes. Despite the important implication that the genomic environment contributes appreciably to the regulation of gene expression, no simple statistical method has been described to identify physical clusters of co-regulated genes. Here we report the development of a model that allows the direct calculation of the significance of such clusters. We have implemented the derived statistical rel...

Chang, Cheng-fu; Wai, Ka-man; Patterton, Hugh G.

2004-01-01

233

Determination and Clinical Verification of Dose-Response Parameters for Esophageal Stricture from Head and Neck Radiotherapy  

Energy Technology Data Exchange (ETDEWEB)

The purpose of this work is to determine the parameters and evaluate the predictive strength of the relative seriality model. This is accomplished by associating the calculated complication rates with the clinical follow-up records. The study is based on 82 patients who received radiation treatment for head and neck cancer. For each patient the 3D dose distribution delivered to the esophagus and the clinical treatment outcome were available. Clinical symptoms and radiological findings were used to assess the manifestation of radiation-induced esophageal strictures. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the relative seriality model (D{sub 50}=68.4 Gy, n=6.55, s=0.22). The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was demonstrated. The best estimate of the parameters was applied to 58 patients of the study material and their esophageal stricture induction probabilities were calculated to illustrate the clinical utilization of the calculated parameters. The calculation of the biological effective dose (BED) appeared to be significantly sensitive to the applied fractionation correction for complex treatment plans. The relative seriality model was proved suitable in reproducing the treatment outcome pattern of the patient material studied (probability of finding a worse fit=61.0%, the area under the ROC curve=0.84 and chi-square test=0.95). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed. Radiation-induced strictures were found to have a strong volume dependence (low relative seriality). The uncertainties of the parameters appear to have a significant supporting role on the estimated dose-response curve.

Mavroidis, Panayiotis [Univ. of Thessaly, Larisa (Greece). Larisa Univ. Hospital; Laurell, Goeran; Kraepelien, Thomas; Fernberg, Jan-Olof; Lind, Bengt K.; Brahme, Anders [Karolinska Inst., Stockholm (Sweden). Dept. of Medical Radiation Physics, and Medical Physics

2003-12-01

234

Determination and Clinical Verification of Dose-Response Parameters for Esophageal Stricture from Head and Neck Radiotherapy  

International Nuclear Information System (INIS)

The purpose of this work is to determine the parameters and evaluate the predictive strength of the relative seriality model. This is accomplished by associating the calculated complication rates with the clinical follow-up records. The study is based on 82 patients who received radiation treatment for head and neck cancer. For each patient the 3D dose distribution delivered to the esophagus and the clinical treatment outcome were available. Clinical symptoms and radiological findings were used to assess the manifestation of radiation-induced esophageal strictures. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the relative seriality model (D50=68.4 Gy, n=6.55, s=0.22). The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was demonstrated. The best estimate of the parameters was applied to 58 patients of the study material and their esophageal stricture induction probabilities were calculated to illustrate the clinical utilization of the calculated parameters. The calculation of the biological effective dose (BED) appeared to be significantly sensitive to the applied fractionation correction for complex treatment plans. The relative seriality model was proved suitable in reproducing the treatment outcome pattern of the patient material studied (probability of finding a worse fit=61.0%, the area under the ROC curve=0.84 and 0%, the area under the ROC curve=0.84 and chi-square test=0.95). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed. Radiation-induced strictures were found to have a strong volume dependence (low relative seriality). The uncertainties of the parameters appear to have a significant supporting role on the estimated dose-response curve

235

Extent of exposure to environmental tobacco smoke (ETS and its dose-response relation to respiratory health among adults  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background There is a dearth of standardized studies examining exposure to environmental tobacco smoke (ETS and its relationship to respiratory health among adults in developing countries. Methods In 2004, the Syrian Center for Tobacco Studies (SCTS conducted a population-based survey using stratified cluster sampling to look at issues related to environmental health of adults aged 18–65 years in Aleppo (2,500,000 inhabitants. Exposure to ETS was assessed from multiple self-reported indices combined into a composite score (maximum 22, while outcomes included both self-report (symptoms/diagnosis of asthma, bronchitis, and hay fever, and objective indices (spirometric assessment of FEV1 and FVC. Logistic and linear regression analyses were conducted to study the relation between ETS score and studied outcomes, whereby categorical (tertiles and continuous scores were used respectively, to evaluate the association between ETS exposure and respiratory health, and explore the dose-response relationship of the association. Results Of 2038 participants, 1118 were current non-smokers with breath CO levels ? 10 ppm (27.1% men, mean age 34.7 years and were included in the current analysis. The vast majority of study participants were exposed to ETS, whereby only 3.6% had ETS score levels ? 2. In general, there was a significant dose-response pattern in the relationship of ETS score with symptoms of asthma, hay fever, and bronchitis, but not with diagnoses of these outcomes. The magnitude of the effect was in the range of twofold increases in the frequency of symptoms reported in the high exposure group compared to the low exposure group. Severity of specific respiratory problems, as indicated by frequency of symptoms and health care utilization for respiratory problems, was not associated with ETS exposure. Exposure to ETS was associated with impaired lung function, indicative of airflow limitation, among women only. Conclusions This study provides evidence for the alarming extent of exposure to ETS among adult non-smokers in Syria, and its dose-response relationship with respiratory symptoms of infectious and non-infectious nature. It calls for concerted efforts to increase awareness of this public health problem and to enforce regulations aimed at protecting non-smokers.

Ward Kenneth D

2005-02-01

236

Model-free approach to estimation of relative potency in dose-response curve analysis  

Energy Technology Data Exchange (ETDEWEB)

The authors have developed a new, general approach to analysis of dose-response curves from bioassay, immunoassay (including radioimmunoassay, immunnoradiouretic assay, enzyme-linked immunosorbent assay), and other experimental procedures. It provides a test for parallelism, a similarity of shape, and a measure of relative potency for any set of two or more curves. The methods uses a constrained smoothing spline function to estimate the curve shape, together with a nonlinear least-squares fitting technique to estimate parameters for relative potency and slope. The use of constrained splines permits the analysis of nonlinear dose-response curves that cannot be described by a simple model or equation such as the symmetric four-parameter logistic. A microcomputer program is used for the analysis, providing relative potencies and their SE and evaluation of goodness of fit.

Guardabasso, V.; Rodbard, D.; Munson, P.J.

1987-03-01

237

Model-free approach to estimation of relative potency in dose-response curve analysis  

International Nuclear Information System (INIS)

The authors have developed a new, general approach to analysis of dose-response curves from bioassay, immunoassay (including radioimmunoassay, immunnoradiouretic assay, enzyme-linked immunosorbent assay), and other experimental procedures. It provides a test for parallelism, a similarity of shape, and a measure of relative potency for any set of two or more curves. The methods uses a constrained smoothing spline function to estimate the curve shape, together with a nonlinear least-squares fitting technique to estimate parameters for relative potency and slope. The use of constrained splines permits the analysis of nonlinear dose-response curves that cannot be described by a simple model or equation such as the symmetric four-parameter logistic. A microcomputer program is used for the analysis, providing relative potencies and their SE and evaluation of goodness of fit

238

A model-free approach to estimation of relative potency in dose-response curve analysis.  

Science.gov (United States)

We have developed a new, general approach to analysis of dose-response curves from bioassay, immunoassay (including radioimmunoassay, immunoradiouretic assay, enzyme-linked immunosorbent assay), and other experimental procedures. It provides a test for parallelism, similarity of shape, and a measure of relative potency for any set of two or more curves. The method uses a constrained smoothing spline function to estimate the curve shape, together with a nonlinear least-squares fitting technique to estimate parameters for relative potency and slope. The use of "constrained splines" permits the analysis of nonlinear dose-response curves that cannot be described by a simple model or equation such as the symmetric four-parameter logistic. A microcomputer program is used for the analysis, providing relative potencies and their SE and evaluation of goodness of fit. PMID:3826362

Guardabasso, V; Rodbard, D; Munson, P J

1987-03-01

239

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

International Nuclear Information System (INIS)

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%

240

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

Energy Technology Data Exchange (ETDEWEB)

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%.

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

241

Dose-response effects of gamma-radiation on several growth functions of Campanularia flexuosa  

International Nuclear Information System (INIS)

The present study is concerned with the dose-response effects of ionizing radiation, specifically gamma radiation, on several growth functions in the colonial hydroid Campanularia flexuosa. The growth functions monitored post-irradiation for this study include the following: (1) addition of new stolon material; (2) addition of hydranth positions to starters; (3) addition of uprights to stolons; (4) addition of hydranths to stolons post-irradiation; and (5) life-span of hydranths. Observations of certain qualitative phenomena associated with the gamma radiation are also presented. Finally, comparisons of the dose-response effects are noted, leading to some tentative conclusions concerning the nature of determination and differentiation underlying the morphogenetic events associated with these growth functions

242

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

Energy Technology Data Exchange (ETDEWEB)

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.

Jost, G; Pietsch, H [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Lengsfeld, P; Voth, M [Global Medical Affairs Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Schmid, E, E-mail: Ernst.Schmid@lrz.uni-muenchen.d [Institute for Cell Biology, Center for Integrated Protein Science, University of Munich (Germany)

2010-06-07

243

A randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European organization for research and treatment of cancer (EORTC) study 22844  

International Nuclear Information System (INIS)

Purpose: Cerebral low-grade gliomas (LGG) in adults are mostly composed of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article. Methods and Materials: For the dose-response trial, 379 adult patients with cerebral LGGs were randomized centrally at the EORTC Data Center to receive irradiation postoperatively (or postbiopsy) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality-controlled radiation therapy. All known parameters with possible influences on prognosis were prospectively recorded. Conventional treatment techniques were recommended. Results: With 343 (91%) eligible and evaluable patients followed up for at least 50 months with a median of 74 months, there is no significant difference in terms of survival (58% for the low-dose arm and 59% for the high-dose arm) or the progression free survival (47% and 50%) between the two arms of the trial. However, this prospective trial has revealed some important facets about the prognostic parameters: The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors (p < 0.0001) omportant prognostic factors (p < 0.0001) on multivariate analysis. Other prognostic factors, most of which are known, have now been quantified and confirmed in this prospective study. Conclusion: The EORTC trial 22844 has not revealed the presence of radiotherapeutic dose-response for patients with LGG for the two dose levels investigated with this conventional setup, but objective prognostic parameters are recognized. The tumor size or T parameter as used in this study appears to be a very important factor

244

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

OpenAIRE

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 tw...

Englund Erling; Malker Hans; Wiesinger Birgitta; Wänman Anders

2009-01-01

245

Differential dose responses of pulmonary tumor types in the rat after inhalation of plutonium dioxide aerosols.  

Science.gov (United States)

Dose responses were compared among primary lung tumors and their histological types induced by a single inhalation exposure of female Wistar strain rats to submicron-size and polydispersed aerosols of plutonium dioxide (239PuO2). While the primary lung tumors were found only in 2.3% of the unexposed control animals, the frequency of all the primary lung tumors in the exposed animals was 44% at the mean lung dose of 0.71 Gy, and increased sharply at the doses of 1.5 Gy or more, reaching the maximum of 97% at 5.4 Gy, and the dose responses around at 1.0 Gy were different between benign and malignant lung tumors. Almost all the pulmonary tumors in the exposed animals were classified into epithelial types such as adenomas, adenocarcinomas, adenosquamous carcinomas, and squamous cell carcinomas. The dose responses were different between these tumor types as shown by the peak incidence of adenomas at 0.71 Gy, adenocarcinomas at 2.9 Gy, adenosquamous and squamous cell carcinomas at 5.4-8.5 Gy, respectively. As the magnitudes of neoplastic lesions in pulmonary carcinomas were expressed by histological scores, metaplasias and adenomatous lesions most frequently appeared at doses of 1.5 Gy, while the appearance and increase of carcinomatous lesions differed in the dose ranges as shown by the peak incidence of adenocarcinomatous lesions at 2.9 Gy, and adenosquamous or squamous lesions at 5.4-6.6 Gy. These results indicate a differential dose response of pulmonary carcinogenesis in which metaplasias and benign adenomas were induced at lower doses ( 1.5 Gy). Together with the increase of carcinomatous lesions at higher doses, the intranuclear p53 protein accumulation was detectable, but only in a few percentages of malignant carcinomas. PMID:9610033

Oghiso, Y; Yamada, Y; Iida, H; Inaba, J

1998-03-01

246

Radiation-induced heart disease: review of experimental data on dose response and pathogenesis  

International Nuclear Information System (INIS)

Clinical and experimental heart irradiation can cause a variety of sequelae. A single dose of ? 15 Gy leads to a reversible exudative pericarditis, occurring in dogs, rabbits or rats at around 100 days. Its time-course is very similar in all species investigated, but there are considerable species and strain differences in severity and incidence. After longer, dose-dependent latency times chronic congestive myocardial failure develops. The paper reviews experimental data concerning dose response and pathogenesis. (author)

247

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

OpenAIRE

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...

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

2009-01-01

248

An EM Algorithm for Fitting a 4-Parameter Logistic Model to Binary Dose-Response Data  

OpenAIRE

This article is motivated by the need of biological and environmental scientists to fit a popular nonlinear model to binary dose-response data. The 4-parameter logistic model, also known as the Hill model, generalizes the usual logistic regression model to allow the lower and upper response asymptotes to be greater than zero and less than one, respectively. This article develops an EM algorithm, which is naturally suited for maximum likelihood estimation under the Hill model after conceptuali...

Dinse, Gregg E.

2011-01-01

249

Dose-response analysis in risk assessment: evaluation of behavioral specificity.  

OpenAIRE

Several methods of quantitative risk assessment that have been described recently are particularly applicable to neurotoxic end points. These methods can be broadly divided into two types of approaches based on their treatment of dose-response data to estimate risks. Benchmark approaches estimate risks using variability in response to a fixed dose level in comparison with background control variability. Probabilistic approaches estimate risks using the variability in the dose to produce a sma...

Glowa, J. R.

1996-01-01

250

A Dose-Response Relationship between Types of Physical Activity and Distress  

OpenAIRE

This study aimed to examine whether a dose-response relationship exists between psychological distress and types of physical activity (total, occupational, and leisure-time). The study subjects (233 men and 313 women) were recruited for a study on cardiovascular disease in the Yangpyeong community located in South Korea. The type and characteristics of physical activity were measured with a modified version of the Stanford 5 city project's questionnaire by well-trained interviewers using a st...

Kim, Kirang; Shin, Young Jeon; Nam, Joung Hyun; Choi, Bo Youl; Kim, Mi Kyung

2008-01-01

251

Improved dose response modeling for normal tissue damage and therapy optimization  

OpenAIRE

The present thesis is focused on the development and application of dose response models for radiation therapy. Radiobiological models of tissue response to radiation are an integral part of the radiotherapeutic process and a powerful tool to optimize tumor control and minimize damage to healthy tissues for use in clinical trials. Ideally, the models could work as a historical control arm of a clinical trial eliminating the need to randomize patents to suboptimal therapies. In the thesis over...

Adamus-go?rka, Magdalena

2008-01-01

252

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

International Nuclear Information System (INIS)

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

253

Statistical significance of hierarchical multi-body potentials based on Delaunay tessellation and their application in sequence-structure alignment.  

OpenAIRE

Statistical potentials based on pairwise interactions between C alpha atoms are commonly used in protein threading/fold-recognition attempts. Inclusion of higher order interaction is a possible means of improving the specificity of these potentials. Delaunay tessellation of the C alpha-atom representation of protein structure has been suggested as a means of defining multi-body interactions. A large number of parameters are required to define all four-body interactions of 20 amino acid types ...

Munson, P. J.; Singh, R. K.

1997-01-01

254

Statistics  

International Nuclear Information System (INIS)

For the year 1998 and the year 1999, 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-June 1999, Energy exports by recipient country in January-June 1999, 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 tprices of some energy sources and Energy taxes and precautionary stock fees on oil products

255

Dose-response effect of fish oil substitution in parturition feed on erythrocyte membrane characteristics and sow performance.  

