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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 Applets: Statistical Significance  

Science.gov (United States)

Created by authors Duckworth, McCabe, Moore and Sclove for W.H. Freeman of Co., this applet is designed to help students visualize the rejection region of a statistical test by allowing them to set null and alternate hypotheses, population parameters, sample statistics, and significance level. It accompanies "ÃÂÃÂPractice of Business Statistics," but can be used without this text. Even though brief, this is a nice interactive resource for an introductory statistics course.

Duckworth, William; Mccabe, George; Moore, David; Sclove, Stanley

2009-03-05

3

Is statistical significance always significant?  

Science.gov (United States)

One way in which we learn new information is to read the medical literature. Whether or not we do primary research, it is important to be able to read literature in a critical fashion. A seemingly simple concept in reading is to interpret p values. For most of us, if we find a p value that is conclusion to heart and quote it at every opportunity. If the p value is >.05, we discard the paper and look elsewhere for useful information. Unfortunately, this is too simplistic an approach. The real utility of p values is to consider them within the context of the experiment being performed. Defects in study design can make an interpretation of a p value useless. One has to be wary of type I (seeing a "statistically significant" difference just because of chance) and type II (failing to see a difference that really exists) errors. Examples of the former are publication bias and the performance of multiple analyses; the latter refers to a trial that is too small to demonstrate the difference. Finding significant differences in surrogate or intermediate endpoints may not help us. We need to know if those endpoints reflect the behavior of clinical endpoints. Selectively citing significant differences and disregarding studies that do not find them is inappropriate. Small differences, even if they are statistically significant, may require too much resource expenditure to be clinically useful. This article explores these problems in depth and attempts to put p values in the context of studies. PMID:16207667

Koretz, Ronald L

2005-06-01

4

Statistical significance for genomewide studies  

Digital Repository Infrastructure Vision for European Research (DRIVER)

With the increase in genomewide experiments and the sequencing of multiple genomes, the analysis of large data sets has become commonplace in biology. It is often the case that thousands of features in a genomewide data set are tested against some null hypothesis, where a number of features are expected to be significant. Here we propose an approach to measuring statistical significance in these genomewide studies based on the concept of the false discovery rate. This ...

Storey, John D.; Tibshirani, Robert

2003-01-01

5

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

6

Statistical significance of the gallium anomaly  

International Nuclear Information System (INIS)

We calculate the statistical significance of the anomalous deficit of electron neutrinos measured in the radioactive source experiments of the GALLEX and SAGE solar neutrino detectors, taking into account the uncertainty of the detection cross section. We found that the statistical significance of the anomaly is ?3.0?. A fit of the data in terms of neutrino oscillations favors at ?2.7? short-baseline electron neutrino disappearance with respect to the null hypothesis of no oscillations.

7

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

Science.gov (United States)

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

Rosen, Brittany L.; DeMaria, Andrea L.

2012-01-01

8

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

9

The Insignificance of Statistical Significance Testing  

Science.gov (United States)

This excellent article by Douglas H. Johnson was published this summer in the Journal of Wildlife Management, 63(3):763-772 and is made available now in electronic version by the Northern Prairie Wildlife Research Center. In the article, Johnson argues that "statistical hypothesis tests add very little value to the products of research." Through a series of simple examples and clear text, Johnson criticizes several often-praised statistical hypothesis methods, and offers alternatives (in the form of estimation and confidence intervals, decision theory, and Bayesian approaches to "hypothesis testing and other statistical practices"). For any student or researcher of ecology, this article makes several fundamental points that should not be overlooked.

Johnson, Douglas H.

10

Transformations of summary statistics as input in meta-analysis for linear dose–response models on a logarithmic scale: a methodology developed within EURRECA  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background To derive micronutrient recommendations in a scientifically sound way, it is important to obtain and analyse all published information on the association between micronutrient intake and biochemical proxies for micronutrient status using a systematic approach. Therefore, it is important to incorporate information from randomized controlled trials as well as observational studies as both of these provide information on the association. However, original research papers present their data in various ways. Methods This paper presents a methodology to obtain an estimate of the dose–response curve, assuming a bivariate normal linear model on the logarithmic scale, incorporating a range of transformations of the original reported data. Results The simulation study, conducted to validate the methodology, shows that there is no bias in the transformations. Furthermore, it is shown that when the original studies report the mean and standard deviation or the geometric mean and confidence interval the results are less variable compared to when the median with IQR or range is reported in the original study. Conclusions The presented methodology with transformations for various reported data provides a valid way to estimate the dose–response curve for micronutrient intake and status using both randomized controlled trials and observational studies.

Souverein Olga W

2012-04-01

11

Determining the statistical significance of experimental results  

CERN Document Server

The results of an experiment are usually expressed as one of the following: 1. The measurement of one or more numerical values, parameters of a theory, or 2. Evidence that one theoretical hypothesis is more likely to be true than another hypothesis, or 3. Evidence for or against one hypothesis being true (without mention of other possible hypotheses). The author presents the theoretical basis for assigning numerical values to the significance of such results, and discusses the practical application of that theory. (6 refs).

James, F

1981-01-01

12

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

13

Spironolactone dose-response relationships in healthy subjects.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

14

Caveats for using statistical significance tests in research assessments  

DEFF Research Database (Denmark)

This article 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 by Opthof and Leydesdorff (2010). 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 are highly problematic and detrimental to critical thinking. We claim that the use of such tests do not provide any advantages in relation to deciding whether differences between citation indicators are important or not. On the contrary their use may be harmful. Like many other critics, we generally believe that statistical significance tests are over- and misused in the empirical sciences including scientometrics and we encourage a reform on these matters.

Schneider, Jesper Wiborg

2013-01-01

15

Dose response relationship in local radiotherapy for hepatocellular carcinoma  

Energy Technology Data Exchange (ETDEWEB)

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

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

2001-06-01

16

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 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

17

Identification of Statistically Significant Features from Random Forests  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Embedded feature selection can be performed by analyzing the variables used in a Random Forest. Such a multivariate selection takes into account the interactions between variables but is not easy to interpret in a statistical sense. We propose a statistical procedure to measure variable importance that tests if variables are significantly useful in combination with others in a forest. We show experimentally that this new importance index correctly identifies relevant variables. The top of the...

Paul, Je?ro?me; Verleysen, Michel; Dupont, Pierre; Ecml, Workshop On Solving Complex Machine Learning Problems With Ensemble Methods

2013-01-01

18

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

19

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

International Nuclear Information System (INIS)

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

20

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

 
 
 
 
21

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

22

Significance levels for studies with correlated test statistics.  

Science.gov (United States)

When testing large numbers of null hypotheses, one needs to assess the evidence against the global null hypothesis that none of the hypotheses is false. Such evidence typically is based on the test statistic of the largest magnitude, whose statistical significance is evaluated by permuting the sample units to simulate its null distribution. Efron (2007) has noted that correlation among the test statistics can induce substantial interstudy variation in the shapes of their histograms, which may cause misleading tail counts. Here, we show that permutation-based estimates of the overall significance level also can be misleading when the test statistics are correlated. We propose that such estimates be conditioned on a simple measure of the spread of the observed histogram, and we provide a method for obtaining conditional significance levels. We justify this conditioning using the conditionality principle described by Cox and Hinkley (1974). Application of the method to gene expression data illustrates the circumstances when conditional significance levels are needed. PMID:18089626

Shi, Jianxin; Levinson, Douglas F; Whittemore, Alice S

2008-07-01

23

Test for the statistical significance of differences between ROC curves  

International Nuclear Information System (INIS)

A test for the statistical significance of observed differences between two measured Receiver Operating Characteristic (ROC) curves has been designed and evaluated. The set of observer response data for each ROC curve is assumed to be independent and to arise from a ROC curve having a form which, in the absence of statistical fluctuations in the response data, graphs as a straight line on double normal-deviate axes. To test the significance of an apparent difference between two measured ROC curves, maximum likelihood estimates of the two parameters of each curve and the associated parameter variances and covariance are calculated from the corresponding set of observer response data. An approximate Chi-square statistic with two degrees of freedom is then constructed from the differences between the parameters estimated for each ROC curve and from the variances and covariances of these estimates. This statistic is known to be truly Chi-square distributed only in the limit of large numbers of trials in the observer performance experiments. Performance of the statistic for data arising from a limited number of experimental trials was evaluated. Independent sets of rating scale data arising from the same underlying ROC curve were paired, and the fraction of differences found (falsely) significant was compared to the significance level, ?, used with the test. Although test performance was found to be somewhat dependent on both the number of trials in the data and the positumber of trials in the data and the position of the underlying ROC curve in the ROC space, the results for various significance levels showed the test to be reliable under practical experimental conditions

24

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

25

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.)

26

Dose-Response Calculator for ArcGIS  

Science.gov (United States)

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

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

2011-01-01

27

Statistical significance and extremal ensemble of gapped local hybrid alignment  

Science.gov (United States)

A "semi-probabilistic" alignment algorithm which combines ideas from Smith-Waterman and probabilistic alignment is proposed and studied in detail. It is predicted that the score statistics of this "hybrid" algorithm is of the universal Gumbel form, with the key Gumbel parameter ? taking on a fixed asymptotic value for a wide variety of scoring parameters. We have also characterized the "extrema l ensemble", i.e., the collection of sequence pairs exhibiting similarities that a given scoring system is most sensitive to. Based on this extremal ensemble, a simple recipe for the computation of the "relative entropy", and from it the correction to ? due to finite sequence length is also given. This allows us to assign p-values to the alignment results for arbitrary scoring parameters and gap costs. The predictions compare w ell with direct numerical simulations for a broad range of sequence lengths with various choices of the substitution scores and affine gap parameters. Key words: sequence alignment; statistical significance; maximum likelihood; hidden Markov model

Yu, Yi-Kuo; Bundschuh, Ralf; Hwa, Terence

28

Computer Simulation of Quantal Dose-Response Relationships.  

Science.gov (United States)

Describes a program which simulates animal pharmacology experiments involving "all-or-none" responses. Use of the Applesoft BASIC program in the pharmacology teaching laboratory provides students with a rapid and economical way to gain experience in the design and statistical analysis of quantal dose-response experiments. Information on obtaining…

McGilliard, Kip L.

1985-01-01

29

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2012-12-01

30

Learning from positive and unlabeled examples by enforcing statistical significance  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Given a finite but large set of objects de- scribed by a vector of features, only a small subset of which have been labeled as ‘positive’ with respect to a class of interest, we consider the problem of characterizing the positive class. We formalize this as the problem of learning a feature based score function that minimizes the p-value of a non parametric statistical hypothesis test. For lin- ear score functions over the original feature space or over one of its kernelized versions, we ...

Geurts, Pierre

2011-01-01

31

Dose/response relationships and policy formulation  

International Nuclear Information System (INIS)

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

32

A New Method for Synthesizing Radiation Dose-Response Data From Multiple Trials Applied to Prostate Cancer  

International Nuclear Information System (INIS)

Purpose: A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high). Methods and Materials: Nine published prostate cancer dose escalation studies including 6,539 patients were identified in the MEDLINE and CINAHL databases and reviewed to assess the relationship between dose and biochemical control. A novel method of analysis is presented in which the normalized dose-response gradient, ?50, is estimated for each study and subsequently synthesized across studies. Our method does not assume that biochemical control rates are directly comparable between studies. Results: Nonrandomized studies produced a statistically significantly higher ?50 than randomized studies for intermediate- to high-risk patients (?50 = 1.63 vs. ?50 = 0.93, p = 0.03) and a borderline significantly higher (?50 = 1.78 vs. ?50 = 0.56, p = 0.08) for low-risk patients. No statistically significant difference in ?50 was found between low- and intermediate- to high-risk patients (p = 0.31). From the pooled data of low and intermediate- to high-risk patients in randomized trials, we obtain the overall best estimate of ?50 = 0.84 with 95% confidence interval 0.54-1.15. Conclusions: Nonrandomized studies overestimate the steepness of the dose-response curve as comparethe dose-response curve as compared with randomized trials. This is probably the result of stage migration, improved treatment techniques, and a shorter follow-up in higher dose patients that were typically entered more recently. This overestimation leads to inflated expectations regarding the benefit from dose-escalation and could lead to underpowered clinical trials. There is no evidence of a steeper dose response for intermediate- to high-risk compared with low-risk patients.

33

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.

34

Experimental data and dose-response models  

International Nuclear Information System (INIS)

Dose-response relationships for radiation carcinogenesis have been of interest to biologists, modelers, and statisticians for many years. Despite his interest there are few instances in which there are sufficient experimental data to allow the fitting of various dose-response models. In those experimental systems for which data are available the dose-response curves for tumor induction for the various systems cannot be described by a single model. Dose-response models which have been observed following acute exposures to gamma rays include threshold, quadratic, and linear models. Data on sex, age, and environmental influences of dose suggest a strong role of host factors on the dose response. With decreasing dose rate the effectiveness of gamma ray irradiation tends to decrease in essentially every instance. In those cases in which the high dose rate dose response could be described by a quadratic model, the effect of dose rate is consistent with predictions based on radiation effects on the induction of initial events. Whether the underlying reasons for the observed dose-rate effect is a result of effects on the induction of initial events or is due to effects on the subsequent steps in the carcinogenic process is unknown. Information on the dose response for tumor induction for high LET (linear energy transfer) radiations such as neutrons is even more limited. The observed dose and dose rate data for tumor induction following neutron exposure are complex and do not g neutron exposure are complex and do not appear to be consistent with predictions based on models for the induction of initial events

35

Dose Response Model of Biological Reaction to Low Dose Rate Gamma Radiation  

International Nuclear Information System (INIS)

It is necessary to use reproducible and stable indicators to evaluate biological responses to long term irradiation at low dose-rate. They should be simple and quantitative enough to produce the results statistically accurate, because we have to analyze the subtle changes of biological responses around background level at low dose. For these purposes we chose micronucleus formation of U2OS, a human osteosarcoma cell line, as indicators of biological responses. Cells were exposed to gamma ray in irradiation rom bearing 50,000 Ci 60Co. After irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide, respectively. the number of binuclear cells bearing micronuclei was counted under a fluorescence microscope. Dose rate in the irradiation room was measured with PLD. Dose response of PLD is linear between 1 mGy to 10 Gy, and standard deviation of triplicate count was several percent of mean value. We fitted statistically dose response curves to the data, and they were plotted on the coordinate of linearly scale response and dose. The results followed to the straight line passing through the origin of the coordinate axes between 0.1-5 Gy, and dose and does rate effectiveness factor (DDREF) was less than 2 when cells were irradiated for 1-10 min. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose above 0.1 Gy when 5,000 binuclear cells were analyzed. In contrast, dose response curves never followed LNT, when cells were irradiated for 7 to 124 days. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose below 6 Gy, when cells were continuously irradiated for 124 days. These results suggest that dose response curve of biological reaction is remarkably affected by exposure time, and that dose rate effect changes as a function of dose-rate and irradiation time. Many epidemiological and experimental studies have been demonstrated that biological responses to radiation at low dose/low dose rate does not follow LNT. Our study supports their observations with sufficient statistical power. Threshold of radiation risk will be discussed. (Author)

36

Bayesian multimodel inference for dose-response studies  

Science.gov (United States)

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

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

2007-01-01

37

Analytical modelling of regional radiotherapy dose response of lung  

Science.gov (United States)

Knowledge of the dose-response of radiation-induced lung disease (RILD) is necessary for optimization of radiotherapy (RT) treatment plans involving thoracic cavity irradiation. This study models the time-dependent relationship between local radiation dose and post-treatment lung tissue damage measured by computed tomography (CT) imaging. Fifty-eight follow-up diagnostic CT scans from 21 non-small-cell lung cancer patients were examined. The extent of RILD was segmented on the follow-up CT images based on the increase of physical density relative to the pre-treatment CT image. The segmented RILD was locally correlated with dose distribution calculated by analytical anisotropic algorithm and the Monte Carlo method to generate the corresponding dose-response curves. The Lyman-Kutcher-Burman (LKB) model was fit to the dose-response curves at six post-RT time periods, and temporal change in the LKB parameters was recorded. In this study, we observed significant correlation between the probability of lung tissue damage and the local dose for 96% of the follow-up studies. Dose-injury correlation at the first three months after RT was significantly different from later follow-up periods in terms of steepness and threshold dose as estimated from the LKB model. Dependence of dose response on superior-inferior tumour position was also observed. The time-dependent analytical modelling of RILD might provide better understanding of the long-term behaviour of the disease and could potentially be applied to improve inverse treatment planning optimization.

Lee, Sangkyu; Stroian, Gabriela; Kopek, Neil; AlBahhar, Mahmood; Seuntjens, Jan; El Naqa, Issam

2012-06-01

38

Analytical modelling of regional radiotherapy dose response of lung  

International Nuclear Information System (INIS)

Knowledge of the dose–response of radiation-induced lung disease (RILD) is necessary for optimization of radiotherapy (RT) treatment plans involving thoracic cavity irradiation. This study models the time-dependent relationship between local radiation dose and post-treatment lung tissue damage measured by computed tomography (CT) imaging. Fifty-eight follow-up diagnostic CT scans from 21 non-small-cell lung cancer patients were examined. The extent of RILD was segmented on the follow-up CT images based on the increase of physical density relative to the pre-treatment CT image. The segmented RILD was locally correlated with dose distribution calculated by analytical anisotropic algorithm and the Monte Carlo method to generate the corresponding dose–response curves. The Lyman–Kutcher–Burman (LKB) model was fit to the dose–response curves at six post-RT time periods, and temporal change in the LKB parameters was recorded. In this study, we observed significant correlation between the probability of lung tissue damage and the local dose for 96% of the follow-up studies. Dose–injury correlation at the first three months after RT was significantly different from later follow-up periods in terms of steepness and threshold dose as estimated from the LKB model. Dependence of dose response on superior–inferior tumour position was also observed. The time-dependent analytical modelling of RILD might provide better understanding of the long-term behaviour of the diseg-term behaviour of the disease and could potentially be applied to improve inverse treatment planning optimization. (paper)

39

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.

Hayek Lee-Ann C.

2005-01-01

40

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.)

 
 
 
 
41

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

42

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

43

Induction of formaldehyde contact sensitivity : dose response relationship in the guinea pig maximization test  

DEFF Research Database (Denmark)

The sensitizing potential of aqueous formaldehyde was evaluated with the guinea pig maximization test (GPMT) in two laboratories (Copenhagen and Stockholm) using different guinea pig strains. Six intradermal (0.01%-3%), and 6 topical (0.5%-20%) concentrations were used for induction, and formaldehyde 1% and 0.1% was used for challenge. The incidence of contact sensitivity depended on the intradermal, but not on the topical induction dose. Statistical analyses showed a non-monotonous (non-linear) dose response relationship. The estimated maximal sensitization rate in Copenhagen was 80% after intradermal induction with 0.65% formaldehyde; in Stockholm it was 84% after induction with 0.34%. The data from the two laboratories could be described by parallel displaced dose response curves suggesting that the guinea pig strain used in Stockholm was significantly more susceptible to formaldehyde than the strain used in Copenhagen. The EC50 (formaldehyde concentration at which 50% of the guinea pigs were sensitized) at the 72 h scoring and a 1% challenge concentration, was 0.061% in Copenhagen and 0.024% in Stockholm.

Andersen, Klaus Ejner; Boman, A

1985-01-01

44

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)

45

Dose-response relations from epidemiological studies  

Energy Technology Data Exchange (ETDEWEB)

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.

Acheson, E.D.; Gardner, M.J. (Southampton General Hospital (UK))

1981-04-30

46

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

47

TESS-based dose-response using pediatric clonidine exposures  

International Nuclear Information System (INIS)

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

48

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

49

Dose-response curves and cell killing  

International Nuclear Information System (INIS)

In the literature on dose-response curves (drc) for radiation-induced cancer, it is customary to include an exponential term to describe the downturn of drcs at high doses. This term is supposed to describe the effect of cell killing on the frequency of radiation-induced cancers. A closer look at the point estimates, which are fit by mathematical models, reveals that most authors plot frequency estimates without considerations of time since exposure and of competing risks. The authors suggest plots of the estimated frequency of tumor appearance corrected for independent competing risks at a fixed and equal time since exposure against dose to correct these short comings and demonstrate with several examples (e.g. /sup 239/Pu in beagles and /sup 226/Ra in man) the disappearance of the downtrend in such plots. Application of Ockham's razor suggests, therefore, the abandonment of the cell killing hypothesis as the complete explanation of the downturn

50

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

51

An Efficient Resampling Method for Assessing Genome-Wide Statistical Significance in Mapping Quantitative Trait Loci  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Assessing genome-wide statistical significance is an important and difficult problem in multipoint linkage analysis. Due to multiple tests on the same genome, the usual pointwise significance level based on the chi-square approximation is inappropriate. Permutation is widely used to determine genome-wide significance. Theoretical approximations are available for simple experimental crosses. In this article, we propose a resampling procedure to assess the significance of genome-wide QTL mappin...

Zou, Fei; Fine, Jason P.; Hu, Jianhua; Lin, D. Y.

2004-01-01

52

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

DEFF Research Database (Denmark)

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

Larsen, Thomas Schou; Krogh, Anders Stærmose

2003-01-01

53

Selection of statistical significance test according to the distribution of the visual evaluation in diagnostic imaging  

International Nuclear Information System (INIS)

We examined how to select the method of statistical significance test as to the evaluation obtained by diagnostic imaging. We used 6-10 pairs of small data, and classified the distribution style using skewness and kurtosis. In statistical significance test, we used the paired t-test as a parametric test, and the Wilcoxon test as a non-parametric test. We tried to select the method of the statistical significance test in consideration of the power of test in each distribution style. The result of the X2 test, which is a test of normalization, there was no significance. In the case the paired t-test may be adecuate, considering the power of test, we should use the Wilcoxon test, in case that the both bottoms spread or the right bottom spreads. (author)

54

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)

55

Testing the statistical significance of microsimulation results: Often easier than you think ; a technical note  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In the microsimulation literature, it is still uncommon to test the statistical significance of results. In this paper we argue that this situation is both undesirable and unnecessary. Provided the parameters used in the microsimulation are exogenous, as is often the case in static microsimulation of the first-order effects of policy changes, simple statistical tests can be sufficient. Moreover, standard routines have been developed which enable applied researchers to calculate the sampling v...

Goedeme?, Tim; Den Bosch, Karel; Salanauskaite, Lina; Verbis, Gerlinde

2013-01-01

56

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

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

57

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

Directory of Open Access Journals (Sweden)

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

FionaFidler

2010-07-01

58

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

Science.gov (United States)

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

Kieffer, Kevin M.; Thompson, Bruce

59

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

Science.gov (United States)

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

Deegear, James

60

Quantification of Hormesis in Anticancer-Agent Dose-Responses  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

 
 
 
 
61

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

62

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

63

Characterization of the bronchodilatory dose response to indacaterol in patients with chronic obstructive pulmonary disease using model-based approaches  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Indacaterol is a once-daily long-acting inhaled ?2-agonist indicated for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD. The large inter-patient and inter-study variability in forced expiratory volume in 1 second (FEV1 with bronchodilators makes determination of optimal doses difficult in conventional dose-ranging studies. We considered alternative methods of analysis. Methods We utilized a novel modelling approach to provide a robust analysis of the bronchodilatory dose response to indacaterol. This involved pooled analysis of study-level data to characterize the bronchodilatory dose response, and nonlinear mixed-effects analysis of patient-level data to characterize the impact of baseline covariates. Results The study-level analysis pooled summary statistics for each steady-state visit in 11 placebo-controlled studies. These study-level summaries encompassed data from 7476 patients at indacaterol doses of 18.75-600 ?g once daily, and showed that doses of 75 ?g and above achieved clinically important improvements in predicted trough FEV1 response. Indacaterol 75 ?g achieved 74% of the maximum effect on trough FEV1, and exceeded the midpoint of the 100-140 mL range that represents the minimal clinically important difference (MCID; ?120 mL vs placebo, with a 90% probability that the mean improvement vs placebo exceeded the MCID. Indacaterol 150 ?g achieved 85% of the model-predicted maximum effect on trough FEV1 and was numerically superior to all comparators (99.9% probability of exceeding MCID. Indacaterol 300 ?g was the lowest dose that achieved the model-predicted maximum trough response. The patient-level analysis included data from 1835 patients from two dose-ranging studies of indacaterol 18.75-600 ?g once daily. This analysis provided a characterization of dose response consistent with the study-level analysis, and demonstrated that disease severity, as captured by baseline FEV1, significantly affects the dose response, indicating that patients with more severe COPD require higher doses to achieve optimal bronchodilation. Conclusions Comprehensive assessment of the bronchodilatory dose response of indacaterol in COPD patients provided a robust confirmation that 75 ?g is the minimum effective dose, and that 150 and 300 ?g are expected to provide optimal bronchodilation, particularly in patients with severe disease.

