Statistical and low dose response
International Nuclear Information System (INIS)
The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem
Demidenko, Eugene; Williams, Benjamin B.; Flood, Ann Barry; Swartz, Harold M
2012-01-01
This paper develops a new metric, the standard error of inverse prediction (SEIP), for a dose–response relationship (calibration curve) when dose is estimated from response via inverse regression. SEIP can be viewed as a generalization of the coefficient of variation to regression problem when x is predicted using y-value. We employ nonstandard statistical methods to treat the inverse prediction, which has an infinite mean and variance due to the presence of a normally distributed variable in...
Demidenko, Eugene; Williams, Benjamin B.; Flood, Ann Barry; Swartz, Harold M.
2013-01-01
This paper develops a new metric, the standard error of inverse prediction (SEIP), for a dose–response relationship (calibration curve) when dose is estimated from response via inverse regression. SEIP can be viewed as a generalization of the coefficient of variation to regression problem when x is predicted using y-value. We employ nonstandard statistical methods to treat the inverse prediction, which has an infinite mean and variance due to the presence of a normally distributed variable in the denominator. We develop confidence intervals and hypothesis testing for SEIP on the basis of the normal approximation and using the exact statistical inference based on the noncentral t-distribution. We derive the power functions for both approaches and test them via statistical simulations. The theoretical SEIP, as the ratio of the regression standard error to the slope, is viewed as reciprocal of the signal-to-noise ratio, a popular measure of signal processing. The SEIP, as a figure of merit for inverse prediction, can be used for comparison of calibration curves with different dependent variables and slopes. We illustrate our theory with electron paramagnetic resonance tooth dosimetry for a rapid estimation of the radiation dose received in the event of nuclear terrorism. PMID:23124816
Demidenko, Eugene; Williams, Benjamin B; Flood, Ann Barry; Swartz, Harold M
2013-05-30
This paper develops a new metric, the standard error of inverse prediction (SEIP), for a dose-response relationship (calibration curve) when dose is estimated from response via inverse regression. SEIP can be viewed as a generalization of the coefficient of variation to regression problem when x is predicted using y-value. We employ nonstandard statistical methods to treat the inverse prediction, which has an infinite mean and variance due to the presence of a normally distributed variable in the denominator. We develop confidence intervals and hypothesis testing for SEIP on the basis of the normal approximation and using the exact statistical inference based on the noncentral t-distribution. We derive the power functions for both approaches and test them via statistical simulations. The theoretical SEIP, as the ratio of the regression standard error to the slope, is viewed as reciprocal of the signal-to-noise ratio, a popular measure of signal processing. The SEIP, as a figure of merit for inverse prediction, can be used for comparison of calibration curves with different dependent variables and slopes. We illustrate our theory with electron paramagnetic resonance tooth dosimetry for a rapid estimation of the radiation dose received in the event of nuclear terrorism. PMID:23124816
Lack of Statistical Significance
Kehle, Thomas J.; Bray, Melissa A.; Chafouleas, Sandra M.; Kawano, Takuji
2007-01-01
Criticism has been leveled against the use of statistical significance testing (SST) in many disciplines. However, the field of school psychology has been largely devoid of critiques of SST. Inspection of the primary journals in school psychology indicated numerous examples of SST with nonrandom samples and/or samples of convenience. In this…
When is statistical significance not significant?
Scientific Electronic Library Online (English)
Dalson Britto, Figueiredo Filho; Ranulfo, Paranhos; Enivaldo C. da, Rocha; Mariana, Batista; José Alexandre da, Silva Jr.; Manoel L. Wanderley D., Santos; Jacira Guiro, Marino.
Full Text Available The article provides a non-technical introduction to the p value statistics. Its main purpose is to help researchers make sense of the appropriate role of the p value statistics in empirical political science research. On 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.
Statistical or biological significance?
Saxon, Emma
2015-01-01
Oat plants grown at an agricultural research facility produce higher yields in Field 1 than in Field 2, under well fertilised conditions and with similar weather exposure; all oat plants in both fields are healthy and show no sign of disease. In this study, the authors hypothesised that the soil microbial community might be different in each field, and these differences might explain the difference in oat plant growth. They carried out a metagenomic analysis of the 16 s ribosomal 'signature' sequences from bacteria in 50 randomly located soil samples in each field to determine the composition of the bacterial community. The study identified >1000 species, most of which were present in both fields. The authors identified two plant growth-promoting species that were significantly reduced in soil from Field 2 (Student's t-test P?
Biological importance and statistical significance.
Lovell, David P
2013-09-01
Statistical ideas behind the analysis of experiments related to crop composition and the genetic factors underlying composition are discussed. The emphasis is on concepts rather than statistical formulations. Statistical analysis and biological considerations are shown to be complementary rather than contradictory, in that the statistical analysis of a data set depends on the experimental design, that no amount of statistical sophistication can rescue a badly designed study, and that good experimental design is crucial. The traditional null hypothesis significance testing approach has severe limitations, but p values and statistical significance still often seem to be the primary objective of an analysis. Emphasis instead should be on identifying the size of effects that are biologically important and, with the involvement of the "domain" scientist, using these to help design experiments with appropriate sample sizes and statistical power. The issues discussed here are also directly applicable to other areas of research. PMID:23909755
Statistically significant relational data mining :
Energy Technology Data Exchange (ETDEWEB)
Berry, Jonathan W.; Leung, Vitus Joseph; Phillips, Cynthia Ann; Pinar, Ali; Robinson, David Gerald; Berger-Wolf, Tanya; Bhowmick, Sanjukta; Casleton, Emily; Kaiser, Mark; Nordman, Daniel J.; Wilson, Alyson G.
2014-02-01
This report summarizes the work performed under the project (3z(BStatitically significant relational data mining.(3y (BThe goal of the project was to add more statistical rigor to the fairly ad hoc area of data mining on graphs. Our goal was to develop better algorithms and better ways to evaluate algorithm quality. We concetrated on algorithms for community detection, approximate pattern matching, and graph similarity measures. Approximate pattern matching involves finding an instance of a relatively small pattern, expressed with tolerance, in a large graph of data observed with uncertainty. This report gathers the abstracts and references for the eight refereed publications that have appeared as part of this work. We then archive three pieces of research that have not yet been published. The first is theoretical and experimental evidence that a popular statistical measure for comparison of community assignments favors over-resolved communities over approximations to a ground truth. The second are statistically motivated methods for measuring the quality of an approximate match of a small pattern in a large graph. The third is a new probabilistic random graph model. Statisticians favor these models for graph analysis. The new local structure graph model overcomes some of the issues with popular models such as exponential random graph models and latent variable models.
Statistical significance of combinatorial regulations.
Terada, Aika; Okada-Hatakeyama, Mariko; Tsuda, Koji; Sese, Jun
2013-08-01
More than three transcription factors often work together to enable cells to respond to various signals. The detection of combinatorial regulation by multiple transcription factors, however, is not only computationally nontrivial but also extremely unlikely because of multiple testing correction. The exponential growth in the number of tests forces us to set a strict limit on the maximum arity. Here, we propose an efficient branch-and-bound algorithm called the "limitless arity multiple-testing procedure" (LAMP) to count the exact number of testable combinations and calibrate the Bonferroni factor to the smallest possible value. LAMP lists significant combinations without any limit, whereas the family-wise error rate is rigorously controlled under the threshold. In the human breast cancer transcriptome, LAMP discovered statistically significant combinations of as many as eight binding motifs. This method may contribute to uncover pathways regulated in a coordinated fashion and find hidden associations in heterogeneous data. PMID:23882073
Energy Technology Data Exchange (ETDEWEB)
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
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.
International Nuclear Information System (INIS)
Poisson regression methods are used to describe dose-response relations for cancer mortality for a subcohort of 28,347 white male radiation workers. Age specific baseline rates are described using both internal and external (US white male) rates. Regression analyses are based on an analytic data structure (ADS) that consists of a table of observed deaths, expected deaths, and person-years at risk for each combination of levels of seven risk factors. The factors are socioeconomic status, length of employment, birth cohort, age at risk, facility, internal exposure, and external exposure. Each observation in the ADS consists of the index value of each of the stratifying factors, the observed deaths, the expected deaths, the person-years, and the ten year lagged average cumulative dose. Regression diagnostics show that a linear exponential relative risk model is not appropriate for these data. Results are presented using a main effects model for factors other than external radiation, and an excess relative risk term for cumulative external radiation dose
Common pitfalls in statistical analysis: Clinical versus statistical significance.
Ranganathan, Priya; Pramesh, C S; Buyse, Marc
2015-01-01
In clinical research, study results, which are statistically significant are often interpreted as being clinically important. While statistical significance indicates the reliability of the study results, clinical significance reflects its impact on clinical practice. The third article in this series exploring pitfalls in statistical analysis clarifies the importance of differentiating between statistical significance and clinical significance. PMID:26229754
Alternatives to Statistical Significance Testing.
Palomares, Ronald S.
Researchers increasingly recognize that significance tests are limited in their ability to inform scientific practice. Common errors in interpreting significance tests and three strategies for augmenting the interpretation of significance test results are illustrated. The first strategy for augmenting the interpretation of significance tests…
Statistical significance of communities in networks
Lancichinetti, Andrea; Radicchi, Filippo; Ramasco, José J.
2010-04-01
Nodes in real-world networks are usually organized in local modules. These groups, called communities, are intuitively defined as subgraphs with a larger density of internal connections than of external links. In this work, we define a measure aimed at quantifying the statistical significance of single communities. Extreme and order statistics are used to predict the statistics associated with individual clusters in random graphs. These distributions allows us to define one community significance as the probability that a generic clustering algorithm finds such a group in a random graph. The method is successfully applied in the case of real-world networks for the evaluation of the significance of their communities.
Statistical Significance vs. Practical Significance: An Exploration through Health Education
Rosen, Brittany L.; DeMaria, Andrea L.
2012-01-01
The purpose of this paper is to examine the differences between statistical and practical significance, including strengths and criticisms of both methods, as well as provide information surrounding the application of various effect sizes and confidence intervals within health education research. Provided are recommendations, explanations and…
Mining Statistically Significant Substrings using the Chi-Square Statistic
Sachan, Mayank; Bhattacharya, Arnab
2012-01-01
The problem of identification of statistically significant patterns in a sequence of data has been applied to many domains such as intrusion detection systems, financial models, web-click records, automated monitoring systems, computational biology, cryptology, and text analysis. An observed pattern of events is deemed to be statistically significant if it is unlikely to have occurred due to randomness or chance alone. We use the chi-square statistic as a quantitative measur...
The Statistical Significance of the "Dark Flow"
Keisler, Ryan
2009-12-01
We revisit recent claims of a significant detection of a bulk flow of distant galaxy clusters. We do not find a statistically significant detection of a bulk flow. Instead we find that cosmic microwave background correlations between the eight Wilkinson Microwave Anisotropy Probe channels used in this analysis decrease the inferred significance of the detection to 0.7?.
Statistical significance of the gallium anomaly
Giunti, Carlo; Laveder, Marco
2011-06-01
We calculate the statistical significance of the anomalous deficit of electron neutrinos measured in the radioactive source experiments of the GALLEX and SAGE solar neutrino detectors, taking into account the uncertainty of the detection cross section. We found that the statistical significance of the anomaly is ~3.0?. A fit of the data in terms of neutrino oscillations favors at ~2.7? short-baseline electron neutrino disappearance with respect to the null hypothesis of no oscillations.
Determining the Statistical Significance of Relative Weights
Tonidandel, Scott; LeBreton, James M.; Johnson, Jeff W.
2009-01-01
Relative weight analysis is a procedure for estimating the relative importance of correlated predictors in a regression equation. Because the sampling distribution of relative weights is unknown, researchers using relative weight analysis are unable to make judgments regarding the statistical significance of the relative weights. J. W. Johnson…
Statistical significance of normalized global alignment.
Peris, Guillermo; Marzal, Andrés
2014-03-01
The comparison of homologous proteins from different species is a first step toward a function assignment and a reconstruction of the species evolution. Though local alignment is mostly used for this purpose, global alignment is important for constructing multiple alignments or phylogenetic trees. However, statistical significance of global alignments is not completely clear, lacking a specific statistical model to describe alignments or depending on computationally expensive methods like Z-score. Recently we presented a normalized global alignment, defined as the best compromise between global alignment cost and length, and showed that this new technique led to better classification results than Z-score at a much lower computational cost. However, it is necessary to analyze the statistical significance of the normalized global alignment in order to be considered a completely functional algorithm for protein alignment. Experiments with unrelated proteins extracted from the SCOP ASTRAL database showed that normalized global alignment scores can be fitted to a log-normal distribution. This fact, obtained without any theoretical support, can be used to derive statistical significance of normalized global alignments. Results are summarized in a table with fitted parameters for different scoring schemes. PMID:24400820
Assessing the statistical significance of periodogram peaks
Baluev, R. V.
2008-04-01
The least-squares (or Lomb-Scargle) periodogram is a powerful tool that is routinely used in many branches of astronomy to search for periodicities in observational data. The problem of assessing the statistical significance of candidate periodicities for a number of periodograms is considered. Based on results in extreme value theory, improved analytic estimations of false alarm probabilities are given. These include an upper limit to the false alarm probability (or a lower limit to the significance). The estimations are tested numerically in order to establish regions of their practical applicability.
Swiss solar power statistics 2007 - Significant expansion
International Nuclear Information System (INIS)
This article presents and discusses the 2007 statistics for solar power in Switzerland. A significant number of new installations is noted as is the high production figures from newer installations. The basics behind the compilation of the Swiss solar power statistics are briefly reviewed and an overview for the period 1989 to 2007 is presented which includes figures on the number of photovoltaic plant in service and installed peak power. Typical production figures in kilowatt-hours (kWh) per installed kilowatt-peak power (kWp) are presented and discussed for installations of various sizes. Increased production after inverter replacement in older installations is noted. Finally, the general political situation in Switzerland as far as solar power is concerned are briefly discussed as are international developments.
Assessment of statistical significance and clinical relevance.
Kieser, Meinhard; Friede, Tim; Gondan, Matthias
2013-05-10
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. PMID:23018516
Social significance of community structure: Statistical view
Li, Hui-Jia; Daniels, Jasmine J.
2015-01-01
Community structure analysis is a powerful tool for social networks that can simplify their topological and functional analysis considerably. However, since community detection methods have random factors and real social networks obtained from complex systems always contain error edges, evaluating the significance of a partitioned community structure is an urgent and important question. In this paper, integrating the specific characteristics of real society, we present a framework to analyze the significance of a social community. The dynamics of social interactions are modeled by identifying social leaders and corresponding hierarchical structures. Instead of a direct comparison with the average outcome of a random model, we compute the similarity of a given node with the leader by the number of common neighbors. To determine the membership vector, an efficient community detection algorithm is proposed based on the position of the nodes and their corresponding leaders. Then, using a log-likelihood score, the tightness of the community can be derived. Based on the distribution of community tightness, we establish a connection between p -value theory and network analysis, and then we obtain a significance measure of statistical form . Finally, the framework is applied to both benchmark networks and real social networks. Experimental results show that our work can be used in many fields, such as determining the optimal number of communities, analyzing the social significance of a given community, comparing the performance among various algorithms, etc.
Statistical Significance of Trends in Exoplanetary Atmospheres
Harrington, Joseph; Bowman, M.; Blumenthal, S. D.; Loredo, T. J.; UCF Exoplanets Group
2013-10-01
Cowan and Agol (2011) and we (Harrington et al. 2007, 2010, 2011, 2012, 2013) have noted that at higher equilibrium temperatures, observed exoplanet fluxes are substantially higher than even the elevated equilibrium temperature predicts. With a substantial increase in the number of atmospheric flux measurements, we can now test the statistical significance of this trend. We can also cast the data on a variety of axes to search further for the physics behind both the jump in flux above about 2000 K and the wide scatter in fluxes at all temperatures. This work was supported by NASA Planetary Atmospheres grant NNX12AI69G and NASA Astrophysics Data Analysis Program grant NNX13AF38G.
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
Dose response relationship in local radiotherapy for hepatocellular carcinoma
Energy Technology Data Exchange (ETDEWEB)
Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)
2001-06-01
In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2{+-}7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver volume.
On the statistical significance of climate trends
Franzke, Christian
2010-05-01
One of the major problems in climate science is the prediction of future climate change due to anthropogenic green-house gas emissions. The earth's climate is not changing in a uniform way because it is a complex nonlinear system of many interacting components. The overall warming trend can be interrupted by cooling periods due to natural variability. Thus, in order to statistically distinguish between internal climate variability and genuine trends one has to assume a certain null model of the climate variability. Traditionally a short-range, and not a long-range, dependent null model is chosen. Here I show evidence for the first time that temperature data at 8 stations across Antarctica are long-range dependent and that the choice of a long-range, rather than a short-range, dependent null model negates the statistical significance of temperature trends at 2 out of 3 stations. These results show the short comings of traditional trend analysis and imply that more attention should be given to the correlation structure of climate data, in particular if they are long-range dependent. In this study I use the Empirical Mode Decomposition (EMD) to decompose the univariate temperature time series into a finite number of Intrinsic Mode Functions (IMF) and an instantaneous mean. While there is no unambiguous definition of a trend, in this study we interpret the instantaneous mean as a trend which is possibly nonlinear. The EMD method has been shown to be a powerful method for extracting trends from noisy and nonlinear time series. I will show that this way of identifying trends is superior to the traditional linear least-square fits.
Assessing statistical significance in causal graphs
Directory of Open Access Journals (Sweden)
Chindelevitch Leonid
2012-02-01
Full Text Available Abstract Background Causal graphs are an increasingly popular tool for the analysis of biological datasets. In particular, signed causal graphs--directed graphs whose edges additionally have a sign denoting upregulation or downregulation--can be used to model regulatory networks within a cell. Such models allow prediction of downstream effects of regulation of biological entities; conversely, they also enable inference of causative agents behind observed expression changes. However, due to their complex nature, signed causal graph models present special challenges with respect to assessing statistical significance. In this paper we frame and solve two fundamental computational problems that arise in practice when computing appropriate null distributions for hypothesis testing. Results First, we show how to compute a p-value for agreement between observed and model-predicted classifications of gene transcripts as upregulated, downregulated, or neither. Specifically, how likely are the classifications to agree to the same extent under the null distribution of the observed classification being randomized? This problem, which we call "Ternary Dot Product Distribution" owing to its mathematical form, can be viewed as a generalization of Fisher's exact test to ternary variables. We present two computationally efficient algorithms for computing the Ternary Dot Product Distribution and investigate its combinatorial structure analytically and numerically to establish computational complexity bounds. Second, we develop an algorithm for efficiently performing random sampling of causal graphs. This enables p-value computation under a different, equally important null distribution obtained by randomizing the graph topology but keeping fixed its basic structure: connectedness and the positive and negative in- and out-degrees of each vertex. We provide an algorithm for sampling a graph from this distribution uniformly at random. We also highlight theoretical challenges unique to signed causal graphs; previous work on graph randomization has studied undirected graphs and directed but unsigned graphs. Conclusion We present algorithmic solutions to two statistical significance questions necessary to apply the causal graph methodology, a powerful tool for biological network analysis. The algorithms we present are both fast and provably correct. Our work may be of independent interest in non-biological contexts as well, as it generalizes mathematical results that have been studied extensively in other fields.
Treatments of Effect Sizes and Statistical Significance Tests in Textbooks.
Capraro, Robert M.; Capraro, Mary Margaret
2002-01-01
Reviewed statistics textbooks published since 1995 to determine the treatment of effect sizes and statistical significance tests. Each of the 89 textbooks included statistical significance, while only 60 included information on effect sizes. (SLD)
Significant Statistics: Viewed with a Contextual Lens
Tait-McCutcheon, Sandi
2010-01-01
This paper examines the pedagogical and organisational changes three lead teachers made to their statistics teaching and learning programs. The lead teachers posed the research question: What would the effect of contextually integrating statistical investigations and literacies into other curriculum areas be on student achievement? By finding the…
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
The significant digit law in statistical physics
Shao, Lijing; Ma, Bo-Qiang
2010-08-01
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.
Statistical significance of optical map alignments.
Sarkar, Deepayan; Goldstein, Steve; Schwartz, David C; Newton, Michael A
2012-05-01
The Optical Mapping System constructs ordered restriction maps spanning entire genomes through the assembly and analysis of large datasets comprising individually analyzed genomic DNA molecules. Such restriction maps uniquely reveal mammalian genome structure and variation, but also raise computational and statistical questions beyond those that have been solved in the analysis of smaller, microbial genomes. We address the problem of how to filter maps that align poorly to a reference genome. We obtain map-specific thresholds that control errors and improve iterative assembly. We also show how an optimal self-alignment score provides an accurate approximation to the probability of alignment, which is useful in applications seeking to identify structural genomic abnormalities. PMID:22506568
Social significance of community structure: Statistical view
Li, Hui-Jia
2015-01-01
Community structure analysis is a powerful tool for social networks, which can simplify their topological and functional analysis considerably. However, since community detection methods have random factors and real social networks obtained from complex systems always contain error edges, evaluating the significance of community structure partitioned is an urgent and important question. In this paper, integrating the specific characteristics of real society, we present a novel framework analyzing the significance of social community specially. The dynamics of social interactions are modeled by identifying social leaders and corresponding hierarchical structures. Instead of a direct comparison with the average outcome of a random model, we compute the similarity of a given node with the leader by the number of common neighbors. To determine the membership vector, an efficient community detection algorithm is proposed based on the position of nodes and their corresponding leaders. Then, using log-likelihood sco...
Mass spectrometry based protein identification with accurate statistical significance assignment
Alves, Gelio; Yu, Yi-Kuo
2014-01-01
Motivation: Assigning statistical significance accurately has become increasingly important as meta data of many types, often assembled in hierarchies, are constructed and combined for further biological analyses. Statistical inaccuracy of meta data at any level may propagate to downstream analyses, undermining the validity of scientific conclusions thus drawn. From the perspective of mass spectrometry based proteomics, even though accurate statistics for peptide identificat...
Caveats for using statistical significance tests in research assessments
Schneider, Jesper W
2011-01-01
This paper raises concerns about the advantages of using statistical significance tests in research assessments as has recently been suggested in the debate about proper normalization procedures for citation indicators. Statistical significance tests are highly controversial and numerous criticisms have been leveled against their use. Based on examples from articles by proponents of the use statistical significance tests in research assessments, we address some of the numerous problems with such tests. The issues specifically discussed are the ritual practice of such tests, their dichotomous application in decision making, the difference between statistical and substantive significance, the implausibility of most null hypotheses, the crucial assumption of randomness, as well as the utility of standard errors and confidence intervals for inferential purposes. We argue that applying statistical significance tests and mechanically adhering to their results is highly problematic and detrimental to critical thinki...
Significance Analysis and Statistical Mechanics: An Application to Clustering
?uksza, Marta; Lässig, Michael; Berg, Johannes
2010-11-01
This Letter addresses the statistical significance of structures in random data: Given a set of vectors and a measure of mutual similarity, how likely is it that a subset of these vectors forms a cluster with enhanced similarity among its elements? The computation of this cluster p value for randomly distributed vectors is mapped onto a well-defined problem of statistical mechanics. We solve this problem analytically, establishing a connection between the physics of quenched disorder and multiple-testing statistics in clustering and related problems. In an application to gene expression data, we find a remarkable link between the statistical significance of a cluster and the functional relationships between its genes.
Human Perception of Statistical Significance and Effect Size.
Sheth, Bhavin; Patel, Jasmine
2015-09-01
Statistics are ubiquitous in the information age. While they are fundamental to scientific discovery, understanding the layperson's intuitive grasp of statistics is necessary if scientific advances and policies are to garner popular support. We asked two questions: First, how tightly matched are our perceptions of statistical significance and statistics? Second, are perceptual judgments of discriminability driven by statistical significance or by effect size? To address the first question, we displayed scatter plots of differently colored points chosen from two gaussian distributions had different mean/variance; observers judged if the two patterns of dots were similar or different. Perceptual judgments were compared to the results of statistical tests. Observers perceived the two arrangements of dots as "different" when there was no true difference at all (Type I: false positives), but were more conservative than statistics when the level of true discriminability increased (Type II: misses). When distributions overlap in space, we seem to be, by and large, immune to statistical significance. To address the second question, we displayed two plots in which we varied the level of statistical significance and effect size in opposite directions. Each plot contained red and blue points chosen from two Gaussian distributions of different mean and variance and observers had to judge, in a binary choice task, which of the two plots had red and blue points that appeared more different. The plots were designed so that one had the larger effect size (effect size is defined as the difference in means over the pooled standard deviation: Cohen's d), and the other the higher level of statistical significance. Over a range of effect sizes and p-values, observes chose the plot with the larger effect size as being more different. Our results suggest that effect size, rather than statistical significance, drives perceptual judgments. Meeting abstract presented at VSS 2015. PMID:26326025
Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease
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Purpose: To assess the shape of the dose–response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy?1 of 0.082 (95% CI 0.031–0.140), and ischemic heart disease, with an excess relative risk Gy?1 of 0.102 (95% CI 0.039–0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose–response. There were significant (p 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose–response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The 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.
Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease
Energy Technology Data Exchange (ETDEWEB)
Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mabuchi, Kiyohiko [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States)
2012-12-01
Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.
Exploring the dose response of radiochromic dosimeters
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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.
Exploring the dose response of radiochromic dosimeters
Skyt, P. S.; Wahlstedt, I.; Yates, E. S.; Muren, L. P.; Petersen, J. B. B.; Balling, P.
2013-06-01
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.
A Statistical Significance Simulation Study for the General Scientist
Levman, Jacob
2011-01-01
When a scientist performs an experiment they normally acquire a set of measurements and are expected to demonstrate that their results are "statistically significant" thus confirming whatever hypothesis they are testing. The main method for establishing statistical significance involves demonstrating that there is a low probability that the observed experimental results were the product of random chance. This is typically defined as p < 0.05, which indicates there is less th...
Caveats for using statistical significance tests in research assessments
DEFF Research Database (Denmark)
Schneider, Jesper Wiborg
2013-01-01
This article raises concerns about the advantages of using statistical significance tests in research assessments as has recently been suggested in the debate about proper normalization procedures for citation indicators by Opthof and Leydesdorff (2010). Statistical significance tests are highly controversial and numerous criticisms have been leveled against their use. Based on examples from articles by proponents of the use statistical significance tests in research assessments, we address some of the numerous problems with such tests. The issues specifically discussed are the ritual practice of such tests, their dichotomous application in decision making, the difference between statistical and substantive significance, the implausibility of most null hypotheses, the crucial assumption of randomness, as well as the utility of standard errors and confidence intervals for inferential purposes. We argue that applying statistical significance tests and mechanically adhering to their results are highly problematic and detrimental to critical thinking. We claim that the use of such tests do not provide any advantages in relation to deciding whether differences between citation indicators are important or not. On the contrary their use may be harmful. Like many other critics, we generally believe that statistical significance tests are over- and misused in the empirical sciences including scientometrics and we encourage a reform on these matters.
The use of meta-analytic statistical significance testing.
Polanin, Joshua R; Pigott, Terri D
2015-03-01
Meta-analysis multiplicity, the concept of conducting multiple tests of statistical significance within one review, is an underdeveloped literature. We address this issue by considering how Type I errors can impact meta-analytic results, suggest how statistical power may be affected through the use of multiplicity corrections, and propose how meta-analysts should analyze multiple tests of statistical significance. The context for this study is a meta-review of meta-analyses published in two leading review journals in education and psychology. Our review of 130 meta-analyses revealed a strong reliance on statistical significance testing without consideration of Type I errors or the use of multiplicity corrections. In order to provide valid conclusions, meta-analysts must consider these issues prior to conducting the review. PMID:26035470
Statistical significance test for transition matrices of atmospheric Markov chains
Vautard, Robert; Mo, Kingtse C.; Ghil, Michael
1990-01-01
Low-frequency variability of large-scale atmospheric dynamics can be represented schematically by a Markov chain of multiple flow regimes. This Markov chain contains useful information for the long-range forecaster, provided that the statistical significance of the associated transition matrix can be reliably tested. Monte Carlo simulation yields a very reliable significance test for the elements of this matrix. The results of this test agree with previously used empirical formulae when each cluster of maps identified as a distinct flow regime is sufficiently large and when they all contain a comparable number of maps. Monte Carlo simulation provides a more reliable way to test the statistical significance of transitions to and from small clusters. It can determine the most likely transitions, as well as the most unlikely ones, with a prescribed level of statistical significance.