Science.gov (United States)

The present study aimed to investigate whether n-3 polyunsaturated fatty acids (PUFA) incorporate into erythrocyte membranes of peripartal sows in a dose-responsive manner and whether the altered fatty acid profile affects the cell membrane characteristics. At day 109 of gestation (day 0), 51 sows were divided into five treatment groups. Each group received a diet with a different ratio of fish oil to pork lard for nine consecutive days. Blood samples were taken at day 0 and 10 days later. The fatty acid profile of erythrocytes was determined, as well as the osmotic fragility and oxidative stability of erythrocytes. Thiobarbituric acid reactive substances (TBARS) and ferric reducing ability of plasma (FRAP) were determined in plasma samples. Finally, reproductive and performance parameters of both sows and piglets were recorded until weaning. Supplementation of fish oil during the peripartal period changed the fatty acid profile of erythrocyte membranes in a dose-responsive manner. Although the n-3 PUFA content of erythrocyte membranes increased with increasing amounts of fish oil in the diet, no significant effect on erythrocyte osmotic fragility could be recorded. In contrast, oxidative stability of erythrocytes decreased linearly with increasing amounts of fish oil in the diet. Similarly, both TBARS and FRAP linearly increased with increasing percentages of fish oil in the diet. Neither piglet nor sow performance was influenced by dietary treatments, except for a decrease of both piglet survival and weaning weight with increasing quantities of fish oil supplemented. It is concluded that changes in dietary lipid sources can affect the membrane's fatty acid profile within days, and mainly influences oxidative stability of the cells. PMID:21175879

Cools, A; Maes, D; Papadopoulos, G; Vandermeiren, J-A; Meyer, E; Demeyere, K; De Smet, S; Janssens, G P J

2011-02-01

256

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

International Nuclear Information System (INIS)

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

257

The shape of the cancer mortality dose-response curve for atomic bomb survivors  

International Nuclear Information System (INIS)

The shape of the cancer mortality dose-response in the atomic bomb survivor data is analyzed in the context of linear-quadratic (LQ) models. Results are given for all cancers except leukemia as a group, for leukemia, and for combined inferences assuming common curvature. Since there is substantial information aside from these data suggesting a dose-response concave from above, the emphasis here is not on estimating the best-fitting dose-response curve, but rather on assessing the maximal extent of curvature under LQ models which is consistent with the data. Such inferences are substantially affected by imprecision in the dose estimates, and methods are applied which make explicit allowances for biases due to this. The primary means used here to express the extent of curvature is the factor by which linear risk estimates should be divided to arrive at appropriate low-dose risk estimates. In the past, influential committees have recommended ranges of 2-10 and of 1.5-3 for such a factor. Results here suggest that values greater than about 2 are at least moderately inconsistent with these data, within the context of LQ models. It is emphasized, however, that there is little direct information in these data regarding low-dose risks; the inferences here depend strongly on the link between low-dose and high-dose risks provided by the assumption of an LQ model. (author)

258

Benzene adducts with rat nucleic acids and proteins: dose-response relationship after treatment in vivo.  

Science.gov (United States)

The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 x 10(7) starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was initially performed with tritium-labeled benzene, administered by IP injection. In order to exclude the possibility that part of the detected radioactivity was due to tritium incorporated into DNA from metabolic processes, 14C-benzene was then also used following a similar experimental design. By HPLC analysis, a single adduct from benzene-treated DNA was detected; adduct identification will be attempted in the near future. Linear dose-response relationship was observed within most of the range of explored doses. Linearity was particularly evident within low and very low dosages. Saturation of benzene metabolism did occur at the highest dosages for most of the assayed macromolecules and organs, especially in rat liver. This finding could be considered as indicative of the dose-response relationship of tumor induction and could be used in risk assessment. PMID:2477240

Mazzullo, M; Bartoli, S; Bonora, B; Colacci, A; Grilli, S; Lattanzi, G; Niero, A; Turina, M P; Parodi, S

1989-07-01

259

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

International Nuclear Information System (INIS)

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)

260

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1983-10-01

261

Effects of glycerol co-solvent on the rate and form of polymer gel dose response  

Energy Technology Data Exchange (ETDEWEB)

A factor currently limiting the clinical utility of x-ray CT polymer gel dosimetry is the overall low dose sensitivity (and hence low dose resolution) of the system. Hence, active research remains in the investigation of polymer gel formulations with increased CT dose response. An ideal polymer gel dosimeter will exhibit a sensitive CT response which is linear over a suitable dose range, making clinical implementation reasonably straightforward. This study reports on the variations in rate and form of the CT dose response of irradiated polymer gels manufactured with glycerol, which is a co-solvent that permits dissolution of additional bisacrylamide above its water solubility limit (3% by weight). This study focuses on situations where the concentration of bisacrylamide is kept at or below its water solubility limit so that the influence of the co-solvent on the dose response can be explored separately from the effects of increased cross-linker concentration. CT imaging and Raman spectroscopy are used to construct dose-response curves for irradiated gels varying in (i) initial total monomer (%T) and (ii) initial co-solvent concentration. Results indicate that: (i) for a fixed glycerol concentration, gel response increases linearly with %T. Furthermore, the functional form of the dose response remains constant, in agreement with a previous model of polymer formation. (ii) Polymer gels with constant %T and increasing co-solvent concentrations also show enhanced CT response. In addition, the functional form of the response is altered in these gels as co-solvent concentration is increased. Raman data indicate that the fraction of bis-acrylamide incorporated into polymerization, as opposed to cyclization, increases as co-solvent concentration increases. The changes in functional form indicate varying polymer yields (per unit dose), akin to relative fractional monomer/cross-linker (i.e. %C) changes in earlier studies. These results are put into context of the model of polymer formation. The implications of these results on the clinical utility of polymer gels with co-solvent are highlighted.

Jirasek, A; Berman, A [Department of Physics and Astronomy, University of Victoria, Victoria BC V8W 3P6 (Canada); Hilts, M [Medical Physics, BC Cancer Agency-Vancouver Island Centre, Victoria BC V6R 2B6 (Canada); McAuley, K B [Department of Chemical Engineering, Queens University, Kingston, ON K7 L 3N6 (Canada)], E-mail: jirasek@uvic.ca

2009-02-21

262

Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays.  

Science.gov (United States)

The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of ?2, 4, 6, 8, 10, 16 and 20 Gy of acute (60)?? gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the underdispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ?6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.098-0.129×cell(-1)×Gy(-1) and 0.039-0.034×cell(-1)×Gy(-2), respectively, depending on the fitting method. The actual radiation-induced aberration yield was markedly lower than expected from a calibration curve, generated earlier within a lower dose range. Interlaboratory variations in reported dicentric yields induced by medium-to-high radiation doses in vitro are discussed. PMID:22923248

Vinnikov, Volodymyr A; Maznyk, Nataliya A

2013-04-01

263

Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays  

International Nuclear Information System (INIS)

The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of 2, 4, 6, 8, 10, 16 and 20 Gy of acute 60Co gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the under dispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ?6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.098-0.129xcell-1xGy-1 and 0.039-0.034xcell-1xGy-2, respectively, depending on the fitting method. The actual radiation-induced aberration yield was markedly lower than expected from a calibration curve, generated earlier within a lower dose range. Interlaboratory variations in reported dicentric yields induced by medium-to-high radiation doses in vitro are discussed. (authors)

264

Hydrothermal synthesis of ZnO nanorods: a statistical determination of the significant parameters in view of reducing the diameter.  

Science.gov (United States)

In this paper a 2(8-4) fractional factorial design of experiments is applied to identify the important parameters that affect the average diameter of ZnO rods, synthesized by means of a hydrothermal procedure. A water-based Zn(2+) precursor is used for the formation of one-dimensional ZnO particles, without the presence of an organic additive. Results indicate that, at the investigated levels, four of the parameters have a significant effect on the mean diameter. These are the temperature, the heating rate, stirring and an ultrasonic pre-treatment of the precursor solution. Experiments carried out with zinc acetate and zinc chloride do not show a significant difference in rod diameter. Other parameters that do not show a significant effect are the concentration of Zn(2+), the molar ratio between the hydroxyl and the zinc ions, and the reaction time. Interactions are observed between stirring and an ultrasonic pre-treatment and between the zinc concentration and the OH:Zn ratio. By fixing the significant factors at their optimal value it is possible to decrease the mean diameter. The particles are characterized by means of x-ray diffraction (XRD) and transmission electron microscopy (TEM). PMID:19417355

Elen, Ken; Van den Rul, Heidi; Hardy, An; Van Bael, Marlies K; D'Haen, Jan; Peeters, Roos; Franco, Dirk; Mullens, Jules

2009-02-01

265

Hydrothermal synthesis of ZnO nanorods: a statistical determination of the significant parameters in view of reducing the diameter  

International Nuclear Information System (INIS)

In this paper a 28-4 fractional factorial design of experiments is applied to identify the important parameters that affect the average diameter of ZnO rods, synthesized by means of a hydrothermal procedure. A water-based Zn2+ precursor is used for the formation of one-dimensional ZnO particles, without the presence of an organic additive. Results indicate that, at the investigated levels, four of the parameters have a significant effect on the mean diameter. These are the temperature, the heating rate, stirring and an ultrasonic pre-treatment of the precursor solution. Experiments carried out with zinc acetate and zinc chloride do not show a significant difference in rod diameter. Other parameters that do not show a significant effect are the concentration of Zn2+, the molar ratio between the hydroxyl and the zinc ions, and the reaction time. Interactions are observed between stirring and an ultrasonic pre-treatment and between the zinc concentration and the OH:Zn ratio. By fixing the significant factors at their optimal value it is possible to decrease the mean diameter. The particles are characterized by means of x-ray diffraction (XRD) and transmission electron microscopy (TEM).

266

Effects of crosslinking and temperature on the dose response of a BANG polymer gel dosimeter  

International Nuclear Information System (INIS)

The effects of varying the weight fraction (%C) of the crosslinker N,N'-methylene-bisacrylamide (bis) per total amount of monomer (6% w/w), and the NMR measurement temperature, on the dose response of the transverse relaxation rate (R2) of bis-acrylamide-nitrogen-gelatin (BANG) aqueous polymer gel dosimeters have been investigated. The gel samples were irradiated in test tubes with 250 kV x-rays, and the water proton NMR transverse relaxation rates were measured at 0.47 T using a arr-Purcell-Meiboom-Gill multiecho pulse sequence. Both the dose sensitivity slope of the linear portion of an R2-dose response) and the maximum rate at which the R2-dose response saturated (R2max), were found to depend strongly on the crosslinker fraction and on the temperature of the R2 measurement. The dose sensitivity peaked at approximately 50% C, and, for this composition, varied from 0.14 s-1 Gy-1 at 40 deg. C to 0.48 s-1 y-1 at 10 deg. C. The maximum transverse relaxation rates ranged from 0.8 -1 at 33% C and 40 deg. C to 11.8 s-1 at 83% C and 5 deg. C. These results suggest that water proton transverse relaxation in the gel is controlled by an exchange of magnetization between the aqueous phase and the semi-solid protons associated with the polymer, and that the latter experience spectral broadening from immobilization which increases with crosslinking ozation which increases with crosslinking or cooling. Theoretical and practical implications of the above findings are discussed in the paper. (author)

267

Dose-response efficacy and long-term effect of the hypocholesterolemic effect of octadecylpectinamide in rats.  

Science.gov (United States)

The dose-response efficiency and long-term effect of the hypocholesterolemic effect of octadecylpectinamide was examined in female rats fed diets containing cholesterol at 10 g/kg. In our first experiment, amidated pectin supplied at 20 g/kg, 40 g/kg and 60 g/kg significantly decreased serum cholesterol from 3.32 ?mol/ml (control) to 1.23 ?mol/ml in a dose-dependent manner. In a second experiment, the hypocholesterolemic effect of amidated pectin supplied at 20 g/kg persisted after 3 months of feeding. In both experiments, the amidated pectin significantly decreased the concentrations of cholesterol in hepatic tissue and triacylglycerols in serum. The serum concentration of aspartate aminotransferase significantly increased in rats fed amidated pectin at 60 g/kg for 4 weeks, and at 20 g/kg for 3 months. In conclusion, amidated pectin at a low dose and used for a period shorter than 3 months might be considered as an effective hypocholesterolemic and lipid-lowering agent that may substitute typical antilipidemic drugs. PMID:23911514

Marounek, Milan; Volek, Zden?k; Dušková, Dagmar; T?ma, Jan; Taubner, Tomáš

2013-09-12

268

The size distribution of innovations revisited: an application of extreme value statistics to citation and value measures of patent significance  

OpenAIRE

This paper focuses on the analysis of size distributions of innovations, which are known to be highly skewed. We use patent citations as one indicator of innovation significance, constructing two large datasets from the European and US Patent Offices at a high level of aggregation, and the Trajtenberg (1990) dataset on CT scanners at a very low one. We also study self-assessed reports of patented innovation values using two very recent patent valuation datasets from the Netherlands and the UK...

Silverberg, Gerald; Verspagen, Bart

2004-01-01

269

One slope or two? Detecting statistically significant breaks of slope in geophysical data, with application to fracture scaling relationships  

OpenAIRE

The scaling of displacement as a function of length is important for a variety of applications which depend on the mechanical and hydraulic properties of faults and fractures. Recently it has been suggested that the power-law exponent nu which has been found to characterise this relationship may change significantly at a characteristic length for a variety of reasons, for example when cracks begin to interact, or when faults grow to a length comparable to a characteristic size in the brittle ...

Main, I. G.; Leonard, T.; Papasouliotis, O.; Hatton, C. G.; Meredith, P. G.

1999-01-01

270

Analytic estimation of statistical significance maps for support vector machine based multi-variate image analysis and classification  

OpenAIRE

Multivariate pattern analysis (MVPA) methods such as support vector machines (SVMs) have been increasingly applied to fMRI and sMRI analyses, enabling the detection of distinctive imaging patterns. However, identifying brain regions that significantly contribute to the classification/group separation requires computationally expensive permutation testing. In this paper we show that the results of SVM-permutation testing can be analytically approximated. This approximation leads to more than a...

Gaonkar, Bilwaj; Davatzikos, Christos

2013-01-01

271

Modeling and regression analysis of semiochemical dose-response curves of insect antennal reception and behavior.  

Science.gov (United States)

Dose-response curves of the effects of semiochemicals on neurophysiology and behavior are reported in many articles in insect chemical ecology. Most curves are shown in figures representing points connected by straight lines, in which the x-axis has order of magnitude increases in dosage vs. responses on the y-axis. The lack of regression curves indicates that the nature of the dose-response relationship is not well understood. Thus, a computer model was developed to simulate a flux of various numbers of pheromone molecules (10(3) to 5 × 10(6)) passing by 10(4) receptors distributed among 10(6) positions along an insect antenna. Each receptor was depolarized by at least one strike by a molecule, and subsequent strikes had no additional effect. The simulations showed that with an increase in pheromone release rate, the antennal response would increase in a convex fashion and not in a logarithmic relation as suggested previously. Non-linear regression showed that a family of kinetic formation functions fit the simulated data nearly perfectly (R(2) >0.999). This is reasonable because olfactory receptors have proteins that bind to the pheromone molecule and are expected to exhibit enzyme kinetics. Over 90 dose-response relationships reported in the literature of electroantennographic and behavioral bioassays in the laboratory and field were analyzed by the logarithmic and kinetic formation functions. This analysis showed that in 95% of the cases, the kinetic functions explained the relationships better than the logarithmic (mean of about 20% better). The kinetic curves become sigmoid when graphed on a log scale on the x-axis. Dose-catch relationships in the field are similar to dose-EAR (effective attraction radius, in which a spherical radius indicates the trapping effect of a lure) and the circular EARc in two dimensions used in mass trapping models. The use of kinetic formation functions for dose-response curves of attractants, and kinetic decay curves for inhibitors, will allow more accurate predictions of insect catch in monitoring and control programs. PMID:23897111

Byers, John A

2013-08-01

272

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

OpenAIRE

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...

Burns, Fredric J.; Uddin, Ahmed N.; Wu, Feng; Na?das, Arthur; Rossman, Toby G.

2004-01-01

273

Dose–response relationship of ultrasound contrast agent in an in vivo murine melanoma model  

OpenAIRE

Many factors affect the sensitivity and reliability of tumor vasculature assessment at the small doses of contrast agent necessary for imaging mice. In this study we investigate the dose–response relationship of ultrasound contrast agent for a minimal exposure power Doppler technique (minexPD) in a murine melanoma model. K1735 murine melanomas grown in 25 C3H/HeN mice were imaged by power Doppler ultrasound using different doses of contrast agents, Optison® and Definity®. Six mice were tr...

Seiler, Gabriela S.; Ziemer, Lisa S.; Schultz, Susan; Lee, William M. F.; Sehgal, Chandra M.

2007-01-01

274

Acute dose-response studies in bronchial asthma with a new corticosteroid, budesonide.  

OpenAIRE

1 Budesonide is an epimeric mixture of a new synthetic non-halogenated glucocorticoid (16 alpha, 17 alpha,-(22R,S)-prophylmethylenedioxypregna-1,4-diene-11/3,21-diol-3, 20-dione). 2 Acute dose response studies with three different inhaled doses of budesonide, have been carried out in a group of 12 chronic asthmatic patients. 3 The lowest dose (100 micrograms) of inhaled budesonide produced a more marked effect in relieving airflow obstruction, than a much larger (1600 micrograms) oral dose of...

Ellul-micallef, R.; Johansson, S. A.