Lawrence David

2011-04-01

64

Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis.  

Science.gov (United States)

The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transformation frequency. J-shaped dose response curves have been captured with consideration of cell cycle checkpoint control mechanisms. The simulation results indicate the shape of the dose response curve relates to the behavior of the saddle-node points of the model in the bifurcation diagram. A simplified version of the model in previous work of the authors was used mathematically to analyze behaviors relating to the saddle-node points for the J-shaped dose response curve. It indicates that low-linear energy transfer (LET) is more likely to have a J-shaped dose response curve. This result emphasizes the significance of systems biology approach, which encourages collaboration of multidiscipline of biologists, toxicologists and mathematicians, to illustrate complex cancer-related events, and confirm the biphasic dose-response at low doses. PMID:23983661

Lou, In Chio; Zhao, Yuchao; Wu, Yingjie; Ricci, Paolo F

2012-01-01

65

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

66

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)

67

Statistical significance of clusters of motifs represented by position specific scoring matrices in nucleotide sequences.  

Science.gov (United States)

The human genome encodes the transcriptional control of its genes in clusters of cis-elements that constitute enhancers, silencers and promoter signals. The sequence motifs of individual cis- elements are usually too short and degenerate for confident detection. In most cases, the requirements for organization of cis-elements within these clusters are poorly understood. Therefore, we have developed a general method to detect local concentrations of cis-element motifs, using predetermined matrix representations of the cis-elements, and calculate the statistical significance of these motif clusters. The statistical significance calculation is highly accurate not only for idealized, pseudorandom DNA, but also for real human DNA. We use our method 'cluster of motifs E-value tool' (COMET) to make novel predictions concerning the regulation of genes by transcription factors associated with muscle. COMET performs comparably with two alternative state-of-the-art techniques, which are more complex and lack E-value calculations. Our statistical method enables us to clarify the major bottleneck in the hard problem of detecting cis-regulatory regions, which is that many known enhancers do not contain very significant clusters of the motif types that we search for. Thus, discovery of additional signals that belong to these regulatory regions will be the key to future progress. PMID:12136103

Frith, Martin C; Spouge, John L; Hansen, Ulla; Weng, Zhiping

2002-07-15

68

On determining the statistical significance of discontinuities within ordered ecological data  

International Nuclear Information System (INIS)

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

69

Dose-response analyses using restricted cubic spline functions in public health research.  

Science.gov (United States)

Taking into account a continuous exposure in regression models by using categorization, when non-linear dose-response associations are expected, have been widely criticized. As one alternative, restricted cubic spline (RCS) functions are powerful tools (i) to characterize a dose-response association between a continuous exposure and an outcome, (ii) to visually and/or statistically check the assumption of linearity of the association, and (iii) to minimize residual confounding when adjusting for a continuous exposure. Because their implementation with SAS® software is limited, we developed and present here an SAS macro that (i) creates an RCS function of continuous exposures, (ii) displays graphs showing the dose-response association with 95 per cent confidence interval between one main continuous exposure and an outcome when performing linear, logistic, or Cox models, as well as linear and logistic-generalized estimating equations, and (iii) provides statistical tests for overall and non-linear associations. We illustrate the SAS macro using the third National Health and Nutrition Examination Survey data to investigate adjusted dose-response associations (with different models) between calcium intake and bone mineral density (linear regression), folate intake and hyperhomocysteinemia (logistic regression), and serum high-density lipoprotein cholesterol and cardiovascular mortality (Cox model). PMID:20087875

Desquilbet, Loic; Mariotti, François

2010-04-30

70

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

Science.gov (United States)

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

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

2013-01-01

71

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

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

Poleksic Aleksandar

2009-04-01

72

Temporal analysis of a dose-response relationship leukemia mortality in atomic bomb survivors  

International Nuclear Information System (INIS)

A data analysis, which incorporates time dependencies, is demonstrated for the dose response of leukemia mortality in the atomic bomb survivors. The time dependencies are initially left unspecified and the data are used to infer them. Two principal findings based on the T65 revised dose estimates are obtained. First, it is shown that the fits to the data of constant risk L-Q-L, L-L, and Q-L dose-response models are significantly improved (p < .001) by using time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to gamma irradiation decreases in time at an exponential-like rate, while the increased risk due to neutron exposure changes very little, if at all, in time. Consequently, the relative biological effectiveness of neutrons is shown to increase in time (p = .002). Finally, it is conjectured that these findings will remain valid with a reappraisal of dosimetry. (author)

73

Dose-response relationship for prophylactic cranial irradiation in small cell lung cancer  

International Nuclear Information System (INIS)

Purpose: To determine the dose-response relationship for prophylactic cranial irradiation (PCI) in small cell lung cancer, to quantify the growth kinetics of subclinical metastases, and to determine the influence of time-delay in initiating PCI on its utility. Methods and Materials: Published reports of brain relapse rates in small cell lung cancer with and without PCI were collected. The reduction in brain relapse rate as a function of radiation dose was analyzed. The time interval between treatment of the primary tumor and the initiation of PCI was analyzed as a factor potentially influencing dose-response. Results: A shallow dose-response curve without any threshold in the dose intercept was demonstrated for control of subclinical brain metastases in 'early PCI' (delay between initiation of treatment for primary tumor and PCI less than 60 days). By contrast 'late PCI' (delay over 60 days) was associated with a significant displacement of the dose intercept. Doses over 30-35 Gy in 2-Gy fractions did not result in a further reduction in brain relapse rate, but there were too few high-dose studies to draw any definite conclusion. Conclusions: The nearly linear dose-response relationship for reduction in brain relapses demonstrated for 'early PCI' in the range of doses from zero up to 35 Gy given in 2-Gy fractions supports the model of a fairly logarithmically uniform distribution of metastatic cell number within a series of patients. When PCI is delayed, a significant threshold in dose-response was observed, consistent with a fast growth rate of untreated subclinical brain metastases from small cell lung cancer. The exact shape and locations of dose-response curves is not well established by this retrospective analysis of diverse data. A high probability of eliminating brain relapses following PCI requires a dose of about 30-35 Gy in 2-Gy fractions. Control rates in brain can be enhanced if PCI is applied early

74

Defining a dose-response relationship with radiotherapy for prostate cancer: is more really better?  

International Nuclear Information System (INIS)

Purpose: Data were reviewed addressing the association between radiation therapy (RT) dose and treatment outcome for localized prostate cancer to help clarify the existence of a potential dose-response relationship. Methods and Materials: Articles were identified through the MEDLINE database, CancerLit database, and reference lists of relevant articles. Studies were categorized into four groups based upon the endpoint analyzed, including biochemical control (BC), local control (LC), pathologic control (PC), and cause-specific survival (CSS). The impact of increasing RT dose with each endpoint was recorded. Results: Twenty-two trials involving a total of 11,297 patients were identified. Of the 11 trials addressing the association of RT dose with LC, 9 showed statistically significant improvements. Of the 12 trials that reported BC with RT dose, all showed statistically significant improvements. Two out of 4 studies analyzing PC with increasing dose showed a positive correlation. Finally, 3 out of 9 studies addressing RT dose with CSS showed statistically significant improvements. Despite inconclusive results, patients with poor risk features (e.g., prostate-specific antigen [PSA] ?10, Gleason score [GS] ?7, or tumor stage ?T2b) were most likely to benefit from increasing dose with respect to each endpoint. However, the optimal RT dose and the magnitude of benefit of dose escalation could not be identified. Conclusions: Although RT dose appears to correlate with v RT dose appears to correlate with various measures of treatment outcome, objective, high-quality data addressing this critical issue are still lacking. At the present time, the absolute improvement in outcome due to dose escalation, the subset of patients benefiting most, and the optimal dose remain to be defined

75

A method to evaluate hormesis in nanoparticle dose-responses.  

Science.gov (United States)

The term hormesis describes a dose-response relationship that is characterized by a response that is opposite above and below the toxicological or pharmacological threshold. Previous reports have shown that this relationship is ubiquitous in the response of pharmaceuticals, metals, organic chemicals, radiation, and physical stressor agents. Recent reports have also indicated that certain nanoparticles (NPs) may also exhibit a hormetic dose-response. We describe the application of three previously described methods to quantify the magnitude of the hormetic biphasic dose-responses in nanotoxicology studies. This methodology is useful in screening assays that attempt to parse the observed toxicological dose-response data into categories based on the magnitude of hormesis in the evaluation of NPs. For example, these methods may be used to quickly identify NP induced hormetic responses that are either desirably enhanced (e.g., neuronal cell viability) or undesirably stimulated (e.g., low dose stimulation of tumor cells). PMID:22942868

Nascarella, Marc A; Calabrese, Edward J

2012-01-01

76

A Method to Evaluate Hormesis in Nanoparticle Dose-Responses  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The term hormesis describes a dose-response relationship that is characterized by a response that is opposite above and below the toxicological or pharmacological threshold. Previous reports have shown that this relationship is ubiquitous in the response of pharmaceuticals, metals, organic chemicals, radiation, and physical stressor agents. Recent reports have also indicated that certain nanoparticles (NPs) may also exhibit a hormetic dose-response. We describe the application of three previo...

Nascarella, Marc A.; Calabrese, Edward J.

2012-01-01

77

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

International Nuclear Information System (INIS)

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

78

Immunomodulating potential of supplementation with probiotics : a dose-response study in healthy young adults  

DEFF Research Database (Denmark)

Certain probiotic microorganisms have been found beneficial in the treatment of immune-related diseases and may also affect immune function in healthy people. Intervention studies of probiotics in healthy humans are urgently required. Here, the immunomodulating potential of Bifidobacterium animalis ssp. lactis (BB-12) and Lactobacillus paracasei ssp. paracasei (CRL-431) was studied in a double-blind placebo-controlled parallel dose-response trial (n=71) based on five randomly assigned groups of young healthy adults supplemented for 3 weeks with 0, 10(8), 10(9), 10(10) and 10(11) CFU day(-1), respectively, of a mixture of BB-12 and CRL-431. No statistically significant dose-dependent effect was found for phagocytic activity in blood leukocytes, fecal immunoglobulin A (IgA) concentrations or production of interferon-gamma and interleukin-10 in blood cells. When evaluating data according to the amount of viable BB-12 recovered from faeces, the interferon-gamma production in blood cells was significantly reduced.In conclusion, no solid effect on the immune function of young healthy adults supplemented with even high doses of B. animalis ssp. lactis BB-12 and L. paracasei ssp. paracasei CRL-431 was demonstrated in this study.

Christensen, Hanne Risager; Rosholm, Lisbeth Buus

2006-01-01

79

Cumulative lognormal distributions of dose-response vs. dose distributions  

International Nuclear Information System (INIS)

A review of the author's findings over four decades will show that the lognormal probability density function can be fit to many types of positive-variate radiation measurement and response data. The cumulative lognormal plot on probability vs. logarithmic coordinate graph paper can be shown to be useful in comparing trends in exposure distributions or responses under differing conditions or experimental parameters. For variates that can take on only positive values, such a model is more natural than the 'normal' (Gaussian) model. Such modeling can also be helpful in elucidating underlying mechanisms that cause the observed data distributions. It is important, however, to differentiate between the cumulative plot of a dose distribution, in which successive percentages of data are not statistically independent, and the plots of dose-response data for which independent groups of animals or persons are irradiated or observed for selected doses or dose intervals. While independent response points can often be best fitted by appropriate regression methods, the density functions for cumulative dose or concentration distributions must be fit by particular maximum likelihood estimates from the data. Also, as indicated in the texts by D.J. Finney and by R.O. Gilbert, for example, a simple plot of such data on available probability (or probit) vs. log scale graph paper will quickly show whether an adequate representation of the data is a lognormal function. Processes that naturally generate lognormal variates are sometimes estimated by statistics that follow the lognormal straight line for a cumulative plot on a probability vs. log scale; on the other hand, sometimes the statistics of interpretation follow such a line only over a certain range. Reported examples of lognormal occupational exposure distributions include those in some facilities in which roundoff biases were removed for some years. However, for a number of exposure distributions at licensed facilities in the United States, the cumulative exposure distributions curved upward above about 1 rem, showing the pressure of the 5 rem limit in constraining the natural' distribution of occupational exposure. The United Nations Scientific Committee (UNSCEAR) adopted this type of display in some of its reports. Kumazawa and associates (1981, 1982) fitted some of these distributions by a function named 'the hybrid lognormal', which has been used to describe exposure distributions in Canada (Sont and Ashmore 1988). Examples of the suitability of the lognormal dose-response function for animal data on lethality and carcinogenesis have been reported earlier by the author. In 1998, the close representation of a lognormal fit to the excess absolute mortality from solid cancers was reported by the author for the Hiroshima-Hagasaki cohorts reported by UNSCEAR. The close representation of a two-stage model of carcinogenesis by families of lognormal functions has also been reported. In 1999, the author showed that the deviation (in the low range) from lognormality of plutonium in urine measured by fission track analysis can be explained as the result of convoluting observed lognormal human sample data with the randomly varying and also lognormally distributed tracks of the subtracted reagent blanks. The sum or difference of two lognormally distributed variates is not lognormal; yet, in the higher range of interpreted plutonium activity in urine samples - well above the range of variation of the blanks - the 'true' lognormality of excreted plutonium can be exhibited. Thus, reasons for the departure from an actual lognormal distribution of a fundamental quantity of interest can often be explained by examining the actual measurements and calculations leading to the interpreted results. A sample of these phenomena, as observed by the author, are presented and discussed in this paper. (author)

80

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

Science.gov (United States)

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

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

2013-01-01

 
 
 
 
81

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

82

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

83

A network-based method to assess the statistical significance of mild co-regulation effects.  

Science.gov (United States)

Recent development of high-throughput, multiplexing technology has initiated projects that systematically investigate interactions between two types of components in biological networks, for instance transcription factors and promoter sequences, or microRNAs (miRNAs) and mRNAs. In terms of network biology, such screening approaches primarily attempt to elucidate relations between biological components of two distinct types, which can be represented as edges between nodes in a bipartite graph. However, it is often desirable not only to determine regulatory relationships between nodes of different types, but also to understand the connection patterns of nodes of the same type. Especially interesting is the co-occurrence of two nodes of the same type, i.e., the number of their common neighbours, which current high-throughput screening analysis fails to address. The co-occurrence gives the number of circumstances under which both of the biological components are influenced in the same way. Here we present SICORE, a novel network-based method to detect pairs of nodes with a statistically significant co-occurrence. We first show the stability of the proposed method on artificial data sets: when randomly adding and deleting observations we obtain reliable results even with noise exceeding the expected level in large-scale experiments. Subsequently, we illustrate the viability of the method based on the analysis of a proteomic screening data set to reveal regulatory patterns of human microRNAs targeting proteins in the EGFR-driven cell cycle signalling system. Since statistically significant co-occurrence may indicate functional synergy and the mechanisms underlying canalization, and thus hold promise in drug target identification and therapeutic development, we provide a platform-independent implementation of SICORE with a graphical user interface as a novel tool in the arsenal of high-throughput screening analysis. PMID:24039936

Horvát, Em?ke-Ágnes; Zhang, Jitao David; Uhlmann, Stefan; Sahin, Özgür; Zweig, Katharina Anna

2013-01-01

84

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

International Nuclear Information System (INIS)

Purpose: In this era of dose escalation, the benefit of higher radiation doses for low-risk prostate cancer remains controversial. For intermediate-risk patients, the data suggest a benefit from higher doses. However, the quantitative characterization of the benefit for these patients is scarce. We investigated the radiation dose-response relation of tumor control probability in low-risk and intermediate-risk prostate cancer patients treated with radiotherapy alone. We also investigated the differences in the dose-response characteristics using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition vs. an alternative biochemical failure definition. Methods and materials: This study included 235 low-risk and 387 intermediate-risk prostate cancer patients treated with external beam radiotherapy without hormonal treatment between 1987 and 1998. The low-risk patients had 1992 American Joint Committee on Cancer Stage T2a or less disease as determined by digital rectal examination, prostate-specific antigen (PSA) levels of ?10 ng/mL, and biopsy Gleason scores of ?6. The intermediate-risk patients had one or more of the following: Stage T2b-c, PSA level of ?20 ng/mL but >10 ng/mL, and/or Gleason score of 7, without any of the following high-risk features: Stage T3 or greater, PSA >20 ng/mL, or Gleason score ?8. The logistic models were fitted to the data at varying points after treatment, and the dose-response parameters were estimated. We used two biochemical failure definitions. The ASTRO PSA failure was defined as three consecutive PSA rises, with the time to failure backdated to the mid-point between the nadir and the first rise. The second biochemical failure definition used was a PSA rise of ?2 ng/mL above the current PSA nadir (CN + 2). The failure date was defined as the time at which the event occurred. Local, nodal, and distant relapses and the use of salvage hormonal therapy were also failures. Results: On the basis of the ASTRO definition, at 5 years after radiotherapy, the dose required for 50% tumor control (TCD50) for low-risk patients was 57.3 Gy (95% confidence interval [CI], 47.6-67.0). The ?50 was 1.4 (95% CI, -0.1 to 2.9) around 57 Gy. A statistically significant dose-response relation was found using the ASTRO definition. However, no dose-response relation was noted using the CN + 2 definition for these low-risk patients. For the intermediate-risk patients, using the ASTRO definition, the TCD50 was 67.5 Gy (95% CI, 65.5-69.5) Gy and the ?50 was 2.2 (95% CI, 1.1-3.2) around TCD50. Using the CN + 2 definition, the TCD50 was 57.8 Gy (95% CI, 49.8-65.9) and the ?50 was 1.4 (95% CI, 0.2-2.5). Recursive partitioning analysis identified two subgroups within the low-risk group, as well as the intermediate-risk group: PSA level 78 Gy for these patients. A dose-response relation was noted for the intermediate-risk patients using either the CN + 2 or ASTRO definition. Most of the benefit from the higher doses also derived from the intermediate-risk patients with higher PSA levels. Some room for improvement appears to exist with additional dose increases in this group

85

COMPASS: a tool for comparison of multiple protein alignments with assessment of statistical significance.  

Science.gov (United States)

We present a novel method for the comparison of multiple protein alignments with assessment of statistical significance (COMPASS). The method derives numerical profiles from alignments, constructs optimal local profile-profile alignments and analytically estimates E-values for the detected similarities. The scoring system and E-value calculation are based on a generalization of the PSI-BLAST approach to profile-sequence comparison, which is adapted for the profile-profile case. Tested along with existing methods for profile-sequence (PSI-BLAST) and profile-profile (prof_sim) comparison, COMPASS shows increased abilities for sensitive and selective detection of remote sequence similarities, as well as improved quality of local alignments. The method allows prediction of relationships between protein families in the PFAM database beyond the range of conventional methods. Two predicted relations with high significance are similarities between various Rossmann-type folds and between various helix-turn-helix-containing families. The potential value of COMPASS for structure/function predictions is illustrated by the detection of an intricate homology between the DNA-binding domain of the CTF/NFI family and the MH1 domain of the Smad family. PMID:12547212

Sadreyev, Ruslan; Grishin, Nick

2003-02-01

86

Estimates of statistical significance for comparison of individual positions in multiple sequence alignments  

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Full Text Available Abstract Background Profile-based analysis of multiple sequence alignments (MSA allows for accurate comparison of protein families. Here, we address the problems of detecting statistically confident dissimilarities between (1 MSA position and a set of predicted residue frequencies, and (2 between two MSA positions. These problems are important for (i evaluation and optimization of methods predicting residue occurrence at protein positions; (ii detection of potentially misaligned regions in automatically produced alignments and their further refinement; and (iii detection of sites that determine functional or structural specificity in two related families. Results For problems (1 and (2, we propose analytical estimates of P-value and apply them to the detection of significant positional dissimilarities in various experimental situations. (a We compare structure-based predictions of residue propensities at a protein position to the actual residue frequencies in the MSA of homologs. (b We evaluate our method by the ability to detect erroneous position matches produced by an automatic sequence aligner. (c We compare MSA positions that correspond to residues aligned by automatic structure aligners. (d We compare MSA positions that are aligned by high-quality manual superposition of structures. Detected dissimilarities reveal shortcomings of the automatic methods for residue frequency prediction and alignment construction. For the high-quality structural alignments, the dissimilarities suggest sites of potential functional or structural importance. Conclusion The proposed computational method is of significant potential value for the analysis of protein families.

Sadreyev Ruslan I

2004-08-01

87

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

Energy Technology Data Exchange (ETDEWEB)

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{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 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.

Appelt, Ane L., E-mail: ane.lindegaard.appelt@slb.regionsyddanmark.dk [Department of Oncology, Vejle Hospital, Vejle (Denmark); University of Southern Denmark, Odense (Denmark); Ploen, John [Department of Oncology, Vejle Hospital, Vejle (Denmark); Vogelius, Ivan R. [Department of Radiation Oncology, Rigshospitalet, University of Copenhagen (Denmark); Bentzen, Soren M. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Jakobsen, Anders [Department of Oncology, Vejle Hospital, Vejle (Denmark); University of Southern Denmark, Odense (Denmark)

2013-01-01

88

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

89

Theory of thermoluminescence gamma dose response: The unified interaction model  

Energy Technology Data Exchange (ETDEWEB)

We describe the development of a comprehensive theory of thermoluminescence (TL) dose response, the unified interaction model (UNIM). The UNIM is based on both radiation absorption stage and recombination stage mechanisms and can describe dose response for heavy charged particles (in the framework of the extended track interaction model - ETIM) as well as for isotropically ionising gamma rays and electrons (in the framework of the TC/LC geminate recombination model) in a unified and self-consistent conceptual and mathematical formalism. A theory of optical absorption dose response is also incorporated in the UNIM to describe the radiation absorption stage. The UNIM is applied to the dose response supralinearity characteristics of LiF:Mg,Ti and is especially and uniquely successful in explaining the ionisation density dependence of the supralinearity of composite peak 5 in TLD-100. The UNIM is demonstrated to be capable of explaining either qualitatively or quantitatively all of the major features of TL dose response with many of the variable parameters of the model strongly constrained by ancilliary optical absorption and sensitisation measurements.