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Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P?1 of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI ?0.002, 0.119), and 1.087 (95% CI ?0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the 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.
The ongoing tyranny of statistical significance testing in biomedical research
Stang, Andreas; Poole, Charles; Kuss, Oliver
2010-01-01
Abstract 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 i...
BEYOND STATISTICAL SIGNIFICANCE: CLINICAL INTERPRETATION OF REHABILITATION RESEARCH LITERATURE
Page, Phil
2014-01-01
Evidence?based practice requires clinicians to stay current with the scientific literature. Unfortunately, rehabilitation professionals are often faced with research literature that is difficult to interpret clinically. Clinical research data is often analyzed with traditional statistical probability (p?values), which may not give rehabilitation professionals enough information to make clinical decisions. Statistically significant differences or outcomes simply address whether to accept or re...
Hormetic dose-responses in nanotechnology studies.
Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Calabrese, Edward J
2014-07-15
While exposure to nanoparticles is a growing concern, research into their toxicological impact and possible hazard for human health is limited. There remains a lack of information concerning the nature of the dose-response relationship especially at low level exposures. The present paper assesses the occurrence of hormetic-like biphasic dose responses within the nanotoxicology literature. The findings indicate that nanoparticles may induce hormetic-like biphasic dose responses in a wide range of biological cell types, and that these responses can be highly dependent upon the physical and chemical properties of the agent. While the mechanistic foundations of hormetic dose responses induced by chemicals and pharmaceuticals have markedly advanced over the past decade, this remains an important data need for nanotoxicology. PMID:24793332
On detection and assessment of statistical significance of Genomic Islands
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Chaudhuri Probal
2008-04-01
Full Text Available Abstract Background Many of the available methods for detecting Genomic Islands (GIs in prokaryotic genomes use markers such as transposons, proximal tRNAs, flanking repeats etc., or they use other supervised techniques requiring training datasets. Most of these methods are primarily based on the biases in GC content or codon and amino acid usage of the islands. However, these methods either do not use any formal statistical test of significance or use statistical tests for which the critical values and the P-values are not adequately justified. We propose a method, which is unsupervised in nature and uses Monte-Carlo statistical tests based on randomly selected segments of a chromosome. Such tests are supported by precise statistical distribution theory, and consequently, the resulting P-values are quite reliable for making the decision. Results Our algorithm (named Design-Island, an acronym for Detection of Statistically Significant Genomic Island runs in two phases. Some 'putative GIs' are identified in the first phase, and those are refined into smaller segments containing horizontally acquired genes in the refinement phase. This method is applied to Salmonella typhi CT18 genome leading to the discovery of several new pathogenicity, antibiotic resistance and metabolic islands that were missed by earlier methods. Many of these islands contain mobile genetic elements like phage-mediated genes, transposons, integrase and IS elements confirming their horizontal acquirement. Conclusion The proposed method is based on statistical tests supported by precise distribution theory and reliable P-values along with a technique for visualizing statistically significant islands. The performance of our method is better than many other well known methods in terms of their sensitivity and accuracy, and in terms of specificity, it is comparable to other methods.
Assigning statistical significance to proteotypic peptides via database searches
Alves, Gelio; Ogurtsov, Aleksey Y; Yu, Yi-Kuo
2010-01-01
Querying MS/MS spectra against a database containing only proteotypic peptides reduces data analysis time due to reduction of database size. Despite the speed advantage, this search strategy is challenged by issues of statistical significance and coverage. The former requires separating systematically significant identifications from less confident identifications, while the latter arises when the underlying peptide is not present, due to single amino acid polymorphisms (SAPs) or post-transla...
Your Chi-Square Test Is Statistically Significant: Now What?
Sharpe, Donald
2015-01-01
Applied researchers have employed chi-square tests for more than one hundred years. This paper addresses the question of how one should follow a statistically significant chi-square test result in order to determine the source of that result. Four approaches were evaluated: calculating residuals, comparing cells, ransacking, and partitioning. Data…
Changes in temperature records and extremes: Are they statistically significant?
Christiansen, Bo
2013-04-01
We investigate whether the increasing number of warm records and extreme warm values in the extra-tropical northern hemisphere over the last decades are statistically significant. For the extremes we focus on summer mean temperature and for warm records we focus on daily and monthly means. The statistical significance is a highly non-trivial problem because the atmosphere is both spatially and temporally strongly autocorrelated and the records and extremes will therefore have a tendency to appear clustered in both space and time. To deal with this we apply a numerical method to produce a surrogate ensemble of fields that are statistically similar to the observed temperature field except that the surrogates are stationary and do not include the observed secular variations. The significance is then estimated by comparing the annual or seasonal number of records or extremes in the observations to the similar numbers in the surrogates. We find that the number of warm daily and monthly records as well as the extreme summer mean temperatures have the same general temporal development with a slow decrease from the late 1940s (the beginning of the reanalysis data set used here) to a minimum in the 1970s followed by an increase to the present high values. However, there is a strong difference in the statistical significance of the different quantities. We find with very strong statistical significance that the recent large number of warm daily records as well as the number of summers with extreme mean temperatures cannot be explained as chance occurrences. Both these quantities show a number of recent consecutive years (11 and 10) with values above the 95 % level that is much larger than any similar number found in the ensemble of 1000 surrogates. We do not find any significant change in the number of monthly warm records. The statistical significance weakens when considering the individual seasons or smaller regions like Europe. But for the annual number of daily warm records we still find a significant increase in Europe and for the extra-tropical northern hemisphere a significant increase in all seasons except spring.
Zeiger, Errol; Hoffmann, George R
2012-07-01
A recent report (Calabrese et al., Mutat. Res. 726 (2011) 91-97) concluded that an analysis of Ames test mutagenicity data provides evidence of hormesis in mutagenicity dose-response relationships. An examination of the data used in this study and the conclusions regarding hormesis reveal a number of concerns regarding the analyses and possible misinterpretations of the Salmonella data. The claim of hormesis is based on test data from the National Toxicology Program using Salmonella strain TA100. Approximately half of the chemicals regarded as hormetic, and the majority of the specific dose-responses identified as hormetic, were actually nonmutagenic. We conclude that the data provide no evidence of hormetic effects. The Ames test is an excellent measure of bacterial mutagenicity, but the numbers of revertant (mutant) colonies on the plate are the result of a complex interaction between mutagenicity and toxicity, which renders the test inappropriate for demonstrating hormesis in bacterial mutagenicity experiments. PMID:22484510
Test for the statistical significance of differences between ROC curves
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A test for the statistical significance of observed differences between two measured Receiver Operating Characteristic (ROC) curves has been designed and evaluated. The set of observer response data for each ROC curve is assumed to be independent and to arise from a ROC curve having a form which, in the absence of statistical fluctuations in the response data, graphs as a straight line on double normal-deviate axes. To test the significance of an apparent difference between two measured ROC curves, maximum likelihood estimates of the two parameters of each curve and the associated parameter variances and covariance are calculated from the corresponding set of observer response data. An approximate Chi-square statistic with two degrees of freedom is then constructed from the differences between the parameters estimated for each ROC curve and from the variances and covariances of these estimates. This statistic is known to be truly Chi-square distributed only in the limit of large numbers of trials in the observer performance experiments. Performance of the statistic for data arising from a limited number of experimental trials was evaluated. Independent sets of rating scale data arising from the same underlying ROC curve were paired, and the fraction of differences found (falsely) significant was compared to the significance level, ?, used with the test. Although test performance was found to be somewhat dependent on both the number of trials in the data and the position of the underlying ROC curve in the ROC space, the results for various significance levels showed the test to be reliable under practical experimental conditions
Bayesian multimodel inference for dose-response studies
Link, W.A.; Albers, P.H.
2007-01-01
Statistical inference in dose?response studies is model-based: The analyst posits a mathematical model of the relation between exposure and response, estimates parameters of the model, and reports conclusions conditional on the model. Such analyses rarely include any accounting for the uncertainties associated with model selection. The Bayesian inferential system provides a convenient framework for model selection and multimodel inference. In this paper we briefly describe the Bayesian paradigm and Bayesian multimodel inference. We then present a family of models for multinomial dose?response data and apply Bayesian multimodel inferential methods to the analysis of data on the reproductive success of American kestrels (Falco sparveriuss) exposed to various sublethal dietary concentrations of methylmercury.
Increasing the Statistical Significance of Entanglement Detection in Experiments
Jungnitsch, Bastian; Niekamp, Sönke; Kleinmann, Matthias; Gühne, Otfried; Lu, He; Gao, Wei-Bo; Chen, Yu-Ao; Chen, Zeng-Bing; Pan, Jian-Wei
2010-05-01
Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. Experimentally, we observe this phenomenon in a four-photon experiment, testing the Mermin and Ardehali inequality for different levels of noise. Furthermore, we provide a way to develop entanglement tests with high statistical significance.
On the Atmospheric Neutrino Anomaly and its Statistical Significance
Fogli, G L; Lisi, E.
1995-01-01
An analysis of the existing data on the atmospheric neutrino anomaly is presented, focused on the statistical significance that can be attributed to its experimental evidence. Our approach is alternative to the usual analyses in terms of the $\\mu/e$ ratio of event rates. In fact, we perform a comparison between data and expectations, by {\\em separating\\/} the information on $e$-like and $\\mu$-like events, with a careful estimate of the different errors and of their correlati...
The statistical significance of the superhump signal in U Geminorum
Schreiber, M. R.
2007-05-01
Context: Although its well-determined mass ratio of q=M_sec/M_wd=0.357±0.007 should avoid superoutbursts according to the thermal tidal instability model, in 1985 the prototypical dwarf nova U Gem experienced an extraordinary long outburst very much resembling 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. Aims: 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. Methods: 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 analysis to previous superhump detections. Results: The 160 data points of the outburst alone do not contain a statistically significant period. However, using the characteristics of superhumps detected previously in other SU UMa systems additionally and searching only for signals that are consistent with these, we derive a 2? significance for the superhump signal. The alleged appearance of an additional superhump at the end of the outbursts appears to be statistically insignificant. Conclusions: Although of weak statistical significance, the superhump signal of the long 1985 outburst of U Gem can be interpreted as further indication of the SU UMa nature of this outburst. This further contradicts the tidal instability model as the explanation of the superhump phenomenon.
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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)
Ranganathan, Priya; Pramesh, C S; Buyse, Marc
2015-01-01
In the second part of a series on pitfalls in statistical analysis, we look at various ways in which a statistically significant study result can be expressed. We debunk some of the myths regarding the 'P' value, explain the importance of 'confidence intervals' and clarify the importance of including both values in a paper. PMID:25878958
Statistical significance of epidemiological data. Seminar: Evaluation of epidemiological studies
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In stochastic damages, the numbers of events, e.g. the persons who are affected by or have died of cancer, and thus the relative frequencies (incidence or mortality) are binomially distributed random variables. Their statistical fluctuations can be characterized by confidence intervals. For epidemiologic questions, especially for the analysis of stochastic damages in the low dose range, the following issues are interesting: - Is a sample (a group of persons) with a definite observed damage frequency part of the whole population? - Is an observed frequency difference between two groups of persons random or statistically significant? - Is an observed increase or decrease of the frequencies with increasing dose random or statistically significant and how large is the regression coefficient (= risk coefficient) in this case? These problems can be solved by sttistical tests. So-called distribution-free tests and tests which are not bound to the supposition of normal distribution are of particular interest, such as: - ?2-independence test (test in contingency tables); - Fisher-Yates-test; - trend test according to Cochran; - rank correlation test given by Spearman. These tests are explained in terms of selected epidemiologic data, e.g. of leukaemia clusters, of the cancer mortality of the Japanese A-bomb survivors especially in the low dose range as well as on the sample of the cancer mortality in the high background area in Yangjiang (China). (orig.) in Yangjiang (China). (orig.)
Significance analysis and statistical dissection of variably methylated regions.
Jaffe, Andrew E; Feinberg, Andrew P; Irizarry, Rafael A; Leek, Jeffrey T
2012-01-01
It has recently been proposed that variation in DNA methylation at specific genomic locations may play an important role in the development of complex diseases such as cancer. Here, we develop 1- and 2-group multiple testing procedures for identifying and quantifying regions of DNA methylation variability. Our method is the first genome-wide statistical significance calculation for increased or differential variability, as opposed to the traditional approach of testing for mean changes. We apply these procedures to genome-wide methylation data obtained from biological and technical replicates and provide the first statistical proof that variably methylated regions exist and are due to interindividual variation. We also show that differentially variable regions in colon tumor and normal tissue show enrichment of genes regulating gene expression, cell morphogenesis, and development, supporting a biological role for DNA methylation variability in cancer. PMID:21685414
Increasing the statistical significance of entanglement detection in experiments
Jungnitsch, Bastian; Kleinmann, Matthias; Gühne, Otfried; Lu, He; Gao, Wei-Bo; Chen, Yu-Ao; Chen, Zeng-Bing; Pan, Jian-Wei
2009-01-01
Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. Experimentally, we observe this phenomenon in a four-photon experiment, testing the Mermin and Ardehali inequality for different levels of noise.
Large SDSS Quasar Groups and Their Statistical Significance
Park, Changbom; Song, Hyunmi; Einasto, Maret; Lietzen, Heidi; Heinamaki, Pekka
2015-02-01
We use a volume-limited sample of quasars in the Sloan Digital Sky Survey (SDSS) DR7 quasar catalog to identify quasar groups and address their statistical significance. This quasar sample has a uniform selection function on the sky and nearly a maximum possible contiguous volume that can be drawn from the DR7 catalog. Quasar groups are identified by using the Friend-of-Friend algorithm with a set of fixed comoving linking lengths. We find that the richness distribution of the richest 100 quasar groups or the size distribution of the largest 100 groups are statistically equivalent with those of randomly-distributed points with the same number density and sky coverage when groups are identified with the linking length of 70 h-1 Mpc. It is shown that the large-scale structures like the huge Large Quasar Group (U1.27) reported by Clowes et al. (2013) can be found with high probability even if quasars have no physical clustering, and does not challenge the initially homogeneous cosmological models. Our results are statistically more reliable than those of Nadathur (2013), where the test was made only for the largest quasar group. It is shown that the linking length should be smaller than 50 h-1 Mpc in order for the quasar groups identified in the DR7 catalog not to be dominated by associations of quasars grouped by chance. We present 20 richest quasar groups identified with the linking length of 70 h-1 Mpc for further analyses.
Vermeesch, Pieter
2011-02-01
In my Eos Forum of 24 November 2009 (90(47), 443), I used the chi-square test to reject the null hypothesis that earthquakes occur independent of the weekday to make the point that statistical significance should not be confused with geological significance. Of the five comments on my article, only the one by Sornette and Pisarenko [2011] disputes this conclusion, while the remaining comments take issue with certain aspects of the geophysical case study. In this reply I will address all of these points, after providing some necessary further background about statistical tests. Two types of error can result from a hypothesis test. A Type I error occurs when a true null hypothesis is erroneously rejected by chance. A Type II error occurs when a false null hypothesis is erroneously accepted by chance. By definition, the p value is the probability, under the null hypothesis, of obtaining a test statistic at least as extreme as the one observed. In other words, the smaller the p value, the lower the probability that a Type I error has been made. In light of the exceedingly small p value of the earthquake data set, Tseng and Chen's [2011] assertion that a Type I error has been committed is clearly wrong. How about Type II errors?
Statistical significance of climate sensitivity predictors obtained by data mining
Caldwell, Peter M.; Bretherton, Christopher S.; Zelinka, Mark D.; Klein, Stephen A.; Santer, Benjamin D.; Sanderson, Benjamin M.
2014-03-01
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.
A new approach to evaluating statistical significance of spectral identifications.
Mohimani, Hosein; Kim, Sangtae; Pevzner, Pavel A
2013-04-01
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
Statistical significance of displacements in heterogeneous control networks
Nowel, Krzysztof; Kami?ski, Waldemar
2013-12-01
This paper proposes a modification of the classical process for evaluating the statistical significance of displacements in the case of heterogeneous (e.g. linear-angular) control networks established to deformation measurements and analysis. The basis for the proposed solution is the idea of local variance factors. The theoretical discussion was complemented with an example of its application on a simulated horizontal control network. The obtained results showed that the evaluation of the statistical significance of displacements in the case of heterogeneous control networks should be carried out using estimators of local variance factors. W pracy zaproponowano modyfikacj? klasycznego procesu oceny statystycznej istotno?ci przemieszcze? w przypadku niejednorodnych sieci kontrolnych (np. k?towo - liniowych) zak?adanych do pomiarów i analizy deformacji. Podstaw? proponowanego rozwi?zania jest idea lokalnych wspó?czynników wariancji. Rozwa?ania teoretyczne uzupe?niono przyk?adem zastosowania na symulowanej poziomej sieci kontrolnej. Uzyskane wyniki pokaza?y, ?e ocena statystycznej istotno?ci przemieszcze? w przypadku niejednorodnych sieci kontrolnych powinna by? przeprowadzana z u?yciem w?a?nie estymatorów lokalnych wspó?czynników wariancji.
Increasing the statistical significance of entanglement detection in experiments
International Nuclear Information System (INIS)
Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. We show this to be the case for an error model in which the variance of an observable is interpreted as its error and for the standard error model in photonic experiments. Specifically, we demonstrate that the Mermin inequality yields a Bell test which is statistically more significant than the Ardehali inequality in the case of a photonic four-qubit state that is close to a GHZ state. Experimentally, we observe this phenomenon in a four-photon experiment, testing the above inequalities for different levels of noise.
The significant digit law: a paradigm of statistical scale symmetries. The significant digit law
Pocheau, A.
2006-02-01
In many different topics, the most significant digits of data series display a non-uniform distribution which points to an equiprobability of logarithms. This surprising ubiquitous property, known as the significant digit law, is shown here to follow from two similar, albeit different, scale symmetries: the scale-invariance and the scale-ratio invariance. After having legitimized these symmetries in the present context, the corresponding symmetric distributions are determined by implementing a covariance criterion. The logarithmic distribution is identified as the only distribution satisfying both symmetries. Attraction of other distributions to this most symmetric distribution by dilation, stretching and merging is investigated and clarified. The natures of both the scale-invariance and the scale-ratio invariance are further analyzed by determining the structure of the sets composed by the corresponding symmetric distributions. Altogether, these results provide new insights into the meaning and the role of scale symmetries in statistics.
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.)
Energy Technology Data Exchange (ETDEWEB)
Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States)
2013-02-01
Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.
Statistical significance of landcover change detection using multitemporal satellite images
Chiang, J. L.; Wei, C.; Lin, Y. B.; Cheng, K. S.; Chiu, H. P.
2009-04-01
Landcover change detection using remote sensing images is a powerful tool for watershed management. Determination of threshold of gray level difference for change detection is essential for such practices. In addition, accuracy assessment for change detection results is particularly difficult due to lack of ground-truth landcover data of pre- and post-periods. Therefore, a probabilistic approach based on test of hypothesis for landcover change detection was developed in this study. Assuming the digital numbers are bivariate normal distribution. It provides a confidence level for deciding a pixel is changed or not, which can be an alternative to the producer's accuracy achieved by post-classification change detection approach. Instead of using a not so meaningful threshold, we provide a statistical confidence level to explain how much confidence we have when some pixels are detected as changed pixels. In the study area in central Taiwan, the major change is from vegetation to bare soil/ built-up. The change areas detected by 5% significance contribute 7.05% of this entire area.
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
International stock return predictability: statistical evidence and economic significance
Giot, Pierre; Petitjean, Mikael
2006-01-01
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 ...
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
Tipping points in the arctic: eyeballing or statistical significance?
Carstensen, Jacob; Weydmann, Agata
2012-02-01
Arctic ecosystems have experienced and are projected to experience continued large increases in temperature and declines in sea ice cover. It has been hypothesized that small changes in ecosystem drivers can fundamentally alter ecosystem functioning, and that this might be particularly pronounced for Arctic ecosystems. We present a suite of simple statistical analyses to identify changes in the statistical properties of data, emphasizing that changes in the standard error should be considered in addition to changes in mean properties. The methods are exemplified using sea ice extent, and suggest that the loss rate of sea ice accelerated by factor of ~5 in 1996, as reported in other studies, but increases in random fluctuations, as an early warning signal, were observed already in 1990. We recommend to employ the proposed methods more systematically for analyzing tipping points to document effects of climate change in the Arctic. PMID:22246634
Confidence bounds for nonlinear dose-response relationships.
Baayen, C; Hougaard, P
2015-11-30
An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve. It is well known that Wald confidence intervals are based on linear approximations and are often unsatisfactory in nonlinear models. Apart from incorrect coverage rates, they can be unreasonable in the sense that the lower confidence limit of the difference to placebo can be negative, even when an overall test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated using a public dataset and simulations based on the Emax and sigmoid Emax models. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26112765
Changing Statistical Significance with the Amount of Information: The Adaptive ? Significance Level.
Pérez, María-Eglée; Pericchi, Luis Raúl
2014-02-01
We put forward an adaptive alpha which changes with the amount of sample information. This calibration may be interpreted as a Bayes/non-Bayes compromise, and leads to statistical consistency. The calibration can also be used to produce confidence intervals whose size take in consideration the amount of observed information. PMID:24511173
Statistical downscaling rainfall using artificial neural network: significantly wetter Bangkok?
Vu, Minh Tue; Aribarg, Thannob; Supratid, Siriporn; Raghavan, Srivatsan V.; Liong, Shie-Yui
2015-08-01
Artificial neural network (ANN) is an established technique with a flexible mathematical structure that is capable of identifying complex nonlinear relationships between input and output data. The present study utilizes ANN as a method of statistically downscaling global climate models (GCMs) during the rainy season at meteorological site locations in Bangkok, Thailand. The study illustrates the applications of the feed forward back propagation using large-scale predictor variables derived from both the ERA-Interim reanalyses data and present day/future GCM data. The predictors are first selected over different grid boxes surrounding Bangkok region and then screened by using principal component analysis (PCA) to filter the best correlated predictors for ANN training. The reanalyses downscaled results of the present day climate show good agreement against station precipitation with a correlation coefficient of 0.8 and a Nash-Sutcliffe efficiency of 0.65. The final downscaled results for four GCMs show an increasing trend of precipitation for rainy season over Bangkok by the end of the twenty-first century. The extreme values of precipitation determined using statistical indices show strong increases of wetness. These findings will be useful for policy makers in pondering adaptation measures due to flooding such as whether the current drainage network system is sufficient to meet the changing climate and to plan for a range of related adaptation/mitigation measures.
The statistical significance of selected sense-antisense peptide interactions.
Illingworth, Christopher J R; Chintipalli, Sree V; Serapian, Stefano A; Miller, Andrew D; Veverka, Vaclav; Carr, Mark D; Reynolds, Christopher A
2012-06-15
Sense and antisense peptides, encoded by sense and corresponding antisense DNA strands, are capable of specific interactions that could be a driving force to mediate protein-protein or protein-peptide binding associations. The complementary residue hypothesis suggests that these interactions are founded upon the sum of pairwise interactions between amino acids encoded by corresponding sense and antisense codons. Despite many successful experimental results obtained with the hypothesis, however, the physicochemical basis for these interactions is poorly understood. We examined the potential of the hypothesis for general identification of protein-protein interaction sites, and the possible role of the hypothesis in determining folding in a broad set of protein structures. In addition, we performed a structural study to investigate the binding of a complementary peptide to IL-1F2. Our results suggest that complementary residue pairs are no more frequent or conserved than average in protein-protein interfaces, and are statistically under-represented amongst contacting residue pairs in folded protein structures. Although our structural results matched experimental observations of binding between the peptide and IL-1F2, complementary residue interactions do not appear to be dominant in the bound structure. Overall, our data do not allow us to conclude that the complementary residue hypothesis accounts for specific sense-antisense peptide interactions. PMID:22488506
Two Test Statistics for Cross-Modal Graph Community Significance
Richiardi, Jonas; Altmann, Andre; Greicius, Michael
2013-01-01
Comparing and combining data from different brain imaging and non-imaging modalities is challenging, in particular due to the different dimensionalities and resolutions of the modalities. Using an abstract and expressive enough representation for the data, such as graphs, enables gainful inference of relationship between biological scales and mechanisms. Here, we propose a test for the significance of groups of graph vertices in a modality when the grouping is defined in another modality. We ...
Statistically significant data base of rock properties for geothermal use
Koch, A.; Jorand, R.; Clauser, C.
2009-04-01
The high risk of failure due to the unknown properties of the target rocks at depth is a major obstacle for the exploration of geothermal energy. In general, the ranges of thermal and hydraulic properties given in compilations of rock properties are too large to be useful to constrain properties at a specific site. To overcome this problem, we study the thermal and hydraulic rock properties of the main rock types in Germany in a statistical approach. An important aspect is the use of data from exploration wells that are largely untapped for the purpose of geothermal exploration. In the current project stage, we have been analyzing mostly Devonian and Carboniferous drill cores from 20 deep boreholes in the region of the Lower Rhine Embayment and the Ruhr area (western North Rhine Westphalia). In total, we selected 230 core samples with a length of up to 30 cm from the core archive of the State Geological Survey. The use of core scanning technology allowed the rapid measurement of thermal conductivity, sonic velocity, and gamma density under dry and water saturated conditions with high resolution for a large number of samples. In addition, we measured porosity, bulk density, and matrix density based on Archimedes' principle and pycnometer analysis. As first results we present arithmetic means, medians and standard deviations characterizing the petrophysical properties and their variability for specific lithostratigraphic units. Bi- and multimodal frequency distributions correspond to the occurrence of different lithologies such as shale, limestone, dolomite, sandstone, siltstone, marlstone, and quartz-schist. In a next step, the data set will be combined with logging data and complementary mineralogical analyses to derive the variation of thermal conductivity with depth. As a final result, this may be used to infer thermal conductivity for boreholes without appropriate core data which were drilled in similar geological settings.
Statistical significance tests for spatially embedded complex networks
Donges, J. F.; Zou, Y.; Marwan, N.; Kurths, J.
2009-04-01
The analysis of spatially embedded complex networks, i.e. networks with vertices embedded in a metric space, is of increasing interest in many fields of science. Examples are power grids in electrical engineering, the internet and world wide web in computer science or social networks in social science. In many cases, there is some degree of uncertainty about the network structure, e.g. edges might be missing in the network that exist in the system under study (the opposite may also be true). This is particularly true for networks constructed from multivariate data using the tools of time series analysis. Given this uncertainty, it is very important to evaluate the significance of measured network properties such as clustering coefficient, average path length, degree distribution or various vertex centrality sequences with respect to a given null hypothesis. Here we present different types of surrogates for spatially embedded networks, i.e. random networks with prescribed spatial constraints such as fixed edge distance distribution or a fixed average edge distance sequence, and show how to use them for testing the associated null hypotheses. We demonstrate the proposed significance tests for a global climate network constructed from coupled model surface air temperature data.
Understanding the Sampling Distribution and Its Use in Testing Statistical Significance.
Breunig, Nancy A.
