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1

On the Statistical Significance  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A definition for the statistical significance by constructing a correlation between the normal distribution integral probability and the p-value observed in an experiment is proposed, which is suitable for both counting experiment and continuous test statistics.

Zhu, Yongsheng

2005-01-01

2

On Statistical Significance of Signal  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A definition for the statistical significance of a signal in an experiment is proposed by establishing a correlation between the observed p-value and the normal distribution integral probability, which is suitable for both counting experiment and continuous test statistics. The explicit expressions to calculate the statistical significance for both cases are given.

Zhu, Yong-sheng

2008-01-01

3

When is statistical significance not significant?  

Scientific Electronic Library Online (English)

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

Figueiredo Filho, Dalson Britto; Paranhos, Ranulfo; Rocha, Enivaldo C. da; Batista, Mariana; Silva Jr., José Alexandre da; Santos, Manoel L. Wanderley D.; Marino, Jacira Guiro.

4

Gene batteries and synexpression groups applied in a multivariate statistical approach to dose-response analysis of toxicogenomic data.  

Science.gov (United States)

Univariate statistical analyses have limited strength when employed in low-dose toxicogenomic studies, due to diminished magnitudes and frequencies of gene expression responses, compounded by high data dimensionality. Analysis using co-regulated gene sets and a multivariate statistical test based upon ranks of expression were explored as means to improve statistical confidence and biological insight at low-doses. Sixteen gene regulatory groups were selected in order to investigate murine hepatic gene expression changes following low-dose oral exposure to the beta-adrenergic agonist, isoproterenol (IPR). Gene sets in this focussed analysis included well-defined gene batteries and synexpression groups with co-regulated responses to toxin exposures and linkage of chronic responses to adverse outcomes. Significant changes of target gene expression within Nfkb, Stat3 and 5' terminal oligopryrimidine (5'TOP) batteries, as well as the acute phase and angiogenesis synexpression groups, were detected at IPR doses 100-fold lower than doses producing significant individual gene expression values. IPR-induced changes in these target gene groups were confirmed using a similar analysis of rat toxicogenomic data from published IPR-induced cardiotoxicity studies. Cumulative expression differences within gene sets were useful as aggregated metrics for benchmark dose calculations. The results supported the conclusion that toxicologically-relevant, co-regulated genes provide an effective means to reduce microarray dimensionality, thereby providing substantial statistical and interpretive power for quantitative analysis of low-dose, toxin-induced gene expression changes. PMID:23831126

Parfett, C; Williams, A; Zheng, J L; Zhou, G

2013-10-01

5

Statistical significance of communities in networks  

CERN Multimedia

We introduce a new measure aimed to quantify the statistical significance of communities in networks. Communities are seen as groups of nodes which maximize the densities of internal connections. Extreme Statistics is used to predict the statistics associated with communities, including confidence intervals. This allows us to quantify the statistical significance of communities in networks, detecting "artificial" communities arising as structural fluctuations in random graphs without intrinsic structure. The method is successfully applied in the case of real-world networks for the evaluation of the significance of their communities.

Lancichinetti, Andrea; Ramasco, Jose J

2009-01-01

6

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

Energy Technology Data Exchange (ETDEWEB)

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.

Frome, E.L. [Oak Ridge National Lab., TN (United States); Watkins, J.P. [Oak Ridge Inst. for Science and Education, TN (United States). Center for Epidemiologic Research

1997-11-01

7

Statistical Significance of the Gallium Anomaly  

CERN Document Server

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 about 2.9 sigma. A fit of the data in terms of neutrino oscillations favors at about 3.5 sigma short-baseline electron neutrino disappearance with respect to the null hypothesis of no oscillations.

Giunti, Carlo

2010-01-01

8

Systematic identification of statistically significant network measures  

Science.gov (United States)

We present a graph embedding space (i.e., a set of measures on graphs) for performing statistical analyses of networks. Key improvements over existing approaches include discovery of “motif hubs” (multiple overlapping significant subgraphs), computational efficiency relative to subgraph census, and flexibility (the method is easily generalizable to weighted and signed graphs). The embedding space is based on scalars, functionals of the adjacency matrix representing the network. Scalars are global, involving all nodes; although they can be related to subgraph enumeration, there is not a one-to-one mapping between scalars and subgraphs. Improvements in network randomization and significance testing—we learn the distribution rather than assuming Gaussianity—are also presented. The resulting algorithm establishes a systematic approach to the identification of the most significant scalars and suggests machine-learning techniques for network classification.

Ziv, Etay; Koytcheff, Robin; Middendorf, Manuel; Wiggins, Chris

2005-01-01

9

Assessment of statistical significance and clinical relevance  

DEFF Research Database (Denmark)

In drug development, it is well accepted that a successful study will demonstrate not only a statistically significant result but also a clinically relevant effect size. Whereas standard hypothesis tests are used to demonstrate the former, it is less clear how the latter should be established. In the first part of this paper, we consider the responder analysis approach and study the performance of locally optimal rank tests when the outcome distribution is a mixture of responder and non-responder distributions. We find that these tests are quite sensitive to their planning assumptions and have therefore not really any advantage over standard tests such as the t-test and the Wilcoxon-Mann-Whitney test, which perform overall well and can be recommended for applications. In the second part, we present a new approach to the assessment of clinical relevance based on the so-called relative effect (or probabilistic index) and derive appropriate sample size formulae for the design of studies aiming at demonstrating both a statistically significant and clinically relevant effect. Referring to recent studies in multiple sclerosis, we discuss potential issues in the application of this approach.

Kieser, M.; Friede, T.

2013-01-01

10

Biomarker discovery using statistically significant gene sets.  

Science.gov (United States)

Analysis of large gene expression data sets in the presence and absence of a phenotype can lead to the selection of a group of genes serving as biomarkers jointly predicting the phenotype. Among gene selection methods, filter methods derived from ranked individual genes have been widely used in existing products for diagnosis and prognosis. Univariate filter approaches selecting genes individually, although computationally efficient, often ignore gene interactions inherent in the biological data. On the other hand, multivariate approaches selecting gene subsets are known to have a higher risk of selecting spurious gene subsets due to the overfitting of the vast number of gene subsets evaluated. Here we propose a framework of statistical significance tests for multivariate feature selection that can reduce the risk of selecting spurious gene subsets. Using three existing data sets, we show that our proposed approach is an essential step to identify such a gene set that is generated by a significant interaction of its members, even improving classification performance when compared to established approaches. This technique can be applied for the discovery of robust biomarkers for medical diagnosis. PMID:21457009

Kim, Hoon; Watkinson, John; Anastassiou, Dimitris

2011-10-01

11

Statistical significance of close pairs of QSOs  

Energy Technology Data Exchange (ETDEWEB)

Previous workers have proposed a method of statistical analysis of close pairs of quasistellar objects (QSOs) to test the null hypothesis that the redshifts of QSOs are of cosmological origin. Close pairs of QSOs have been discovered and the statistical test can be applied. However the authors show that the probability of finding so many close pairs by chance, as required by the cosmological hypothesis, is as small as < or approx. 10 U, depending on observational uncertainties.

Burbidge, G.R.; Narlikar, J.V.; Hewitt, A.

1985-10-03

12

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.

13

The Significant Digit Law in Statistical Physics  

CERN Document Server

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

Shao, Lijing; 10.1016/j.physa.2010.04.021

2010-01-01

14

The significant digit law in statistical physics  

Science.gov (United States)

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

Shao, Lijing; Ma, Bo-Qiang

2010-08-01

15

Finding statistically significant communitites in networks  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Community structure is one of the main structural features of networks, revealing both their internal organization and the similarity of their elementary units. Despite the large variety of methods proposed to detect communities in graphs, there is a big need for multi-purpose techniques, able to handle different types of datasets and the subtleties of community structure. In this paper we present OSLOM (Order Statistics Local Optimization Method), the first method capable to detect clusters ...

Lancichinetti, A.; Radicchi, Filippo; Ramasco, Jose? J.; Fortunato, Santo

2011-01-01

16

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

17

Nonlinearity of dose responses in thermoluminescence dosimetry  

International Nuclear Information System (INIS)

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

1995-01-01

18

A Statistical Significance Simulation Study for the General Scientist  

CERN Multimedia

When a scientist performs an experiment they normally acquire a set of measurements and are expected to demonstrate that their results are "statistically significant" thus confirming whatever hypothesis they are testing. The main method for establishing statistical significance involves demonstrating that there is a low probability that the observed experimental results were the product of random chance. This is typically defined as p < 0.05, which indicates there is less than a 5% chance that the observed results occurred randomly. This research study visually demonstrates that the commonly used definition for "statistical significance" can erroneously imply a significant finding. This is demonstrated by generating random Gaussian noise data and analyzing that data using statistical testing based on the established two-sample t-test. This study demonstrates that insignificant yet "statistically significant" findings are possible at moderately large sample sizes which are very common in many fields of mode...

Levman, Jacob

2011-01-01

19

Test for the Statistical Significance of Differences Between ROC Curves.  

Science.gov (United States)

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 a...

C. E. Metz H. B. Kronman

1979-01-01

20

Beyond Statistical Significance: Implications of Network Structure on Neuronal Activity  

Digital Repository Infrastructure Vision for European Research (DRIVER)

It is a common and good practice in experimental sciences to assess the statistical significance of measured outcomes. For this, the probability of obtaining the actual results is estimated under the assumption of an appropriately chosen null-hypothesis. If this probability is smaller than some threshold, the results are deemed statistically significant and the researchers are content in having revealed, within their own experimental domain, a “surprising” anomaly, possibly indicative of ...

Vlachos, Ioannis; Aertsen, Ad; Kumar, Arvind

2012-01-01

 
 
 
 
21

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

2001-06-01

22

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

23

Cancer dose-response extrapolations  

Energy Technology Data Exchange (ETDEWEB)

Quantitative dose-response modeling is an important contributor to cancer risk assessment; hence, it is a major factor in cancer risk management and the regulatory process. The dose-response models now used in the regulatory process are overly simplistic, probabilistic representations of highly complex biological phenomena; these models are not biological models. Several of these simplistic models provide similar fits to the high-dose data generated in chronic animal bioassays but provide dissimilar projections of risk at the lower doses of interest to man. The possibilities for the low-dose behavior of a simplistic model can be so independent of the fit of that model to the experimental data that an upper confidence limit, or upper bound, on the risk at a low dose can be orders of magnitude larger than the fitted model. The potency measures, such as unit risks and relative risks, cited by the regulatory agencies are based on upper bounds and not on fitted model values. These measurements do not differentiate between carcinogens on the basis of available experimental data about the shapes of the dose-response relationship. In order to obtain more useful quantitative dose-response assessments, the plethora of simplistic models must be replaced by more biologically reflective dose-response models that utilize the available scientific information. New dose-response modeling techniques can incorporate representations of the exposure in terms of dose scales based on cell turnover rates, repair processes, immune system responses, and physiological and pharmacokinetic models of the absorption, delivery, metabolism, and elimination of chemicals.

Sielken, R.L. Jr.

1987-11-01

24

A Comparison of Statistical Significance Tests for Selecting Equating Functions  

Science.gov (United States)

This study compared the accuracies of nine previously proposed statistical significance tests for selecting identity, linear, and equipercentile equating functions in an equivalent groups equating design. The strategies included likelihood ratio tests for the loglinear models of tests' frequency distributions, regression tests, Kolmogorov-Smirnov…

Moses, Tim

2009-01-01

25

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

1986-01-01

26

Curvilinearity in the dose-response curve for cancer in Japanese atomic bomb survivors.  

Science.gov (United States)

Recently released data on cancer incidence in Japanese atomic bomb survivors are analyzed using a variety of relative risk models that take account of errors in estimates of dose to assess the dose response at low doses. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to solid cancer data, a threshold of more than about 0.2 Sv is inconsistent with the data, whereas these data are consistent with there being no threshold. Among solid cancer subtypes there is strong evidence for a possible dose threshold only for nonmelanoma skin cancer. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to the leukemia data, a threshold of more than about 0.3 Sv is inconsistent with the data. In contrast to the estimates for the threshold level for solid cancer data, the best estimate for the threshold level in the leukemia data is significantly different from zero even when allowance is made for a possible quadratic term in the dose response, albeit at borderline levels of statistical significance (p = 0.04). There is little evidence for curvature in the leukemia dose response from 0.2 Sv upwards. However, possible underestimation of the errors in the estimates of the dose threshold as a result of confounding and uncertainties not taken into account in the analysis, together with the lack of biological plausibility of a threshold, makes interpretation of this finding questionable.

Little, M P; Muirhead, C R

1997-01-01

27

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

International Nuclear Information System (INIS)

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

2005-02-01

28

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

1979-01-01

29

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

30

The ongoing tyranny of statistical significance testing in biomedical research.  

Science.gov (United States)

Since its introduction into the biomedical literature, statistical significance testing (abbreviated as SST) caused much debate. The aim of this perspective article is to review frequent fallacies and misuses of SST in the biomedical field and to review a potential way out of the fallacies and misuses associated with SSTs. Two frequentist schools of statistical inference merged to form SST as it is practised nowadays: the Fisher and the Neyman-Pearson school. The P-value is both reported quantitatively and checked against the alpha-level to produce a qualitative dichotomous measure (significant/nonsignificant). However, a P-value mixes the estimated effect size with its estimated precision. Obviously, it is not possible to measure these two things with one single number. For the valid interpretation of SSTs, a variety of presumptions and requirements have to be met. We point here to four of them: study size, correct statistical model, correct causal model, and absence of bias and confounding. It has been stated that the P-value is perhaps the most misunderstood statistical concept in clinical research. As in the social sciences, the tyranny of SST is still highly prevalent in the biomedical literature even after decades of warnings against SST. The ubiquitous misuse and tyranny of SST threatens scientific discoveries and may even impede scientific progress. In the worst case, misuse of significance testing may even harm patients who eventually are incorrectly treated because of improper handling of P-values. For a proper interpretation of study results, both estimated effect size and estimated precision are necessary ingredients. PMID:20339903

Stang, Andreas; Poole, Charles; Kuss, Oliver

2010-04-01

31

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.)

1993-09-28

32

Statistical significance of climate sensitivity predictors obtained by data mining  

Science.gov (United States)

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

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

2014-03-01

33

A new approach to evaluating statistical significance of spectral identifications.  

Science.gov (United States)

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

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

2013-04-01

34

Beyond statistical significance: implications of network structure on neuronal activity.  

Science.gov (United States)

It is a common and good practice in experimental sciences to assess the statistical significance of measured outcomes. For this, the probability of obtaining the actual results is estimated under the assumption of an appropriately chosen null-hypothesis. If this probability is smaller than some threshold, the results are deemed statistically significant and the researchers are content in having revealed, within their own experimental domain, a "surprising" anomaly, possibly indicative of a hitherto hidden fragment of the underlying "ground-truth". What is often neglected, though, is the actual importance of these experimental outcomes for understanding the system under investigation. We illustrate this point by giving practical and intuitive examples from the field of systems neuroscience. Specifically, we use the notion of embeddedness to quantify the impact of a neuron's activity on its downstream neurons in the network. We show that the network response strongly depends on the embeddedness of stimulated neurons and that embeddedness is a key determinant of the importance of neuronal activity on local and downstream processing. We extrapolate these results to other fields in which networks are used as a theoretical framework. PMID:22291581

Vlachos, Ioannis; Aertsen, Ad; Kumar, Arvind

2012-01-01

35

Skull base chordomas: analysis of dose-response characteristics  

International Nuclear Information System (INIS)

Objective: To extract dose-response characteristics from dose-volume histograms and corresponding actuarial survival statistics for 115 patients with skull base chordomas. Materials and Methods: We analyzed data for 115 patients with skull base chordoma treated with combined photon and proton conformal radiotherapy to doses in the range 66.6Gy - 79.2Gy. Data set for each patient included gender, histology, age, tumor volume, prescribed dose, overall treatment time, time to recurrence or time to last observation, target dose-volume histogram, and several dosimetric parameters (minimum/mean/median/maximum target dose, percent of the target volume receiving the prescribed dose, dose to 90% of the target volume, and the Equivalent Uniform Dose (EUD). Data were analyzed using the Kaplan-Meier survivor function estimate, the proportional hazards (Cox) model, and parametric modeling of the actuarial probability of recurrence. Parameters of dose-response characteristics were obtained using the maximum likelihood method. Results: Local failure developed in 42 (36%) of patients, with actuarial local control rates at 5 years of 59.2%. The proportional hazards model revealed significant dependence of gender on the probability of recurrence, with female patients having significantly poorer prognosis (hazard ratio of 2.3 with the p value of 0.008). The Wilcoxon and the log-rank tests of the corresponding Kaplan-Meier recurrence-free survival curves confirmed statistical significance of this effect. The Cox model with stratification by gender showed significance of tumor volume (p=0.01), the minimum target dose (p=0.02), and the EUD (p=0.02). Other parameters were not significant at the ? level of significance of 0.05, including the prescribed dose (p=0.21). Parametric analysis using a combined model of tumor control probability (to account for non-uniformity of target dose distribution) and the Weibull failure time model (to account for censoring) allowed us to estimate parameters of the time-dose-response relationship for the analyzed group of patients. For example, the maximum likelihood estimates of surviving fraction at 2Gy (SF2) are 0.47 with 95% confidence limits of [0.45-0.49] for male and 0.53 [0.51-0.55] for female, with the coefficient of inter-patient variation in SF2 of 4.3%. The density of clonogens was estimated to be 108.2 clonogens per cubic centimeter. In effect, the slope of the dose-response curve, ?50, was estimated to be 2.7 [1.9-3.2] for both male and female, and the ED50 doses to be 67Gy and 73Gy respectively. Skull base chordomas of the female patients seemed to be not only more resistant to radiation but also recurring faster than that for male patients (the maximum likelihood estimates of the Weibull shape parameter ? are 2.6 for female and 1.7 for male patients). Conclusions: This analysis revealed several clinically important characteristics of radioresponsiveness of skull base chordomas. The comprehensive patient data obtained using three-dimensional treatment planning system allowed us to demonstrate and quantify the existence of dose-response and dose-volume relationships. In consequence, we are able to estimate prospectively the individual's probability of staying recurrence-free and her/his overall survival characteristics as a function of the applied three-dimensional dose distribution and time after treatment. Based on the analysis our treatment protocols have been modified to account for differences in radiosensitivity between female and male patients

1997-01-01

36

Lexical Co-occurrence, Statistical Significance, and Word Association  

CERN Document Server

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

Chaudhari, Dipak; Laxman, Srivatsan

2010-01-01

37

Effect of irradiation and storage temperature on PRESAGETM dose response  

International Nuclear Information System (INIS)

The temperature dependence of the PRESAGETM dosimeter dose response has been investigated. Two series of measurements were performed. The first for measuring the temperature dependence during irradiation and the second for temperature dependence during post-irradiation storage. These measurements shows significant temperature dependence on dose response both during irradiation and storage with activation energies of respectively 1.4±0.2 eV and 1.9±0.2 eV.

2010-11-01

38

The statistical significance of the superhump signal in U Gem  

CERN Document Server

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

Schreiber, M R

2007-01-01

39

International stock return predictability: statistical evidence and economic significance  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The predictability of stock returns in ten countries is assessed taking into account recently developed out-of-sample statistical tests and risk-adjusted metrics. Predictive variables include both valuation ratios and interest rate variables. Out-of-sample predictive power is found to be greatest for the short-term and long-term interest rate variables. Given the importance of trading profitability in assessing market efficiency, we show that such statistical predictive power is economically ...

Giot, Pierre; Petitjean, Mikael

2006-01-01

40

In vitro human cytogenetic dose-response systems  

International Nuclear Information System (INIS)

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

1979-10-20

 
 
 
 
41

Classic dose-response and time postinoculation models for leptospira.  

Science.gov (United States)

Leptospirosis is a preeminent zoonotic disease concentrated in tropical areas, and prevalent in both industrialized and rural settings. Dose-response models were generated from 22 data sets reported in 10 different studies. All of the selected studies used rodent subjects, primarily hamsters, with the predominant endpoint as mortality with the challenge strain administered intraperitoneally. Dose-response models based on a single evaluation postinfection displayed median lethal dose (LD50 ) estimates that ranged between 1 and 10(7) leptospirae depending upon the strain's virulence and the period elapsed since the initial exposure inoculation. Twelve of the 22 data sets measured the number of affected subjects daily over an extended period, so dose-response models with time-dependent parameters were estimated. Pooling between data sets produced seven common dose-response models and one time-dependent model. These pooled common models had data sets with different test subject hosts, and between disparate leptospiral strains tested on identical hosts. Comparative modeling was done with parallel tests to test the effects of a single different variable of either strain or test host and quantify the difference by calculating a dose multiplication factor. Statistical pooling implies that the mechanistic processes of leptospirosis can be represented by the same dose-response model for different experimental infection tests even though they may involve different host species, routes, and leptospiral strains, although the cause of this pathophysiological phenomenon has not yet been identified. PMID:24117870

Watanabe, Toru; Teske, Sondra S; Haas, Charles N

2014-03-01

42

Exploring the dose response of radiochromic dosimeters  

International Nuclear Information System (INIS)

The aim of this study was to explore the dose response of a newly developed radio-chromic hydrogel dosimeter based on leuco malachite green dye in a gelatine matrix. The original dosimeter composition was first investigated in terms of dose response and dose-rate dependence. In addition, the initiating compounds producing chlorine radicals were substituted with compounds producing fluorine radicals, oxygen-centered radicals, carbon-centered radicals and bromine radicals. Also the surfactant was substituted by other compounds of different molecular size and charge. The original composition gave a dose response of 3.5·10?3 Gy?1cm?1 at 6 Gy/min with a dose rate dependence giving a 27 % increase when decreasing the dose rate to 1 Gy/min. None of the substituted initiating components contributed to an increase in dose response while only one surfactant increased the dose response slightly.

2013-06-26

43

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

44

Library Statistics and User Satisfaction: No Significant Correlation.  

Science.gov (United States)

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

De Gennaro, Richard

1980-01-01

45

Cluster analysis: significance, empty space, clustering tendency, non-uniformity. I--Statistical tests on the significance of clusters.  