1983-01-01

275

Investigation of the NMR relaxation rate dose-response of a ceric sulphate dosimeter  

International Nuclear Information System (INIS)

The relationship between the radiation absorbed dose and the NMR longitudinal and transversal relaxation rates, R1 and R2, respectively, of a ceric sulphate dosimeter was examined. By adding copper sulphate, the R1 and R2 dose-responses were found to be linear up to 60 kGy with dose sensitivities of 13x10-6 and 15x10-6 s-1 Gy-1, respectively. There is thus the potential for a three-dimensional ceric dosimeter for high dose applications, provided a suitable gelling substance is used

276

Linear dose response of gene conversion in Saccharomyces cerevisiae after ionizing radiation  

International Nuclear Information System (INIS)

A series of populations of the D7 strain D7.52a of Saccharomyces cerevisiae was irradiated with 150-kVp x rays while bubbling with either O2 or N2. Linear dose responses were observed for all the populations. In O2, the effects were proportional to dose from 0.01 to 10 Gy. Effects in nitrogen were proportional to dose over the range 0.125 to 50 Gy. The OER for gene conversion in these experiments was 2.5. At the dose rates used (1.03 to 0.034 Gy/min) there was no evidence of a dose-rate effect

277

Benzene adducts with rat nucleic acids and proteins: dose-response relationship after treatment in vivo.  

OpenAIRE

The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 x 10(7) starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was initially performed with tritium-labeled benzene, administered by IP injection. In order to exclude the possibility that part of the detected radioactivity was due to tritium inco...

Mazzullo, M.; Bartoli, S.; Bonora, B.; Colacci, A.; Grilli, S.; Lattanzi, G.; Niero, A.; Turina, M. P.; Parodi, S.

1989-01-01

278

Asystasia intrusa : Penyebaran Biji Dan Dose Response Terhadap Parakuat, Glifosat, Dan Campuran Glifosat + 2,4 - D  

OpenAIRE

Pot experiment was placed outdoors at experimental field of Agriculture Faculty, North Sumatera University with a high place ± 25 m above the sea level, from May until July 2009. The objective of the study is to determined dose response Asystasia intrusa to paraquat, glyphosate, and mixture of glyphosate and 2,4 - D and distance of seeds break from parent. The first experiment is to decide dose response Asystasia intrusa to paraquat, glyphosate, and mixture of glyphosate and 2,4 - D and ...

Sitohang, Romali K. D.

2011-01-01

279

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

OpenAIRE

Most arsenic cancer risk assessments have been based solely on epidemiological studies to characterize the dose-response relationship for arsenic-associated cancer and to perform risk calculations. However, current epidemiological evidence is too inconsistent and fraught with uncertainty regarding arsenic exposure to provide reliable estimates. This makes it hard to draw a firm conclusion about the shape and slope of the dose-response relationship from individual studies. Meta-analysis is a s...

Douglas Crawford-Brown; Huei-An Chu

2007-01-01

280

Analytic estimation of statistical significance maps for support vector machine based multi-variate image analysis and classification.  

Science.gov (United States)

Multivariate pattern analysis (MVPA) methods such as support vector machines (SVMs) have been increasingly applied to fMRI and sMRI analyses, enabling the detection of distinctive imaging patterns. However, identifying brain regions that significantly contribute to the classification/group separation requires computationally expensive permutation testing. In this paper we show that the results of SVM-permutation testing can be analytically approximated. This approximation leads to more than a thousandfold speedup of the permutation testing procedure, thereby rendering it feasible to perform such tests on standard computers. The speedup achieved makes SVM based group difference analysis competitive with standard univariate group difference analysis methods. PMID:23583748

Gaonkar, Bilwaj; Davatzikos, Christos

2013-09-01

281

Development of dose response to Y-90 microsphere treatment of metastatic liver cancer by quantitative analysis of SPECT and PET images  

Science.gov (United States)

Y-90 microsphere radiotherapy is an option for treating inoperable metastatic liver tumors. This takes advantage of the differing vascular supply of the tumor and normal liver. The radiation dosimetry can be complex due to the non-uniform distribution of the particles. Because of this difficulty, the recorded treatment absorbed dose is often calculated assuming a uniform distribution throughout the entire liver segment. This work represents a retrospective analysis of twelve consecutive patients treated with Y-90 microspheres for colorectal liver metastasis. Absorbed dose to tumor and normal liver tissue was calculated by two methods for comparison. Both were partition methods, one using an average tumor to normal liver vascularity ratio and the other a patient specific vascularity ratio derived from SPECT scans performed pre-treatment. Tumor response was quantitatively evaluated from pre and post treatment PET scans. Site-specific thresholding ROI volumes were used to determine tumor SUV in the image analysis. PET analysis showed a significant response as a whole with an average of 52% +/- 22% decrease in total tumor burden. The range of decrease, representing tumor response in size and metabolism was 17-91%. Dose versus response curves were generated based on the above calculations. The results and statistical analysis indicate that there is a significant difference in the tumor absorbed dose value when calculated by the traditional partition method using an average tumor to normal liver ratio as compared to use of a patient specific tumor to normal liver ratio derived from SPECT images. The paired t-test result demonstrated a significant difference with the t value of 3.06 corresponding to a P of 0.009. A linear regression analysis of each dose response curve allowed a comparison of each dose calculation method as well. There was an increase in the r value for the absorbed dose calculated by the patient specific method in all response parameters. The best fits to the data were achieved using the patient specific method, thus demonstrating that this method better predicts therapeutic outcome than currently practiced methods.

Campbell, Janice M.

282

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

International Nuclear Information System (INIS)

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

283

Low dose radiation and cancer in A-bomb survivors: latency and non-linear dose-response in the 1950–90 mortality cohort  

OpenAIRE

Abstract Background Analyses of Japanese A-bomb survivors' cancer mortality risks are used to establish recommended annual dose limits, currently set at 1 mSv (public) and 20 mSv (occupational). Do radiation doses below 20 mSv have significant impact on cancer mortality in Japanese A-bomb survivors, and is the dose-response linear? Methods I analyse stomach, liver, lung, colon, uterus, and all-solid cancer mortality in the 0 – 20 mSv colon dose subcohort of th...

Dropkin Greg

2007-01-01

284

Are low but statistically significant levels of genetic differentiation in marine fishes ‘biologically meaningful’? A case study of coastal Atlantic cod  

OpenAIRE

A key question in many genetic studies on marine organisms is how to interpret a low but statistically significant level of genetic differentiation. Do such observations reflect a real phenomenon, or are they caused by confounding factors such as unrepresentative sampling or selective forces acting on the marker loci? Further, are low levels of differentiation biologically trivial, or can they represent a meaningful and perhaps important finding? We explored these issues in an empirical study...

Knutsen, Halvor; Olsen, Esben Moland; Jorde, Per Erik; Espeland, Sigurd Heiberg; Andre?, Carl

2010-01-01

285

Statistical evaluation of the significance of the influence of abrupt changes in solar activity on the dynamics of the epidemic process  

Science.gov (United States)

Statistical evaluations of the significance of the relationship of abrupt changes in solar activity and discontinuities in the multi-year pattern of an epidemic process are reported. They reliably (with probability of more than 99.9%) show the real nature of this relationship and its great specific weight (about half) in the formation of discontinuities in the multi-year pattern of the processes in question.

Druzhinin, I. P.; Khamyanova, N. V.; Yagodinskiy, V. N.

1974-01-01

286

Dose-response stability and integrity of the dose distribution of various polymer gel dosimeters  

International Nuclear Information System (INIS)

In this study the stability of different polymer gel dosimeters is investigated. Further to a previous chemical stability study on a (6%T, 50%C) PAG gel, the change in slope and intercept of the linear part of the R2-dose plot is recorded with time for different gel formulations. In addition to this R2-dose-response stability study, the dose edge of a half-blocked field was recorded with time. Three different PAG type polymer gels, a hydroxyethyl acrylate (HEA) gel and two different normoxic polymer gels were investigated. In the PAG type polymer gels, the relative concentration of gelatin and comonomers was varied in order to study the influence of the different components, that constitute the dosimeter, on the stability. It is shown that the R2-dose-response stability is largely determined by the chemical composition of the gel dosimeters. All the PAG gel dosimeters and the normoxic gel dosimeters are found to preserve the integrity of the dose distribution up to 22 days after irradiation. The half-life of the change in dose sensitivity of a MAGIC gel is found to be 18 h compared to 5.7 h for a (6%T, 50%C) PAG gel. A maximum relative decrease in dose sensitivity of 21% was noted for the MAGIC gel compared to an increase of 50% for a (6%T, 50%C) PAG gel. A loss of integrity of the dose distribution was found in the HEA gel. (author)

287

Dose-response relationship for lung cancer induction at radiotherapy dose  

International Nuclear Information System (INIS)

Cancer induction after radiation therapy is a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the treated patient. Currently there is large uncertainty about the shape of the dose-response relationship for carcinogenesis for most cancer types at high dose levels. In this work a dose-response relationship for lung cancer is derived based on (i) the analysis of lung cancer induction after Hodgkin's disease, (ii) a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii) the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy. The fitted model parameters for an ?/? = 3 Gy were ? = 0.061Gy-1 and R = 0.84. The value for ? 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.)

288

Neutron dose response of tradescantia stamen hair pink mutations and RBE  

International Nuclear Information System (INIS)

Dose response for one of biological end-points (gene mutation) in somatic cells of tradescantia 4430 clones were studied using neutrons coming out of a californium-252 isotopic source. And the Relative Biological Effectiveness (RBE) of neutrons in relation to X-ray in the induction of TSH pink mutations was assessed. Inflorescences were irradiated with X-ray from X-ray generator and neutrons from 252Cf source. Irradiated cuttings were incubated with aeration in nutrient solution under the controlled condition. For more than 4 weeks after irradiation cell mutations were scored. Pink mutation frequencies were calculated from the pooled data for the peak interval (days 6 to 13 post-irradiation). Somatic cell mutations in TSH showed linear dose response relationships in the range of neutron doses available for the experiment. The RBE values estimated for neutrons in relation to X-rays were in the range 3.1 to 6.8, which were much lower than normally recognized value

289

Dose response evaluation of a low-density normoxic polymer gel dosimeter using MRI  

Energy Technology Data Exchange (ETDEWEB)

A low-density ({approx}0.6 g cm{sup -3}) normoxic polymer gel, containing the antioxidant tetrakis (hydroxymethyl) phosponium (THP), has been investigated with respect to basic absorbed dose response characteristics. The low density was obtained by mixing the gel with expanded polystyrene spheres. The depth dose data for 6 and 18 MV photons were compared with Monte Carlo calculations. A large volume phantom was irradiated in order to study the 3D dose distribution from a 6 MV field. Evaluation of the gel was carried out using magnetic resonance imaging. An approximately linear response was obtained for 1/T2 versus dose in the dose range of 2 to 8 Gy. A small decrease in the dose response was observed for increasing concentrations of THP. A good agreement between measured and Monte Carlo calculated data was obained, both for test tubes and the larger 3D phantom. It was shown that a normoxic polymer gel with a reduced density could be obtained by adding expanded polystyrene spheres. In order to get reliable results, it is very important to have a uniform distribution of the gel and expanded polystyrene spheres in the phantom volume.

Haraldsson, P [Medical Radiation Physics, Department of Clinical Sciences, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Department of Radiation Physics, Finsen Centre, Copenhagen University Hospital, DK-2100 Copenhagen (Denmark); Karlsson, A [Medical Radiation Physics, Department of Clinical Sciences, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Wieslander, E [Medical Radiation Physics, Department of Clinical Sciences, Lund University Hospital, SE-221 85 Lund (Sweden); Gustavsson, H [Medical Radiation Physics, Department of Clinical Sciences, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Baeck, S A J [Medical Radiation Physics, Department of Clinical Sciences, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden)

2006-02-21

290

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

DEFF Research Database (Denmark)

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 pain relief than the control group (p <0.01). Participants who adhered "per protocol" decreased pain by 35 mm VAS (95% confidence interval: -26 to -44) from baseline to follow-up corresponding to a 70% reduction. In the dose-response analyses, participants with medium and high training adherence showed 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 1-2 training sessions per week for 20 weeks ( approximately 30 training sessions) seems sufficient for optimal pain relief.

Andersen, C. H.; Andersen, Lars L.

2013-01-01

291

Dose-response of diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] in the urothelial mucosa of Wistar rats.  

Science.gov (United States)

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a herbicide that induced urothelial tumors in the urinary bladder of Wistar rats fed 2500ppm during a long-term study. The currently suggested non-genotoxic mode of action (MOA) of diuron encompasses in succession urothelial necrosis induced by direct cytotoxicity, regenerative cell proliferation and sustained urothelial hyperplasia that increases the likelihood of neoplasia development. This study evaluated the dose-response profile of urothelial histological and ultrastructural lesions induced by diuron. Sixty male Wistar rats were fed ad libitum diuron mixed in the diet at 0, 60, 125, 500, 1250, or 2500ppm for 20 weeks. The incidences of urothelial simple hyperplasia and the cell proliferation index were significantly increased in the diuron-fed 1250 and 2500ppm groups. By scanning electron microscopy, the incidences and severity of lesions were significantly increased in the 500 and 1250ppm groups. The incidences of urothelial hyperplasia in the kidney pelvis were significantly increased in the 500, 1250 and 2500ppm groups. The present study documents the dose-response influence of diuron on the rat urothelium, with a no observed effect level (NOEL) at 125ppm; 1250ppm was as effective as 2500ppm at inducing urothelial lesions. PMID:23876856

Cardoso, Ana Paula Ferragut; Ihlaseh Catalano, Shadia Muhammad; da Rocha, Mitscheli Sanches; Nascimento E Pontes, Merielen Garcia; de Camargo, João Lauro Viana; de Oliveira, Maria Luiza Cotrim Sartor

2013-10-01

292

Dose–response of diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] in the urothelial mucosa of Wistar rats  

International Nuclear Information System (INIS)

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a herbicide that induced urothelial tumors in the urinary bladder of Wistar rats fed 2500 ppm during a long-term study. The currently suggested non-genotoxic mode of action (MOA) of diuron encompasses in succession urothelial necrosis induced by direct cytotoxicity, regenerative cell proliferation and sustained urothelial hyperplasia that increases the likelihood of neoplasia development. This study evaluated the dose–response profile of urothelial histological and ultrastructural lesions induced by diuron. Sixty male Wistar rats were fed ad libitum diuron mixed in the diet at 0, 60, 125, 500, 1250, or 2500 ppm for 20 weeks. The incidences of urothelial simple hyperplasia and the cell proliferation index were significantly increased in the diuron-fed 1250 and 2500 ppm groups. By scanning electron microscopy, the incidences and severity of lesions were significantly increased in the 500 and 1250 ppm groups. The incidences of urothelial hyperplasia in the kidney pelvis were significantly increased in the 500, 1250 and 2500 ppm groups. The present study documents the dose–response influence of diuron on the rat urothelium, with a no observed effect level (NOEL) at 125 ppm; 1250 ppm was as effective as 2500 ppm at inducing urothelial lesions

293

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

International Nuclear Information System (INIS)

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 the e-only configuration

294

Dose-response modeling of life shortening in a retrospective analysis of the combined data from the JANUS program at Argonne National Laboratory  

International Nuclear Information System (INIS)

Life shortening was investigated in both sexes of the B6CF1 (C57BL/6 x BALB/c) mouse exposed to fission neutrons and 60Co gamma rays. Three basic exposure patterns for both neutrons and gamma rays were compared: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. Ten different dose-response models were fitted to the data for animals exposed to neutrons. The response variable used for all dose-response modeling was mean after-survival. A simple linear model adequately described the response to neutrons for females and males at doses less than or equal to 80 cGy. At higher neutron dose levels a linear-quadratic equation was required to describe the life-shortening response. An effect of exposure pattern was observed prior to the detection of curvature in the dose response for neutrons and emerged as a potentially significant factor at neutron doses in the range of 40-60 cGy. Augmentation of neutron injury with dose protraction was observed in both sexes and began at doses as low as 60 cGy. The life-shortening response for all animals exposed to gamma rays (22-1918 cGy) was linear and inversely dependent upon the protraction period (1 day, 24 weeks, 60 weeks). Depending on the exposure pattern used for the gamma-ray baseline, relative biological effectiveness (RBE) values ranged from 6 to 43. Augmentation, because it occurred only at higher levels of neutron exposure, had no influence on the estimation of RBEmon the estimation of RBEm

295

Dose-response relationship in locoregional control for patients with stage II-III esophageal cancer treated with concurrent chemotherapy and radiotherapy  

International Nuclear Information System (INIS)