Despite the increasing criticism of statistical significance testing by researchers, particularly in the publication of the 1994 American Psychological Association's style manual, statistical significance test results are still popular in journal articles. For this reason, it remains important to understand the logic of inferential statistics. A…
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)
Wilkinson, Michael
2014-03-01
Decisions about support for predictions of theories in light of data are made using statistical inference. The dominant approach in sport and exercise science is the Neyman-Pearson (N-P) significance-testing approach. When applied correctly it provides a reliable procedure for making dichotomous decisions for accepting or rejecting zero-effect null hypotheses with known and controlled long-run error rates. Type I and type II error rates must be specified in advance and the latter controlled by conducting an a priori sample size calculation. The N-P approach does not provide the probability of hypotheses or indicate the strength of support for hypotheses in light of data, yet many scientists believe it does. Outcomes of analyses allow conclusions only about the existence of non-zero effects, and provide no information about the likely size of true effects or their practical/clinical value. Bayesian inference can show how much support data provide for different hypotheses, and how personal convictions should be altered in light of data, but the approach is complicated by formulating probability distributions about prior subjective estimates of population effects. A pragmatic solution is magnitude-based inference, which allows scientists to estimate the true magnitude of population effects and how likely they are to exceed an effect magnitude of practical/clinical importance, thereby integrating elements of subjective Bayesian-style thinking. While this approach is gaining acceptance, progress might be hastened if scientists appreciate the shortcomings of traditional N-P null hypothesis significance testing. PMID:24248505
International Nuclear Information System (INIS)
We performed analyses of cancer and noncancer mortality in the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) to determine whether the observed increased risk of noncancer death due to radiation exposure could be attributed solely to misclassification of causes of death on death certificates. Cancer and noncancer misclassification rates and their dependence on age at death were estimated from a series of autopsies performed on LSS participants between 1961 and 1975. The crude misclassification rates were 20% for cancer and 2.8% for noncancer. Although the noncancer dose response remained significant, correcting for this amount of misclassification reduced the estimated noncancer excess relative risk (ERR) at 1 Gy exposure by 21% and the number of excess noncancer deaths in the cohort by 23%. The estimated cancer ERR at 1 Gy was increased by 12% and the excess cancer deaths by 16% as a result of the correction. The statistical significance of the noncancer dose response was relatively insensitive to underestimating the cancer misclassification rate, but was sensitive to assuming that cancer misclassification was positively associated with dose. We discuss the implementation of the EM algorithm for adjusting for misclassification and extensions of the method to more than two causes of death. (author)
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
Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.
2011-01-01
Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…
Pulmonary inflammation and crystalline silica in respirable coal mine dust: dose-response
Indian Academy of Sciences (India)
E D Kuempel; M D Attfield; V Vallyathan; N L Lapp; J M Hale; R J Smith; V Castranova
2003-02-01
This study describes the quantitative relationships between early pulmonary responses and the estimated lungburden or cumulative exposure of respirable-quartz or coal mine dust. Data from a previous bronchoalveolar lavage (BAL) study in coal miners ( = 20) and nonminers ( = 16) were used including cell counts of alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs), and the antioxidant superoxide dismutase (SOD) levels. Miners’ individual working lifetime particulate exposures were estimated from work histories and mine air sampling data, and quartz lung-burdens were estimated using a lung dosimetry model. Results show that quartz, as either cumulative exposure or estimated lung-burden, was a highly statistically significant predictor of PMN response ( < 0.0001); however cumulative coal dust exposure did not significantly add to the prediction of PMNs ( = 0.2) above that predicted by cumulative quartz exposure ( < 0.0001). Despite the small study size, radiographic category was also significantly related to increasing levels of both PMNs and quartz lung burden (-values < 0.04). SOD in BAL fluid rose linearly with quartz lung burden ( < 0.01), but AM count in BAL fluid did not ( > 0.4). This study demonstrates dose-response relationships between respirable crystalline silica in coal mine dust and pulmonary inflammation, antioxidant production, and radiographic small opacities.
Statistical significance criteria for the rWG and average deviation interrater agreement indices.
Smith-Crowe, Kristin; Burke, Michael J; Cohen, Ayala; Doveh, Etti
2014-03-01
Despite the widespread use of interrater agreement statistics for multilevel modeling and other types of research, the existing guidelines for inferring the statistical significance of interrater agreement are quite limited. They are largely relevant only under conditions that numerous researchers have argued rarely exist. Here we address this problem by generating guidelines for inferring statistical significance under a number of conditions via a computer simulation. As a set, these guidelines cover many of the conditions researchers commonly face. We discuss how researchers can use the guidelines presented to more reasonably infer the statistical significance of interrater agreement relative to using the limited guidelines available in the extant literature. PMID:24099346
Assessing genome-wide statistical significance for large p small n problems.
Diao, Guoqing; Vidyashankar, Anand N
2013-07-01
Assessing genome-wide statistical significance is an important issue in genetic studies. We describe a new resampling approach for determining the appropriate thresholds for statistical significance. Our simulation results demonstrate that the proposed approach accurately controls the genome-wide type I error rate even under the large p small n situations. PMID:23666935
Thompson, Bruce
Given some consensus that statistical significance tests are broken, misused, or at least have somewhat limited utility, the focus of discussion within the field ought to move beyond additional bashing of statistical significance tests, and toward more constructive suggestions for improved practice. Five suggestions for improved practice are…
"What If" Analyses: Ways to Interpret Statistical Significance Test Results Using EXCEL or "R"
Ozturk, Elif
2012-01-01
The present paper aims to review two motivations to conduct "what if" analyses using Excel and "R" to understand the statistical significance tests through the sample size context. "What if" analyses can be used to teach students what statistical significance tests really do and in applied research either prospectively to estimate what sample size…
Norris, John M.
2015-01-01
Traditions of statistical significance testing in second language (L2) quantitative research are strongly entrenched in how researchers design studies, select analyses, and interpret results. However, statistical significance tests using "p" values are commonly misinterpreted by researchers, reviewers, readers, and others, leading to…
Obrochta, S. P.; Crowley, T. J.
2005-12-01
Multitaper and maximum entropy methods were used to determine the statistical significance and frequency, respectively, of millennial-band peaks in late Pleistocene glacial intervals of geochemical, petrological, and physical property time series generated from marine sediment cores, including ODP Site 980 and IODP Site U1308 (Reoccupied DSDP Site 609). A preliminary age model for Site U1308 was created by correlating the sediment lightness (L*) record to the Site 980 ?18O record. Marine Isotope Stages (MIS) 2-3 (Wisconsin glaciation), 6 (Penultimate glaciation), 8, 10, and 12 were analyzed as individual time series and interpolated to the average sampling resolution of each respective glacial interval. Results indicate the existence of many peaks statistically significant at a 95% or greater confidence interval within each individual glacial-interval time series. One may be tempted to accept each of these peaks as physically significant; however, the probability that a particular peak is significant by chance alone (i.e., 5% chance given a 95% confidence interval), must be considered. For example, Hyde and Crowley (2002) generated millennial-scale peaks significant at a 95% confidence interval in a 120 k.y. model run forced by white noise at a 100-year time step. Given these model results, we exercise caution in the interpretation of physical significance of peaks in the sediment core time series, placing physical significance only on peaks that consistently appear in most of the series.
Directory of Open Access Journals (Sweden)
Hayek Lee-Ann C.
2005-01-01
Full Text Available Several analytic techniques have been used to determine sexual dimorphism in vertebrate morphological measurement data with no emergent consensus on which technique is superior. A further confounding problem for frog data is the existence of considerable measurement error. To determine dimorphism, we examine a single hypothesis (Ho = equal means for two groups (females and males. We demonstrate that frog measurement data meet assumptions for clearly defined statistical hypothesis testing with statistical linear models rather than those of exploratory multivariate techniques such as principal components, correlation or correspondence analysis. In order to distinguish biological from statistical significance of hypotheses, we propose a new protocol that incorporates measurement error and effect size. Measurement error is evaluated with a novel measurement error index. Effect size, widely used in the behavioral sciences and in meta-analysis studies in biology, proves to be the most useful single metric to evaluate whether statistically significant results are biologically meaningful. Definitions for a range of small, medium, and large effect sizes specifically for frog measurement data are provided. Examples with measurement data for species of the frog genus Leptodactylus are presented. The new protocol is recommended not only to evaluate sexual dimorphism for frog data but for any animal measurement data for which the measurement error index and observed or a priori effect sizes can be calculated.
Proton therapy radiation pneumonitis local dose–response in esophagus cancer patients
International Nuclear Information System (INIS)
Purpose: This study quantifies pulmonary radiation toxicity in patients who received proton therapy for esophagus cancer. Materials/methods: We retrospectively studied 100 esophagus cancer patients treated with proton therapy. The linearity of the enhanced FDG uptake vs. proton dose was evaluated using the Akaike Information Criterion (AIC). Pneumonitis symptoms (RP) were assessed using the Common Toxicity Criteria for Adverse Events version 4.0 (CTCAEv4). The interaction of the imaging response with dosimetric parameters and symptoms was evaluated. Results: The RP scores were: 0 grade 4/5, 7 grade 3, 20 grade 2, 37 grade 1, and 36 grade 0. Each dosimetric parameter was significantly higher for the symptomatic group. The AIC winning models were 30 linear, 52 linear quadratic, and 18 linear logarithmic. There was no significant difference in the linear coefficient between models. The slope of the FDG vs. proton dose response was 0.022 for the symptomatic and 0.012 for the asymptomatic (p = 0.014). Combining dosimetric parameters with the slope did not improve the sensitivity or accuracy in identifying symptomatic cases. Conclusions: The proton radiation dose response on FDG PET/CT imaging exhibited a predominantly linear dose response on modeling. Symptomatic patients had a higher dose response slope
DEFF Research Database (Denmark)
Appelt, A. L.; Ploen, J.
2013-01-01
Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D-50,D-TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), gamma(50,TRG1) = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D-50,D-TRG1&2 = 72.1 Gy (CI 65.3-94.0 Gy), gamma(50,TRG1&2) = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered. (C) 2013 Elsevier Inc.
Statistically significant length-scale of filaments as a robust measure of galaxy distribution
Pandey, Biswajit
2010-02-01
We have used a statistical technique `Shuffle' in seven nearly two-dimensional strips from the Sloan Digital Sky Survey Data Release 6 (SDSS DR6) to test if the statistically significant length-scale of filaments depends on luminosity, colour and morphology of galaxies. We find that although the average filamentarity depends on these galaxy properties, the statistically significant length-scale of filaments does not depend on them. We compare its measured values in SDSS against the predictions of ? cold dark matter (?CDM) N-body simulations and find that ?CDM model is consistent with observations. The average filamentarity is known to be very sensitive to the bias parameter. Using ?CDM N-body simulations, we simulate mock galaxy distributions for SDSS Northern Galactic Cap equatorial strip for different biases and test if the statistically significant length-scale of filaments depends on bias. We find that statistically significant length-scale of filaments is nearly independent of bias. This result is possibly related to the fact that statistically significant length-scale of filaments is nearly the same for different classes of galaxies which are differently biased with respect to underlying dark matter distribution. The average filamentarity is also known to be dependent on the galaxy number density and size of the samples. We use ?CDM dark matter N-body simulations to test if the statistically significant length-scale of filaments depends on number density of galaxies and size of the samples. Our analysis shows that the statistically significant length-scale of filaments very weakly depends on these factors. Finally, we test the reliability of our method by applying it to controlled samples of segment Cox process and find that our method successfully recovers the length of the inputted segments. Summarizing these results, we conclude that the length-scale up to which the filaments are statistically significant is a robust measure of galaxy distribution.
The statistical significance of the North-South asymmetry of solar activity revisited
Carbonell, M.; Terradas, J.; Oliver, R.; Ballester, J. L.
2007-12-01
Aims:Many studies of the North-South asymmetry of solar activity and its features have been performed. However, most of these studies do not consider whether or not the asymmetry of the time series under consideration is statistically significant. If the asymmetry is statistically insignificant, any study about its behavior is meaningless. Here, we discuss the difficulties found when trying to assess the statistical significance of the North-South asymmetry (hereafter SSNSA) of the most usually considered time series of solar activity. Methods: We distinguish between solar activity time series composed of integer or non-integer and dimensionless data, or composed of non-integer and dimensional data. For each of these cases, we discuss the most suitable statistical tests which can be applied and highlight the difficulties in obtaining valid information about the statistical significance of solar activity time series. Results: Our results suggest that, apart from the need to apply suitable statistical tests, other effects such as data binning, the considered units and the need, in some tests, to consider groups of data, substantially affect the determination of the statistical significance of the asymmetry. Conclusions: The assessment of the statistical significance of the N-S asymmetry of solar activity is difficult and an absolute answer cannot be given, since many different effects influence the results given by the statistical tests. The quantitative results about the statistical significance of the N-S asymmetry of solar activity provided by different authors, as well as studies of its behaviour, must be considered with care because they depend on the chosen values of different parameters or on the considered units.
Fidalgo, Angel M.; Alavi, Seyed Mohammad; Amirian, Seyed Mohammad Reza
2014-01-01
This study examines three controversial aspects in differential item functioning (DIF) detection by logistic regression (LR) models: first, the relative effectiveness of different analytical strategies for detecting DIF; second, the suitability of the Wald statistic for determining the statistical significance of the parameters of interest; and…
Sullivan, Jeremy R.
2001-01-01
Summarizes the post-1994 literature in psychology and education regarding statistical significance testing, emphasizing limitations and defenses of statistical testing and alternatives or supplements to statistical significance testing. (SLD)
Tornetta Paul; Siegel Judith; Sung Jinsil; Bhandari Mohit
2008-01-01
Abstract Background Evidence-based medicine posits that health care research is founded upon clinically important differences in patient centered outcomes. Statistically significant differences between two treatments may not necessarily reflect a clinically important difference. We aimed to quantify the sample sizes and magnitude of treatment effects in a review of orthopaedic randomized trials with statistically significant findings. Methods We conducted a comprehensive search (PubMed, Cochr...
Statistical power and significance testing in large-scale genetic studies.
Sham, Pak C; Purcell, Shaun M
2014-05-01
Significance testing was developed as an objective method for summarizing statistical evidence for a hypothesis. It has been widely adopted in genetic studies, including genome-wide association studies and, more recently, exome sequencing studies. However, significance testing in both genome-wide and exome-wide studies must adopt stringent significance thresholds to allow multiple testing, and it is useful only when studies have adequate statistical power, which depends on the characteristics of the phenotype and the putative genetic variant, as well as the study design. Here, we review the principles and applications of significance testing and power calculation, including recently proposed gene-based tests for rare variants. PMID:24739678
Setting the Statistical Significance of Detections of Non-Gaussianity in the WMAP Data
Cayón, L.
2007-11-01
Several works have claimed the detection of deviations from Gaussianity in the WMAP data. Different test statistics have been used in the multiple analyses carried out in real, spherical harmonic and wavelet spaces. The statistical significance of these detections has, in most cases, been set either by considering a single configuration or by defining a ? ^2 function that takes into account the multiple tests performed. I. Szapudi raises a very important question in his contribution. He introduces the application of the False Discovery Rate as a method for massive hypothesis testing in CMB data analyses. Could this be a viable method to set the statistical significance of the claimed non-Gaussian detections?, is it possible to define a method to set the statistical significance taking into account all tests performed?. We will comment on these issues and will present some examples of the application of False Discovery Rate in this context.
Scientific Electronic Library Online (English)
Lee-Ann C., Hayek; W. Ronald, Heyer.
2005-03-01
Full Text Available Técnicas analíticas variadas têm sido usadas para avaliar o dimorfismo sexual em medidas de vertebrados, mas não há consenso sobre o melhor procedimento. Um problema adicional, no caso dos anfíbios, é a presença de ponderável erro de medida. Para analisar dimorfismo sexual examinamos uma única hipót [...] ese (Ho = médias iguais) para dois grupos (fêmeas e machos). Demonstramos que dados de anfíbios preenchem as premissas para hipóteses estatísticas claramente definidas, usando modelos lineares em vez de técnicas exploratórias multivaraiadas, tais como components principais, correlação ou análise de correspondências. Para distinguir significância biológica de significância estatística nas hipóteses, propomos um protocolo incorporando erro de medida e "effect size". O erro de medida é avaliado por meio de um novo índice específico. Demonstramos que "effect size", amplamente usado nas ciências do comportamento e em meta-análises biológicas, é a medida mais útil na discriminação entre significância biológica e significância estatística. São dadas definições de uma ampla gama de "effect sizes" para dados anfibiológicos. São apresentados exemplos com medidas do gênero Leptodactylus. O novo protocolo é recomenadado não apenas no caso de anfíbios, mas em todos os casos de vertebrados em que possam ser calculados erros de medida e "effect sizes" observados ou determinados a priori. Abstract in english Several analytic techniques have been used to determine sexual dimorphism in vertebrate morphological measurement data with no emergent consensus on which technique is superior. A further confounding problem for frog data is the existence of considerable measurement error. To determine dimorphism, w [...] e examine a single hypothesis (Ho = equal means) for two groups (females and males). We demonstrate that frog measurement data meet assumptions for clearly defined statistical hypothesis testing with statistical linear models rather than those of exploratory multivariate techniques such as principal components, correlation or correspondence analysis. In order to distinguish biological from statistical significance of hypotheses, we propose a new protocol that incorporates measurement error and effect size. Measurement error is evaluated with a novel measurement error index. Effect size, widely used in the behavioral sciences and in meta-analysis studies in biology, proves to be the most useful single metric to evaluate whether statistically significant results are biologically meaningful. Definitions for a range of small, medium, and large effect sizes specifically for frog measurement data are provided. Examples with measurement data for species of the frog genus Leptodactylus are presented. The new protocol is recommended not only to evaluate sexual dimorphism for frog data but for any animal measurement data for which the measurement error index and observed or a priori effect sizes can be calculated.
On the statistical significance of surface air temperature trends in the Eurasian Arctic region
Franzke, Christian
2013-04-01
This study investigates the statistical significance of the trends of station temperature time series from the European Climate Assessment & Data archive poleward of 60°N. The trends are identified by different methods and their significance is assessed by three different null models of climate noise. We find that all stations have a warming trend. The statistical significance depends on the null model used. We also find that the signal-to-noise ratio of the stations is low. The implications for Arctic climate change and predictability will be discussed.
Dose response curve of 60Co for premature condensed chromosome fragments of human lymphocytes
International Nuclear Information System (INIS)
The dose-response curves obtained by premature condensed chromosome (PCC) and conventional cellular genetic methods can be represented by two linear equations. The ratio of the slopes, KPCC/KM1, is about 28. In comparison to the conventional method, the PCC method has many advantages; e.g. it is faster, simpler, more sensitive and accurate. Its significance in the study of radiation damage is also discussed
Testing effect of a drug using multiple nested models for the dose-response
DEFF Research Database (Denmark)
Baayen, C; Hougaard, P
2015-01-01
During development of a drug, typically the choice of dose is based on a Phase II dose-finding trial, where selected doses are included with placebo. Two common statistical dose-finding methods to analyze such trials are separate comparisons of each dose to placebo (using a multiple comparison procedure) or a model-based strategy (where a dose-response model is fitted to all data). The first approach works best when patients are concentrated on few doses, but cannot conclude on doses not tested. Model-based methods allow for interpolation between doses, but the validity depends on the correctness of the assumed dose-response model. Bretz et al. (2005, Biometrics 61, 738-748) suggested a combined approach, which selects one or more suitable models from a set of candidate models using a multiple comparison procedure. The method initially requires a priori estimates of any non-linear parameters of the candidate models, such that there is still a degree of model misspecification possible and one can only evaluateone or a few special cases of a general model. We propose an alternative multiple testing procedure, which evaluates a candidate set of plausible dose-response models against each other to select one final model. The method does not require any a priori parameter estimates and controls the Type I error rate of selecting a too complex model.
Testing effect of a drug using multiple nested models for the dose–response
DEFF Research Database (Denmark)
Baayen, C.; Hougaard, P.
2015-01-01
During development of a drug, typically the choice of dose is based on a Phase II dose?finding trial, where selected doses are included with placebo. Two common statistical dose?finding methods to analyze such trials are separate comparisons of each dose to placebo (using a multiple comparison procedure) or a model?based strategy (where a dose–response model is fitted to all data). The first approach works best when patients are concentrated on few doses, but cannot conclude on doses not tested. Model?based methods allow for interpolation between doses, but the validity depends on the correctness of the assumed dose–response model. Bretz et al. (2005, Biometrics 61, 738–748) suggested a combined approach, which selects one or more suitable models from a set of candidate models using a multiple comparison procedure. The method initially requires a priori estimates of any non?linear parameters of the candidate models, such that there is still a degree of model misspecification possible and one can only evaluate one or a few special cases of a general model. We propose an alternative multiple testing procedure, which evaluates a candidate set of plausible dose–response models against each other to select one final model. The method does not require any a priori parameter estimates and controls the Type I error rate of selecting a too complex model.
Directory of Open Access Journals (Sweden)
Zhang Zhang
2012-03-01
Full Text Available Abstract Background Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB. Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis. Results Here we propose a novel measure--Codon Deviation Coefficient (CDC--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance. Conclusions As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions.
Zhang, Zhang
2012-03-22
Background: Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis.Results: Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance.Conclusions: As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions. 2012 Zhang et al; licensee BioMed Central Ltd.
Rudd, James; Moore, Jason H.; Urbanowicz, Ryan J
2013-01-01
Permutation-based statistics for evaluating the significance of class prediction, predictive attributes, and patterns of association have only appeared within the learning classifier system (LCS) literature since 2012. While still not widely utilized by the LCS research community, formal evaluations of test statistic confidence are imperative to large and complex real world applications such as genetic epidemiology where it is standard practice to quantify the likelihood that a seemingly mean...
Chládek, J; Brázdil, M; Halámek, J; Plešinger, F; Jurák, P
2013-01-01
We present an off-line analysis procedure for exploring brain activity recorded from intra-cerebral electroencephalographic data (SEEG). The objective is to determine the statistical differences between different types of stimulations in the time-frequency domain. The procedure is based on computing relative signal power change and subsequent statistical analysis. An example of characteristic statistically significant event-related de/synchronization (ERD/ERS) detected across different frequency bands following different oddball stimuli is presented. The method is used for off-line functional classification of different brain areas. PMID:24109865
International Nuclear Information System (INIS)
Purpose: To apply a statistical bootstrap analysis to assess the uncertainty in the dose–response relation for the endpoints pneumonitis and myelopathy reported in the QUANTEC review. Methods and Materials: The bootstrap method assesses the uncertainty of the estimated population-based dose-response relation due to sample variability, which reflects the uncertainty due to limited numbers of patients in the studies. A large number of bootstrap replicates of the original incidence data were produced by random sampling with replacement. The analysis requires only the dose, the number of patients, and the number of occurrences of the studied endpoint, for each study. Two dose–response models, a Poisson-based model and the Lyman model, were fitted to each bootstrap replicate using maximum likelihood. Results: The bootstrap analysis generates a family of curves representing the range of plausible dose–response relations, and the 95% bootstrap confidence intervals give an estimated upper and lower toxicity risk. The curve families for the 2 dose–response models overlap for doses included in the studies at hand but diverge beyond that, with the Lyman model suggesting a steeper slope. The resulting distributions of the model parameters indicate correlation and non-Gaussian distribution. For both data sets, the likelihood of the observed data was higher for the Lyman model in >90% of the bootstrap replicates. Conclusions: The bootstrap method provides a statistical analysis of the uncertainty in the estimated dose–response relation for myelopathy and pneumonitis. It suggests likely values of model parameter values, their confidence intervals, and how they interrelate for each model. Finally, it can be used to evaluate to what extent data supports one model over another. For both data sets considered here, the Lyman model was preferred over the Poisson-based model
Statistical Significance of the Trends in the Extremes of Precipitation Over the US
Mahajan, S.; North, G. R.; Saravanan, R.; Genton, M. G.
2005-12-01
Extremes of precipitation have significant social and economic impacts. Recently, it has been postulated that the extremes of precipitation are on the increase over the past decades, and that this is due to anthropogenic climate change. Any systematic increase in the extremes of precipitation is a matter of great concern as extreme events can significantly disrupt human lives. Observational studies also suggest that there has been an increase in floods and droughts in the past decades, but it is difficult to assess their statistical significance as the real world provides just one realization of the stochastic behavior associated with precipitation variability. In this study, we attempt to test the statistical significance of increasing trends in the extremes of precipitation over the United States over the past few decades using the Monte Carlo technique. We use monthly precipitation data from various stations spread out across the US to look for a statistically significant trend. It is assumed that the distribution of monthly precipitation over a station can be approximated by the log-normal distribution. Multivariate analysis is used to generate synthetic data for the Monte Carlo tests, taking into account spatial correlations between different stations. Trends in precipitation extremes are computed for different realizations of the synthetic data, and this ensemble of trends is used to establish the 95% confidence interval for the trends. The observed trend is tested for statistical significance under these confidence intervals. A positive trend is observed but is found not to be statistically significant. We also apply the Monte Carlo test to precipitation data obtained from various coupled and uncoupled general circulation models for different climate change scenario integrations. No significant trends are found in most of the control integrations for the climate of the 20th century, thus establishing the robustness of our test. Climate change projections for the 21st century, however, display a significant positive trend, implying a role for anthropogenic forcing in the increasing extremes of precipitation in the future.
Effect of specific resistance training on musculoskeletal pain symptoms : dose-response relationship
DEFF Research Database (Denmark)
Pedersen, Mogens Theisen; Andersen, Lars L
2013-01-01
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.
Directory of Open Access Journals (Sweden)
FionaFidler
2010-07-01
Full Text Available A statistically significant result, and a non-significant result may differ little, although significance status may tempt an interpretation of difference. Two studies are reported that compared interpretation of such results presented using null hypothesis significance testing (NHST, or confidence intervals (CIs. Authors of articles published in psychology, behavioural neuroscience, and medical journals were asked, via email, to interpret two fictitious studies that found similar results, one statistically significant, and the other non-significant. Responses from 330 authors varied greatly, but interpretation was generally poor, whether results were presented as CIs or using NHST. However, when interpreting CIs respondents who mentioned NHST were 60% likely to conclude, unjustifiably, the two results conflicted, whereas those who interpreted CIs without reference to NHST were 95% likely to conclude, justifiably, the two results were consistent. Findings were generally similar for all three disciplines. An email survey of academic psychologists confirmed that CIs elicit better interpretations if NHST is not invoked. Improved statistical inference can result from encouragement of meta-analytic thinking and use of CIs but, for full benefit, such highly desirable statistical reform requires also that researchers interpret CIs without recourse to NHST.
Radiation Dose-Response Relationships and Risk Assessment
International Nuclear Information System (INIS)
The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is also the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of individual risk is presented. The chapter ends with conclusions and recommendations.
Telford, R. J.; Birks, H. J. B.
2011-05-01
We present a method to test the statistical significance of a quantitative palaeoenvironmental reconstruction inferred from biotic assemblages with a transfer function. A reconstruction is considered statistically significant if it explains more of the variance in the fossil data than most reconstructions derived from transfer functions trained on random environmental data. Given reconstructions of several environmental variables from the same fossil proxy, the method can determine which is the best reconstruction, and if there is sufficient information in the proxy data to support multiple independent reconstructions. Reconstructions that fail this test have limited credibility and should be interpreted with considerable caution.