Science.gov (United States)

The agglomerative clustering methods and the tests usually applied to evaluate the significance of clusters are critically evaluated. Many clustering techniques can provide erroneous information about the existence of clusters. The single linkage technique is suggested to identify natural, well separated, clusters. The existing statistical tests on the significance of clusters are not satisfactory. A new statistical test, based on the distribution of the distances between the objects and their first nearest neighbor, is presented. The performances of the test are compared with those of the Sneath test and of the variance-ratio test on some artificial and real data sets. PMID:12650574

Forina, M; Casolino, C; Lanteri, S

2003-01-01

46

Study on relationships of time-response and dose-response of radiation-induced DNA damages using single cell gel electrophoresis for rapid dose assessment  

International Nuclear Information System (INIS)

The relationships of time-response and dose-response of DNA damages of peripheral blood cell induced by 60Co ? radiation were studied using single cell gel electrophoresis and the feasibility of SCGE as a biological dosimeter was discussed. Mice and human peripheral blood cells were irradiated in vivo an in vitro respectively, for drawing up curves of time-response and dose-response. In vivo, DNA damages in mice peripheral blood cells were the most serious immediately after irradiation, and were essentially repaired 2 h after irradiation and had no statistically significant difference (p>0.05) between irradiation and control groups 24 h after irradiation. In vitro, TM value of human peripheral blood cells increased in a dose dependent manner, and a extremely statistically significant difference was observed between irradiation and control groups after irradiation immediately. The dose-response relationship well fitted with linear model: Y=0.3619 + 2.1834D (r=0.9946). However, there has been no statistical difference (p>0.05) between irradiation and control groups 6 h after irradiation. The results indicate that SCGE is a rapid, sensitive method for examining radiation-induced DNA damages, and has showed a well linear dose-response relation although it can only measure in a limited time range as damages repaired more rapidly. (authors)

2006-11-01

47

Dose response models for chemical carcinogens  

International Nuclear Information System (INIS)

The response to exposure to chemical carcinogenic agents depends not only on dose but also on a number of time variables. The variation of response with time after exposure of limited duration has been shown to depend on the mode of action of the exposure. Multistage models of carcinogenesis provide a framework for describing the observed range of behaviour, in which agents are classified as primary early stage or primarily late stage in their action. Response curves as a function of dose rate for continuous exposures vary widely for agents which are classified as late stage in action. Early stage agents show greater regularity, tumour yield typically increasing as a linear to quadratic function of dose rate. Dose response curves may be modified by the presence of other agents, and joint dose responses, the effect of exposure to several agents, can take a variety of forms. Multistage models again provide a powerful unifying framework

1983-01-01

48

Dose-Response—A Challenge for Allelopathy?  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of no...

Belz, Regina G.; Hurle, Karl; Duke, Stephen O.

2005-01-01

49

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

Science.gov (United States)

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

Xu, Kuan-Man

2006-01-01

50

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

51

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.)

1989-01-01

52

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)

1981-04-30

53

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

54

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

55

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

56

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

57

Low doses of gamma-radiation induce nonlinear dose responses in Mammalian and plant cells.  

Science.gov (United States)

The percentage of cells with chromosome aberrations or micronuclei induced by low doses of acute (dose rate of 47 cGy/min) or chronic (dose rate of 0.01 cGy/min) gamma-irradiation was studied in vitro in Chinese hamster fibroblasts, human lymphocytes, and Vicia faba seeds and seedlings. The sensitivity of the indicated biological entities to low doses was greater than expected based on linear extrapolation from higher doses. The dose-response curves for cytogenetic damage that were obtained were nonlinear when evaluated over the full range of the doses used. At very low doses, the dose-response curves appeared linear, followed by a plateau region at intermediate doses. At high doses the dose response curves again appeared linear with a slope different from that for the low-dose region. There was no statistically significant difference between the yields of cells with micronuclei induced by low doses of acute versus chronic irradiation. Similar data were obtained both for human lymphocyte culture and for roots and seeds of Vicia faba. Our experiments revealed that the dose range over which the plateau occurs depends on the type of cells irradiated. We have also shown that the modifying effects of the repair inhibitor caffeine and the radioprotector mercaptoethylenamine (MEA) are absent at low doses of gamma irradiation and that caffeine increased the number of cells with cytogenetic damage when evaluated over the plateau region. In the presence of MEA, the upper end of the plateau region was extended from just above 1 Gy to about 2 Gy. We therefore provide direct evidence that a plateau exists in the dose-response curve for the indicated radiation-induced stochastic effects. Furthermore, our results suggest that, for low linear energy transfer radiation, the induction of DNA repair occurs only after a threshold level of cytogenetic damage and that the higher yield of cytogenetic damage per unit dose at low radiation doses is attributable to an insignificant contribution or the absence of DNA repair processes. PMID:19330144

Zaichkina, S I; Rozanova, O M; Aptikaeva, G F; Achmadieva, A Ch; Klokov, D Y

2004-07-01

58

Effect of irradiation and storage temperature on PRESAGE{sup TM} dose response  

Energy Technology Data Exchange (ETDEWEB)

The temperature dependence of the PRESAGE{sup TM} dosimeter dose response has been investigated. Two series of measurements were performed. The first for measuring the temperature dependence during irradiation and the second for temperature dependence during post-irradiation storage. These measurements shows significant temperature dependence on dose response both during irradiation and storage with activation energies of respectively 1.4{+-}0.2 eV and 1.9{+-}0.2 eV.

Skyt, P S; Balling, P; Petersen, J B; Yates, E S; Muren, L P, E-mail: skyt@phys.au.d

2010-11-01

59

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

1984-03-01

60

Radiation dose-response of human tumors  

International Nuclear Information System (INIS)

The dose of radiation that locally controls human tumors treated electively or for gross disease is rarely well defined. These doses can be useful in understanding the dose requirements of novel therapies featuring inhomogeneous dosimetry and in an adjuvant setting. The goal of this study was to compute the dose of radiation that locally controls 50% (TCD50) of tumors in human subjects. Logit regression was used with data collected from single institutions or from combinations of local control data accumulated from several institutions treating the same disease. 90 dose response curves were calculated: 62 of macroscopic tumor therapy, 28 of elective therapy with surgery for primary control. The mean and median TCD50 for gross disease were 50.0 and 51.9 Gy, respectively. The mean and median TCD50 for microscopic disease control were 39.3 and 37.9 Gy, respectively. At the TCD50, an additional dose of 1 Gy controlled an additional 2.5% (median) additional patients with macroscopic disease and 4.2% (median) additional patients with microscopic disease. For both macro- and microscopic disease, an increase of 1% of dose at the TCD50 increased control rates ? 1% (median) or 2-3% (mean). A predominance of dose response curves had shallow slopes accounting for the discrepancy between mean and median values. Doses to control microscopic disease are approximately 12 Gy less than that required to control macroscopic disease and about 79% of the dose required to control macroscopic disease. The percentage increase in cures expected for a 1% increase in dose is similar for macroscopic and microscopic disease, with a median value of ? 1%/% and a mean of ? 2.7%/%. 94 refs., 4 figs., 6 tabs

1995-07-15

 
 
 
 
61

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

Science.gov (United States)

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

Spinella, Sarah

2011-01-01

62

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

Science.gov (United States)

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

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

2011-01-01

63

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

2004-01-01

64

Leisure-time physical activity and endometrial cancer risk: dose-response meta-analysis of epidemiological studies.  

Science.gov (United States)

Although considerable evidence suggests that leisure-time physical activity is associated with a reduced risk of endometrial cancer (EC), the shape of dose-response relationship has not been investigated and previous meta-analyses have not accounted for differences in measures of physical activity. To address such issues, we conducted linear and nonlinear dose-response meta-analyses by metabolic equivalent of task (MET)-hour/week and hour/week, respectively, based on observational studies published up to September 2013 identified from PubMed and Embase databases. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. In the linear dose-response analysis, an increase in leisure-time physical activity by 3 MET-hour/week was associated with an ?2% reduced risk of EC (summary RR?=?0.98, p?=?0.02, 95% CI?=?0.95-1.00, I(2) ?=?53%, p(heterogeneity) ?=?0.06, three case-control studies and three cohort studies, 3,460 cases, range of activity?=?0-50 MET-hour/week) and an increase by an hour/week was associated with an ?5% reduced risk of EC (summary RR?=?0.95, p?activity?=?0-12 hour/week). Nonlinear dose-response meta-analysis suggested that the curve may plateau at 10 MET-hour/week (p(change) in slope ?=?0.04) but this statistical significance was sensitive to one study. No evidence of a nonlinear association was indicated by hour/week (p(change) in slope ?>?0.69). In conclusion, an increase in leisure-time physical activity may continue to decrease EC risk, within the range of 0-50 MET-hour/week or 0-15 hour/week. Future studies should evaluate possible independent role of intensity of physical activity and effect modification by obesity. PMID:24375149

Keum, NaNa; Ju, Woong; Lee, Dong Hoon; Ding, Eric L; Hsieh, Chung C; Goodman, Julie E; Giovannucci, Edward L

2014-08-01

65

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)

1993-07-01

66

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

67

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

Science.gov (United States)

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

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

2003-12-01

68

When is Chemical Similarity Significant? The Statistical Distribution of Chemical Similarity Scores and Its Extreme Values  

Digital Repository Infrastructure Vision for European Research (DRIVER)

As repositories of chemical molecules continue to expand and become more open, it becomes increasingly important to develop tools to search them efficiently and assess the statistical significance of chemical similarity scores. Here we develop a general framework for understanding, modeling, predicting, and approximating the distribution of chemical similarity scores and its extreme values in large databases. The framework can be applied to different chemical representations and similarity me...

Baldi, Pierre; Nasr, Ramzi

2010-01-01

69

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

Directory of Open Access Journals (Sweden)

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

70

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)

1997-01-01

71

On the statistical uncertainty in long term predictions of significant wave height  

Energy Technology Data Exchange (ETDEWEB)

This work examines some aspects involved in the estimation of the parameters of the probability distribution of significant wave height, in particular the homogeneity of the data sets and the statistical methods of fitting a distribution to data. More homogeneous data sets are organized by collecting the data on a monthly basis and by separating the simple sea states from the combined ones. The parameters of the fitted distribution are estimated by the method of maximum likelihood, of regression and of the moments. The uncertainty involved in estimating the probability distribution with the three methods is compared with the one that results from using more homogeneous data sets and it is concluded that the uncertainty involved in the fitting procedure can be more significant.

Guedes Soares, C.; Henriques, A.C. [Technical Univ. of Lisbon (Portugal). Dept. of Naval Architecture and Ocean Engineering

1994-12-31

72

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

CERN Multimedia

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

Hu, R; Hu, Rui; Wang, Bin

2000-01-01

73

Sample size and significance – somewhere between statistical power and judgment prostration  

Directory of Open Access Journals (Sweden)

Full Text Available When performing scientific research we are so “embraced” to use the tool of inductive logic in our reasoning that we often express more generalized opinions on the population of interest based on relatively small sample(s of a general population. What we take care about in such situations is that chosen segments are representative for a whole set of elements in the general population. To cope with such a demand we always want to know how large our selected subpopulation should be to enable us to detect the experimental effect of interest not only at a certain level of significance, but also with the highest possible power of statistical reasoning. Thus, when designing our experiment, we have to compromise between a sample size not too small to ensure that our sample is sufficiently representative, and not too large to benefit from the sampling procedure at all. The tools for the estimation of minimum required sample size and the analysis of power, which help us to make quick decisions on how to compromise reasonably between significance, statistical power and sample size, are discussed in this paper.

Cezary Wata?a

2007-03-01

74

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

Directory of Open Access Journals (Sweden)

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

Zakaria M. Sawan

2011-05-01

75

Time-frequency microstructure and statistical significance of ERD and ERS.  

Science.gov (United States)

ERD and ERS were introduced as the time courses of the average changes of energy in given frequency bands. These curves are naturally embedded in the time-frequency plane. Time-frequency density of signals energy can be estimated by means of a variety of transforms. In general, resolution of these methods depends on a priori choices of parameters regulating the tradeoff between the time and frequency resolutions. As an exception, adaptive time-frequency approximations adapt resolution to the local structures of the analyzed signal. Matching pursuit (MP) algorithm is a reliable implementation of this approach. Its application to the event-related EEG allows for a detailed presentation of the time-frequency microstructure of changes of the average energy density, as well as calculation of high-resolution maps of ERD/ERS in the time-frequency plane. However, even with such a detailed picture of the signal energy changes, their significance remains an open issue. Owing to a stochastic character of the EEG, a visible increase or decrease of energy can occur due to a pure chance or a phenomenon unrelated to the event. For a proper estimation of the statistical significance of ERD/ERS, that is, the average changes of signals energy density in relation to the reference period, we must take into account possibly non-normal distributions of energy, and, especially, the problem of multiple comparisons appearing in hypotheses related to different frequency bands and time epochs. This chapter presents and discusses a complete framework for high-resolution estimation of the ERD/ERS microstructure in the time-frequency regions, revealing statistically significant changes. PMID:17071227

Durka, P J

2006-01-01

76

On the validity versus utility of activity landscapes: are all activity cliffs statistically significant?  

Science.gov (United States)

Background Most work on the topic of activity landscapes has focused on their quantitative description and visual representation, with the aim of aiding navigation of SAR. Recent developments have addressed applications such as quantifying the proportion of activity cliffs, investigating the predictive abilities of activity landscape methods and so on. However, all these publications have worked under the assumption that the activity landscape models are “real” (i.e., statistically significant). Results The current study addresses for the first time, in a quantitative manner, the significance of a landscape or individual cliffs in the landscape. In particular, we question whether the activity landscape derived from observed (experimental) activity data is different from a randomly generated landscape. To address this we used the SALI measure with six different data sets tested against one or more molecular targets. We also assessed the significance of the landscapes for single and multiple representations. Conclusions We find that non-random landscapes are data set and molecular representation dependent. For the data sets and representations used in this work, our results suggest that not all representations lead to non-random landscapes. This indicates that not all molecular representations should be used to a) interpret the SAR and b) combined to generate consensus models. Our results suggest that significance testing of activity landscape models and in particular, activity cliffs, is key, prior to the use of such models.

2014-01-01

77

Statistically significant faunal differences among Middle Ordovician age, Chickamauga Group bryozoan bioherms, central Alabama  

Energy Technology Data Exchange (ETDEWEB)

Middle Ordovician age Chickamauga Group carbonates crop out along the Birmingham and Murphrees Valley anticlines in central Alabama. The macrofossil contents on exposed surfaces of seven bioherms have been counted to determine their various paleontologic characteristics. Twelve groups of organisms are present in these bioherms. Dominant organisms include bryozoans, algae, brachiopods, sponges, pelmatozoans, stromatoporoids and corals. Minor accessory fauna include predators, scavengers and grazers such as gastropods, ostracods, trilobites, cephalopods and pelecypods. Vertical and horizontal niche zonation has been detected for some of the bioherm dwelling fauna. No one bioherm of those studied exhibits all 12 groups of organisms; rather, individual bioherms display various subsets of the total diversity. Statistical treatment (G-test) of the diversity data indicates a lack of statistical homogeneity of the bioherms, both within and between localities. Between-locality population heterogeneity can be ascribed to differences in biologic responses to such gross environmental factors as water depth and clarity, and energy levels. At any one locality, gross aspects of the paleoenvironments are assumed to have been more uniform. Significant differences among bioherms at any one locality may have resulted from patchy distribution of species populations, differential preservation and other factors.

Crow, C.J.

1985-01-01

78

Mining Statistically Significant Substrings Based on the Chi-Square Measure  

CERN Multimedia

Given the vast reservoirs of data stored worldwide, efficient mining of data from a large information store has emerged as a great challenge. Many databases like that of intrusion detection systems, web-click records, player statistics, texts, proteins etc., store strings or sequences. Searching for an unusual pattern within such long strings of data has emerged as a requirement for diverse applications. Given a string, the problem then is to identify the substrings that differs the most from the expected or normal behavior, i.e., the substrings that are statistically significant. In other words, these substrings are less likely to occur due to chance alone and may point to some interesting information or phenomenon that warrants further exploration. To this end, we use the chi-square measure. We propose two heuristics for retrieving the top-k substrings with the largest chi-square measure. We show that the algorithms outperform other competing algorithms in the runtime, while maintaining a high approximation...

Bhattacharya, Sourav Dutta Arnab

2010-01-01

79

Pairwise statistical significance of local sequence alignment using multiple parameter sets and empirical justification of parameter set change penalty  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Accurate estimation of statistical significance of a pairwise alignment is an important problem in sequence comparison. Recently, a comparative study of pairwise statistical significance with database statistical significance was conducted. In this paper, we extend the earlier work on pairwise statistical significance by incorporating with it the use of multiple parameter sets. Results Results for a knowledge discovery application of homology detection reveal that using multiple parameter sets for pairwise statistical significance estimates gives better coverage than using a single parameter set, at least at some error levels. Further, the results of pairwise statistical significance using multiple parameter sets are shown to be significantly better than database statistical significance estimates reported by BLAST and PSI-BLAST, and comparable and at times significantly better than SSEARCH. Using non-zero parameter set change penalty values give better performance than zero penalty. Conclusion The fact that the homology detection performance does not degrade when using multiple parameter sets is a strong evidence for the validity of the assumption that the alignment score distribution follows an extreme value distribution even when using multiple parameter sets. Parameter set change penalty is a useful parameter for alignment using multiple parameter sets. Pairwise statistical significance using multiple parameter sets can be effectively used to determine the relatedness of a (or a few pair(s of sequences without performing a time-consuming database search.

Huang Xiaoqiu

2009-03-01

80

Statistical Significance of Periodicity and Log-Periodicity with Heavy-Tailed Correlated Noise  

CERN Document Server

We estimate the probability that random noise, of several plausible standard distributions, creates a false alarm that a periodicity (or log-periodicity) is found in a time series. We investigate general situations with non-Gaussian correlated noises and present synthetic tests on the detectability and statistical significance of periodic components. Increasing heavy-tailness (respectively correlations describing persistence) tends to decrease (respectively increase) the false-alarm probability of finding a large spurious Lomb peak. Increasing anti-persistence tends to decrease the false-alarm probability. We also study the interplay between heavy-tailness and long-range correlations. In order to fully determine if a Lomb peak signals a genuine rather than a spurious periodicity, one should in principle characterize the Lomb peak height, its width and its relations to other peaks in the complete spectrum. As a step towards this full characterization, we construct the joint-distribution of the frequency positi...

Zhou, W X; Zhou, Wei-Xing; Sornette, Didier

2001-01-01

 
 
 
 
81

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

82

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)

1983-01-01

83

On the statistical significance of correlations between synthetic mantle plumes and tomographic models  

Science.gov (United States)

In a recent article, [Boschi, L., Becker, T.W., Steinberger, B., 2007. Mantle plumes: dynamic models and seismic images. Geochem. Geophys. Geosyst. 8, Q10006. doi:10.1029/2007GC001733] (BBS07) have re-evaluated the degree to which slow seismic tomography anomalies correlate with the possible locations of plume-like mantle upwellings connected to surface hotspots. They showed that several, but not all, hotspots are likely to have a deep mantle origin. Importantly, they found that when advection of plume conduits in mantle flow is considered, such correlations are significantly higher than when conduits are assumed to be vertical under hotspots. The validity of these statements depends, however, on the definition of statistical significance. BBS07 evaluated the significance of correlation through simple Student's t tests. Anderson (personal communication, July 2007) questioned this approach, given that the true information content of published tomography models is generally unknown, and proposed, instead, to evaluate the significance of correlation by comparing tomographic results with Monte Carlo simulations of randomly located plumes. Following this approach, we show here that the correlation found by BBS07 between advected plumes and slow anomalies in S-velocity tomography is less significant than previously stated, but still significant (at the 99.7% confidence level). We also find an indication that the seismic/geodynamic correlation observed by BBS07 does not only reflect the natural tendency of plumes to cluster in slow/hot regions of the mantle: although realistically advected, and thereby biased towards such regions, our random plumes correlate with slow tomographic anomalies significantly less than the plume models of BBS07. A less significant correlation with plume models characterizes P-velocity tomography; the correlation is, however, enhanced, if flow is computed from tomographic models with amplified heterogeneity, possibly accounting for the known resolution limits of global seismic data. In summary, the conclusions of BBS07 are confirmed: even at relatively long wavelengths, tomographic models are consistent with the presence of a number of tilted, whole-mantle plume-shaped slow anomalies, connected to surface hotspots.

Boschi, L.; Becker, Thorsten W.; Steinberger, Bernhard

2008-04-01

84

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

International Nuclear Information System (INIS)

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

1978-01-01

85

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

Science.gov (United States)

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

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

2011-01-01

86

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

1998-03-01

87

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

CERN Multimedia

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

Atrio-Barandela, F

2013-01-01

88

Model for dose-response with alternative change of sign  

International Nuclear Information System (INIS)

A new mathematical model of dose-response relationships is proposed, suitable for calculating stochastic effects of low level exposure. The corresponding differential equations are presented as well as their solution. (A.K.)

1997-09-08

89

Effect of Cesium–137 Gamma Rays and High-Energy Electrons on Dose Response of Glycine Dosimeter  

Directory of Open Access Journals (Sweden)

Full Text Available Glycine (50 mg / 10 mL FX system can be used in the dose range of 500 to 4000 Gy for Cobalt-60 gamma rays. The energy dependency study for the glycine system was carried out by comparing its dose response for Cesium–137 gamma rays and 7 MeV electron beam with the dose response for Cobalt-60 gamma rays. It was found that for both the radiations viz.: Cesium-137 gamma rays and electrons, there is no significant change in dose response as compared with that for Cobalt-60.

T. Mukherjee

2010-06-01

90

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

Science.gov (United States)

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

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

2011-01-01

91

Triclosan produces statistically significant reduction in plaque, gingivitis and caries but not clinically important benefit.  

Science.gov (United States)

Data sourcesThe Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase and the US National Institutes of Health Trials Register.Study selectionRandomised controlled trials (RCTs) of parallel or crossover design, (with a sufficient wash-out period) of at least six months duration, and irrespective of language or publication status.Data extraction and synthesisStudy assessment and data extraction were carried out independently by at least two reviewers. Meta-analysis was conducted using random-effects models when there were at least four studies (fixed-effect models when fewer than four studies), reporting mean differences (MD) for continuous data and risk ratios (RR) for dichotomous data.ResultsThirty studies involving 14,835 patients were included. Ten studies were considered to be a low risk of bias, nine at high risk and the remaining 11 were assessed as at unclear risk. After six to seven months use of triclosan/copolymer toothpaste there was a statistically significant reduction in plaque in favour of triclosan/copolymer of 22% (20 studies, 2675 patients, moderate-quality evidence).There was also a statistically significant reduction in plaque severity of 41% (13 studies, 1850 patients, moderate-quality evidence). Triclosan/copolymer toothpaste also reduced gingival inflammation statistically significantly by 22% after six to nine months of use (20 studies, 2743 patients, moderate-quality evidence). After 36 months of use there was no evidence of a difference between triclosan/copolymer toothpaste and control in the development of periodontitis (attachment loss) (RR 0.92, 95% CI 0.67 to 1.27, one study, 480 patients, low-quality evidence). After 24 to 36 months of use, triclosan/copolymer toothpaste slightly reduced coronal caries by about 5% (four studies, 9692 patients, high-quality evidence). One study (1357 patients, moderate-quality evidence) suggested that after 36 months of use triclosan/copolymer toothpaste probably reduced root caries.After six months of use triclosan/copolymer toothpaste may have reduced the mean total calculus by about 15%. There were no data available for meta-analysis regarding adverse effects, but 22 studies (73%) reported that there were no adverse effects caused by either the experimental or control toothpaste.There was considerable heterogeneity present in the meta-analyses for plaque, gingivitis and calculus. Plaque and gingivitis showed such consistent results that it did not affect our conclusions, but the reader may wish to interpret the results with more caution.ConclusionsThere was moderate-quality evidence showing that toothpastes containing triclosan/copolymer, in addition to fluoride, reduced plaque, gingival inflammation and gingival bleeding when compared with fluoride toothpastes without triclosan/copolymer. These reductions may or may not be clinically important, and are evident regardless of initial plaque and gingivitis levels, or whether a baseline oral prophylaxis had taken place or not.High-quality evidence showed that triclosan/copolymer toothpastes led to a small reduction in coronal caries. There was weaker evidence to show that triclosan/copolymer toothpastes may have reduced root caries and calculus, but insufficient evidence to show whether or not they prevented periodontitis. There do not appear to be any serious safety concerns regarding the use of triclosan/copolymer toothpastes in studies up to three years in duration. PMID:24763165

Kraglund, Ferne

2014-03-01

92

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

Directory of Open Access Journals (Sweden)

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

93

Dose-response relationship in multistage carcinogenesis: promoters.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Published dose-response curves of promoters of multistage carcinogenesis were selected that met the combined criteria of long study times, multiple doses, and low doses. In rat liver, 12 dose-response studies of 7 different promoters (phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], clophen A-50 (a polychlorinated biphenyl), alpha-, beta-, and gamma-hexachlorocyclohexane [HCH], and chloroform) were selected. These promoters were studied for 7-86 weeks and either altered hepatic foci...