Purpose: To evaluate the correlation between radiation dose and locoregional control (LRC) for patients with Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy. Methods and materials: The medical records of 69 consecutive patients with clinical Stage II or III esophageal cancer treated with definitive chemoradiotherapy at the University of Texas M. D. Anderson Cancer Center between 1990 and 1998 were retrospectively reviewed. Of the 69 patients, 43 had received ?51 Gy (lower dose group) and 26 >51 Gy (higher dose group). The median dose in the lower and higher dose groups was 30 Gy (range, 30-51 Gy) and 59.4 Gy (range, 54-64.8 Gy), respectively. Two fractionation schedules were used: rapid fractionation, delivering 30 Gy at 3 Gy/fraction within 2 weeks, and standard fractionation, delivering ?45 Gy at 1.8-2 Gy/fraction daily. Total doses of 5% (46.2% vs. 23.3%). The lower dose group had more N1 tumors, but the tumor classification and stage grouping were similar in the two groups. The median follow-up time for all patients was 22 months (range, 2-56 months). Patients in the higher dose group had a statistically significant better 3-year localically significant better 3-year local control rate (36% vs. 19%, p = 0.011), disease-free survival rate (25% vs. 10%, p = 0.004), and overall survival rate (13% vs. 3%, p = 0.054). A trend toward a better distant-metastasis-free survival rate was noted in the higher dose group (72% vs. 59%, p = 0.12). The complete clinical response rate was significantly greater in the higher dose group (46% vs. 23%, p = 0.048). In both groups, the most common type of first failure was persistence of the primary tumor. Significantly fewer patients in the higher dose group had tumor persistence after treatment (p = 0.02). No statistically significant difference was found between the two groups in the pattern of locoregional or distant failure. The long-term side effects of chemoradiotherapy were similar in the two groups, although it was difficult to assess the side effects accurately in a retrospective fashion. On multivariate analysis, Stage II (vs. III) disease and radiation dose >51 Gy were independent predictors of improved LRC, and locoregional failure was an independent predictor of worse overall survival. Conclusion: Our data suggested a positive correlation between radiation dose and LRC in the population studied. A higher radiation dose was associated with increased LRC and survival in the dose range studied. The data also suggested that better LRC was associated with a lower rate of distant metastasis. A threshold of tumor response to radiation dose might be present, as suggested by the flattened slope in the high-dose area on the dose-response curve. A carefully designed dose-escalation study is required to confirm this assumption

296

Dose-response relationship of the sensitivity of neuroblastoma detection with MIBG  

International Nuclear Information System (INIS)

This paper reports on the evaluation of neuroblastoma with metaiodobenzylguanidine (MIBG) labeled with either iodine-131 or iodine-123 has become prominent in clinical staging and therapeutic response monitoring. Indeed, I-131-labeled MIBG has shown effectiveness as a systemic radiotherapeutic agent in neuroblastoma, and its role in the treatment of this unfortunate children's cancer is currently being evaluated. We postulated a likely dose-response relationship of neuroblastoma detection in MIBG and that its characterization might permit an understanding of the degree of which diagnostic MIBG scans estimate true tumor burden. Seven patients with stage IV neuroblastoma had a total of 14 therapeutic administrations (1-4 per patient) of I-131 MIBG (150-350 mCi per dose). Posttherapy scans with I-131 (n = 6) and I-123 (n = 8) had been obtained within 4 weeks of the therapy. The scans were compared, and the tumor burden was estimated

297

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

Science.gov (United States)

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

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

298

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

1980-09-01

299

The shape of the radiation dose response for DNA double-strand break induction and repair.  

Science.gov (United States)

DNA double-strand breaks are among the most deleterious lesions induced by ionising radiation. A range of inter-connected cellular response mechanisms has evolved to enable their efficient repair and thus protect the cell from the harmful consequences of un- or mis-repaired breaks which may include early effects such as cell killing and associated acute toxicities and late effects such as cancer. A number of studies suggest that the induction and repair of double-strand breaks may not always occur linearly with ionising radiation dose. Here we have aimed to identify and discuss some of the biological and methodological factors that can potentially modify the shape of the dose response curve obtained for these endpoints using the most common assays for double-strand breaks, pulsed-field gel electrophoresis and microscopic scoring of radiation-induced foci. PMID:23522792

Barnard, Stephen; Bouffler, Simon; Rothkamm, Kai

2013-01-01

300

Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats  

Energy Technology Data Exchange (ETDEWEB)

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 +/- 6.6 for Sham, 7.8 +/- 4.1 for Beam only, 4.4 +/- 5.6 for BPA-BNCT I and 0.45 +/- 0.20 for BPA-BNCT II; tumor nodule weight was 750 +/- 480 mg for Sham, 960 +/- 620 mg for Beam only, 380 +/- 720 mg for BPA-BNCT I and 7.3 +/- 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.

Emiliano C. C. Pozzi; Veronica A. Trivilin; Lucas L. Colombo; Andrea Monti Hughes; Silvia I. Thorp; Jorge E. Cardoso; Marcel A. Garabalino; Ana J. Molinari; Elisa M. Heber; Paula Curotto; Marcelo Miller; Maria E. Itoiz; Romina F. Aromando; David W. Nigg; Amanda E. Schwint

2013-11-01

301

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

International Nuclear Information System (INIS)

Experiments were performed with several plant species in natural environments as well in a greenhouse and/or tissue culture facilities to establish dose-response functions of plant responses to simulated acidic rain in order to determine environmental risk assessments to ambient levels of acidic rain. Response functions of foliar injury, biomass of leaves and seed of soybean and pinto beans, root yields of radishes and garden beets, and reproduction of bracken fern are considered. The dose-response function of soybean seed yields with the hydrogen ion concentration of simulated acidic rainfalls was expressed by the equation y = 21.06-1.01 log x where y = seed yield in grams per plant and x = the hydrogen concentration if ?eq 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

302

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

Energy Technology Data Exchange (ETDEWEB)

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

Evans, L.S.

1981-01-01

303

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

DEFF Research Database (Denmark)

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 regression program with variance weighting and proper inverse estimation. The Weibull model provides the best fit to the data for all four chemicals. Predicted EC10s (95% confidence limits) from our derived equations are quite accurate; for example, with 4-4-(trifluoromethyl)phenoxy-phenol and the probit model, we obtain 1.40 (1.22-1.61) mg/L versus 1.40 (1.20-1.64) mg/L obtained from the nonlinear regression program. The main advantage of the approach is that EC10 or ECx (where x = 1 - 99) can be predicted from well-determined responses around EC20 to EC80 without experimental data in the low- or high-response range. Problems with the estimation of confidence interval for EClow,x (concentration predicted to cause x% inhibition) from algal growth inhibition also are addressed. Large confidence intervals may be the result of experimental error and lack of a well-defined reference response value.

Christensen, Erik R.; Kusk, Kresten Ole

2009-01-01

304

Defining a dose-response relationship for prostate external beam radiotherapy  

International Nuclear Information System (INIS)

We aimed to quantify a relationship between radiotherapy dose and freedom from biochemical failure (FFBF) in low- and intermediate-risk prostate cancer. To reduce confounding we used data with a standardised end–point, mature follow-up, low competing risk of metastatic failure, conventional fractionation and separate reporting for outcomes with hormonal therapy (HT). A systematic review of the literature was carried out. Studies that reported the use of radiotherapy alone in 1.8–2Gy fractions in low- and intermediate-risk prostate cancer were included. The primary end–point was Phoenix definition 5-year FFBF. A logistic regression was used to quantify the dose–response relationship. Data from eight studies with 3037 patients met the inclusion criteria. The data from 810 low-risk patients and 2245 intermediate-risk patients were analysed. A strong association between radiotherapy dose and FFBF was found in low- and intermediate-risk patients managed with radiotherapy alone. In low-risk patients not treated with HT the dose required to achieve 50% biochemical tumour control (TCD50) is 52.0?Gy and the slope of the dose–response curve at TCD50 (?50) is 2.1%/Gy. At 78Gy this represented a FFBF of 90.3%. In intermediate-risk patients not treated with HT the TCD50 is 64.7Gy and ?50 is 3.2%/Gy. At 78 Gy this translated into a FFBF of 84.3%. HT had a small effect for low-risk patients and an inconsistent effect for intermediate-risk men. A strong association was found between radiation dose and biochemical outcome in both low- and intermediate-risk patients. Standardised reporting of results from future studies will make future analyses more robust.

305

Dose-response relationship for breast cancer induction at radiotherapy dose  

Directory of Open Access Journals (Sweden)

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 ?/? = 3 Gy were ? = 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.

Gruber Günther

2011-06-01

306

Epidemiological methods for assessing dose-response and dose-effect relationships  

DEFF Research Database (Denmark)

Description Handbook of the Toxicology of Metals is the standard reference work for physicians, toxicologists and engineers in the field of environmental and occupational health. This new edition is a comprehensive review of the effects on biological systems from metallic elements and their compounds. An entirely new structure and illustrations represent the vast array of advancements made since the last edition. Special emphasis has been placed on the toxic effects in humans with chapters on the diagnosis, treatment and prevention of metal poisoning. This up-to-date reference provides easy access to a broad range of basic toxicological data and also gives a general introduction to the toxicology of metallic compounds. Audience Toxicologists, physicians, and engineers in the fields of environmental and occupational health as well as libraries in these disciplines. Will also be a useful reference for governmental regulatory agencies and public health officers. Contents Introduction - General Considerations and International Perspectives General Chemistry, Sampling, Analytical Methods and Speciation Routes of Exposure, Dose, and Metabolism of Metals Biological Monitoring and Biomarkers Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity General Considerations of Dose-Effect and Dose-Response Relationships Interactions in Metal Toxicology Epidemiological Methods for Assessing Dose-Response and Dose-Effect Relationships Essential Metals: Assessing Risks from Deficiency and Toxicity Carcinogenicity of Metal Compounds Immunotoxicology of Metals Reproductive and Developmental Toxicity of Metals Ecotoxicology of Metals - Sources, Transport, and Effects in the Ecosystem Risk Assessment Diagnosis and Treatment of Metal Poisoning - General Aspects Principles for Prevention of the Toxic Effects of Metals Aluminum Antimony Arsenic Barium Beryllium Bismuth Cadmium Chromium Cobalt Copper Gallium and Semiconductor Compounds Germanium Indium Iron Lead Manganese Mercury Molybdenum Nickel Palladium Platinum Selenium Silver Tellurium Thallium Tin Titanium Tungsten Uranium Vanadium Zinc

Kjellström, Tord; Grandjean, Philippe

2007-01-01

307

Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh  

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Full Text Available Abstract Background Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. Methods A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS. The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP, aspartate transaminase (AST and alanine transaminase (ALT were then assayed. Results Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails, the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics. Conclusions The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a novel exposure- and dose- response relationship between arsenic exposure metrics and serum hepatic enzyme activity. Elevated serum hepatic enzyme activities in the higher exposure gradients provided new insights into arsenic-induced liver toxicity that might be helpful for the early prognosis of arsenic-induced liver diseases.

Hossain Mostaque

2011-07-01

308

Dose escalation with 3-D CRT in prostate cancer: five year dose responses and optimal treatment  

International Nuclear Information System (INIS)

Purpose: To report 5 yr dose responses in prostate cancer patients treated with 3D-CRT and describe optimal treatment based on dose response. Methods: Dose escalation was studied in 233 consecutive patients treated with 3D-CRT between 3/89 and 10/92. All surviving patients have >32 mo follow-up, the median follow-up is 55 mo. Estimated logistic cumulative distribution functions (logit response models) fit to 5 yr actuarial bNED outcome are reported for 3 dose groups in each of 3 pretreatment PSA groupings (10-19.9 ng/ml and 20+ ng/ml); no dose response is observed for patients with pretreatment PSA <10 ng/ml. Logit response models fit to 5 yr actuarial late morbidity rates (grade 2 GI, grade 2 GU, grade 3,4 GI) are also reported for 4 dose groups. Patients are treated with CT planned 4-field conformal technique where the PTV encompasses the CTV by 1.0 cm in all directions including the anterior rectal wall margin. Patients are followed at 6 mo intervals with PSA and DRE, and bNED failure is defined as PSA ?1.5 ng/ml and rising on two consecutive measures. The Fox Chase modification of the LENT morbidity scale is used for GI morbidity including any blood transfusion and/or more than 2 coagulations as a grade 3 event. GU morbidity follows the RTOG scale. Results: The logit response models based on 5 yr bNED results have slopes of 27% and 18% for pretreatment PSA grouping 10-19.9 ng/ml and 20+ ng/ml, respectively. The 50% bNED response is observed at 71 Gy and 80 Gy response is observed at 71 Gy and 80 Gy respectively, while the 80% bNED response is observed at 76 Gy for the 10-19.9 ng/ml group and estimated at 88 Gy for the 20+ ng/ml group. Logit dose response models for grade 2 GI and grade 2 GU morbidity show markedly different slopes, 23% versus 4%, respectively. The slope for grade 3,4 GI is 12%. The dose response model indicates grade 3,4 GI complication rates at 5 yrs are 8% at 76 Gy and 12% at 80 Gy. Conclusion: Based on 5 yr results, we can draw some conclusions about appropriate dose from these studies. (1) There is little advantage to be gained from dose levels above 75-76 Gy for the PSA grouping 10-19.9 ng/ml as 5 yr bNED at that dose is 80%. It is possible, however, that local failure between 5 and 10 yrs may be improved by higher dose and it may be worthwhile to investigate 80 Gy in these patients. (2) Optimal dose level for the pretreatment PSA 20+ ng/ml group is not defined by observed dose response but the logit plot strongly suggests dose levels of ?80 Gy should be investigated. The 5 yr bNED rate observed in our study at 76 Gy is ?33% and less than satisfactory. The dose of 70 Gy commonly given in the U.S. with conventional treatment will result in ? 15% bNED at 5 yrs and is clearly inadequate. It is possible that the problem of high rates of failure in patients with pretreatment PSA 20+ ng/ml can be improved by higher dose as the pattern of failure for these patients treated to ?76 Gy shows 60% have slowly rising PSA levels suggesting local failure, while 40% have rapidly rising PSA levels, and metastasis. This possibility needs further study. With longer follow-up and 5 yr actuarial rates of morbidity, the slopes of grade 2 GU and grade 3,4 GI morbidity have become more shallow, 4% and 12% respectively. Grade 2 GI morbidity which is largely rectal bleeding, however, remains steep (23%). With the technique used, morbidity at 76 Gy is grade 2 GI 40%, grade 3,4 GI 8%, Grade 2 GU 12%. Morbidity at 80 Gy is grade 2 GI 61%, grade 3,4 GI 12%, and grade 2 GU 13%. We currently limit dose to 71-72 Gy to the anterior rectal wall, and have previously demonstrated that grade 2 and 3,4 GI morbidity is favorably influenced by this change

309

A novel pairwise comparison method for in silico discovery of statistically significant cis-regulatory elements in eukaryotic promoter regions: Application to Arabidopsis.  

Science.gov (United States)

Cis regulatory elements (CREs), located within promoter regions, play a significant role in the blueprint for transcriptional regulation of genes. There is a growing interest to study the combinatorial nature of CREs including presence or absence of CREs, the number of occurrences of each CRE, as well as of their order and location relative to their target genes. Comparative promoter analysis has been shown to be a reliable strategy to test the significance of each component of promoter architecture. However, it remains unclear what level of difference in the number of occurrences of each CRE is of statistical significance in order to explain different expression patterns of two genes. In this study, we present a novel statistical approach for pairwise comparison of promoters of Arabidopsis genes in the context of number of occurrences of each CRE within the promoters. First, using the sample of 1000 Arabidopsis promoters, the results of the goodness of fit test and non-parametric analysis revealed that the number of occurrences of CREs in a promoter sequence is Poisson distributed. As a promoter sequence contained functional and non-functional CREs, we addressed the issue of the statistical distribution of functional CREs by analyzing the ChIP-seq datasets. The results showed that the number of occurrences of functional CREs over the genomic regions was determined as being Poisson distributed. In accordance with the obtained distribution of CREs occurrences, we suggested the Audic and Claverie (AC) test to compare two promoters based on the number of occurrences for the CREs. Superiority of the AC test over Chi-square (2×2) and Fisher's exact tests was also shown, as the AC test was able to detect a higher number of significant CREs. The two case studies on the Arabidopsis genes were performed in order to biologically verify the pairwise test for promoter comparison. Consequently, a number of CREs with significantly different occurrences was identified between the promoters. The results of the pairwise comparative analysis together with the expression data for the studied genes revealed the biological significance of the identified CREs. PMID:25303887

Shamloo-Dashtpagerdi, Roohollah; Razi, Hooman; Aliakbari, Massumeh; Lindlöf, Angelica; Ebrahimi, Mahdi; Ebrahimie, Esmaeil

2015-01-01

310

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  

Science.gov (United States)

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 ? = 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) The transition probability, An4o, for electron capture into the initially-present vacancies is ?40 times greater than An4, the transition probability for the radiation-created vacancies. These two factors marginalize the effect of the created vacancies at low dose resulting in a linear dose response.