Horowitz, Y.S. E-mail: yigal@bgumail.bgu.ac.il

2001-09-01

90

Theory of thermoluminescence gamma dose response: The unified interaction model  

International Nuclear Information System (INIS)

We describe the development of a comprehensive theory of thermoluminescence (TL) dose response, the unified interaction model (UNIM). The UNIM is based on both radiation absorption stage and recombination stage mechanisms and can describe dose response for heavy charged particles (in the framework of the extended track interaction model - ETIM) as well as for isotropically ionising gamma rays and electrons (in the framework of the TC/LC geminate recombination model) in a unified and self-consistent conceptual and mathematical formalism. A theory of optical absorption dose response is also incorporated in the UNIM to describe the radiation absorption stage. The UNIM is applied to the dose response supralinearity characteristics of LiF:Mg,Ti and is especially and uniquely successful in explaining the ionisation density dependence of the supralinearity of composite peak 5 in TLD-100. The UNIM is demonstrated to be capable of explaining either qualitatively or quantitatively all of the major features of TL dose response with many of the variable parameters of the model strongly constrained by ancilliary optical absorption and sensitisation measurements

91

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

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Full Text Available Introduction: Toxoplasmosis is a zoonosis that represents a serious public health problem, caused by Toxoplasma gondii, which affects 20-90% of the world human population [1,2]. It is a serious problem especially when considering the congenital transmission due to congenital sequels. Treatment with highly diluted substances is one of the alternative/complementary medicines most employed in the world [3,4]. The current ethical rules regarding the number of animals used in animal experimental protocols with the use of more conservative statistical methods [5] can not enhance the biological effects of highly diluted substances observed by the experience of the researcher. Aim: To evaluate the minimum number of animals per group to achieve a significant difference among the groups of animals treated with biotherapic T. gondii and infected with the protozoan regarding the number of cysts observed in the brain. Material and methods: A blind randomized controlled trial was performed using eleven Swiss male mice, aged 57 days, divided into two groups: BIOT-200DH - treated with biotherapic (n=6 and CONTROL - treated with hydroalcoholic solution 7% (n=7.The animals of the group BIOT-200DH were treated for 3 consecutive days in a single dose 0.1ml/dose/day. The animals of BIOT – 200DH group were orally infected with 20 cysts of ME49-T. gondii. The animals of the control group were treated with cereal alcohol 7% (n=7 for 3 consecutive days and then were infected with 20 cysts of ME49 -T. gondii orally. The biotherapic 200DH T. gondii was prepared with homogenized mouse brain, with 20 cysts of T. gondii / 100μL according to the Brazilian Homeopathic Pharmacopoeia [6] in laminar flow. After 60 days post-infection the animals were killed in a chamber saturated with halothane, the brains were homogenized and resuspended in 1 ml of saline solution. Cysts were counted in 25 ml of this suspension, covered with a 24x24 mm coverglass, examined in its full length. This study was approved by the Ethics Committee for animal experimentation of the UEM - Protocol 036/2009. The data were compared using the tests Mann Whitney and Bootstrap [7] with the statistical software BioStat 5.0. Results and discussion: There was no significant difference when analyzed with the Mann-Whitney, even multiplying the "n" ten times (p=0.0618. The number of cysts observed in BIOT 200DH group was 4.5 ± 3.3 and 12.8 ± 9.7 in the CONTROL group. Table 1 shows the results obtained using the bootstrap analysis for each data changed from 2n until 2n+5, and their respective p-values. With the inclusion of more elements in the different groups, tested one by one, randomly, increasing gradually the samples, we observed the sample size needed to statistically confirm the results seen experimentally. Using 17 mice in group BIOT 200DH and 19 in the CONTROL group we have already observed statistical significance. This result suggests that experiments involving highly diluted substances and infection of mice with T. gondii should work with experimental groups with 17 animals at least. Despite the current and relevant ethical discussions about the number of animals used for experimental procedures the number of animals involved in each experiment must meet the characteristics of each item to be studied. In the case of experiments involving highly diluted substances, experimental animal models are still rudimentary and the biological effects observed appear to be also individualized, as described in literature for homeopathy [8]. The fact that the statistical significance was achieved by increasing the sample observed in this trial, tell us about a rare event, with a strong individual behavior, difficult to demonstrate in a result set, treated simply with a comparison of means or medians. Conclusion: Bootstrap seems to be an interesting methodology for the analysis of data obtained from experiments with highly diluted substances. Experiments involving highly diluted

Ana Lúcia Falavigna Guilherme

2011-09-01

92

Kinetic modeling of optical absorption dose response in TLD-100  

International Nuclear Information System (INIS)

Optical absorption (OA) dose response is modeled in the framework of a single electron-trapping-center (TC), single hole-luminescent-center (LC) and single electron-competitive-center (CC). It is demonstrated that the 'always-experimentally-observed' linear/exponentially saturating OA dose response arises if there is approximate equality (within an order of magnitude) of the dose filling constants and the total available trap density associated with the TC and CC, as is apparently the case in LiF:Mg,Ti (TLD-100) and other investigated TL materials. In principle, however, OA dose response supralinearity can occur if either of these are sufficiently dissimilar leading to early saturation of one of the electron trapping entities

93

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

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Full Text Available This paper illustrates the utility of multivariate statistical techniques for analysis and interpretation of water quality data sets and identification of pollution sources/factors with a view to get better information about the water quality and design of monitoring network for effective management of water resources. Multivariate statistical techniques, such as factor analysis (FA/principal component analysis (PCA and cluster analysis (CA, were applied for the evaluation of variations and for the interpretation of a water quality data set of the natural water bodies obtained during 2010 year of monitoring of 13 parameters at 33 different sites. FA/PCA attempts to explain the correlations between the observations in terms of the underlying factors, which are not directly observable. Factor analysis is applied to physico-chemical parameters of natural water bodies with the aim classification and data summation as well as segmentation of heterogeneous data sets into smaller homogeneous subsets. Factor loadings were categorized as strong and moderate corresponding to the absolute loading values of >0.75, 0.75-0.50, respectively. Four principal factors were obtained with Eigenvalues >1 summing more than 78 % of the total variance in the water data sets, which is adequate to give good prior information regarding data structure. Each factor that is significantly related to specific variables represents a different dimension of water quality. The first factor F1 accounting for 28 % of the total variance and represents the hydrochemical dimension of water quality. The second factor F2 accounting for 18% of the total variance and may be taken factor of water eutrophication. The third factor F3 accounting 17 % of the total variance and represents the influence of point sources of pollution on water quality. The fourth factor F4 accounting 13 % of the total variance and may be taken as an ecological dimension of water quality. Cluster analysis (CA is an objective technique to identify natural groupings in the set of data. CA divides a large number of objects into smaller number of homogenous groups on the basis of their correlation structure. CA combines the data objects together to form the natural groups involving objects with similar cluster properties and separates the objects with different cluster properties. CA showed similarities and dissimilarities among the sampling sites and explain the observed clustering in terms of affected conditions. Using FA/PCA and CA have been identified water bodies that are under the highest pressure. With regard to the factors identified water bodies are: for factor F1 (Plazovi?, Bosut, Studva, Zlatica, Stari Begej, Krivaja, for factor F2 (Krivaja, Kereš, for factor F3 (Studva, Zlatica, Tamiš, Krivaja i Kereš and for factor F4 (Studva, Zlatica, Krivaja, Kereš.

Vujovi? Svetlana R.

2013-01-01

94

Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition  

DEFF Research Database (Denmark)

BACKGROUND: In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. RESULTS: First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based methodfor assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological interpretations. CONCLUSION: Time independent summary statistics may aid the understanding of drugs' action mechanism on tumour cells and potentially renew previous drug sensitivity evaluation studies.

Falgreen, Steffen; Laursen, Maria Bach

2014-01-01

95

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

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

Helmut Kern

2012-06-01

96

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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, ...

Stern, J. M.

2010-01-01

97

Corresponding dose response of radiographic film with layered Gafchromic film  

International Nuclear Information System (INIS)

This note investigates the dose response of layered HS Gafchromic film compared to Kodak EDR-2 radiographic film. Using five layers of HS type Gafchromic film a dose response greater than EDR-2 film is achieved at the peak wavelength (0.55 OD/Gy versus 0.3 OD/Gy for EDR-2 film). Even over a broader waveband of 30 nm, which is similar to that found in ultra bright LED scanners, the response was found to be 0.38 OD/Gy as opposed to 0.29 OD/Gy. Measurements averaged over the entire visible spectrum produce a relative dose response of 0.165 OD/Gy for five layer HS and 0.29 OD/Gy for EDR-2 film. Due to this high dose response that is achievable, the five layer HS could be used in applications where small doses are delivered to certain areas and a low dependence of energy response is required for measurement. (note)

98

DOSE-RESPONSE ANALYSIS OF INGESTED BENZO[A]PYRENE  

Science.gov (United States)

This report represents the first part of the Office of Health and Environmental Assessment's dose-response analysis of polycyclic aromatic hydrocarbons (PAHs). Because of the tremendous amount of information bearing on approaches that can be developed to estimate risks from expos...

99

Dose-response relationship with radiotherapy: an evidence?  

International Nuclear Information System (INIS)

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

100

Dose response of squamous cell carcinomas of the upper respiratory and digestive tracts  

International Nuclear Information System (INIS)

Dose-response curves were computed for 5 tumour sites of the head and neck region, using 2 regression models. In agreement with clinical observation, a significant increase was found from moderate to high control rates with modest dose increases for exophytic tumours (T1 + T2 retromolar trigone-anterior faucial pillar and T2 + T3 supraglottic larynx). Further significant increases in local control after modest dose increases were not obtained when the control rate was already high and the slope of the dose-response curve consequently diminished. Despite unsatisfactory (50%) control rates for large heterogeneous tumours (T3 + T4 pharyngeal walls), further increases cannot be obtained without excessive doses because the curve flattens at the 50% control rate level. (author)

 
 
 
 
101

In vivo quantification of human lung dose response relationship  

Science.gov (United States)

Purpose: To implement a new non-invasive in-vivo assay to compute the dose-response relationship following radiation-induced injury to normal lung tissue, using computed tomography (CT) scans of the chest. Methods and Materials: Follow-up volumetric CT scans were acquired in patients with metastatic tumors to the lung treated using stereotactic radiation therapy. The images reveal a focal region of fibrosis corresponding to the high-dose region and no observable long-term damage in distant sites. For each pixel in the follow-up image the treatment dose and the change in apparent tissue density was compiled. For each of 12 pre-selected dose levels the average pixel tissue density change was computed and fit to a two-parameter dose-response model. The sensitivity of the resulting fits to registration error was also quantified. Results: Complete in vivo dose-response relationships in human normal lung tissue were computed. Increasing radiation sensitivity was found with larger treatment volume. Radiation sensitivity increased also over time up to 12 months, but decreased at later time points. The time-course of dose response correlated with the time-course of levels of circulating IL-1?, TGF? and MCP-1. The method was found to be robust to registration errors up to 3 mm. Conclusions: This approach for the first time enables the quantification of the full range dose response relationship in human subjects. The method may be used to assess quantitatively the efficacy of various agents thought to illicit radiation protection to the lung.

O'Dell, Walter; Wang, Peng; Liu, Haisong; Fuller, David; Schell, Michael C.; Okunieff, Paul

2007-03-01

102

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

103

Characteristics of dose-response relationships for late radiation effects  

International Nuclear Information System (INIS)

The dose-response characteristics were analysed for late skin telangiectasia in patients for 1, 2 and 5 fractions/week and 3-4 dose levels per schedule. Altogether 286 fields were used. Skin telangiectasia was scored on an arbitrary scale and dose-response analysis was performed at 10 year's follow-up for various degrees of telangiectasia, score >=1 to>=4. The following parameters were determined for each schedule and the equivalent single dose-response curves for each endpoint using probit analysis: the ED50, the absolute steepness, measured as the probit width, K, the relative steepness, K/ED50, and the normalised effect gradient, ?50. The inverse radiosensitivity, D0eff or D0, was estimated using the Poisson and LQ-models for tissue response. The ?/? value was found to be independent of the degree of telangiectasia used as endpoint. The absolute steepness of the dose-incidence curve increased with increasing dose per fraction when the dose-response curve was generated by a fixed dose per fraction, and was less than if generated by a fixed number of fractions. The relative steepness increased with higher degree of damage. D0eff decreased with increasing dose per fraction, and also with higher degree of telangiectasia. The highest steepness determined for telangiectasia score >=4 (partially confluent or more) at 10 years correspond to K=0.8 Gy, K/ED50=5 percent, ?50=7 and D=5 percent, ?50=7 and D0=0.7 Gy. The dose-response characteristics found for late skin telangiectasia score >=2 to >=4 were consistent with those determined for necrosis and fatal complications 5 years after radiotherapy to head and neck tumours in our department. (author). 23 refs.; 1 fig.; 9 tabs

104

Radiation Dose-Response Relationships and Risk Assessment  

Energy Technology Data Exchange (ETDEWEB)

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

Strom, Daniel J.

2005-07-05

105

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

106

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

107

External beam radiotherapy dose response of prostate cancer  

International Nuclear Information System (INIS)

Purpose: To determine the external beam radiotherapy dose response of palpable Stage T1-T4, mostly Nx, patients with adenocarcinoma of the prostate. Methods and Materials: There were 938 men consecutively treated between 1987 and 1995 who had pretreatment prostate specific antigen (PSA) levels. Posttreatment failure was defined as disease recurrence and/or two elevations in PSA on consecutive follow-up visits. The radiotherapy technique consisted of a four-field box with a small four-field reduction after 46 Gy in 844 patients (total dose of 60-70 Gy) or with a six-field conformal boost after 46 Gy in 94 patients (total dose of 74-78 Gy). Neoadjuvant or adjuvant androgen ablation was not used in any patient. Median follow-up was 40 months. Results: The mean and median radiotherapy doses for the entire group were 67.8 ± 13.3 Gy (±SEM) and 66 Gy. The mean radiotherapy dose was higher in those who had Stage T3/T4 disease, Gleason scores of 8-10, or pretreatment PSAs of >4 ng/ml. In general, patients with more aggressive pretreatment prognostic features were treated to higher doses; yet, those that relapsed or had a rising PSA were treated to significantly lower doses. Actuarial analyses were facilitated by dividing patients into three dose groups: ?67, >67-77, and >77 Gy. The actuarial freedom from failure rates at 3 years were 61, 74, and 96% for the low, intermediate, and high dose groups. Stratification of the patients by pretreatment PSA revealed that dose was a significant correlate of freedom from relapse or a rising PSA for those with PSAs >4-10, >10-20, and >20 ng/ml. The only patients in which an improvement in outcome was not related to higher doses were those with a pretreatment PSA ?4 ng/ml. Dose was significantly associated with freedom from failure for Stage T1/T2 and Stage T3/T4 patients, as well as for those stratified by Gleason score. Multivariate analysis using Cox proportional hazards models showed that dose was an independent and highly significant predictor of relapse or a rising PSA. Conclusion: This retrospective review strongly indicates that radiotherapy dose to the prostate is critical to the cure of prostate cancer, even for favorable patients with pretreatment PSAs of >4-10 ng/ml, Stages T1/T2, or Gleason scores of 2-6. Final confirmation awaits the results of our randomized trial

108

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

International Nuclear Information System (INIS)

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

109

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

110

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

111

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 (? = -0.16, p = 0.045), and there was a significant dose-response relationship between training volume per session and change in pain index (? = -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 L

2013-01-01

112

Dose-responsive model of smoke inhalation injury. Severity-related alteration in cardiopulmonary function  

Energy Technology Data Exchange (ETDEWEB)

The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by unit), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration.

Shimazu, T.; Yukioka, T.; Hubbard, G.B.; Langlinais, P.C.; Mason, A.D. Jr.; Pruitt, B.A. Jr.

1987-07-01

113

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)

114

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)

115

On the statistical significance of possible variations in the solar neutrino flux  

International Nuclear Information System (INIS)

A statistical study has been made on the flux of the solar neutrinos as recorded in the experiment of Davis et al. to see if there is any evidence for its variation with time. It is found that there are certain correlations and fluctuations in the data which when grouped indicate a pattern of temporal variation. The probability that this pattern of variation would have been caused purely by chance is estimated to be ? 10-4. (author)

116

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

117

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)

118

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

Science.gov (United States)

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

Alves, Gelio

119

External beam radiotherapy dose-response of prostate cancer  

International Nuclear Information System (INIS)

Purpose/Objective: Relatively few studies have documented the dose-response of prostate cancer to external beam radiotherapy. We describe here the effect of dose on biochemical failure in 938 patients treated between 1987 and 1995 who had pretreatment prostate specific antigen (PSA) levels. Materials and Methods: The study cohort was comprised of patients with Stage T1-T4, Nx (841) or N0 (97), M0 adenocarcinoma of the prostate. There were 643 with Stage T1/T2 disease and 295 with Stage T3/T4 disease. Post-treatment failure was defined as disease recurrence and/or two elevations in PSA on consecutive follow-up visits. The radiotherapy technique consisted of a four-field box with a small four-field reduction after 46 Gy in 844 patients (total isocenter dose of 60-70 Gy) or with a six-field conformal boost after 46 Gy in 94 patients (total isocenter dose of 74-78 Gy). Neoadjuvant or adjuvant androgen ablation was not used in any patient. Median follow-up was 40 months. The median follow-up was shorter for the patients treated to the higher doses: 59 mo for ?67 Gy (n=500), 27 mo for >67-77 Gy (n=356), and 19 mo for >77 Gy (n=82). These dose groupings were used for the actuarial analyses. Results: The mean and median radiotherapy isocenter doses for the entire group were 67.8±13.3 Gy (±SEM) and 66 Gy (range 60 - 78 Gy). The mean radiotherapy dose was higher in those who had Stage T3/T4 disease, Gleason scores of 8-10, or pretreatment PSAs of >4 ng/ml. In general, patients with more aggressive pretreatment prognostic features were treated to higher doses; yet, those that relapsed or had a rising PSA were treated to significantly lower doses. The 3 yr actuarial freedom from failure rates were 61%, 74%, and 96% for the low, intermediate, and high dose groups (Figure 1). Stratification of the patients by pretreatment PSA revealed that dose was a significant correlate of freedom from relapse or a rising PSA for those with PSAs >4-10, >10-20, and >20 ng/ml. The only patients in which an improvement in outcome was not related to higher doses were those with a pretreatment PSA ?4 ng/ml. Dose was significantly associated with freedom from failure for Stage T1/T2 and Stage T3/T4 patients, as well as for those stratified by Gleason score. Multivariate analysis using Cox proportional hazards models showed that dose was an independent and highly significant (p4-10 ng/ml, Stages T1/T2, or Gleason scores of 2-6. Final confirmation awaits the results of our randomized trial

120

Statistics  

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121

Redressing the Power and Effect of Significance. A New Approach to an Old Problem: Teaching Statistics to Nursing Students.  

Science.gov (United States)

In teaching research methods, introducing effect size, then power, then statistical significance will improve understanding of Type I and Type II errors. Students will develop a better grasp of decision-making processes involved in hypothesis testing, which nurses need in an environment stressing evidence-based practice. (SK)

Taylor, Shirley; Muncer, Steven

2000-01-01

122

Test for the statistical significance of differences between ROC curves. [For analysis of nuclear medical diagnostic data  

Energy Technology Data Exchange (ETDEWEB)

A test for the statistical significance of observed differences between two measured Receiver Operating Characteristic (ROC) curves has been designed and evaluated. The set of observer response data for each ROC curve is assumed to be independent and to arise from a ROC curve having a form which, in the absence of statistical fluctuations in the response data, graphs as a straight line on double normal-deviate axes. To test the significance of an apparent difference between two measured ROC curves, maximum likelihood estimates of the two parameters of each curve and the associated parameter variances and covariance are calculated from the corresponding set of observer response data. An approximate Chi-square statistic with two degrees of freedom is then constructed from the differences between the parameters estimated for each ROC curve and from the variances and covariances of these estimates. This statistic is known to be truly Chi-square distributed only in the limit of large numbers of trials in the observer performance experiments. Performance of the statistic for data arising from a limited number of experimental trials was evaluated. Independent sets of rating scale data arising from the same underlying ROC curve were paired, and the fraction of differences found (falsely) significant was compared to the significance level, ..cap alpha.., used with the test. Although test performance was found to be somewhat dependent on both the number of trials in the data and the position of the underlying ROC curve in the ROC space, the results for various significance levels showed the test to be reliable under practical experimental conditions.

Metz, C. E.; Kronman, H. B.

1979-01-01

123

2-D radiation therapy dosimetry using EPIDs: Dose response variation between 3 siemens electronic portal imaging devices (EPIDs)  

International Nuclear Information System (INIS)

Prerequisite for any new clinical dosimeter is a detailed understanding of the detector’s dose response behavior. The purpose of the present study was to investigate the level of variability in dose response characteristics of 3 siemens EPIDs for both 6 and 18 MV photons. Dose response tests for linearity, field size, short- and long-term reproducibilities, ghosting effects and dose rate dependence were undertaken for three different model Siemens EPIDs on three dosimetrically matched linear accelerators. All three EPIDs showed a linear dose response above 20 monitor units. The pixel sensitivity for EPID2 and EPID3 agreed to within 0.5%. EPID1 was 6.3% (6 MV) and 2.3% (18 MV) greater than for EPID2 and EPID3. The field size response and dose rate response agreed within 1% for all three EPIDs. The short-term and long-term reproducibilities for all EPIDs were within 0.5% and 1% respectively. The maximum increase in relative response due to the ghosting effect was 0.5%. The off-axis profiles from uncorrected gain files agreed to within 2% for EPID2 and EPID3 at 6 MV and 18 MV respectively. The off-axis profiles for EPID1 had more pronounced horns. The different dose response behavior of EPID1 is due to a thicker phosphor scintillator compared to EPID2 and EPID3. EPID1 was significantly more sensitive to dose and energy variations and would require separate calibration data for EPID dosimetry. EPIDs with the same phosphor had no significant difference in dose response. Differences in EPID/phosphor design must be considered when commissioning EPIDs for clinical dosimetry.

124

Method for Expressing Clinical and Statistical Significance of Ocular and Corneal Wavefront Error Aberrations  

Science.gov (United States)

Purpose The significance of ocular or corneal aberrations may be subject to misinterpretation whenever eyes with different pupil sizes or the application of different Zernike expansion orders are compared. A method is shown that uses simple mathematical interpolation techniques based on normal data to rapidly determine the clinical significance of aberrations, without concern for pupil and expansion order. Methods Corneal topography (Tomey, Inc.; Nagoya, Japan) from 30 normal corneas was collected and the corneal wavefront error analyzed by Zernike polynomial decomposition into specific aberration types for pupil diameters of 3, 5, 7, and 10 mm and Zernike expansion orders of 6, 8, 10 and 12. Using this 4×4 matrix of pupil sizes and fitting orders, best-fitting 3-dimensional functions were determined for the mean and standard deviation of the RMS error for specific aberrations. The functions were encoded into software to determine the significance of data acquired from non-normal cases. Results The best-fitting functions for 6 types of aberrations were determined: defocus, astigmatism, prism, coma, spherical aberration, and all higher-order aberrations. A clinical screening method of color-coding the significance of aberrations in normal, postoperative LASIK, and keratoconus cases having different pupil sizes and different expansion orders is demonstrated. Conclusions A method to calibrate wavefront aberrometry devices by using a standard sample of normal cases was devised. This method could be potentially useful in clinical studies involving patients with uncontrolled pupil sizes or in studies that compare data from aberrometers that use different Zernike fitting-order algorithms. PMID:22157570

Smolek, Michael K.