Kitchin, K. T.; Brown, J. L.; Setzer, R. W.

1994-01-01

94

Cardiac dose-response relationships of oral and intravenous pindolol  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Carruthers, S. George

1982-01-01

95

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

We use p-values to identify the threshold level at which a regression function leaves 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...

2011-01-01

96

Dose-response relationship in multistage carcinogenesis: promoters.  

Science.gov (United States)

Published dose-response curves of promoters of multistage carcinogenesis were selected that met the combined criteria of long study times, multiple doses, and low doses. In rat liver, 12 dose-response studies of 7 different promoters (phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], clophen A-50 (a polychlorinated biphenyl), alpha-, beta-, and gamma-hexachlorocyclohexane [HCH], and chloroform) were selected. These promoters were studied for 7-86 weeks and either altered hepatic foci or hepatic cancer were determined. The doses ranged from 1 ng (TCDD) to 400 mg (chloroform). In mouse skin, 10 dose-response studies of 4 promoters (12-O-tetradecanoylphorbol-13-acetate [TPA], anthralin, chrysarobin, and 2,6-di-tert-butyl-4-hydroperoxyl-2,5-cyclohexadienone [BHTOOH]) were selected. In these mouse skin studies the doses ranged from 0.425 nmole (TPA) to 20,000 nmole (BHTOOH) per mouse. The length of time promoters were applied to the skin varied between 15 and 60 weeks. Either skin papillomas or carcinomas were determined. The dose-response relationships are presented on the basis of moles of promoter, percentage of the fully effective promoting dose, or percentage of the acute oral rat LD50. The degree of concavity of the dose-response curves was determined. The available dose-response data are critiqued and discussed on the basis of future research needs for biologically based cancer risk assessment models. PMID:8187717

Kitchin, K T; Brown, J L; Setzer, R W

1994-01-01

97

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)

2000-05-01

98

Post hoc pattern matching: assigning significance to statistically defined expression patterns in single channel microarray data  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Researchers using RNA expression microarrays in experimental designs with more than two treatment groups often identify statistically significant genes with ANOVA approaches. However, the ANOVA test does not discriminate which of the multiple treatment groups differ from one another. Thus, post hoc tests, such as linear contrasts, template correlations, and pairwise comparisons are used. Linear contrasts and template correlations work extremely well, especially when the researcher has a priori information pointing to a particular pattern/template among the different treatment groups. Further, all pairwise comparisons can be used to identify particular, treatment group-dependent patterns of gene expression. However, these approaches are biased by the researcher's assumptions, and some treatment-based patterns may fail to be detected using these approaches. Finally, different patterns may have different probabilities of occurring by chance, importantly influencing researchers' conclusions about a pattern and its constituent genes. Results We developed a four step, post hoc pattern matching (PPM algorithm to automate single channel gene expression pattern identification/significance. First, 1-Way Analysis of Variance (ANOVA, coupled with post hoc 'all pairwise' comparisons are calculated for all genes. Second, for each ANOVA-significant gene, all pairwise contrast results are encoded to create unique pattern ID numbers. The # genes found in each pattern in the data is identified as that pattern's 'actual' frequency. Third, using Monte Carlo simulations, those patterns' frequencies are estimated in random data ('random' gene pattern frequency. Fourth, a Z-score for overrepresentation of the pattern is calculated ('actual' against 'random' gene pattern frequencies. We wrote a Visual Basic program (StatiGen that automates PPM procedure, constructs an Excel workbook with standardized graphs of overrepresented patterns, and lists of the genes comprising each pattern. The visual basic code, installation files for StatiGen, and sample data are available as supplementary material. Conclusion The PPM procedure is designed to augment current microarray analysis procedures by allowing researchers to incorporate all of the information from post hoc tests to establish unique, overarching gene expression patterns in which there is no overlap in gene membership. In our hands, PPM works well for studies using from three to six treatment groups in which the researcher is interested in treatment-related patterns of gene expression. Hardware/software limitations and extreme number of theoretical expression patterns limit utility for larger numbers of treatment groups. Applied to a published microarray experiment, the StatiGen program successfully flagged patterns that had been manually assigned in prior work, and further identified other gene expression patterns that may be of interest. Thus, over a moderate range of treatment groups, PPM appears to work well. It allows researchers to assign statistical probabilities to patterns of gene expression that fit a priori expectations/hypotheses, it preserves the data's ability to show the researcher interesting, yet unanticipated gene expression patterns, and assigns the majority of ANOVA-significant genes to non-overlapping patterns.

Blalock Eric M

2007-07-01

99

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

Directory of Open Access Journals (Sweden)

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

100

Effect of Cesium–137 Gamma Rays and High-Energy Electrons on Dose Response of Glycine Dosimeter  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Glycine (50 mg / 10 mL FX) system can be used in the dose range of 500 to 4000 Gy for Cobalt-60 gamma rays. The energy dependency study for the glycine system was carried out by comparing its dose response for Cesium–137 gamma rays and 7 MeV electron beam with the dose response for Cobalt-60 gamma rays. It was found that for both the radiations viz.: Cesium-137 gamma rays and electrons, there is no significant cha...

2010-01-01

 
 
 
 
101

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

Science.gov (United States)

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

Daniel, Larry G.

1998-01-01

102

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

International Nuclear Information System (INIS)

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

2000-01-01

103

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

104

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

Dose-response curves have been computed for 5 tumour sites of the head and neck region, using 2 regression models. In agreement with clinical observation, a significant increase has been 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 are not obtained when the control rate is already high and...

Thames, H. D.; Peters, L. J.; Spanos, W.; Fletcher, G. F.

1980-01-01

105

Dose-response curves for stochastic radiation intensity  

International Nuclear Information System (INIS)

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

1990-01-01

106

Mechanisms of carcinogenesis and dose-response models  

International Nuclear Information System (INIS)

Radiobiological data are usually fitted with a linear or so-called linear-quadratic curve. However, it is not clear what the shape of the curve should be for any specific cancer. The dose-response relationships must depend on the mechanism involved, but the mechanisms of cancer induction are not known, or at least not in the detail necessary to choose one model over another. Furthermore, it has become clear that neither linear-dose models nor the square root of the dose models are capable of describing the dose-response curves of tumor induction by high-LET radiation. Commonly, dose-response curves for radiation induction of cancer are plots of incidence or mortality rates for specific tumors as a function of dose, whereas most of the models, especially those based purely on the biophysical aspects, are only relevant to the initial events. In some cancers it is the events subsequent to initiation that appear to be the determining factors. Using so-called promoters and hormone manipulation, the form of dose-response curves can be altered. These studies can give some information about how such agents may influence the carcinogenic process, but the important mechanistic aspects that determine expression of the initial events are understood poorly

1985-11-01

107

Dose response curves for organ function or cell survival  

International Nuclear Information System (INIS)

The importance of maintaining the distinction between clonogenic and functional dose-response curves in relation to radiotherapy planning is discussed, with reference to several workers' multifraction experiments. It is concluded that for investigating tolerance doses in radiotherapy, the important point is not the shape of any single-dose response curve, but the amount of repair occurring after doses of about 200 cGy (the range of interest being 50-600 cGy). The amount of repair actually occurring is measured directly in multifraction experiments provided sufficiently small fractions are used and proliferation avoided or allowed for correctly. The dose-response curve constructed from multifraction experimental data by making simple assumptions is a functional dose-response curve, deduced from data where repair after each fractional dose is basically the quantity being measured. It is just such curves that are required in order to elucidate the relationship between tolerance dose in radiotherapy and size of dose per fraction, with overally time considered separately. (U.K.)

1983-01-01

108

Parity and Pancreatic Cancer Risk: A Dose-Response Meta-Analysis of Epidemiologic Studies  

Science.gov (United States)

Background Previous epidemiologic studies have reported inconsistent results between parity and pancreatic cancer (PC) risk. To our knowledge, a comprehensive and quantitative assessment of this association has not been conducted. Methods Relevant published studies of parity and PC were identified using MEDLINE (PubMed) and Web of Science databases until November 2013. Two authors (H-BG and LW) independently assessed eligibility and extracted data. Eleven prospective and 11 case-control studies reported relative risk (RR) estimates and 95% confidence intervals (CIs) of PC associated with parity. Fixed- and random-effects models were used to estimate the summary RR depending on the heterogeneity of effects. Results The summary RR for PC comparing the highest versus lowest parity was 0.86 (95% CI: 0.73–1.02; Q?=?50.49, P<0.001, I2?=?58.4%). Significant inverse associations were also observed in the studies that adjusted for cigarette smoking (RR?=?0.81; 95% CI: 0.68–0.98), Type 2 diabetes mellitus (RR?=?0.83; 95% CI: 0.75–0.93), and those that included all confounders or important risk factors (RR?=?0.85; 95% CI: 0.76–0.96). Additionally, in the dose-response analysis, the summary RR for per one live birth was 0.97 (95% CI: 0.94–1.01; Q?=?62.83, P<0.001, I2?=?69.8%), which also indicated a borderline statistically significant inverse effect of parity on PC risk. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. Conclusion In summary, these findings suggest that higher parity is associated with a decreased risk of PC. Future large consortia or pooled studies are warranted to fully adjust for potential confounders to confirm this association.

Guan, Hong-Bo; Wu, Lang; Wu, Qi-Jun; Zhu, Jingjing; Gong, Tingting

2014-01-01

109

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

Directory of Open Access Journals (Sweden)

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

Erinijus Getautis

2011-04-01

110

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)

1980-01-01

111

Statistics  

...DataPublications and FormsStatisticsBuildings AdviceMonuments Advice...of HeritageConservation PhilosophyStatisticsLinksContact UsEducation...Northern Ireland's Historic EnvironmentStatisticsLast updated: 4 February 2011...

112

Statistical determination of significant curved I-girder bridge seismic response parameters  

Science.gov (United States)

Curved steel bridges are commonly used at interchanges in transportation networks and more of these structures continue to be designed and built in the United States. Though the use of these bridges continues to increase in locations that experience high seismicity, the effects of curvature and other parameters on their seismic behaviors have been neglected in current risk assessment tools. These tools can evaluate the seismic vulnerability of a transportation network using fragility curves. One critical component of fragility curve development for curved steel bridges is the completion of sensitivity analyses that help identify influential parameters related to their seismic response. In this study, an accessible inventory of existing curved steel girder bridges located primarily in the Mid-Atlantic United States (MAUS) was used to establish statistical characteristics used as inputs for a seismic sensitivity study. Critical seismic response quantities were captured using 3D nonlinear finite element models. Influential parameters from these quantities were identified using statistical tools that incorporate experimental Plackett-Burman Design (PBD), which included Pareto optimal plots and prediction profiler techniques. The findings revealed that the potential variation in the influential parameters included number of spans, radius of curvature, maximum span length, girder spacing, and cross-frame spacing. These parameters showed varying levels of influence on the critical bridge response.

Seo, Junwon

2013-06-01

113

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

1997-12-01

114

Do statistically significant correlations exist between the Homestake solar neutrino data and sunspots?  

Digital Repository Infrastructure Vision for European Research (DRIVER)

It has been suggested by various authors that a significant anticorrelation exists between the Homestake solar neutrino data and the sunspot cycle. Some of these claims rest on smoothing the data by taking running averages, a method that has recently undergone criticism. We demonstrate that no significant anticorrelation can be found in the Homestake, data, or in standard 2- and 4-point averages of that data. However, when 3-, 5-, and 7-point running averages are taken, an a...

Boger, J.; Hahn, R. L.; Cumming, J. B.

2000-01-01

115

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 Louis

2013-01-01

116

The Hall current system revealed as a statistical significant pattern during fast flows  

Directory of Open Access Journals (Sweden)

Full Text Available We have examined the dawn-dusk component of the magnetic field, BY, in the night side current sheet during fast flows in the neutral sheet. 237 h of Cluster data from the plasma sheet between 2 August 2002 and 2 October 2002 have been analysed. The spatial pattern of BY as a function of the distance from the centre of the current sheet has been estimated by using a Harris current sheet model. We have used the average slopes of these patterns to estimate earthward and tailward currents. For earthward fast flows there is a tailward current in the inner central plasma sheet and an earthward current in the outer central plasma sheet on average. For tailward fast flows the currents are oppositely directed. These observations are interpreted as signatures of Hall currents in the reconnection region or as field aligned currents which are connected with these currents. Although fast flows often are associated with a dawn-dusk current wedge, we believe that we have managed to filter out such currents from our statistical patterns.

K. Snekvik

2008-11-01

117

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

118

A New Method for Assessing the Statistical Significance in the Differential Functioning of Items and Tests (DFIT) Framework  

Science.gov (United States)

A new item parameter replication method is proposed for assessing the statistical significance of the noncompensatory differential item functioning (NCDIF) index associated with the differential functioning of items and tests framework. In this new method, a cutoff score for each item is determined by obtaining a (1-alpha ) percentile rank score…

Oshima, T. C.; Raju, Nambury S.; Nanda, Alice O.

2006-01-01

119

Clinical Significance: A Statistical Approach to Defining Meaningful Change in Psychotherapy Research.  

Science.gov (United States)

Describes ways of operationalizing clinically significant change, defined as extent to which therapy moves someone outside range of dysfunctional population or within range of functional population. Uses examples to show how clients can be categorized on basis of this definition. Proposes reliable change index (RC) to determine whether magnitude…

Jacobson, Neil S.; Truax, Paula

1991-01-01

120

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

 
 
 
 
121

Dose response in the tetrazolium test for skin carcinogenicity.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The tetrazolium test for skin carcinogenicity was performed with different doses of (i) a strong, complete carcinogen with moderate cytotoxicity, 20-methylcholanthrene; (ii) a weak carcinogen with strong cytotoxicity, the promoter 12-O-tetradecanoylphorbol-13-acetate; (iii) a strong toxic substance with very weak carcinogenicity for the skin, cantharidin; and (iv) X-rays. The dose-response relationship was determined, and the validity of the tetrazolium test was confirmed. However, substances...

Iversen, O. H.

1980-01-01

122

Dose response of ipratropium bromide assessed by two methods  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The dose-response relationships of ipratropium bromide were assessed by two different techniques in two groups of 10 male patients with partially reversible airways obstruction. In a randomised double-blind fashion on four days, 10 patients were given 40 ?g, 80 ?g, or 120 ?g of ipratropium bromide or placebo from identical containers. Baseline FEV1 and vital capacity were measured and the measurements repeated after 40 minutes, one, two, four, and six hours, and any symptoms were elicited....

Allen, Christopher J.; Campbell, Alastair H.

1980-01-01

123

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

1984-01-01

124

Quantitative Methods in Toxicology for Human Dose-Response Assessment  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The process of human risk assessment can be divided into hazard identification, dose-response assessment, exposure assessment and risk characterisation. For human risk assessment quantitative methods and models are applied. Which model should be applied depends on the nature of the question to be answered. A simple model can be applied if a standard has to be established, while a more complex model is required in the case a standard is exceeded and the health impact on a pop...

Hj, Kramer; Ehjm, Jansen; Mj, Zeilmaker; Hj, Kranen; Ed, Kroese

2007-01-01

125

Controlled Optimal Design Program for the Logit Dose Response Model  

Directory of Open Access Journals (Sweden)

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

Jiaqiao Hu

2010-10-01

126

Dose-response prediction for radiation-induced chromosomal instability  

International Nuclear Information System (INIS)

Radiation induces chromosome aberrations (CA) that are detected in the first post-irradiation cell cycle and in descendants of irradiated cells. Unstable aberrations in the progeny of exposed cells are referred to as one of the hallmarks of chromosomal instability (CIN). One of the important questions is what is the relationship between the dose response for radiation-induced CA and delayed CA, or CIN. To address this question, a mechanistic model for CIN was developed. Delayed CA are assumed to be formed both by transmission from previous mitotic cycles owing to chromosome breakage-fusion mechanism and by means of generation of DNA/chromosome breakage de novo in each cell cycle of survived cells. Monte Carlo simulation of DNA/chromosome breakage, CA production, cell death due to unstable CA and cell cycle kinetics was performed to predict the dose response for CIN. Different shapes of CIN dose-response curves were predicted for various time points after irradiation and under several assumptions on delayed DNA/chromosome breakage generation. For one of the scenarios studied, the pronounced dose dependence at early time points flattened or even turned into dose independence in a wide dose range after many rounds of replication where a stationary state between CA generation and elimination was achieved. This dose independence was shown to be in concert with the experimental data. (authors)

2009-10-25

127

Pseudomonas aeruginosa dose response and bathing water infection.  

Science.gov (United States)

Pseudomonas aeruginosa is the opportunistic pathogen mostly implicated in folliculitis and acute otitis externa in pools and hot tubs. Nevertheless, infection risks remain poorly quantified. This paper reviews disease aetiologies and bacterial skin colonization science to advance dose-response theory development. Three model forms are identified for predicting disease likelihood from pathogen density. Two are based on Furumoto & Mickey's exponential 'single-hit' model and predict infection likelihood and severity (lesions/m2), respectively. 'Third-generation', mechanistic, dose-response algorithm development is additionally scoped. The proposed formulation integrates dispersion, epidermal interaction, and follicle invasion. The review also details uncertainties needing consideration which pertain to water quality, outbreaks, exposure time, infection sites, biofilms, cerumen, environmental factors (e.g. skin saturation, hydrodynamics), and whether P. aeruginosa is endogenous or exogenous. The review's findings are used to propose a conceptual infection model and identify research priorities including pool dose-response modelling, epidermis ecology and infection likelihood-based hygiene management. PMID:24229610

Roser, D J; van den Akker, B; Boase, S; Haas, C N; Ashbolt, N J; Rice, S A

2014-03-01

128

Statistics  

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

129

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

Science.gov (United States)

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

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

2012-05-01

130

Dose-response curves for radiation-induced gene mutations in mouse oocytes and their interpretation  

International Nuclear Information System (INIS)

Previous work, in which female mice had been given fractionated doses of 20x10 rad X-rays, had confirmed and extended Russell's observations that the dose-response relationship for specific-locus mutations in mature-mouse oocytes is curved at low doses. The present work was intended to study the relationship at relatively high doses. Adult female mice were given doses of 200, 400 or 600 rad X-rays at 52 or 72 rad/min, and mated immediately. Off-spring conceived in the first 7 days (i.e. using oocytes which were mature at time of treatment) were scored for specific-locus mutations. The data indicate that the departure from linearity of the dose-response curve is marginally significant at the 5% level. A quadratic dose-response curve (y=c+aD+bD2) and a square-law relationship (y=c+bD2) both give a good fit to the data. Both curves fit data of other authors obtained at low doses or dose rates. These results could be interpreted either in terms of dose-dependent repair phenomena, or by considering specific-locus mutations as two-track events. In view of knowledge of other phenomena concerning mutation and cell killing in mouse oocytes, such as the variation in sensitivity of different cell stages, the interpretation in terms of repair phenomena is preferred. (Auth.)

1979-01-01

131

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

International Nuclear Information System (INIS)

A data analysis that 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 on leukemia mortality, up to the end of 1978, are used to infer them. Several findings based on T65 revised doses (T65DR) are obtained. First, it is shown that the fits to the data of time-independent L (linear in ? dose)-Q (quadratic in ? dose)-L (linear in nuetron dose, L-L, and Q-L dose-response models are significantly improved by using the corresponding time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to ? irradiation decreases in time while the increased risk due to neutron exposure decreases more slowly, if at all, in time. Consequently, relative biological effectiveness (RBE) of neutrons is shown to increase in time and the current definition of RBE as a time-dependent quantity is therefore challenged. It is demonstrated with time-dependent models that the L-L model has a poor fit to the data for the first 7 years of study, but has an adequate fit for the remaining 21 years. In contrast the Q-L model has an adequate fit for the entire follow-up period

1984-01-01

132

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

Science.gov (United States)

A data analysis that 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 on leukemia mortality--up to the end of 1978--are used to infer them. Several findings based on T65 revised doses (T65DR) are obtained. First, it is shown that the fits to the data of time-dependent L (linear in gamma dose)-Q (quadratic in gamma dose)-L (linear in neutron dose), L-L, and Q-L dose-response models are significantly improved (P less than 0.001) by using the corresponding time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to gamma irradiation decreases in time while the increased risk due to neutron exposure decreases more slowly, if at all, in time. Consequently, relative biological effectiveness (RBE) of neutrons is shown to increase in time (P = 0.002) and the current definition of RBE as a time-independent quantity is therefore challenged. It is demonstrated with time-dependent models that the L-L model has a poor fit (P = 0.01) to the data for the first 7 years of study, but has an adequate fit for the remaining 21 years. In contrast the Q-L model has an adequate fit for the entire follow-up period (P greater than 0.30). PMID:6473713

Brodsky, J B; Groer, P G; Liddell, R; Ishimaru, T; Ichimaru, M

1984-09-01

133

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

Energy Technology Data Exchange (ETDEWEB)

A data analysis that 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 on leukemia mortality, up to the end of 1978, are used to infer them. Several findings based on T65 revised doses (T65DR) are obtained. First, it is shown that the fits to the data of time-independent L (linear in ..gamma.. dose)-Q (quadratic in ..gamma.. dose)-L (linear in nuetron dose, L-L, and Q-L dose-response models are significantly improved by using the corresponding time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to ..gamma.. irradiation decreases in time while the increased risk due to neutron exposure decreases more slowly, if at all, in time. Consequently, relative biological effectiveness (RBE) of neutrons is shown to increase in time and the current definition of RBE as a time-dependent quantity is therefore challenged. It is demonstrated with time-dependent models that the L-L model has a poor fit to the data for the first 7 years of study, but has an adequate fit for the remaining 21 years. In contrast the Q-L model has an adequate fit for the entire follow-up period.

Brodsky, J.B.; Groer, P.G.; Liddell, R.; Ishimaru, T.; Ichimaru, M.

1984-09-01

134

Determination of dose- response relationship in cultured human by lymphocytes for biological dosimetry  

International Nuclear Information System (INIS)

Background: lymphocyte- dicentric assay is the most generally accepted method for biological dosimetry of overexposed individuals. In this study, the frequency of unstable chromosome aberration in blood lymphocytes was used to estimate radiation dose received by individuals. Evaluation of dose using a calibration curve produced elsewhere may have a significant uncertainty; therefore, experiments were performed to produce a dose-response curve using an established protocol of international atomic energy agency. Materials and methods: lymphocytes in whole peripheral blood obtained from healthy individuals, were exposed to various doses of gamma radiation (0.25-4 Gy). Then after 1 hour of incubation in 37digC , were cultured in complete RPMI-1640 medium. 500 mitoses were analyzed for the presence or absence of unstable chromosomal aberrations for each radiation dose after the standard metaphase preparation and staining slides. Results and conclusion: Intercellular distribution chromosomes at each radiation dose has been used to contrast a dose- response curve. It seems that dose-effect relationship follows with the linear-quadratic model. There is a good agreement between our dose- response curves with similar published studies by other laboratories

2004-09-01

135

An in vitro biofilm model for enamel demineralization and antimicrobial dose-response studies.  