Eliyahu, I.; Horowitz, Y. S.; Oster, L.; Mardor, I.; Druzhyna, S.; Biderman, S.

2015-01-01

311

Maximum likelihood estimation of dose-response parameters for therapeutic operating characteristic (TOC) analysis of carcinoma of the nasopharynx  

International Nuclear Information System (INIS)

A Therapeutic Operating Characteristic (TOC) curve for radiation therapy plots, for all possible treatment doses, the probability of tumor ablation as a function of the probability of radiation-induced complication. Application of this analysis to actual therapeutic situation requires that dose-response curves for ablation and for complication be estimated from clinical data. We describe an approach in which ''maximum likelihood estimates'' of these dose-response curves are made, and we apply this approach to data collected on responses to radiotherapy for carcinoma of the nasopharynx. TOC curves constructed from the estimated dose-response curves are subject to moderately large uncertainties because of the limitations of available data.These TOC curves suggest, however, that treatment doses greater than 1800 rem may substantially increase the probability of tumor ablation with little increase in the risk of radiation-induced cervical myelopathy, especially for T1 and T2 tumors

312

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

International Nuclear Information System (INIS)

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

313

Thermoluminescence dose Response Study of Natural Salt (NaCl:Cu,Mg,Mn,O,Cu,As obtained from Mizoram, India  

Directory of Open Access Journals (Sweden)

Full Text Available This paper reports the dose response study of natural salt (local name Dap Chi extracted from salty water sources in Mizoram, India. XRD and SEM of the sample were done and TL studies have been carried out using TLD reader TL1009I and sample was irradiated with gamma radiation using Theratron machine fitted with cobalt-60 source. Chen and Mckeever method has been applied to analyze linearity, sub-linearity and super linearity properties of the sample. The corrections for zero dose reading were done. The fifth degree polynomial dose responses had also been investigated. From the investigations, it may be concluded that the natural salt extracted from Mizoram shows a linear dose response in the range of 0.5 Gy – 2.0 Gy and may be a candidate for low radiation dose-meter, however further studies are needed for confirmation in this regard.

Ramesh Chandra Tiwari

2014-08-01

314

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

315

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

International Nuclear Information System (INIS)

This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of 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

316

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

International Nuclear Information System (INIS)

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

317

Calcium intake and colorectal adenoma risk: Dose-response meta-analysis of prospective observational studies.  

Science.gov (United States)

Evidence from randomized controlled trials suggests that calcium may protect against recurrence of colorectal adenomas, which could lead to the subsequent prevention of cancer. Yet the trials used only a large single dose and were of small sizes, and thus, knowledge of the dose-response relationship and influence on high-risk adenomas is limited. To address these issues, we conducted linear and nonlinear dose-response meta-analyses primarily based on prospective observational studies published up to July 2014 identified from PubMed and Embase. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated for total and supplemental calcium intake, respectively, using a random-effects model. For total calcium intake, summary RR for each 300 mg/day increase was 0.95 (95% CI?=?0.92-0.98; I(2) ?=?45%; eight studies with 11,005 cases; range of intake?=?333-2,229 mg/day). Evidence of nonlinearity was indicated: approximately, compared to 550 mg/day of total calcium intake, the summary RR was 0.92 (95% CI?=?0.89-0.94) at 1,000 mg/day and 0.87 (95% CI?=?0.84-0.90) at 1,450 mg/day (pnonlinearity ?

Keum, NaNa; Lee, Dong Hoon; Greenwood, Darren C; Zhang, Xuehong; Giovannucci, Edward L

2015-04-01

318

Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer  

Science.gov (United States)

When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ?2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (?18%), whereas maximum and mean doses decreased (?0.8 and ?4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ?1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range. Presented in part at the European Society for Therapeutic Radiotherapy and Oncology Annual Meeting, April 5-8, 2014, Vienna, Austria.

Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

2014-07-01

319

Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer  

DEFF Research Database (Denmark)

When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ?2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (?18%), whereas maximum and mean doses decreased (?0.8 and ?4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ?1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range.

Olsson, C; Thor, M

2014-01-01

320

Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children  

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Full Text Available Abstract Background In addition to stimulating linear growth in children, growth hormone (GH influences metabolism and body composition. These effects should be considered when individualizing GH treatment as dose-dependent changes in metabolic markers have been reported. Hypothesis: There are different dose-dependent thresholds for metabolic effects in response to GH treatment. Method A randomized, prospective, multicentre trial TRN 98-0198-003 was performed for a 2-year catch-up growth period, with two treatment regimens (a individualized GH dose including six different dose groups ranging from 17–100 ?g/kg/day (n=87 and (b fixed GH dose of 43 ?g/kg/day (n=41. The individualized GH dose group was used for finding dose–response effects, where the effective GH dose (ED 50% required to achieve 50% ? effect was calculated with piecewise linear regressions. Results Different thresholds for the GH dose were found for the metabolic effects. The GH dose to achieve half of a given effect (ED 50%, with 90% confidence interval was calculated as 33(±24.4 ?g/kg/day for ? left ventricular diastolic diameter (cm, 39(±24.5 ?g/kg/day for ? alkaline phosphatase (?kat/L, 47(±43.5 ?g/kg/day for ? lean soft tissue (SDS, 48(±35.7 ?g/kg/day for ? insulin (mU/L, 51(±47.6 ?g/kg/day for ? height (SDS, and 57(±52.7 ?g/kg/day for ? insulin-like growth factor I (IGF-I SDS. Even though lipolysis was seen in all subjects, there was no dose–response effect for ? fat mass (SDS or ? leptin ng/ml in the dose range studied. None of the metabolic effects presented here were related to the dose selection procedure in the trial. Conclusions Dose-dependent thresholds were observed for different GH effects, with cardiac tissue being the most responsive and level of IGF-I the least responsive. The level of insulin was more responsive than that of IGF-I, with the threshold effect for height in the interval between.

Decker Ralph

2012-11-01

321

Linearization of dose–response curve of the radiochromic film dosimetry system  

International Nuclear Information System (INIS)

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 [?= (?1)·netOD(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™ 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 R2 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™ 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 found that criteria of 3%/3 mm for an IMRT QA plan and 3%/2 mm for a brachytherapy QA plan are passing 95% gamma function points. Conclusions: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.

322

Plasma and liver acetaminophen-protein adduct levels in mice after acetaminophen treatment: Dose–response, mechanisms, and clinical implications  

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At therapeutic doses, acetaminophen (APAP) is a safe and effective analgesic. However, overdose of APAP is the principal cause of acute liver failure in the West. Binding of the reactive metabolite of APAP (NAPQI) to proteins is thought to be the initiating event in the mechanism of hepatotoxicity. Early work suggested that APAP-protein binding could not occur without glutathione (GSH) depletion, and likely only at toxic doses. Moreover, it was found that protein-derived APAP-cysteine could only be detected in serum after the onset of liver injury. On this basis, it was recently proposed that serum APAP-cysteine could be used as diagnostic marker of APAP overdose. However, comprehensive dose–response and time course studies have not yet been done. Furthermore, the effects of co-morbidities on this parameter have not been investigated. We treated groups of mice with APAP at multiple doses and measured liver GSH and both liver and plasma APAP-protein adducts at various timepoints. Our results show that protein binding can occur without much loss of GSH. Importantly, the data confirm earlier work that showed that protein-derived APAP-cysteine can appear in plasma without liver injury. Experiments performed in vitro suggest that this may involve multiple mechanisms, including secretion of adducted proteins and diffusion of NAPQI directly into plasma. Induction of liver necrosis through ischemia–reperfusion significantly increased the plasma concentration of protein-derived APAP-cysteine after a subtoxic dose of APAP. While our data generally support the measurement of serum APAP-protein adducts in the clinic, caution is suggested in the interpretation of this parameter. - Highlights: • Extensive GSH depletion is not required for APAP-protein binding in the liver. • APAP-protein adducts appear in plasma at subtoxic doses. • Proteins are adducted in the cell and secreted out. • Coincidental liver injury increases plasma APAP-protein adducts at subtoxic doses. • Plasma APAP-protein adducts are diagnostically useful, but interpret with care.

McGill, Mitchell R.; Lebofsky, Margitta [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Norris, Hye-Ryun K.; Slawson, Matthew H. [Center for Human Toxicology, University of Utah, Salt Lake City, UT (United States); Bajt, Mary Lynn; Xie, Yuchao; Williams, C. David [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Wilkins, Diana G.; Rollins, Douglas E. [Center for Human Toxicology, University of Utah, Salt Lake City, UT (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

2013-06-15

323

Dose response evaluation of gene expression profiles in the skin of K6/ODC mice exposed to sodium arsenite  

International Nuclear Information System (INIS)

Chronic drinking water exposure to inorganic arsenic and its metabolites increases tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, we characterized gene expression profiles from analysis of K6/ODC mice administered 0, 0.05, 0.25, 1.0 and 10 ppm sodium arsenite in their drinking water for 4 weeks. Following exposure, total RNA was isolated from mouse skin and processed to biotin-labeled cRNA for microarray analyses. Skin gene expression was analyzed with Affymetrix Mouse Genome 430A 2.0 GeneChips (registered) , and pathway analysis was conducted with DAVID (NIH), Ingenuity (registered) Systems and MetaCore's GeneGo. Differential expression of several key genes was verified through qPCR. Only the highest dose (10 ppm) resulted in significantly altered KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, including MAPK, regulation of actin cytoskeleton, Wnt, Jak-Stat, Tight junction, Toll-like, phosphatidylinositol and insulin signaling pathways. Approximately 20 genes exhibited a dose response, including several genes known to be associated with carcinogenesis or tumor progression including cyclin D1, CLIC4, Ephrin A1, STAT3 and DNA methyltransferase 3a. Although transcription changes in all identified genes have not previously been linked to arsenic carcinogenesis, their association with carcinogenesis in other systems suggests that these genes may play a role in the early staese genes may play a role in the early stages of arsenic-induced skin carcinogenesis and can be considered potential biomarkers

324

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

Science.gov (United States)

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.

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

2011-01-01

325

On the necessity of different statistical treatment for Illumina BeadChip and Affymetrix GeneChip data and its significance for biological interpretation  

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Full Text Available Abstract Background The original spotted array technology with competitive hybridization of two experimental samples and measuring relative expression levels is increasingly displaced by more accurate platforms that allow determining absolute expression values for a single sample (for example, Affymetrix GeneChip and Illumina BeadChip. Unfortunately, cross-platform comparisons show a disappointingly low concordance between lists of regulated genes between the latter two platforms. Results Whereas expression values determined with a single Affymetrix GeneChip represent single measurements, the expression results obtained with Illumina BeadChip are essentially statistical means from several dozens of identical probes. In the case of multiple technical replicates, the data require, therefore, different stistical treatment depending on the platform. The key is the computation of the squared standard deviation within replicates in the case of the Illumina data as weighted mean of the square of the standard deviations of the individual experiments. With an Illumina spike experiment, we demonstrate dramatically improved significance of spiked genes over all relevant concentration ranges. The re-evaluation of two published Illumina datasets (membrane type-1 matrix metalloproteinase expression in mammary epithelial cells by Golubkov et al. Cancer Research (2006 66, 10460; spermatogenesis in normal and teratozoospermic men, Platts et al. Human Molecular Genetics (2007 16, 763 significantly identified more biologically relevant genes as transcriptionally regulated targets and, thus, additional biological pathways involved. Conclusion The results in this work show that it is important to process Illumina BeadChip data in a modified statistical procedure and to compute the standard deviation in experiments with technical replicates from the standard errors of individual BeadChips. This change leads also to an improved concordance with Affymetrix GeneChip results as the spermatogenesis dataset re-evaluation demonstrates. Reviewers This article was reviewed by I. King Jordan, Mark J. Dunning and Shamil Sunyaev.

Eisenhaber Frank

2008-06-01

326

Are low but statistically significant levels of genetic differentiation in marine fishes 'biologically meaningful'? A case study of coastal Atlantic cod.  

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A key question in many genetic studies on marine organisms is how to interpret a low but statistically significant level of genetic differentiation. Do such observations reflect a real phenomenon, or are they caused by confounding factors such as unrepresentative sampling or selective forces acting on the marker loci? Further, are low levels of differentiation biologically trivial, or can they represent a meaningful and perhaps important finding? We explored these issues in an empirical study on coastal Atlantic cod, combining temporally replicated genetic samples over a 10-year period with an extensive capture-mark-recapture study of individual mobility and population size. The genetic analyses revealed a pattern of differentiation between the inner part of the fjord and the open skerries area at the fjord entrance. Overall, genetic differentiation was weak (average F(ST) ?=?0.0037), but nevertheless highly statistical significant and did not depend on particular loci that could be subject to selection. This spatial component dominated over temporal change, and temporal replicates clustered together throughout the 10-year period. Consistent with genetic results, the majority of the recaptured fish were found close to the point of release, with <1% of recaptured individuals dispersing between the inner fjord and outer skerries. We conclude that low levels of genetic differentiation in this marine fish can indeed be biologically meaningful, corresponding to separate, temporally persistent, local populations. We estimated the genetically effective sizes (N(e) ) of the two coastal cod populations to 198 and 542 and found a N(e) /N (spawner) ratio of 0.14. PMID:21199035

Knutsen, H; Olsen, E M; Jorde, P E; Espeland, S H; André, C; Stenseth, N C

2011-02-01

327

Skin sensitization in chemical risk assessment: report of a WHO/IPCS international workshop focusing on dose-response assessment.  

Science.gov (United States)

An international workshop was held in 2006 to evaluate experimental techniques for hazard identification and hazard characterization of sensitizing agents in terms of their ability to produce data, including dose-response information, to inform risk assessment. Human testing to identify skin sensitizers is discouraged for ethical reasons. Animal-free alternatives, such as quantitative structure-activity relationships and in vitro testing approaches, have not been sufficiently developed for such application. Guinea pig tests do not generally include dose-response assessment and are therefore not designed for the assessment of potency, defined as the relative ability of a chemical to induce sensitization in a previously naive individual. In contrast, the mouse local lymph node assay does include dose-response assessment and is appropriate for this purpose. Epidemiological evidence can be used only under certain circumstances for the evaluation of the sensitizing potency of chemicals, as it reflects degree of exposure as well as intrinsic potency. Nevertheless, human diagnostic patch test data and quantitative elicitation data have provided very important information in reducing allergic contact dermatitis risk and sensitization in the general population. It is therefore recommended that clinical data, particularly dose-response data derived from sensitized patients, be included in risk assessment. PMID:18237832

van Loveren, Henk; Cockshott, Amanda; Gebel, Tom; Gundert-Remy, Ursula; de Jong, Wim H; Matheson, Joanna; McGarry, Helen; Musset, Laurence; Selgrade, Maryjane K; Vickers, Carolyn

2008-03-01

328

Acute administration of methylphenidate alters the prefrontal cortex neuronal activity in a dose–response characteristic  

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Full Text Available Catherine M Claussen, Nachum Dafny Department of Neurobiology and Anatomy, University of Texas Health Science Center Medical School at Houston, Houston, TX, USA Abstract: The prefrontal cortex (PFC is part of the collective structures known as the motive circuit. The PFC acts to enhance higher cognitive functions as well as mediate the effects of psychostimulants. Previous literature shows the importance of PFC neuronal adaptation in response to acute and chronic psychostimulant exposure. The PFC receives input from other motive circuit structures, including the ventral tegmental area, which mediates and facilitates the rewarding effects of psychostimulant exposure. PFC neuronal and locomotor activity from freely behaving rats previously implanted with permanent semimicroelectrodes were recorded concomitantly using a telemetric (wireless recording system. Methylphenidate (MPD is used as a leading treatment for behavioral disorders and more recently as a cognitive enhancer. Therefore, the property of MPD dose response on PFC neuronal activity was investigated. The results indicate that MPD modulates PFC neuronal activity and behavioral activity in a dose-dependent manner. PFC neuronal responses to 0.6 mg/kg elicited mainly a decrease in PFC neuronal activity, while higher MPD doses (2.5 and 10.0 mg/kg elicited mainly increased neuronal activity in response to MPD. The correlation between MPD effects on PFC neuronal activity and animal behavior is discussed. Keywords: prefrontal cortex, Ritalin, behavior, neuronal, acute

Claussen CM

2014-02-01

329

In vivo dose response relationship between physostigmine and cholinesterase activity in RBC and tissues of rats  

International Nuclear Information System (INIS)