2011-01-01

125

Why Publishing Everything Is More Effective than Selective Publishing of Statistically Significant Results  

Science.gov (United States)

Background De Winter and Happee [1] examined whether science based on selective publishing of significant results may be effective in accurate estimation of population effects, and whether this is even more effective than a science in which all results are published (i.e., a science without publication bias). Based on their simulation study they concluded that “selective publishing yields a more accurate meta-analytic estimation of the true effect than publishing everything, (and that) publishing nonreplicable results while placing null results in the file drawer can be beneficial for the scientific collective” (p.4). Methods and Findings Using their scenario with a small to medium population effect size, we show that publishing everything is more effective for the scientific collective than selective publishing of significant results. Additionally, we examined a scenario with a null effect, which provides a more dramatic illustration of the superiority of publishing everything over selective publishing. Conclusion Publishing everything is more effective than only reporting significant outcomes. PMID:24465448

van Assen, Marcel A. L. M.; van Aert, Robbie C. M.; Nuijten, Michele B.; Wicherts, Jelte M.

2014-01-01

126

Dose response of various radiation detectors to synchrotron radiation  

Science.gov (United States)

Accurate dosimetry is particularly difficult for low- to medium-energy x-rays as various interaction processes with different dependences on material properties determine the dose distribution in tissue and radiation detectors. Monoenergetic x-rays from synchrotron radiation offer the unique opportunity to study the dose response variation with photon energy of radiation detectors without the compounding effect of the spectral distribution of x-rays from conventional sources. The variation of dose response with photon energies between 10 and 99.6 keV was studied for two TLD materials (LiF:Mg, Ti and LiF:Mg, Cu, P), MOSFET semiconductors, radiographic and radiochromic film. The dose response at synchrotron radiation energies was compared with the one for several superficial/orthovoltage radiation qualities (HVL 1.4 mm Al to 4 mm Cu) and megavoltage photons from a medical linear accelerator. A calibrated parallel plate ionization chamber was taken as the reference dosimeter. The variation of response with x-ray energy was modelled using a two-component model that allows determination of the energy for maximum response as well as its magnitude. MOSFET detectors and the radiographic film were found to overrespond to low-energy x-rays by up to a factor of 7 and 12 respectively, while the radiochromic film underestimated the dose by approximately a factor of 2 at 24 keV. The TLDs showed a slight overresponse with LiF:Mg, Cu, P demonstrating better tissue equivalence than LiF:Mg, Ti (maximum deviation from water less than 25%). The results of the present study demonstrate the usefulness of monoenergetic photons for the study of the energy response of radiation detectors. The variations in energy response observed for the MOSFET detectors and GAF chromic film emphasize the need for a correction for individual dosimeters if accurate dosimetry of low- to medium-energy x-rays is attempted.

Kron, Tomas; Duggan, Lisa; Smith, Tony; Rosenfeld, Anatoly; Butson, Martin; Kaplan, Greg; Howlett, Steve; Hyodo, Kazuyuki

1998-11-01

127

Dose response of various radiation detectors to synchrotron radiation  

International Nuclear Information System (INIS)

Accurate dosimetry is particularly difficult for low- to medium-energy x-rays as various interaction processes with different dependences on material properties determine the dose distribution in tissue and radiation detectors. Monoenergetic x-rays from synchrotron radiation offer the unique opportunity to study the dose response variation with photon energy of radiation detectors without the compounding effect of the spectral distribution of x-rays from conventional sources. The variation of dose response with photon energies between 10 and 99.6 keV was studied for two TLD materials (LiF:Mg, Ti and LiF:Mg, Cu, P), MOSFET semiconductors, radiographic and radiochromic film. The dose response at synchrotron radiation energies was compared with the one for several superficial/orthovoltage radiation qualities (HVL 1.4 mm Al to 4 mm Cu) and megavoltage photons from a medical linear accelerator. A calibrated parallel plate ionization chamber was taken as the reference dosimeter. The variation of response with x-ray energy was modelled using a two-component model that allows determination of the energy for maximum response as well as its magnitude. MOSFET detectors and the radiographic film were found to overrespond to low-energy x-rays by up to a factor of 7 and 12 respectively, while the radiochromic film underestimated the dose by approximately a factor of 2 at 24 keV. The TLDs showed a slight overresponse with LiF:Mg, Cu, P demonstrating better tissue equivalence than LiF:Mg, Ti (maximum deviation from water less than 25%). The results of the present study demonstrate the usefulness of monoenergetic photons for the study of the energy response of radiation detectors. The variations in energy response observed for the MOSFET detectors and GAF chromic film emphasize the need for a correction for individual dosimeters if accurate dosimetry of low- to medium-energy x-rays is attempted. (author)

128

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

129

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

International Nuclear Information System (INIS)

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

130

WISCOD: A Statistical Web-Enabled Tool for the Identification of Significant Protein Coding Regions.  

Science.gov (United States)

Classically, gene prediction programs are based on detecting signals such as boundary sites (splice sites, starts, and stops) and coding regions in the DNA sequence in order to build potential exons and join them into a gene structure. Although nowadays it is possible to improve their performance with additional information from related species or/and cDNA databases, further improvement at any step could help to obtain better predictions. Here, we present WISCOD, a web-enabled tool for the identification of significant protein coding regions, a novel software tool that tackles the exon prediction problem in eukaryotic genomes. WISCOD has the capacity to detect real exons from large lists of potential exons, and it provides an easy way to use global P value called expected probability of being a false exon (EPFE) that is useful for ranking potential exons in a probabilistic framework, without additional computational costs. The advantage of our approach is that it significantly increases the specificity and sensitivity (both between 80% and 90%) in comparison to other ab initio methods (where they are in the range of 70-75%). WISCOD is written in JAVA and R and is available to download and to run in a local mode on Linux and Windows platforms. PMID:25313355

Vilardell, Mireia; Parra, Genis; Civit, Sergi

2014-01-01

131

WISCOD: A Statistical Web-Enabled Tool for the Identification of Significant Protein Coding Regions  

Science.gov (United States)

Classically, gene prediction programs are based on detecting signals such as boundary sites (splice sites, starts, and stops) and coding regions in the DNA sequence in order to build potential exons and join them into a gene structure. Although nowadays it is possible to improve their performance with additional information from related species or/and cDNA databases, further improvement at any step could help to obtain better predictions. Here, we present WISCOD, a web-enabled tool for the identification of significant protein coding regions, a novel software tool that tackles the exon prediction problem in eukaryotic genomes. WISCOD has the capacity to detect real exons from large lists of potential exons, and it provides an easy way to use global P value called expected probability of being a false exon (EPFE) that is useful for ranking potential exons in a probabilistic framework, without additional computational costs. The advantage of our approach is that it significantly increases the specificity and sensitivity (both between 80% and 90%) in comparison to other ab initio methods (where they are in the range of 70–75%). WISCOD is written in JAVA and R and is available to download and to run in a local mode on Linux and Windows platforms.

Vilardell, Mireia; Parra, Genis

2014-01-01

132

An assessment of false discovery rates and statistical significance in label-free quantitative proteomics with combined filters  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Many studies have provided algorithms or methods to assess a statistical significance in quantitative proteomics when multiple replicates for a protein sample and a LC/MS analysis are available. But, confidence is still lacking in using datasets for a biological interpretation without protein sample replicates. Although a fold-change is a conventional threshold that can be used when there are no sample replicates, it does not provide an assessment of statistical significance such as a false discovery rate (FDR which is an important indicator of the reliability to identify differentially expressed proteins. In this work, we investigate whether differentially expressed proteins can be detected with a statistical significance from a pair of unlabeled protein samples without replicates and with only duplicate LC/MS injections per sample. A FDR is used to gauge the statistical significance of the differentially expressed proteins. Results We have experimented to operate on several parameters to control a FDR, including a fold-change, a statistical test, and a minimum number of permuted significant pairings. Although none of these parameters alone gives a satisfactory control of a FDR, we find that a combination of these parameters provides a very effective means to control a FDR without compromising the sensitivity. The results suggest that it is possible to perform a significance analysis without protein sample replicates. Only duplicate LC/MS injections per sample are needed. We illustrate that differentially expressed proteins can be detected with a FDR between 0 and 15% at a positive rate of 4–16%. The method is evaluated for its sensitivity and specificity by a ROC analysis, and is further validated with a [15N]-labeled internal-standard protein sample and additional unlabeled protein sample replicates. Conclusion We demonstrate that a statistical significance can be inferred without protein sample replicates in label-free quantitative proteomics. The approach described in this study would be useful in many exploratory experiments where a sample amount or instrument time is limited. Naturally, this method is also suitable for proteomics experiments where multiple sample replicates are available. It is simple, and is complementary to other more sophisticated algorithms that are not designed for dealing with a small number of sample replicates.

Li Qingbo

2009-02-01

133

Dose responses of alkaline-earth sulfate doped with rare earth ions  

International Nuclear Information System (INIS)

Thermoluminescence (TL) and optical stimulated luminescence (OSL) dose response curves of alkaline-earth sulfate doped with rare earth ions were measured. The non-linear dose response parameters were obtained by using the composite action dose response model. It is concluded that the linearity of dose response is relative to the species of rare earth ions and the defect structure. The one-hit factors (R) are closes to 1 in sulfate phosphors doped with Eu ions, which means that the dose responses are sublinear. But the dose responses are supralinear since R<0.5 when sulfate phosphors were doped with Tm or Dy ions. The value of R decreases with the increasing of TL peak temperatures, which means that contribution to dose response from the two-hit events is increased. The experiments also show that the dose response parameters of OSL are similar to those to TL. (authors)

134

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

International Nuclear Information System (INIS)

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

135

Statistical Intercomparison of Significant Wave Height from Envisat, Jason-1 and GFO  

Science.gov (United States)

Altimeter significant wave height (SWH) data play an increasingly important role in the ocean wave application and research. Altimeter SWH retrievals are validated during testing after launch. However, operational use of these data require continuous monitoring of there quality. We present an intercomparison of two years of altimeter data from the Envisat, Jason-1 and GFO altimeters, and provide a long-term assessment of their quality using collocations with buoy data. After bias corrections based on collocations with buoy data have been applied, the two-year l average of the three altimeters SWHs are nearly identical. The difference is within 0.1m, and is tentatively consistent with the different and sparse sampling of the three altimeters. The ENVSAT SWH are marginally lower than the average, and the Jason-1 SWH are marginally higher than the average in the area close to northern hemisphere continents. In the southern hemisphere, the ENVSAT SWH are marginally higher, and the Jason-1 SWH are marginally lower. The GFO SWH are marginally lower than the average of the three altimeters for most of the global oceans. It is now planned to assimilate these data into the operational global wave forecast model (WaveWatch III) at NCEP.

Cao, D.; Tolman, H.; Gerald, V.

2006-05-01

136

Characterization of statin dose response in 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 a 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 preselected variants. Two large biobanks were used to construct dose-response curves for 2,026 and 2,252 subjects on simvastatin and atorvastatin, respectively. Atorvastatin was more efficacious, was more potent, and demonstrated less interindividual 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 subjects homozygous for the minor allele vs. 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 the genetic factors contributing to drug response. PMID:24096969

Wei, W-Q; Feng, Q; Jiang, L; Waitara, M S; Iwuchukwu, O F; Roden, D M; Jiang, M; Xu, H; Krauss, R M; Rotter, J I; Nickerson, D A; Davis, R L; Berg, R L; Peissig, P L; McCarty, C A; Wilke, R A; Denny, J C

2014-03-01

137

Some hybrid models applicable to dose-response relationships  

International Nuclear Information System (INIS)

A new type of models of dose-response relationships has been studied as an initial stage to explore a reliable extrapolation of the relationships decided by high dose data to the range of low dose covered by radiation protection. The approach is to use a 'hybrid scale' of linear and logarithmic scales; the first model is that the normalized surviving fraction (? S > 0) in a hybrid scale decreases linearly with dose in a linear scale, and the second is that the induction in a log scale increases linearly with the normalized dose (? D > 0) in a hybrid scale. The hybrid scale may reflect an overall effectiveness of a complex system against adverse events caused by various agents. Some data of leukemia in the atomic bomb survivors and of rodent experiments were used to show the applicability of hybrid scale models. The results proved that proposed models fit these data not less than the popular linear-quadratic models, providing the possible interpretation of shapes of dose-response curves, e.g. shouldered survival curves varied by recovery time. (author)

138

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

139

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

140

Maximum likelihood estimation for cytogenetic dose-response curves  

International Nuclear Information System (INIS)

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

 
 
 
 
141

Dose-response relationships implied by stochastic model of carcinogenesis  

International Nuclear Information System (INIS)

A stochastic model of carcinogenesis, in order to be consistent with both radiation and chemical experiments, must involve at least two sequential cell changes in which the second change is governed by a probability of a specific second event conditioned on the initial occurrence of a specific first event. Such a model has been derived, incorporating parameters that specifically represent certain observables in carcinogenesis (Health Physics, in press). Computations with this model show that it has the potential for representing a broad class of dose-response phenomena in both radiation and chemical carcinogenesis. The model also predicts observed decreases in median tumor appearance times with increasing dose, and under certain circumstances, predicts a somewhat greater number of tumors for the same dose (concentration-time product) delivered at a lower dose rate. This effect at low dose rates is explained in the model by the required convolution over time of the conditional probability of the second transition times the probability of the first transition. Predictions of the model, agreement of the model with a limited amount of radiation dose-response data, and other implications of the model will be presented. (author)

142

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

143

Statistics  

...Heritage CrimeValue of HeritageConservation PhilosophyStatisticsLinksContact UsEducationMaintenanceThe Normans...Value of Northern Ireland's Historic EnvironmentStatisticsLast updated: 4 February 2011Northern Ireland...

144

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

Science.gov (United States)

High-throughput molecular biology studies, such as microarray assays of gene expression, two-hybrid experiments for detecting protein interactions, or ChIP-Seq experiments for transcription factor binding, often result in an "interesting" set of genes - say, genes that are co-expressed or bound by the same factor. One way of understanding the biological meaning of such a set is to consider what processes or functions, as defined in an ontology, are over-represented (enriched) or under-represented (depleted) among genes in the set. Usually, the significance of enrichment or depletion scores is based on simple statistical models and on the membership of genes in different classifications. We consider the more general problem of computing p-values for arbitrary integer additive statistics, or weighted membership functions. Such membership functions can be used to represent, for example, prior knowledge on the role of certain genes or classifications, differential importance of different classifications or genes to the experimenter, hierarchical relationships between classifications, or different degrees of interestingness or evidence for specific genes. We describe a generic dynamic programming algorithm that can compute exact p-values for arbitrary integer additive statistics. We also describe several optimizations for important special cases, which can provide orders-of-magnitude speed up in the computations. We apply our methods to datasets describing oxidative phosphorylation and parturition and compare p-values based on computations of several different statistics for measuring enrichment. We find major differences between p-values resulting from these statistics, and that some statistics recover "gold standard" annotations of the data better than others. Our work establishes a theoretical and algorithmic basis for far richer notions of enrichment or depletion of gene sets with respect to gene ontologies than has previously been available. PMID:22375144

Iacucci, Ernesto; Zingg, Hans H; Perkins, Theodore J

2012-01-01

145

Dose-response characteristics of an amorphous silicon EPID.  

Science.gov (United States)

Electronic portal imaging devices (EPIDs) were originally developed for the purpose of patient setup verification. Nowadays, they are increasingly used as dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite for any clinical dosimetric application is a detailed understanding of the detector's dose-response behavior. The aim of this study is to investigate the dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent temporal stability on short term as well as on long term scales. The stability throughout the day was strongly influenced by warming up, which took several hours and affected EPID response by 2.5%. Ghosting effects increased the sensitivity of the EPID. They became more pronounced with decreasing time intervals between two exposures as well as with increasing dose. Due to ghosting, changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon beam. It was observed that the response characteristics of our EPID depended on dose as well as on dose rate. Doubling the dose rate increased the EPID sensitivity by 1.5%. This behavior was successfully attributed to a dose per frame effect, i.e., a nonlinear relationship between the EPID signal and the dose which was delivered to the panel between two successive readouts. The sensitivity was found to vary up to 10% in the range of 1 to 1000 monitor units. This variation was governed by two independent effects. For low doses, the EPID signal was reduced due to the linac's changing dose rate during startup. Furthermore, the detector reading was influenced by intrabeam variations of EPID sensitivity, namely, an increase of detector response during uniform exposure. For the beam qualities which were used, the response characteristics of the EPID did not depend on energy. Differences in relative dose-response curves resulted from energy dependent temporal output characteristics of the accelerator. If ghosting is prevented from affecting the results and all dose-response effects are properly corrected for, the EPID signal becomes independent of dose rate, dose, and exposure time. PMID:16279061

Winkler, Peter; Hefner, Alfred; Georg, Dietmar

2005-10-01

146

Dose response curves for effects of low-level radiation  

International Nuclear Information System (INIS)

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

147

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.)

148

Application of Dempster–Shafer theory in dose response outcome analysis  

International Nuclear Information System (INIS)

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

149

Application of Dempster-Shafer theory in dose response outcome analysis  

Science.gov (United States)

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

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

2012-09-01

150

Linear dose response curves in fungi and tradescantia  

Energy Technology Data Exchange (ETDEWEB)

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

Unrau, P. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)

1999-07-15

151

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

Science.gov (United States)

Various interpretations of the notion of a trend in the context of global warming are discussed, contrasting the difference between viewing a trend as the deterministic response to an external forcing and viewing it as a slow variation which can be separated from the background spectral continuum of long-range persistent climate noise. The emphasis in this paper is on the latter notion, and a general scheme is presented for testing a multi-parameter trend model against a null hypothesis which models the observed climate record as an autocorrelated noise. The scheme is employed to the instrumental global sea-surface temperature record and the global land temperature record. A trend model comprising a linear plus an oscillatory trend with period of approximately 70 yr, and the statistical significance of the trends, are tested against three different null models: first-order autoregressive process, fractional Gaussian noise, and fractional Brownian motion. The parameters of the null models are estimated from the instrumental record, but are also checked to be consistent with a Northern Hemisphere temperature reconstruction prior to 1750 for which an anthropogenic trend is negligible. The linear trend in the period 1850-2010 AD is significant in all cases, but the oscillatory trend is insignificant for ocean data and barely significant for land data. However, by using the significance of the linear trend to constrain the null hypothesis, the oscillatory trend in the land record appears to be statistically significant. The results suggest that the global land record may be better suited for detection of the global warming signal than the ocean record.

Østvand, L.; Rypdal, K.; Rypdal, M.

2014-03-01

152

A dose-response model for refractory ceramic fibers.  

Science.gov (United States)

Refractory ceramic fibers (RCFs) are man-made vitreous fibers commonly used in insulation applications above 1000 degrees C. Although they have been subjected to considerable toxicologic evaluation, only the pooled results from two rat inhalation studies provide data that may be suitable for performing a numerical risk assessment. Even in these inhalation studies, good evidence exists that the maximum tolerated dose (MTD) was exceeded and that pulmonary overload occurred, a condition that will cause tumors whatever the dust responsible. Indeed, a significant yield of tumors was only obtained at the highest dose tested. If these results are omitted, there is no statistically significant evidence of carcinogenicity within the RCF results. Although there is little evidence that overload-related tumors are relevant to human risk, we adopted a conservative approach to obtain the estimates of risk regardless of overload, using a biologically based model, the two-stage clonal expansion model, as well as various statistical models, including the benchmark dose model. We argue that the data favor the use of a biologically based model, which gives the best fit when the highest dose RCF exposures are omitted. Continuing with this model, we show that available data from the RCF experiment, less outliers, coupled with results from other experiments with man-made mineral fibers (MMVFs), demonstrate that all MMVFs are potentially carcinogenic, with any risk mediated by the fibers' biopersistence. Application of this "all MMVF data set" model yields a maximum likely estimate for RCF excess unit risk of 4.6 x 10(-5) (95% upper confidence limit = 9.2 x 10(-5) per fiber/ml). This implies that the risk from occupational exposure to RCFs at 1 fiber/ml for a typical working lifetime would not exceed 10(-4). PMID:12955616

Turim, J; Brown, R C

2003-09-15

153

Time Series Analysis of Land Cover Change: Developing Statistical Tools to Determine Significance of Land Cover Changes in Persistence Analyses  

Directory of Open Access Journals (Sweden)

Full Text Available Despite the existence of long term remotely sensed datasets, change detection methods are limited and often remain an obstacle to the effective use of time series approaches in remote sensing applications to Land Change Science. This paper establishes some simple statistical tests to be applied to NDVI-derived time series of remotely sensed data products. Specifically, the methods determine the statistical significance of three separate metrics of the persistence of vegetation cover or changes within a landscape by comparison to various forms of “benchmarks”; directional persistence (changes in sign relative to some fixed reference value, relative directional persistence (changes in sign relative to the preceding value, and massive persistence (changes in magnitude relative to the preceding value. Null hypotheses are developed on the basis of serially independent, normally distributed random variables. Critical values are established theoretically through consideration of the numeric properties of those variables, application of extensive Monte Carlo simulations, and parallels to random walk processes. Monthly pixel-level NDVI values for the state of Florida are analyzed over 25 years, illustrating the techniques’ abilities to identify areas and/or times of significant change, and facilitate a more detailed understanding of this landscape. The potential power and utility of such techniques is diverse within the area of remote sensing studies and Land Change Science, especially in the context of global change.

Peter Waylen

2014-05-01

154

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

Science.gov (United States)

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) data from Salmonella typhimurium reverse mutagenicity assays conducted by the U.S. National Toxicology Program, and (3) hepatotoxicity data published in the Registry of Toxic Effects of Chemical Substances. Enrichments of structural features in toxic compounds are evaluated for their statistical significance and compiled into a simple additive model of toxicity and then used to score new compounds for potential toxicity. The predictive power of the model for cytotoxicity was validated using an independent set of compounds from the U.S. Environmental Protection Agency tested also at the National Institutes of Health Chemical Genomics Center. We compared the performance of our WFS approach with classical classification methods such as Naive Bayesian clustering and support vector machines. In most test cases, WFS showed similar or slightly better predictive power, especially in the prediction of hepatotoxic compounds, where WFS appeared to have the best performance among the three methods. The new algorithm has the important advantages of simplicity, power, interpretability, and ease of implementation. PMID:19805409

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

155

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

Directory of Open Access Journals (Sweden)

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

E. M. Dunne

2012-12-01

156

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

Directory of Open Access Journals (Sweden)

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

E. M. Dunne

2012-06-01

157

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

158

Weighted feature significance: a simple, interpretable model of compound toxicity based on the statistical enrichment of structural features.  

Science.gov (United States)

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) data from Salmonella typhimurium reverse mutagenicity assays conducted by the U.S. National Toxicology Program, and (3) hepatotoxicity data published in the Registry of Toxic Effects of Chemical Substances. Enrichments of structural features in toxic compounds are evaluated for their statistical significance and compiled into a simple additive model of toxicity and then used to score new compounds for potential toxicity. The predictive power of the model for cytotoxicity was validated using an independent set of compounds from the U.S. Environmental Protection Agency tested also at the National Institutes of Health Chemical Genomics Center. We compared the performance of our WFS approach with classical classification methods such as Naive Bayesian clustering and support vector machines. In most test cases, WFS showed similar or slightly better predictive power, especially in the prediction of hepatotoxic compounds, where WFS appeared to have the best performance among the three methods. The new algorithm has the important advantages of simplicity, power, interpretability, and ease of implementation. PMID:19805409

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

2009-12-01

159

A dose-responsive model of smoke inhalation injury. Severity-related alteration in cardiopulmonary function.  

Science.gov (United States)

The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by "unit"), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration. Images Fig. 3. Fig. 4A. Fig. 4B. PMID:3606236

Shimazu, T; Yukioka, T; Hubbard, G B; Langlinais, P C; Mason, A D; Pruitt, B A

1987-01-01

160

Symptom overreporting obscures the dose-response relationship between trauma severity and symptoms.  