Science.gov (United States)

Microcosm biofilms formed in microplates have demonstrated complex community dynamics similar to natural dental biofilm. No simplified microcosm models to evaluate enamel demineralization and dose-response effect to anticariogenic therapies have yet been established, thus this study was designed to develop a pre-clinical model fulfilling this purpose. Experiments were carried out to establish the time of biofilm formation and the sucrose concentration and exposure regimen. Biofilms were initiated from saliva and grown for up to 10 days on bovine enamel discs in 24-well plates, with a saliva analogue medium. Data were collected as pH readings and the percentage enamel surface hardness change. A dose-response evaluation was performed with chlorhexidine, which significantly affected the pH and mineral loss. Overall, the established model parameters, 5 days of biofilm growth with intermittent 1% sucrose exposure of 6 h per day, was suitable as a pre-clinical model for enamel demineralization and dose-response studies. PMID:22044385

van de Sande, F H; Azevedo, M S; Lund, R G; Huysmans, M C D N J M; Cenci, M S

2011-10-01

136

Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI, usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine. Methods Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models. Results The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively. Conclusions A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials. Trial Registration The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723.

Cardozo Linda

2010-08-01

137

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)

2007-03-01

138

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

1997-01-01

139

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 p...

2012-01-01

140

Statistical trend analysis and extreme distribution of significant wave height from 1958 to 1999 – an application to the Italian Seas  

Directory of Open Access Journals (Sweden)

Full Text Available The study is a statistical analysis of sea states timeseries derived using the wave model WAM forced by the ERA-40 dataset in selected areas near the Italian coasts. For the period 1 January 1958 to 31 December 1999 the analysis yields: (i the existence of a negative trend in the annual- and winter-averaged sea state heights; (ii the existence of a turning-point in late 80's in the annual-averaged trend of sea state heights at a site in the Northern Adriatic Sea; (iii the overall absence of a significant trend in the annual-averaged mean durations of sea states over thresholds; (iv the assessment of the extreme values on a time-scale of thousand years. The analysis uses two methods to obtain samples of extremes from the independent sea states: the r-largest annual maxima and the peak-over-threshold. The two methods show statistical differences in retrieving the return values and more generally in describing the significant wave field. The r-largest annual maxima method provides more reliable predictions of the extreme values especially for small return periods (<100 years. Finally, the study statistically proves the existence of decadal negative trends in the significant wave heights and by this it conveys useful information on the wave climatology of the Italian seas during the second half of the 20th century.

G. Martucci

2010-06-01

 
 
 
 
141

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)

1998-11-01

142

Dose response of oral timolol combined with adrenaline.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Oral timolol, a beta-adrenergic receptor blocker, was given in 5 different doses from 5 mg to 30 mg a day to 12 healthy volunteers in a double-blind cross-over trial. Adrenaline was instilled into one eye in each subject. Recording of intraocular pressure during the trial suggested the presence of a dose-response relationship between the dose of timolol and the decrease of intraocular pressure. An analysis of the interaction of timolol and adrenaline showed that the adrenaline effect diminish...

Ohrstro?m, A.

1982-01-01

143

Dose-response relationships for radicals trapped in irradiated solids.  

Science.gov (United States)

This work develops a modified description of the dose-response relationships for radical production by ionizing radiation. The main new feature is incorporation of the concept of the target and the possibility that the population of targets can undergo depletion at increased doses. The resulting mathematical relationships are capable of describing the decrease in product yield at increasing doses as is sometime observed. In addition, the description preserves the general properties of the widely used relationships. Finally, the expressions provide the possibility for estimating the average mass of the target. PMID:15913399

Nelson, William H

2005-06-01

144

Short-term psychodynamic psychotherapy for depression: an examination of statistical, clinically significant, and technique-specific change.  

Science.gov (United States)

This study investigates the effectiveness of short-term psychodynamic psychotherapy (STPP) for depression in a naturalistic setting utilizing a hybrid effectiveness/efficacy treatment research model. Twenty-one patients were assessed pre- and post-treatment through clinician ratings and patient self-report on scales representing specific DSM-IV depressive, global symptomatology, relational, social, and occupational functioning. Treatment credibility, fidelity, and satisfaction were examined, all of which were found to be high. All areas of functioning assessed exhibited significant and positive changes. These adaptive changes in functioning demonstrated large statistical effects. Likewise, changes in depressive symptoms evaluated at the patient level utilizing clinical significance methodology were found to be high. A significant direct process/outcome link between STPP therapist techniques and changes in depressive symptoms was observed. Alternative treatment interventions within STPP were evaluated in relation to subsequent improvements in depression and were found to be nonsignificant. The present results demonstrate that robust statistical and clinically significant improvement can occur in a naturalistic/hybrid model of outpatient STPP for depression. PMID:12826915

Hilsenroth, Mark J; Ackerman, Steven J; Blagys, Matthew D; Baity, Matthew R; Mooney, Megan A

2003-06-01

145

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

The non-cancer mortality data for cerebrovascular disease (CVD) and cardiovascular diseases from Report 13 on the atomic bomb survivors published by the Radiation Effects Research Foundation were analysed to investigate the dose–response for the influence of radiation on these detrimental health effects. Various parametric and categorical models (such as linear-no-threshold (LNT) and a number of threshold and step models) were analysed with a statistical selection protocol that rated the mo...

Scho?llnberger, H.; Kaiser, J. C.; Jacob, P.; Walsh, L.

2012-01-01

146

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)d"2], where t is the time and d is dose. The coefficient of the d"2 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

1983-01-01

147

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

1986-01-01

148

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)

1992-03-18

149

Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects.  

Science.gov (United States)

Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 microg-500 microg) of vitamin K(1) supplements (K(1)) taken daily for 7 days. The threshold K(1) dose causing a statistically significant lowering of the INR was 150 microg/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 microg/day. Circulating undercarboxylated osteocalcin did not decrease until 300 microg K(1)/day compared with 100 microg K(1)/day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic gamma-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that short-term variability in intake of K(1) is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 microg/day of vitamin K(1) do not significantly interfere with oral anticoagulant therapy. PMID:15231565

Schurgers, Leon J; Shearer, Martin J; Hamulyák, Karly; Stöcklin, Elisabeth; Vermeer, Cees

2004-11-01

150

Statistical trend analysis and extreme distribution of significant wave height from 1958 to 1999 – an application to the Italian Seas  

Directory of Open Access Journals (Sweden)

Full Text Available The study is a statistical analysis of sea states timeseries derived using the wave model WAM forced by the ERA-40 dataset in selected areas near the Italian coasts. For the period 1 January 1958 to 31 December 1999 the analysis yields: (i the existence of a negative trend in the annual- and winter-averaged sea state heights; (ii the existence of a turning-point in late 70's in the annual-averaged trend of sea state heights at a site in the Northern Adriatic Sea; (iii the overall absence of a significant trend in the annual-averaged mean durations of sea states over thresholds; (iv the assessment of the extreme values on a time-scale of thousand years. The analysis uses two methods to obtain samples of extremes from the independent sea states: the r-largest annual maxima and the peak-over-threshold. The two methods show statistical differences in retrieving the return values and more generally in describing the significant wave field. The study shows the existence of decadal negative trends in the significant wave heights and by this it conveys useful information on the wave climatology of the Italian seas during the second half of the 20th century.

G. Martucci

2009-09-01

151

A study on dose response of NIPAM-based dosimeter used in radiotherapy  

International Nuclear Information System (INIS)

The newly manufactured N-isopropylacrylamide (NIPAM) polymer gel is composed of four components, i.e., gelatin, monomer (NIPAM), crosslinker (N,N'-methylenebisacrylamide, Bis), and antioxidant (tetrakis hydroxymethyl phosphonium chloride, THPC). In this study, we investigated the effects of gel composition on the dose response of NIPAM polymer gel. A statistical experiment to analyze the contribution of each composition to the linearity and sensitivity of NIPAM gel was performed. Results indicate that the amount of gelatin, NIPAM (15.17%), Bis, and THPC have dominant effects on the sensitivity of the gel, with contributions of 59.73, 15.17, 10.64, and 14.45%, respectively. The amount of gelatin and Bis mainly affected the linearity of the gel, with contributions of 44.70 and 50.99%, respectively. The linearity of most compositions of the gel was greater than 0.99 when (%C)/(%T) was lower than 8.0. Optimal (%C)/(%T) for higher sensitivity should be in the range of 4-9. The temporal stability experiment showed that the dose response curve attained stability at about 5 h after irradiation and persisted up to 3 months. (author)

2011-10-01

152

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

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

Dose-response relationships for traffic noise and annoyance.  

Science.gov (United States)

The annoyance due to road traffic noise was studied in 18 areas in five countries. A total of 1379 interviews was performed and noise measurements were made in each area. The relation between Leq and the extent of the population expressing that they were "very annoyed" was poor (rxy = 0.03). An augmentation of the number of heavy vehicles from 1000/24 hr up to greater than 3000/24 hr did not increase the extent of annoyance. The highest correlation was obtained for the maximum noise level. The dose-response relationship implies that the number of events above a certain limit will not increase the extent of annoyance: it is determined by the highest noise level from single vehicles. It is suggested that this model for the human reaction to environmental noise, which has now been demonstrated for aircraft, train, and traffic noise, should be considered for the establishment of standards. PMID:3963889

Rylander, R; Björkman, M; Ahrlin, U; Arntzen, E; Solberg, S

1986-01-01

155

Dose-response curve estimation: a semiparametric mixture approach.  

Science.gov (United States)

In the estimation of a dose-response curve, parametric models are straightforward and efficient but subject to model misspecifications; nonparametric methods are robust but less efficient. As a compromise, we propose a semiparametric approach that combines the advantages of parametric and nonparametric curve estimates. In a mixture form, our estimator takes a weighted average of the parametric and nonparametric curve estimates, in which a higher weight is assigned to the estimate with a better model fit. When the parametric model assumption holds, the semiparametric curve estimate converges to the parametric estimate and thus achieves high efficiency; when the parametric model is misspecified, the semiparametric estimate converges to the nonparametric estimate and remains consistent. We also consider an adaptive weighting scheme to allow the weight to vary according to the local fit of the models. We conduct extensive simulation studies to investigate the performance of the proposed methods and illustrate them with two real examples. PMID:21627631

Yuan, Ying; Yin, Guosheng

2011-12-01

156

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)

1980-09-01

157

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 SSNcycle of the year 1739 and in the solar cycle No. 14 (Shikotsu eruption of 1739 and Ksudach 1907). • Of the historical 8 large volcanic eruptions with index VEI6+, recorded from 1610 to the present, 7 of these were recorded with SSNcycle 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

158

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.)

1982-01-01

159

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 taxes and precautionary stock fees on oil products

1999-01-01

160

Tea consumption and risk of type 2 diabetes: a dose-response meta-analysis of cohort studies.  

Science.gov (United States)

Tea consumption has inconsistently been shown to be associated with the risk of type 2 diabetes (T2D). The aim of the present study was to conduct a dose-response meta-analysis of cohort studies assessing the association between consumption of tea and risk of developing T2D. Pertinent studies were identified by searching PubMed, Web of Science and EMBASE through 31 March 2013. A total of sixteen cohorts from fifteen articles that reported 37,445 cases of diabetes among 545,517 participants were included. A significant linearly inverse association between tea consumption and T2D risk was found (P for linear trend = 0.02). An increase of 2 cups/d in tea consumption was found to be associated with a 4.6 (95% CI 0.9, 8.1) % reduced risk of T2D. On the basis of the dose-response meta-analysis, the predicted relative risks of diabetes for 0, 1, 2, 3, 4, 5 and 6 cups of tea consumed per d were 1.00 (referent), 0.97 (95% CI 0.94, 1.01), 0.95(95% CI 0.92, 0.98), 0.93 (95% CI 0.88, 0.98), 0.90 (95% CI 0.85, 0.96), 0.88 (95 % CI 0.83, 0.93) and 0.85 (95% CI 0.80, 0.91), respectively. There was a statistically significant heterogeneity within the selected studies (Q= 45.32, P< 0.001, I 2= 60.3 %). No evidence of substantial small-study bias was found (P= 0·46). Our findings suggest that tea consumption could be linearly inversely associated with T2D risk. Future well-designed observational studies that account for different characteristics of tea such as tea types, preparation methods and tea strength are needed to fully characterise such an association. PMID:24331002

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

2014-04-28

 
 
 
 
161

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

Directory of Open Access Journals (Sweden)

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

Leitner Dietmar

2005-04-01

162

Dose response from pharmacological interventions for CBF changes in a baboon model using [sup 99]Tc[sup m]-HMPAO and SPECT. [Cerebral blood flow; [sup 99]Tc[sup m]-hexamethylpropyleneamine oxime  

Energy Technology Data Exchange (ETDEWEB)

This study assesses the sensitivity of the baboon model under anaesthesia to determine by single photon emission computed tomography (SPECT) and [sup 99]Tc[sup m]-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 pO[sub 2] 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).

Dormehl, I.C.; Hugo, N. (Pretoria Univ. (South Africa). AEC Inst. for Life Sciences); Oliver, D.W. (Potchefstroom Univ. for Christian Higher Education (South Africa). Dept. of Pharmacology)

1993-07-01

163

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2010-11-01

164

The progression rate of late effects in normal tissue and its impact on dose-response relationships  

International Nuclear Information System (INIS)

The progression of late skin telangiectasia after radiotherapy has been studied prospectively in patients for 1, 2 and 5 fractions per week and various dose levels. The degree of telangiectasia was scored on an arbitrary scale. Skin telangiectasia was found to be a continuously progressing endpoint both in the individual patient and in terms of the number of patients who achieved a certain degree of damage. The rate of progression was dose-dependent. Dose-response analysis were performed at 3, 5 and 9 years follow-up for various endpoints: telangiectasia score ?1, score ?2 and score ?3. Iso-effective doses (ED50s) for score ?1 at 3 years, score ?2 at 5 years and score ?3 at 9 years were very similar. In an iso-effect analysis it is therefore worthwhile and time-saving to include the minimal detectable damage in the endpoint (e.g. using score ?1), even if this mild damage is of no clinical significance, and the dose response becomes somewhat less steep than for more severe damage. The fact that the progression rate is dose-dependent has impact on dose-response analysis. Dose-response anlaysis for score ?3 at various follow-up times showed a very flat curve at 3 years compared to 5 and 9 years. The steepness of the dose-response curves was similar at 5 and 9 years. A minimum follow-up of 5 years is therefore necessary for reliable estimation of the late complication rates in a comparison of two dosage schedules using this endpoint. The implication of the continuous progression of telangiectasia is that the dose-response curves are shifted to the left with follow-up. The ED50s is dramatically reduced between 3 and 5 years. The ED50s is also significantly reduced between 5 and 9 years' follow-up, in spite of no change in the steepness of the dose-response curve during this period. Consequently, the time of response is the most fundamental parameter in any iso-effect analysis with progressive endpoints and the late complication rates always have to be specified at a fixed time of follow-up. (author). 31 refs.; 4 figs.; 2 tabs

1989-01-01

165

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

166

Linear dose response curves in fungi and tradescantia  

International Nuclear Information System (INIS)

Tradescantia Clone 02 data suggests that linear non-threshold dose responses are expected to the lowest doses and dose rates of low linear energy transfer (LET) radiation. This is likely to be true for other living organisms even though Clone 02 is radiation sensitive. It is concluded that Clone 02 is partially defective in the RAD 6 pathway for the repair of DNA interstrand cross-links (ISCL) and other loss of coding damage (LCD), based on its cross sensitivities to EMS and ionizing radiation. Tradescantia Clone 02 data showing linear non-threshold induction of somatic genetic events in part reflects the repair deficiency of this Clone. More DNA damage is repaired by recombinational mechanisms in Clone 02 than would occur in a wild-type strain. Two important classes of DNA lesions are induced by ionizing radiation in DNA - double strand breaks (DSB) which are repaired by recombination mechanisms, and loss of coding information damage (LCD), which is repaired by error prone mechanisms but may also be a substrate for recombinational repair. Based on data from yeast, there are two different repair pathways which deal with these differing lesions with different somatic genetic consequences. From yeast, yield cross sections can be derived and applied to DNA damage and repair in Tradescantia. For Clone 02, per lesion, more visible genetic events are scored than in wild-type strains. In a radiation-derived sub-clone, Clone 0106, which is more variable than Clone 02, even more events occur per lesion. This derivative clone, plus breeding experiments, indicate that Clone 02 is heterozygous, or a 'carrier' for a mutant version of a gene in the Tradescantia RAD 6 repair pathway. Clone 02 is, therefore, much like a Fanconi's anemia carrier in a human population, while the Clone 0106 derivative is much like a homozygous Fanconi's anemia patient, with respect to its response to ionizing radiation damage. Two anomalies in its dose response curves for 'pink' loss of heterozygosity (LOH) events occur because Clone 02 repairs both DSB and LCD by recombination. Clone 02 has a linear dose response for high LET radiation. Starting from the same initial yieId frequency, wild-types have a sublinear response. The sublinear response reflects a smoothly decreasing probability that 'pinks' are generated as a function of increasing high LET dose for wild-type but not Clone 02. This smoothly decreasing response would be expected for LOH in 'wild-type' humans. It reflects an increasing proportion of DNA damage being repaired by non-recombinational pathways and/or an increasing probability of cell death with increasing dose. Clone 02 at low doses and low dose rates of low LET radiation has a linear dose response, reflecting a 1/16 probability of a lesion leading to LOH, relative to high LET lesions. This differential is held to reflect: microdosimetric differences in energy deposition and, therefore, DNA damage by low and high LET radiations; the effects of lesion clustering after high LET on the probability of generating the end wild-types. While no observations have been made at very low doses and dose rates in wild-types, there is no reason to suppose that the low LET linear non-threshold dose response of Clone 02 is abnormal. The importance of the LOH somatic genetic end-point is that it reflects cancer risk in humans. The linear non-threshold low dose low LET response curves reflects either the probability that recombinational Holliday junctions are occasionally cleaved in a rare orientation to generate LOH, or the probability that low LET lesions include a small proportion of clustered events similar to high LET ionization or both. Calculations of the Poisson probability that two or more low LET lesions will be induced in the same target suggest that dose rate effects depend upon the coincidence of DNA lesions in the same target, and that the probability of LOH depends upon lesion and repair factors. But the slope of LOH in Clone 02 and all other strains never approaches the expected slope of predicted for two hit events. This suggests that onl

1999-01-01

167

A dose-response study for I-125 prostate implants  

International Nuclear Information System (INIS)

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

1998-04-01

168

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

169

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

170

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

171

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

172

On the dose response of some CVD diamond thermoluminescent detectors  

International Nuclear Information System (INIS)

The linearity of dose response of chemical vapour deposition (CVD) diamonds grown at the Inst. for Materials Research at Limburg Univ. (Belgium)), was investigated over a dose range relevant for radiotherapy. The following CVD diamonds were investigated: (1) a batch of square 3 x 3 mm2 detectors cut from a CVD wafer and (2) an as-grown CVD wafer of 6 cm diameter. A total of 20 CVD square detectors were irradiated with 137Cs gamma rays over the dose range from 200 mGy to 25 Gy. The CVD wafer, used as a large-area thermoluminescent (TL) detector, was exposed to a 226Ra needle. Very few square detectors showed linearity over a limited dose range, followed by saturation of the TL signal. The dose range of linearity was found to be strongly affected by the thermal annealing procedure of the detector. Owing to its high sensitivity and homogeneity of response, the large CVD diamond wafer was found to be very suitable as a large-area detector for 2-D dose mapping of the 226Ra brachytherapy source, possibly for Quality Assurance purposes. (authors)

2004-07-02

173

Biophysical Monitoring and dose response characteristics of irradiated hemoglobin  

International Nuclear Information System (INIS)

The present work aims to move a step forward towards a deeper understanding of the scattering of x-ray, from lyophilized biological samples. Comparative study has been performed using LAXS and UV-visible spectrophotometry for monitoring the dose response characteristics of the hemoglobin molecule of irradiated blood. Blood samples were irradiated at doses ranging from 5 up to 100 Gy. Diluted hemoglobin solution was scanned in the UV- visible range (200-700 nm), and lyophilized hemoglobin was prepared for LAXS measurement. The radiation-induced changes in the hemoglobin structure have been evaluated. The LAXS profile of hemoglobin molecule is characterized by the presence of two peaks in the forward direction of scattering. These peaks were found to be sensitive to the variations in the molecular structure of a given sample. The obtained results suggest that the 1st peak, recorded at 4.65o, is sensitive to the tertiary and quaternary structure of the globin part, while the major peak, recorded at 10.5o, appeared to be related to its primary and secondary structure

2003-09-01

174

Development of a mid-head radiation dose response function  

International Nuclear Information System (INIS)

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

1979-01-01

175

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

176

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

177

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

International Nuclear Information System (INIS)

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

2003-08-17

178

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

1987-01-01

179

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

Directory of Open Access Journals (Sweden)

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

Zuyderduyn Scott D

2007-08-01

180

Weighted identity test for the comparison of dose-response functions of radiation-induced chromosome aberrations  

Energy Technology Data Exchange (ETDEWEB)

For the analyses of dose-relations of radiation-induced chromosome aberrations a weighted least squares method has to be carried out since the variance of observed aberration yields are different at different doses. Consequently identical statistical weights have to be used for the comparison of dose-response functions. For this reason a weighted identity test is presented. The derivation of the test quantity is described in a generalized form. The practical application of the test and the computation of the test quantity is shown for the linear and linear-quadratic model.

Streng, S.; Bauchinger, M.

1983-10-01

 
 
 
 
181

Weighted identity test for the comparison of dose-response functions of radiation-induced chromosome aberrations  

International Nuclear Information System (INIS)

For the analyses of dose-relations of radiation-induced chromosome aberrations a weighted least squares method has to be carried out since the variance of observed aberration yields are different at different doses. Consequently identical statistical weights have to be used for the comparison of dose-response functions. For this reason a weighted identity test is presented. The derivation of the test quantity is described in a generalized form. The practical application of the test and the computation of the test quantity is shown for the linear and linear-quadratic model. (orig.)