Dose response of physostigmine (Phy) was studied in rat using various doses. Rats were sacrificed 15 min after Phy administration. Blood and tissues were analyzed for ChE activity by radiometric method and Phy concentration by HPLC method. A comparison of ChE values in different tissues of rats indicated that ChE activity was highest in brain and least in diaphragm. The enzyme activity was eleven times more in brain as compared to diaphragm. Phy produced a dose-dependent inhibition of ChE in RBC, brain and diaphragm from 50 to 200 ?g/kg, then ChE inhibition was plateaued from 200 to 500 ?g/kg in these tissues. A dose related ChE inhibition was seen in heart and thigh muscle from 50 to 500 ?g/kg. Phy concentration increased linearly from 50 to 400 ?g/kg in plasma, brain, heart and thigh muscle. These results indicate that ChE inhibition is linear up to 200 ?g/kg in RBC, 150 ?g/kg in brain and 300 ?g/kg in heart. This linearity is not consistent in other tissues

330

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

International Nuclear Information System (INIS)

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

331

Gibberellin dose-response curves and the characterization of dwarf mutants of barley  

Science.gov (United States)

Dose-response curves relating gibberellin (GA) concentration to the maximal leaf-elongation rate (LERmax) defined three classes of recessive dwarf mutants in the barley (Hordeum vulgare L.) 'Himalaya. ' The first class responded to low (10(-8)-10(-6) M) [GA3] (as did the wild type). These grd (GA-responsive dwarf) mutants are likely to be GA-biosynthesis mutants. The second class of mutant, gse (GA sensitivity), differed principally in GA sensitivity, requiring approximately 100-fold higher [GA3] for both leaf elongation and alpha-amylase production by aleurone. This novel class may have impaired recognition between the components that are involved in GA signaling. The third class of mutant showed no effect of GA3 on the LERmax. When further dwarfed by treatment with a GA-biosynthesis inhibitor, mutants in this class did respond to GA3, although the LERmax never exceeded that of the untreated dwarf. These mutants, called elo (elongation), appeared to be defective in the specific processes that are required for elongation rather than in GA signaling. When sln1 (slender1) was introduced into these different genetic backgrounds, sln was epistatic to grd and gse but hypostatic to elo. Because the rapid leaf elongation typical of sln was observed in the grd and gse backgrounds, we inferred that rapid leaf elongation is the default state and suggest that GA action is mediated through the activity of the product of the Sln gene. PMID:10364415

Chandler; Robertson

1999-06-01

332

Calibration of EPR signal dose response of tooth enamel to photons: Experiment and Monte Carlo simulation  

International Nuclear Information System (INIS)

The experimental energy dependence of the electron paramagnetic resonance (EPR) radiation-induced signal at irradiation by photons in the energy range of 13 keV-1.25 MeV was analysed in terms of the absorbed dose in human tooth enamel. The latter was calculated using a Monte Carlo simulation of the photon and electron transport. The dependence of the calculated absorbed dose on the sample thickness was analysed. No energy dependence of the EPR signal on the absorbed dose in enamel was verified in the range of 37 keV-1.25 MeV. At 13 and 20 keV the EPR signal dose response was reduced by 8% probably due to sample powdering. Dose-depth profiles in enamel samples irradiated by 1.25 MeV photons in polymethylmethacrylate and aluminium build-up materials were calculated. It was concluded that secondary electron equilibrium conditions are better fulfilled for irradiation in aluminium, which makes this material preferable for calibration. (authors)

333

Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation.  

Science.gov (United States)

In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of (60)Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small "adapting" stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment. PMID:15063537

Ulsh, B A; Miller, S M; Mallory, F F; Mitchel, R E J; Morrison, D P; Boreham, D R

2004-01-01

334

Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation  

International Nuclear Information System (INIS)

In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of 60Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment-based radioecological risk assessment

335

Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation  

Energy Technology Data Exchange (ETDEWEB)

In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of {sup 60}Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment.

Ulsh, B.A. E-mail: bau6@cdc.gov; Miller, S.M.; Mallory, F.F.; Mitchel, R.E.J.; Morrison, D.P.; Boreham, D.R

2004-07-01

336

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

International Nuclear Information System (INIS)

The track structure theory developed by Katz and co-workers ascribes the effect of high-LET radiation to the highly inhomogeneous dose distribution due to low energy ?-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 ? = 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)

337

Dose-Response Relationship Of Chromosome Aberration Induced By Low Doses Gamma Rays  

International Nuclear Information System (INIS)

The detection method of chromosome aberration is highly valuable as a biological dosimeter to support physical dosimeter. Dicentric is a specific type of chromosome aberration caused by ionizing radiation exposure that can be detected from a radiation dose of 0.2 Gy. To prove this presumption, a research had been conducted by exposing lymphocyte cell of peripheral blood taken from four male donors to Co-60 gamma rays at doses of 0 (control), 0.2, 0.4, 0.6, 0.8, and 1 Gy. The blood samples were cultured with standard procedures. The results showed that dicentric type can be detected starting from 0.2 Gy dose, i.e. 0.002 + 0.001/cell. The higher radiation dose the higher dicentric chromosome induced. The equation of dose-response curve obtained with linier quadratic model is Y = 0.678 x 10-3 - 0.166 x 10-4 X + 0.147 x 10-5 X2 with corellation value R of 0.969

338

Dose–response analysis of parotid gland function: What is the best measure of xerostomia?  

International Nuclear Information System (INIS)

Purpose: To describe the dose–response relationships for the different measures of salivary gland recovery following radical radiotherapy for locally advanced head and neck squamous cell cancers (LA-HNSCC). Methods and materials: Dosimetric analysis of data from the PARSPORT trial, a Phase III study of conventional RT (RT) and intensity modulated radiotherapy (IMRT) for LA-HNSCC was undertaken to determine the relationship between parotid gland mean dose and toxicity endpoints: high-grade subjective and objective xerostomia and xerostomia-related quality of life scores. LKB-NTCP parameters (TD50, m and n) were generated and tolerance doses (D50) reported using non-linear logistic regression analysis. Results: Data were available on 63 patients from the PARSPORT trial. Parotid saliva flow rate provided the strongest association between mean dose and recovery, D50 = 23.4 Gy (20.6–26.2) and k = 3.2 (1.9–4.5), R2 = 0.85. Corresponding LKB parameters were TD50 = 26.3 Gy (95% CI: 24.0–30.1), m = 0.25 (0.18–1.0 and n = 1). LENTSOMA subjective xerostomia also demonstrated a strong association D50 = 33.3 Gy (26.7–39.8), k = 2.8 (91.4–4.4), R2 = 0.77). Conclusion: We recommend using the LENT SOMA subjective xerostomia score to predict recovery of salivation due to its strong association with dosimetry and ease of recording

339

Low dose radiation and cancer in A-bomb survivors: latency and non-linear dose-response in the 1950–90 mortality cohort  

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Full Text Available Abstract Background Analyses of Japanese A-bomb survivors' cancer mortality risks are used to establish recommended annual dose limits, currently set at 1 mSv (public and 20 mSv (occupational. Do radiation doses below 20 mSv have significant impact on cancer mortality in Japanese A-bomb survivors, and is the dose-response linear? Methods I analyse stomach, liver, lung, colon, uterus, and all-solid cancer mortality in the 0 – 20 mSv colon dose subcohort of the 1950–90 (grouped mortality cohort, by Poisson regression using a time-lagged colon dose to detect latency, while controlling for gender, attained age, and age-at-exposure. I compare linear and non-linear models, including one adapted from the cellular bystander effect for ? particles. Results With a lagged linear model, Excess Relative Risk (ERR for the liver and all-solid cancers is significantly positive and several orders of magnitude above extrapolations from the Life Span Study Report 12 analysis of the full cohort. Non-linear models are strongly superior to the linear model for the stomach (latency 11.89 years, liver (36.90, lung (13.60 and all-solid (43.86 in fitting the 0 – 20 mSv data and show significant positive ERR at 0.25 mSv and 10 mSv lagged dose. The slope of the dose-response near zero is several orders of magnitude above the slope at high doses. Conclusion The standard linear model applied to the full 1950–90 cohort greatly underestimates the risks at low doses, which are significant when the 0 – 20 mSv subcohort is modelled with latency. Non-linear models give a much better fit and are compatible with a bystander effect.

Dropkin Greg

2007-01-01

340

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

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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.

Tamrakar Sushil B

2012-03-01

341

Efeito dose-resposta de fatores de risco para a doença isquêmica do coração Dose-response effect of risk factors to ischaemic heart disease  

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Full Text Available Resultados de diversos estudos têm apontado a relevância da hipertensão arterial, do hábito de fumar e da hipercolesterolemia como fatores de risco para a doença isquêmica do coração (DIC. Poucos autores têm investigado a existência de gradiente linear relacionando a quantidade destas exposições com os eventos coronarianos. Com o objetivo de avaliar o efeito de diferentes graus de exposição a estas variáveis sobre a DIC, procedendo-se ao ajustamento para possíveis variáveis de confusão, foi feito estudo planejado sob a forma de desenho tipo caso-controle, tendo a coleta de dados se estendido de março de 1993 a fevereiro de 1994. Foram estudados 833 indivíduos de ambos os sexos, na faixa etária compreendida entre 30 e 69 anos completos, sendo todos residentes no Município de São Paulo, SP (Brasil. Foram comparados 280 casos com 553 controles (285 controles de vizinhança e 268 controles hospitalares. A técnica estatística utilizada para a análise dos dados foi a regressão logística multivariada. Os resultados permitiram identificar gradiente linear para as variáveis duração da hipertensão arterial e para número de cigarros consumidos/dia. As variáveis duração do hábito de fumar e duração da hipercolesterolemia, embora tendo apresentado "odds ratios" significantes para as respectivas categorias de exposição, não apresentaram gradiente linear. Foram discutidos aspectos metodológicos que poderiam exercer influência sobre a tendência dos "odds ratios" nas categorias de exposição das variáveis duração do hábito de fumar e duração da hipercolesterolemia. Conclui-se que os efeitos dose-resposta observados para as variáveis duração da hipertensão arterial e número de cigarros consumidos/dia foram independentes da presença nos modelos de potentes fatores de risco para a doença isquêmica do coração.Several authors have reported hypertension, smoking and hypercholesterolemia as independent risk factors to ischaemic heart disease (IHD. However few of them have investigated the existence of a linear gradient related to the levels of these exposures and IHD. The effect of different levels of these exposures and IHD after adjusting for known confounders of effect, is assessed. The project was designed as a case-control study and the data were collected over one year from March/93 to February/94. The sample was composed of a total of 833 individuals of both genders aged 30-69 living in the city of S. Paulo, SP (Brazil, 280 of whom were compared with 553 controls (285 neighbourhood controls and 268 hospital controls. Logistic regression was the statistical method wold for the analysis of the data. The results showed a linear gradient for known duration of hypertension and daily number of cigarettes consumed. Although the variables duration of hypercholesterolemia and duration of the habit smoking presented statistically significant odds ratio in the respective strata there was no indication of a linear gradient. Some methodological issues are presented to explain this absence of a linear gradient for known duration of hypercholesterolemia and duration of the smoking habit. It is concluded that the dose response effect detected for known duration of hypertension and daily number of cigarettes consumed were independent of the presence of major risk factors ischaemic heart disease.

Suzana Alves de Moraes

1996-10-01

342

Detection by voxel-wise statistical analysis of significant changes in regional cerebral glucose uptake in an APP/PS1 transgenic mouse model of Alzheimer's disease.  

Science.gov (United States)

Biomarkers and technologies similar to those used in humans are essential for the follow-up of Alzheimer's disease (AD) animal models, particularly for the clarification of mechanisms and the screening and validation of new candidate treatments. In humans, changes in brain metabolism can be detected by 1-deoxy-2-[(18)F] fluoro-D-glucose PET (FDG-PET) and assessed in a user-independent manner with dedicated software, such as Statistical Parametric Mapping (SPM). FDG-PET can be carried out in small animals, but its resolution is low as compared to the size of rodent brain structures. In mouse models of AD, changes in cerebral glucose utilization are usually detected by [(14)C]-2-deoxyglucose (2DG) autoradiography, but this requires prior manual outlining of regions of interest (ROI) on selected sections. Here, we evaluate the feasibility of applying the SPM method to 3D autoradiographic data sets mapping brain metabolic activity in a transgenic mouse model of AD. We report the preliminary results obtained with 4 APP/PS1 (64+/-1 weeks) and 3 PS1 (65+/-2 weeks) mice. We also describe new procedures for the acquisition and use of "blockface" photographs and provide the first demonstration of their value for the 3D reconstruction and spatial normalization of post mortem mouse brain volumes. Despite this limited sample size, our results appear to be meaningful, consistent, and more comprehensive than findings from previously published studies based on conventional ROI-based methods. The establishment of statistical significance at the voxel level, rather than with a user-defined ROI, makes it possible to detect more reliably subtle differences in geometrically complex regions, such as the hippocampus. Our approach is generic and could be easily applied to other biomarkers and extended to other species and applications. PMID:20206704

Dubois, Albertine; Hérard, Anne-Sophie; Delatour, Benoît; Hantraye, Philippe; Bonvento, Gilles; Dhenain, Marc; Delzescaux, Thierry

2010-06-01

343

Non-Targeted Effects and the Dose Response for Heavy Ion Tumorigenesis  

Science.gov (United States)

BACKGROUND: There is no human epidemiology data available to estimate the heavy ion cancer risks experienced by astronauts in space. Studies of tumor induction in mice are a necessary step to estimate risks to astronauts. Previous experimental data can be better utilized to model dose response for heavy ion tumorigenesis and plan future low dose studies. DOSE RESPONSE MODELS: The Harderian Gland data of Alpen et al.[1-3] was re-analyzed [4] using non-linear least square regression. The data set measured the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron, niobium and lanthanum with LET s ranging from 0.4 to 950 keV/micron. We were able to strengthen the individual ion models by combining data for all ions into a model that relates both radiation dose and LET for the ion to tumor prevalence. We compared models based on Targeted Effects (TE) to one motivated by Non-targeted Effects (NTE) that included a bystander term that increased tumor induction at low doses non-linearly. When comparing fitted models to the experimental data, we considered the adjusted R2, the Akaike Information Criteria (AIC), and the Bayesian Information Criteria (BIC) to test for Goodness of fit.In the adjusted R2test, the model with the highest R2values provides a better fit to the available data. In the AIC and BIC tests, the model with the smaller values of the summary value provides the better fit. The non-linear NTE models fit the combined data better than the TE models that are linear at low doses. We evaluated the differences in the relative biological effectiveness (RBE) and found the NTE model provides a higher RBE at low dose compared to the TE model. POWER ANALYSIS: The final NTE model estimates were used to simulate example data to consider the design of new experiments to detect NTE at low dose for validation. Power and sample sizes were calculated for a variety of radiation qualities including some not considered in the Harderian Gland data set and with different background tumor incidences. We considered different experimental designs with varying number of doses and varying low doses dependant on the LET of the radiation. The optimal design to detect a NTE for an individual ion had 4 doses equally spaced below a maximal dose where bending due to cell sterilization was < 2%. For example at 100 keV/micron we would irradiate at 0.03 Gy, 0.065 Gy, 0.13 Gy, and 0.26 Gy and require 850 mice including a control dose for a sensitivity to detect NTE with 80% power. Sample sizes could be improved by combining ions similar to the methods used with the Harderian Gland data.

Chappelli, Lori J.; Cucinotta, Francis A.

2010-01-01

344

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

International Nuclear Information System (INIS)

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

345

Simulated and measured dose response characteristics of detectors used for CT dosimetry.  

Science.gov (United States)

A CT-SD16 semiconductor detector was calibrated in terms of the computed tomography (CT) air kerma index for the integration length L = 100 mm, C(K,PMMA,100), in the cylindrical CT head and body dosimetry phantoms using a DCT10 pencil ionization chamber as a reference instrument. Using IEC RQT 9 120-kV x-ray radiation quality and 25-62.5 mm nominal beam widths free in air, a C(K,PMMA,100)(DCT10)/C(K,PMMA,100)(CT-SD16) ratio of 0.97 was observed, while in the centre of 300 mm long CT head and body dosimetry phantoms, C(K,PMMA,100)(DCT10)/C(K,PMMA,100)(CT-SD16) ratios ranged from 1.02 to 1.09. Using IEC RQT 8-10 radiation qualities free in air, Monte Carlo simulated dose response characteristics of CT-SD16 and DCT10 were comparable with those obtained from the measurements. Simulations were also used to determine C(K,PMMA,100)(DCT10) in the centre of the CT head and body phantoms. At IEC RQT 9 and 25-62.5 mm nominal beam widths, the relative values of the simulated dose agreed with the measured values within 2-10% for the head and body phantoms, respectively. A k(q) correction factor between dose measurements in the phantom and free in air was determined for the model of DCT10 and for the real detectors using measured C(K,PMMA,100) data. Simulations were performed using the EGSnrc CAVRZ code. PMID:22850226

Hakanen, Arvi

2012-08-21

346

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

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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.  