Science.gov (United States)

We investigated whether symptom overreporting affects the dose-response relationship between self-reported abuse severity and psychiatric symptoms in two samples. The first sample (N=599) consisted of adults who had previously reported to a public commission that they had been witnesses to or victims of childhood sexual abuse by Roman Catholic Church representatives. The second sample (N=1756) consisted of general population respondents who indicated that they had been victims of non-familial childhood sexual abuse. Using a web-based data collection procedure, both samples completed the Brief Symptom Inventory (BSI-18), items addressing abuse severity, and items flagging symptom overreporting. Adjusting for overreporting reduced the proportion of participants with clinically raised BSI-18 scores from 60% to 47% in sample 1 and from 26% to 22% in sample 2. Also, in both samples, normal range reporting participants exhibited the typical dose-response relationship between trauma severity and BSI-18 scores, whereas this pattern was largely non-significant in overreporting participants. Our findings show that symptom overreporting has a psychometric impact that may obscure relationships between clinically relevant variables and should therefore preferably be monitored in surveys. PMID:24704260

Merckelbach, Harald; Langeland, Willie; de Vries, Gerard; Draijer, Nel

2014-07-30

 
 
 
 
161

Significant statistically relationship between the great volcanic eruptions and the count of sunspots from 1610 to the present  

Science.gov (United States)

The assertion that solar activity may play a significant role in the trigger of large volcanic eruptions is, and has been discussed by many geophysicists. Numerous scientific papers have established a possible correlation between these events and the electromagnetic coupling between the Earth and the Sun, but none of them has been able to highlight a possible statistically significant relationship between large volcanic eruptions and any of the series, such as geomagnetic activity, solar wind, sunspots number. In our research, we compare the 148 volcanic eruptions with index VEI4, the major 37 historical volcanic eruptions equal to or greater than index VEI5, recorded from 1610 to 2012 , with its sunspots number. Staring, as the threshold value, a monthly sunspot number of 46 (recorded during the great eruption of Krakatoa VEI6 historical index, August 1883), we note some possible relationships and conduct a statistical test. • Of the historical 31 large volcanic eruptions with index VEI5+, recorded between 1610 and 1955, 29 of these were recorded when the SSNPinatubo of June 1991, recorded in the solar maximum of cycle 22. • Of the historical 6 major volcanic eruptions with index VEI5+, recorded after 1955, 5 of these were not recorded during periods of low solar activity, but rather during solar maxima, of the cycles 19,21 and 22. The significant tests, conducted with the chi-square ? ² = 7,782, detect a p-value equal to 0,005. Applying a correction of Yates, p-value assume the value of 0,009. We affirm therefore that the occurrence of a major volcanic eruption, greater or equal to VEI4 index, during the weak solar cycles, is statistically significant and justifies the hypothesis of large volcanic eruptions in the next decade, with reference not only to the weakness of the current solar cycle SC24, but the probable entrance, in a long and deep solar minimum, during the transition to the next solar cycle SC25. Assumption formulated by many solar physicists.

Casati, Michele

2014-05-01

162

Hycanthone dose-response in Schistosoma mansoni infection in Kenya.  

Science.gov (United States)

The recommended doses of the drugs now used to cure schistosomiasis mansoni may be associated with toxic side-effects. Since Schistosoma mansoni does not multiply in the human host and the disease seems to be closely associated with the intensity of infection, it may not be necessary to use 100% lethal antischistosomal doses, particularly in endemic areas. A dose-response to the antischistosomal drug, hycanthone was established for three different doses in 169 patients with heavy S. mansoni infections in the Machakos district of Kenya. The highest dose used (1.5 mg/kg or half the recommended package-insert dose) resulted in a 96% decrease in egg output (equivalent ot death of the worms); 0.75 mg/kg in an 85% decrease; and 0.375 mg/kg in an 11% decrease one month after treatment. In contrast to the vomiting common with the package-insert dose (3.0 mg/kg), there were no side-effects with any of the lower doses. PMID:75394

Warren, K S; Siongok, T K; Ouma, J H; Houser, H B

1978-02-18

163

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

164

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 deg

165

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

166

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.

167

Nonlinear dose-response relationships and inducible cellular defence mechanisms  

Energy Technology Data Exchange (ETDEWEB)

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

Schoellnberger, Helmut; Hofmann, Werner [Institute of Physics and Biophysics, University of Salzburg, Salzburg (Austria); Mitchel, Ron E. [Radiation Biology and Health Physics Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River (Canada); Crawford-Brown, Douglas J. [Carolina Environmental Program, University of North Carolina, Chapel Hill, NC (United States)

2002-09-01

168

Biological and functional analysis of statistically significant pathways deregulated in colon cancer by using gene expression profiles  

Directory of Open Access Journals (Sweden)

Full Text Available Gene expression profiling offers a great opportunity for studying multi-factor diseases and for understanding the key role of genes in mechanisms which drive a normal cell to a cancer state. Single gene analysis is insufficient to describe the complex perturbations responsible for cancer onset, progression and invasion. A deeper understanding of the mechanisms of tumorigenesis can be reached focusing on deregulation of gene sets or pathways rather than on individual genes. We apply two known and statistically well founded methods for finding pathways and biological processes deregulated in pathological conditions by analyzing gene expression profiles. In particular, we measure the amount of deregulation and assess the statistical significance of predefined pathways belonging to a curated collection (Molecular Signature Database in a colon cancer data set. We find that pathways strongly involved in different tumors are strictly connected with colon cancer. Moreover, our experimental results show that the study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. Our study shows the importance of using gene sets rather than single genes for understanding the main biological processes and pathways involved in colorectal cancer. Our analysis evidences that many of the genes involved in these pathways are strongly associated to colorectal tumorigenesis. In this new perspective, the focus shifts from finding differentially expressed genes to identifying biological processes, cellular functions and pathways perturbed in the phenotypic conditions by analyzing genes co-expressed in a given pathway as a whole, taking into account the possible interactions among them and, more importantly, the correlation of their expression with the phenotypical conditions.

Angela Distaso, Luca Abatangelo, Rosalia Maglietta, Teresa Maria Creanza, Ada Piepoli, Massimo Carella, Annarita D'Addabbo, Nicola Ancona

2008-01-01

169

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

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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

170

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

171

The Maturing of Hormesis as a Credible Dose-Response Model  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Hormesis is a dose-response phenomenon that has received little recognition, credibility and acceptance as evidenced by its absence from major toxicological/risk assessment texts, governmental regulatory dose-response modeling for risk assessment, and non-visibility in major professional toxicological society national meetings. This paper traces the historical evolution of the hormetic dose-response hypothesis, why this model is not only credible but also more common than the widely accepted ...

Calabrese, Edward J.

2003-01-01

172

Investigating the performance improvement of HRV Indices in CHF using feature selection methods based on backward elimination and statistical significance.  

Science.gov (United States)

In this study, the best combination of short-term heart rate variability (HRV) measures was investigated to distinguish 29 patients with congestive heart failure from 54 healthy subjects in the control group. In the analysis performed, wavelet packet transform based frequency-domain measures and several non-linear parameters were used in addition to standard HRV measures. The backward elimination and unpaired statistical analysis methods were used to select the best one among all possible combinations of these measures. Five distinct typical classifiers with different parameters were evaluated in discriminating these two groups using the leave-one-out cross validation method. Each algorithm was tested 30 times to determine the repeatability of the results. The results imply that the backward elimination method gives better performance when compared to the statistical significance method in the feature selection stage. The best performance (82.75%, 96.29%, and 91.56% for the sensitivity, specificity, and accuracy) was obtained by using the SVM classifier with 27 selected features including non-linear and wavelet-based measures. PMID:24480166

Narin, Ali; Isler, Yalcin; Ozer, Mahmut

2014-02-01

173

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

174

Dose-Response Effect of Human Equivalent Radiation in the Murine Mandible. Part I. A Histomorphometric Assessment  

Science.gov (United States)

Background Our lab previously demonstrated that radiation significantly alters new bone formation in the murine mandible impeding the use of distraction osteogenesis (DO) as a viable reconstructive option after radiatiotherapy in Head and Neck Cancer (HNC). We hypothesize that the deleterious effects of radiation on regenerate formation results from a dose response (DR) depletion of essential osteogenic cells. Our specific aim is to use quantitative histomorphometry (QHM) to objectively measure the human equivalent DR effects of radiation on the integrity of the mandible’s cellular and tissue composition. Methods 20 Sprague-Dawley rats were randomIzed into three radiation dosage groups: low (5.91Gy), middle (7Gy) and high (8.89Gy) delivered in 5 daily fractions. These dosages approximated 75%, 100%, and 150% respectively of the bioequivalent dose the mandible experiences in the clinical regimen of HNC patients. Hemimandibles were harvested 56 days post-radiation, and stained with Gomori Trichrome. QHM was performed using Bioquant software and analysis with a one-way ANOVA Kruskal-Wallis test. Results Our data revealed a statistically significant diminution in the mean number of osteocytes . We also demonstrated a corresponding significant increase in the mean values of empty lacunae. Both of these QHM changes demonstrated a DR relationship. Conclusion Our study supports our hypothesis that radiation induces a DR depletion in osteocytes and an increase in empty lacunae. These reliable and reproducible metrics can now be utilized to determine the efficacy of therapies aimed at safeguarding the cells essential for optimal bone regeneration and potentially enhance the use of DO in HNC patients. PMID:21701328

Tchanque-Fossuo, Catherine N.; Monson, Laura A.; Farberg, Aaron S.; Donneys, Alexis; Zehtabzadeh, Aria J.; Razdolsky, Elizabeth R.; Buchman, Steven R.

2011-01-01

175

Statistics  

International Nuclear Information System (INIS)

For the year 2000, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy Review appear in more detail from the publication Energiatilastot - Energy Statistics issued annually, which also includes historical time series over a longer period (see e.g. Energiatilastot 1999, Statistics Finland, Helsinki 2000, 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 from the use of fossil fuels, Total energy consumption by source and CO2-emissions, Electricity supply, Energy imports by country of origin in 2000, Energy exports by recipient country in 2000, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Average electricity price by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes and precautionary stock fees on oil products

176

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

177

Analysis of thermal-dose response to heat  

International Nuclear Information System (INIS)

The authors reasoned that if hyperthermia alone has a clinical anti-tumor effect, response should have a thermal dose relationship. The authors analyzed 100 patients with advanced cancer treated with magnetic-induction. Three methods of determining thermal dose were used: (A) t1x10, the lowest temperature sustained throughout the tumor for 30-60min during the first of ten daily treatments, which represents one usual course of ten hourly sessions; (B) t43 (equivalent minutes at 43C) which accounts for non-linear tumor heating by combining serially measured temperatures during the first treatment with a mathematical description of the time-temperature relationship for thermal inactivation or damage; (C) Ct43 (cumulative t43), which represents the t43 value multiplied by the actual number of subsequent daily treatments received. Response was defined as CR+PR+MR. The results show a statistically significant effect of heat alone for t1x10, t43, and Ct43. These analyses demonstrate a thermal-dose relationship between hyperthermia therapy and tumor response as a sole independent variable, which indicates that heat therapy has clinical anti-cancer activity

178

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

Energy Technology Data Exchange (ETDEWEB)

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.

Wedenberg, Minna, E-mail: minna.wedenberg@raysearchlabs.com

2013-11-15

179

Statistics  

International Nuclear Information System (INIS)

For the year 1999 and 2000, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy also includes historical time series over a longer period (see e.g., Energiatilastot 1999, Statistics Finland, Helsinki 2000, 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 2000, Energy exports by recipient country in January-June 2000, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Average electricity price by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes and precautionary stock fees on oil products

180

Statistics  

International Nuclear Information System (INIS)

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

 
 
 
 
181

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

182

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

183

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

184

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

International Nuclear Information System (INIS)

Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 ?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.

185

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

DEFF Research Database (Denmark)

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.

Appelt, Ane Lindegaard; Vogelius, Ivan R

2012-01-01

186

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 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

187

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

188

Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition  

Science.gov (United States)

Background In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves’ dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. Results First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological interpretations. Conclusion Time independent summary statistics may aid the understanding of drugs’ action mechanism on tumour cells and potentially renew previous drug sensitivity evaluation studies. PMID:24902483

2014-01-01

189

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

Energy Technology Data Exchange (ETDEWEB)

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 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.

Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H. (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (USA))

1990-05-01

190

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

191

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

192

MINISIZE2: A Computer Program for Determining Effect Size and Minimum Sample Size for Statistical Significance for Univariate, Multivariate, and Nonparametric Tests.  

Science.gov (United States)

Describes the MINISIZE 2 computer program, which permits the user to determine the effect size and the minimum sample size needed so that results of a given analysis will be statistically significant. Explains the program's operation and provides examples. (SLD)

Morse, David T.

1999-01-01

193

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

Energy Technology Data Exchange (ETDEWEB)

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

Jordan, K; Battista, J [London Regional Cancer Centre, London, Ontario, N6A 4L6 (Canada); University of Western Ontario, London, Ontario, N6A 5B8 (Canada)

2004-01-01

194

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

International Nuclear Information System (INIS)

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

195

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

Science.gov (United States)

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

Jordan, K.; Battista, J.

2004-01-01

196

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

197

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

198

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)

199

ASTIN: a Bayesian adaptive dose-response trial in acute stroke.  

Science.gov (United States)

Understanding the dose-response is critical for successful drug development. We describe an adaptive design to efficiently learn about the dose-response and the ED95. A dynamic termination rule allows for early discontinuation either for efficacy or futility. The design was deployed in ASTIN, a phase II proof-of-concept trial of the neuroprotectant, neutrophil inhibitory factor (NIF), in acute stroke. We discuss the learning from this trial. PMID:16281432

Grieve, Andrew P; Krams, Michael

2005-01-01

200

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

 
 
 
 
201

A Grid Algorithm for High Throughput Fitting of Dose-Response Curve Data  

Science.gov (United States)

We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program’s performance in reproducing the actual values that were used to generate the simulated data and compared it with the DRC package for the language and environment R and the XLfit add-in for Microsoft Excel. The Grid program was robust and consistently recovered the actual values for both complete and partial curves with or without noise. Both DRC and XLfit performed well on data without noise, but they were sensitive to and their performance degraded rapidly with increasing noise. The Grid program is automated and scalable to millions of dose-response curves, and it is able to process 100,000 dose-response curves from high throughput screening experiment per CPU hour. The Grid program has the potential of greatly increasing the productivity of large-scale dose-response data analysis and early drug discovery processes, and it is also applicable to many other curve fitting problems in chemical, biological, and medical sciences. PMID:21331310

Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

2010-01-01

202

A grid algorithm for high throughput fitting of dose-response curve data.  

Science.gov (United States)

We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program's performance in reproducing the actual values that were used to generate the simulated data and compared it with the DRC package for the language and environment R and the XLfit add-in for Microsoft Excel. The Grid program was robust and consistently recovered the actual values for both complete and partial curves with or without noise. Both DRC and XLfit performed well on data without noise, but they were sensitive to and their performance degraded rapidly with increasing noise. The Grid program is automated and scalable to millions of dose-response curves, and it is able to process 100,000 dose-response curves from high throughput screening experiment per CPU hour. The Grid program has the potential of greatly increasing the productivity of large-scale dose-response data analysis and early drug discovery processes, and it is also applicable to many other curve fitting problems in chemical, biological, and medical sciences. PMID:21331310

Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

2010-01-01

203

Low dose response analysis through a cytogenetic end-point  

International Nuclear Information System (INIS)

The effects of low doses were studied on human lymphocytes of various individuals. The frequency of micronuclei in cytokinesis-blocked cultured lymphocytes was taken as end-point. The probability distribution of radiation-induced increment was statistically proved and identified as to be asymmetric when the blood samples had been irradiated with doses of 0.01-0.05 Gy of X-rays, similarly to that in unirradiated control population. On the contrary, at or above 1 Gy the corresponding normal curve could be accepted only reflecting an approximately symmetrical scatter of the increments about their mean value. It was found that the slope as well as the closeness of correlation of the variables considerably changed when lower and lower dose ranges had been selected. Below approximately 0.2 Gy even an unrelatedness was found betwen the absorbed dose and the increment

204

Low dose responses of different glyphosate formulations on plants  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

205

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

206

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

207

Pilot dose-response trial of i.v. ketamine in treatment-resistant depression.  

Science.gov (United States)

Abstract Objectives. Research studies have reported impressive antidepressant effects with ketamine but significant knowledge gaps remain over the best method of administering ketamine, and the relationships between dose, antidepressant response and adverse effects. Methods. In this pilot dose-finding study, the efficacy and tolerability of ketamine given by rapid intravenous (i.v.) infusion were assessed in a double-blind, placebo-controlled, crossover design, in four subjects with treatment- resistant depression. Each subject received up to four i.v. doses of ketamine (0.1, 0.2, 0.3, 0.4 mg/kg), given over 2-5 min, 1 week apart, and one randomly inserted placebo treatment. Results. Three of four subjects achieved antidepressant response (? 50% decrease in Montgomery-Asberg Depression Rating Scale scores), two at the minimum 0.1 mg/kg dose, though all relapsed within a week. For two subjects, the greatest improvement occurred at the highest dose received. Rapid infusion over 2 min led to significant adverse psychotomimetic effects which also increased proportionately with ketamine dosage. Conclusions. This is the first trial to present dose-response data of ketamine efficacy and psychomimetic effects in depressed subjects. Antidepressant efficacy may be dose-related. Psychotomimetic effects were dose-related. Rapid infusion over 2 min may not be a feasible clinical approach to treatment, given poor tolerability. PMID:24910102

Lai, Rosalyn; Katalinic, Natalie; Glue, Paul; Somogyi, Andrew A; Mitchell, Philip B; Leyden, John; Harper, Simon; Loo, Colleen K

2014-09-01

208

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

209

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

International Nuclear Information System (INIS)

e radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose-response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals

210

Prognostic Significance of Perineural Invasion in Patients with Rectal Cancer using R Environment for Statistical Computing and Graphics  

Directory of Open Access Journals (Sweden)

Full Text Available Purpose: In recent studies perineural invasion (PNI is associated with poor survival rates in rectal cancer, but the impact of PNI it’s still controversial. We assessed PNI as a potential prognostic factor in rectal cancer. Patients and Methods: We analyzed 317 patients with rectal cancer resected at The Oncology Institute”Prof. Dr. Ion Chiricu??” Cluj-Napoca, between January 2000 and December 2008. Tumors were reviewed for PNI by a pathologist. Patients data were reviewed and entered into a comprehensive database. The statistical analysis in our study was carried out in R environment for statistical computing and graphics, version 1.15.1. Overall and disease-free survivals were determined using the Kaplan-Meier method, and multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. Results: In our study PNI was identified in 19% of tumors. The 5-year disease-free survival rate was higher for patients with PNI-negative tumors versus those with PNI-positive tumors (57.31% vs. 36.99%, p=0.009. The 5-year overall survival rate was 59.15% for PNI-negative tumors versus 39.19% for PNI-positive tumors (p=0.014. On multivariate analysis, PNI was an independent prognostic factor for overall survival (Hazard Ratio = 0.6; 95% CI = 0.41 to 0.87; p = 0.0082. Conclusions: PNI can be considered an independent prognostic factor of outcomes in patients with rectal cancer. PNI should be taken into account when selecting patients for adjuvant treatment. R environment for statistical computing and graphics is complex yet easy to use software that has proven to be efficient in our clinical study.

Ioan Catalin VLAD

2012-11-01

211

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

International Nuclear Information System (INIS)

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

212

Dose-response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy  

International Nuclear Information System (INIS)

Purpose: To evaluate dosimetric factors predictive for radiation-induced pneumonitis (RP) after pulmonary stereotactic body radiotherapy (SBRT). Materials and methods: A retrospective analysis was performed based on 59 consecutive patients treated with cone-beam CT-based image-guided SBRT for primary NSCLC (n = 21) or pulmonary metastases (n = 54). The majority of patients were treated with radiosurgery of 26 Gy to 80% (n = 29) or three fractions of 12.5 Gy to 65% (n = 40). To correct for different single fraction doses, local doses were converted to 2 Gy equivalent normalized total doses (NTDs) using ?/? ratio of 3 Gy for RP. Dose-volume parameters and incidences of RP ? grade II SWOG were fitted using NTCP models. Results: Eleven patients developed RP grade II. With an average MLD of 10.3 ± 5.6 Gy to the ipsilateral lung, a significant dose-response relationship was observed: the MLD was 12.5 ± 4.3 Gy and 9.9 ± 5.8 Gy for patients with and without development of RP, respectively. Additionally, volumes of the lung exposed to minimum doses between 2.5 and 50 Gy (V2.5-V50) were correlated with incidences of RP with a continuous decrease of the goodness of fit for higher doses. Conclusions: The MLD and V2.5-V50 of the ipsilateral lung were correlated with incidences of RP after pulmonary SBRT.

213

Effects of temazepam on memory and psychomotor performance: a dose-response study.  

Science.gov (United States)

In a randomised, three-period crossover study, psychomotor performance and memory were tested and mood assessed for 3 h after single doses of placebo (PL), 20 mg temazepam (T20) or 30 mg temazepam (T30) were given to six healthy females aged 21-23. A composite measure of psychomotor speed showed a dose-dependent slowing (Page's L trend test: p Buschke Selective Reminding Task) showed significant impairment of long-term but not short-term memory (Page's L trend test: p < 0.05). The form of the dose-response curve was positively accelerating, with the difference in performance between T20 and T30 at least as great as that between PL and T20. Visual Analogue Scales showed a decrease in a factor representing functional integrity (Page's L trend test: p < 0.05;) sign test (PL vs T20: p < 0.05), but no changes in mood. These results show that 30 mg is a useful extension of the dose range of temazepam, being well tolerated and that it produces a substantially greater impairment of performance than 20 mg. Copyright 2001 John Wiley & Sons, Ltd. PMID:12404556

Begg, Alison; Drummond, Gordon; Tiplady, Brian

2001-08-01

214

The action spectrum and dose response studies of unscheduled DNA synthesis in normal human fibroblasts  

International Nuclear Information System (INIS)

Excision repair of DNA damage by UV has been assessed in normal human fibroblasts in culture by measuring unscheduled DNA synthesis. Dose response experiments indicated that the same chromophore was involved in UV-induced damage and excision repair at three different wave-lengths between 260 and 300 nm. Action spectra for unscheduled DNA synthesis were determined at wavelengths between 260 and 320 nm 30 min after irradiation using 2 doses of UV. 100 Jm-2 and 10 Jm-2. Experiments at the lower dose were carried out because it appeared that repair was saturated with the higher dose at 260 and 280 nm. To explore this part of the spectrum further, experiments were performed with different doses at 260 and 280 nm and unscheduled DNA synthesis assessed 30 min and 24 h after irradiation. At 24 hr after irradiation a significantly greater amount of unscheduled DNA synthesis occurred at 280 nm. It is suggested, therefore, that both DNA and protein are concerned in the absorption of UV which leads to DNA damage and excision repair. (author)

215

Increasing food deprivation relative to baseline influences d-amphetamine dose-response gradients.  