1983-10-01

182

The dose-response of canine focal gastric mucosal blood flow to misoprostol  

International Nuclear Information System (INIS)

The dose-response of focal gastric mucosal blood flow was measured simultaneously by laser-Doppler flowmetry and hydrogen gas clearance in the canine chambered gastric segment to topical misoprostol. Simultaneously obtained mucosal blood flow values showed a highly significant linear correlation in the basal but not misoprostol periods between the two techniques. Laser-Doppler flowmetry measured a dose-dependent increase in blood flow, while in contrast, hydrogen gas clearance showed a gradual decline in blood flow after misoprostol administration throughout all experiments. It is concluded that misoprostol dose-dependently and transiently increases focal gastric mucosal blood flow. However, only laser-Doppler flowmetry is sensitive enough to detect it. Although it can measure steady-state blood flow, owing to the duration of one measurement, hydrogen gas clearance is incapable of detecting rapid flow changes

1989-01-01

183

The dose-response of canine focal gastric mucosal blood flow to misoprostol  

Energy Technology Data Exchange (ETDEWEB)

The dose-response of focal gastric mucosal blood flow was measured simultaneously by laser-Doppler flowmetry and hydrogen gas clearance in the canine chambered gastric segment to topical misoprostol. Simultaneously obtained mucosal blood flow values showed a highly significant linear correlation in the basal but not misoprostol periods between the two techniques. Laser-Doppler flowmetry measured a dose-dependent increase in blood flow, while in contrast, hydrogen gas clearance showed a gradual decline in blood flow after misoprostol administration throughout all experiments. It is concluded that misoprostol dose-dependently and transiently increases focal gastric mucosal blood flow. However, only laser-Doppler flowmetry is sensitive enough to detect it. Although it can measure steady-state blood flow, owing to the duration of one measurement, hydrogen gas clearance is incapable of detecting rapid flow changes.

Gana, T.J.; Pherson, B.R.; Koo, J. (Alberta Univ., Edmonton, AB (Canada))

1989-01-01

184

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

International Nuclear Information System (INIS)

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

1995-01-01

185

Cryptosporidium parvum: determination of ID?? and the dose-response relationship in experimentally challenged dairy calves.  

Science.gov (United States)

The objectives were to determine the median infective dose (ID??) of Cryptosporidium parvum and to describe the dose-response relationship including associated clinical illness in experimentally challenged dairy calves. Within the first 24h of life, 27 test calves were experimentally challenged with C. parvum oocysts and 3 control calves were sham dosed. Test calves received 1 of 8 possible doses (25, 50, 100, 500, 1 × 10(3), 1 × 10(4), 1 × 10(5), and 1 × 10(6) oocysts). All 27 test calves developed diarrhea. Fecal oocyst shedding occurred in 25 (92.6%) test calves and in 0 control calves. The 2 non-shedding test calves both received 25 oocysts. There was an inverse relationship between dose and time to onset of fecal oocyst shedding (P=0.005). There was no relationship found between dose and duration (P=0.2) or cessation (P=0.3) of fecal oocyst shedding. In addition, there was not a significant relationship between log-dose and the log-peak oocysts (P=0.2) or log-total oocysts (P=0.5) counted/g of feces across the dose groups. There was a positive dose-response relationship between log-dose and diarrhea (P=0.01). However, when controlling for other factors, such as onset and cessation of fecal oocyst shedding, dose was not a significant predictor of diarrhea (P=0.5). Onset and cessation of fecal oocyst shedding were found to be the best predictors of diarrhea (P=0.0006 and P=0.04, respectively). The ID?? for fecal oocyst shedding was 5.8 oocysts, for diarrhea was 9.7 oocysts, and for fecal oocyst shedding with diarrhea was 16.6 oocysts. Given that the ID?? of C. parvum is far less than would be excreted into the environment by a naturally infected calf, prevention and control of cryptosporidiosis is a formidable challenge. PMID:23680540

Zambriski, J A; Nydam, D V; Wilcox, Z J; Bowman, D D; Mohammed, H O; Liotta, J L

2013-10-18

186

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.

2011-04-28

187

ENDOCRINE ACTIVE SUBSTANCES AND DOSE-RESPONSE FOR INDIVIDUALS AND POPULATIONS  

Science.gov (United States)

Endocrine Active Substances and Dose-Response for Individuals and Populations Hugh A. Barton Abstract for IUPAC-SCOPE article Dose-response characteristics for endocrine disruption have been major focuses in efforts to understand potential impacts on human and ec...

188

Analysis of late effects data using dose-response models; Application to human skin telangiectasia data  

Energy Technology Data Exchange (ETDEWEB)

The clinical data for skin telangiectasia from previous prospective studies at the Radiotherapy Department in Gothenborg are reanalyzed using two dose-response models - general formulations of the well known linear-quadratic (LQ) and NSD isoeffect models. Assuming that essentially no repopulation appears in the vessel endothelium for overall treatment times up to 68 days, the {alpha}/{beta}-value of 2.75 Gy is obtained for the LQ-model. The time factor is found not to be significant by the NSD-model for the treatment times used ({le}68 days) at the 95% level of confidence. The estimated value of the exponent of the number of fractions, A, is 0.321. The obtained values of the {alpha}/{beta}-ratio and of A show high sensitivity of the vessel endothelium to changes in the dose per fraction. Our results show that within the interval of the number of fractions used, 10-35 fractions, the NSD-model gives predictions comparable to those of the LQ-model. For number of fractions smaller than 5, a high discrepancy occurs between the two models, the NSD-model predicting higher values of the isoeffective total dose. The maximal deviation between the models appears for N = 1;25% and 27% at the 5 and 50% level of effect, respectively. For large N and especially at low effect probabilities the NSD-model again predicts higher isoeffective doses: the dose predicted by the NSD-model for a regimen with 40 fractions and for 5% probability of telangiectasia is 7.5%, higher than that predicted by the LQ-model. Based on the estimated dose-response curves, considering the telangiectasia as the decisive late tissue effect, the requirement of the combined uncertainty in the dose delivery is estimated between 3 and 4.%. (author). 61 refs.; 3 figs.; 5 tabs.

Baltas, D.; Fehrentz, D. (Heidelberg University (Federal Republic of Germany) . Department of Clinical Radiology); Turesson, I. (Gothenborg University (Sweden). Department of Oncology)

1989-09-01

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 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

1990-01-01

191

Body mass index and risk of renal cell cancer: A dose-response meta-analysis of published cohort studies.  

Science.gov (United States)

Obesity is accepted as one of the major risk factors for renal cell cancer (RCC). However, conflicting results persist for the pooled risks based on the results from case-control and cohort studies combined, and the exact shape of the dose-response relationship has not been clearly defined yet. To help elucidate the role of obesity, PubMed and Embase databases were searched for published cohort studies on associations between body mass index (BMI) and risk of RCC. Random-effects models and dose-response meta-analyses were used to pool study results. Subgroup analyses were conducted by the available characteristics of studies and participants. Cohort studies (21) with 15,144 cases and 9,080,052 participants were identified. Compared to normal weight, the pooled relative risks and the corresponding 95% confidence intervals of RCC were 1.28(1.24-1.33) for preobesity and 1.77(1.68-1.87) for obesity, respectively. A nonlinear dose-response relationship was also found for RCC risk with BMI (p?=?0.000), and the risk increased by 4% for each 1 kg/m(2) increment in BMI. There was no significant between-study heterogeneity among studies (I(2) ?=?35.6% for preobesity and I(2) ?=?44.2% for obesity, respectively). Subgroup analysis showed a basically consistent result with the overall analysis. These results suggest that increased BMI are associated with increased risk of RCC both for men and women. PMID:24615287

Wang, Furan; Xu, Yinghua

2014-10-01

192

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2006-07-21

193

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

International Nuclear Information System (INIS)

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

2006-07-21

194

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

Science.gov (United States)

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

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

195

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

Science.gov (United States)

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

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

2014-07-01

196

Dose-response kinetics of chromatid aberration frequencies induced in vicia faba L. by ionizing radiation. I. Gamma rays  

International Nuclear Information System (INIS)

Frequency kinetics and ratio of the different chromatid aberration types induced by varying ?-rays doses in cells of Vicia faba root meristem were investigated. The dose dependence of the individual aberration types was studied by applying statistical models. It was established that the frequency of chromatid breaks surpasses that of interchromosomal exchanges, while isochromatid breaks had highest frequency as compared to the remaining types of aberrations. The frequency of true chromatid breaks was lowest. Chromatid aberration frequencies calculated per cell at a 1 rad dose did not depend on the radiation dose, while the frequency of interchromosomal exchanges rose about 2.5 times with the increase in the dose from 25 to 400 rad. The analysis of the dose-response curves of true chromatid breaks and isochromatid breaks performed by applying several statistical models showed that these aberrations had clearly expressed linear dose-response kinetics. Analysing the two types of breaks according to phases, however, showed also a slightly expressed two-track component in G2, which was absent in S-phase. In respect to interchromosomal exchanges a linear-quadratic kinetics was assessed both in S and in G-phase, with a higher one-track component in S as compared to G2. On the basis of the data conclusions were drawn concerning the probable mechanisms participating in the formation of chromosomal aberrations. (authors)

1981-01-01

197

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 ...

Pahlke Doreen; Freund Christian; Leitner Dietmar; Labudde Dirk

2005-01-01

198

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

International Nuclear Information System (INIS)

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

1987-01-01

199

A dose-response analysis for classical Kaposi's sarcoma management by radiotherapy  

International Nuclear Information System (INIS)

Objective was to evaluate the dose-response relationship in classical Kaposi's sarcoma CKS patients treated with external beam radiotherapy. Between 1993 and 2004, patients with CKS treated at the Department of Radiation Oncology, Gulhane Military Medical School, Ankara, Turkey were evaluated in this retrospective study. The median age at initial presentation was 60 years. First we analyzed the overall response rates for normalized total dose2Gy NTD2Gy of 20Gy. Secondly we searched for whether better response rates could be obtained with the NTD2Gy of >/=20Gy compared to the NTD2Gy of /20Gy and 64% and 24%for NDT2Gyof 20< Gy and these were statistically different p=0.001. Late side effects of radiation therapy were acceptable in all but 4 patients with fibrosis and edema. This retrospective analysis showed that radiotherapy schedules with an NDT2Gy of 20 Gy and above by using local irradiation fields are effective in terms of complete response rates in the management of CKS compared to NDT2Gy of < 20 Gy. (author)

2008-01-01

200

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

2004-01-01

 
 
 
 
201

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

202

Comparative haemodynamic dose response effects of propranolol and labetalol in coronary heart disease.  

Science.gov (United States)

The immediate haemodynamic dose response effects of beta blockade (propranolol: 2 to 16 mg) were compared with those of combined alpha beta blockade (labetalol: 10 to 80 mg) in a randomised study of 20 patients with stable angina pectoris. After control measurements, the circulatory changes induced by four logarithmically cumulative intravenous boluses of each drug in equivalent beta blocking doses were evaluated at rest, after which comparison of the effects of the maximum cumulative dose of each was undertaken during a four minute period of supine bicycle exercise. Propranolol, at rest, induced significant dose related reductions in heart rate and cardiac output, with reciprocal increases in the systemic vascular resistance and pulmonary artery occluded pressure; systemic arterial pressure was unchanged. Labetalol was followed by significant dose related decreases in systemic blood pressure and vascular resistance associated with a significant increase in cardiac output; heart rate and pulmonary artery occluded pressure were unchanged. The slope of the left ventricular pumping function curve relating output to filling pressure from rest to exercise was significantly depressed by propranolol but unchanged after labetalol. The less deleterious effects on left ventricular haemodynamic performance after alpha beta blockade in contrast to beta blockade alone in ischaemic heart disease may be attributable to the concomitant reduction in left ventricular afterload associated with the alpha blocking activity of labetalol.

Silke, B; Nelson, G I; Ahuja, R C; Taylor, S H

1982-01-01

203

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

204

Statistical trend analysis and extreme distribution of significant wave height from 1958 to 1999 – an application to the Italian Seas  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The study is a statistical analysis of sea states timeseries derived using the wave model WAM forced by the ERA-40 dataset in selected areas near the Italian coasts. For the period 1 January 1958 to 31 December 1999 the analysis yields: (i) the existence of a negative trend in the annual- and winter-averaged sea state heights; (ii) the existence of a turning-point in late 80's in the annual-averaged trend of sea state heights at a site in the Northern Adriatic Sea; (iii) the overall absence o...

Martucci, G.; Carniel, S.; Chiggiato, J.; Sclavo, M.; Lionello, P.; Galati, M. B.

2010-01-01

205

Statistical trend analysis and extreme distribution of significant wave height from 1958 to 1999 – an application to the Italian Seas  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The study is a statistical analysis of sea states timeseries derived using the wave model WAM forced by the ERA-40 dataset in selected areas near the Italian coasts. For the period 1 January 1958 to 31 December 1999 the analysis yields: (i) the existence of a negative trend in the annual- and winter-averaged sea state heights; (ii) the existence of a turning-point in late 70's in the annual-averaged trend of sea state heights at a site in the Northern Adriatic Sea; (iii) the overall absence o...

Martucci, G.; Carniel, S.; Chiggiato, J.; Sclavo, M.; Lionello, P.; Galati, M. B.

2009-01-01

206

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

Science.gov (United States)

To understand how benthic biota may respond to the additive or antagonistic effects of metal mixtures in the environment it is first necessary to examine their responses to the individual metals. In this context, laboratory controlled single metal-spiked sediment toxicity tests are useful to assess this. The exposure-dose-response relationships of Hyridella australis to cadmium-spiked sediments were, therefore, investigated in laboratory microcosms. H. australis was exposed to individual cadmium spiked sediments (cadmium accumulation in whole soft body and individual tissues at weekly intervals over the exposure period. Dose was further examined as sub-cellular localisation of cadmium in hepatopancreas tissues. The biological responses in terms of enzymatic and cellular biomarkers were measured in hepatopancreas tissues at day 28. H. australis accumulated cadmium from spiked sediments with an 8-fold (low exposure organisms) and 16-fold (high exposure organisms) increase at day 28 compared to control organisms. The accumulated tissue cadmium concentrations reflected the sediment cadmium exposure at day 28. Cadmium accumulation in high exposure organisms was inversely related to the tissue calcium concentrations. Gills of H. australis showed significantly higher cadmium accumulation than the other tissues. Accumulated cadmium in biologically active and biologically detoxified metal pools was not significantly different in cadmium exposed organisms, which suggests that H. australis has some tolerance to cadmium. The metallothionein like protein fraction played an important role in the sequestration and detoxification of cadmium and the amount sequestered in this fraction increased with increased cadmium exposure. The highest percentage of biologically active cadmium was associated with the lysosome+microsome and mitochondrial fractions. Cadmium concentrations in these two fractions of cadmium exposed organisms were significantly higher with respect to controls. Total antioxidant capacity decreased with increased cadmium exposure and tissue dose. Lipid peroxidation increased and lysosomal membrane stability decreased significantly with increased cadmium exposure and tissue dose. Based on exposure-dose-response analysis in this study, H. australis would be a suitable organism for assessing cadmium sediment exposure and toxicity. PMID:24834859

Marasinghe Wadige, Chamani P M; Maher, William A; Taylor, Anne M; Krikowa, Frank

2014-07-01

207

Comparison of dose response models for predicting normal tissue complications from cancer radiotherapy: application in rat spinal cord.  

Science.gov (United States)

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. PMID:24212817

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

2011-01-01

208

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

209

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

International Nuclear Information System (INIS)

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

2003-02-01

210

Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine. Methods Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response...

2010-01-01

211

The key events dose-response framework: its potential for application to foodborne pathogenic microorganisms  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The Key Events Dose-Response Framework (KEDRF) is an analytical approach that facilitates the use of currently available data to gain insight regarding dose-response relationships. The use of the KEDRF also helps identify critical knowledge gaps that once filled, will reduce reliance on assumptions. The present study considers how the KEDRF might be applied to pathogenic microorganisms, using fetal listeriosis resulting from maternal ingestion of food contaminated with L. monocytogenes as an ...

2009-01-01

212

The Key Events Dose-Response Framework: Its Potential for Application to Foodborne Pathogenic Microorganisms  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The Key Events Dose-Response Framework (KEDRF) is an analytical approach that facilitates the use of currently available data to gain insight regarding dose-response relationships. The use of the KEDRF also helps identify critical knowledge gaps that once filled, will reduce reliance on assumptions. The present study considers how the KEDRF might be applied to pathogenic microorganisms, using fetal listeriosis resulting from maternal ingestion of food contaminated with L. monocytogenes as an ...

2009-01-01

213

Influence of DNA Repair on Nonlinear Dose-Responses for Mutation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is o...

Thomas, Adam D.; Jenkins, Gareth J. S.; Kaina, Bernd; Bodger, Owen G.; Tomaszowski, Karl-heinz; Lewis, Paul D.; Doak, Shareen H.; Johnson, George E.

2013-01-01

214

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

215

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

216

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

International Nuclear Information System (INIS)

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

2005-11-01

217

Dose responses of three 4-aminopyridine derivatives on axonal conduction in spinal cord trauma.  

Science.gov (United States)

To explore novel treatments for enhancing conduction through traumatically injured spinal cord we have synthesized structurally distinct pyridine based compounds; N-(4-pyridyl) methyl carbamate, N-(4-pyridyl) ethyl carbamate, and N-(4-pyridyl) t-butyl carbamate. With the use of a double sucrose gap-recording chamber we perform a dose-response assay to examine the effects of these compounds on axonal conduction following an in vitro stretch injury. The tested compounds significantly enhanced axonal conduction to the stretch injured cord at 1 microM, a dose that coincides with the clinically relevant dose of potassium channel blocker 4-aminopyridine (4-AP). Methyl carbamate enhanced conduction maximally at 100 microM. This is also the most effective concentration of 4-AP in vitro. The other compounds ethyl carbamate and t-butyl carbamate enhanced conduction maximally at lower concentrations of 10 and 1 microM. At higher concentrations each of these compounds continued to increased CAP amplitude, however not significantly. Additionally, two of the compounds ethyl and t-butyl carbamate appear to have negative effects on CAP amplitude when administered at or beyond 100 microM. These compounds demonstrate the possibility that derivatives of 4-AP can retain the ability to increase axonal conduction in the injured spinal cord. PMID:16297607

McBride, Jennifer M; Smith, Daniel T; Byrn, Stephen R; Borgens, Richard B; Shi, Riyi

2006-02-01

218

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

1999-01-01

219

Dose-response effects of customised foot orthoses on lower limb kinematics and kinetics in pronated foot type.  

Science.gov (United States)

Despite the widespread use of customised foot orthoses (FOs) for the pronated foot type there is a lack of reliable information on the dose-response effect on lower limb mechanics. This study investigated these effects in subjects with normal and pronated foot types. Customised FOs were administered to 12 participants with symptomatic pronated foot type and 12 age and gender matched controls. A computer-aided design (CAD) software was used to design nine FOs per participant with dose incrementally changed by varying only the rearfoot post angle. This was done in 2° increments from 6° lateral to 10° medial posting. A 3D printing method was used to manufacture the FOs. Quantification of the dose-response effect was performed using three-dimensional gait analyses for selected rearfoot and knee kinematics and kinetics. Under these experimental conditions, significant and linear effects of posting were seen for the peak (p<0.001) and mean (p<0.001) rearfoot eversions, peak (p=0.003) and mean (p<0.001) ankle eversion moments and peak (p=0.017) and mean (p=0.005) knee adduction moment variables. Group effects were observed for the peak (p=0.007) and mean (p=0.007) forefoot abduction and for the peak (p=0.007) knee adduction moment. A significant interaction between posting and group was seen for internal tibial rotation (p=0.004). These data indicate that a dose-response effect, with a linear trend for both the rearfoot and knee, exists for customised FOs used to treat pronated foot type. PMID:23631857

Telfer, Scott; Abbott, Mandy; Steultjens, Martijn P M; Woodburn, James

2013-05-31

220

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.

Gluud, Christian; Lange, Theis

2014-01-01

 
 
 
 
221

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

International Nuclear Information System (INIS)

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

2011-01-01

222

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

2002-09-05

223

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

2007-07-01

224

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

225

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

International Nuclear Information System (INIS)

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

2006-05-01

226

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.)

1977-11-04

227

Dairy consumption and incidence of hypertension: a dose-response meta-analysis of prospective cohort studies.  

Science.gov (United States)

Observational and clinical studies suggest that dairy intake, particularly low-fat dairy, could have a beneficial effect on blood pressure. We performed a dose-response meta-analysis of prospective cohort studies on dairy intake and risk of hypertension in the general population. A systematic literature search for eligible studies was conducted until July 2011, using literature databases and hand search. Study-specific dose-response associations were computed according to the generalized least squares for trend estimation method, and linear and piecewise regression models were created. Random-effects models were performed with summarized dose-response data. We included 9 studies with a sample size of 57 256, a total of 15 367 incident hypertension cases, and a follow-up time between 2 and 15 years. Total dairy (9 studies; range of intake, ?100-700 g/d), low-fat dairy (6 studies; ?100-500 g/d), and milk (7 studies; ?100-500 g/d) were inversely and linearly associated with a lower risk of hypertension. The pooled relative risks per 200 g/d were 0.97 (95% CI, 0.95-0.99) for total dairy, 0.96 (95% CI, 0.93-0.99) for low-fat dairy, and 0.96 (95% CI, 0.94-0.98) for milk. High-fat dairy (6 studies), total fermented dairy (4 studies), yogurt (5 studies), and cheese (8 studies) were not significantly associated with hypertension incidence (pooled relative risks of ?1). This meta-analysis of prospective cohort studies suggests that low-fat dairy and milk could contribute to the prevention of hypertension, which needs confirmation in randomized controlled trials. PMID:22987924

Soedamah-Muthu, Sabita S; Verberne, Lisa D M; Ding, Eric L; Engberink, Mariëlle F; Geleijnse, Johanna M

2012-11-01

228

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

2013-11-01

229

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 μW/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 μW/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

230

Radiation dose and leukaemia risk: general relative risk techniques for dose-response models in a matched case-control study  

International Nuclear Information System (INIS)

Generalized relative risk functions were used to model radiation dose-response information from a large matched case-control study of leukaemia occurring after treatment for cervical cancer. Models suggested by radiobiological theory were investigated and compared to standard analyses of categorical dose-response to the linear model. Local radiation doses to each of fourteen bone marrow compartments for each patient were incorporated into the models, and the corresponding risks were summed. Conditional maximum likelihood methods were used to estimate risk parameters. Unique features of the analysis include modelling both induction and reduction of risk as a function of radiation dose absorbed by different parts of the body within individuals. Detailed statistical aspects of these analyses are presented and discussed. (author)

1991-01-01

231

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

Directory of Open Access Journals (Sweden)

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

Szomolay Barbara

2012-04-01

232

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

1982-01-01

233

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2010-01-01

234

Mechanisms of Action and Dose-Response Relationships Governing Biological Control of Fusarium Wilt of Tomato by Nonpathogenic Fusarium spp.  