International Nuclear Information System (INIS)
Purpose: MR-Linac devices under development worldwide will require standard calibration, commissioning, and quality assurance. Solid state radiation detectors are often used for dose profiles and percent depth dose measurements. The dose response of selected solid state detectors is therefore evaluated in varying transverse and longitudinal magnetic fields for this purpose. Methods: The Monte Carlo code PENELOPE was used to model irradiation of a PTW 60003 diamond detector and IBA PFD diode detector in the presence of a magnetic field. The field itself was varied in strength, and oriented both transversely and longitudinally with respect to the incident photon beam. The long axis of the detectors was oriented either parallel or perpendicular to the photon beam. The dose to the active volume of each detector in air was scored, and its ratio to dose with zero magnetic field strength was determined as the “dose response” in magnetic field. Measurements at low fields for both detectors in transverse magnetic fields were taken to evaluate the accuracy of the simulations. Additional simulations were performed in a water phantom to obtain few representative points for beam profile and percent depth dose measurements. Results: Simulations show significant dose response as a function of magnetic field in transverse field geometries. This response can be near 20% at 1.5 T, and it is highly dependent on the detectors’ relative orientation to the magnetic field, the energy of the photon beam, and detector composition. Measurements at low transverse magnetic fields verify the simulations for both detectors in their relative orientations to radiation beam. Longitudinal magnetic fields, in contrast, show little dose response, rising slowly with magnetic field, and reaching 0.5%–1% at 1.5 T regardless of detector orientation. Water tank and in air simulation results were the same within simulation uncertainty where lateral electronic equilibrium is present and expectedly differed at the beam edge in transverse field orientations only. Due to the difference in design, the two detectors behaved differently. Conclusions: When transverse magnetic fields are present, great care must be taken when using diamond or diode detectors. Dose response varies with relative detector orientation, magnetic field strength, and between detectors. This response can be considerable (?20% for both detectors). Both detectors in longitudinal fields exhibit little to no dose response as a function of magnetic field. Water tank simulations seem to suggest that the diode detector is better suited to general beam commissioning, and each detector must be investigated separately
DEFF Research Database (Denmark)
Larsen, Steffen Falgreen; Laursen, Maria Bach
2014-01-01
BACKGROUND: In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. RESULTS: First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based methodfor assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological interpretations. CONCLUSION: Time independent summary statistics may aid the understanding of drugs' action mechanism on tumour cells and potentially renew previous drug sensitivity evaluation studies.
Fidler, Fiona; Burgman, Mark A; Cumming, Geoff; Buttrose, Robert; Thomason, Neil
2006-10-01
Over the last decade, criticisms of null-hypothesis significance testing have grown dramatically, and several alternative practices, such as confidence intervals, information theoretic, and Bayesian methods, have been advocated. Have these calls for change had an impact on the statistical reporting practices in conservation biology? In 2000 and 2001, 92% of sampled articles in Conservation Biology and Biological Conservation reported results of null-hypothesis tests. In 2005 this figure dropped to 78%. There were corresponding increases in the use of confidence intervals, information theoretic, and Bayesian techniques. Of those articles reporting null-hypothesis testing--which still easily constitute the majority--very few report statistical power (8%) and many misinterpret statistical nonsignificance as evidence for no effect (63%). Overall, results of our survey show some improvements in statistical practice, but further efforts are clearly required to move the discipline toward improved practices. PMID:17002771
Matsuda, Fumio; Tsugawa, Hiroshi; Fukusaki, Eiichiro
2013-09-01
A novel method for assessing the statistical significance of mass spectral similarities was developed using modified basic local alignment search tool (BLAST; Karlin-Altschul) statistics. In gas chromatography/mass spectrometry-based metabolomics, many signals in raw metabolome data are identified on the basis of unexpected similarities among mass spectra and the spectra of standards. Since there is inevitably noise in the observed spectra, a list of identified metabolites includes some false positives. In the developed method, electron ionization (EI) mass spectrometry-BLAST, a similarity score of two mass spectra is calculated using a general scoring scheme, from which the probability of obtaining the score by chance (P value) is calculated. For this purpose, a simple rule for converting a unit EI mass spectrum to a mass spectral sequence as well as a score matrix for aligned mass spectral sequences was developed. A Monte Carlo simulation using randomly generated mass spectral sequences demonstrated that the null distribution or the expected number of hits (E value) follows modified Karlin-Altschul statistics. A metabolite data set obtained from green tea extract was analyzed using the developed method. Among 171 metabolite signals in the metabolome data, 93 signals were identified on the basis of significant similarities (P < 0.015) with reference data. Since the expected number of false positives is 2.6, the false discovery rate was estimated to be 2.8%, indicating that the search threshold (P < 0.015) is reasonable for metabolite identification. PMID:23944154
Directory of Open Access Journals (Sweden)
Yang Yaning
2003-12-01
Full Text Available Abstract Background With the increasing amount of data generated in molecular genetics laboratories, it is often difficult to make sense of results because of the vast number of different outcomes or variables studied. Examples include expression levels for large numbers of genes and haplotypes at large numbers of loci. It is then natural to group observations into smaller numbers of classes that allow for an easier overview and interpretation of the data. This grouping is often carried out in multiple steps with the aid of hierarchical cluster analysis, each step leading to a smaller number of classes by combining similar observations or classes. At each step, either implicitly or explicitly, researchers tend to interpret results and eventually focus on that set of classes providing the "best" (most significant result. While this approach makes sense, the overall statistical significance of the experiment must include the clustering process, which modifies the grouping structure of the data and often removes variation. Results For hierarchically clustered data, we propose considering the strongest result or, equivalently, the smallest p-value as the experiment-wise statistic of interest and evaluating its significance level for a global assessment of statistical significance. We apply our approach to datasets from haplotype association and microarray expression studies where hierarchical clustering has been used. Conclusion In all of the cases we examine, we find that relying on one set of classes in the course of clustering leads to significance levels that are too small when compared with the significance level associated with an overall statistic that incorporates the process of clustering. In other words, relying on one step of clustering may furnish a formally significant result while the overall experiment is not significant.
Eddy, Sean R
2008-01-01
Sequence database searches require accurate estimation of the statistical significance of scores. Optimal local sequence alignment scores follow Gumbel distributions, but determining an important parameter of the distribution (?) requires time-consuming computational simulation. Moreover, optimal alignment scores are less powerful than probabilistic scores that integrate over alignment uncertainty (“Forward” scores), but the expected distribution of Forward scores remains unknown. Here, I con...
Recent Literature on Whether Statistical Significance Tests Should or Should Not Be Banned.
Deegear, James
This paper summarizes the literature regarding statistical significant testing with an emphasis on recent literature in various discipline and literature exploring why researchers have demonstrably failed to be influenced by the American Psychological Association publication manual's encouragement to report effect sizes. Also considered are…
Interpreting Statistical Significance Test Results: A Proposed New "What If" Method.
Kieffer, Kevin M.; Thompson, Bruce
As the 1994 publication manual of the American Psychological Association emphasized, "p" values are affected by sample size. As a result, it can be helpful to interpret the results of statistical significant tests in a sample size context by conducting so-called "what if" analyses. However, these methods can be inaccurate unless "corrected" effect…
Linting, Marielle; van Os, Bart Jan; Meulman, Jacqueline J.
2011-01-01
In this paper, the statistical significance of the contribution of variables to the principal components in principal components analysis (PCA) is assessed nonparametrically by the use of permutation tests. We compare a new strategy to a strategy used in previous research consisting of permuting the columns (variables) of a data matrix…
Spinella, Sarah
2011-01-01
As result replicability is essential to science and difficult to achieve through external replicability, the present paper notes the insufficiency of null hypothesis statistical significance testing (NHSST) and explains the bootstrap as a plausible alternative, with a heuristic example to illustrate the bootstrap method. The bootstrap relies on…
Statistical significance of trends in monthly heavy precipitation over the US
Mahajan, Salil; North, Gerald R.; Saravanan, R.; Genton, Marc G.
2012-04-01
Trends in monthly heavy precipitation, defined by a return period of one year, are assessed for statistical significance in observations and Global Climate Model (GCM) simulations over the contiguous United States using Monte Carlo non-parametric and parametric bootstrapping techniques. The results from the two Monte Carlo approaches are found to be similar to each other, and also to the traditional non-parametric Kendall's ? test, implying the robustness of the approach. Two different observational data-sets are employed to test for trends in monthly heavy precipitation and are found to exhibit consistent results. Both data-sets demonstrate upward trends, one of which is found to be statistically significant at the 95% confidence level. Upward trends similar to observations are observed in some climate model simulations of the twentieth century, but their statistical significance is marginal. For projections of the twenty-first century, a statistically significant upwards trend is observed in most of the climate models analyzed. The change in the simulated precipitation variance appears to be more important in the twenty-first century projections than changes in the mean precipitation. Stochastic fluctuations of the climate-system are found to be dominate monthly heavy precipitation as some GCM simulations show a downwards trend even in the twenty-first century projections when the greenhouse gas forcings are strong.
International Nuclear Information System (INIS)
The difficulties involved in the control of biological and radioimmunological assay systems, and in the maintenance of standard, as well as, the usual heterogeneity of assayed samples require some evidence of similarity between the dose-response curves obtained with the standard and the sample. Nowadays the parallelism test is used to provide such evidence. However, some indications of non-normal errors distribution, such as the presence of out layers, render the parallelism test both conceptually implausible and statistically inefficient. In such a manner we suggest the non-parametric 'frequencial' test as a more sounding option. (author)
Model Averaging Software for Dichotomous Dose Response Risk Estimation
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Matthew W. Wheeler
2008-02-01
Full Text Available Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD, ?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.
Polebitski, A.; Steinschneider, S.; Brown, C. M.
2011-12-01
The cascade of uncertainty that underscores climate impact assessments of regional hydrology undermines their value for long-term water resources planning and management. Innovative approaches are required to unravel these uncertainties and formally test the significance of hydrologic alteration under future climate scenarios. This study presents a statistical framework that tests the likelihood of significant hydrologic alteration under assumed future climates. Hydrologic model uncertainty is formally characterized to enable accurate prediction intervals that can determine the statistical significance of differences between altered and baseline hydrologic simulations. Different sources of hydrologic model error are accounted for using a Bayesian approach. The sampling distribution of model errors is formally characterized to quantify predictive skill, and Markov-Chain Monte Carlo sampling is used to infer the posterior distributions of both hydrologic and error model parameters. Parameter and model uncertainties are integrated to develop accurate prediction intervals for streamflow estimates. Baseline and future hydrologic regimes are then simulated from historic and future climate data downscaled from global circulation model simulations. Predictive inference is utilized to determine the significance of hydrologic alteration between the baseline and future regimes. A case study is conducted on the White River in Vermont. Results indicate that the statistical method can help distinguish between significant alterations and errors inherent to the hydrologic model. The proposed method could prove valuable for informing climate change adaptation investments for water resources systems.
Padilla, Pablo; Ramírez, Javier; Górriz, Juan Manuel; Salas-González, Diego; Alvarez-Illán, Ignacio
2014-01-01
This paper presents the analysis of the statistical significance in the selection of the ROI for the discriminant analysis of brain images to identify Parkinson patients or subjects without any pathology. The particular features and brain functional patterns of the Parkinson's disease cause that there are regions that conveniently reveal the presence of the pathology, in this case mainly the striatum region. The selection of the brain mask makes incidence in two main aspects: the selection of the region of interest (striatum and surrounding area) for the analysis, but also the selection of the region without significance, which is the reference area for the intensity normalization, previous to the analysis. This work studies the statistical significance in the selection of ROIs in 3D brain images for Parkinson, depending on the objective to be achieved in the posterior analysis process. PMID:25488207
DEFF Research Database (Denmark)
Jones, Allan; Sommerlund, Bo
2007-01-01
The uses of null hypothesis significance testing (NHST) and statistical power analysis within psychological research are critically discussed. The article looks at the problems of relying solely on NHST when dealing with small and large sample sizes. The use of power-analysis in estimating the potential error introduced by small and large samples is advocated. Power analysis is not recommended as a replacement to NHST but as an additional source of information about the phenomena under investigation. Moreover, the importance of conceptual analysis in relation to statistical analysis of hypothesis is emphasised.
Significance Tests and Statistical Inequalities for Segmentation by Region Growing on Graph
Née, Guillaume; Jehan-Besson, Stéphanie; Brun, Luc; Revenu, Marinette
Bottom-up segmentation methods merge similar neighboring regions according to a decision rule and a merging order. In this paper, we propose a contribution for each of these two points. Firstly, under statistical hypothesis of similarity, we provide an improved decision rule for region merging based on significance tests and the recent statistical inequality of McDiarmid. Secondly, we propose a dynamic merging order based on our merging predicate. This last heuristic is justified by considering an energy minimisation framework. Experimental results on both natural and medical images show the validity of our method.
Quantitative Methods in Toxicology for Human Dose-Response Assessment
Kramer HJ; Jansen EHJM; Zeilmaker MJ; Kranen HJ van; Kroese ED
2007-01-01
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...
Haam, E.; Huybers, P.
2011-12-01
Millennial scale climate variations are observed in proxy records from around the world. However, it has been difficult to determine whether the covariance between them implies coupled variations or whether these are independent because of the time-uncertainties between the proxy records. An updated version of a Maximum Covariance of Time-uncertain Series Test is presented and used to compute the significances of the covariance among the 22 time-uncertain proxy records, including those from Greenland, Antarctica, Asia, and the Pacific and Atlantic Oceans. Patterns of statistical significance, especially in the Northern Hemisphere and with Antarctic Ice Cores whose potential physical significance is discussed.
Jewett, M. E.; Dijk, D. J.; Kronauer, R. E.; Dinges, D. F.
1999-01-01
Although it has been well documented that sleep is required for human performance and alertness to recover from low levels after prolonged periods of wakefulness, it remains unclear whether they increase in a linear or asymptotic manner during sleep. It has been postulated that there is a relation between the rate of improvement in neurobehavioral functioning and rate of decline of slow-wave sleep and/or slow-wave activity (SWS/SWA) during sleep, but this has not been verified. Thus, a cross-study comparison was conducted in which dose-response curves (DRCs) were constructed for Stanford Sleepiness Scale (SSS) and Psychomotor Vigilance Task (PVT) tests taken at 1000 hours by subjects who had been allowed to sleep 0 hours, 2 hours, 5 hours or 8 hours the previous night. We found that the DRCs to each PVT metric improved in a saturating exponential manner, with recovery rates that were similar [time constant (T) approximately 2.14 hours] for all the metrics. This recovery rate was slightly faster than, though not statistically significantly different from, the reported rate of SWS/SWA decline (T approximately 2.7 hours). The DRC to the SSS improved much more slowly than psychomotor vigilance, so that it could be fit equally well by a linear function (slope = -0.26) or a saturating exponential function (T = 9.09 hours). We conclude that although SWS/SWA, subjective alertness, and a wide variety of psychomotor vigilance metrics may all change asymptotically during sleep, it remains to be determined whether the underlying physiologic processes governing their expression are different.
Controlled Optimal Design Program for the Logit Dose Response Model
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Jiaqiao Hu
2010-10-01
Full Text Available The assessment of dose-response is an integral component of the drug development process. Parallel dose-response studies are conducted, customarily, in preclinical and phase 1, 2 clinical trials for this purpose. Practical constraints on dose range, dose levels and dose proportions are intrinsic issues in the design of dose response studies because of drug toxicity, efficacy, FDA regulations, protocol requirements, clinical trial logistics, and marketing issues. We provide a free on-line software package called Controlled Optimal Design 2.0 for generating controlled optimal designs that can incorporate prior information and multiple objectives, and meet multiple practical constraints at the same time. Researchers can either run the web-based design program or download its stand-alone version to construct the desired multiple-objective controlled Bayesian optimal designs. Because researchers often adopt ad-hoc design schemes such as the equal allocation rules without knowing how efficient such designs would be for the design problem, the program also evaluates the efficiency of user-supplied designs.
Stern, J M
2010-01-01
This book presents our case in defense of a constructivist epistemological framework and the use of compatible statistical theory and inference tools. The basic metaphor of decision theory is the maximization of a gambler's expected fortune, according to his own subjective utility, prior beliefs an learned experiences. This metaphor has proven to be very useful, leading the development of Bayesian statistics since its XX-th century revival, rooted on the work of de Finetti, Savage and others. The basic metaphor presented in this text, as a foundation for cognitive constructivism, is that of an eigen-solution, and the verification of its objective epistemic status. The FBST - Full Bayesian Significance Test - is the cornerstone of a set of statistical tolls conceived to assess the epistemic value of such eigen-solutions, according to their four essential attributes, namely, sharpness, stability, separability and composability. We believe that this alternative perspective, complementary to the one ofered by dec...
DEFF Research Database (Denmark)
Jakobsen, Janus Christian; Wetterslev, JØrn
2014-01-01
BACKGROUND: Thresholds for statistical significance when assessing meta-analysis results are being insufficiently demonstrated by traditional 95% confidence intervals and P-values. Assessment of intervention effects in systematic reviews with meta-analysis deserves greater rigour. METHODS: Methodologies for assessing statistical and clinical significance of intervention effects in systematic reviews were considered. Balancing simplicity and comprehensiveness, an operational procedure was developed, based mainly on The Cochrane Collaboration methodology and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: We propose an eight-step procedure for better validation of meta-analytic results in systematic reviews (1) Obtain the 95% confidence intervals and the P-values from both fixed-effect and random-effects meta-analyses and report the most conservative results as the main results. (2) Explore the reasons behind substantial statistical heterogeneity using sensitivity analyses. (3) To take account of problems with multiplicity adjust the thresholds for significance according to the number of primary outcomes. (4) Calculate required information sizes ([almost equal to] the a priori required number of participants for a meta-analysis to be conclusive) for all outcomes and analyse each outcome with trial sequential analysis. Report whether the trial sequential monitoring boundaries for benefit, harm, or futility are crossed. (5) Calculate Bayes factors for all primary outcomes. (6) Use subgroup analyses and sensitivity analyses to assess the potential impact of bias on the review results. (7) Assess the risk of publication bias. (8) Assess the clinical significance of the statistically significant review results. CONCLUSIONS: If followed, the proposed eight-step procedure will increase the validity of assessments of intervention effects in systematic reviews of randomised clinical trials.
Martínez-Abraín, Alejandro
2008-07-01
Unfortunately it is quite common to find papers in ecology journals in which the authors confound statistical significance with biological relevance or with strength of evidence against the null hypothesis. These mistakes are not trivial semantic problems because they may finally lead to wrong scientific conclusions, and hence to prevent long-term knowledge accumulation in ecology. Using correlation analysis as an example I present the four possible interactions that can take place between biological relevance (based on the value of the correlation coefficient as an effect size metric) and statistical significance (based on p-values). Importantly, I recall that the strength of evidence that supports the parameter estimate or the null hypothesis, given our data, can only be assessed by means of Bayes' rule.
Henderson, Douglas
2010-01-01
Henry Eyring was, and still is, a towering figure in science. Some aspects of his life and science, beginning in Mexico and continuing in Arizona, California, Wisconsin, Germany, Princeton, and finally Utah, are reviewed here. Eyring moved gradually from quantum theory toward statistical mechanics and the theory of liquids, motivated in part by his desire to understand reactions in condensed matter. Significant structure theory, while not as successful as Eyring thought, is ...
Directory of Open Access Journals (Sweden)
Tornetta Paul
2008-01-01
Full Text Available Abstract Background Evidence-based medicine posits that health care research is founded upon clinically important differences in patient centered outcomes. Statistically significant differences between two treatments may not necessarily reflect a clinically important difference. We aimed to quantify the sample sizes and magnitude of treatment effects in a review of orthopaedic randomized trials with statistically significant findings. Methods We conducted a comprehensive search (PubMed, Cochrane for all randomized controlled trials between 1/1/95 to 12/31/04. Eligible studies include those that focused upon orthopaedic trauma. Baseline characteristics and treatment effects were abstracted by two reviewers. Briefly, for continuous outcome measures (ie functional scores, we calculated effect sizes (mean difference/standard deviation. Dichotomous variables (ie infection, nonunion were summarized as absolute risk differences and relative risk reductions (RRR. Effect sizes >0.80 and RRRs>50% were defined as large effects. Using regression analysis we examined the association between the total number of outcome events and treatment effect (dichotomous outcomes. Results Our search yielded 433 randomized controlled trials (RCTs, of which 76 RCTs with statistically significant findings on 184 outcomes (122 continuous/62 dichotomous outcomes met study eligibility criteria. The mean effect size across studies with continuous outcome variables was 1.7 (95% confidence interval: 1.43–1.97. For dichotomous outcomes, the mean risk difference was 30% (95%confidence interval:24%–36% and the mean relative risk reduction was 61% (95% confidence interval: 55%–66%; range: 0%–97%. Fewer numbers of total outcome events in studies was strongly correlated with increasing magnitude of the treatment effect (Pearson's R = -0.70, p Conclusion Our review suggests that statistically significant results in orthopaedic trials have the following implications-1 On average large risk reductions are reported 2 Large treatment effects (>50% relative risk reduction are correlated with few number of total outcome events. Readers should interpret the results of such small trials with these issues in mind.
Chekanov, S. V.; Levchenko, B. B.
2007-10-01
An analytical relationship between the statistical significance of an observed signal and the signal width in the case of a large background was obtained. It can help to explain why high-energy experiments may have different conclusions on the existence of new particles. We illustrate our approach using the experimental data on searches for the ?+(1530) pentaquark state. The obtained relationship is also useful for planning of future experiments designed to search for signals of new particles in invariant-mass distributions.
On determining the statistical significance of discontinuities within ordered ecological data
International Nuclear Information System (INIS)
Current ecological theory hypothesizes that boundaries between adjacent ecosystem units are important in determining ecosystem structure and function across heterogeneous landscapes, and that such boundaries are potentially important sites for early detection of global climate change effects. Yet traditional data analysis methods focus primarily on homogeneous units rather than on the boundaries between them; thus, new methods are being developed for detecting, characterizing and classifying boundaries, e.g., split moving-window boundary analysis (SMW). SMW is a simple yet sensitive method for locating discontinuities that may exist within multivariate, serial data at various scales relative to the length of the data series. However, SMW is subjective and relative, and therefore locates apparent discontinuities even within random, serial data. In this paper they present two nonparametric methods for determining the statistical significance of discontinuities detected by SMW. First, they describe a Monte Carlo method for determining the statistical significance of scale-dependent discontinuities. Second, they propose a nonparametric, scale-independent method that is more appropriate for locating statistically significant discontinuities that separate different, relatively homogeneous groups of varying size along a series. They examine the robustness of these two methods using computer-generated data having varying intensities of imposed discontinuities, and illustrate their application to locating boundaries between vegetation samples collected at systematic intervals across a desert landscape in southern New Mexico
Alves, Gelio; Wang, Guanghui; Ogurtsov, Aleksey Y.; Drake, Steven K.; Gucek, Marjan; Suffredini, Anthony F.; Sacks, David B.; Yu, Yi-Kuo
2015-10-01
Correct and rapid identification of microorganisms is the key to the success of many important applications in health and safety, including, but not limited to, infection treatment, food safety, and biodefense. With the advance of mass spectrometry (MS) technology, the speed of identification can be greatly improved. However, the increasing number of microbes sequenced is challenging correct microbial identification because of the large number of choices present. To properly disentangle candidate microbes, one needs to go beyond apparent morphology or simple `fingerprinting'; to correctly prioritize the candidate microbes, one needs to have accurate statistical significance in microbial identification. We meet these challenges by using peptidome profiles of microbes to better separate them and by designing an analysis method that yields accurate statistical significance. Here, we present an analysis pipeline that uses tandem MS (MS/MS) spectra for microbial identification or classification. We have demonstrated, using MS/MS data of 81 samples, each composed of a single known microorganism, that the proposed pipeline can correctly identify microorganisms at least at the genus and species levels. We have also shown that the proposed pipeline computes accurate statistical significances, i.e., E-values for identified peptides and unified E-values for identified microorganisms. The proposed analysis pipeline has been implemented in MiCId, a freely available software for Microorganism Classification and Identification. MiCId is available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads.html .
Active Longitudes of the Sun: The Rotation Period and Statistical Significance
Kitchatinov, L. L.; Olemskoi, S. V.
2005-04-01
Using data from the Greenwich catalog, we determined the nonuniformity of the longitudinal distribution of sunspot groups as a function of the rotation period taken for the longitude determination. We estimated the statistical significance of the active longitudes found. A fairly high significance was achieved only for sunspot groups of the Northern Hemisphere and odd activity cycles and only for a synodic rotation period close to 28 days. In this case, one interval of active longitudes was found. The active longitudes are assumed to be associated with the fossil magnetic field frozen in the uniformly rotating radiative zone of the Sun.
Statistical significance of the rich-club phenomenon in complex networks
Jiang, Zhi-Qiang; Zhou, Wei-Xing
2008-04-01
We propose that the rich-club phenomenon in complex networks should be defined in the spirit of bootstrapping, in which a null model is adopted to assess the statistical significance of the rich-club detected. Our method can serve as a definition of the rich-club phenomenon and is applied to analyze three real networks and three model networks. The results show significant improvement compared with previously reported results. We report a dilemma with an exceptional example, showing that there does not exist an omnipotent definition for the rich-club phenomenon.
Energy Technology Data Exchange (ETDEWEB)
Reynolds, M; Fallone, B; Rathee, S [Cross Cancer Institute, Edmonton, AB (Canada)
2014-06-01
Purpose: Solid state radiation detectors are often used for dose profiles and percent depth dose measurements. The dose response of selected solid state detectors is evaluated in varying transverse and longitudinal magnetic fields for eventual use in MR-Linac devices. Methods: A PTW 60003 and IBA PFD detector were modeled in the Monte Carlo code PENELOPE, incorporating a magnetic field which was varied in strength and oriented both transversely and longitudinally with respect to the incident photon beam. The detectors' long axis was in turn oriented either parallel or perpendicular to the photon beam. Dose to the active volume of each detector was scored, and its ratio to dose with zero magnetic field strength (dose response) was determined. Accuracy of the simulations was evaluated by measurements using both chambers taken at low field with a small electromagnet. Simulations were also performed in a water phantom to compare to the in air results. Results: Significant dose response was found in transverse field geometries, nearing 20% at 1.5T. The response is highly dependent on relative orientations to the magnetic field and photon beam, and on detector composition. Low field measurements confirm these results. In the presence of longitudinal magnetic fields, the detectors exhibit little dose response, reaching 0.5–1% at 1.5T regardless of detector orientation. Water tank simulations compared well to the in air simulations when not at the beam periphery, where in transverse magnetic fields only, the water tank simulations differed from the in air results. Conclusion: Transverse magnetic fields can cause large deviations in dose response, and are highly position orientation dependent. Comparatively, longitudinal magnetic fields exhibit little to no dose response in each detector as a function of magnetic field strength. Water tank simulations show longitudinal fields are generally easier to work with, but each detector must be evaluated separately.
Testing statistical significance scores of sequence comparison methods with structure similarity
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Leunissen Jack AM
2006-10-01
Full Text Available Abstract Background In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical significance testing for an alignment. The e-value is the most commonly used statistical validation method for sequence database searching. The CluSTr database and the Protein World database have been created using an alternative statistical significance test: a Z-score based on Monte-Carlo statistics. Several papers have described the superiority of the Z-score as compared to the e-value, using simulated data. We were interested if this could be validated when applied to existing, evolutionary related protein sequences. Results All experiments are performed on the ASTRAL SCOP database. The Smith-Waterman sequence comparison algorithm with both e-value and Z-score statistics is evaluated, using ROC, CVE and AP measures. The BLAST and FASTA algorithms are used as reference. We find that two out of three Smith-Waterman implementations with e-value are better at predicting structural similarities between proteins than the Smith-Waterman implementation with Z-score. SSEARCH especially has very high scores. Conclusion The compute intensive Z-score does not have a clear advantage over the e-value. The Smith-Waterman implementations give generally better results than their heuristic counterparts. We recommend using the SSEARCH algorithm combined with e-values for pairwise sequence comparisons.