Science.gov (United States)

Several studies using non-pharmacological discriminative stimuli have found that stimulus control, as evident in generalization gradients, changes when motivation for (i.e., deprivation of) the relevant reinforcer is altered. Drug-discrimination studies, however, have not consistently revealed such an effect. A procedural detail that may account for the lack of a reliable effect in drug-discrimination studies is that motivation was characteristically reduced relative to the training condition in these studies. The present experiment examined how substantially increasing motivation affects d-amphetamine discrimination. Rats initially were trained to discriminate d-amphetamine (1.0mg/kg) from vehicle (0mg/kg) injections under 22-h food deprivation conditions. Dose-response gradients were then obtained under 22-h and 46-h deprivation levels. The ED50 was significantly higher with greater deprivation. This finding suggests that increasing motivation relative to the training condition may reduce stimulus control by drugs, while decreasing it may sharpen stimulus control. PMID:25179163

Lotfizadeh, Amin D; Zimmermann, Zachary J; Watkins, Erin E; Edwards, Timothy L; Poling, Alan

2014-10-01

216

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

International Nuclear Information System (INIS)

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

217

Multivariate statistical approach to identify significant sources influencing the physico-chemical variables in Aerial Bay, North Andaman, India.  

Science.gov (United States)

Aerial Bay is one of the harbor towns of Andaman and Nicobar Islands, the union territory of India. Nevertheless, it is least studied marine environment, particularly for physico-chemical assessment. Therefore, to evaluate the annual spatiotemporal variations of physico-chemical parameters, seawater samples collected from 20 sampling stations covering three seasons were analyzed. Multivariate statistics is applied to the investigated data in an attempt to understand the causes of variation in physico-chemical parameters. Cluster analysis distinguished mangrove and open sea stations from other areas by considering distinctive physico-chemical characteristics. Factor analysis revealed 79.5% of total variance in physico-chemical parameters. Strong loading included transparency, TSS, DO, BOD, salinity, nitrate, nitrite, inorganic phosphate, total phosphorus and silicate. In addition, box-whisker plots and Geographical Information System based land use data further facilitated and supported multivariate results. PMID:24981105

Jha, Dilip Kumar; Vinithkumar, N V; Sahu, Biraja Kumar; Das, Apurba Kumar; Dheenan, P S; Venkateshwaran, P; Begum, Mehmuna; Ganesh, T; Prashanthi Devi, M; Kirubagaran, R

2014-08-15

218

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.)

219

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

220

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

 
 
 
 
221

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

222

Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation.  

Science.gov (United States)

For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health. PMID:21191485

Zhao, Yuchao; Ricci, Paolo F

2010-01-01

223

Dose-response relationships for female radium dial workers  

International Nuclear Information System (INIS)

Among 1474 women employed in the United States radium dial-painting industry before 1930, there are 61 known cases of bone sarcoma and 21 cases of carcinoma of the paranasal sinuses or the mastoid air cells (''head carcinomas''). The relative effectiveness of 226Ra and 228Ra and dose-incidence relationships were examined for the 759 of these women whose radium body burden has been determined; there are 38 cases of bone sarcoma and 17 cases of head carcinoma in this group. Incidence (I) was expressed as tumor cases per person-year and the dose parameter (D) was the quantity (microcuries) of radium that entered the blood during the period of exposure. To the observed data for each type of tumor were fitted equations that can be formulated from the general form I = (C + alpha dD+ ?D2)e-?/sup D/, where C, the natural incidence for this population, was about 10-5 per person-year. For each equation, the best values of the dose coefficients were found by a least-squares fitting procedure. An equation of the form I = (C + BD2)e-/sup ?D/ provided the best fit for the bone sarcomas, when the dose was expressed as microcuries of 226Ra plus 2.5 times microcuries of 228Ra. An acceptable fit to the head carcinoma data was provided by the linear equation I = C + d alpha ? with D equal to microcuries of 226Ra. As a test of bias due to selection of cases with known symptoms of malignancy, the ath known symptoms of malignancy, the analyses were repeated after removal of all cases for whom radium was determined only after exhumation, and no significant changes in the fitted coefficients were found. The dose-incidence equations obtained when the dose was expressed as average skeletal dose in rad are also given

224

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

225

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).

226

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

Energy Technology Data Exchange (ETDEWEB)

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

Kim, Jin Kyu; Kim, Yeon Ku; Song, Hi Sup [KAERI, Taejon (Korea, Republic of)

1999-10-01

227

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

International Nuclear Information System (INIS)

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

228

The thresholds for statistical and clinical significance - a five-step procedure for evaluation of intervention effects in randomised clinical trials  

DEFF Research Database (Denmark)

BACKGROUND: Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore, assessment of intervention effects in randomised clinical trials deserves more rigour in order to become more valid. METHODS: Several methodologies for assessing the statistical and clinical significance of intervention effects in randomised clinical trials were considered. Balancing simplicity and comprehensiveness, a simple five-step procedure was developed. RESULTS: For a more valid assessment of results from a randomised clinical trial we propose the following five-steps: (1) report the confidence intervals and the exact P-values; (2) report Bayes factor for the primary outcome, being the ratio of the probability that a given trial result is compatible with a 'null' effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance threshold if the trial is stopped early or if interim analyses have been conducted; (4) adjust the confidence intervals and the P-values for multiplicity due to number of outcome comparisons; and (5) assess clinical significance of the trial results. CONCLUSIONS: If the proposed five-step procedure is followed, this may increase the validity of assessments of intervention effects in randomised clinical trials.

Jakobsen, Janus Christian; Gluud, Christian

2014-01-01

229

Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, a...

Zhao, Yuchao; Ricci, Paolo F.

2010-01-01

230

Chromosome damage in human cells by ? rays, ? particles and heavy ions: track interactions in basic dose-response relationships.  

Science.gov (United States)

We irradiated normal human lymphocytes and fibroblasts with (137)Cs ? rays, 3.5 MeV ? particles and 1 GeV/amu (56)Fe ions and measured the subsequent formation of chromosome-type aberrations by mFISH at the first mitosis following irradiation. This was done for the purposes of characterizing the shape of dose-response relationships and determining the frequency distribution of various aberration types with respect to the parameters of dose, radiation quality and cell type. Salient results and conclusions include the following. For low-LET ? rays, lymphocytes showed a more robust dose response for overall damage and a higher degree of upward curvature compared to fibroblasts. For both sources of high-LET radiation, and for both cell types, the response for simple and complex exchanges was linear with dose. Independent of all three parameters considered, the most likely damage outcome was the formation of a simple exchange event involving two breaks. However, in terms of the breakpoints making up exchange events, the majority of damage registered following HZE particle irradiation was due to complex aberrations involving multiple chromosomes. This adds a decidedly nonlinear component to the overall breakpoint response, giving it a significant degree of positive curvature, which we interpret as being due to interaction between ionizations of the primary HZE particle track and long-range ? rays produced by other nearby tracks. While such track interaction had been previously theorized, to the best of our knowledge, it has never been demonstrated experimentally. PMID:23198992

Loucas, Bradford D; Durante, Marco; Bailey, Susan M; Cornforth, Michael N

2013-01-01

231

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

232

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

233

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1995-12-31

234

Dose-response relationship with radiotherapy: an evidence?; Effet dose en radiotherapie: une evidence  

Energy Technology Data Exchange (ETDEWEB)

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

Chauvet, B.; Rauglaudre, G. de; Mineur, L.; Alfonsi, M.; Reboul, F. [Institut Sainte Catherine, 84 - Avignon (France)

2003-11-01

235

A Meta-Analysis To Determine the Dose Response for Strength Development.  

Science.gov (United States)

Examined the quantitative dose-response relationship for strength development by calculating the magnitude of gains elicited by various levels of training intensity, frequency, and volume; thus clarifying the effort to benefit ratio. A meta-analysis of 140 studies with 1,433 effect sizes (ES) was conducted. ES demonstrated different responses…

Rhea, Matthew R.; Alvar, Brent A.; Burkett, Lee N.; Ball, Stephen D.

2003-01-01

236

EVALUATION OF BIOLOGICALLY BASED DOSE-RESPONSE MODELING FOR DEVELOPMENTAL TOXICITY: A WORKSHOP REPORT  

Science.gov (United States)

Evaluation of biologically based dose-response modeling for developmental toxicity: a workshop report. Lau C, Andersen ME, Crawford-Brown DJ, Kavlock RJ, Kimmel CA, Knudsen TB, Muneoka K, Rogers JM, Setzer RW, Smith G, Tyl R. Reproductive Toxicology Division, NHEERL...

237

Radiation dose-response model for locally advanced rectal cancer after preoperative chemoradiation therapy  

DEFF Research Database (Denmark)

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.

Appelt, Ane L; PlØen, John

2013-01-01

238

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

239

Dose-response relationships for adult and prenatal exposures to methylmercury  

International Nuclear Information System (INIS)

Public concern over the health hazards of methylmercury is outlined. Dose-effect, dose-response in adults is studied and comparisons made between adult and prenatal exposures. The logit and Hockey Stick models are presented and discussed. The latter is found to produce a practical threshold which can help set limits for acceptable dosages. The subsequent published discussion is with Clarkson

240

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

 
 
 
 
241

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

International Nuclear Information System (INIS)

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.

242

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

243

Defining EMS and ENU Dose-Response Relationships Using the Pig-a Mutation Assay In Rats  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In recent years, experimental evidence has accumulated that supports the existence of sublinear dose-response relationships at low doses of DNA reactive mutagens. However, creating the in vivo data necessary to allow for a more detailed dose-response modeling with the currently available tools might not always be practical. The purpose of the current work was to evaluate the utility of the Pig-a gene mutation assay to rapidly identify dose response relationships for direct acting genotoxicant...

Dobo, Krista L.; Fiedler, Ronald D.; Gunther, William C.; Thiffeault, Catherine J.; Cammerer, Zoryana; Coffing, Stephanie L.; Shutsky, Thomas; Schuler, Maik

2011-01-01

244

On the existence of a threshold in the dose-response relationship from the epidemiological data of atomic bomb survivors  

International Nuclear Information System (INIS)

Whether or not there is a threshold dose in the dose-response relationship for cancer incidence due to radiation is one of the most important but controversial issues in radiation protection and nuclear policy making. The epidemiological studies on the Life Span Study (LSS) group of atomic bomb survivors in Hiroshima and Nagasaki, conducted by Radiation Effects Research Foundation (RERF) have been regarded to be most authentic, and they keep the view that there is no evidence to deny the linear non-threshold (LNT) hypotheses. The authors have claimed the necessity of reassessment of exposure doses of survivors, by considering the contribution of chronic dose, which comes from fall-out, induced radioactivity, and early entrance near the center of the city. The authors also have stressed the importance of the cases of if 'not-in-city' survivors, frequently reported to be fatal by the heavy chronic exposure. Recently we have noticed that the appearance of acute radiation symptoms is an important index for estimating total dose. In this paper, based on Obos statistical data (in 1957) for the acute symptoms observed for various category of survivors, we present an estimation of the average chronic dose of survivors, which should be added to the instantaneous dose for the directly exposed groups. By assuming the threshold for the appearance of the acute symptom such as epilation as 0.5 Sv, average chronic dose of 0.32 Sv was estimated for all survivors. Then the present dose-response relationship for cancer incidence should be shifted to the right hand side by this amount, and the value of about 0.32 Sv or more is suggested as the threshold for cancer incidence in low radiation level region

245

On the existence of a threshold in the dose-response relationship from the epidemiological data of atomic bomb survivors  

Energy Technology Data Exchange (ETDEWEB)

Whether or not there is a threshold dose in the dose-response relationship for cancer incidence due to radiation is one of the most important but controversial issues in radiation protection and nuclear policy making. The epidemiological studies on the Life Span Study (LSS) group of atomic bomb survivors in Hiroshima and Nagasaki, conducted by Radiation Effects Research Foundation (RERF) have been regarded to be most authentic, and they keep the view that there is no evidence to deny the linear non-threshold (LNT) hypotheses. The authors have claimed the necessity of reassessment of exposure doses of survivors, by considering the contribution of chronic dose, which comes from fall-out, induced radioactivity, and early entrance near the center of the city. The authors also have stressed the importance of the cases of if 'not-in-city' survivors, frequently reported to be fatal by the heavy chronic exposure. Recently we have noticed that the appearance of acute radiation symptoms is an important index for estimating total dose. In this paper, based on Obos statistical data (in 1957) for the acute symptoms observed for various category of survivors, we present an estimation of the average chronic dose of survivors, which should be added to the instantaneous dose for the directly exposed groups. By assuming the threshold for the appearance of the acute symptom such as epilation as 0.5 Sv, average chronic dose of 0.32 Sv was estimated for all survivors. Then the present dose-response relationship for cancer incidence should be shifted to the right hand side by this amount, and the value of about 0.32 Sv or more is suggested as the threshold for cancer incidence in low radiation level region.

Matsuura, Tatsuo [Radiation Education Forum, Tokyo (Japan); Sugahara, Tsutomu [Health Research Foundation, Kyoto (Japan)

2002-07-01

246

Spatial and dose–response analysis of fibrotic lung changes after stereotactic body radiation therapy  

Energy Technology Data Exchange (ETDEWEB)

Purpose: Stereotactic body radiation therapy (SBRT) is becoming the standard of care for early stage nonoperable lung cancers. Accurate dose–response modeling is challenging for SBRT because of the decreased number of clinical toxicity events. As a surrogate for a clinical toxicity endpoint, studies have proposed to use radiographic changes in follow up computed tomography (CT) scans to evaluate lung SBRT normal tissue effects. The purpose of the current study was to use local fibrotic lung regions to spatially and dosimetrically evaluate lung changes in patients that underwent SBRT.Methods: Forty seven SBRT patients treated at our institution from 2003 to 2009 were used for the current study. Our patient cohort had a total of 148 follow up CT scans ranging from 3 to 48 months post-therapy. Post-treatment scans were binned into intervals of 3, 6, 12, 18, 24, 30, and 36 months after the completion of treatment. Deformable image registration was used to align the follow up CT scans with the pretreatment CT and dose distribution. Areas of visible fibrotic changes were contoured. The centroid of each gross tumor volume (GTV) and contoured fibrosis volume was calculated and the fibrosis volume location and movement (magnitude and direction) relative to the GTV and 30 Gy isodose centroid were analyzed. To perform a dose–response analysis, each voxel in the fibrosis volume was sorted into 10 Gy dose bins and the average CT number value for each dose bin was calculated. Dose–response curves were generated by plotting the CT number as a function of dose bin and time posttherapy.Results: Both fibrosis and GTV centroids were concentrated in the upper third of the lung. The average radial movement of fibrosis centroids relative to the GTV centroids was 2.6 cm with movement greater than 5 cm occurring in 11% of patients. Evaluating dose–response curves revealed an overall trend of increasing CT number as a function of dose. The authors observed a CT number plateau at doses ranging from 30 to 50 Gy for the 3, 6, and 12 months posttherapy time points. There was no evident plateau for the dose–response curves generated using data from the 18, 24, 30, and 36 months posttherapy time points.Conclusions: Regions of local fibrotic lung changes in patients that underwent SBRT were evaluated spatially and dosimetrically. The authors found that the average fibrosis movement was 2.6 cm with movement greater than 5 cm possible. Evaluating dose–response curves revealed an overall trend of increasing CT number as a function of dose. Furthermore, our dose–response data also suggest that one of the possible explanations of the CT number plateau effect may be the time posttherapy of the acquired data. Understanding normal tissue dose–response is important for reducing toxicity after SBRT, especially in cases where larger tumors are treated. The methods presented in the current work build on prior quantitative studies and further enhance the understanding of normal lung dose–response after SBRT.

Vinogradskiy, Yevegeniy; Diot, Quentin; Kavanagh, Brian; Schefter, Tracey; Gaspar, Laurie; Miften, Moyed [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado 80045 (United States)

2013-08-15

247

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 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

248

Swiss solar power statistics 2007 - Significant expansion; Solarstromstatistik 2007 mit markantem Zubau. Starker Zubau in allen Anlagegroessen - Spitzenertraege bei neuen Anlagen  

Energy Technology Data Exchange (ETDEWEB)

This article presents and discusses the 2007 statistics for solar power in Switzerland. A significant number of new installations is noted as is the high production figures from newer installations. The basics behind the compilation of the Swiss solar power statistics are briefly reviewed and an overview for the period 1989 to 2007 is presented which includes figures on the number of photovoltaic plant in service and installed peak power. Typical production figures in kilowatt-hours (kWh) per installed kilowatt-peak power (kWp) are presented and discussed for installations of various sizes. Increased production after inverter replacement in older installations is noted. Finally, the general political situation in Switzerland as far as solar power is concerned are briefly discussed as are international developments.

Hostettler, T.

2008-07-01

249

DOSE-RESPONSE BEHAVIOR OF ANDROGENIC AND ANTIANDROGENIC CHEMICALS: IMPLICATIONS FOR LOW-DOSE EXTRAPOLATION AND CUMULATIVE TOXICITY  

Science.gov (United States)

DOSE-RESPONSE BEHAVIOR OF ANDROGENIC AND ANTIANDROGENIC CHEMICALS: IMPLICATIONS FOR LOW-DOSE EXTRAPOLATION AND CUMULATIVE TOXICITY. LE Gray Jr, C Wolf, J Furr, M Price, C Lambright, VS Wilson and J Ostby. USEPA, ORD, NHEERL, EB, RTD, RTP, NC, USA. Dose-response behavior of a...

250

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

251

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

Directory of Open Access Journals (Sweden)

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

Karen Larwin

2014-02-01

252

A clinical review on dose response in radiotherapy for laryngeal carcinoma  

International Nuclear Information System (INIS)

One hundred and fifty consecutive patients with laryngeal carcinoma treated primarily by radiotherapy have been studied with a computerized data retrieval system to reveal the dose response in relation to local control of the primary tumor. Part 1 is a review of the literature with respect to TNM classifications, pre-invasive and invasive carcinomas, other prognestic factors such as sex and host immune defence, complications and voice of the treated patients. In part 2, the patient material of the study, the policy of treatment, the technique, the dose and the results are presented with relevant comments and discussions. Finally, a modified tumor classification is proposed to obtain homogeneous subgroups for further dose response studies. The optimum dose ranges for laryngeal carcinoma are defined with the objective of higher local control with minimum complications

253

A practical guide to dose-response analyses and risk assessment in occupational epidemiology.  

Science.gov (United States)

Dose-response modeling in occupational epidemiology is usually motivated by questions of causal inference (eg, is there a monotonic increase of risk with increasing exposure?) or risk assessment (eg, how much excess risk exists at any given level of exposure?). We focus on several approaches to dose-response in occupational cohort studies. Categorical analyses are useful for detecting the shape of dose-response. However, they depend on the number and location of cutpoints and result in step functions rather than smooth curves. Restricted cubic splines and penalized splines are useful parametric techniques that provide smooth curves. Although splines can complement categorical analyses, they do not provide interpretable parameters. The shapes of these curves will depend on the degree of "smoothing" chosen by the analyst. We recommend combining categorical analyses and some type of smoother, with the goal of developing a reasonably simple parametric model. A simple parametric model should serve as the goal of dose-response analyses because (1) most "true" exposure response curves in nature may be reasonably simple, (2) a simple parametric model is easily communicated and used by others, and (3) a simple parametric model is the best tool for risk assessors and regulators seeking to estimate individual excess risks per unit of exposure. We discuss these issues and others, including whether the best model is always the one that fits the best, reasons to prefer a linear model for risk in the low-exposure region when conducting risk assessment, and common methods of calculating excess lifetime risk at a given exposure from epidemiologic results (eg, from rate ratios). Points are illustrated using data from a study of dioxin and cancer. PMID:14712148

Steenland, Kyle; Deddens, James A

2004-01-01

254

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

255

Gustatory tissue injury in man: radiation dose response relationships and mechanisms of taste loss  

Energy Technology Data Exchange (ETDEWEB)

In this report dose response data for gustatory tissue damage in patients given total radiation doses ranging from 3000 to 6000 cGy are presented. In order to evaluate direct radiation injury to gustatory tissues as a mechanism of taste loss, measurements of damage to specific taste structures in bovine and murine systems following radiation exposure in the clinical range are correlated to taste impairment observed in radiotherapy patients.

Mossman, K.L.

1986-01-01

256

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

International Nuclear Information System (INIS)

ures 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

257

Dose-response relationship for breast cancer induction at radiotherapy dose  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 i...

2011-01-01

258

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

259

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)

260

Non-targeted effects and the dose response for heavy ion tumor induction  

Energy Technology Data Exchange (ETDEWEB)

Non-targeted effects (NTE), including bystander effects in neighbor cells of cells directly hit by radiation tracks and genomic instability in the progeny of irradiated cells, challenge traditional radiation protection paradigms on Earth. It is thus of interest to understand how NTE could impact our understanding of cancer risks from galactic cosmic rays (GCR), which are comprised of high-energy protons and heavy ions. The most comprehensive data set for tumor induction by heavy ions is the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron and niobium ions after doses of 0.05 to several Gy. We report on an analysis of these data that compares a dose response model motivated by the conventional targeted effects (TE) model to one which includes a dose response term descriptive of non-targeted effects (NTE) in cell culture. Results show that a NTE model provides an improved fit to the Harderian gland data over the TE model. Relative biological effectiveness (RBE) factors are shown to have much larger values at low doses based on a NTE model than the maximum RBE estimates based on estimates of the ratio of initial linear slopes of heavy ions compared to {gamma}-rays in the TE model. Our analysis provides important in vivo support for the deviation from linear dose responses at low doses for high LET radiation, which are best explained by a NTE model.

Cucinotta, Francis A., E-mail: Francis.A.Cucinotta@nasa.gov [NASA, Lyndon B. Johnson Space Center, Space Radiation Program, 2101 NASA Parkway, Mail Code SK, Houston, TX 77058 (United States); Chappell, Lori J. [USRA Division of Life Sciences, Houston, TX 77058 (United States)

2010-05-01

 
 
 
 
261

Dose responses for Colletotrichum lindemuthianum elicitor-mediated enzyme induction in French bean cell suspension cultures.  

Science.gov (United States)

The induction of L-phenylalanine ammonialyase (PAL, EC 4.3.1.5) and flavanone synthase in French bean cell suspension cultures in response to heat-released elicitor from cell walls of the phytopathogenic fungus Colletotrichum lindemuthianum is highly dependent upon elicitor concentration. The elicitor dose-response curve for PAL induction shows two maxima at around 17.5 and 50 ?g elicitor carbohydrate per ml culture, whereas the flavanone synthase response shows one maximum at around 100 ?g ml(-1). The PAL response is independent of the elicitor concentration present during the lag phase of enzyme induction; if the initial elicitor concentration is increased after 2 h by addition of extra elicitor, or decreased by dilution of the cultures, the dose response curves obtained reflect the concentration of elicitor present at the time of harvest. PAL induction is not prevented by addition of methyl sugar derivatives to the cultures; ?-methyl-D-glucoside, itself a weak elicitor of PAL activity, elicits a multiphasic PAL response when increasing concentrations are added in the presence of Colletotrichum elicitor. Eight fractions with different monosaccharide compositions, obtained from the crude elicitor by gel-filtration, each elicit different dose-responses for PAL induction; the response to unfractionated elicitor is not the sum of the response to the isolated fractions. There is no correlation between the ability of the fractions to induce PAL in the cultures and their ability to act as elicitors of isoflavonoid phytoalexin accumulation in bean hypocotyls. PMID:24301854

Dixon, R A; Dey, P M; Murphy, D L; Whitehead, I M

1981-03-01

262

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.)

263

Planning a dose-response study with subject-specific doses.  