Science.gov (United States)

ABSTRACT Three isolates of nonpathogenic Fusarium spp. (CS-1, CS-20, and Fo47), previously shown to reduce the incidence of Fusarium wilt diseases of multiple crops, were evaluated to determine their mechanisms of action and antagonist-pathogen inoculum density relationships. Competition for nutrients, as represented by a reduction in pathogen saprophytic growth in the presence of the biocontrol isolates, was observed to be an important mechanism of action for isolate Fo47, but not for isolates CS-1 and CS-20. All three biocontrol isolates demonstrated some degree of induced systemic resistance in tomato (Lycopersicon esculentum) and watermelon (Citrullus lanatus) plants, as determined by split-root tests, but varied in their relative abilities to reduce disease. Isolate CS-20 provided the most effective control (39 to 53% disease reduction), while Fo47 provided the least effective control (23 to 25% reduction) in split-root tests. Dose-response relationships also differed considerably among the three biocon-trol isolates, with CS-20 significantly reducing disease incidence at antagonist doses as low as 100 chlamydospores per g of soil (cgs) and at pathogen densities up to 10(5) cgs. Isolate CS-1 also was generally effective at antagonist densities of 100 to 5,000 cgs, but only when pathogen densities were below 10(4) cgs. Isolate Fo47 was effective only at antagonist densities of 10(4) to 10(5) cgs, regardless of pathogen density. Epidemiological dose-response models (described by linear, negative exponential, hyperbolic saturation [HS], and logistic [LG] functions) fit to the observed data were used to quantify differences among the biocontrol isolates and establish biocontrol characteristics. Each isolate required a different model to best describe its dose-response characteristics, with the HS/HS, LG/HS, and LG/LG models (pathogen/biocontrol components) providing the best fit for isolates CS-1, CS-20, and Fo47, respectively. Model parameters (defining effective biocontrol dose (ED(50)) indicated an ED(50) of 2.6, 36.3, and 2.1 x 10(6) cgs and estimates of biocontrol efficiency of 0.229, 0.539, and 0.774 for isolates CS-1, CS-20, and Fo47, respectively. Differences in dose-response relationships among the biocontrol isolates were attributed to differences in their mechanisms of action, with CS-20 and CS-1 functioning primarily by induced resistance and Fo47 functioning primarily by competition for nutrients. PMID:18944639

Larkin, R P; Fravel, D R

1999-12-01

235

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

1999-10-01

236

Curvilinearity in the dose-response curve for cancer in Japanese atomic bomb survivors.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Recently released data on cancer incidence in Japanese atomic bomb survivors are analyzed using a variety of relative risk models that take account of errors in estimates of dose to assess the dose response at low doses. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to solid cancer data, a threshold of more than about 0.2 Sv is inconsistent with the data, whereas these data are consistent with there being no threshold. Among soli...

1997-01-01

237

Addressing model uncertainty in dose-response: The case of chloroform  

International Nuclear Information System (INIS)

This paper discusses the issues involved in addressing model uncertainty in the analysis of dose-response relationships. A method for addressing model uncertainty is described and applied to characterize the uncertainty in estimates of the carcinogenic potency of chloroform. The approach, which is rooted in Bayesian concepts of subjective probability, uses probability trees and formally-elicited expert judgments to address model uncertainty. It is argued that a similar approach could be used to improve the characterization of model uncertainty in the dose-response relationships for health effects from ionizing radiation

1994-10-01

238

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

International Nuclear Information System (INIS)

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

2006-11-21

239

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

International Nuclear Information System (INIS)

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

1996-11-01

240

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

 
 
 
 
241

Inhaled nitric oxide: Dose response and the effects of blood in the isolated rat lung  

Energy Technology Data Exchange (ETDEWEB)

Inhaled nitric oxide (NO) is a vasodilator selective to the pulmonary circulation. Using isolated rat lungs, the authors determined the dose-response relationship of NO and the role of blood in mediating pulmonary vasodilation and selectivity. Inhaled 20, 50, 100, and 1,000 ppm NO attenuated (P < 0.001) hypoxic pulmonary vasoconstriction by 16.1 [+-] 4.9, 22.6 [+-] 6.8, 28.4 [+-] 3.5, and 69.3 [+-] 4.2%, respectively. Inhaled 13, 34, 67, and 670 ppm NO attenuated the increase in pulmonary arterial pressure secondary to angiotensin II more (P < 0.001) in Greenberg-Bohr buffer- (GB) than in blood-perfused lungs (51.7 [+-] 0.0, 71.9 [+-] 8.9, 78.2 [+-] 5.3, and 91.9 [+-] 2.1% vs. 14.3 [+-] 4.2, 23.8 [+-] 4.6, 28.4 [+-] 3.8, and 55.5 [+-] 5.9%, respectively). Samples from GB- but not blood-perfused lungs contained NO (93.0 [+-] 26.3 nM). Intravascular NO attenuated the response to angiotensin II more (P < 0.001) in GB- (with and without plasma) than in blood- (hematocrit = 41 and 5%) perfused lungs (75.6 [+-] 6.4 and 70.9 [+-] 4.8% vs. 22.2 [+-] 2.4 and 39.4 [+-] 7.6%). In conclusion, inhaled NO produces reversible dose-dependent pulmonary vasodilation over a large range of concentrations. Inhaled NO enters the circulation, but red blood cells prevent systematic vasodilation and also a significant amount of pulmonary vasodilation. 24 refs., 7 figs., 2 tabs.

Rich, G.F.; Roos, C.M.; Anderson, S.M.; Urich, D.C.; Daugherty, M.O.; Johns, R.A. (Univ. of Virginia Health Sciences Center, Charlottesville, VA (United States))

1993-09-01

242

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

2013-04-14

243

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

244

Bayesian semiparametric predictive modeling with applications in dose-response prediction.  

Science.gov (United States)

A framework is proposed for making quality predictions in situations for which only systematically inaccurate data are available. The predictions are based on the systematically inaccurate data, complete data from similar situations, and expert knowledge. The proposed predictive model is well suited to functional data and is computationally simple, fast, and stable. We focus primarily on a particular problem presenting itself in the pharmaceutical industry. Predicting both side effect and endpoint dose responses before the initiation of a clinical trial has enormous ethical and financial importance in the pharmaceutical industry. The proposed Bayesian semiparametric predictive model is used to predict unobserved clinical dose-response curves conditional on preclinical data, data from similar compounds, and prior knowledge. The model allows for nonlinear dose-response curves and the incorporation of relevant prior information. Posterior sampling is achieved through a simple and computationally efficient Gibbs sampler. The predictions from the model are drawn from the posterior distribution of the average dose-response curve for the candidate compound, allowing straightforward incorporation into a risk assessment model unlike the deterministic predictions often used currently. The model is used on actual data from the pharmaceutical industry, showing that the model is capable of predicting lack or presence of trend with appropriate uncertainty. PMID:24605970

Haaland, Ben; Chiang, Alan Y

2014-01-01

245

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

Science.gov (United States)

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

246

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

247

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

248

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

Science.gov (United States)

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

249

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

250

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

251

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

252

Shape and steepness of toxicological dose-response relationships of continuous endpoints.  

Science.gov (United States)

A re-analysis of a large number of historical dose-response data for continuous endpoints indicates that an exponential or a Hill model with four parameters adequately describes toxicological dose-responses. No exceptions were found for the datasets considered, which related to a wide variety of endpoints and to both in vivo and in vitro studies of various types. For a given endpoint/study type dose-response shapes were found to be homogenous among chemicals in the in vitro studies considered, while a mild among-chemical variation in the steepness parameter seemed to be present in the in vivo studies. Our findings have various practical consequences. For continuous endpoints, model selection in the BMD approach is not a crucial issue. The often applied approach of using constraints on the model parameters to prevent "infinite" slopes at dose zero in fitting a model is not in line with our findings, and appears to be unjustified. Instead, more realistic ranges of parameter values could be derived from re-analyses of large numbers of historical dose-response datasets in the same endpoint and study type, which could be used as parameter constraints in future individual datasets. This approach will be particularly useful for weak datasets (e.g. few doses, much scatter). In addition, this approach may open the way to use fewer animals in future studies. In the discussion, we argue that distinctions between linear, sub/supralinear or thresholded dose-response shapes, based on visual inspection of plots, are not biologically meaningful nor useful for risk assessment. PMID:24252121

Slob, Wout; Setzer, R Woodrow

2014-03-01

253

A family-based eating disorder day treatment program for youth: examining the clinical and statistical significance of short-term treatment outcomes.  

Science.gov (United States)

This article describes an innovative family-based day treatment program (DTP) for youth with moderate to severe eating disorders. A sample of 65 youth completed a battery of psychological measures pre- and post-treatment and 6 months after program completion. Treatment outcomes were assessed in three main domains: (a) medical stabilization, (b) normalization of eating behavior, and (c) improved psychological functioning. Overall, patients demonstrated statistically significant and clinically meaningful improvements on all outcome measures. Findings indicate that a comprehensive DTP can successfully facilitate positive outcomes in youth with eating disorders and that these improvements can be maintained 6 months post-treatment. PMID:24365524

Henderson, Katherine; Buchholz, Annick; Obeid, Nicole; Mossiere, Annik; Maras, Danijela; Norris, Mark; Harrison, Megan; Feder, Stephen; Spettigue, Wendy

2014-01-01

254

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

International Nuclear Information System (INIS)

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

2013-08-01

255

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

256

Dose-response effects of gramicidin-D, EDTA, and nonoxynol-9 on sperm motion parameters and acrosome status.  

Science.gov (United States)

Previous reports showed that gramicidin-D (G-D), a polypeptide with antiviral and antimicrobial properties, nonoxynol-9 (N9), a common spermicidal detergent, and EDTA, a Ca-Mg chelating agent, inhibited sperm motility and cervical mucus penetration. The purpose of this study was to determine the dose-response effects of G-D, N9, EDTA and G-D + EDTA on sperm motion parameters and acrosome status. Semen specimens from known fertile donors were subjected to computer-assisted semen analysis of motility, path velocity, progressive velocity, and hyperactivation prior to and after incubation with varying concentrations of gramicidin-D, EDTA and nonoxynol-9. Each specimen was also prepared for acrosome status using rhodamine isothiocyanate conjugated pisum sativum agglutinin (RITC-PSA). There was a significant decrease in motility by G-D, EDTA, G-D + EDTA, and N9 at all doses as compared to the fresh specimen. N9 completely immobilized all sperm at each dose. Progressive velocity and path velocity also decreased in a dose-response manner. Sperm hyperactive motility also significantly decreased in all groups. The majority of sperm remained acrosome intact following exposure to all doses tested, whereas N9 resulted in complete breakdown/release of the acrosomal contents. This study confirms previous reports that G-D, EDTA, and N9 significantly impair sperm motility and motion parameters. The effective 100% inhibitory concentration was seen only with N9, whereas G-D, EDTA, and G-D + EDTA resulted in incomplete impairment of sperm motion parameters. At the concentrations used, N9 demonstrated potent spermostatic activity. Gramicidin-D and EDTA should be further studied for their potential contraceptive spermostatic activity. PMID:9743894

Centola, G M

1998-07-01

257

Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.  

Science.gov (United States)

Application of a sensitive new detection method has revealed widespread perchlorate contamination of groundwater in the southwestern United States, typically at 0.005-0.020 mg/L (5-20 ppb). Perchlorate is a competitive inhibitor of the process by which iodide is actively transported from the bloodstream into the thyroid. This inhibitory action of perchlorate is the basis of its pharmaceutical use (in the treatment of hyperthyroidism) as well as its potential toxicity. To establish the dose response in humans for perchlorate inhibition of thyroidal iodide uptake and any short-term effects on thyroid hormones, we gave perchlorate in drinking water at 0.007, 0.02, 0.1, or 0.5 mg/kg-day to 37 male and female volunteers for 14 days. In 24 subjects we performed 8- and 24-hr measurements of thyroidal (123)I uptake (RAIU) before exposure, on exposure days 2 (E2) and 14 (E14), and 15 days postexposure (P15). In another 13 subjects we omitted both E2 studies and the 8-hr P15 study. We observed a strong correlation between the 8- and 24-hr RAIU over all dose groups and measurement days. We found no difference between E2 and E14 in the inhibition of RAIU produced by a given perchlorate dose. We also found no sex difference. On both E2 and E14, the dose response was a negative linear function of the logarithm of dose. Based on the dose response for inhibition of the 8- and 24-hr RAIU on E14 in all subjects, we derived estimates of the true no-effect level: 5.2 and 6.4 micro g/kg-day, respectively. Given default body weight and exposure assumptions, these doses would be ingested by an adult if the drinking-water supply contained perchlorate at concentrations of approximately 180 and 220 micro g/L (ppb), respectively. On P15, RAIU was not significantly different from baseline. In 24 subjects we measured serum levels of thyroxine (total and free), triiodothyronine, and thyrotropin in blood sampled 16 times throughout the study. Only the 0.5 mg/kg-day dose group showed any effect on serum hormones: a slight downward trend in thyrotropin levels in morning blood draws during perchlorate exposure, with recovery by P15. PMID:12204829

Greer, Monte A; Goodman, Gay; Pleus, Richard C; Greer, Susan E

2002-09-01

258

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2007-02-15

259

Mixed-effects Gaussian process functional regression models with application to dose-response curve prediction.  

Science.gov (United States)

We propose a new semiparametric model for functional regression analysis, combining a parametric mixed-effects model with a nonparametric Gaussian process regression model, namely a mixed-effects Gaussian process functional regression model. The parametric component can provide explanatory information between the response and the covariates, whereas the nonparametric component can add nonlinearity. We can model the mean and covariance structures simultaneously, combining the information borrowed from other subjects with the information collected from each individual subject. We apply the model to dose-response curves that describe changes in the responses of subjects for differing levels of the dose of a drug or agent and have a wide application in many areas. We illustrate the method for the management of renal anaemia. An individual dose-response curve is improved when more information is included by this mechanism from the subject/patient over time, enabling a patient-specific treatment regime. PMID:22865484

Shi, J Q; Wang, B; Will, E J; West, R M

2012-11-20

260

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

International Nuclear Information System (INIS)

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

2007-02-01

 
 
 
 
261

Dose effects of ion beam exposure on Deinococcus radiodurans: survival and dose response  

International Nuclear Information System (INIS)

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

2001-02-01

262

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

Science.gov (United States)

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

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

2001-02-01

263

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

264

The dose response characteristics of FWT-60 radiochromic film to 60Co gamma rays  

International Nuclear Information System (INIS)

The FWT-60 radiochromic films after irradiated by 60Co gamma rays is studied and the dependences of the absorbance response on the temperatures during irradiation and reading and the postirradiation effect also given. The dose response characteristics of the film to 60Co gamma rays at the reading wavelengths of 510 nm and 605 nm are determined. It is found that the absorbance responses and the absorption peaks of the films are dependent on the temperatures during measurement

1994-05-01

265

Therapeutic Time Window and Dose Response of Autologous Bone Marrow Mononuclear Cells for Ischemic Stroke  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Although mononuclear cells (MNCs) from bone marrow are being investigated in phase I clinical trials in stroke patients, dose response, therapeutic time window and biodistribiton have not been well-characterized in animal stroke models. Long Evans rats underwent common carotid artery/middle cerebral artery occlusion (CCA/MCAo) and 24 hrs later were randomized to receive saline IV or a bone marrow aspiration followed by an IV infusion of autologous separated MNCs (1 million, 10 million or 30 m...

Yang, Bing; Strong, Roger; Sharma, Sushil; Brenneman, Miranda; Mallikarjunarao, Kasam; Xi, Xiaopei; Grotta, James C.; Aronowski, Jaroslaw; Savitz, Sean I.

2011-01-01

266

Intranasal oxytocin attenuates the cortisol response to physical stress: a dose–response study  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Rationale/statement of the problem : Intranasal oxytocin attenuates cortisol levels during social stress inductions. However, no research to date has documented the dose–response relationship between intranasal oxytocin administration and cortisol, and researchers examining intranasal oxytocin have not examined the cortisol response to physical stress. We, therefore, examined the effects of 24 and 48 IU of intranasal oxytocin on the cortisol response to vigorous exercise. Methods : Sev...

2012-01-01

267

Compound Optimal Designs for Percentile Estimation in Dose-Response Models with Restricted Design Intervals  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In dose-response studies, the dose range is often restricted due to ethics concerns over drug toxicity and/or efficacy, particularly when human subjects are involved. We present locally optimal designs for the estimation of several percentiles simultaneously on restricted as well as unrestricted design intervals. Our results are applicable to most of the commonly applied link functions with respect to the model under consideration. This work is a generalization of Dai (2000) where he showed t...

Dette, Holger; Biedermann, Stefanie; Zhu, Wei

2005-01-01

268

The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The Organisation for Economic Co-operation and Development has completed phase 2 of an international validation program for the rodent uterotrophic bioassay. The purpose of the validation program was to demonstrate the performance of two versions of the uterotrophic bioassay, the immature female rat and the adult ovariectomized rat, in four standardized protocols. This article reports the dose-response studies of the validation program; the coded single-dose studies are reported in an accompa...

Kanno, Jun; Onyon, Lesley; Peddada, Shyamal; Ashby, John; Jacob, Elard; Owens, William

2003-01-01

269

Comparative haemodynamic dose response effects of propranolol and labetalol in coronary heart disease.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The immediate haemodynamic dose response effects of beta blockade (propranolol: 2 to 16 mg) were compared with those of combined alpha beta blockade (labetalol: 10 to 80 mg) in a randomised study of 20 patients with stable angina pectoris. After control measurements, the circulatory changes induced by four logarithmically cumulative intravenous boluses of each drug in equivalent beta blocking doses were evaluated at rest, after which comparison of the effects of the maximum cumulative dose of...

Silke, B.; Nelson, G. I.; Ahuja, R. C.; Taylor, S. H.

1982-01-01

270

Human jejunal secretion induced by prostaglandin E1: a dose-response study.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

1. Intraluminally infused prostaglandins induce jejunal secretion of water and electrolytes in man, and a receptor-mediated process in the intestinal epithelial cells has been suggested to explain this secretion. In an attempt to obtain data under basal conditions for pharmacological studies, we tested the dose-response effect of PGE1 on jejunal hydroelectrolytic movements in 10 healthy volunteers. 2. Accordingly, a solution with or without PGE1 was infused via a four-lumen tube with a proxim...

Sobhani, I.; Vidon, N.; Huchet, B.; Rambaud, J. C.

1991-01-01

271

Dose response relations for gastro-instestinal pathogens in an animal model  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Dose-response models ar an essential part of quantitative microbiological risk assessment, but not many appropriate data are available for this purpose. Human volunteer studies provide only limited information. Therefore, an animal model for infection with human enteropathogenic bacteria is being developed. Adult, male WU rats were exposed to different doses of three enteropathogenic bacteria (Salmonella enterica serovar Enteritidis, Escherichia coli 0157, and Campylobacter...

Ah, Havelaar; Garssen J; Takumi K; Koedam M; Jb, Dufrenne; Fm, Leusden; La, Fonteyne L.; Jg, Vos

2007-01-01

272

Severity of killer whale behavioral responses to ship noise: A dose-response study  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Critical habitats of at-risk populations of northeast Pacific "resident" killer whales can be heavily trafficked by large ships, with transits occurring on average once every hour in busy shipping lanes. We modeled behavioral responses of killer whales to ship transits during 35 "natural experiments" as a dose-response function of estimated received noise levels in both broadband and audiogram-weighted terms. Interpreting effects is contingent on a subjective and seemingly arb...

2014-01-01

273

Dose response and latency for radiation-induced fibrosis, edema, and neuropathy in breast cancer patients  

International Nuclear Information System (INIS)

Purpose: To study the incidence of various forms of late normal tissue injuries to determine the latency and dose-response relationships. Methods: We retrospectively analyzed the clinical records of 150 breast cancer patients treated with radiotherapy after mastectomy in the mid to late 1960s. None of the patients had received chemotherapy as a part of their primary treatment. Radiotherapy was delivered to the parasternal, axillary, and supraclavicular lymph node regions. Almost all the patients continued to be checked at regular 3-month to 1-year intervals at our Oncology Department. Detailed records were available for the entire 34 years of the follow-up period. The patients were divided into 3 groups. The prescribed dose was either 11x4 Gy (treated with 60Co photons) or 11x4 Gy or 14-15x3 Gy (treated with both 60Co photons and electrons). The dose recalculation at the brachial plexus where the axillary and supraclavicular beams overlapped was performed in the early 1970s and expressed in cumulative radiation effect (CRE) units. It varied widely among the individual patients. The received dose has now been converted to biologic effective dose3 units, and from that into the equivalent dose in 2-Gy fractions to plot the dose-response relationships. Results: We present a comparison of the latency and frequency of fibrosis, edema, brachial plexus neuropathy, and paralysis in the three different subgroups and the total group. Dose-response relationships are shown at 5, 10, and 30 years after irradiation. Conclusion: The use of large daily fractions, combined with hotspots from overlapping fields, was the cause of the complications. Clear dose-response curves were seen for late radiation injuries. The incidence seen at 5 years did not represent the full spectrum of injuries. Doses that seem safe at 5 years can lead to serious complications later

2002-04-01

274

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

Energy Technology Data Exchange (ETDEWEB)

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

Schultz-Hector, S. (Institut fuer Strahlenbiologie, Neuherberg (Germany))

1992-02-01

275

Dose-response analyses of the carcinogenic effects of trichloroethylene in experimental animals.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In lifetime bioassays, trichloroethylene (TCE, CAS No. 79-01-6) causes liver tumors in mice following gavage, liver and lung tumors in mice following inhalation, and kidney tumors in rats following gavage or inhalation. Recently developed pharmacokinetic models provide estimates of internal, target-organ doses of the TCE metabolites thought responsible for these tumor responses. Dose-response analyses following recently proposed methods for carcinogen risk assessment from the U.S. Environment...

Rhomberg, L. R.

2000-01-01

276

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

277

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)

1989-01-01

278

The dose-response relation for the antinociceptive effect of morphine in a fish, rainbow trout.  

Science.gov (United States)

There have been suggestions that analgesics be used by fish researchers. But in the absence of dose-response data for morphine, this suggestion seems imprudent. The purpose of the present study was to develop a dose-response relationship in fish using six doses of morphine. The response (movement of the fins or tail) to a noxious stimulus (electrical shock to the face region) was monitored before and after a dose of morphine intraperitoneally (i.p.). The i.p. dose of morphine ED(50) in rainbow trout was 6.7 ± 0.8 mg/kg (n = 12 at each dose). The plasma morphine concentration EC(50) was 4.1 ± 1.5 mg/L. In a second experiment, rainbow trout tested with equal amounts of morphine and naloxone (30 mg/kg) showed that the antinociceptive effect of morphine was blocked by naloxone. It has been suggested that stress-induced analgesia has been a confounding factor in some fish studies. However, plasma cortisol levels in our study indicated that stress was not a confounding factor in the present experiments. The ED(50) for morphine in fish was higher than that reported for humans or other mammals. Our observation showing a dose-response relation for morphine using a noxious stimulus supports arguments for its effectiveness as an antinociceptive drug in fish. PMID:22229842

Jones, S G; Kamunde, C; Lemke, K; Stevens, E D

2012-12-01

279

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.)

1981-01-01

280

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

International Nuclear Information System (INIS)

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 ?-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.

2010-05-01

 
 
 
 
281

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Public Health | Language: Spanish Abstract in spanish 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. Abstract in english 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; Luis Carlos, Silva Ayçaguer.

282

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

283

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

284

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

Science.gov (United States)

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

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

2011-02-01

285

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

286

Meta-analysis for deriving age- and gender-specific dose-response relationships between urinary cadmium concentration and beta2-microglobulinuria under environmental exposure.  