Santosh H Shinde

2013-07-01

347

Somatic cell genetics of uranium miners and plutonium workers. A biological dose-response indicator  

International Nuclear Information System (INIS)

Two populations of underground uranium miners and plutonium workers work in the state of Colorado, United States of America. We have explored the prevalence of structural chromosome aberrations in peripheral blood lymphocytes as a possible biological indicator of absorbed radiation late-effects in these populations. The uranium miners are divided into four exposure groups expressed in Working Level Months (WLM), the plutonium workers into six groups with estimated 239Pu burdens expressed in nCi. Comparison of chromosome aberration frequency data between controls, miners, and plutonium workers demonstrate: (1) a cytogenetic response to occupational ionizing radiation at low estimated doses; and (2) an increasing monotonic dose-response in the prevalence of complex (all exchange) or total aberrations in all exposure groups in these populations. We also compared trends in the prevalence of aberrations per exposure unit (WLM and nCi) in each exposure subgroup for each population. In the uranium miners, the effects per WLM seem to decrease monotonically with increasing dose, whereas in the Pu workers the change per nCi appears abrupt, with all exposure groups over 1.3 nCi (minimum detectable level) having essentially similar rates. The calculations of aberrations per respective current maximum permissible dose (120 WLM and 40 nCi) for the two populations yield 4.8 X 10-2/100 cells for uranium miners and 90.6 X 10-2/100 cells for Pu workers. 10-2/100 cells for Pu workers. Factors which may have influenced this apparent 20-fold increase in the effectiveness of plutonium in the production of complex aberrations (9-fold increase in total aberrations) are discussed. (author)

348

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

DEFF Research Database (Denmark)

The effect of the fungicides carbendazim, fenpropimorph and propiconazole and of the insecticide dimethoate on plant P uptake via external hyphae of arbuscular mycorrhizal (AM) fungi was examined. Mycorrhizal plants were grown in a two-compartment system where a root-free hyphal compartment was separated from the main root compartment by nylon mesh. After 5 weeks of plant growth external hyphae of the AM fungi had spread throughout the hyphal compartment. At this time aqueous solutions of both P-32 and pesticide were added to the hyphal compartment. Resulting soil pesticide concentrations covered a wide range with the aim of describing the dose-response relationships between pesticide concentration and hyphal P uptake. Plants were harvested 6d after pesticide application. The amount of P-32 taken up into the plant was measured as was hyphal length in the hyphal compartment. Carbendazim had the most negative effect, with concentrations above 0.006 mu g g(-1) leading to a sharp decrease in hyphal P uptake. Concentrations above 0.1 mu g g-l almost completely inhibited hyphal P uptake. This concentration is lower than the expected field concentration following carbendazim application at the recommended field rate. Hyphal P uptake was also negatively affected by propiconazole but only at concentrations above 1 mu g g(-1). This corresponds to an expected field concentration of propiconazole after application of 10 times the recommended field dosage. Fenpropimorph and dimethoate had no negative effects on hyphal P uptake even when applied at concentrations of 125 or 46 mu g g(-1) respectively. These concentrations are equivalent to expected field concentrations following pesticide applications at 100 times the recommended field rate. (C) 1998 Elsevier Science Ltd. All rights reserved.

Schweiger, P.F.; Jakobsen, I.

1998-01-01

349

Study of Cell Line and Dose-response of Human Leukemic Cells  

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Full Text Available Cell type studied in this work is human leukemic cell Jurkat. In order to identify the exponential growth phase, the better time for sampling the population, the cell line was evaluated by monitoring the proliferation and viability of the cells in a 7-days long culture adding no medium to the cells. It was found that the culture within the cellular concentration from 6x105-2.7x106 cells/ml was in the exponential or log phase, where the viability and reproduction for the cells were high. The lag time and population doubling time were calculated and found to be 1 and 5 days respectively. The density dependent survival of cells in culture was remained constant, with the exception at very higher cell densities where it was found to decrease slightly. The viability of the cells was found to remain within 96-97% at incubation temperature range 10-500C, with a maximum at 35-400C. The cells were then incubated with 1 mM ALA at different temperatures and irradiated with different light doses. The dose-response curves were studied and modeled. The cell survival for incubation temperatures 10-370C were modeled as sigmoidal Boltzmann curves, whereas the survival for temperatures 39-500C were modeled as the second-order exponential decay curves. The efficiency for cell inactivation was calculated as the light dose or exposure time required for 50% of cell survival, and it was found that the efficiency was higher at higher temperatures.

M. Idrish Miah

2003-01-01

350

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

Science.gov (United States)

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.

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

2014-05-01

351

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

International Nuclear Information System (INIS)

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 afteference 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)

352

A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal123  

Science.gov (United States)

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20–25 kg/m2) and 18 obese (BMI: >30 kg/m2) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. PMID:24812072

Schwander, Flurina; Kopf-Bolanz, Katrin A.; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G.; Piya, Milan K.; Gijs, Martin A. M.; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergères, Guy

2014-01-01

353

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english No in situ protocol has assessed the dose-response effects of fluoride dentifrices involving low-fluoride formulations. Objective: To assess the ability of an in situ remineralization model in determining dose-response effects of dentifrices containing low fluoride concentrations ([F]) on bovine [...] enamel. Material and Methods: Volunteers wore palatal appliances containing demineralized enamel blocks and brushed their teeth and devices with the dentifrices supplied (double-blind, crossover protocol) separately for 3 and 7 days. Surface hardness (SH), integrated subsurface hardness (?KHN) and [F] in enamel were determined. Data were analyzed by ANOVA, Tukey's test and Pearson's correlation (p

Rebeca Lima, AFONSO; Juliano Pelim, PESSAN; Bruna Babler, IGREJA; Camila Fernandes, CANTAGALLO; Marcelle, DANELON; Alberto Carlos Botazzo, DELBEM.

2013-12-01

354

Lifetime bone cancer dose-response relationships in beagles and people from skeletal burdens of 226Ra and 90Sr  

International Nuclear Information System (INIS)

The lifetime tumor dose-response relationships observed in beagles injected with 226Ra or fed 90Sr at Davis provide the basis for understanding the induction of bone cancer for these bone-seeking radionuclides and for scaling to people. These relationships were found to be well represented by three-dimensional lognormal dose-response surfaces that yield risk as a function of average dose-rate and time after beginning of exposure. All dose-rates suggested a 100% risk at some later time post-exposure but the time required to reach a given level of risk was large for low dose rates so that there exists a practical threshold in that at lower dose rates individuals may die spontaneously from causes associated with natural aging prior to the expected appearance of radiogenic cancer. An analysis of the risks to people has been made using the lognormal model for both 226Ra and 90Sr

355

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

Science.gov (United States)

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.

Kowalska, Maria; Meronka, Katarzyna; Szewczak, Kamil

2012-03-01

356

mFISH analysis of chromosome aberrations induced in vitro by ?-particle radiation: examination of dose-response relationships.  

OpenAIRE

A multicolored FISH (mFISH) technique was used to characterize the cytogenetic damage associated with exposure to ?-particle radiation with particular emphasis on the quality and quantity that is likely to be transmitted through cell division to descendant cells. Peripheral blood lymphocytes were irradiated in vitro with (238)Pu ? particles with a range of mean doses up to 936 mGy and were cultured for 47 h. The dose responses for total aberrant cells, stable and unstable cells, and cells w...

Curwen, Gb; Tawn, Ej; Cadwell, Kk; Guyatt, L.; Thompson, J.; Hill, Ma

2012-01-01

357

Estimation of quantal dose response of drugs by the Spearman-Karber method: a computer program written in BASIC.  

Science.gov (United States)

Quantal-dose response is an important concept in pharmacology and toxicology. The best known variables are the median effective dose and the median lethal dose. These are measured according to the frequency of dichotomous response of the subjects being studied. The Spearman-Karber method is a simple and convenient algorithm to evaluate these indices. A highly portable computer program in BASIC language is also included for the convenience of computation. PMID:2638718

Fung, K P; Wong, T W

1989-01-01

358

Doe Program—Developing a Scientific Basis for Responses to Low-Dose Exposures: Impact on Dose-Response Relationships  

OpenAIRE

The DOE Low Dose Radiation Research Program focuses on biological mechanisms involved in response to low doses of both low and high-LET radiation (<0.1Gy). This research program represents a merging of new technologies with cutting edge biological techniques associated with genomics. This merger enables observation of radiation-induced cellular and molecular changes previously undetectable. These low-dose responses define mechanisms of interaction of radiation with living systems, and charact...

Brooks, Antone L.; Couch, Lezlie

2006-01-01

359

Clinically derived dose-response relations for urinary bladder and prostate from combined photon and proton prostate radiotherapy  

OpenAIRE

The aim of this study is the clinical derivation of the dose-response relations of bladder and prostate regarding PSA progression and urinary complications using patients treated for prostate cancer with both photon and proton beams. Such data are necessary for a prospective estimation of the clinical effectiveness of radiation therapy using combinations of different radiation modalities. Material During the period from 2002 until 2006, at the Academic Hospital in Uppsala, Sweden 189 p...

????????????, ???????

2009-01-01

360

Differences in first dose response to angiotensin converting enzyme inhibition in congestive heart failure: a placebo controlled study.  

OpenAIRE

OBJECTIVE--To compare the first dose responses to low dose angiotensin converting enzyme inhibitors (captopril, enalapril, and perindopril) in elderly patients with stable chronic heart failure. DESIGN--Double blind, randomised, placebo controlled, parallel, group prospective study of elderly patients with stable chronic heart failure. SETTING--General hospital in-patient admissions for supervised diuretic withdrawal (24-48 hours) and the introduction of angiotensin converting enzyme inhibito...

Macfadyen, R. J.; Lees, K. R.; Reid, J. L.

1991-01-01

361

Miniaturized Flow Cytometric In Vitro Micronucleus Assay Represents an Efficient Tool for Comprehensively Characterizing Genotoxicity Dose-Response Relationships  

OpenAIRE

This laboratory has developed a flow cytometric approach for scoring in vitro micronuclei (In Vitro MicroFlow®) whose characteristics are expected to benefit studies designed to comprehensively investigate genotoxicity dose-response relationships. In particular, new experimental designs become possible when automated scoring is combined with treatment, processing and sampling that all occur in microtiter plates. To test this premise, experiments described herein investigated micronucleus (MN...

Bryce, Steven M.; Avlasevich, Svetlana L.; Bemis, Jeffrey C.; Phonethepswath, Souk; Dertinger, Stephen D.

2010-01-01

362

Benchmarking B-Cell Epitope Prediction with Quantitative Dose-Response Data on Antipeptide Antibodies: Towards Novel Pharmaceutical Product Development  

OpenAIRE

B-cell epitope prediction can enable novel pharmaceutical product development. However, a mechanistically framed consensus has yet to emerge on benchmarking such prediction, thus presenting an opportunity to establish standards of practice that circumvent epistemic inconsistencies of casting the epitope prediction task as a binary-classification problem. As an alternative to conventional dichotomous qualitative benchmark data, quantitative dose-response data on antibody-mediated biological ef...

Caoili, Salvador Eugenio C.

2014-01-01

363

Dose Response Effects of Dermally applied Diethanolamine on Neurogenesis in Fetal Mouse Hippocampus and Potential Exposure of Humans  

OpenAIRE

Diethanolamine (DEA) is a common ingredient of personal care products. Dermal administration of DEA diminishes hepatic stores of the essential nutrient choline and alters brain development. We previously reported that 80 mg/kg/day of DEA during pregnancy in mice reduced neurogenesis and increased apoptosis in the fetal hippocampus. This study was designed to establish the dose-response relationships for this effect of DEA. Timed-pregnant C57BL/6 mouse dams were dosed dermally from gestation d...

Craciunescu, Corneliu N.; Niculescu, Mihai D.; Guo, Zhong; Johnson, Amy R.; Fischer, Leslie; Zeisel, Steven H.

2009-01-01

364

Laboratory measurement error in external dose estimates and its effects on dose-response analyses of Hanford worker mortality data  

International Nuclear Information System (INIS)

This report addresses laboratory measurement error in estimates of external doses obtained from personnel dosimeters, and investigates the effects of these errors on linear dose-response analyses of data from epidemiologic studies of nuclear workers. These errors have the distinguishing feature that they are independent across time and across workers. Although the calculations made for this report were based on Hanford data, the overall conclusions are likely to be relevant for other epidemiologic studies of workers exposed to external radiation

365

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

Energy Technology Data Exchange (ETDEWEB)

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.

NONE

2005-07-01

366

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

International Nuclear Information System (INIS)

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

367

Dose-Response Relationships in Expression of Biomarkers of Cell Proliferation in in vitro Assays and Inhalation Experiments  

OpenAIRE

Asbestos is a group of naturally occurring mineral fibers which are associated in occupational settings with increased risks of malignant mesothelioma (MM), lung cancers, and pulmonary fibrosis (asbestosis). The six recognized types of asbestos fibers (chrysotile, crocidolite, amosite, tremolite, anthophyllite, and actinolite) are different chemically and physically and may have different dose-response relationships in the development of various asbestos-associated diseases. For example, epid...

Shukla, Arti; Vacek, Pamela; Mossman, Brooke T.

2004-01-01

368

Thermoluminescence dose Response Study of Natural Salt (NaCl:Cu,Mg,Mn,O,Cu,As) obtained from Mizoram, India  

OpenAIRE

This paper reports the dose response study of natural salt (local name Dap Chi) extracted from salty water sources in Mizoram, India. XRD and SEM of the sample were done and TL studies have been carried out using TLD reader TL1009I and sample was irradiated with gamma radiation using Theratron machine fitted with cobalt-60 source. Chen and Mckeever method has been applied to analyze linearity, sub-linearity and super linearity properties of the sample. The corrections for zero...

Ramesh Chandra Tiwari

2014-01-01

369

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

OpenAIRE

Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)¿lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C¿lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to d...

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

2009-01-01

370

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

Science.gov (United States)

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 ?-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-6?7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA. PMID:24293226

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

2014-03-01

371

Construction of dose response calibration curves for dicentrics and micronuclei for X radiation in a Serbian population.  

Science.gov (United States)

Biological dosimetry using chromosome damage biomarkers is a valuable dose assessment method in cases of radiation overexposure with or without physical dosimetry data. In order to estimate dose by biodosimetry, any biological dosimetry service have to have its own dose response calibration curve. This paper reveals the results obtained after irradiation of blood samples from fourteen healthy male and female volunteers in order to establish biodosimetry in Serbia and produce dose response calibration curves for dicentrics and micronuclei. Taking into account pooled data from all the donors, the resultant fitted curve for dicentrics is: Ydic=0.0009 (±0.0003)+0.0421 (±0.0042)×D+0.0602 (±0.0022)×D(2); and for micronuclei: Ymn=0.0104 (±0.0015)+0.0824 (±0.0050)×D+0.0189 (±0.0017)×D(2). Following establishment of the dose response curve, a validation experiment was carried out with four blood samples. Applied and estimated doses were in good agreement. On this basis, the results reported here give us confidence to apply both calibration curves for future biological dosimetry requirements in Serbia. PMID:25308702

Pajic, J; Rakic, B; Jovicic, D; Milovanovic, A

2014-10-01

372

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

International Nuclear Information System (INIS)

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 PortalVisionTM 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 response of the EPID. Thirdly, a dosimetric response curve was drawn by the pixel values against their corresponding dose rates. A set of similar dosimetric response curves were obtained by changing gantry angle, field size and acquisition mode in the same way described above. Results: The relationship between the dose rates and pixel values was not linear, so all the characteristic curves had been fitted using polynomial functions. The dose response was strongly innctions. The dose response was strongly influenced by image acquisition mode including pulse repetition frequency and EPID sampling mode, and slightly varied with gantry angle position to the points away from the central axis but kept unchanged at the central axis, while the dosimetric response curves were found to be independent of radiation field size. Conclusions: For different image acquisition modes, calibrations must be done separately as the acquisition mode obviously affects the shape of dosimetric response curve. Gantry angle effects can be limited by doing calibrations at different gantry angles. The fact that the dose response is independent of field sizes will offer authors much convenience of using one field size calibration data for the others

373

Dose-response relationships within the parotid gland after radiotherapy for head and neck cancer  

International Nuclear Information System (INIS)