Science.gov (United States)

This article is concerned with a dose-response study where the doses are subject-specific. The motivating example is a study on the use of radioiodine in metastatic thyroid cancer where the dose is individualized for each subject based on pharmacokinetic models of clearance of the agent. The goal is to design a study that will estimate the probability of response within a specified precision. This setup does not fit into well-studied dose-response designs primarily because doses are subject-specific. Here the dose-response relationship is modelled using logistic regression and a second-order approximation to the asymptotic variance of the model parameters is developed. The resulting procedure is simple to apply and requires minimal assumptions regarding the distribution of the dose levels. Simulation studies establish that, for a reasonable range of parameter values, the approximation is reasonably accurate. A Monte Carlo procedure is developed as well for cases when the approximation performs poorly. The proposed method is applied to the thyroid cancer study, including elicitation of parameters and a sensitivity analysis. Computer code in SAS and R are provided in the Appendix. PMID:15977297

Gönen, Mithat

2005-09-15

264

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

International Nuclear Information System (INIS)

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

265

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

266

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) 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

267

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

Science.gov (United States)

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 relation in a software program, Pyxis, and have analyzed a selection of Saccharomyces cerevisiae gene expression microarray data sets. We have identified many gene clusters where constituent genes exhibited a regulatory dependence on proteins previously implicated in chromatin structure. Specifically, we found that Tup1p-dependent gene domains were enriched close to telomeres, which suggested a new role for Tup1p in telomere silencing. In addition, we identified Sir2p-, Sir3p- and Sir4p-dependent clusters, which suggested the presence of Sir-mediated heterochromatin in previously unidentified regions of the yeast genome. We also showed the presence of Sir4p-dependent gene clusters bordering the HMRa heterothallic locus, which suggested leaky termination of the heterochromatin by the boundary elements. These results demonstrate the utility of Pyxis in identifying possible higher order genomic features that may contribute to gene regulation in extended domains. PMID:15034148

Chang, Cheng-Fu; Wai, Ka-Man; Patterton, Hugh G

2004-01-01

268

Effect of heterogeneity of human population in cell radiosensitivity on the extrapolation of dose-response relationships to low doses  

International Nuclear Information System (INIS)

Presented are the results of an investigation of the dose-response relationship for the yield of chromosome aberrations in peripheral blood lymphocytes of persons with some hereditary diseases which represent the high risk group with respect to the increased incidence of malignant tumors and decreased life span. Despite substantially different absolute radiosensitivities of chromosomes, the variations of the alpha/beta ratio determining the extrapolation of experimental dose-response relationships to low doses did not prove to be too high, the mean deviation from the control being 15%. This points to the possible practical use of the dose-response relationships averaged over the human population as a whole

269

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

International Nuclear Information System (INIS)

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

270

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

Science.gov (United States)

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

Jordan, K.; Battista, J.

2004-01-01

271

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

Energy Technology Data Exchange (ETDEWEB)

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

Jordan, K; Battista, J [London Regional Cancer Centre, London, Ontario, N6A 4L6 (Canada); University of Western Ontario, London, Ontario, N6A 5B8 (Canada)

2004-01-01

272

Las pruebas de significación estadística en tres revistas biomédicas: una revisión crítica Tests of statistical significance in three biomedical journals: a critical review  

Directory of Open Access Journals (Sweden)

Full Text Available OBJETIVOS: Caracterizar el empleo de las pruebas convencionales de significación estadística y las tendencias actuales que muestra su uso en tres revistas biomédicas del ámbito hispanohablante. MÉTODOS: Se examinaron todos los artículos originales descriptivos o explicativos que fueron publicados en el quinquenio de 1996­2000 en tres publicaciones: Revista Cubana de Medicina General Integral, Revista Panamericana de Salud Pública/Pan American Journal of Public Health y Medicina Clínica. RESULTADOS: En las tres revistas examinadas se detectaron diversos rasgos criticables en el empleo de las pruebas de hipótesis basadas en los "valores P" y la escasa presencia de las nuevas tendencias que se proponen en su lugar: intervalos de confianza (IC e inferencia bayesiana. Los hallazgos fundamentales fueron los siguientes: mínima presencia de los IC, ya fuese como complemento de las pruebas de significación o como recurso estadístico único; mención del tamaño muestral como posible explicación de los resultados; predominio del empleo de valores rígidos de alfa; falta de uniformidad en la presentación de los resultados, y alusión indebida en las conclusiones de la investigación a los resultados de las pruebas de hipótesis. CONCLUSIONES: Los resultados reflejan la falta de acatamiento de autores y editores en relación con las normas aceptadas en torno al uso de las pruebas de significación estadística y apuntan a que el empleo adocenado de estas pruebas sigue ocupando un espacio importante en la literatura biomédica del ámbito hispanohablante.OBJECTIVE: To describe the use of conventional tests of statistical significance and the current trends shown by their use in three biomedical journals read in Spanish-speaking countries. METHODS: All descriptive or explanatory original articles published in the five-year period of 1996 through 2000 were reviewed in three journals: Revista Cubana de Medicina General Integral [Cuban Journal of Comprehensive General Medicine], Revista Panamericana de Salud Pública/Pan American Journal of Public Health, and Medicina Clínica [Clinical Medicine] (which is published in Spain. RESULTS: In the three journals that were reviewed various shortcomings were found in their use of hypothesis tests based on P values and in the limited use of new tools that have been suggested for use in their place: confidence intervals (CIs and Bayesian inference. The basic findings of our research were: minimal use of CIs, as either a complement to significance tests or as the only statistical tool; mentions of a small sample size as a possible explanation for the lack of statistical significance; a predominant use of rigid alpha values; a lack of uniformity in the presentation of results; and improper reference in the research conclusions to the results of hypothesis tests. CONCLUSIONS: Our results indicate the lack of compliance by authors and editors with accepted standards for the use of tests of statistical significance. The findings also highlight that the stagnant use of these tests continues to be a common practice in the scientific literature.

Madelaine Sarria Castro

2004-05-01

273

Spectral and cross-spectral analysis of uneven time series with the smoothed Lomb-Scargle periodogram and Monte Carlo evaluation of statistical significance  

Science.gov (United States)

Many spectral analysis techniques have been designed assuming sequences taken with a constant sampling interval. However, there are empirical time series in the geosciences (sediment cores, fossil abundance data, isotope analysis, …) that do not follow regular sampling because of missing data, gapped data, random sampling or incomplete sequences, among other reasons. In general, interpolating an uneven series in order to obtain a succession with a constant sampling interval alters the spectral content of the series. In such cases it is preferable to follow an approach that works with the uneven data directly, avoiding the need for an explicit interpolation step. The Lomb-Scargle periodogram is a popular choice in such circumstances, as there are programs available in the public domain for its computation. One new computer program for spectral analysis improves the standard Lomb-Scargle periodogram approach in two ways: (1) It explicitly adjusts the statistical significance to any bias introduced by variance reduction smoothing, and (2) it uses a permutation test to evaluate confidence levels, which is better suited than parametric methods when neighbouring frequencies are highly correlated. Another novel program for cross-spectral analysis offers the advantage of estimating the Lomb-Scargle cross-periodogram of two uneven time series defined on the same interval, and it evaluates the confidence levels of the estimated cross-spectra by a non-parametric computer intensive permutation test. Thus, the cross-spectrum, the squared coherence spectrum, the phase spectrum, and the Monte Carlo statistical significance of the cross-spectrum and the squared-coherence spectrum can be obtained. Both of the programs are written in ANSI Fortran 77, in view of its simplicity and compatibility. The program code is of public domain, provided on the website of the journal (http://www.iamg.org/index.php/publisher/articleview/frmArticleID/112/). Different examples (with simulated and real data) are described in this paper to corroborate the methodology and the implementation of these two new programs.

Pardo-Igúzquiza, Eulogio; Rodríguez-Tovar, Francisco J.

2012-12-01

274

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

Directory of Open Access Journals (Sweden)

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

275

An assessment of non-linear dose response in chemiluminescence dosimetry  

International Nuclear Information System (INIS)

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

276

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 or cooling. Theoretical and practical implications of the above findings are discussed in the paper. (author)

277

Fractional poisson-a simple dose-response model for human norovirus.  

Science.gov (United States)

This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (<100), estimation error is small for the fractional Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. PMID:24724739

Messner, Michael J; Berger, Philip; Nappier, Sharon P

2014-10-01

278

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

279

Comparison of total dose responses on high resolution analog-to-digital converter technologies  

International Nuclear Information System (INIS)

Two different 12-bit analog-to-digital converter technologies, CMOS and BiCMOS, from Burr-Brown were compared for total dose responses. The BiCMOS converter appears to be a better candidate for space applications. CMOS devices showed larger degradation with both high dose rate (HDR) and low dose rate (LDR). An external voltage reference can be used for a radiation hardened process 12-bit converter from Analog Devices to maintain accuracy up to 1 Mrad(Si). DATEL's 16-bit hybrid converter showed a low failure level with HDR

280

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

 
 
 
 
281

A threshold in the dose-response relationship for X-ray induced somatic mutation frequency in drosophila melanogaster  

International Nuclear Information System (INIS)

The dose-response relationship of ionizing radiation and its stochastic effects has been thought to be linear without any thresholds for a long time. The basic data for this model was obtained from mutational assays using germ cells of male fruit fly Drosophila melanogaster. However, cancer-causing activity should be examined more appropriately in somatic cells than in germ cells. In this paper, we examined the dose-response relationship of X-ray irradiation and somatic mutation in drosophila, and found a threshold at approximately 1 Gy in the DNA repair proficient flies. In the repair deficient siblings, the threshold was smaller and the inclination of the dose-response curve was five times steeper. These results suggest that the dose-response relationship between X-ray irradiation and somatic mutation has a threshold, and that the DNA repair function contributes to its formation. (author)

282

Normal Liver Tissue Density Dose Response in Patients Treated With Stereotactic Body Radiation Therapy for Liver Metastases  

International Nuclear Information System (INIS)

Purpose: To evaluate the temporal dose response of normal liver tissue for patients with liver metastases treated with stereotactic body radiation therapy (SBRT). Methods and Materials: Ninety-nine noncontrast follow-up computed tomography (CT) scans of 34 patients who received SBRT between 2004 and 2011 were retrospectively analyzed at a median of 8 months post-SBRT (range, 0.7-36 months). SBRT-induced normal liver tissue density changes in follow-up CT scans were evaluated at 2, 6, 10, 15, and 27 months. The dose distributions from planning CTs were mapped to follow-up CTs to relate the mean Hounsfield unit change (?HU) to dose received over the range 0-55 Gy in 3-5 fractions. An absolute density change of 7 HU was considered a significant radiographic change in normal liver tissue. Results: Increasing radiation dose was linearly correlated with lower post-SBRT liver tissue density (slope, ?0.65 ?HU/5 Gy). The threshold for significant change (?7 ?HU) was observed in the range of 30-35 Gy. This effect did not vary significantly over the time intervals evaluated. Conclusions: SBRT induces a dose-dependent and relatively time-independent hypodense radiation reaction within normal liver tissue that is characterized by a decrease of >7 HU in liver density for doses >30-35 Gy.

283

Normal Liver Tissue Density Dose Response in Patients Treated With Stereotactic Body Radiation Therapy for Liver Metastases  

Energy Technology Data Exchange (ETDEWEB)

Purpose: To evaluate the temporal dose response of normal liver tissue for patients with liver metastases treated with stereotactic body radiation therapy (SBRT). Methods and Materials: Ninety-nine noncontrast follow-up computed tomography (CT) scans of 34 patients who received SBRT between 2004 and 2011 were retrospectively analyzed at a median of 8 months post-SBRT (range, 0.7-36 months). SBRT-induced normal liver tissue density changes in follow-up CT scans were evaluated at 2, 6, 10, 15, and 27 months. The dose distributions from planning CTs were mapped to follow-up CTs to relate the mean Hounsfield unit change ({Delta}HU) to dose received over the range 0-55 Gy in 3-5 fractions. An absolute density change of 7 HU was considered a significant radiographic change in normal liver tissue. Results: Increasing radiation dose was linearly correlated with lower post-SBRT liver tissue density (slope, -0.65 {Delta}HU/5 Gy). The threshold for significant change (-7 {Delta}HU) was observed in the range of 30-35 Gy. This effect did not vary significantly over the time intervals evaluated. Conclusions: SBRT induces a dose-dependent and relatively time-independent hypodense radiation reaction within normal liver tissue that is characterized by a decrease of >7 HU in liver density for doses >30-35 Gy.

Howells, Christopher C.; Stinauer, Michelle A.; Diot, Quentin; Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Miften, Moyed, E-mail: Moyed.Miften@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States)

2012-11-01

284

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1994-06-01

285

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

286

Biological dosimetry in radiation accidents. Dose-response curve by chromosomal aberrations analysis  

International Nuclear Information System (INIS)

The aim of this paper is to obtain a dose-response relationship for chromosomal aberrations induced in human lymphocytes after in vitro irradiation. Peripheral blood samples of 7 different donors were used. The blood irradiation was done with Cs137 gamma-rays at different doses: 0.0, 0.05, 0.1, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0 and 3.0 Gy. Lymphocyte cultures were established and maintain for 48 hours at 370C in CO2 incubator for chromosomal aberration analysis. The dose response relationship has been established based on dysenteric and ring chromosomes yield. The relationship can be described by the following equation: Y = 0.0274D + 0.0251 D2, where (Y) = dysenteric and ring chromosomes yield, (D) = radiation dose obtained. EXCEL software was established for calculation of the received dose by using this equation, as a whole body equivalent dose acute irradiation

287

Triphasic low-dose response in zebrafish embryos irradiated by microbeam protons.  

Science.gov (United States)

The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym as SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed to irradiate dechorionated zebrafish embryos at the 2-cell stage at 0.75 h post fertilization (hpf) by microbeam protons. Either one or both of the cells of the embryos were irradiated with 10, 20, 40, 50, 80, 100, 160, 200, 300 and 2000 protons each with an energy of 3.37 MeV. The embryos were then returned back to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay, with the apoptotic signals captured by a confocal microscope. The results revealed a triphasic dose-response for zebrafish embryos with both cells irradiated at the 2-cell stage, namely, (1) increase in apoptotic signals for hormesis to reduce the apoptotic signals below the spontaneous number for 200-400 protons (at doses of 30-60 mGy), and (3) increase in apoptotic signals again for > 600 protons (at doses > 90 mGy). The dose response for zebrafish embryos with only one cell irradiated at the 2-cell stage was also likely a triphasic one, but the apoptotic signals in the first zone (radiation-induced bystander effect as well as rescue effect in the zebrafish embryos, particular in those embryos with unirradiated cells. PMID:22498889

Choi, Viann Wing Yan; Yum, Emily Hoi Wa; Konishi, Teruaki; Oikawa, Masakazu; Cheng, Shuk Han; Yu, Kwan Ngok

2012-01-01

288

Dose responsive effects of cisplatin in L02 cells using NMR-based metabolomics.  

Science.gov (United States)

Cisplatin is an effective chemotherapeutic agent for the treatment of various cancers, such as bladder cancer, epithelial ovarian cancer, cervical cancer, and so on. However, cisplatin can cause various side effects. In this study, the dose-responsive effects of cisplatin were investigated in an in vitro model of human liver cells (L02) using NMR-based metabolomics. The inverted U-shaped curve of cell proliferation confirmed the hormetic effects of cisplatin (from 1 nM to 1 mM) in L02 cells. However, the metabolite changes revealed both U-shaped (ethanol, lactate, aspartate, choline, etc.) and inverted U-shaped (glutamate, glutamine, 4-aminobutyrate, myo-inositol, etc.) curves induced by three typical concentrations of cisplatin which covered the inverted U-shaped curve as indicated by the cell proliferation assay. These findings suggested that a macroscopic hormesis phenomenon on the cell proliferation could be reflected by both stimulated and inhibited metabolites and corresponding metabolic pathways to cisplatin treatments. Therefore, a global analysis using metabolomics may give a broader view into the dose-response relationship than using a single endpoint at molecular levels. PMID:24322623

Liu, Shu; Wang, Wei; Zhou, Xueyi; Gu, Runhuan; Ding, Zongli

2014-01-01

289

Histamine dose-response relationships in normal and asthmatic subjects. The importance of starting airway caliber.  

Science.gov (United States)

We examined the effects of pharmacologic antagonists on the bronchial response to inhaled histamine in 11 normal and 11 asthmatic subjects. We constructed cumulative log dose-response curves and determined the steepest slope and the provocative dose of histamine (PD35) needed to cause a 35% fall in specific airway conductance (SGaw). The slope was positively related to starting SGaw in both groups. Starting SGaw and slope were approximately 2-fold lower in asthmatics. After inhaling salbutamol (200 micrograms) and atropine (4 mg), there was an increase in starting SGaw and slope of the histamine response by approximately 1.5-fold in normal subjects and 2-fold in asthmatics, the relationship between starting SGaw and slope being preserved. Chlorpheniramine (4 mg) had little effect on starting SGaw and slope.l Atropine, salibutamol, and chlorpheniramine increased PD35 by approximately 4-fold in normal subjects and 6-fold in asthmatics. Afte bronchodilatation with atropine or salbutamol, mean starting SGaw, slope, and PD35 of the responses in asthmatics were similar to those of unpremedicated normal subjects. Thus, the slope of the histamine dose-response curve is largely determined by the starting airway caliber, increases in PD35 by drugs reflect in part the effects of bronchodilatation and in part their specific pharmacologic antagonist activity. PMID:7149450

Chung, K F; Morgan, B; Keyes, S J; Snashall, P D

1982-11-01

290

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

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 due to a multitude of confounding factors a direct estimation of small risks requires impracticably large samples. Therefore, risk estimates for low doses have to be derived indirectly by extrapolation from high-exposure data and are heavily dependent on assumptions about the shape of the dose-response curve. Although radiobiological theories tested mostly on in vitro systems predict a quadratic term in the dose-response equation, which should dominate the shape of the curve at least for sparsely ionizing radiation, the epidemiological data available are not yet sufficient to exclude the possibility of a purely linear relationship. In some cases, apparent thresholds may result from latent periods inversely related to dose. Besides depending on the quality of the radiation, the shape also seems to differ with the type of cancer induced. The huge epidemiological data base on atomic bomb survivors, irradiated patients, miners, and other exposed groups can most consistently be fitted to a linear quadratic model. For lung cancer in miners resulting from high linear energy transfer alpha radiation and for female breast cancer, the linear component seems to be dominant

291

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

Science.gov (United States)

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation- induced disruption of dopaminergic function disrupts a variety of behaviors that are dependent upon the integrity of the dopaminergic system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, spatial learning and memory (Morris water maze), and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current presentation will review the data relevant to the degree to which these characteristics are in fact common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. Supported by N.A.S.A. Grant NAG9-1190.

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

292

Neutron dose response of tradescantia stamen hair pink mutations and RBE  

Energy Technology Data Exchange (ETDEWEB)

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 {sup 252}Cf 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.

Kim, Jin Kyu; Kim, Won Rok [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1998-03-01

293

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

Science.gov (United States)

A low-density (~0.6 g cm-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.; Karlsson, A.; Wieslander, E.; Gustavsson, H.; Bäck, S. Å. J.

2006-02-01

294

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

295

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

International Nuclear Information System (INIS)

A low-density (?0.6 g cm-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

296

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

297

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

DEFF Research Database (Denmark)

Objective: This study was performed to investigate the dose-response effects of supplementation with Bifidobacterium animalis subsp lactis (BB-12) and Lactobacillus paracasei subsp paracasei (CRL-431) on blood lipids, recovery from feces and bowel habits. Changes of the fecal microflora was analyzed in the 10(10) CFU/day probiotic and placebo group. Design: The study was designed as a randomized, placebo-controlled, double-blinded, parallel dose-response study. Subjects: Healthy young adults (18 - 40 years) were recruited by advertising in local newspapers. Of the 75 persons enrolled, 71 ( 46 women, 25 men, mean age 25.6 years ( range 18 - 40 years)) completed the study. Intervention: The volunteers were randomly assigned into five groups receiving either placebo or a mixture of the two probiotics in the concentration of 10(8), 10(9), 10(10) or 10(11) CFU/day in 2 weeks run-in period, 3 weeks intervention and 2 weeks wash-out. Diary reporting bowel habits and well being (abdominal bloating, flatulence and headache) was kept for all 7 weeks and blood lipids, fecal recovery of BB-12 and CRL-431, as well as fecal microflora was tested before, immediately and 2 weeks after intervention. Results: The fecal recovery of BB-12 increased significantly (P <0.001) with increasing dose. In the group receiving 10(11) CFU/day BB-12 was recovered from 13 out of 15 volunteers. CRL-431 was not recovered in any of the fecal samples. Supplementation with probiotics did not change the fecal bacterial composition. A significant linear increase in fecal consistency (looser stool) with increasing probiotic dose (P=0.018) was observed. No overall dose - response effect was found on the blood lipids. High doses of probiotics were well tolerated. Conclusion: A dose-related recovery of BB-12 from feces was observed. Sponsorship: The study was sponsored by Chr. Hansen A/S, Hoersholm, Denmark.

Christensen, Hanne Risager

2006-01-01

298

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

International Nuclear Information System (INIS)

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

299

Dose-response relationship of radiation-induced harderian gland tumors and myeloid leukemia of the CBA/Cne mouse  

International Nuclear Information System (INIS)

Transplantation of harderian gland cells from CBA/-Cne mice into the fat pad of isogenic recipients was used for a quantitative in vivo study of cell survival and risk of transformation after x-ray irradiation (1-7 Gy). A survival curve for gland cells was generated in vivo with a D0 of 1.83 Gy and an extrapolation number of 7.23. Subsequently, the dose-response curve for lesions observed in nodules after cell transplantation was compared with that for lesions observed in glands irradiated in situ. A high incidence of epithelial hyperplasias with severe dysplasia was observed in transplantation nodules after x-irradiation. Gland tumors were significantly induced in whole-body irradiated animals; the tumors reached a maximum incidence after doses of 3 Gy. The risk of transformation per surviving cell was estimated both for dysplastic lesions and for tumors. These results approximated a dose-squared relationship in both cases, suggesting a common induction mechanism at the cellular level. Myeloid leukemia was observed at all doses in whole-body irradiated mice, and the maximum tumor incidence was reached at doses around 3 Gy

300

Home dampness, childhood asthma, hay fever, and airway symptoms in Shanghai, China: associations, dose-response relationships, and lifestyle's influences.  

Science.gov (United States)

Numerous studies of associations between dampness and respiratory diseases have been conducted, but their implications remain inconclusive. In this study of 13,335 parent-reported questionnaires (response rate: 85.3%), we analyzed associations between home dampness and asthma and related symptoms in 4- to 6-year-old children in a cross-sectional study of Shanghai. Indicators of home dampness were strongly and significantly associated with dry cough, wheeze, and rhinitis symptoms. In the current residence, children with visible mold spots (VMS) exposure had 32% higher risk of asthma (adjusted OR, 95% CI: 1.32, 1.07-1.64); damp clothing and/or bedding (frequently) was strongly associated with dry cough (1.78, 1.37-2.30); condensation on windows was strongly associated with hay fever (1.60, 1.27-2.01). In the early-life residence, VMS or damp stains (frequently) were strongly associated with dry cough (2.20, 1.55-3.11) and rhinitis ever (1.57, 1.11-2.21). Associations between dampness and diseases among children with or without family history of atopy were similar. The total number of dampness indicators had strong dose-response relationships with investigated health outcomes. Actions, including opening windows of the child's room at night and cleaning the child's room frequently, could potentially mitigate 25% of home VMS, thereby preventing more than 1.5% of attributable risk of the studied symptoms. PMID:24571077

Hu, Y; Liu, W; Huang, C; Zou, Z J; Zhao, Z H; Shen, L; Sundell, J

2014-10-01

 
 
 
 
301

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

302

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

International Nuclear Information System (INIS)

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

303

Muller's Nobel lecture on dose-response for ionizing radiation: ideology or science?  