Science.gov (United States)

A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and beta2-microglobulinuria (beta2MG-uria) under environmental exposure. beta2MG-uria was defined by a cutoff point of 1000 microg beta2-microglobulin/g creatinine. We proposed a model for describing the relationships among the interindividual variabilities in urinary Cd concentration, the ratio of Cd concentrations in the target organ and in urine, and the threshold Cd concentration in the target organ. The parameters in the model were determined so that good agreement might be achieved between the prevalence rates of beta2MG-uria reported in the literature and those estimated by the model. In this analysis, only the data from the literature on populations environmentally exposed to Cd were used. Using the model and estimated parameters, the prevalence rate of beta2MG-uria can be estimated for an age- and gender-specific subpopulation for which the distribution of urinary Cd concentrations is known. The maximum permissible level of urinary Cd concentration was defined as the maximum geometric mean of the urinary Cd concentration in an age- and gender-specific subpopulation that would not result in a statistically significant increase in the prevalence rate of beta2MG-uria. This was estimated to be approximately 3 microg/g creatinine for a population in a small geographical area and approximately 2 microg/g creatinine for a nationwide population. PMID:16298359

Gamo, Masashi; Ono, Kyoko; Nakanishi, Junko

2006-05-01

287

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)

By 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 idealized 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 the 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 the paper is likely to be of general applicability. (author)

1977-11-04

288

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

289

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

International Nuclear Information System (INIS)

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

2013-01-01

290

The effects of heating rate on the dose response characteristics of TLD-200, TLD-300 and TLD-400  

Energy Technology Data Exchange (ETDEWEB)

In the given study; the effects of heating rates on the dose response characteristics of CaF{sub 2}:Dy (TLD-200), CaF{sub 2}:Tm (TLD-300) and CaF{sub 2}:Mn (TLD-400) crystals have been investigated using the dose dependence curve and dose response function f(D). It was observed from the dose response functions that the linearity and behaviour of the TL glow peaks of TLD-200 and TLD-400 are affected, but the TLD-300 is not affected from the heating rate.

Kafadar, V. Emir [University of Gaziantep, Department of Engineering Physics, 27310 Gaziantep (Turkey)], E-mail: kafadar@gantep.edu.tr; Necmeddin Yazici, A.; Gueler Yildirim, R. [University of Gaziantep, Department of Engineering Physics, 27310 Gaziantep (Turkey)

2009-10-01

291

The effects of heating rate on the dose response characteristics of TLD-200, TLD-300 and TLD-400  

International Nuclear Information System (INIS)

In the given study; the effects of heating rates on the dose response characteristics of CaF2:Dy (TLD-200), CaF2:Tm (TLD-300) and CaF2:Mn (TLD-400) crystals have been investigated using the dose dependence curve and dose response function f(D). It was observed from the dose response functions that the linearity and behaviour of the TL glow peaks of TLD-200 and TLD-400 are affected, but the TLD-300 is not affected from the heating rate.

2009-10-01

292

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

2004-01-01

293

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

294

X-ray stage sensitivity of mouse oocytes and its bearing on dose-response curves  

International Nuclear Information System (INIS)

A detailed cytogenetic study of maturing mouse oocyte radiosensitivity was performed. Oocytes were collected at various intervals ranging from 1.5 days to 28.5 days after irradiation with 50, 100, 200, and 300R of acute x rays. The observed sensitivity to chromatid aberration induction varied greatly over this time span. Sensitivity was lowest at the shortest time interval before ovulation and gradually increased up to 9.5 days; it then remained constant until insufficient numbers of oocytes could be collected. The data were analyzed in three ways. First, the data from all time intervals at each dose were pooled; second the data from the least sensitive time intervals, at each dose, were pooled, and third, the data from the period of uniform sensitivity, at each dose, were pooled. Dose-response regression analyses were done on these pooled data and the best fits obtained were to the models Y = a + bD + cD2 and Y = a + cD2 for both deletions and interchanges. This result is interpreted as indicating that the aberrations result from a predominantly two-track process. The cytogenetic data were compared to specific-locus mutation induction data in comparable oocyte stages, and qualitative similarity in dose-response characteristics were observed. This similarity is interpreted to mean that both events result from the same mechanism, and that the large dose-rate effect, observed for both events, is a reflection of the two-track component in the dose-response curves

1979-01-01

295

Dose-response modeling of etoposide-induced DNA damage response.  

Science.gov (United States)

The 2007 National Research Council Report "Toxicity Testing in the 21st Century: A Vision and A Strategy" recommended an integrated, toxicity pathway-oriented approach for chemical testing. As an integral component of the recommendation, computational dose-response modeling of toxicity pathways promises to provide mechanistic interpretation and prediction of adverse cellular outcomes. Among the many toxicity pathways, the DNA damage response is better characterized and thus more suited for computational modeling. In the present study, we formulated a minimal mathematical model of this pathway to examine the dose response for etoposide (ETP), an anticancer drug that causes DNA double strand breaks (DSBs). In the model, DSB results from inhibition of topoisomerase by ETP and p53 is activated by a bistable switch composed of a positive feedback loop between ATM and ?H2AX. Our stochastic model recapitulated the dose response for several molecular biomarkers measured with flow cytometry in HT1080 cells, including phosphorylated p53, ATM, ?H2AX, and micronuclei. Model simulations were consistent with a bimodal pattern of p53 activation and a graded population-averaged response at high ETP concentrations. The graded response was a result of heterogeneous activation of individual cells due to molecular stochasticity. This work shows the value of combining data collection on single cell responses and mechanistic, stochastic modeling to develop and test hypothesis for the circuitry of important toxicity pathways. Future studies will determine how well this initial modeling effort agrees with a broader set of experimental studies on pathway responses by examining a more diverse group of DNA-damaging compounds. PMID:24241721

Li, Zhenhong; Sun, Bin; Clewell, Rebecca A; Adeleye, Yeyejide; Andersen, Melvin E; Zhang, Qiang

2014-02-01

296

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

International Nuclear Information System (INIS)

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

1996-11-17

297

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

International Nuclear Information System (INIS)

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

1988-01-01

298

Low Doses of Gamma-Radiation Induce Nonlinear Dose Responses in Mammalian and Plant Cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The percentage of cells with chromosome aberrations or micronuclei induced by low doses of acute (dose rate of 47 cGy/min) or chronic (dose rate of 0.01 cGy/min) gamma-irradiation was studied in vitro in Chinese hamster fibroblasts, human lymphocytes, and Vicia faba seeds and seedlings. The sensitivity of the indicated biological entities to low doses was greater than expected based on linear extrapolation from higher doses. The dose-response curves for cytogenetic damage that were obtained w...

2004-01-01

299

Stage-sensitivity and dose-response study after ?-irradiation of mouse primary spermatocytes  

International Nuclear Information System (INIS)

The sensitivity pattern for X-ray-induced chromatid aberrations was analysed in primary spermatocytes irradiated at 1 to 11 days before diakinesis-metaphase I of meiosis. Using a dose of 300 R (60 R/min) of ?-rays zygotene (day 9) was found to be the most sensitive and leptotene (day 11) the most insensitive stage. The dose-response to ?-ray-induced aberrations was evaluated in cells irradiated at zygotene. Both the yields of rearrangements as well as the yields of fragments gave a best fit to a quadratic model. (author)

1977-01-01

300

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

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

2007-01-01

 
 
 
 
301

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

Science.gov (United States)

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

Byers, John A

2013-08-01

302

Dose response relationships for chromosome aberrations induced by low doses of alpha-particle radiation  

International Nuclear Information System (INIS)

Using a single colour fluorescence in situ hybridisation technique, dose-responses were derived for a range of chromosomally aberrant cell types and categories of aberrations induced in peripheral blood lymphocytes by alpha-particle radiation and analysed in their first in vitro division. For a range of doses that resulted predominantly in targeted cells receiving a single hit, i.e. 0-200 mGy, linear models fitted all the different categories of aberrant cells and aberration types but the profile of chromosome damage differed for 500 mGy, reflecting the effect of different track structure. (authors)

2009-01-01

303

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 O_2 or N_2. Linear dose responses were observed for all the populations. In O_2, 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

1981-01-01

304

The use of the dose-response curve in the assessment of normal and asymptomatic asthmatic patients.  

Science.gov (United States)

We studied bronchial reactivity, the slope of the dose-response curve to inhaled methacholine, in normal subjects (N), young asthmatics with normal respiratory resistance (Rrs) (YAL), young asthmatics with high Rrs (YAH), and old asthmatics with high Rrs (OAH) by three different methods: linear reactivity (slope of the linear cumulative dose-conductance (Grs = 1/Rrs) curve), timed reactivity (slope of the log concentration-Grs or time-Grs curve), and log reactivity (slope of the log cumulative dose-Grs curve). There were significant differences in linear reactivity between the N and the three asthmatics but no difference among the three asthmatic groups. On the other hand, both timed and log reactivities showed significant differences between the three asthmatic groups. Log and timed reactivities corrected by baseline Grs did not differentiate the YAL from the YAH but showed a significant difference between the YAH and OAH. This study suggests that timed and log reactivities may be better indices of bronchial reactivity than linear reactivity because they differentiate asthmatics, and that bronchial reactivity in asthmatics may be dependent on not only baseline airway caliber in asthmatics but also other factors such as atopic status or age. PMID:2919802

Suzuki, S; Ishii, M; Sasaki, H; Takishima, T

1989-02-01

305

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

306

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

Directory of Open Access Journals (Sweden)

Full Text Available Normal 0 false false false EN-GB X-NONE X-NONE Glycine dosimeter based on spectrophotometric read-out method has great potential for gamma dosimetry in low dose applications of radiation processing. However, external factors such as relative humidity, dose rate, and dose fractionation, may have a profound effect on its gamma dose response Influence of these factors on the gamma dose response of glycine dosimeter was studied in the present work.

T. Mukherjee

2011-07-01

307

Dose-response relationships of intravenous hyoscine butylbromide and atropine sulphate on heart rate in healthy volunteers.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Heart-rate responses to intravenous hyoscine butylbromide, atropine and physiological saline in cumulative dosage regimens have been recorded in six healthy subjects. Atropine sulphate induced bradycardia at low, and tachycardia at higher, dose levels whereas hyoscine butylbromide caused only tachycardia but with a flatter dose-response relationship. Exact potency ratios could not be calculated because of the differing dose-response curves. However, an approximate estimate from a comparison o...

Grainger, S. L.; Smith, S. E.

1983-01-01

308

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

1998-03-01

309

Hierarchical dose-response modeling for high-throughput toxicity screening of environmental chemicals.  

Science.gov (United States)

High-throughput screening (HTS) of environmental chemicals is used to identify chemicals with high potential for adverse human health and environmental effects from among the thousands of untested chemicals. Predicting physiologically relevant activity with HTS data requires estimating the response of a large number of chemicals across a battery of screening assays based on sparse dose-response data for each chemical-assay combination. Many standard dose-response methods are inadequate because they treat each curve separately and under-perform when there are as few as 6-10 observations per curve. We propose a semiparametric Bayesian model that borrows strength across chemicals and assays. Our method directly parametrizes the efficacy and potency of the chemicals as well as the probability of response. We use the ToxCast data from the U.S. Environmental Protection Agency (EPA) as motivation. We demonstrate that our hierarchical method provides more accurate estimates of the probability of response, efficacy, and potency than separate curve estimation in a simulation study. We use our semiparametric method to compare the efficacy of chemicals in the ToxCast data to well-characterized reference chemicals on estrogen receptor ? (ER?) and peroxisome proliferator-activated receptor ? (PPAR?) assays, then estimate the probability that other chemicals are active at lower concentrations than the reference chemicals. PMID:24397816

Wilson, Ander; Reif, David M; Reich, Brian J

2014-03-01

310

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

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

2004-01-01

311

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

312

The full simulation of dose response curves using the local effect model  

International Nuclear Information System (INIS)

The purpose of the Local Effect Model (LEM) is to calculate the dose dependent relative biological effectiveness (RBE) of charged particle radiation with respect to conventional photon radiation. The linear-quadratic parameters ? and ? (the initial slope and the curvature of ion dose response curves) are modelled based on their values for the photon dose response. Usually this is done within a low fluence approximation where the biological damage of a radiation field at arbitrarily high irradiation dose is deduced from the damage pattern deposited by one single charged particle. To investigate the reliability of the approximation, the LEM has been extended to simulate the actual damage pattern of an arbitrarily high number of ion traversals and their stochastic distribution by means of a full Monte Carlo simulation. The analysis of the resulting survival curves revealed that the ?-term in the full simulation increases compared to the original formalism. Furthermore, investigation of the dose dependence of the RBE showed that the RBE approaches values >1 even at very high doses. This is in line with experimental results and can be understood mechanistically within the LEM formalism.

2011-03-13

313

Ceruletide intravenous dose-response study by a simplified scintigraphic technique  

International Nuclear Information System (INIS)

The intravenous dose response of a ceruletide diethylamine (ceruletide) was established by a simplified scintigraphic technique where multiple graded doses were given sequentially on a single occasion. The gallbladder volume was presented nongeometrically by /sup 99m/Tc-IDA counts. The mean latent period, ejection period, and ejection rate were similar for all four groups of subjects given 1-20 ng/kg of ceruletide. The ejection fractions were similar to the values when the identical dose of ceruletide was administered sequentially either before or after another dose. A dose of 5 ng/kg produced the most physiologic type of emptying. Intravenous doses of 10 ng/kg and larger caused adverse reactions in 42% of the total doses in the form of abdominal pain, nausea, systolic and diastolic hypotension, or bradycardia. It is concluded that the dose response of a cholecystokininlike agent (ceruletide) can be established reliably by a scintigraphic technique where multiple graded doses are given on a single occasion

1985-04-01

314

The assessment of antibody affinity distribution by thiocyanate elution: a simple dose-response approach.  

Science.gov (United States)

We describe a simple dose-response approach to assess the affinity distribution of polyclonal antibodies. The proportion of antigen-specific antibodies dissociated by increasing concentrations of the mild chaotropic agent ammonium thiocyanate (NH4SCN) was measured by enzyme immunoassay, and the distribution of tolerances to this agent was presented in a histogram form. Such 'tolerance distribution', which is analogous to that described in classical dose-response bioassays, is proposed as a representation of the actual antibody affinity distribution. To test this approach, we assessed affinity maturation patterns of anti-Plasmodium falciparum IgG antibodies in paired sera obtained from 22 malaria patients during the acute infection and convalescence. We obtained patterns of antibody affinity distributions consistent with those previously described in immunization experiments with the aid of more complex laboratory and computational approaches. Therefore, we suggest the thiocyanate elution technique as an alternative method for rapid assessment of affinity distributions of polyclonal antibodies elicited against complex antigens, readily applicable to large number of serum samples. PMID:7499889

Ferreira, M U; Katzin, A M

1995-12-01

315

Dose-response relationship for lung cancer induction at radiotherapy dose  

International Nuclear Information System (INIS)

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

2010-01-01

316

The dose–response of the anal sphincter region – An analysis of data from the MRC RT01 trial  

International Nuclear Information System (INIS)

Purpose: Most studies investigating the dose–response of the rectum focus on rectal bleeding. However, it has been reported that other symptoms such as urgency or sphincter control have a large impact on quality-of-life and that different symptoms are related to the dose to different parts of the anorectal wall. In this study correlations between the 3D dose distribution to the anal-sphincter region and radiation-induced side-effects were quantified. Materials and methods: Dose–surface maps of the anal canal were generated. Next, longitudinal and lateral extent and eccentricity were calculated at different dose levels; DSHs and DVHs were also determined. Correlations between these dosimetric measures and seven clinically relevant endpoints were determined by assessing dosimetric constraints. Furthermore, an LKB model was generated. The study was performed using the data of 388 prostate patients from the RT01 trial (ISRCTN 47772397). Results: Subjective sphincter control was significantly correlated with the dose to the anal surface. The strongest correlations were found for lateral extent at 53 Gy (p = 0.01). Outcome was also significantly correlated with the DSH and the mean dose to the anal surface. Conclusions: The dose to the anal sphincter region should be taken into account when generating treatment-plans. This could be done using shape-based tools, DSH/DVH-based tools or an NTCP model.

2012-06-01

317

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

DEFF Research Database (Denmark)

Viral hemorrhagic septicemia (VHS) in rainbow trout Oncorhynchus mykiss is caused by VHS virus (VHSV), which belongs to the rhabdovirus family. Among the different strategies for immunizing fish with a recombinant vaccine, genetic immunization has recently proven to be highly effective. To further investigate the potential for protecting fish against VHS by DNA vaccination, experiments were conducted to determine the amount of plasmid DNA needed for induction of protective immunity. The time to onset of immunity and the duration of protection following administration of a protective vaccine dose were also analyzed. The dose-response analysis revealed that significant protection of rainbow trout fingerlings was obtained following intramuscular injection of only 0.01 mug of plasmid DNA encoding the VHSV glycoprotein gene. In addition, higher doses of DNA induced immunity to a virus isolate serologically different from the isolate used for vaccine development. Following administration of 1 mug of a DNA vaccine, significant protection against VHS was observed in the fish as early as 8 d postvaccination. At 168 d postvaccination, the fish had increased in size by a factor of 10 and protection against a lethal dose of VHSV was still evident. The results confirm the great potential for DNA vaccination in inducing efficient immunoprophylaxis against viral diseases in aquacultured fish.

Lorenzen, Ellen; Einer-Jensen, Katja

2000-01-01

318

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.

Larsen, C.N.; Nielsen, S.

2006-01-01

319

Effect of processing time delay on the dose response of Kodak EDR2 film  

International Nuclear Information System (INIS)

Kodak EDR2 film is a widely used two-dimensional dosimeter for intensity modulated radiotherapy (IMRT) measurements. Our clinical use of EDR2 film for IMRT verifications revealed variations and uncertainties in dose response that were larger than expected, given that we perform film calibrations for every experimental measurement. We found that the length of time between film exposure and processing can affect the absolute dose response of EDR2 film by as much as 4%-6%. EDR2 films were exposed to 300 cGy using 6 and 18 MV 10x10 cm2 fields and then processed after time delays ranging from 2 min to 24 h. An ion chamber measured the relative dose for these film exposures. The ratio of optical density (OD) to dose stabilized after 3 h. Compared to its stable value, the film response was 4%-6% lower at 2 min and 1% lower at 1 h. The results of the 4 min and 1 h processing time delays were verified with a total of four different EDR2 film batches. The OD/dose response for XV2 films was consistent for time periods of 4 min and 1 h between exposure and processing. To investigate possible interactions of the processing time delay effect with dose, single EDR2 films were irradiated to eight different dose levels between 45 and 330 cGy using smaller 3x3 cm2 areas. These films were processed after time delays of 1, 3, and 6 h, using 6 and 18 MV photon qualities. The results at all dose levels were consistent, indicating that there is no change in the processing time delay effect for different doses. The difference in the time delay effect between the 6 and 18 MV measurements was negligible for all experiments. To rule out bias in selecting film regions for OD measurement, we compared the use of a specialized algorithm that systematically determines regions of interest inside the 10x10 cm2 exposure areas to manually selected regions of interest. There was a maximum difference of only 0.07% between the manually and automatically selected regions, indicating that the use of a systematic algorithm to determine regions of interest in large and fairly uniform areas is not necessary. Based on these results, we recommend a minimum time of 1 h between exposure and processing for all EDR2 film measurements

2004-08-01

320

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

Energy Technology Data Exchange (ETDEWEB)

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.

Reynolds, M. [Department of Oncology, Medical Physics Division, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Fallone, B. G. [Department of Medical Physics, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Departments of Oncology and Physics, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Rathee, S. [Department of Medical Physics, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Department of Oncology, Medical Physics Division, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

2013-04-15

 
 
 
 
321

Systematic overview of preoperative (neoadjuvant) chemoradiotherapy trials in oesophageal cancer: Evidence of a radiation and chemotherapy dose response  

International Nuclear Information System (INIS)

Background and purpose: Numerous trials have shown that pathological complete response (pCR) following preoperative chemoradiotherapy (CRT) and surgery for oesophageal cancer is associated with improved survival. However, different radiotherapy doses and fractionations and chemotherapy drugs, doses and scheduling were used, which may account for the differences in observed pCR and survival rates. A dose-response relationship may exist between radiotherapy and chemotherapy dose and pCR. Patients and methods: Trials using a single radiotherapy and chemotherapy regimen (5FU, cisplatin or mitomycin C-based) and providing information on patient numbers, age, resection and pCR rates were eligible. The endpoint used was pCR and the covariates analysed were prescribed radiotherapy dose, radiotherapy dosexdose per fraction, radiotherapy treatment time, prescribed chemotherapy (5FU, cisplatin and mitomycin C) dose and median age of patients within the trial. The model used was a multivariate logistic regression. Results: Twenty-six trials were included (1335 patients) in which 311 patients (24%) achieved pCR. The probability of pCR improved with increasing dose of radiotherapy (P=0.006), 5FU (P=0.003) and cisplatin (P=0.018). Increasing radiotherapy treatment time (P=0.035) and increasing median age (P=0.019) reduced the probability of pCR. The estimated ?/? ratio of oesophageal cancer was 4.9 Gy (95% confidence interval (CI) 1.5-17 Gy) and the estimated radiotherapy dose lost per day was 0.59 Gy (95% CI 0.18-0.99 Gy). One gram per square metre of 5FU was estimated to be equivalent to 1.9 Gy (95% CI 0.8-5.2 Gy) of radiation and 100 mg/m2 of cisplatin was estimated to be equivalent to 7.2 Gy (95% CI 2.1-28 Gy). Mitomycin C dose did not appear to influence pCR rates (P=0.60). Conclusions: There was evidence of a dose-response relationship between increasing protocol prescribed radiotherapy, 5FU and cisplatin dose and pCR. Additional significant factors were radiotherapy treatment time and median age of patients within the trial

2006-03-01

322

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

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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

323

Clinical application of Chamomilla recutita in phlebitis: dose response curve study.  

Science.gov (United States)

This experimental and dose-response curve study aimed to carry out the quality control of the Chamomilla recutita sample, as well as to estimate the ideal dose, for anti-inflammatory effect, of the extract of its capitula, in patients with phlebitis due to peripheral intravenous infusion of antineoplastic chemotherapy and to evaluate the toxicity of this extract in human beings. The therapeutic efficacy, concerning the anti-inflammatory potential, of different doses of Chamomilla recutita extract were analyzed and compared in 25 patients. The time of regression of phlebitis was shorter for groups with 2.5% concentration (mean=29.2h, standard deviation = 8.98) and 5% concentration (mean = 38.8h, standard deviation = 17.47). Local toxicity was almost not observed. This research contributes to the innovation of the nursing clinical practice, since it suggests an alternative for the treatment of phlebitis through the clinical use of phytotherapeutic drugs. PMID:21412623

Reis, Paula Elaine Diniz Dos; Carvalho, Emilia Campos de; Bueno, Paula Carolina Pires; Bastos, Jairo Kenupp

2011-01-01

324

Experimental design strategy for the Weibull dose-response model (journal version)  

Energy Technology Data Exchange (ETDEWEB)

The objective of the research was to determine optimum design-point allocation for estimation of relative yield losses from ozone pollution when the true and fitted yield-ozone dose-response relationship follows the Weibull. The optimum design is dependent on the values of the Weibull model parameters. A transformation was developed that allowed the optimum design (by the determinant criterion) for one parametric situation to be translated to any other, and permitted the search for optimum designs to be restricted to one set of Weibull parameters. Optimum designs were determined for the case where the Weibull parameters are assumed known, and effects of deviating from the optimum designs were investigated. Several alternative design strategies were considered for protecting against incorrectly guessing the Weibull model parameters when their true values are not known.

Dassel, K.A.; Rawlings, J.O.