Calabrese, Edward J
2008-01-01
This article traces the historical foundations of the Yerkes-Dodson Law from its experimental foundations in the first decade of the 20th century, to its recognition as a generalizable phenomenon in multiple species including humans and to more current attempts to understand its molecular basis within the framework of stress-related biological processes. Within this context, the biological and dose-response characteristics of the Yerkes-Dodson Law are evaluated and compared to the hormesis dose-response model. Based on this evaluation, which includes study design analysis, statistical models of multiple factor/chemical interaction, and a comparative assessment of the quantitative features of these respective dose-response relationships and their molecular foundations, the Yerkes-Dodson Law is shown to represent a special case of the general concept of hormesis illustrating the interaction of two independent study variables, which has typically been observed to be an additive response, although not theoretically restricted to one. The conceptual integration of the Yerkes-Dodson Law within the hormetic dose response framework adds further support for the generalization of the hormesis concept. PMID:18568865
Rudd, James; Moore, Jason H; Urbanowicz, Ryan J
2013-11-01
Permutation-based statistics for evaluating the significance of class prediction, predictive attributes, and patterns of association have only appeared within the learning classifier system (LCS) literature since 2012. While still not widely utilized by the LCS research community, formal evaluations of test statistic confidence are imperative to large and complex real world applications such as genetic epidemiology where it is standard practice to quantify the likelihood that a seemingly meaningful statistic could have been obtained purely by chance. LCS algorithms are relatively computationally expensive on their own. The compounding requirements for generating permutation-based statistics may be a limiting factor for some researchers interested in applying LCS algorithms to real world problems. Technology has made LCS parallelization strategies more accessible and thus more popular in recent years. In the present study we examine the benefits of externally parallelizing a series of independent LCS runs such that permutation testing with cross validation becomes more feasible to complete on a single multi-core workstation. We test our python implementation of this strategy in the context of a simulated complex genetic epidemiological data mining problem. Our evaluations indicate that as long as the number of concurrent processes does not exceed the number of CPU cores, the speedup achieved is approximately linear. PMID:24358057
The Statistical Significance of Planetary Transit and Occultation Detections at Dome A in Antarctica
Oelkers, Ryan J.; DePoy, D.
2012-01-01
The increased discovery of planets through transit detections has created a demand for the characterization of exoplanets. In particular, occultation detections associated with transit events can help determine properties of extra-solar-system planets not possible with other techniques. Unfortunately, many occultation measurements are weakly detected and proper statistical assessment of the significance of the measurement is difficult. We describe a simple approach to determine the statistical significance of an occultation or transit-like detection. We employ a chi-square goodness of fit to multiple eclipse depths and eclipse times over the entire light curve. This allows us to remove the bias associated with an assumed detection time and eclipse depth and thus provide a more accurate description of whether or not the detection could be random or systematic noise or an actual event. Using data from the Antarctic telescope at Dome A (Wang et al. 2011) we are able to confirm the detection of a transit-like event at a statistical level of 4 sigma. This confirms our technique but also gives confidence in the Dome A telescope's ability to find exoplanets.
Kumar, A.; Liess, S.; Kawale, J.; Kumar, V.; Chatterjee, S.
2011-12-01
Identifying trends in time series is necessary to increase the confidence level of the analysis of climate data. This entails finding trends that are statistically significant and categorizing them as linear, quadratic or cubic. Current methods identifying trends use various techniques such as polynomial regression, variate differencing and others. We propose methods such as boot strapping and frequency domain analysis that additionally address other key issues such as identifying the presence of trends within a segment of the time series and computing their individual statistical significances, and further perform a qualitative analysis in finally understanding how trend removal affects global statistics. The methods proposed play an important role in data driven discovery of climate dipoles that represent pairs of regions for which climate anomaly time series are in opposite polarities to each other. In such cases, the methods proposed can be used to identify spurious negative correlations that are caused primarily due to trends but not due to climate teleconnections. Given the general applicability of these methods, it may also prove useful to many time series data other than climate. This research is funded by NSF grant 1029711.
Eggert, Silke; Walter, Thomas R.
2009-06-01
The study of volcanic triggering and interaction with the tectonic surroundings has received special attention in recent years, using both direct field observations and historical descriptions of eruptions and earthquake activity. Repeated reports of clustered eruptions and earthquakes may imply that interaction is important in some subregions. However, the subregions likely to suffer such clusters have not been systematically identified, and the processes responsible for the observed interaction remain unclear. We first review previous works about the clustered occurrence of eruptions and earthquakes, and describe selected events. We further elaborate available databases and confirm a statistically significant relationship between volcanic eruptions and earthquakes on the global scale. Moreover, our study implies that closed volcanic systems in particular tend to be activated in association with a tectonic earthquake trigger. We then perform a statistical study at the subregional level, showing that certain subregions are especially predisposed to concurrent eruption-earthquake sequences, whereas such clustering is statistically less significant in other subregions. Based on this study, we argue that individual and selected observations may bias the perceptible weight of coupling. The activity at volcanoes located in the predisposed subregions (e.g., Japan, Indonesia, Melanesia), however, often unexpectedly changes in association with either an imminent or a past earthquake.
Prediction of the mortality dose-response relationship in man
International Nuclear Information System (INIS)
Based upon an extensive data base including 100 separate animal studies, an estimate of the mortality dose-response relationship due to continuous photon radiation is predicted for 70 kg man. The model used in this prediction exercise includes fixed terms accounting for effects of body weight and dose rate, and random terms accounting for inter- and intra-species variation and experimental error. Point predictions and 95% prediction intervals are given for the LD05, LD10, LD25, LD50, LD75, LD90, and LD95, for dose rates ranging from 1 to 50 R/min. 6 refs., 5 tabs
Mutans Streptococci Dose Response to Xylitol Chewing Gum
Milgrom, P; Ly, K.A.; Roberts, M. C.; Rothen, M; Mueller, G.; Yamaguchi, D.K.
2006-01-01
Xylitol is promoted in caries-preventive strategies, yet its effective dose range is unclear. This study determined the dose-response of mutans streptococci in plaque and unstimulated saliva to xylitol gum. Participants (n = 132) were randomized: controls (G1) (sorbitol/maltitol), or combinations giving xylitol 3.44 g/day (G2), 6.88 g/day (G3), or 10.32 g/day (G4). Groups chewed 3 pellets/4 times/d. Samples were taken at baseline, 5 wks, and 6 mos, and were cultured on modified Mitis Salivari...
Dose response of oral timolol combined with adrenaline.
Ohrström, A.
1982-01-01
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...
Dose Response of Alanine Detectors Irradiated with Carbon Ion Beams
DEFF Research Database (Denmark)
Herrmann, Rochus; Jäkel, Oliver; Palmans, Hugo; Sharpe, Peter; Bassler, Niels
2011-01-01
Purpose: The dose response of the alanine detector shows a dependence on particle energy and type, when irradiated with ion beams. The purpose of this study is to investigate the response behaviour of the alanine detector in clinical carbon ion beams and compare the results with model predictions. Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Br...
Hayek, Lee-Ann C.; W. RONALD HEYER
2005-01-01
Several analytic techniques have been used to determine sexual dimorphism in vertebrate morphological measurement data with no emergent consensus on which technique is superior. A further confounding problem for frog data is the existence of considerable measurement error. To determine dimorphism, we examine a single hypothesis (Ho = equal means) for two groups (females and males). We demonstrate that frog measurement data meet assumptions for clearly defined statistical hypothesis testing wi...
Szpak, B.; Dudek, J.; Porquet, M.-G.; Fornal, B.
2011-01-01
We present examples and illustrate associated tests of statistical significance of the parameter fitting procedures in the nuclear mean-field context using a phenomenological toy-model based on the spherical Woods-Saxon Hamiltonian. We calculate the variance-covariance matrix and compare the standard estimates of the confidence intervals (and more generally - the uncertainty distributions) based on the standard ?2-fitting as opposed to a more general Monte-Carlo simulations. We give arguments for the superiority of the latter approach.
Dudek, J.; Szpak, B.; Porquet, M.-G.; Fornal, B.
2011-01-01
In this and the follow-up article we briefly discuss what we believe represents one of the most serious problems in contemporary nuclear structure: the question of statistical significance of parametrizations of nuclear microscopic Hamiltonians and the implied predictive power of the underlying theories. In the present Part I, we introduce the main lines of reasoning of the so-called Inverse Problem Theory, an important sub-field in the contemporary Applied Mathematics, here illustrated on the example of the Nuclear Mean-Field Approach.
Pérez-Guaita, David; Kuligowski, Julia; Garrigues, Salvador; Quintás, Guillermo; Wood, Bayden R
2015-04-01
Fourier transform infrared (IR) spectroscopy in combination with multivariate data analysis is a versatile tool that can be applied to disease diagnosis. However, a rigorous validation of the obtained models is necessary in order to obtain robust results. This work evaluates the advantages of the use of permutation testing for determining the statistical significance of the misclassification errors obtained from IR based diagnostic models through cross validation (CV). The model performance, estimated by CV, is compared to a distribution of CV-performance values obtained using randomly permuted class labels. The distribution of 'random CV-values' is considered as a null distribution and used to establish the significance of the model estimators obtained using real class labels. ATR-FTIR spectra of serum samples were classified using random forest (RF) classifiers according to two criteria, the tag number (a randomly assigned pseudo class membership) and the level of urea (real class). CV errors obtained were compared to the null distribution of CV errors from a permutation test and an independent validation set. The procedure was evaluated testing typical conditions leading to overoptimistic estimations provided by the CV like e.g. the size of subsamples used during CV, variable selection and the use of replicates. Results show that for the tag number (pseudo class), CV indicated classification errors between 23 and 33% depending on the subsample size employed. Those values were even lower when variable selection or replicates were used. However, permutation testing indicated that those CV errors were non-significant. In contrast, for sample classification according to their levels of urea, all cross validation errors were found to be significant. Although the proposed method is computationally intensive, it provides a simple way of calculating an empirical p-value of the CV-estimator, thus establishing the statistical significance and providing a feasibility indicator especially useful for studies where the number of samples is limited. PMID:25382314
Maximum likelihood estimation for cytogenetic dose-response curves
International Nuclear Information System (INIS)
In vitro dose-response curves are used to describe the relation between the yield of dicentric chromosome aberrations and radiation dose for human lymphocytes. The dicentric yields follow the Poisson distribution, and the expected yield depends on both the magnitude and the temporal distribution of the dose for low LET radiation. A general dose-response model that describes this relation has been obtained by Kellerer and Rossi using the theory of dual radiation action. The yield of elementary lesions is kappa[?d + g(t, tau)d2], where t is the time and d is dose. The coefficient of the d2 term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure
Dose-response relationships for radium-induced bone sarcomas
International Nuclear Information System (INIS)
The incidence of bone sarcomas among 3055 female radium-dial workers who entered the dial industry before 1950 was used to determine dose-response relationships for the induction of bone sarcomas by radium. Two subpopulations were analyzed: all measured cases who survived at last five years after the start of employment and all cases who survived at least two years after first measurement. The first constituted a group based on year of entry; it contained 1468 women who experienced 42 bone sarcomas; the expected number was 0.4. The second comprised a group based on first measurement; it contained 1257 women who experienced 13 bone sarcomas; the expected number was 0.2. The dose-response function, I = (C + ?D + #betta#D2)e/sup -#betta#D/, and simplifications of this general form, were fit to each data set. Two functions, I = (C + ?D + #betta#D2)e/sup -#betta#D/ and I = (C + #betta#D2)e/sup -#betta#D/, fit the data for year of entry (p greater than or equal to 0.05); both these functions and I = (C + ?D) fit the data for first measurement. The function I = (C + #betta#D2)e/sup -#betta#D/ was used to predict the number of bone sarcomas in all other pre-1950 radium cases (medical, laboratory, and other exposure); fewer were actually observed than the fit of this function to the female dial workers predicted
Ritter, Axel; Muñoz-Carpena, Rafael
2013-02-01
SummarySuccess in the use of computer models for simulating environmental variables and processes requires objective model calibration and verification procedures. Several methods for quantifying the goodness-of-fit of observations against model-calculated values have been proposed but none of them is free of limitations and are often ambiguous. When a single indicator is used it may lead to incorrect verification of the model. Instead, a combination of graphical results, absolute value error statistics (i.e. root mean square error), and normalized goodness-of-fit statistics (i.e. Nash-Sutcliffe Efficiency coefficient, NSE) is currently recommended. Interpretation of NSE values is often subjective, and may be biased by the magnitude and number of data points, data outliers and repeated data. The statistical significance of the performance statistics is an aspect generally ignored that helps in reducing subjectivity in the proper interpretation of the model performance. In this work, approximated probability distributions for two common indicators (NSE and root mean square error) are derived with bootstrapping (block bootstrapping when dealing with time series), followed by bias corrected and accelerated calculation of confidence intervals. Hypothesis testing of the indicators exceeding threshold values is proposed in a unified framework for statistically accepting or rejecting the model performance. It is illustrated how model performance is not linearly related with NSE, which is critical for its proper interpretation. Additionally, the sensitivity of the indicators to model bias, outliers and repeated data is evaluated. The potential of the difference between root mean square error and mean absolute error for detecting outliers is explored, showing that this may be considered a necessary but not a sufficient condition of outlier presence. The usefulness of the approach for the evaluation of model performance is illustrated with case studies including those with similar goodness-of-fit indicators but distinct statistical interpretation, and others to analyze the effects of outliers, model bias and repeated data. This work does not intend to dictate rules on model goodness-of-fit assessment. It aims to provide modelers with improved, less subjective and practical model evaluation guidance and tools.
Cheng, Riyan; Palmer, Abraham A
2013-03-01
We used simulations to evaluate methods for assessing statistical significance in association studies. When the statistical model appropriately accounted for relatedness among individuals, unrestricted permutation tests and a few other simulation-based methods effectively controlled type I error rates; otherwise, only gene dropping controlled type I error but at the expense of statistical power. PMID:23267053
Cheng, Riyan; Palmer, Abraham A.
2013-01-01
We used simulations to evaluate methods for assessing statistical significance in association studies. When the statistical model appropriately accounted for relatedness among individuals, unrestricted permutation tests and a few other simulation-based methods effectively controlled type I error rates; otherwise, only gene dropping controlled type I error but at the expense of statistical power.
Sample size and significance – somewhere between statistical power and judgment prostration
Directory of Open Access Journals (Sweden)
Cezary Wata?a
2007-03-01
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.
Witten, Daniela M; Noble, William Stafford
2012-05-01
A growing body of experimental evidence supports the hypothesis that the 3D structure of chromatin in the nucleus is closely linked to important functional processes, including DNA replication and gene regulation. In support of this hypothesis, several research groups have examined sets of functionally associated genomic loci, with the aim of determining whether those loci are statistically significantly colocalized. This work presents a critical assessment of two previously reported analyses, both of which used genome-wide DNA-DNA interaction data from the yeast Saccharomyces cerevisiae, and both of which rely upon a simple notion of the statistical significance of colocalization. We show that these previous analyses rely upon a faulty assumption, and we propose a correct non-parametric resampling approach to the same problem. Applying this approach to the same data set does not support the hypothesis that transcriptionally coregulated genes tend to colocalize, but strongly supports the colocalization of centromeres, and provides some evidence of colocalization of origins of early DNA replication, chromosomal breakpoints and transfer RNAs. PMID:22266657
Hatch, M; Furukawa, K; Brenner, A; Olinjyk, V; Ron, E; Zablotska, L; Terekhova, G; McConnell, R; Markov, V; Shpak, V; Ostroumova, E; Bouville, A; Tronko, M
2010-12-01
Relatively few data are available on the prevalence of hyperthyroidism (TSH concentrations of <0.3 mIU/liter, with normal or elevated concentrations of free T4) in individuals exposed to radioiodines at low levels. The accident at the Chornobyl (Chernobyl) nuclear plant in Ukraine on April 26, 1986 exposed large numbers of residents to radioactive fallout, principally to iodine-131 ((131)I) (mean and median doses ?=? 0.6 Gy and 0.2 Gy). We investigated the relationship between (131)I and prevalent hyperthyroidism among 11,853 individuals exposed as children or adolescents in Ukraine who underwent an in-depth, standardized thyroid gland screening examination 12-14 years later. Radioactivity measurements taken shortly after the accident were available for all subjects and were used to estimate individual thyroid doses. We identified 76 cases of hyperthyroidism (11 overt, 65 subclinical). Using logistic regression, we tested a variety of continuous risk models and conducted categorical analyses for all subjects combined and for females (53 cases, n ?=? 5,767) and males (23 cases, n ?=? 6,086) separately but found no convincing evidence of a dose-response relationship between (131)I and hyperthyroidism. There was some suggestion of elevated risk among females in an analysis based on a dichotomous dose model with a threshold of 0.5 Gy chosen empirically (OR ?=? 1.86, P ?=? 0.06), but the statistical significance level was reduced (P ?=? 0.13) in a formal analysis with an estimated threshold. In summary, after a thorough exploration of the data, we found no statistically significant dose-response relationship between individual (131)I thyroid doses and prevalent hyperthyroidism. PMID:21128800
Hatch, M.; Furukawa, K.; Brenner, A.; Olinjyk, V.; Ron, E.; Zablotska, L.; Terekhova, G.; McConnell, R.; Markov, V.; Shpak, V.; Ostroumova, E.; Bouville, A.; Tronko, M.
2013-01-01
Relatively few data are available on the prevalence of hyperthyroidism (TSH concentrations of < 0.3 mIU/L, with normal or elevated concentrations of free T4) in individuals exposed to radioiodines at low levels. The accident at the Chornobyl (Chernobyl) nuclear plant in Ukraine on April 26, 1986 exposed large numbers of residents to radioactive fallout, principally to iodine-131 (I-131) (mean and median doses = 0.6 Gray (Gy) and 0.2 Gy). We investigated the relationship of I-131 and prevalent hyperthyroidism among 11,853 individuals exposed as children or adolescents in Ukraine who underwent an in-depth, standardized thyroid gland screening examination 12–14 years later. Radioactivity measurements taken shortly after the accident were available for all subjects and were used to estimate individual thyroid doses. We identified 76 cases of hyperthyroidism (11 overt, 65 subclinical). Using logistic regression, we tested a variety of continuous risk models and conducted categorical analyses for all subjects combined and for females (53 cases, n=5,767) and males (23 cases, n=6,086) separately, but found no convincing evidence of a dose response relationship between I-131 and hyperthyroidism. There was some suggestion of elevated risk among females in an analysis based on a dichotomous dose model with a threshold of 0.5 Gy chosen empirically (OR=1.86, P=0.06), but the statistical significance level was reduced (P=0.13) in a formal analysis with an estimated threshold. In summary, after a thorough exploration of the data, we found no statistically significant dose response relationship between individual I-131 thyroid doses and prevalent hyperthyroidism. PMID:21128800
Dose-response characteristics of an amorphous silicon EPID.
Winkler, Peter; Hefner, Alfred; Georg, Dietmar
2005-10-01
Electronic portal imaging devices (EPIDs) were originally developed for the purpose of patient setup verification. Nowadays, they are increasingly used as dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite for any clinical dosimetric application is a detailed understanding of the detector's dose-response behavior. The aim of this study is to investigate the dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent temporal stability on short term as well as on long term scales. The stability throughout the day was strongly influenced by warming up, which took several hours and affected EPID response by 2.5%. Ghosting effects increased the sensitivity of the EPID. They became more pronounced with decreasing time intervals between two exposures as well as with increasing dose. Due to ghosting, changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon beam. It was observed that the response characteristics of our EPID depended on dose as well as on dose rate. Doubling the dose rate increased the EPID sensitivity by 1.5%. This behavior was successfully attributed to a dose per frame effect, i.e., a nonlinear relationship between the EPID signal and the dose which was delivered to the panel between two successive readouts. The sensitivity was found to vary up to 10% in the range of 1 to 1000 monitor units. This variation was governed by two independent effects. For low doses, the EPID signal was reduced due to the linac's changing dose rate during startup. Furthermore, the detector reading was influenced by intrabeam variations of EPID sensitivity, namely, an increase of detector response during uniform exposure. For the beam qualities which were used, the response characteristics of the EPID did not depend on energy. Differences in relative dose-response curves resulted from energy dependent temporal output characteristics of the accelerator. If ghosting is prevented from affecting the results and all dose-response effects are properly corrected for, the EPID signal becomes independent of dose rate, dose, and exposure time. PMID:16279061
On the statistical significance of the bulk flow measured by the Planck satellite
Atrio-Barandela, F.
2013-09-01
A recent analysis of data collected by the Planck satellite detected a net dipole at the location of X-ray selected galaxy clusters, corresponding to a large-scale bulk flow extending at least to z ~ 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 statistically significant. Here, we 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. Random simulations of the sky do not take into account that the actual realization of the sky leads to filtered data that have a 12% lower root-mean-square dispersion than the average simulation. Using rotations 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 detection from 98-99% to less than 90% confidence. When either effect is taken into account, the corrected errors agree with those obtained using random distributions of clusters on Planck data, and the resulting statistical significance of the dipole measured by Planck is consistent with that of the WMAP results.
A dose-response trial of nebivolol in essential hypertension.
Van Nueten, L; Dupont, A G; Vertommen, C; Goyvaerts, H; Robertson, J I
1997-02-01
A double-blind placebo-controlled dose-response trial of nebivolol, a cardioselective beta-blocking drug which also induces endothelium-dependent dilatation via nitric oxide, has been performed. Nebivolol reduced blood pressure (BP) in a dose dependent way, and was shown to be effective given once daily, without appreciable differences between peak and trough drug levels. There was no postural component to the BP fall. There was no clear inferiority of efficacy in black patients. A single daily dose of 5 mg was appropriate, with no evident advantage at 10 mg. The drug was well tolerated, even at 10 mg daily. BP control was achieved largely in the absence of typical side effects of beta-blockade. The combination of properties of nebivolol renders it an attractive addition to the antihypertensive repertoire. PMID:9140802
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)
A broadly applicable function for describing luminescence dose response
Burbidge, C. I.
2015-07-01
The basic form of luminescence dose response is investigated, with the aim of developing a single function to account for the appearance of linear, superlinear, sublinear, and supralinear behaviors and variations in saturation signal level and rate. A function is assembled based on the assumption of first order behavior in different major factors contributing to measured luminescence-dosimetric signals. Different versions of the function are developed for standardized and non-dose-normalized responses. Data generated using a two trap two recombination center model and experimental data for natural quartz are analyzed to compare results obtained using different signals, measurement protocols, pretreatment conditions, and radiation qualities. The function well describes a range of dose dependent behavior, including sublinear, superlinear, supralinear, and non-monotonic responses and relative response to ? and ? radiation, based on change in relative recombination and trapping probability affecting signals sourced from a single electron trap.
Energy Technology Data Exchange (ETDEWEB)
Crow, C.J.
1985-01-01
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.
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.)
Henderson, Douglas
2010-01-01
Henry Eyring was, and still is, a towering figure in science. Some aspects of his life and science, beginning in Mexico and continuing in Arizona, California, Wisconsin, Germany, Princeton, and finally Utah, are reviewed here. Eyring moved gradually from quantum theory toward statistical mechanics and the theory of liquids, motivated in part by his desire to understand reactions in condensed matter. Significant structure theory, while not as successful as Eyring thought, is better than his critics realize. Eyring won many awards. However, most chemists are surprised, if not shocked, that he was never awarded a Nobel Prize. He joined Lise Meitner, Rosalind Franklin, John Slater, and others, in an even more select group, those who should have received a Nobel Prize but did not.
A network-based method to assess the statistical significance of mild co-regulation effects.
Horvát, Em?ke-Ágnes; Zhang, Jitao David; Uhlmann, Stefan; Sahin, Özgür; Zweig, Katharina Anna
2013-01-01
Recent development of high-throughput, multiplexing technology has initiated projects that systematically investigate interactions between two types of components in biological networks, for instance transcription factors and promoter sequences, or microRNAs (miRNAs) and mRNAs. In terms of network biology, such screening approaches primarily attempt to elucidate relations between biological components of two distinct types, which can be represented as edges between nodes in a bipartite graph. However, it is often desirable not only to determine regulatory relationships between nodes of different types, but also to understand the connection patterns of nodes of the same type. Especially interesting is the co-occurrence of two nodes of the same type, i.e., the number of their common neighbours, which current high-throughput screening analysis fails to address. The co-occurrence gives the number of circumstances under which both of the biological components are influenced in the same way. Here we present SICORE, a novel network-based method to detect pairs of nodes with a statistically significant co-occurrence. We first show the stability of the proposed method on artificial data sets: when randomly adding and deleting observations we obtain reliable results even with noise exceeding the expected level in large-scale experiments. Subsequently, we illustrate the viability of the method based on the analysis of a proteomic screening data set to reveal regulatory patterns of human microRNAs targeting proteins in the EGFR-driven cell cycle signalling system. Since statistically significant co-occurrence may indicate functional synergy and the mechanisms underlying canalization, and thus hold promise in drug target identification and therapeutic development, we provide a platform-independent implementation of SICORE with a graphical user interface as a novel tool in the arsenal of high-throughput screening analysis. PMID:24039936
Boschi, L.; Becker, Thorsten W.; Steinberger, Bernhard
2008-04-01
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.
DEFF Research Database (Denmark)
Simon, Ted W; Simons, S Stoney
2014-01-01
The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative dose-response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the dose-response and timing of KEs resulting from a dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative dose-response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic responses in rodents, which demonstrate how quantitative dose-response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.
Symptom overreporting obscures the dose-response relationship between trauma severity and symptoms.
Merckelbach, Harald; Langeland, Willie; de Vries, Gerard; Draijer, Nel
2014-07-30
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
Directory of Open Access Journals (Sweden)
Sadreyev Ruslan I
2004-08-01
Full Text Available Abstract Background Profile-based analysis of multiple sequence alignments (MSA allows for accurate comparison of protein families. Here, we address the problems of detecting statistically confident dissimilarities between (1 MSA position and a set of predicted residue frequencies, and (2 between two MSA positions. These problems are important for (i evaluation and optimization of methods predicting residue occurrence at protein positions; (ii detection of potentially misaligned regions in automatically produced alignments and their further refinement; and (iii detection of sites that determine functional or structural specificity in two related families. Results For problems (1 and (2, we propose analytical estimates of P-value and apply them to the detection of significant positional dissimilarities in various experimental situations. (a We compare structure-based predictions of residue propensities at a protein position to the actual residue frequencies in the MSA of homologs. (b We evaluate our method by the ability to detect erroneous position matches produced by an automatic sequence aligner. (c We compare MSA positions that correspond to residues aligned by automatic structure aligners. (d We compare MSA positions that are aligned by high-quality manual superposition of structures. Detected dissimilarities reveal shortcomings of the automatic methods for residue frequency prediction and alignment construction. For the high-quality structural alignments, the dissimilarities suggest sites of potential functional or structural importance. Conclusion The proposed computational method is of significant potential value for the analysis of protein families.