Science.gov (United States)

In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose-response for radiation-induced germ cell mutations was linear and that there was "no escape from the conclusion that there is no threshold". However, assessment of correspondence between Muller and Curt Stern 1 month prior to his Nobel Prize Lecture reveals that Muller knew the results and implications of a recently completed study at the University of Rochester under the direction of Stern, which directly contradicted his Nobel Prize Lecture. This finding is of historical importance since Muller's Nobel Lecture gained considerable international attention and is a turning point in the acceptance of the linearity model in risk assessment for germ cell mutations and carcinogens. PMID:21717110

Calabrese, Edward J

2011-12-01

304

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

305

Dose-response relationships after incorporation of ?-active radionuclides by mycobacteria  

International Nuclear Information System (INIS)

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

306

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

307

A dose-response relationship between imitational suicides and newspaper distribution.  

Science.gov (United States)

Although the Werther effect is well known, up to now a correlation between the differential distribution of particular media reports and subsequent imitational suicides could not be found. This study investigates a celebrity suicide by gun in Austria, which led to extensive reports in the largest Austrian newspaper, whose distribution shows substantial regional differences. The numbers of suicides by firearm in the 3 weeks after the reporting showed an increase over the 3 weeks prior. Regional analysis revealed a strong correlation of suicides by firearm and distribution of the newspaper (log odds ratios; r(9) = .62; p = .04, one-tailed). This dose-response effect explains 40% of the variability of changes. These results underline the influence of media reports on suicidal behavior. PMID:16006399

Etzersdorfer, Elmar; Voracek, Martin; Sonneck, Gernot

2004-01-01

308

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

International Nuclear Information System (INIS)

hytherapy 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.

309

Dose-response effect of isometric force production on the perception of pain.  

Science.gov (United States)

Isometric contractions can influence the way that we perceive pain, but conclusions on the dose-response effect of force amplitude on pain perception are limited because previous studies have not held the duration of force contractions constant while varying force amplitude. To address this issue we designed an experiment that allowed us to accurately guide the amplitude of an isometric pinch grip force contraction on a trial-by-trial basis, while a thermal pain eliciting stimulus was simultaneously delivered for the same duration to the non-contracting hand. Our results show that an increase in the amplitude of force produced by one hand corresponded with a decrease in pain perception in the opposite hand. Our observations provide novel evidence that the centralized inhibitory response that underlies analgesia is sensitive to and enhanced by stronger isometric contractions. PMID:24505397

Misra, Gaurav; Paris, Tiffany A; Archer, Derek B; Coombes, Stephen A

2014-01-01

310

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

International Nuclear Information System (INIS)

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

311

A DoseResponse Study of Magnesium Sulfate in Suppressing Cardiovascular Responses to Laryngoscopy & Endotracheal Intubation  

Directory of Open Access Journals (Sweden)

Full Text Available Background: The effects of pretreatment with magnesium on cardiovascular responses associated with intubation have been studied previously. In this study we wanted to find optimal dose of magnesium that causes decreased cardiovascular responses after laryngoscopy & endotracheal intubation. Methods: In a double-blind , randomized, clinical trial ,120 ASA-1 patients with ages between 15-50 years old , who were candidates for elective surgery, were selected and classified in 6 groups (20 patients in each . The pulse rate and arterial blood pressure were measured and recorded at 5 minutes before taking any drug then, according to different groups, patients took magnesium sulfate (10, 20, 30, 40, 50mg/kg and lidocaine (1.5 mg/kg. The induction of anesthesia was same in all groups and the pulse rate and arterial blood pressure were measured and recorded just before intubation and also at 1, 3 , and 5 minutes after intubation (before surgical incision . Statistical analysis was performed by use of ANOVA, Post Hoc test (Duncan, Pearson correlation, and Chi square test. Results: there were no statistically significant differences in blood pressure, pulse rate, Train Of Four (TOF, and complications between groups who received magnesium but the significant differences in these parameters were seen between magnesium and lidocaine groups. Conclusion: We concluded that pretreatment with different doses of magnesium sulfate have a safe decreasing effect on cardiovascular responses that is more effective than pretreatment with lidocaine. Keywords: magnesium sulfate, cardiovascular responses, lidocaine.

K Montazeri

2005-03-01

312

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

313

Origin of the linearity no threshold (LNT) dose-response concept.  

Science.gov (United States)

This paper identifies the origin of the linearity at low-dose concept [i.e., linear no threshold (LNT)] for ionizing radiation-induced mutation. After the discovery of X-ray-induced mutations, Olson and Lewis (Nature 121(3052):673-674, 1928) proposed that cosmic/terrestrial radiation-induced mutations provide the principal mechanism for the induction of heritable traits, providing the driving force for evolution. For this concept to be general, a LNT dose relationship was assumed, with genetic damage proportional to the energy absorbed. Subsequent studies suggested a linear dose response for ionizing radiation-induced mutations (Hanson and Heys in Am Nat 63(686):201-213, 1929; Oliver in Science 71:44-46, 1930), supporting the evolutionary hypothesis. Based on an evaluation of spontaneous and ionizing radiation-induced mutation with Drosophila, Muller argued that background radiation had a negligible impact on spontaneous mutation, discrediting the ionizing radiation-based evolutionary hypothesis. Nonetheless, an expanded set of mutation dose-response observations provided a basis for collaboration between theoretical physicists (Max Delbruck and Gunter Zimmer) and the radiation geneticist Nicolai Timoféeff-Ressovsky. They developed interrelated physical science-based genetics perspectives including a biophysical model of the gene, a radiation-induced gene mutation target theory and the single-hit hypothesis of radiation-induced mutation, which, when integrated, provided the theoretical mechanism and mathematical basis for the LNT model. The LNT concept became accepted by radiation geneticists and recommended by national/international advisory committees for risk assessment of ionizing radiation-induced mutational damage/cancer from the mid-1950s to the present. The LNT concept was later generalized to chemical carcinogen risk assessment and used by public health and regulatory agencies worldwide. PMID:23887208

Calabrese, Edward J

2013-09-01

314

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2012-07-15

315

Dose-response relationship for lung cancer induction at radiotherapy dose  

Energy Technology Data Exchange (ETDEWEB)

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 {alpha}/{beta} = 3 Gy were {alpha} = 0.061Gy{sup -1} and R = 0.84. The value for {alpha} 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.)

Schneider, Uwe [Zuerich Univ. (Switzerland). Vetsuisse Faculty; Radiotherapy Hirslanden AG, Aarau (Switzerland). Hirslanden Medical Center; Stipper, Andrea; Besserer, Juergen [Radiotherapy Hirslanden AG, Aarau (Switzerland). Hirslanden Medical Center

2010-07-01

316

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

International Nuclear Information System (INIS)

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

317

An Experimental Toxoplasma gondii Dose Response Challenge Model to Study Therapeutic or Vaccine Efficacy in Cats  

Science.gov (United States)

High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10), and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application. PMID:25184619

Cornelissen, Jan B. W. J.; van der Giessen, Joke W. B.; Takumi, Katsuhisa; Teunis, Peter F. M.; Wisselink, Henk J.

2014-01-01

318

Effect of contrast water therapy duration on recovery of cycling performance: a dose-response study.  

Science.gov (United States)

This study investigated whether contrast water therapy (CWT) has a dose-response effect on recovery from high-intensity cycling. Eleven trained male cyclists completed four trials, each commencing with a 75-min cycling protocol containing six sets of five 15-s sprints and three 5-min time-trials in thermoneutral conditions. Ten minutes post-exercise, participants performed one of four recovery protocols: CWT for 6 min (CWT6), 12 min (CWT12), or 18 min (CWT18) duration, or a seated rest control trial. The CWT commenced in hot water (38.4 ± 0.6°C) and alternated between hot and cold water (14.6 ± 0.3°C) every minute with a 5-s changeover. The cycling protocol was repeated 2 h after completion of exercise bout one. Prior to exercise bout two, core temperature was lower in CWT12 (-0.19 ± 0.14°C, mean ± 90% CL) and CWT18 (-0.21 ± 0.10°C) than control. Compared with control, CWT6 substantially improved time-trial (1.5 ± 2.1%) and sprint performance (3.0 ± 3.1%), and CWT12 substantially improved sprint total work (4.3 ± 3.4%) and peak power (2.7 ± 3.8%) in exercise bout two. All CWT conditions generally improved thermal sensation, whole body fatigue and muscle soreness compared with control, but no differences existed between conditions in heart rate or rating of perceived exertion. In conclusion, CWT duration did not have a dose-response effect on recovery from high-intensity cycling; however, CWT for up to 12 min assisted recovery of cycling performance. PMID:20809231

Versey, Nathan; Halson, Shona; Dawson, Brian

2011-01-01

319

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

320

Pharmacokinetics and dose response of anti-TB drugs in rat infection model of tuberculosis.  

Science.gov (United States)

Robust and physiologically relevant infection models are required to investigate pharmacokinetic-pharmacodynamic (PK/PD) correlations for anti-tuberculosis agents at preclinical discovery. We have validated an inhalation-based rat infection model of tuberculosis harbouring mycobacteria in a replicating state, that is suitable for investigating pharmacokinetics and drug action of anti-tubercular agents. A reproducible and actively replicating lung infection was established in Wistar rats by inhalation of a series of graded inocula of Mycobacterium tuberculosis. Following an initial instillation of ?10(5) log10 CFU/lung, M. tuberculosis grew logarithmically for the first 3 weeks, and then entered into a chronic phase with no net increase in pulmonary bacterial loads. Dose response of front-line anti-TB drugs was investigated following pharmacokinetic measurements in the plasma of infected rats. Rifampicin, Isoniazid, and Ethambutol dosed per orally exhibited bactericidality and good dose response with maximal effect of 5.66, 4.66, and 4.80 log10 CFU reductions in the lungs, respectively. In contrast, Pyrazinamide was merely bacteriostatic with 1.92 log10 CFU/lung reduction and did not reduce the bacterial burden beyond the initial bacterial loads present at beginning of treatment in spite of high Pyrazinamide blood levels. Rat infection model with actively replicating bacilli provides a physiologically distinct and pharmacologically relevant model that can be exploited to distinguish investigational compounds in to bacteriostatic or bactericidal scaffolds. We propose that this rat infection model though need more drug substance, can be used in early discovery settings to investigate pharmacology of novel anti-tubercular agents for the treatment of active pulmonary tuberculosis. PMID:24629633

Kumar, Naveen; Vishwas, K G; Kumar, Mahesh; Reddy, Jitendar; Parab, Manish; Manikanth, C L; Pavithra, B S; Shandil, R K

2014-05-01

 
 
 
 
321

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

322

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

323

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

324

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

325

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  

Directory of Open Access Journals (Sweden)

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

326

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

327

Hormesis: from marginalization to mainstream A case for hormesis as the default dose-response model in risk assessment  

International Nuclear Information System (INIS)

The paper provides an account of how the hormetic dose response has emerged in recent years as a serious dose-response model in toxicology and risk assessment after decades of extreme marginalization. In addition to providing the toxicological basis of this dose-response revival, the paper reexamines the concept of a default dose model in toxicology and risk assessment and makes the argument that the hormetic model satisfies criteria (e.g., generalizability, frequency, application to risk assessment endpoints, false positive/negative potential, requirements for hazard assessment, reliability of estimating risks, capacity for validation of risk estimates, public health implications of risk estimates) for such a default model better than its chief competitors, the threshold and linear at low dose models. The selection of the hormetic model as the default model in risk assessment for noncarcinogens and specifically for carcinogens would have a profound impact on the practice of risk assessment and its societal implications

328

The dose-response for X-ray induction of myeloid leukaemia in male CBA/H mice  

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The form of the dose-response for induction of malignant diseases in vivo by ionizing radiation is not yet established in spite of its scientific interest and its practical importance. Considerably extended observations have confirmed that the dose-response for acute myeloid leukaemia induced in male CBA/H mice by X-ray exposure is highly curvilinear. The dose-response was well fitted by the expression aD2esup(-#betta#D) (D = dose) in agreement with induction at the cellular level in proportion to D2 over the whole dose range 0.25-6.0 Gy. The factor esup(-#betta#D) accounts for the inescapable concomitant inactivating action of the inducing irradiation. The quantitative aspects of induction of myeloid leukaemia by ionizing radiation are unlike the induction of genetic mutation or cell inactivation and suggest that interaction of two adjoining cells is an essential element in radiation leukaemogenesis. (author)

329

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

330

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

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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

331

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

332

A quantitative microbial risk assessment model for Legionnaires' disease: animal model selection and dose-response modeling.  

Science.gov (United States)

Legionnaires' disease (LD), first reported in 1976, is an atypical pneumonia caused by bacteria of the genus Legionella, and most frequently by L. pneumophila (Lp). Subsequent research on exposure to the organism employed various animal models, and with quantitative microbial risk assessment (QMRA) techniques, the animal model data may provide insights on human dose-response for LD. This article focuses on the rationale for selection of the guinea pig model, comparison of the dose-response model results, comparison of projected low-dose responses for guinea pigs, and risk estimates for humans. Based on both in vivo and in vitro comparisons, the guinea pig (Cavia porcellus) dose-response data were selected for modeling human risk. We completed dose-response modeling for the beta-Poisson (approximate and exact), exponential, probit, logistic, and Weibull models for Lp inhalation, mortality, and infection (end point elevated body temperature) in guinea pigs. For mechanistic reasons, including low-dose exposure probability, further work on human risk estimates for LD employed the exponential and beta-Poisson models. With an exposure of 10 colony-forming units (CFU) (retained dose), the QMRA model predicted a mild infection risk of 0.4 (as evaluated by seroprevalence) and a clinical severity LD case (e.g., hospitalization and supportive care) risk of 0.0009. The calculated rates based on estimated human exposures for outbreaks used for the QMRA model validation are within an order of magnitude of the reported LD rates. These validation results suggest the LD QMRA animal model selection, dose-response modeling, and extension to human risk projections were appropriate. PMID:18093054

Armstrong, T W; Haas, C N

2007-12-01

333

Research toward the development of a biologically based dose response assessment for inorganic arsenic carcinogenicity: A progress report  

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Cancer risk assessments for inorganic arsenic have been based on human epidemiological data, assuming a linear dose response below the range of observation of tumors. Part of the reason for the continued use of the linear approach in arsenic risk assessments is the lack of an adequate biologically based dose response (BBDR) model that could provide a quantitative basis for an alternative nonlinear approach. This paper describes elements of an ongoing collaborative research effort between the CIIT Centers for Health Research, the U.S. Environmental Protection Agency, ENVIRON International, and EPRI to develop BBDR modeling approaches that could be used to inform a nonlinear cancer dose response assessment for inorganic arsenic. These efforts are focused on: (1) the refinement of physiologically based pharmacokinetic (PBPK) models of the kinetics of inorganic arsenic and its metabolites in the mouse and human; (2) the investigation of mathematical solutions for multi-stage cancer models involving multiple pathways of cell transformation; (3) the review and evaluation of the literature on the dose response for the genomic effects of arsenic; and (4) the collection of data on the dose response for genomic changes in the urinary bladder (a human target tissue for arsenic carcinogenesis) associated with in vivo drinking water exposures in the mouse as well as in vitro exposures of both mouse and human cells. An approach is proposed for conducting a biologically based marginfor conducting a biologically based margin of exposure risk assessment for inorganic arsenic using the in vitro dose response for the expression of genes associated with the obligatory precursor events for arsenic tumorigenesis

334

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

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

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

2012-08-15

335

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

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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

336

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

337

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

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Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model. PMID:24879005

Loth, Eduardo Alexandre; Biazim, Samia Khalil; dos Santos, Jose Henrique Fermino Ferreira; Puccia, Rosana; Brancalhao, Rosimeire Costa; Chasco, Lucineia de Fatima; Gandra, Rinaldo Ferreira; Simao, Rita de Cassia Garcia; de Franco, Marcello Fabiano

2014-01-01

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

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

Science.gov (United States)

Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model. PMID:24879005

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

2014-01-01

340

Dose responses in a normoxic polymethacrylic acid gel dosimeter using optimal CT scanning parameters  

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The dosimetric characteristics of normoxic polymethacrylic acid gels are investigated using optimal CT scanning parameters and the possibility of their clinical application is also considered. The effects of CT scanning parameters (tube voltage, tube current, scan time, slick thickness, field of view, and reconstruction algorithm) are experimentally investigated to determine the optimal parameters for minimizing the amount of noise in images obtained using normoxic polymethacrylic acid gel. In addition, the dose sensitivity, dose response, accuracy, and reproducibility of the normoxic polymethacrylic acid gel are evaluated. CT images are obtained using a head phantom that is fabricated for clinical applications. In addition, IMRT treatment planning is performed using a Tomotherapy radiation treatment planning system. A program for analyzing the results is produced using Visual C. A comparison between the treatment planning and the CT images of irradiated gels is performed. The dose sensitivity is found to be 2.41{+-}0.04 HGy{sup -1}. The accuracies of dose evaluation at doses of 2 Gy and 4 Gy are 3.0% and 2.6%, respectively, and their reproducibilities are 2.0% and 2.1%, respectively. In the comparison of gel and Tomotherpay planning, the pass rate of the {gamma}-index, based on the reference values of a dose error of 3% and a DTA of 3 mm, is 93.7%.

Cho, K.H. [Department of Radiation Oncology, College of Medicine, Soonchunhyang University, Bucheon 420-767 (Korea, Republic of); Department of Medical Physics, Kyonggi University, Suwon 443-760 (Korea, Republic of); Cho, S.J. [Department of Radiation Oncology, College of Medicine, Eulji University, Seongnam 461-713 (Korea, Republic of); Lee, S. [Department of Radiation Oncology, College of Medicine, Korea University, Seoul 130-701 (Korea, Republic of); Lee, S.H. [Cheil General Hospital and Women' s Healthcare Center, Kwandong University College of Medicine, Seoul 100-380 (Korea, Republic of); Min, C.K.; Kim, Y.H.; Moon, S.K.; Kim, E.S.; Chang, A.R. [Department of Radiation Oncology, College of Medicine, Soonchunhyang University, Bucheon 420-767 (Korea, Republic of); Kwon, S.I., E-mail: sikwon@kyonggi.ac.kr [Department of Medical Physics, Kyonggi University, Suwon 443-760 (Korea, Republic of)

2012-05-21

 
 
 
 
341

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)

342

Using plant biomonitors and flux modelling to develop O3 dose-response relationships in Catalonia  

International Nuclear Information System (INIS)

We used tobacco Bel-W3 biomonitoring data and ozone flux modelling (WINDEP model) with the aim of developing the absorbed dose-response relationship, and comparing this approach with the most commonly used AOT40 (the sum of hourly ozone concentrations above a cut-off of 40 ppb during daylight hours, when global radiation exceeds 50 W m-2) in the estimation of exposure-damage curves. Leaf damage values were more related to OAD15days,potential (potential ozone absorbed dose calculated over 15 consecutive days) than to AOT40 in all the studied stations. An OAD15days,potential of 180 mg m-2 was found to be the threshold for damage to the most sensitive species in this region under well watered conditions. The results show the applicability of the flux approach for risk assessment at the local scale, the improvement of the ozone damage estimation when the potential absorbed dose is modelled and used instead of just the ozone exposure, and finally, the possibilities opened by the use of biomonitoring networks. - Modelling of biomonitors ozone absorbed dose improves damage estimation in comparison with exposure indices such as AOT40

343

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

344

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

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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

345

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

346

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

347

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

International Nuclear Information System (INIS)

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

348

Dose-response relationship in cyclophosphamide-treated B-cell lymphoma xenografts monitored with [18F]FDG PET  

International Nuclear Information System (INIS)

Although [18F]FDG PET can measure therapy response sooner and more accurately than morphological imaging techniques, there is still some debate as to whether [18F]FDG uptake really reflects changes in the viable cell fraction. In this study changes in [18F]FDG uptake were investigated in a lymphoma model at several time-points after treatment and with different doses of chemotherapy. Data were analysed in terms of several parameters. SCID mice were subcutaneously inoculated with 5 x 106 Daudi cells in the right thigh. One group was not treated (control group). The other groups received cyclophosphamide 75 mg/kg (low-dose group), 125 mg/kg (medium-dose group) and 175 mg/kg (high-dose group) on day 0. Sequential [18F]FDG small-animal PET (?PET) scans were performed on days 0, 2, 6, 9, 13 and 16 after treatment. The mean and maximum standardized uptake value (SUVmean and SUVmax), metabolic tumour volume (Volmetab) and total lesion glycolysis (TLG) were calculated. A significant decrease in [18F]FDG uptake was observed on day 2 in the medium-dose and high-dose groups and on day 6 in the low-dose group, all preceding morphological changes. SUVmean and SUVmax formed a plateau from day 6 to day 9, corresponding to the known influx of inflammatory cells. No obvious plateau was observed with TLG which was found to be the most sensitive parameter clearly dif the most sensitive parameter clearly differentiating the low-dose group from the medium- and high-dose groups early after therapy. [18F]FDG uptake was able to reflect the dose-response relationship for cyclophosphamide. TLG was the best parameter for dose-related response assessment in this tumour model. (orig.)

349

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

350

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

International Nuclear Information System (INIS)

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

351

Gestational exposure to chlorpyrifos: dose response profiles for cholinesterase and carboxylesterase activity.  

Science.gov (United States)

This study investigates the in vivo dose response profiles of the target enzyme cholinesterase (ChE) and the detoxifying enzymes carboxylesterase (CaE) in the fetal and maternal compartments of pregnant rats dosed with chlorpyrifos [(O,O'-diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate], a commonly used organophosphorus insecticide. Pregnant rats were dosed daily (po) with chlorpyrifos in corn oil (0, 3, 5, 7, or 10 mg/kg) on gestational days (GD) 14-18. Animals were sacrificed 5 h after the last chlorpyrifos dose (time of maximum brain cholinesterase inhibition) for analysis of ChE and CaE activity in maternal blood, liver, brain, placenta, and fetal liver and brain. The in vitro sensitivity (i.e., IC50, 30 min, 26 degrees C) of CaE also was determined by assaying the activity remaining after incubation with a range of chlorpyrifos-oxon concentrations. In vivo exposure to 10 mg/kg chlorpyrifos from GD14-18 caused overt maternal toxicity, with dose-related decreases in ChE activity more notable in maternal brain than fetal brain. Dose-related effects were also seen with chlorpyrifos-induced inhibition of fetal liver ChE and maternal brain CaE activities. Gestational exposure caused no inhibition of placental ChE or CaE, fetal brain CaE, or maternal blood CaE. ChE activities in the maternal blood and liver, as well as fetal and maternal liver CaE, however, were maximally inhibited by even the lowest dosage of chlorpyrifos. The in vitro sensitivity profiles of CaE to chlorpyrifos-oxon inhibition were valuable in predicting and verifying the in vivo CaE response profiles. Both the in vivo and in vitro findings indicated that fetal liver CaE inhibition was an extremely sensitive indicator of fetal chlorpyrifos exposure. PMID:10568702

Lassiter, T L; Barone, S; Moser, V C; Padilla, S

1999-11-01

352

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

353

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

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

Spigset Olav

2001-08-01

354

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

355

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

356

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

Energy Technology Data Exchange (ETDEWEB)

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 {mu}M and 0, 4, 10, 20 {mu}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 tool for detection of biological risk due to environmental toxicants or synthetic chemicals.

Kim, J. K.; Cheon, K. J.; Lee, B. H. [KAERI, Taejon (Korea, Republic of); Shin, H. S.; Lee, J. H. [Chungnam National Univ., Taejon (Korea, Republic of)

2002-05-01

357

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 tool for detection of biological risk due to environmental toxicants or synthetic chemicals

358

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 existe