Background and purpose: To determine the salivary function, after parotid-sparing radiotherapy (RT), of different regions within the parotid gland and to evaluate dose-function relationships within the parotid glands and between patients. Patients and methods: Sixteen head and neck cancer patients, irradiated between September 1999 and November 2000 using a conformal parotid-sparing technique, were included in this study. Before RT and 7 months after RT (range 6-10 months), a salivary gland scintigraphy was performed in all patients combined with a single photon emission computed tomography (SPECT). The salivary excretion fraction (SEF) was measured, after stimulation, in 8-12 transverse 5 mm SPECT slices of each parotid. Loss of salivary excretion fraction (dSEF %) of these slices was calculated as the proportion of SEF after RT as compared to SEF before RT. Since the planning CT-scan and the SPECT-scintigraphy were performed in the same treatment position, the dose to a transverse slice within the parotid gland could be matched to the loss of salivary excretion fraction of that respective slice. A non-linear model was fitted to the dose-loss of function data and the dose resulting in 50% loss of salivary excretion fraction (D50) was calculated. Results: Before RT, all but one patient presented with normal salivary excretion fractions (SEF) of both parotid glands. Within the same parotid gland, the SEF's of the different slices were almost equal. Seven monferent slices were almost equal. Seven months after RT, the reduction in SEF was statistically significant (P-value 50%). After fitting a non-linear model to these plots, the mean dose resulting in 50% loss of salivary excretion fraction (D50) 7 months after RT was 22.5 Gy. A large inter-patient variability was found in D50. Conclusions: Salivary SPECT is a useful tool for the evaluation of the salivary function of different slices within the parotid gland. Before irradiation, the different slices within one parotid gland act as functional sub-units contributing equally to the function of the entire gland. Seven months after an average dose of 22.5 Gy (D50) the functional sub-unit has lost 50% of its excretion fraction. The high inter-patient variability in D50 and the observation that low doses (10-15 Gy) can induce serious loss of function should prompt us in the clinic to reduce the dose to the parotids even lower than the threshold of 22.5 Gy

374

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

International Nuclear Information System (INIS)

Background: The bioeffect of a physical dose depends on the nature of the tissue, fractionation scheme, dose rate and treatment time. Certainly, experienced radiotherapists are convinced of the existence of patient-to-patient variability in normal tissue response to radiotherapy for malignant tumours. The absorbed dose needs to be translated into a bioeffect dose, which takes into account treatment variables and the radiobiological characteristics of the relevant tissue. Various bioeffect models such as NSD, CRE, TDF and BED have been proposed to predict the biological effect of radiotherapy treatments. Aim: This study was aimed at deriving tolerance bioeffect dose values for normal tissue complication rate. Materials/Methods: Compiled clinical data of time dose fractionation schedules and incidence of erythema, desquamation and telangiectasia were used for the present analysis. Results: For erythema and desquamation the radiation dose varied from 23.9 to 55.1 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 40 days. For telangiectasia (score .1 at 3 years) the radiation dose varied from 25.8 to 55.1 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 40 days. For telangiectasia (score .2 at 5 years) the radiation dose varied from 25.8 to 63.0 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 68 days. For telangiectasia (score .1, .2, .3, .4 at 10 years) the radiation dose varied from 25.8 to 63.0 Gy in 04 to 35 fraaried 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)

375

Lack of radiation dose response for patients with low-risk clinically localized prostate cancer: a retrospective analysis  

International Nuclear Information System (INIS)

Purpose: The need for dose escalation for patients with low-risk clinically localized prostate cancer remains controversial. In this study, we report our pooled institutional experience of low-risk patients treated with a range of 'standard' radiation doses to assess outcome in regard to biochemical failure and to determine whether a dose-response relationship exists within this conventional dose range. Methods and Materials: Patients with low-risk clinically localized prostate cancer (T1 or T2a, Gleason grade ?6, and prostate-specific antigen ?10 ng/mL) treated at Joint Center for Radiation Therapy-affiliated institutions between October 1989 and September 1997 were retrospectively analyzed for freedom from biochemical failure. The dose was prescribed volumetrically with 95% normalization to between 5760 and 6900 cGy (6100 and 7300 cGy ICRU reference point dose). Patients were stratified into 3 groups with relatively equal numbers of patients (6660 cGy). To ensure that any differences in biochemical failure between patients at the lower and higher ends of the dose range used were not masked by analysis of the entire cohort, patients receiving ?6500 cGy or ?6800 cGy were subsequently analyzed separately. Biochemical failure was defined per the ASTRO consensus definition. The log-rank test was used to assess for differences in follow-up and time to biochemical failure. A Kaplan-Meier plot of time to biochemical failure for the initial 3 subgrol failure for the initial 3 subgroups was generated. Results: A total of 264 patients were identified. Sixteen patients whose dose was not recorded in the database were excluded from analysis. The median follow-up was 35 months. No significant differences were found in baseline prostate-specific antigen, Gleason grade, or clinical stage among the groups. The overall actuarial rate of 5-year freedom from biochemical failure was 80.2%. By dose level, the 5-year biochemical failure-free rate was 79.2%, 78.4%, and 84.5% for 6660 cGy, respectively. These differences were not significant. Subsequently, 45 patients receiving ?6500 cGy were compared with 23 patients receiving ?6800 cGy. The difference between these groups was not significant. The 5-year freedom from biochemical failure rate for the patients receiving ?6500 cGy was 89.9%. Conclusion: Within a range of doses considered standard for treatment of low-risk clinically localized prostate cancer during an 8-year period, no improvement in biochemical freedom from failure was noted with the higher doses. The overall 5-year rate of freedom from biochemical failure is consistent with that reported by others with standard and escalated external beam doses used in this low-risk population. A prospective randomized study is necessary to define the optimal dose in this patient population

376

Dose-response relationship of {gamma}-H2AX foci induction in human lymphocytes after X-rays exposure  

Energy Technology Data Exchange (ETDEWEB)

Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of {gamma}-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 {gamma}-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y{sub (0.5h)} = 11.66D + 0.15 (R{sup 2} = 0.99), Y{sub (5h)} = 2.44D + 0.15 (R{sup 2} = 0.99), Y{sub (8h)} = 1.57D + 0.22 (R{sup 2} = 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 {gamma}-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 {gamma}-H2AX foci kinetics after gamma- and X-irradiation in vitro.

Mandina, Tania [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Roch-Lefevre, Sandrine H.; Voisin, Pascale [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France); Gonzalez, Jorge E.; Lamadrid, Ana I.; Romero, Ivonne [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Garcia, Omar, E-mail: omar@cphr.edu.cu [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Voisin, Philippe; Roy, Laurence [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France)

2011-09-15

377

Dose-response relationship of ?-H2AX foci induction in human lymphocytes after X-rays exposure  

International Nuclear Information System (INIS)

Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of ?-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 ?-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 ?-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 ?-H2AX foci kinetics after gamma- and X-irradiation in vitro.

378

An apparent threshold dose response in ferrous xylenol-orange gel dosimeters when scanned with a yellow light source  

International Nuclear Information System (INIS)

Freshly prepared radiochromic ferrous xylenol-orange (FX) gels optically scanned with a light source exhibit a threshold dose response that is thermally and wavelength dependent. Correction for this threshold dose leads to accurate dose calibration and better reproducibility in multiple fraction radiation exposures. The objective of this study was to determine the cause of the threshold dose effect and to control it through improved dose calibration procedures. The results of a systematic investigation into the chemical cause revealed that impurities within the various FX gel constituents (i.e. xylenol-orange, gelatin, sulfuric acid and ferrous ammonium sulfate) were not directly responsible for the threshold dose. Rather, it was determined that the threshold dose response stems from a spectral sensitivity to different chemical complexes that are formed at different dose levels in FX gels between ferric (Fe(III)) ions and xylenol-orange (XO), i.e. Fe(III)i:XOj. A double Fe(III)2:XO1 complex preferentially absorbs at longer wavelengths (i.e. yellow), while at shorter wavelengths (i.e. green) the sensitivity is biased toward the single Fe(III)1:XO1 complex. As a result, when scanning with yellow light, freshly prepared FX gels require a minimum concentration of Fe(III) ions to shift the equilibrium concentration to favor the predominant production of the double Fe(III)2:XO1 complex a(III)2:XO1 complex at low doses. This can be accomplished via pre-irradiation of freshly prepared gels to a priming dose of ?0.5 Gy or allowing auto-oxidation to generate the startup concentration of Fe(III) ions required to negate the apparent threshold dose response

379

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

International Nuclear Information System (INIS)

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

380

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

381

Dose-response assessment of naphthalene-induced genotoxicity and glutathione detoxication in human TK6 lymphoblasts.  

Science.gov (United States)

The dose-response relationship for the induction of micronuclei (MN) and the impact of glutathione (GSH) detoxication on naphthalene-induced cytotoxicity and genotoxicity were investigated in human TK6 cells. TK6 cells were exposed to 10 concentrations ranging from 0.0625 to 30?M naphthalene in the presence of ?-naphthoflavone- and phenobarbital (?NP/PB)-induced rat liver S9 with a nicotinamide adenine dinucleotide phosphate-generating system. Three approaches were used to identify a no-observed-effect level (NOEL) for naphthalene-induced genotoxicity: (1) laboratory criteria of ? twofold increase over the concurrent solvent controls (NOEL = 10?M), (2) ANOVA with Bonferroni correction (NOEL = 2.5?M), and (3) the benchmark dose approach (BMCL(10) = 3.35?M). The NOEL and point of departure micronucleus frequency for naphthalene-induced MN are between the tested naphthalene concentrations of 2.5-10.0?M in this experimental system. Supplementation of the exposure system with physiological relevant concentrations of 5mM GSH eliminated naphthalene-induced cytotoxicity and genotoxicity; no increased cytotoxicity or genotoxicity was observed at concentrations of up to 500?M naphthalene in the presence of GSH compared with 2.5-10.0?M in the absence of GSH. Naphthalene bioactivation by ?NP/PB-induced rat liver S9 exhibits a nonlinear dose-response for the induction of MN in TK6 cells with a NOEL of 2.5-10?M that in the presence of GSH is shifted upward greater than 50- to 200-fold. These data demonstrate a nonlinear dose-response for naphthalene-induced genotoxicity that is eliminated by GSH, and both observations should be considered when assessing human risk from naphthalene exposures. PMID:22253058

Recio, Leslie; Shepard, Kim G; Hernández, Lya G; Kedderis, Gregory L

2012-04-01

382

BIOLOGICALLY-BASED DOSE-RESPONSE MODELING IN DEVELOPMENTAL TOXICOLOGY: BIOCHEMICAL AND CELLULAR SEQUELAE OF 5-FLUOROURACIL EXPOSURE IN THE DEVELOPING RAT  

Science.gov (United States)

Mechanistically-based dose-response models for developmental toxicity require elucidation of biological events that intervene between maternal exposure and adverse developmental outcome. We examined some of the major events in the rat embryo following subcutaneous injection of 5-...

383

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

International Nuclear Information System (INIS)

Program PSOD was written to simulate the distribution in responses of membrane populations subjected to random radiation doses and dose rates. It computes the response (damage) according to one of three formulas selected by the user, and outputs statistical results to the terminal. It will plot simulated dose- and response-frequency distributions in two or three dimensions. Doses and dose rates are selected from the log normal distribution; other distributions can be incorporated as the need arises. A true log normal curve with defined mean and standard deviation can also be generated. The purpose of this documentation is to provide a complete operating manual for the program. A user guide is available on-line after initiating a session of PSOD. Detailed examinations of the statistical validity of various steps have been included to aid future modifications and updating

384

Dose-response relationships in chemical carcinogenesis: renal mesenchymal tumours induced in the rat by single dose dimethylnitrosamine.  

OpenAIRE

A single intraperitoneal dose of dimethylnitrosamine (DMN) given to weanling rats after 3 days' treatment with a protein-free diet results in the induction of renal mesenchymal tumours, the incidence of which is related to the dose of DMN in a sigmoid dose-response curve. The number of tumours per kidney is small, most animals given 40 mg/kg DMN (the TD100) having either one or two tumours in each kidney. However, within a few days of dosing a large number of small proliferative foci of mesen...

Driver, H. E.; White, I. N.; Butler, W. H.

1987-01-01

385

Effect of nitric oxide inhibition on blood pressure and renal sodium handling : a dose-response study in healthy man  

DEFF Research Database (Denmark)

Nitric oxide (NO) is a ubiquitous vasodilator and an important regulator of renal sodium excretion. To further investigate the role of NO in renal sodium handling, we studied the effects of the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in a crossover dose-response study. During NO inhibition mean arterial pressure increased dose-dependently and reached a plateau after 20 minutes of infusion. On the contrary, the fractional excretion of sodium was reduced equally in all three L-NMMA doses. This indicates that sodium excretion is highly sensitive to even small changes in renal NO bioavailability in healthy human.

Larsen, Thomas; Mose, Frank Holden

2012-01-01

386

Investigation of dose response characteristics and relative dose distribution for polymer gel dosimeter evaluated using X-ray CT  

International Nuclear Information System (INIS)

In recent years polymer gel dosimetry systems are widely used for the verification of three dimensional dose distributions produced by complicated radiotherapy techniques. The aim of this study was to investigate the X-ray CT polymer gel dosimetry system for dose response characteristics and relative dose distribution for therapeutic photon and electron beams. The percentage depth doses and profile studies were carried out for both photon and electron beam. The same study was carried out using RFA-200 with RK-ion chamber and film and compared with polymer gel measurements

387

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

OpenAIRE

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 ?-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 br...

Qiang Liu; Bing Wang; Takanori Katsube; Sai Jun Fan; Fei-Yue Fan; Hui Zhao; Xu (Kevin) Su; Jian Xiang Liu; Jia Cao; Li Qing Du; Chang Xu; Yan Wang

2013-01-01

388

Interpretation of the shoulder of dose-response curves with immediate plating in terms of repair of potentially lethal lesions during a restricted time period  

International Nuclear Information System (INIS)

It is shown theoretically that a shouldered dose-response curve may be obtained when repair of Poisson-distributed potentially lethal lesions occurs during a restricted time period between plating x-irradiated cells on nutrient agar and fixation of potentially lethal lesions. This interpretation is supported by experiments showing that an increased shoulder width of the dose-response curve is observed when irradiated cells are given more time for repair of potentially lethal lesions. (author)

389

Dose-response modeling : Evaluation, application, and development of procedures for benchmark dose analysis in health risk assessment of chemical substances  

OpenAIRE

In this thesis, dose-response modeling and procedures for benchmark dose (BMD) analysis in health risk assessment of chemical substances have been investigated. The BMD method has been proposed as an alternative to the NOAEL (no-observedadverse- effect-level) approach in health risk assessment of non-genotoxic agents. According to the BMD concept, a dose-response model is fitted to data and the BMD is defined as the dose causing a predetermined change in response. A lowe...

Sand, Salomon

2005-01-01

390

Dose-response analysis of bromate-induced DNA damage and mutagenicity is consistent with low-dose linear, nonthreshold processes.  

Science.gov (United States)

Mutagenic agents have long been inferred to act through low-dose linear, nonthreshold processes. However, there is debate about this assumption, with various studies interpreting datasets as showing thresholds for DNA damage and mutation. We have applied rigorous statistical analyses to investigate the shape of dose-response relationships for a series of in vitro and in vivo genotoxicity studies using potassium bromate (KBrO(3) ), a water ozonation byproduct that is bioactivated to a reactive species causing oxidative damage to DNA. We analyzed studies of KBrO(3) genotoxicity where no-effect/threshold levels were reported as well as other representative datasets. In all cases, the data were consistent with low-dose linear models. In the majority of cases, the data were fit either by a linear (straight line) model or a model which was linear at low doses and showed a saturation-like downward curvature at high doses. Other datasets with apparent upward curvature were still adequately represented by models that were linear at low dose. Sensitivity analysis of datasets showing upward curvature revealed that both low-dose linear and nonlinear models provide adequate fits. Additionally, a simple biochemical model of selected key processes in bromate-induced DNA damage was developed and illustrated a situation where response for early primary events suggested an apparent threshold while downstream events were linear. Overall, the statistical analyses of DNA damage and mutations induced by KBrO(3) are consistent with a low-dose linear response and do not provide convincing evidence for the presence of a threshold. PMID:23015362

Spassova, Maria A; Miller, David J; Eastmond, David A; Nikolova, Nadejda S; Vulimiri, Suryanarayana V; Caldwell, Jane; Chen, Chao; White, Paul D

2013-01-01

391

Inhibition of the early asthmatic response to inhaled allergen by the 5-lipoxygenase activating protein inhibitor GSK2190915: a dose–response study  

Directory of Open Access Journals (Sweden)

Full Text Available Dave Singh,1 Malcolm Boyce,2 Virginia Norris,3 Sandra E Kent,3 Jane H Bentley31University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester, Manchester, UK; 2Hammersmith Medicines Research, London, UK; 3GlaxoSmithKline, Middlesex, UKBackground: GSK2190915, a 5-lipoxygenase activating protein inhibitor, inhibits the production of cysteinyl leukotrienes and leukotriene B4 and 5-oxo-6,8,11,14-eicosatetraenoic acid. We have previously reported that GSK2190915 100 mg daily inhibits early and late asthmatic responses to inhaled allergen; the effects of lowe