Directory of Open Access Journals (Sweden)
Bergamini F
2012-11-01
Full Text Available Paolo Milani, Amedeo Massacesi, Stefano Ciaccia, Marco Setaccioli, Stefania Moschini, Fulvio BergaminiDipartimento di Oculistica, Istituto Auxologico Italiano, Milano, ItalyBackground: The aim of this study was to evaluate the efficacy of intravitreal bevacizumab when administered on an as-needed basis for the treatment of myopic choroidal neovascularization (CNV, and to assess visual changes upon treatment.Methods: This study was designed as a retrospective, interventional case series, for which the inclusion criteria were pathologic myopia, and documentation of untreated active macular CNV on fluorescein angiography and optical coherence tomography. Monthly changes in best-corrected visual acuity (BCVA, visual gain after each treatment, and correlation with refraction, age, location, and dimension of CNV were considered. The data were analyzed using the one-tailed, paired Wilcoxon test.Results: Nineteen naive eyes were found suitable for the study. The mean number of treatments was 3.32 ± 2.36 (confidence interval 2.25–4.37 during a mean follow-up period of 18.95 ± 8.3 months. At baseline, mean BCVA was 0.58 ± 0.37 logarithm of the minimum angle of resolution (logMAR units. At 12 months, mean BCVA was 0.39 ± 0.35 logMAR and at 24 months was 0.39 ± 0.40. Mean improvement in BCVA from baseline was +0.17 ± 0.25 logMAR (P < 0.05 at month 12, +0.14 ± 0.25 logMAR (P = 0.1 at month 18, and +0.09 ± 0.32 logMAR (P = 0.5 at month 24. Improvement on pretreatment BCVA was significant (+0.16 logMAR, P < 0.01 after the first injection, but not after the second (?0.01 logMAR, P = 0.5 or third (+0.02 logMAR, P = 0.5 injections. There was a statistically significant correlation between age and number of treatments, and between improvement in BCVA of foveal versus extrafoveal location of CNV.Conclusion: The use of intravitreal bevacizumab "as needed" is an effective treatment for myopic CNV, but visual gain is statistically significant only after the first injection and decreases in the second year.Keywords: choroidal neovascularization, macular degeneration, pathologic myopia, bevacizumab, optical coherence tomography
Linear dose response curves in fungi and tradescantia
Energy Technology Data Exchange (ETDEWEB)
Unrau, P. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)
1999-07-15
Tradescantia Clone 02 data suggests that linear non-threshold dose responses are expected to the lowest doses and dose rates of low linear energy transfer (LET) radiation. This is likely to be true for other living organisms even though Clone 02 is radiation sensitive. It is concluded that Clone 02 is partially defective in the RAD 6 pathway for the repair of DNA interstrand cross-links (ISCL) and other loss of coding damage (LCD), based on its cross sensitivities to EMS and ionizing radiation. Tradescantia Clone 02 data showing linear non-threshold induction of somatic genetic events in part reflects the repair deficiency of this Clone. More DNA damage is repaired by recombinational mechanisms in Clone 02 than would occur in a wild-type strain. Two important classes of DNA lesions are induced by ionizing radiation in DNA - double strand breaks (DSB) which are repaired by recombination mechanisms, and loss of coding information damage (LCD), which is repaired by error prone mechanisms but may also be a substrate for recombinational repair. Based on data from yeast, there are two different repair pathways which deal with these differing lesions with different somatic genetic consequences. From yeast, yield cross sections can be derived and applied to DNA damage and repair in Tradescantia. For Clone 02, per lesion, more visible genetic events are scored than in wild-type strains. In a radiation-derived sub-clone, Clone 0106, which is more variable than Clone 02, even more events occur per lesion. This derivative clone, plus breeding experiments, indicate that Clone 02 is heterozygous, or a 'carrier' for a mutant version of a gene in the Tradescantia RAD 6 repair pathway. Clone 02 is, therefore, much like a Fanconi's anemia carrier in a human population, while the Clone 0106 derivative is much like a homozygous Fanconi's anemia patient, with respect to its response to ionizing radiation damage. Two anomalies in its dose response curves for 'pink' loss of heterozygosity (LOH) events occur because Clone 02 repairs both DSB and LCD by recombination. Clone 02 has a linear dose response for high LET radiation. Starting from the same initial yieId frequency, wild-types have a sublinear response. The sublinear response reflects a smoothly decreasing probability that 'pinks' are generated as a function of increasing high LET dose for wild-type but not Clone 02. This smoothly decreasing response would be expected for LOH in 'wild-type' humans. It reflects an increasing proportion of DNA damage being repaired by non-recombinational pathways and/or an increasing probability of cell death with increasing dose. Clone 02 at low doses and low dose rates of low LET radiation has a linear dose response, reflecting a 1/16 probability of a lesion leading to LOH, relative to high LET lesions. This differential is held to reflect: microdosimetric differences in energy deposition and, therefore, DNA damage by low and high LET radiations; the effects of lesion clustering after high LET on the probability of generating the end wild-types. While no observations have been made at very low doses and dose rates in wild-types, there is no reason to suppose that the low LET linear non-threshold dose response of Clone 02 is abnormal. The importance of the LOH somatic genetic end-point is that it reflects cancer risk in humans. The linear non-threshold low dose low LET response curves reflects either the probability that recombinational Holliday junctions are occasionally cleaved in a rare orientation to generate LOH, or the probability that low LET lesions include a small proportion of clustered events similar to high LET ionization or both. Calculations of the Poisson probability that two or more low LET lesions will be induced in the same target suggest that dose rate effects depend upon the coincidence of DNA lesions in the same target, and that the probability of LOH depends upon lesion and repair factors. But the slope of LOH in Clone 02 and all other strains never approaches the expected slope of pr
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
Statistics, Probability, Significance, Likelihood: Words Mean What We Define Them to Mean
Drummond, Gordon B.; Tom, Brian D. M.
2011-01-01
Statisticians use words deliberately and specifically, but not necessarily in the way they are used colloquially. For example, in general parlance "statistics" can mean numerical information, usually data. In contrast, one large statistics textbook defines the term "statistic" to denote "a characteristic of a "sample", such as the average score",…
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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
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.
Homeopathy: statistical significance versus the sample size in experiments with Toxoplasma gondii
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Ana LÃƒÂºcia Falavigna Guilherme
2011-09-01
Full Text Available Introduction: Toxoplasmosis is a zoonosis that represents a serious public health problem, caused by Toxoplasma gondii, which affects 20-90% of the world human population [1,2]. It is a serious problem especially when considering the congenital transmission due to congenital sequels. Treatment with highly diluted substances is one of the alternative/complementary medicines most employed in the world [3,4]. The current ethical rules regarding the number of animals used in animal experimental protocols with the use of more conservative statistical methods [5] can not enhance the biological effects of highly diluted substances observed by the experience of the researcher. Aim: To evaluate the minimum number of animals per group to achieve a significant difference among the groups of animals treated with biotherapic T. gondii and infected with the protozoan regarding the number of cysts observed in the brain. Material and methods: A blind randomized controlled trial was performed using eleven Swiss male mice, aged 57 days, divided into two groups: BIOT-200DH - treated with biotherapic (n=6 and CONTROL - treated with hydroalcoholic solution 7% (n=7.The animals of the group BIOT-200DH were treated for 3 consecutive days in a single dose 0.1ml/dose/day. The animals of BIOT Ã¢â‚¬â€œ 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 / 100ÃŽÂ¼L 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 Ã‚Â± 3.3 and 12.8 Ã‚Â± 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
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Marasinghe Wadige, Chamani P.M., E-mail: chamani.marasinghe.wadige@canberra.edu.au; Maher, William A.; Taylor, Anne M.; Krikowa, Frank
2014-07-01
Highlights: • The exposure–dose–response approach was used to assess cadmium exposure and toxicity. • Accumulated cadmium in H. australis reflected the sediment cadmium exposure. • Spill over of cadmium into the biologically active pool was observed. • Increased cadmium resulted in measurable biological effects. • H. australis has the potential to be a cadmium biomonitor in freshwater environments. - Abstract: To understand how benthic biota may respond to the additive or antagonistic effects of metal mixtures in the environment it is first necessary to examine their responses to the individual metals. In this context, laboratory controlled single metal-spiked sediment toxicity tests are useful to assess this. The exposure–dose–response relationships of Hyridella australis to cadmium-spiked sediments were, therefore, investigated in laboratory microcosms. H. australis was exposed to individual cadmium spiked sediments (<0.05 (control), 4 ± 0.3 (low) and 15 ± 1 (high) ?g/g dry mass) for 28 days. Dose was measured as cadmium accumulation in whole soft body and individual tissues at weekly intervals over the exposure period. Dose was further examined as sub-cellular localisation of cadmium in hepatopancreas tissues. The biological responses in terms of enzymatic and cellular biomarkers were measured in hepatopancreas tissues at day 28. H. australis accumulated cadmium from spiked sediments with an 8-fold (low exposure organisms) and 16-fold (high exposure organisms) increase at day 28 compared to control organisms. The accumulated tissue cadmium concentrations reflected the sediment cadmium exposure at day 28. Cadmium accumulation in high exposure organisms was inversely related to the tissue calcium concentrations. Gills of H. australis showed significantly higher cadmium accumulation than the other tissues. Accumulated cadmium in biologically active and biologically detoxified metal pools was not significantly different in cadmium exposed 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.
Optimal designs for dose-response models with restricted design spaces
Dette, Holger; Biedermann, Stefanie; Zhu, Wei
2004-01-01
In dose response studies, the dose range is often restricted due to concerns over drug toxicity and/or efficacy. We present restricted and unrestricted interval locally optimal designs with respect to a very general class of optimality criteria for estimating the underlying dose response curve. The underlying curve belongs to a diversified set of link functions suitable for the dose response studies and having a common canonical form. These include the fundamental binary response models – the...
Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.
Johnston, Sara C; Lin, Kenny L; Twenhafel, Nancy A; Raymond, Jo Lynne W; Shamblin, Joshua D; Wollen, Suzanne E; Wlazlowski, Carly B; Wilkinson, Eric R; Botto, Miriam A; Goff, Arthur J
2015-01-01
Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies. PMID:26413900
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Blalock Eric M
2007-07-01
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.
Wang, Bo; Shi, Zhanquan; Weber, Georg F; Kennedy, Michael A
2013-10-01
Nuclear magnetic resonance (NMR) spectroscopy-based metabonomics is of growing importance for discovery of human disease biomarkers. Identification and validation of disease biomarkers using statistical significance analysis (SSA) is critical for translation to clinical practice. SSA is performed by assessing a null hypothesis test using a derivative of the Student's t test, e.g., a Welch's t test. Choosing how to correct the significance level for rejecting null hypotheses in the case of multiple testing to maintain a constant family-wise type I error rate is a common problem in such tests. The multiple testing problem arises because the likelihood of falsely rejecting the null hypothesis, i.e., a false positive, grows as the number of tests applied to the same data set increases. Several methods have been introduced to address this problem. Bonferroni correction (BC) assumes all variables are independent and therefore sacrifices sensitivity for detecting true positives in partially dependent data sets. False discovery rate (FDR) methods are more sensitive than BC but uniformly ascribe highest stringency to lowest p value variables. Here, we introduce standard deviation step down (SDSD), which is more sensitive and appropriate than BC for partially dependent data sets. Sensitivity and type I error rate of SDSD can be adjusted based on the degree of variable dependency. SDSD generates fundamentally different profiles of critical p values compared with FDR methods potentially leading to reduced type II error rates. SDSD is increasingly sensitive for more concentrated metabolites. SDSD is demonstrated using NMR-based metabonomics data collected on three different breast cancer cell line extracts. PMID:24026514
Dose-response patterns of Radix Glycyrrhizae in Shanghan Lun
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Xue YANG
2009-03-01
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.
Dose response of alanine detectors irradiated with carbon ion beams
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Herrmann, Rochus; Jaekel, Oliver; Palmans, Hugo; Sharpe, Peter; Bassler, Niels [Department of Physics and Astronomy, Aarhus University, 8000 Aarhus (Denmark); Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg (Germany) and Department of Experimental Clinical Oncology, Aarhus University Hospital, 8000 Aarhus (Denmark); Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg (Germany) and Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg (Germany); National Physical Laboratory, Teddington, Middlesex, TW 11 OLW (United Kingdom); Department of Physics and Astronomy, Aarhus University, 8000 Aarhus (Denmark); Division of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg (Germany) and Department of Experimental Clinical Oncology, Aarhus University Hospital, 8000 Aarhus (Denmark)
2011-04-15
Purpose: The dose response of the alanine detector shows a dependence on particle energy and type when irradiated with ion beams. The purpose of this study is to investigate the response behavior of the alanine detector in clinical carbon ion beams and compare the results to model predictions. Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track structure based alanine response model developed by Hansen and Olsen has been implemented in the Monte Carlo code FLUKA and calculations were compared to experimental results. Results: Calculations of the relative effectiveness deviate less than 5% from the measured values for monoenergetic beams. Measured depth-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. Conclusions: The used model and its implementation show a good overall agreement for quasimonoenergetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.
Dose response of alanine detectors irradiated with carbon ion beams
International Nuclear Information System (INIS)
Purpose: The dose response of the alanine detector shows a dependence on particle energy and type when irradiated with ion beams. The purpose of this study is to investigate the response behavior of the alanine detector in clinical carbon ion beams and compare the results to model predictions. Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track structure based alanine response model developed by Hansen and Olsen has been implemented in the Monte Carlo code FLUKA and calculations were compared to experimental results. Results: Calculations of the relative effectiveness deviate less than 5% from the measured values for monoenergetic beams. Measured depth-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. Conclusions: The used model and its implementation show a good overall agreement for quasimonoenergetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.
A universal dose–response curve for radiochromic films
International Nuclear Information System (INIS)
Purpose: This paper presents a model for dose–response curves of radiochromic films. It is based on a modified version of single-hit model to take into account the growth experienced by lithium salt of pentacosa-10,12-diynoic acid polymers after irradiation. Methods: Polymer growth in radiochromic films is a critical phenomenon that can be properly described by means of percolation theory to provide an appropriate distribution function for polymer sizes. Resulting functional form is a power function featuring a critical exponent and two adjustable parameters. Moreover, these parameters act as scaling factors setting a natural scale for sensitometric curves where the dependence on channel sensitivity is removed. A unique reduced response curve is then obtained from all the color channels describing film behavior independently of film dosimetry system. Results: Resulting functional form has been successfully tested in several sensitometric curves from different Gafchromic EBT models, providing excellent agreement with experimental data in a wide dose range up to about 40 Gy and low dose uncertainty. Conclusions: The model presented in this paper describes accurately the sensitometric curves of radiochromic films in wide dose ranges covering all typical ranges used in external radiotherapy. Resulting dose uncertainty is low enough to render a reasonably good performance in clinical applications. Due to cross-correlation, only one of the adjustable parameters is totally independent and characterizes film batches
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Vujovi? Svetlana R.
2013-01-01
Full Text Available This paper illustrates the utility of multivariate statistical techniques for analysis and interpretation of water quality data sets and identification of pollution sources/factors with a view to get better information about the water quality and design of monitoring network for effective management of water resources. Multivariate statistical techniques, such as factor analysis (FA/principal component analysis (PCA and cluster analysis (CA, were applied for the evaluation of variations and for the interpretation of a water quality data set of the natural water bodies obtained during 2010 year of monitoring of 13 parameters at 33 different sites. FA/PCA attempts to explain the correlations between the observations in terms of the underlying factors, which are not directly observable. Factor analysis is applied to physico-chemical parameters of natural water bodies with the aim classification and data summation as well as segmentation of heterogeneous data sets into smaller homogeneous subsets. Factor loadings were categorized as strong and moderate corresponding to the absolute loading values of >0.75, 0.75-0.50, respectively. Four principal factors were obtained with Eigenvalues >1 summing more than 78 % of the total variance in the water data sets, which is adequate to give good prior information regarding data structure. Each factor that is significantly related to specific variables represents a different dimension of water quality. The first factor F1 accounting for 28 % of the total variance and represents the hydrochemical dimension of water quality. The second factor F2 accounting for 18% of the total variance and may be taken factor of water eutrophication. The third factor F3 accounting 17 % of the total variance and represents the influence of point sources of pollution on water quality. The fourth factor F4 accounting 13 % of the total variance and may be taken as an ecological dimension of water quality. Cluster analysis (CA is an 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.
The dose-response of canine focal gastric mucosal blood flow to misoprostol
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Gana, T.J.; Pherson, B.R.; Koo, J. (Alberta Univ., Edmonton, AB (Canada))
1989-01-01
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.
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
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.
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The incidence of leukemia during 1950 to 1971 in a fixed mortality sample of atomic bomb survivors in Hiroshima and Nagasaki was analyzed as a function of neutron and ? kerma and marrow doses. Two dose-response models were tested for acute leukemia, chronic granulocytic leukemia, and all types of leukemia, respectively. Each model postulates that the leukemia incidence depends upon the sum of separate risks imposed by ? and neutron doses. In Model I the risk from both types of radiation is assumed to be directly proportional to the respective doses, while Model II assumes that whereas the risk from neutrons is directly proportional to the dose, the risk from ? rays is proportional to dose-squared. The analysis demonstrated that the dose-response of the two types of leukemia differed by type of radiation. The data suggested that the response of acute leukemia was best explained by Model II, while the response of chronic granulocytic leukemia depended almost linearly upon neutron dose alone, because the regression coefficients associated with ? radiation for both Models I and II were not significant. The relative biological effectiveness (RBE) of neutrons in relation to ? rays for incidence of acute leukemia was estimated to be approximately 30/(Dn)/sup 1/2/ [95% confidence limits; 17/(Dn)/sup 1/2/ approx. 54/(Dn)/sup 1/2/] for kerma and 32/(Dn)/sup 1/2/ [95% confidence limits; 18/(Dn)/sup 1/2/ approx. 58/(Dn)/sup 1/2/] for marrow dose (Dn = neutron dose). If acute and chronic granulocytic leukemias are considered together as all types of leukemia, Model II appears to fit the data slightly better than Model I, but neither model is statistically rejected by the data
Cellular Mechanism of the Nonmonotonic Dose Response of Bisphenol A in Rat Cardiac Myocytes
Liang, Qian; Gao, Xiaoqian; Chen, Yamei; HONG, KUI; Wang, Hong-Sheng
2014-01-01
Background: The need for mechanistic understanding of nonmonotonic dose responses has been identified as one of the major data gaps in the study of bisphenol A (BPA). Previously we reported that acute exposure to BPA promotes arrhythmogenesis in female hearts through alteration of myocyte Ca2+ handling, and that the dose response of BPA was inverted U-shaped.
Dose response study using micronucleus cytome assay-useful tool for biodosimetry application
International Nuclear Information System (INIS)
The in vitro cytokinesis-block micronucleus cytome (CBMN-cytome) assay is a modified CBMN assay based on the assessment of micronuclei (MNi) in nucleated cells that have completed only one nuclear division. Along with micronucleus measurement, the CBMN cytome assay allows to assess relevant biodosimetric markers like nucleoplasmic bridges (NPBs), nuclearbuds (NBUDs), apoptotic and necrotic cells. The present study is aimed at obtaining in vitro dose response data for the induction of MNi, NPBs, NBUDs, apoptotic and necrotic cells in human lymphocytes using 60Co-gamma rays. An attempt has been made to validate possibility of applying NPBs and NBUDs as new biodosimetry endpoints. The 60Co gamma chamber with dose rate 1.2 Gy was used for irradiation. The dose range was selected was 0 to 6 Gy. A total of 1000 binucleated cells per dose were evaluated for the frequency of MNi, NPBs, NBUDs, apoptotic and necrotic cells. The MN induction was found to be linear quadratic and the dose response relationship can be represented by Y(MNi) = (0.04 ± 0.016) + (0.041 ± 0.014) D + (0.038 ± 0.002) D2 (with R2=0.998, and p < 0.0001). The NPBs are narrow DNA-containing bridges linking the two daughter nuclei, and represent an indicator of dicentric chromosomes resulting from mis-repaired DNA breaks or telomere end fusions, which can be a useful tool for biodosimetry. The results show a linear quadratic increase in NPBs with the radiation dose, and the dose response relation can be written as Y(NPBs) = (0.002 ± 8.57 x 10-4 ) + (0.0026 ± 8.57 x 10-5) D + (0.00243 ± 5.4 x 10-4 ) D2 (with R2=0.99, and p = 0.0046). The study concludes that NPBs frequency against radiation dose can be used for biodosimetry application, where as NBUDs frequency does not vary significantly with the radiation dose. (author)
Energy Technology Data Exchange (ETDEWEB)
Fhager, V
2000-01-01
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%.
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%
Woodruff, J. D.; Donnelly, J. P.; Emanuel, K.
2007-12-01
Coastal overwash deposits preserved within backbarrier sediments extend the documented record of tropical cyclone strikes back several millennia, providing valuable new data that help to elucidate links between tropical cyclone activity and climate variability. Certain caveats should be considered, however, when assessing trends observed within these paleo-storm records. For instance, gaps in overwash activity at a particular site could simply be artifacts produced by the random nature of these episodic events. Recently, a 5000 year record of intense hurricane strikes has been developed using coarse-grained overwash deposits from Laguna Playa Grande (LPG), a coastal lagoon located on the island of Vieques, Puerto Rico. The LPG record exhibits periods of frequent and infrequent hurricane-induced overwash activity spanning many centuries. These trends are consistent with overwash reconstructions from western Long Island, NY, and have been linked in part to variability in the El Niño/Southern Oscillation and the West African monsoon. Here we assess the statistical significance for active and inactive periods at LPG by creating thousands of synthetic overwash records for the site using storm tracks generated by a coupled ocean-atmosphere hurricane model set to mimic modern climatology. Results show that periods of infrequent overwash activity at the LPG site between 3600 and 1500 yrs BP and 1000 and 250 yrs BP are extremely unlikely to occur under modern climate conditions (above 99 percent confidence). This suggests that the variability observed in the Vieques record is consistent with changing climatic boundary conditions. Overwash frequency is greatest over the last 300 years, with 2 to 3 deposits/century compared to 0.6 deposits/century for earlier active regimes from 2500 to 1000 yrs BP and 5000 to 3600 yrs BP. While this may reflect an unprecedented level of activity over the last 5000 years, it may also in part be due to an undercounting of events in older sediments. Accounting for the 75 % lower accumulation rates in older sediments is alone not enough to explain the increased frequency of event deposits observed in the historic record. However, the most recent active interval is only 300 yrs. The variance in frequency over this time period is relatively high (2? = 1.4 deposits/yr) and demonstrates the limitations associated with estimating reoccurrence intervals for extreme flooding using sediments from a single location.
Dose response considerations in risk assessment--an overview of recent ILSI activities.
Holsapple, Michael P; Wallace, Kendall B
2008-08-15
This paper will provide some perspective on the role that a consideration of the dose-response has played (past), is playing (present) and will play (future) in human risk assessment with special emphasis on a number of recent activities undertaken by various components of the International Life Sciences Institute (ILSI). The dose-response is a critically important concept in every aspect of biomedical science, including toxicology. A characterization of the dose response has been recognized as one of the four essential components of risk assessment since the release of the NRC/NAS report in 1983, and understanding the dose-response curve is the basis for regulatory toxicology. The introduction of concepts such as hormesis, thresholds of toxicological concern (TTC), and dose-dependent transitions in mechanisms of toxicity have emphasized the complexities associated with a characterization of the dose-response. The transitions to emphasizing predictive toxicology, systems biology, the new 'omics technologies, and high-throughput screening (HTS) have provided a new vision for toxicity testing. One impact of fully integrating these new concepts and technologies is that we will have unprecedented capabilities to explore the dose-response relationship, especially at low doses. How these new insights into the dose-response will affect our definition of threshold, and our understanding of the distinction between adverse and adaptive effects remain to be determined. PMID:18588961
International Nuclear Information System (INIS)
We present a practical methodology for evaluating 3D PET reconstruction methods. It includes generation of random samples from a statistically described ensemble of 3D images resembling those to which PET would be applied in a medical situation, generation of corresponding projection data with noise and detector point spread function simulating those of a 3D PET scanner, assignment of figures of merit appropriate for the intended medical applications, optimization of the reconstruction algorithms on a training set of data, and statistical testing of the validity of hypotheses that say that two reconstruction algorithms perform equally well (from the point of view of a particular figure of merit) as compared to the alternative hypotheses that say that one of the algorithms outperforms the other. Although the methodology was developed with the 3D PET in mind, it can be used, with minor changes, for other 3D data collection methods, such as fully 3D CT or SPECT. (Author)
Alves, Gelio
After the sequencing of many complete genomes, we are in a post-genomic era in which the most important task has changed from gathering genetic information to organizing the mass of data as well as under standing how components interact with each other. The former is usually undertaking using bioinformatics methods, while the latter task is generally termed proteomics. Success in both parts demands correct statistical significance assignments for results found. In my dissertation. I study two concrete examples: global sequence alignment statistics and peptide sequencing/identification using mass spectrometry. High-performance liquid chromatography coupled to a mass spectrometer (HPLC/MS/MS), enabling peptide identifications and thus protein identifications, has become the tool of choice in large-scale proteomics experiments. Peptide identification is usually done by database searches methods. The lack of robust statistical significance assignment among current methods motivated the development of a novel de novo algorithm, RAId, whose score statistics then provide statistical significance for high scoring peptides found in our custom, enzyme-digested peptide library. The ease of incorporating post-translation modifications is another important feature of RAId. To organize the massive protein/DNA data accumulated, biologists often cluster proteins according to their similarity via tools such as sequence alignment. Homologous proteins share similar domains. To assess the similarity of two domains usually requires alignment from head to toe, ie. a global alignment. A good alignment score statistics with an appropriate null model enable us to distinguish the biologically meaningful similarity from chance similarity. There has been much progress in local alignment statistics, which characterize score statistics when alignments tend to appear as a short segment of the whole sequence. For global alignment, which is useful in domain alignment, there is still much room for exploration/improvement. Here we present a variant of the direct polymer problem in random media (DPRM) to study the score distribution of global alignment. We have demonstrate that upon proper transformation the score statistics can be characterized by Tracy-Widom distributions, which correspond to the distributions for the largest eigenvalue of various ensembles of random matrices.
Schelter, Björn; Winterhalder, Matthias; Maiwald, Thomas; Brandt, Armin; Schad, Ariane; Schulze-Bonhage, Andreas; Timmer, Jens
2006-03-01
Nonlinear time series analysis techniques have been proposed to detect changes in the electroencephalography dynamics prior to epileptic seizures. Their applicability in practice to predict seizure onsets is hampered by the present lack of generally accepted standards to assess their performance. We propose an analytic approach to judge the prediction performance of multivariate seizure prediction methods. Statistical tests are introduced to assess patient individual results, taking into account that prediction methods are applied to multiple time series and several seizures. Their performance is illustrated utilizing a bivariate seizure prediction method based on synchronization theory.
Staubert, R.
1985-01-01
Methods for calculating the statistical significance of excess events and the interpretation of the formally derived values are discussed. It is argued that a simple formula for a conservative estimate should generally be used in order to provide a common understanding of quoted values.
Threshold estimation based on a p-value framework in dose-response and regression settings
Mallik, Atul; Banerjee, Moulinath; Michailidis, George
2011-01-01
We use p-values to identify the threshold level at which a regression function takes off from its baseline value, a problem motivated by applications in toxicological and pharmacological dose-response studies and environmental statistics. We study the problem in two sampling settings: one where multiple responses can be obtained at a number of different covariate-levels and the other the standard regression setting involving limited number of response values at each covariate. Our procedure involves testing the hypothesis that the regression function is at its baseline at each covariate value and then computing the potentially approximate p-value of the test. An estimate of the threshold is obtained by fitting a piecewise constant function with a single jump discontinuity, otherwise known as a stump, to these observed p-values, as they behave in markedly different ways on the two sides of the threshold. The estimate is shown to be consistent and its finite sample properties are studied through simulations. Ou...
Threshold estimation based on a p-value framework in dose-response and regression settings.
Mallik, A; Sen, B; Banerjee, M; Michailidis, G
2011-12-01
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 testing the hypothesis that the regression function is at its baseline at each covariate value and then computing the potentially approximate p-value of the test. An estimate of the threshold is obtained by fitting a piecewise constant function with a single jump discontinuity, known as a stump, to these observed p-values, as they behave in markedly different ways on the two sides of the threshold. The estimate is shown to be consistent and its finite sample properties are studied through simulations. Our approach is computationally simple and extends to the estimation of the baseline value of the regression function, heteroscedastic errors and to time series. It is illustrated on some real data applications. PMID:23049132
Statistical determination of significant curved I-girder bridge seismic response parameters
Seo, Junwon
2013-06-01
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.
Directory of Open Access Journals (Sweden)
Dominic Beaulieu-Prévost
2006-03-01
Full Text Available For the last 50 years of research in quantitative social sciences, the empirical evaluation of scientific hypotheses has been based on the rejection or not of the null hypothesis. However, more than 300 articles demonstrated that this method was problematic. In summary, null hypothesis testing (NHT is unfalsifiable, its results depend directly on sample size and the null hypothesis is both improbable and not plausible. Consequently, alternatives to NHT such as confidence intervals (CI and measures of effect size are starting to be used in scientific publications. The purpose of this article is, first, to provide the conceptual tools necessary to implement an approach based on confidence intervals, and second, to briefly demonstrate why such an approach is an interesting alternative to an approach based on NHT. As demonstrated in the article, the proposed CI approach avoids most problems related to a NHT approach and can often improve the scientific and contextual relevance of the statistical interpretations by testing range hypotheses instead of a point hypothesis and by defining the minimal value of a substantial effect. The main advantage of such a CI approach is that it replaces the notion of statistical power by an easily interpretable three-value logic (probable presence of a substantial effect, probable absence of a substantial effect and probabilistic undetermination. The demonstration includes a complete example.