1988-01-01

325

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

International Nuclear Information System (INIS)

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

2000-10-15

326

ESR signal features of 60Co ?-ray irradiated bone tissue and its dose response relationship  

International Nuclear Information System (INIS)

Electron spin resonance (ESR) technique was used to study the radiation-induced ESR signal features of different paramagnetic species of 60Co ?-ray irradiated bone tissue. The results showed that the intensity of an ESR signal at that the intensity of an ESR signal at g 2.0022 of human bones exposed to a dose range of 0-50 Gy had linear dose response relationships. The lower limit of detectable dose was about 2 Gy and the detecting error was about 10%. The signal was stable at room temperature during 60 days, and the effect of radiation dose rate of 0.5-8.0 Gy/min could be neglected. This signal was insensitive to microwave power and temperature, which was suitable for rapid and direct detection with ESR technique. These features suggest that human bones could be used for radiation accident dose evaluation by ESR

1993-08-01

327

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

328

Dose response relationships for radiation induced chromosome aberrations in human lymphocytes in vivo and in vitro  

International Nuclear Information System (INIS)

Chromosome aberrations have been analysed in cultured lymphocytes from a patient undergoing whole-body treatment with split doses of gamma-rays up to a cumulative dose of 1.4 Gy. The dependence on dose of the yield of dicentrics was best fitted to the linear-quadratic relationship with a linear component predominating in the low dose range (below 0.56 Gy). These observations were compared with the data obtained when blood samples were exposed in vitro to low acute doses of gamma-rays (from 0.05 up to 2.0 Gy). The frequencies of induced chromosome aberrations were similar in both cases and little deviation was found between the dose response curves (a/b ratio equal to 0.56 and 0.69 Gy, respectively in vivo and in vitro). These results confirm that in vitro calibration curves can be utilized confidently for the biological estimate of an in vivo absorbed dose. (orig.)

1986-01-01

329

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.)

1981-01-01

330

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

Science.gov (United States)

The purpose of this study was to determine the long-term dose-response relationship of exercise frequency on areal bone mineral density (aBMD) in early post-menopausal women with osteopenia. Based on the 12-year results of the consequently supervised exercise group (EG) of the Erlangen Fitness and Osteoporosis Prevention Study, we retrospectively structured two exercise groups according to the overall exercise frequency. Changes in aBMD at lumbar spine and proximal femur as assessed by dual-energy x-ray absorptiometry technique were compared between a low-frequency exercise group (LEF-EG, n = 16) with 1.5-mean value ± standard deviation) 1.1 ± 4.7% vs -4.1 ± 3.0%; P = 0.001, ES: d'?= 1.26; total hip: -4.4 ± 3.9% vs -6.7 ± 3.5%, P = 0.045, ES: d' = 0.70). BMD results of the LEF-EG did not significantly differ from the data of the non-training control group (lumbar spine: -4.4 ± 5.2%, total hip: -6.9 ± 5.0%). Although this result might not be generalizable across all exercise types and cohorts, it indicates that to impact bone, an overall exercise frequency of at least 2 sessions/week may be crucial, even if exercise is applied with high intensity/impact. PMID:23190199

Kemmler, W; von Stengel, S

2014-06-01

331

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

International Nuclear Information System (INIS)

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

1986-10-01

332

Dose response of experimental Pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence for resistance to "late" treatment of infections.  

Science.gov (United States)

Single intravitreal doses of ciprofloxacin, gentamicin, or imipenem were administered to rabbits with pseudomonas endophthalmitis for determination of the maximally effective dose. Treatment was given 24 hr ("early") or 48 hr ("late") after infection. With early treatment the dose-response relationship between the drug concentration and the diminution in bacterial counts in the vitreous humor was linear with all three drugs. By contrast, with late treatment the same vitreal concentrations had no significant effect on bacterial counts. The failure of late treatment was not due to an increased rate of clearance of drugs from the eyes and could not be reproduced with a similar bacterial inoculum in vitro. Bacteria cultured from treated eyes were fully sensitive when plated directly onto drug-containing agar. The poor bactericidal effect of late treatment may in part be related to transient phenotypic alterations in the bacteria in response to changes in the environment of infection such as hypoxia, low pH, and exhaustion of critical bacterial nutrients. PMID:3100661

Davey, P G; Barza, M; Stuart, M

1987-03-01

333

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

334

Kidney dysfunction and cadmium exposure--factors influencing dose-response relationships.  

Science.gov (United States)

Our early toxicological studies showed that metallothionein (MT) is a protein that carries cadmium (Cd) to the kidney, explaining why Cd exposures during long time periods may give rise to kidney dysfunction. This dysfunction is usually considered to be the critical effect, i.e. the adverse effect that occurs at the lowest exposure level. MT also provides intracellular protection against cadmium toxicity. In studies of population groups in cadmium contaminated areas in China, we investigated factors that affected the relationship between internal dose of Cd, as indicated by blood Cd (BCd) or urinary Cd (UCd), and the prevalence of kidney dysfunction. We found dose-response relationships between UCd and the prevalence of increased levels of biomarkers of renal tubular dysfunction (urinary beta-2-microglobulin, B2M, or N-acetyl-beta-d-glucosaminidase - NAG) or urinary albumin (UAlb), a biomarker of glomerular kidney dysfunction. Two years after Cd intake from contaminated rice was diminished, renal tubular dysfunction appeared unchanged or aggravated among those with higher UCd; Another 8 years later, i.e. 10 years after Cd intake was decreased, the prevalence of renal tubular dysfunction was still increased but UAlb had returned to normal. Factors that influenced the dose-response relationships were: (1) time after maximum exposure. (2) Concomitant exposure to other nephrotoxic agents such as inorganic arsenic. (3) Cd induced metallothionein mRNA levels in peripheral blood lymphocytes, used as a biomarker of the ability of each person, to synthesize MT. (4) The occurrence of increased levels in blood plasma of autoantibodies against MT. The two last points further support a role in humans of MT as a protective protein against tissue damage from cadmium and gives support to previous ideas developed partly in experimental systems. PMID:22565016

Nordberg, Gunnar; Jin, Taiyi; Wu, Xunwei; Lu, Jian; Chen, Liang; Liang, Yihuai; Lei, Lijian; Hong, Feng; Bergdahl, Ingvar A; Nordberg, Monica

2012-06-01

335

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.

2012-07-01

336

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

337

Dose-response analysis of cadmium in man: body burden vs kidney dysfunction  

Energy Technology Data Exchange (ETDEWEB)

The primary objective of this study was to develop dose-response relationships of cadmium in human beings. In vivo measurements of kidney, liver, urine, and blood cadmium, and urinary levels of ..beta../sub 2/-microglobulin and total protein were obtained in 82 industrially exposed workers and 30 control subjects. The values of 200 ..mu..g/g creatinine for urinary ..beta../sub 2/-microglobulin and 250 mg/g creatinine for urinary total protein were used to define the upper limit for normal kidney function. Forty-one of the cadmium workers (18 active, 23 retired) were classified as having abnormal kidney function; all control subjects had normal kidney function. Most workers with Cd above 70 ppm in the liver were judged to have some evidence of kidney abnormalities. The dose-response relationship for liver cadmium for the actively employed workers could be described by a linear logistic regression model: In p/(1-p) = 0.118 x liver cadmium (ppm) - 5.00 where p is the individual's probability of having kidney dysfunction. The loss of cadmium from the kidney following dysfunction prohibited a direct logistic analysis of the kidney cadmium data. However, when the linear relationship between kidney and liver cadmium for the subjects with normal kidney function was combined with the logistic equation for the liver, a predicted-response curve was obtained for the kidney. The logistic models predict a 50% probability of having kidney dysfunction at 38.4 mg for the kidney and 42.3 ppm for the liver, respectively.

Ellis, K.J.; Yuen, K.; Yasumura, S.; Cohn, S.H.

1984-02-01

338

Dose-response effects of diphenylhydantoin on pregnant dams and embryo-fetal development in rats.  

Science.gov (United States)

Despite the widespread use of diphenylhydantoin (DPH), there is a lack of reliable information on the teratogenic effects, correlation with maternal and developmental toxicity, and dose-response relationship of DPH. This study investigated the dose-response effects of DPH on pregnant dams and embryo-fetal development as well as the relationship between maternal and developmental toxicity. DPH was orally administered to pregnant rats from gestational days 6 through 15 at 0, 50, 150, and 300 mg/kg/day. At 300 mg/kg, maternal toxicity including increased clinical signs, suppressed body weight, decreased food intake, and increased weights of adrenal glands, liver, kidneys, and brain were observed in dams. Developmental toxicity, including a decrease in fetal and placental weights, increased incidence of morphological alterations, and a delay in fetal ossification delay also occurred. At 150 mg/kg, maternal toxicity manifested as an increased incidence of clinical signs, reduced body weight gain and food intake, and increased weights of adrenal glands and brain. Only minimal developmental toxicity, including decreased placental weight and an increased incidence of visceral and skeletal variations, was observed. No treatment-related maternal or developmental effects were observed at 50 mg/kg. These results show that DPH is minimally embryotoxic at a minimal maternotoxic dose (150 mg/kg/day) but is embryotoxic and teratogenic at an overt maternotoxic dose (300 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of DPH for pregnant dams and embryo-fetal development is considered to be 50 mg/kg/day. These data indicate that DPH is not a selective developmental toxicant in the rat. PMID:22887608

Kim, Sung-Hwan; Lee, In-Chul; Baek, Hyung-Seon; Lim, Jeong-Hyeon; Moon, Changjong; Shin, Dong-Ho; Kim, Sung-Ho; Park, Seung-Chun; Kim, Jong-Choon

2012-10-01

339

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

340

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.  

Science.gov (United States)

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. PMID:24077963

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

2013-11-01

 
 
 
 
341

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

342

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

International Nuclear Information System (INIS)

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

2005-03-01

343

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

2007-07-01

344

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

1982-01-01

345

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)

1983-01-01

346

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

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

Thompson Sally

2010-11-01

347

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 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

348

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

2010-05-01

349

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

Science.gov (United States)

When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ?2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (?18%), whereas maximum and mean doses decreased (?0.8 and ?4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ?1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range. PMID:24936956

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

2014-07-21

350

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

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

Decker Ralph

2012-11-01

351

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

352

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 {mu}g/kg, then ChE inhibition was plateaued from 200 to 500 {mu}g/kg in these tissues. A dose related ChE inhibition was seen in heart and thigh muscle from 50 to 500 {mu}g/kg. Phy concentration increased linearly from 50 to 400 {mu}g/kg in plasma, brain, heart and thigh muscle. These results indicate that ChE inhibition is linear up to 200 {mu}g/kg in RBC, 150 {mu}g/kg in brain and 300 {mu}g/kg in heart. This linearity is not consistent in other tissues.

Somani, S.M.; Dube, S.N. (Southern Illinois Univ., Springfield (USA))

1989-01-01

353

Antihypertensive dose-response relationships: studies with the selective alpha 1-blocking agent terazosin.  

Science.gov (United States)

Terazosin is a selective alpha 1-adrenergic-blocking agent indicated for the treatment of hypertension. The aim of this multicenter study, performed in 256 patients with mild to moderate essential hypertension, was to define the dosing characteristics of terazosin (in the range of 1 to 80 mg) administered once daily. Patients were randomly assigned to placebo or active treatment groups; each group received 3 months of treatment, which comprised three ascending doses of terazosin, each administered for a 1-month period. As determined by conventional office measurements of supine diastolic blood pressure and by automated ambulatory blood pressure monitoring, there was a clear antihypertensive dose-response relationship for terazosin in the range of 1 to 5 mg daily. Except for the 80 mg dose, none of the doses above 5 mg (10 to 40 mg) appeared to provide additional efficacy. Both the office measurements and the monitoring data indicated that the ratio of trough (effect at the end of the dosing interval) to peak (maximum effect during the dosing interval) was at least 50% or greater during treatment with the 5 mg dose. Thus the 5 mg dose appeared to provide meaningful clinical antihypertensive efficacy and to sustain its effects throughout the full 24-hour period. PMID:1678921

Weber, M A; Cheung, D G; Laddu, A R; Luther, R R

1991-09-01

354

Continuous functional magnetic resonance imaging reveals dynamic nonlinearities of "dose-response" curves for finger opposition.  

Science.gov (United States)

Linear experimental designs have dominated the field of functional neuroimaging, but although successful at mapping regions of relative brain activation, the technique assumes that both cognition and brain activation are linear processes. To test these assumptions, we performed a continuous functional magnetic resonance imaging (MRI) experiment of finger opposition. Subjects performed a visually paced bimanual finger-tapping task. The frequency of finger tapping was continuously varied between 1 and 5 Hz, without any rest blocks. After continuous acquisition of fMRI images, the task-related brain regions were identified with independent components analysis (ICA). When the time courses of the task-related components were plotted against tapping frequency, nonlinear "dose- response" curves were obtained for most subjects. Nonlinearities appeared in both the static and dynamic sense, with hysteresis being prominent in several subjects. The ICA decomposition also demonstrated the spatial dynamics with different components active at different times. These results suggest that the brain response to tapping frequency does not scale linearly, and that it is history-dependent even after accounting for the hemodynamic response function. This implies that finger tapping, as measured with fMRI, is a nonstationary process. When analyzed with a conventional general linear model, a strong correlation to tapping frequency was identified, but the spatiotemporal dynamics were not apparent. PMID:10407059

Berns, G S; Song, A W; Mao, H

1999-07-15

355

Support vector regression and least squares support vector regression for hormetic dose-response curves fitting.  

Science.gov (United States)

Accurate description of hormetic dose-response curves (DRC) is a key step for the determination of the efficacy and hazards of the pollutants with the hormetic phenomenon. This study tries to use support vector regression (SVR) and least squares support vector regression (LS-SVR) to address the problem of curve fitting existing in hormesis. The SVR and LS-SVR, which are entirely different from the non-linear fitting methods used to describe hormetic effects based on large sample, are at present only optimum methods based on small sample often encountered in the experimental toxicology. The tuning parameters (C and p1 for SVR, gam and sig2 for LS-SVR) determining SVR and LS-SVR models were obtained by both the internal and external validation of the models. The internal validation was performed by using leave-one-out (LOO) cross-validation and the external validation was performed by splitting the whole data set (12 data points) into the same size (six data points) of training set and test set. The results show that SVR and LS-SVR can accurately describe not only for the hermetic J-shaped DRC of seven water-soluble organic solvents consisting of acetonitrile, methanol, ethanol, acetone, ether, tetrahydrofuran, and isopropanol, but also for the classical sigmoid DRC of six pesticides including simetryn, prometon, bromacil, velpar, diquat-dibromide monohydrate, and dichlorvos. PMID:19906401

Qin, Li-Tang; Liu, Shu-Shen; Liu, Hai-Ling; Zhang, Yong-Hong

2010-01-01

356

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

357

Dose-response effect of a novel functional fibre, PolyGlycopleX(®), PGX(®), on satiety.  

Science.gov (United States)

The objective of this research was to determine the dose-response effects of a palatable, viscous and gel forming fibre, PolyGlycopleX(®) (PGX(®)), [(?-D-glucurono-?-manno-?-D-manno-?-D-gluco), (?-Lgulurono-?-D mannurono), (?-D-gluco-?-D-mannan)] on satiety, and to gain insight into the underlying mechanisms that lead to appetite inhibition. Healthy subjects (n?=?10), aged between 20.3 and 29.2 years, consumed PGX(®), in granular form at 2.5, 5.0 and 7.5?g, and a 5g inulin control, with a standard breakfast. The PGX(®) doses of 2.5 and 7.5?g mixed with water at the start of breakfast increased satiety (iAUC of 140.0 and 157.7, P?=?0.025 and 0.001, respectively) compared to the control. The most effective dose (7.5g) was palatable and corresponded to a 34% increase in fullness, measured using a visual analogue scale and incremental area under the curve, and resulted in a delayed postprandial glycaemic response when compared with the control. PMID:24631638

Solah, Vicky A; Brand-Miller, Jennie C; Atkinson, Fiona S; Gahler, Roland J; Kacinik, Veronica; Lyon, Michael R; Wood, Simon

2014-06-01

358

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

Energy Technology Data Exchange (ETDEWEB)

The response to radiation of polymer gel dosimeters has most often been described by measuring the nuclear magnetic resonance transverse relaxation rate as a function of dose. This approach is highly dependent upon the choice of experimental parameters, such as the echo spacing time for Carr-Purcell-Meiboom-Gill-type pulse sequences, and is difficult to optimize in imaging applications where a range of doses are applied to a single gel, as is typical for practical uses of polymer gel dosimetry. Moreover, errors in computing dose can arise when there are substantial variations in the radiofrequency (B{sub 1}) field or resonant frequency, as may occur for large samples. Here we consider the advantages of using magnetization transfer imaging as an alternative approach and propose the use of a simplified quantity, the magnetization transfer proportion (MTP), to assess doses. This measure can be estimated through two simple acquisitions and is more robust in the presence of some sources of system imperfections. It also has a dependence upon experimental parameters that is independent of dose, allowing simultaneous optimization at all dose levels. The MTP is shown to be less susceptible to B{sub 1} errors than are CPMG measurements of R{sub 2}. The dose response can be optimized through appropriate choices of the power and offset frequency of the pulses used in magnetization transfer imaging.

Whitney, Heather M; Gochberg, Daniel F; Gore, John C [Vanderbilt University Institute of Imaging Science, Nashville, TN 37232-2675 (United States)], E-mail: heather.whitney@vanderbilt.edu

2008-12-21

359

Dose-response for bone regeneration after single doses of WCo irradiation  

Energy Technology Data Exchange (ETDEWEB)

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

Jacobsson, M.; Joensson, A.A.; Albrektsson, T.; Turesson, I.

1985-11-01

360

Dose response in rodents and nonhuman primates after hydrodynamic limb vein delivery of naked plasmid DNA.  

Science.gov (United States)

The efficacy of gene therapy mediated by plasmid DNA (pDNA) depends on the selection of suitable vectors and doses. Using hydrodynamic limb vein (HLV) injection to deliver naked pDNA to skeletal muscles of the limbs, we evaluated key parameters that affect expression in muscle from genes encoded in pDNA. Short-term and long-term promoter comparisons demonstrated that kinetics of expression differed between cytomegalovirus (CMV), muscle creatine kinase, and desmin promoters, but all gave stable expression from 2 to 49 weeks after delivery to mouse muscle. Expression from the CMV promoter was highest. For mice, rats, and rhesus monkeys, the linear range for pDNA dose response could be defined by the mass of pDNA relative to the mass of target muscle. Correlation between pDNA dose and expression was linear between a threshold dose of 75 ?g/g and maximal expression at approximately 400 ?g/g. One HLV injection into rats of a dose of CMV-LacZ yielding maximal expression resulted in an average transfection of 28% of all hind leg muscle and 40% of the gastrocnemius and soleus. Despite an immune reaction to the reporter gene in monkeys, a single injection transfected an average of 10% of all myofibers in the targeted muscle of the arms and legs and an average of 15% of myofibers in the gastrocnemius and soleus. PMID:21338336

Wooddell, Christine I; Hegge, Julia O; Zhang, Guofeng; Sebestyén, Magdolna G; Noble, Mark; Griffin, Jacob B; Pfannes, Loretta V; Herweijer, Hans; Hagstrom, James E; Braun, Serge; Huss, Thierry; Wolff, Jon A

2011-07-01

 
 
 
 
361

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

Energy Technology Data Exchange (ETDEWEB)

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.

Rowland, R.E.

1994-05-01

362

A two phase dose-response relationship at low dose rates  

International Nuclear Information System (INIS)

With a new model concerning the dose-effect relation, the Random Coincidence Model (RCM), it is possible to explain the radiobiological effect of a two phase dose-response relationship. This model describes the formation of cancer caused by a multistep series of fixed lesions in the critical regions of tumor associated genes such as proto-oncogenes or tumor-suppressor genes. It is the central thesis of the model that in the case of spontaneously occurring mutations mainly the random coincidence of two base lesions or two single strand breaks of complementary DNA bases (strands) during the repair time of the first base lesion or single strand break leads to a fixation. In that case the stimulation of detoxification and repair systems by radiation reduces the mutation rate to a large extend. On the other hand the energy transfer of radiation generates a large number of radicals at each single point of interaction, so that the cloud of radicals can neither be reduced by detoxification to a large extend nor is there any possibility to repair in between the interaction with the DNA; a so called causal coincidence leads to a fixation. (author)

1997-11-01

363

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

Science.gov (United States)

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.

Claussen, Catherine M; Dafny, Nachum

2014-01-01

364

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

Science.gov (United States)

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-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 ?-index, based on the reference values of a dose error of 3% and a DTA of 3 mm, is 93.7%.

Cho, K. H.; Cho, S. J.; Lee, S.; Lee, S. H.; Min, C. K.; Kim, Y. H.; Moon, S. K.; Kim, E. S.; Chang, A. R.; Kwon, S. I.

2012-05-01

365

Optical and NMR dose response of N-isopropylacrylamide normoxic polymer gel for radiation therapy dosimetry  

Science.gov (United States)

Background Application of less toxic normoxic polymer gel of N-isopropyl acrylamide (NIPAM) for radiation therapy has been studied in recent years. Aim In the current study the optical and NMR properties of NIPAM were studied for radiation therapy dosimetry application. Materials and methods NIPAM normoxic polymer gel was prepared and irradiated by 9 MV photon beam of a medical linac. The optical absorbance was measured using a conventional laboratory spectrophotometer in different wavelengths ranging from 390 to 860 nm. R2 measurements of NIPAM gels were performed using a 1.5 T scanner and R2–dose curve was obtained. Results Our results showed R2 dose sensitivity of 0.193 ± 0.01 s?1 Gy?1 for NIPAM gel. Both R2 and optical absorbance showed a linear relationship with dose from 1.5 to 11 Gy for NIPAM gel dosimeter. Moreover, absorbance–dose response varied considerably with light wavelength and highest sensitivity was seen for the blue part of the spectrum. Conclusion Our results showed that both optical and NMR approaches have acceptable sensitivity and accuracy for dose determination with NIPAM gel. However, for optical reading of the gel, utilization of an optimum optical wavelength is recommended.

Mesbahi, Asghar; Jafarzadeh, Vahid; Gharehaghaji, Nahideh

2012-01-01

366

Effect of Composition Interactions on the Dose Response of an N-Isopropylacrylamide Gel Dosimeter  

Science.gov (United States)

In this study, a two-level full factorial design was used to identify the effects of the interactions between compositions in an N-isopropylacrylamide (NIPAM) gel dosimeter involving the following variables: (A) gelatin, (B) NIPAM, (C) the crosslinker N, N?-methylene-bis-acrylamide (Bis), and (D) the antioxidant tetrakis (hydroxymethyl) phosphonium chloride (THPC). The dose range was from 0 Gy to 5 Gy. Optical computed tomography was used to scan the polymer gel dosimeter. Each component was set to two levels for all four variables, including (A) 4% and 6%, (B) 4% and 6%, (C) 2% and 4%, as well as (D) 5 and 15 mM. Response surface methodology and a central composite design were adopted for the quantitative investigation of the respective interaction effects on the dose response curve of the gel. The results showed that the contributions of the interaction effects, i.e., AB (6.22%), AC (8.38%), AD (7.74%), BC (9.44%), ABC (18.24%), BCD (12.66%), and ABCD (13.4%), were greater than those of the four main effects, accounting for over 76.08% of the total variability. These results also indicated that the NIPAM gel recipe with the highest sensitivity was at 40%C (mass fraction of Bis).

Chang, Yuan-Jen; Hsieh, Bor-Tsung

2012-01-01

367

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)

1981-09-10

368

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

1994-04-18

369

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