Island method for estimating the statistical significance of profile-profile alignment scores
Poleksic Aleksandar
2009-01-01
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 simulation...
Non-linear dose-response relationships for later health effects: a sensitivity analysis
International Nuclear Information System (INIS)
The use of non-linear dose-response relationships in predicting the incidence of late health effects following three hypothetical accidental releases of radioactive material has been investigated. Two forms of non-linear dose-response relationship were considered: 1) the linear-quadratic and 2) the pure quadratic relationships, both containing a dose-squared term. For the three release categories, a comparison was made of the ratios of the expectation value of the probability distribution of health effects evaluated using a non-linear dose-response relationship to that using a linear relationship. For larger releases the ratio varies with the health effect and the form of the non-linear relationship. For smaller releases, the ratio depends only on the non-linear dose-response relationship. (U.K.)
PCBS: CANCER DOSE-RESPONSE ASSESSMENT AND APPLICATION TO ENVIRONMENTAL MIXTURES (1996)
This report updates the cancer dose-response assessment for polychlorinated biphenyls (PCBs) and shows how information on toxicity, disposition, and environmental processes can be considered together to evaluate health risks from PCB mixtures in the environment. Processes that ch...
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
De, Subhajyoti; Pedersen, Brent S; Kechris, Katerina
2014-11-01
Integrative analyses of genomic, epigenomic and transcriptomic features for human and various model organisms have revealed that many such features are nonrandomly distributed in the genome. Significant enrichment (or depletion) of genomic features is anticipated to be biologically important. Detection of genomic regions having enrichment of certain features and estimation of corresponding statistical significance rely on the expected null distribution generated by a permutation model. We discuss different genome-wide permutation approaches, present examples where the permutation strategy affects the null model and show that the confidence in estimating statistical significance of genome-wide enrichment might depend on the choice of the permutation approach. In those cases, where biologically relevant constraints are unclear, it is preferable to examine whether key conclusions are consistent, irrespective of the choice of the randomization strategy. PMID:23956260
Cellular Mechanism of the Nonmonotonic Dose Response of Bisphenol A in Rat Cardiac Myocytes
Liang, Qian; Gao, Xiaoqian; Chen, Yamei; Hong, Kui
2014-01-01
Background: The need for mechanistic understanding of nonmonotonic dose responses has been identified as one of the major data gaps in the study of bisphenol A (BPA). Previously we reported that acute exposure to BPA promotes arrhythmogenesis in female hearts through alteration of myocyte Ca2+ handling, and that the dose response of BPA was inverted U-shaped. Objective: We sought to define the cellular mechanism underlying the nonmonotonic dose response of BPA in the heart. Methods: We examined rapid effects of BPA in female rat ventricular myocytes using video-edge detection, confocal and conventional fluorescence imaging, and patch clamp. Results: The rapid effects of BPA in cardiac myocytes, as measured by multiple end points, including development of arrhythmic activities, myocyte mechanics, and Ca2+ transient, were characterized by nonmonotonic dose responses. Interestingly, the effects of BPA on individual processes of myocyte Ca2+ handling were monotonic. Over the concentration range of 10–12 to 10–6 M, BPA progressively increased sarcoplasmic reticulum (SR) Ca2+ release and Ca2+ reuptake and inhibited the L-type Ca2+ current (ICaL). These effects on myocyte Ca2+ handling were mediated by estrogen receptor (ER) ? signaling. The nonmonotonic dose responses of BPA can be accounted for by the combined effects of progressively increased SR Ca2+ reuptake/release and decreased Ca2+ influx through ICaL. Conclusion: The rapid effects of BPA on female rat cardiac myocytes are characterized by nonmonotonic dose responses as measured by multiple end points. The nonmonotonic dose response was produced by ER?-mediated monotonic effects on multiple cellular Ca2+ handling processes. This represents a distinct mechanism underlying the nonmonotonicity of BPA’s actions. Citation: Liang Q, Gao X, Chen Y, Hong K, Wang HS. 2014. Cellular mechanism of the nonmonotonic dose response of bisphenol A in rat cardiac myocytes. Environ Health Perspect 122:601–608;?http://dx.doi.org/10.1289/ehp.1307491 PMID:24569941
Lagarde, Fabien; Beausoleil, Claire; Belcher, Scott M.; Belzunces, Luc P; Emond, Claude; Guerbet, Michel; Rousselle, Christophe
2015-01-01
Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships wit...
Onwuegbuzie, Anthony J.; Roberts, J. Kyle; Daniel, Larry G.
2005-01-01
In this article, the authors (a) illustrate how displaying disattenuated correlation coefficients alongside their unadjusted counterparts will allow researchers to assess the impact of unreliability on bivariate relationships and (b) demonstrate how a proposed new "what if reliability" analysis can complement null hypothesis significance tests of…
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
The Hall current system revealed as a statistical significant pattern during fast flows
Snekvik, K.; Nakamura, R.; Østgaard, N.; Haaland, S.; Retinò, A.
2008-11-01
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.
Krumbholz, Aniko; Anielski, Patricia; Gfrerer, Lena; Graw, Matthias; Geyer, Hans; Schänzer, Wilhelm; Dvorak, Jiri; Thieme, Detlef
2014-01-01
Clenbuterol is a well-established ?2-agonist, which is prohibited in sports and strictly regulated for use in the livestock industry. During the last few years clenbuterol-positive results in doping controls and in samples from residents or travellers from a high-risk country were suspected to be related the illegal use of clenbuterol for fattening. A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to detect low clenbuterol residues in hair with a detection limit of 0.02?pg/mg. A sub-therapeutic application study and a field study with volunteers, who have a high risk of contamination, were performed. For the application study, a total dosage of 30?µg clenbuterol was applied to 20 healthy volunteers on 5 subsequent days. One month after the beginning of the application, clenbuterol was detected in the proximal hair segment (0-1?cm) in concentrations between 0.43 and 4.76?pg/mg. For the second part, samples of 66 Mexican soccer players were analyzed. In 89% of these volunteers, clenbuterol was detectable in their hair at concentrations between 0.02 and 1.90?pg/mg. A comparison of both parts showed no statistical difference between sub-therapeutic application and contamination. In contrast, discrimination to a typical abuse of clenbuterol is apparently possible. Due to these findings results of real doping control samples can be evaluated. PMID:25388545
Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms
DEFF Research Database (Denmark)
Urbain, Paul; Jakobsen, Jette
2015-01-01
The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 ?g/g up to 3.9 ± 0.8 ?g/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 ?g/g DW (P <0.0001), which is equivalent to 17.6 ?g (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon.
International Nuclear Information System (INIS)
Asymptotic significance levels of tests for monotone trends in rates or proportions can be profoundly anticonservative when applied to small numbers of events and when distributions of exposure to risk are highly skewed. In such cases Monte Carlo (MC) estimation of observed levels of significance (''p-values'') can be very useful. We describe a simple technique of importance sampling (IS) which can greatly improve the efficiency of MC estimation in this setting. Implementation of the IS technique is described, and the variance of the IS estimator is derived. It is shown that, in many situations likely to occur in practice, the variance is substantially less than that of a simple MC estimator proposed earlier. Generalizations beyond the case of survival data without ties are described, and the use of IS is illustrated with data regarding mortality among atomic bomb survivors. (author)
Andrade, MA; Ponting, CP; Gibson, TJ; Bork, P.
2000-01-01
Short protein repeats, frequently with a length between 20 and 40 residues, represent a significant fraction of known proteins. Many repeats appear to possess high amino acid substitution rates and thus recognition of repeat homologues is highly problematic. Even if the presence of a certain repeat family is known, the exact locations and the number of repetitive units often cannot be determined using current methods. We have devised an iterative algorithm based on optimal and sub-optimal sco...
Orife, Tobore; Lisle, Richard J.
2006-06-01
Fault-slip analysis assumes that measured slip lineations on faults represent the direction of maximum resolved stress produced by single homogenous state of stress. To devise criteria for recognising natural data that do not comply with this assumption, the performance of fault-slip methods is examined when used to analyse unsuitable data; namely, faults and slip lineations with randomly chosen orientations. Data quality is often judged by examining the average discrepancy between the orientation of actual slip lineation on each fault and the lineation theoretically predicted from the best-fit tensor. In this work, however, it is found that random faults also yield small angular misfits in conditions where eight or less faults are used. This criterion is therefore only useful for large samples of faults. Another test of data quality is to use the existence of tensors that are compatible with a given data set. However, even for random data, tensors can be found that are capable of explaining the lineation orientations. For example, the existence of compatible stress orientations deduced from the right dihedra method is no proof that the data meet the assumptions of the method. The probability of finding such tensors depends on the tolerance used when assessing fit, and the total number of trial tensors used. A more useful check on data quality is the proportion of trial tensors that fit data sets. For random data this proportion is found to decrease rapidly with sample size. For sample sizes greater than five faults, the expected proportion of tensors fitting is very small (<1%). Statistical tests are proposed. This study emphasises the dangers of palaeostress determinations from small numbers of faults. All of the tests of quality increase in power as the number of faults in the sample increases. It is concluded that stress estimates based on eight or less faults should be treated with grave suspicion.
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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)
Massey, J. L.
1976-01-01
The very low error probability obtained with long error-correcting codes results in a very small number of observed errors in simulation studies of practical size and renders the usual confidence interval techniques inapplicable to the observed error probability. A natural extension of the notion of a 'confidence interval' is made and applied to such determinations of error probability by simulation. An example is included to show the surprisingly great significance of as few as two decoding errors in a very large number of decoding trials.
Pardo-Igúzquiza, Eulogio; RodríGuez-Tovar, Francisco J.
2006-05-01
One of the most often used methods in the spectral analysis of climatic time series is the parametric method of maximum entropy based on an autoregressive model. The method of maximum entropy is particularly appealing because of its high resolution and its good performance with short time series. Its main drawback is that the statistical significance of the spectral peaks is difficult to assess; consequently, there is a risk of accepting spurious peaks as having a physical origin. We propose to use a computer intensive method, the permutation test, for assessing the statistical significance of the spectral peaks, showing its implementation and the results using simulated and real data. With the simulated data we illustrate the applicability to a short time series but with rich signal content, while with the time series of the Southern Oscillation Index (SOI) we illustrate how it may be used in the estimation of the spectrogram.
Ye, Xiaohua; Li, LiXia; Gao, Yanhui; Zhou, Shudong; Yang, Yi; Chen, Sidong
2015-09-30
A growing body of evidence indicates a strong association between smoking and depression. However, little is known about the possible effects of second-hand smoke (SHS) exposure on depression. This study aimed to examine the potential dose-response relation between SHS exposure and depressive symptoms among non-smoking middle-aged women. A cross-sectional survey was conducted using a stratified three-stage sampling method. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale with a cut-off point of 16. Self-reported SHS exposure was defined as non-smokers? inhalation of the smoke exhaled from smokers on at least one day a week. The multivariable logistic regression analysis was completed with adjustment for potential confounders. Among 1280 middle-aged women, 19.4% were classified as having depressive symptoms. There was a 104% increased odds of depressive symptoms corresponding to SHS exposure in general (OR=2.04, 95% CI 1.48-2.79) using no exposure as reference. There were significant positive relations between SHS exposure in general and depressive symptoms in a dose-response manner. These significant trends were observed consistently whether SHS exposure occurred in homes or workplaces. Our findings suggest that long-term and regular SHS exposure is associated with a significant, dose-dependent increase in risk of depressive symptoms. PMID:26231582
Karmakar, Bikram; Dhara, Kumaresh; Dey, Kushal Kumar; Basu, Analabha; Ghosh, Anil
2012-01-01
For testing the statistical significance of a treatment effect, we usually compare between two parts of a population, one is exposed to the treatment, and the other is not exposed to it. Standard parametric and nonparametric two-sample tests are often used for this comparison. But direct applications of these tests can yield misleading results, especially when the population has some hidden sub-populations, and the impact of this sub-population difference on the study variab...
Habitual Chocolate Consumption May Increase Body Weight in a Dose-Response Manner
Greenberg, James A.; Buijsse, Brian
2013-01-01
Objective Habitual chocolate intake was recently found to be associated with lower body weight in three cross-sectional epidemiological studies. Our objective was to assess whether these cross-sectional results hold up in a more rigorous prospective analysis. Methods We used data from the Atherosclerosis Risk in Communities cohort. Usual dietary intake was assessed by questionnaire at baseline (1987–98), and after six years. Participants reported usual chocolate intake as the frequency of eating a 1-oz (?28 g) serving. Body weight and height were measured at the two visits. Missing data were replaced by multiple imputation. Linear mixed-effects models were used to evaluate cross-sectional and prospective associations between chocolate intake and adiposity. Results Data were from 15,732 and 12,830 participants at the first and second visit, respectively. More frequent chocolate consumption was associated with a significantly greater prospective weight gain over time, in a dose-response manner. For instance, compared to participants who ate a chocolate serving less often than monthly, those who ate it 1–4 times a month and at least weekly experienced an increase in Body Mass Index (kg/m2) of 0.26 (95% CI 0.08, 0.44) and 0.39 (0.23, 0.55), respectively, during the six-year study period. In cross-sectional analyses the frequency of chocolate consumption was inversely associated with body weight. This inverse association was attenuated after excluding participants with preexisting obesity-related illness. Compared to participants without such illness, those with it had higher BMI and reported less frequent chocolate intake, lower caloric intake, and diets richer in fruits and vegetables. They tended to make these dietary changes after becoming ill. Conclusions Our prospective analysis found that a chocolate habit was associated with long-term weight gain, in a dose-response manner. Our cross-sectional finding that chocolate intake was associated with lower body weight did not apply to participants without preexisting serious illness. PMID:23950919
The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields
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Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a 60Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The alanine detector can be used without difficulty in neutron fields. The response has been understood with the model used which includes the relative effectiveness. Results and the corresponding discussion lead to the conclusion that application in neutron fields for medical purpose is limited by its sensitivity but that it is a useful tool as supplement to other detectors and verification of neutron source descriptions
Martucci, G.; Carniel, S.; Chiggiato, J.; Sclavo, M.; Lionello, P.; Galati, M. B.
2010-06-01
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.
Soedamah-Muthu, Sabita S; Verberne, Lisa D M; Ding, Eric L; Engberink, Mariëlle F; Geleijnse, Johanna M
2012-11-01
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
Iacucci, Ernesto; Zingg, Hans H; Perkins, Theodore J
2012-01-01
High-throughput molecular biology studies, such as microarray assays of gene expression, two-hybrid experiments for detecting protein interactions, or ChIP-Seq experiments for transcription factor binding, often result in an "interesting" set of genes - say, genes that are co-expressed or bound by the same factor. One way of understanding the biological meaning of such a set is to consider what processes or functions, as defined in an ontology, are over-represented (enriched) or under-represented (depleted) among genes in the set. Usually, the significance of enrichment or depletion scores is based on simple statistical models and on the membership of genes in different classifications. We consider the more general problem of computing p-values for arbitrary integer additive statistics, or weighted membership functions. Such membership functions can be used to represent, for example, prior knowledge on the role of certain genes or classifications, differential importance of different classifications or genes to the experimenter, hierarchical relationships between classifications, or different degrees of interestingness or evidence for specific genes. We describe a generic dynamic programming algorithm that can compute exact p-values for arbitrary integer additive statistics. We also describe several optimizations for important special cases, which can provide orders-of-magnitude speed up in the computations. We apply our methods to datasets describing oxidative phosphorylation and parturition and compare p-values based on computations of several different statistics for measuring enrichment. We find major differences between p-values resulting from these statistics, and that some statistics recover "gold standard" annotations of the data better than others. Our work establishes a theoretical and algorithmic basis for far richer notions of enrichment or depletion of gene sets with respect to gene ontologies than has previously been available. PMID:22375144
Statistical Intercomparison of Significant Wave Height from Envisat, Jason-1 and GFO
Cao, D.; Tolman, H.; Gerald, V.
2006-05-01
Altimeter significant wave height (SWH) data play an increasingly important role in the ocean wave application and research. Altimeter SWH retrievals are validated during testing after launch. However, operational use of these data require continuous monitoring of there quality. We present an intercomparison of two years of altimeter data from the Envisat, Jason-1 and GFO altimeters, and provide a long-term assessment of their quality using collocations with buoy data. After bias corrections based on collocations with buoy data have been applied, the two-year l average of the three altimeters SWHs are nearly identical. The difference is within 0.1m, and is tentatively consistent with the different and sparse sampling of the three altimeters. The ENVSAT SWH are marginally lower than the average, and the Jason-1 SWH are marginally higher than the average in the area close to northern hemisphere continents. In the southern hemisphere, the ENVSAT SWH are marginally higher, and the Jason-1 SWH are marginally lower. The GFO SWH are marginally lower than the average of the three altimeters for most of the global oceans. It is now planned to assimilate these data into the operational global wave forecast model (WaveWatch III) at NCEP.
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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)
Dose-response algorithms for water-borne Pseudomonas aeruginosa folliculitis.
Roser, D J; Van Den Akker, B; Boase, S; Haas, C N; Ashbolt, N J; Rice, S A
2015-05-01
We developed two dose-response algorithms for P. aeruginosa pool folliculitis using bacterial and lesion density estimates, associated with undetectable, significant, and almost certain folliculitis. Literature data were fitted to Furumoto & Mickey's equations, developed for plant epidermis-invading pathogens: N l = A ln(1 + BC) (log-linear model); P inf = 1-e(-r c C) (exponential model), where A and B are 2.51644 × 107 lesions/m2 and 2.28011 × 10-11 c.f.u./ml P. aeruginosa, respectively; C = pathogen density (c.f.u./ml), N l = folliculitis lesions/m2, P inf = probability of infection, and r C = 4·3 × 10-7 c.f.u./ml P. aeruginosa. Outbreak data indicates these algorithms apply to exposure durations of 41 ± 25 min. Typical water quality benchmarks (?10-2 c.f.u./ml) appear conservative but still useful as the literature indicated repeated detection likely implies unstable control barriers and bacterial bloom potential. In future, culture-based outbreak testing should be supplemented with quantitative polymerase chain reaction and organic carbon assays, and quantification of folliculitis aetiology to better understand P. aeruginosa risks. PMID:25275553
A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage.
Wang, J F; Schramm, D D; Holt, R R; Ensunsa, J L; Fraga, C G; Schmitz, H H; Keen, C L
2000-08-01
Evidence from epidemiological studies suggests that a diet high in plant foods and rich in polyphenols is inversely associated with a risk for cardiovascular and other chronic diseases. Chocolate, like red wine and green tea, is a polyphenol-rich food, primarily containing procyanidin polyphenols. These polyphenols are hypothesized to provide cardioprotective effects due to their ability to scavenge free radicals and inhibit lipid oxidation. Herein, we demonstrate that 2 h after the ingestion of a procyanidin-rich chocolate containing 5.3 mg total procyanidin/g, of which 1.3 mg/g was (-)-epicatechin (epicatechin), plasma levels of epicatechin increased 133 +/- 27, 258 +/- 29 and 355 +/- 49 nmol/L in individuals who consumed 27, 53 and 80 g of chocolate, respectively. That the rise in plasma epicatechin levels was functionally significant is suggested by observations of trends for dose-response increases in the plasma antioxidant capacity and decreases in plasma lipid oxidation products. The above data support the theories that in healthy adults, 1) a positive relationship exists between procyanidin consumption and plasma procyanidin concentration and 2) the rise in plasma epicatechin contributes to the ability of plasma to scavenge free radicals and to inhibit lipid peroxidation. PMID:10917932
Dose - response relationship between noise exposure and the risk of occupational injury.
Yoon, Jin-Ha; Hong, Jeong-Suk; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk
2015-01-01
Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers' Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively). Workplace dust exposure was classified as noise exposure as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals) derived from a logistic regression model were 1.68 (1.27-2.24) and 3.42 (2.26-5.17) at 80-89 dB and ? 90 dB versus Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury. PMID:25599757
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
Kossobokov, Vladimir; Le Mouël, Jean-Louis; Courtillot, Vincent
2010-05-01
We study the effect of solar variability on temperatures recorded in three European stations with the longest gapless series available (Prague, Bologna and Uccle). Following a pattern recognition approach, we partition daily temperature “indices” (minimum, maximum and range) in two separate classes with respect to the level of solar activity (high H vs low L 11 year cycles). Using the two-sample Kolmogorov-Smirnov statistics, multiple shuffles of data, and other partitions, we demonstrate that the separation between the probability distribution functions of H and L temperatures is statistically significant and robust. We find that average annual variations for the H and L classes display common and site-specific patterns. For practically all series considered, differences between graphs of annual change for the two classes H and L are large (˜1 °C). Solar activity accounts, at least in part, for the multi-decadal variations in temperature observed at these European sites in the past two centuries.
Park, M. Y.; Lee, D.-Y.; Ohtani, S.; Kim, K. C.
2010-11-01
Magnetic dipolarization has been considered as a key element of substorm phenomena. In this work we investigate the spectral features of the magnetic dipolarization fluctuations in frequency-time space by using the continuous wavelet transform technique. We present details of the analysis for three specific examples and the statistical results for 82 magnetic dipolarizations that occurred at X > ˜-11.5 RE in the near-Earth plasma sheet. We focus on a low-frequency regime defined here as 0.005 to 0.03 Hz for convenience sake (typically well below local proton gyrofrequency). On the basis of the three specific events, we explicitly demonstrate that the magnetic dipolarization fluctuations can be dominated by intense waves at one or more (typically 2-3) discrete frequencies in the low-frequency regime. Statistically, we find that this is the case for 59 (about 72%) out of the 82 events. In addition, we find that such a wave starts to grow in amplitude, thus implying occurrence of instability, typically minutes prior to the dipolarization onset time. The estimated exponential growth time is less than 2 min for ˜68% out of the 72% events. The statistically averaged frequency for the strongest wave is ˜0.01Hz, which we argue is in the regime of ballooning instability. All these features are most clearly seen in the compressional component of magnetic fluctuations. For two of the three example events, it is demonstrated that the magnetic fluctuations on the perpendicular plane are linearly polarized for a given frequency while a more comprehensive statistical study of polarization features is left for a future work. On the basis of the results obtained in this work we conclude that the association of low-frequency instability with substorm-associated dipolarizations can be quite significant from a statistical viewpoint.
Scientific Electronic Library Online (English)
Reinaldo Alberto, Sánchez Turcios.
2015-03-01
Full Text Available Todas la pruebas estadísticas tienen un valor de p significativo a partir de [...] rafos, por lo que se establece un debate en la comunidad científica donde clásicamente se consideraba obtener la significancia de p un sello de garantía, que el proyecto de investigación era capaz de aceptar o rechazar la hipótesis. El objetivo de este artículo es discutir los cuestionamientos de la significancia de p. Abstract in english All statistical tests have a p value that is significant when [...] bate among the scientific community: obtaining p significance was considered as a guarantee that the research project would be an appropriate contrast between the hypothesis and the acceptance, or rejection, of it. The purpose of this paper is to construct a discussion about p significance.
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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
Energy Technology Data Exchange (ETDEWEB)
Kim, Jin Kyu; Kim, Yeon Ku; Song, Hi Sup [KAERI, Taejon (Korea, Republic of)
1999-10-01
This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronucleus showed a good dose-response relationship in the range of dose 0{approx}50 cGy. On the basis of the relationship, a dose of 1 cGy resulted in two additional micronuclei in 100 tetrads. The radiation dose-response relationship of micronucleus occurrence is prerequisite to biological monitoring of radiation and can be modified for biological risk assessment of toxicants, and to safety test of water or soil integrity.
Baluev, Roman V.
2013-11-01
We consider the `multifrequency' periodogram, in which the putative signal is modelled as a sum of two or more sinusoidal harmonics with independent frequencies. It is useful in cases when the data may contain several periodic components, especially when their interaction with each other and with the data sampling patterns might produce misleading results. Although the multifrequency statistic itself was constructed earlier, for example by G. Foster in his CLEANest algorithm, its probabilistic properties (the detection significance levels) are still poorly known and much of what is deemed known is not rigorous. These detection levels are nonetheless important for data analysis. We argue that to prove the simultaneous existence of all n components revealed in a multiperiodic variation, it is mandatory to apply at least 2n - 1 significance tests, among which most involve various multifrequency statistics, and only n tests are single-frequency ones. The main result of this paper is an analytic estimation of the statistical significance of the frequency tuples that the multifrequency periodogram can reveal. Using the theory of extreme values of random fields (the generalized Rice method), we find a useful approximation to the relevant false alarm probability. For the double-frequency periodogram, this approximation is given by the elementary formula (?/16)W2e- zz2, where W denotes the normalized width of the settled frequency range, and z is the observed periodogram maximum. We carried out intensive Monte Carlo simulations to show that the practical quality of this approximation is satisfactory. A similar analytic expression for the general multifrequency periodogram is also given, although with less numerical verification.
Assessment of mechanisms driving non-linear dose-response relationships in genotoxicity testing.
Guérard, M; Baum, M; Bitsch, A; Eisenbrand, G; Elhajouji, A; Epe, B; Habermeyer, M; Kaina, B; Martus, H J; Pfuhler, S; Schmitz, C; Sutter, A; Thomas, A D; Ziemann, C; Froetschl, R
2015-01-01
In genetic toxicology, risk assessment has traditionally adopted linear dose-responses for any compound that causes genotoxic effects. Increasing evidence of non-linear dose-responses, however, suggests potential cellular tolerance to low levels of many genotoxicants with diverse modes of action. Such putative non-linear dose-responses need to be substantiated by strong mechanistic data that identifies the mechanisms responsible for the tolerance to low doses. This can be achieved by experimental demonstration of cytoprotective mechanisms and by providing experimental support for the existence of tolerance mechanisms against low dose effects. By highlighting key experiments into low dose mechanisms, this review aims to clarify which mechanistic data are required to support the use of non-linear dose-response models in risk assessment. Such key experiments are presented and discussed for alkylating agents, oxidants, particulate matter, nucleoside analogues, topoisomerase inhibitors and aneugens and exemplify the use of gene knockout models or transgenic models as well as chemical modulators of key effectors of relevant pathways and their impact on dose-response relationships. In vitro studies are particularly valuable to elucidate mechanisms of low-dose protection or lack thereof, while in vivo experiments are most appropriate for deriving a safe dose. In order to evaluate the existence of non-linear dose-response relationships for genotoxicants, we suggest that careful attention should be given to the mode of genotoxic action, relevant biomarkers of exposure, as well as to the existence and impact of potential cytoprotective mechanisms like detoxifying metabolism and DNA repair. PMID:25795120
Ju, Sang-Yhun; Choi, Whan-Seok; Ock, Sun-Myeong; Kim, Chul-Min; Kim, Do-Hoon
2014-01-01
Increasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational studies reporting risk ratios with 95% confidence intervals (CIs) for metabolic syndrome in ?3 categories of dietary magnesium intake levels were selected. The data extraction was performed independently by two authors, and the quality of the studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Based on eight cross-sectional studies and two prospective cohort studies, the pooled relative risks of metabolic syndrome per 150 mg/day increment in magnesium intake was 0.88 (95% CI, 0.84–0.93; I2 = 36.3%). The meta-regression model showed a generally linear, inverse relationship between magnesium intake (mg/day) and metabolic syndrome. This dose-response meta-analysis indicates that dietary magnesium intake is significantly and inversely associated with the risk of metabolic syndrome. However, randomized clinical trials will be necessary to address the issue of causality and to determine whether magnesium supplementation is effective for the prevention of metabolic syndrome. PMID:25533010
Directory of Open Access Journals (Sweden)
Sang-Yhun Ju
2014-12-01
Full Text Available ncreasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational studies reporting risk ratios with 95% confidence intervals (CIs for metabolic syndrome in ?3 categories of dietary magnesium intake levels were selected. The data extraction was performed independently by two authors, and the quality of the studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS. Based on eight cross-sectional studies and two prospective cohort studies, the pooled relative risks of metabolic syndrome per 150 mg/day increment in magnesium intake was 0.88 (95% CI, 0.84–0.93; I2 = 36.3%. The meta-regression model showed a generally linear, inverse relationship between magnesium intake (mg/day and metabolic syndrome. This dose-response meta-analysis indicates that dietary magnesium intake is significantly and inversely associated with the risk of metabolic syndrome. However, randomized clinical trials will be necessary to address the issue of causality and to determine whether magnesium supplementation is effective for the prevention of metabolic syndrome.
Østvand, L.; Rypdal, K.; Rypdal, M.
2014-03-01
Various interpretations of the notion of a trend in the context of global warming are discussed, contrasting the difference between viewing a trend as the deterministic response to an external forcing and viewing it as a slow variation which can be separated from the background spectral continuum of long-range persistent climate noise. The emphasis in this paper is on the latter notion, and a general scheme is presented for testing a multi-parameter trend model against a null hypothesis which models the observed climate record as an autocorrelated noise. The scheme is employed to the instrumental global sea-surface temperature record and the global land temperature record. A trend model comprising a linear plus an oscillatory trend with period of approximately 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.
Dose-response assessment by a fuzzy linear-regression method.
Lee, Y W; Chung, S Y; Bogardi, I; Dahab, M F; Oh, S E
2001-01-01
Regression analysis has been used to characterize the relationship between an exposure dose and the incidence of an adverse health effect such as cancer. However, the regression rarely describes the true relationship due to uncertainties in dose-response data and relationships. Therefore, a method is developed to perform dose-response assessments by a fuzzy linear regression which explicitly exhibit these uncertainties. This method is applied to define the relationship between a particular nitrate dose to humans and its corresponding cancer risk. PMID:11380171
Dose response and fading characteristics of an alanine-agarose gel
International Nuclear Information System (INIS)
The dose response of an alanine-agarose gel, analyzed by ESR spectrometry, and the stability of the radiation-induced free radicals have been investigated. The stability of the ESR signal is higher for dosimeter samples analyzed at 77 K than for dried samples, analyzed at room-temperature. The dose response is linear to within ±2% in the absorbed dose interval 2-100 Gy. The variations in spectral line shape were analyzed at temperatures between 77 and 270 K. The experimental ESR spectrum at 77 K was compared with a simulated spectrum of polycrystals of L-?-alanine. (Author)
International Nuclear Information System (INIS)
Cultured peripheral blood lymphocytes of controls and uranium miners were analyzed for the prevalence of structural chromosomal aberrations. The frequency data are compared between controls and five groups of miners with exposures expressed in working level months (WLM). The results demonstrate: (i) the prevalence of dicentrics + rings is not a good biological dose-response indicator; (ii) there is a marked decrease in the prevalence of deletions or dicentrics + rings + deletions in the most highly exposed individuals (Group V; >3000 WLM); (iii) apart from the Group V results, all aberration categories except dicentrics + rings demonstrate a significant and monotonic biological response increasing uniformly with estimated radiation dose through Group IV (1740 to 2890 WLM); (iv) including Group V individuals, the aberration category which shows the most consistent pattern of increase with dose is the pericentric inversions + translocations grouping (Spearman's r/sub s/ = 0.943; P = 0.01); (v) excepting dicentrics + rings, the prevalence of chromosome aberrations is a sensitive biological indicator of low-level uranium miner irradiation; and (vi) significant (P = 0.01) differences in the prevalence of chromosome aberrations are observed between miners with regular to mildly atypical bronchial cell cytology and those with markedly atypical cells to carcinoma in situ. A marked increase in the prevalence of chromosome aberrations is probably a valid indicator of health risk in the miner groups. The relevance of the chromosome aberrations test for individual miners is more difficult to assess, but the absence of a high frequency of aberrations in an individual cannot be construed as a lack of risk. The application of radiation cytogenetic monitoring to other populations potentially exposed to high doses of radon daughters is discussed
Dose-Response Relationship of Phototherapy for Hyperbilirubinemia
DEFF Research Database (Denmark)
Vandborg, Pernille Kure; Hansen, Bo Moelholm
2012-01-01
BACKGROUND AND OBJECTIVE:Using light-emitting diodes during conventional phototherapy, it is possible to reduce the distance from light source to infant, thus increasing light irradiance. The objective of this study was to search for a "saturation point" (ie, an irradiation level above which there is no further decrease in total serum bilirubin [TsB]). This was a prospective randomized study performed in the NICU of Aalborg Hospital, Denmark.METHODS:One hundred fifty-one infants (gestational age ?33 weeks) with uncomplicated hyperbilirubinemia were randomized to 1 of 4 distances from the phototherapy device to the mattress (20, 29, 38, and 47 cm). TsB was measured before and after 24 hours of phototherapy and irradiance every eighth hour. Main outcome was 24-hour decrease of TsB expressed in percent, ( TsB(0-24), difference between TsB(0) and TsB(24) [%]).RESULTS:A highly significant linear relation was seen between light irradiance and TsB(0-24) (%) (P <.001): when the irradiance increased from 20 to 55 ?W/cm(2)/nm, TsB(0-24) (%) increased from approximately 30% to 50%. In addition, smooth regression showed no tendency for TsB(0-24) (%) to level off as irradiance increased. TsB(0-24) (%) was negatively correlated to birth weight and positively to formula volume. Average weight gain during phototherapy was 1%, independent of light irradiance.CONCLUSIONS:By using light-emitting diodes, we found a linear relation between light irradiance in the range of 20 to 55 ?W/cm(2)/nm and a decrease in TsB after 24 hours of therapy, with no evidence of a saturation point.
Dose-response relationships for female radium dial workers
International Nuclear Information System (INIS)
Among 1474 women employed in the United States radium dial-painting industry before 1930, there are 61 known cases of bone sarcoma and 21 cases of carcinoma of the paranasal sinuses or the mastoid air cells (''head carcinomas''). The relative effectiveness of 226Ra and 228Ra and dose-incidence relationships were examined for the 759 of these women whose radium body burden has been determined; there are 38 cases of bone sarcoma and 17 cases of head carcinoma in this group. Incidence (I) was expressed as tumor cases per person-year and the dose parameter (D) was the quantity (microcuries) of radium that entered the blood during the period of exposure. To the observed data for each type of tumor were fitted equations that can be formulated from the general form I = (C + alpha dD+ ?D2)e-?/sup D/, where C, the natural incidence for this population, was about 10-5 per person-year. For each equation, the best values of the dose coefficients were found by a least-squares fitting procedure. An equation of the form I = (C + BD2)e-/sup ?D/ provided the best fit for the bone sarcomas, when the dose was expressed as microcuries of 226Ra plus 2.5 times microcuries of 228Ra. An acceptable fit to the head carcinoma data was provided by the linear equation I = C + d alpha ? with D equal to microcuries of 226Ra. As a test of bias due to selection of cases with known symptoms of malignancy, the analyses were repeated after removal of all cases for whom radium was determined only after exhumation, and no significant changes in the fitted coefficients were found. The dose-incidence equations obtained when the dose was expressed as average skeletal dose in rad are also given
Baluev, Roman V
2013-01-01
We consider the "multi-frequency" periodogram, in which the putative signal is modelled as a sum of two or more sinusoidal harmonics with idependent frequencies. It is useful in the cases when the data may contain several periodic components, especially when their interaction with each other and with the data sampling patterns might produce misleading results. Although the multi-frequency statistic itself was already constructed, e.g. by G. Foster in his CLEANest algorithm, its probabilistic properties (the detection significance levels) are still poorly known and much of what is deemed known is unrigourous. These detection levels are nonetheless important for the data analysis. We argue that to prove the simultaneous existence of all $n$ components revealed in a multi-periodic variation, it is mandatory to apply at least $2^n-1$ significance tests, among which the most involves various multi-frequency statistics, and only $n$ tests are single-frequency ones. The main result of the paper is an analytic estima...
Dunne, E. M.; Lee, L. A.; Reddington, C. L.; Carslaw, K. S.
2012-12-01
Observed correlations between short-term decreases in cosmic ray ionisation and cloud and aerosol properties have been attributed to short-term decreases in the ion-induced nucleation rate. We use a global aerosol microphysics model to determine whether a 10 day reduction of 15% in the nucleation rate could generate a statistically significant response in aerosol concentrations and optical properties. As an upper limit to the possible effect of changes in ion-induced nucleation rate, we perturb the total nucleation rate, which has been shown to generate particle concentrations and nucleation events in reasonable agreement with global observations. When measured against a known aerosol control state, the model predicts a 0.15% decrease in global mean cloud condensation nucleus concentration at the surface. However, taking into account the variability in aerosol, no statistically significant response can be detected in concentrations of particles with diameters larger than 10 nm, in cloud condensation nuclei with diameters larger than 70 nm, or in the Ångström exponent. The results suggest that the observed correlation between short-term decreases in cosmic ray ionisation and cloud and aerosol properties cannot be explained by associated changes in the large-scale nucleation rate.
Hwang, J. A.; Lee, D.-Y.; Lyons, L. R.; Smith, A. J.; Zou, S.; Min, K. W.; Kim, K.-H.; Moon, Y.-J.; Park, Y. D.
2007-09-01
During high-speed solar wind streams, substorms occur repetitively and relativistic electron fluxes enhance significantly. It has recently been proposed that enhanced dawnside chorus waves lead to the energization of the relativistic electrons and that they are associated with the periods of enhanced convection that precede substorm expansions, rather than with the expansions themselves. In this paper, we have evaluated the statistical significance of this association using a total of 657 substorms during high-speed solar wind streams observed by the ACE spacecraft and whistler-mode chorus waves observed from the VLF/ELF Logger Experiment (VELOX) at Halley station, Antarctica. We find that ~66% of the substorm events identified at 0400-1400 MLT show the association with the chorus enhancement that starts to increase ~35 min, on average, prior to substorm onsets and remains elevated until declining back to near the preenhancement level in ~16 min, on average, after substorm onsets. Our statistical results suggest that a large number of the chorus wave enhancements at dawn to postnoon local times occur during the enhanced convection period of the substorm growth phase. This is distinguished from the chorus wave enhancement near midnight that is caused by substorm-injected electrons after onsets. We find that ~59% of the events identified at 2200-0200 MLT show chorus enhancements that start on average ~6 min after substorm onsets and remain elevated for ~32 min on average.
Maslova, I.; Kokoszka, P.; Sojka, J.; Zhu, L.
2010-02-01
In recent years, the interaction of the auroral substorms with the equatorial and mid-latitude currents has been the subject of extensive research. We introduce a new statistical technique that allows us to test at a specified significance level whether such a dependence exists, and how long it persists. This quantitative statistical technique, relying on the concepts and tools of functional data analysis, uses directly magnetometer records in one minute resolution, and it can be applied to similar geophysical data which can be represented as daily curves. It is conceptually similar to testing the nullity of the slope in the straight line regression, but both the regressors and the responses are curves rather than points. When the regressors are daily high latitude H-component curves during substorm days and the responses are daily mid- or low latitude H-component curves, our test shows significant dependence (the nullity hypothesis is rejected) which exists not only on the same UT day but also extends into the next day for strong substorms.
Jiang, Luo; Hou, Rui; Gong, Ting-Ting; Wu, Qi-Jun
2015-01-01
Epidemiological studies have provided controversial evidence of the association between dietary fat intake and endometrial cancer (EC) risk. To address this inconsistency, we conducted this dose-response meta-analysis by total dietary fat intake, based on epidemiological studies published up to the end of June 2015 identified from PubMed, EMBASE and Web of Science. Two authors (RH and Q-JW) independently performed the eligibility evaluation and data extraction. All differences were resolved by discussion with the third investigator (LJ). Random-effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). Overall, the search yielded 16 studies (6 cohort and 10 case-control studies) that involved a total of 7556 EC cases and 563,781 non-cases. The summary RR for EC for each 30g/day increment intake was 0.98 (95%CI?=?0.95-1.001; I(2)?=?0%; n?=?11) for total dietary fat. Non-significant results were observed in plant-based fat (summary RR?=?1.05, 95%CI?=?0.94-1.18; I(2)?=?0%; n?=?5) and animal-based fat (summary RR?=?1.17, 95%CI?=?0.92-1.36; I(2)?=?85.0%; n?=?6). Additionally, the null associations were observed in almost all the subgroup and sensitivity analyses. In conclusion, findings of the present meta-analysis suggested a lack of association between total dietary fat intake and EC risk. Further studies, especially prospective designed studies are warranted to confirm our findings. PMID:26568366
Mechanistic interpretation of radiation dose-response relationship for subclinical metastasis
International Nuclear Information System (INIS)
To use a biophysical model based on the kinetics of metastatic formation to interpret radiation dose-response relationship for subclinical metastasis, and compare with what is predicted by the empirical model of Withers et al.. Methods: The metastases control probability (MCP) was formulated as a function of radiation dose and metastatic cell burden (MCB). The MCB was expressed to be log-uniformly distributed, as suggested by Withers et al.. In the mechanistic model, it was derived from the kinetics of primary tumor growth and subsequent metastatic colony formation and growth. A limiting resolution for clinical detection of metastasis (e.g. 109 cells) was assumed, and heterogeneous distributions for various biological parameters were considered. Mathematical expressions for both empirical and mechanistic models were solved analytically, and numerical simulations were performed using Mathcad software. Results: Withers et al. had presented clinical data to support a sigmoid-shaped MCP curve with a slope that is flatter than the control probability for gross tumor. This was verified by assuming the MCB to be log-uniformly distributed from 1 to 109 cells, provided that patients without subclinical metastasis are excluded. However, for patients diagnosed to have localized primary tumor, whether or not subclinical metastases are present remains unknown. This difficulty is alleviated in the mechanistic model, as an explicit expression for the metastasis-free cohort was obtained by subjecting all patients to undergo the Poisson process of metastatic establishment. Numerical simulations confirmed that the sigmoid MCP curve has a shallower slope if heterogeneity in metastatic rate is considered using log-normal distribution. Heterogeneity in metastatic growth rate with Gaussian distribution also resulted in significant flattening from an otherwise sharply-rising deterministic MCP curve. Conclusion: The mechanistic model of metastatogenesis appears to be more versatile for clinical application than the empirical model. It may help in formulating appropriate therapeutic strategy for subclinical metastases
Assessment of dose-response relationship in carcinogenesis following low radiation dosage
International Nuclear Information System (INIS)
The quantitative experimental study of low-level radiation carcinogenesis entails numerous complex problems. Observation of large animal samples over the entire life span is required for definition of the basic (naturally occurring) and modulated (following irradiation) tumour spectrum. As a consequence, a detailed study of the spontaneous tumour incidence in the control population is essential. The data presented are based on a total of 8229 C57 Black/6M mice, of both sexes, observed over their whole life span which, under pathogen-free conditions, extended to about 1200 days. The basic tumour spectrum was defined and subsequently used as a reference system for the comparative evaluaton of the tumour yield following small doses of neutrons or gamma radiation or tritiated thymidine. The experiment was aimed at providing dose-response relationships from external versus internal iradiation. The following conclusions can be tentatively drawn: (1) In control mice, a very high incidence of tumour was observed, namely 84.4% in females versus 66.7% in males. As a consequence, it would seem that the whole concept of tumour induction versus natural tumour incidence should be re-evaluated. (2) Modulation of the basic tumour spectrum incidence following irradiaton appeared to be, in some instances, not only quantitative but also qualitative in nature, as evidenced by an observed shift from type A to type B reticulum cell lymphoma in irradiated mice at all dose levels. (3)In age-specific incidence rates for lymphocytic lymphomas, the time shift of observed values was twofold, towards relatively higher incidence earlier in life and towards relatively lower incidence in late survivors. These observtions suggest an in-depth re-evaluation of some current concepts on the modulation of tumour incidence by carcinogenic agents, from the point of view of their qualitative significance and quantitative assessment
Stein, Mark A; Waldman, Irwin; Newcorn, Jeffrey; Bishop, Jeffrey; Kittles, Rick; Cook, Edwin H
2014-01-01
Objectives: This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD).
Long-term dose-response studies of inhaled or injected radionuclides
International Nuclear Information System (INIS)
This document is the third annual report focussed specifically on the life-span dose-response studies being conducted at the Inhalation Toxicology Research Institute, ITRI, and the University of Utah. The information presented here provides a complete summary status of these studies as of September 30, 1991. This report has been prepared as a stand-alone document for informational purposes
Dose-response measurement in gel dosimeter using various imaging modalities
International Nuclear Information System (INIS)
Measurement methods that accurately measure radiation dose distribution in a three dimensional manner in order to allow comparisons of treatment plans are needed for quality assurance. One such measurement method involves the use of a polymer gel dosimeter to measure the dose distribution in three dimensions. During irradiation, a polymerization reaction makes new chemical bonds and induces changes of the chemical structure of the gel of the gel dosimeter. In the present study, dose-response measurement of an environment-friendly material used in the gel dosimeter was performed by imaging with computed tomography (CT) and R1, R2, and fluid-attenuated inversion-recovery (FLAIR) magnetic resonance imaging (MRI) under various imaging conditions. Dose-response characteristics in the gel dosimeter used in the experiment were observed at doses of 5–20 Gy administered by X-ray CT and MRI. Although the FLAIR signal was a relative value, the dose-response values with FLAIR were excellent compared to those with R1, R2, and CT. Determination of more appropriate imaging conditions could help expand the dose-response parameters of each measurement method.
Dose-response curves with semiochemicals are reported in many articles in insect chemical ecology regarding neurophysiology and behavioral bioassays. Most such curves are shown in figures where the x-axis has order of magnitude increases in dosages versus responses on the y-axis represented by point...
Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors
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, ...
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
A direct dynamic dose-response model of propofol for individualized anesthesia care.
Hahn, Jin-Oh; Dumont, Guy A; Ansermino, J Mark
2012-02-01
In an effort to open up new opportunities in individualized anesthesia care, this paper presents a dynamic dose-response model of propofol that relates propofol dose (i.e., infusion rate) directly to a clinical effect. The proposed model consists of a first-order equilibration dynamics plus a nonlinear Hill equation model, each representing the transient distribution of propofol dose from the plasma to the effect site and the steady-state dose-effect relationship. Compared to traditional pharmacokinetic-pharmacodynamic (PKPD) models, the proposed model has structural parsimony and comparable predictive capability, making it more attractive than its PKPD counterpart for identifying an individualized dose-response model in real-time. The efficacy of the direct dynamic dose-response model over a traditional PKPD model was assessed using a mixed effects modeling analysis of the electroencephalogram (EEG)-based state entropty (SE) response to intravenous propofol administration in 34 pediatric subjects. An improvement in the mean-squared error and r(2) value of individual prediction, as well as the Akaike's information criterion (AIC) was seen with the direct dynamic dose-response model. PMID:22127991
Harrison, Judith; Thompson, Bruce; Vannest, Kimberly J.
2009-01-01
This article reviews the literature on interventions targeting the academic performance of students with attention-deficit/hyperactivity disorder (ADHD) and does so within the context of the statistical significance testing controversy. Both the arguments for and against null hypothesis statistical significance tests are reviewed. Recent standards…
Directory of Open Access Journals (Sweden)
Leitner Dietmar
2005-04-01
Full Text Available Abstract Background A reliable prediction of the Xaa-Pro peptide bond conformation would be a useful tool for many protein structure calculation methods. We have analyzed the Protein Data Bank and show that the combined use of sequential and structural information has a predictive value for the assessment of the cis versus trans peptide bond conformation of Xaa-Pro within proteins. For the analysis of the data sets different statistical methods such as the calculation of the Chou-Fasman parameters and occurrence matrices were used. Furthermore we analyzed the relationship between the relative solvent accessibility and the relative occurrence of prolines in the cis and in the trans conformation. Results One of the main results of the statistical investigations is the ranking of the secondary structure and sequence information with respect to the prediction of the Xaa-Pro peptide bond conformation. We observed a significant impact of secondary structure information on the occurrence of the Xaa-Pro peptide bond conformation, while the sequence information of amino acids neighboring proline is of little predictive value for the conformation of this bond. Conclusion In this work, we present an extensive analysis of the occurrence of the cis and trans proline conformation in proteins. Based on the data set, we derived patterns and rules for a possible prediction of the proline conformation. Upon adoption of the Chou-Fasman parameters, we are able to derive statistically relevant correlations between the secondary structure of amino acid fragments and the Xaa-Pro peptide bond conformation.
Narin, Ali; Isler, Yalcin; Ozer, Mahmut
2014-02-01
In this study, the best combination of short-term heart rate variability (HRV) measures was investigated to distinguish 29 patients with congestive heart failure from 54 healthy subjects in the control group. In the analysis performed, wavelet packet transform based frequency-domain measures and several non-linear parameters were used in addition to standard HRV measures. The backward elimination and unpaired statistical analysis methods were used to select the best one among all possible combinations of these measures. Five distinct typical classifiers with different parameters were evaluated in discriminating these two groups using the leave-one-out cross validation method. Each algorithm was tested 30 times to determine the repeatability of the results. The results imply that the backward elimination method gives better performance when compared to the statistical significance method in the feature selection stage. The best performance (82.75%, 96.29%, and 91.56% for the sensitivity, specificity, and accuracy) was obtained by using the SVM classifier with 27 selected features including non-linear and wavelet-based measures. PMID:24480166
Wang, H. J.; Shi, W. L.; Chen, X. H.
2006-05-01
The West Development Policy being implemented in China is causing significant land use and land cover (LULC) changes in West China. With the up-to-date satellite database of the Global Land Cover Characteristics Database (GLCCD) that characterizes the lower boundary conditions, the regional climate model RIEMS-TEA is used to simulate possible impacts of the significant LULC variation. The model was run for five continuous three-month periods from 1 June to 1 September of 1993, 1994, 1995, 1996, and 1997, and the results of the five groups are examined by means of a student t-test to identify the statistical significance of regional climate variation. The main results are: (1) The regional climate is affected by the LULC variation because the equilibrium of water and heat transfer in the air-vegetation interface is changed. (2) The integrated impact of the LULC variation on regional climate is not only limited to West China where the LULC varies, but also to some areas in the model domain where the LULC does not vary at all. (3) The East Asian monsoon system and its vertical structure are adjusted by the large scale LULC variation in western China, where the consequences axe the enhancement of the westward water vapor transfer from the east east and the relevant increase of wet-hydrostatic energy in the middle-upper atmospheric layers. (4) The ecological engineering in West China affects significantly the regional climate in Northwest China, North China and the middle-lower reaches of the Yangtze River; there are obvious effects in South, Northeast, and Southwest China, but minor effects in Tibet.
Hoeben, Eef; Smit, Johan W; Upmalis, David; Rusch, Sarah; Schaffler, Klaus; Reitmeir, Peter; Mangold, Bernhard
2012-08-01
The aim of the study was to evaluate the analgesic/antihyperalgesic efficacy and to establish the dose-response relationship of morphine immediate release (IR) and oxycodone IR in a human experimental algesimetric model. Calculated effect ratios for peak-to-peak (PtP) amplitudes of laser-evoked potentials (LEPs) and visual analog scales (VAS) postlaser pain on UVB-irradiated skin (main target variables) were 1.68 and 1.18 respectively for oxycodone 10mg/morphine 20mg, 3.00 and 1.63 respectively for oxycodone 15 mg/morphine 30 mg, and 1.12 and 1.25 respectively for oxycodone 20mg/morphine 40 mg. The effect on the laser-PtP amplitude of morphine at the highest dose (40 mg) and of oxycodone at all doses (10, 15, 20mg) was considered to be clinically relevant based on a difference from placebo of ? 2.5 ?V. For both compounds, a statistically significant linear trend was observed between dose groups in at least 1 of the 2 main target variables (adjusted P value for both end points solution. For both compounds, the principal onset of analgesic/antihyperalgesic drug effects was around 0.5 hours with an average peak at about 1 to 2 hours and the effect lasting for more than 3 hours (morphine 20 and 30 mg) or 6 hours (morphine 40 mg and oxycodone all doses). In conclusion, the study demonstrated a solid outcome of a mixed objective/subjective human experimental algesimetric model to approach dose-response relationships and analgesic/antihyperalgesic effects of 2 opioids. PMID:22703892
DEFF Research Database (Denmark)
Skyt, Peter S; Balling, Peter; Petersen, Jørgen B B; Yates, Esben S; Muren, Ludvig P
2011-01-01
The dose response of radiochromic dosimeters is based on radiation-induced chemical reactions and is thus likely to be thermally influenced. In this study we have therefore investigated the temperature dependence of the dose response for such dosimeters, regarding both irradiation and storage conditions.
Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?
International Nuclear Information System (INIS)
Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was ?0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF
The impact of different dose-response parameters on biologically optimized IMRT in breast cancer
Energy Technology Data Exchange (ETDEWEB)
Ferreira, Brigida Costa; Mavroidis, Panayiotis; Adamus-Gorka, Magdalena; Svensson, Roger; Lind, Bengt K [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University (Sweden)], E-mail: brigida@ua.pt
2008-05-21
The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I-II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P{sub +}), the biologically effective uniform dose, dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P{sub +} between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P{sub +} are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose-response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.
Dose-response study of thimerosal-induced murine systemic autoimmunity
International Nuclear Information System (INIS)
The organic compound ethylmercurithiosalicylate (thimerosal), which is primarily present in the tissues as ethylmercury, has caused illness and several deaths due to erroneous handling when used as a disinfectant or as a preservative in medical preparations. Lately, possible health effects of thimerosal in childhood vaccines have been much discussed. Thimerosal is a well-known sensitizing agent, although usually of no clinical relevance. In rare cases, thimerosal has caused systemic immune reactions including acrodynia. We have studied if thimerosal might induce the systemic autoimmune condition observed in genetically susceptible mice after exposure to inorganic mercury. A.SW mice were exposed to 1.25-40 mg thimerosal/l drinking water for 70 days. Antinucleolar antibodies, targeting the 34-kDa protein fibrillarin, developed in a dose-related pattern and first appeared after 10 days in the two highest dose groups. The lowest observed adverse effect level (LOAEL) for antifibrillarin antibodies was 2.5 mg thimerosal/l, corresponding to an absorbed dose of 147 ?g Hg/kg bw and a concentration of 21 and 1.9 ?g Hg/g in the kidney and lymph nodes, respectively. The same LOAEL was found for tissue immune-complex deposits. The total serum concentration of IgE, IgG1, and IgG2a showed a significant dose-related increase in thimerosal-treated mice, with a LOAEL of 5 mg thimerosal/l for IgG1 and IgE, and 20 mg thimerosal/l for IgG2a. The polyclonal B-cell activation showed a significant dose-response relationship with a LOAEL of 10 mg thimerosal/l. Therefore, thimerosal induces in genetically susceptible mice a systemic autoimmune syndrome very similar to that seen after treatment with inorganic mercury, although a higher absorbed dose of Hg is needed using thimerosal. The autoimmune syndrome induced by thimerosal is different from the weaker and more restricted autoimmune reaction observed after treatment with an equipotent dose of methylmercury
The impact of different dose-response parameters on biologically optimized IMRT in breast cancer
International Nuclear Information System (INIS)
The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I-II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose, dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose-response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals
International Nuclear Information System (INIS)
The aim of this study was to investigate the dose response relationship of dicentrics in human lymphocytes after CT scans at tube voltages of 80 and 140 kV. Blood samples from a healthy donor placed in tissue equivalent abdomen phantoms of standard, pediatric and adipose sizes were exposed at dose levels up to 0.1 Gy using a 64-slice CT scanner. It was found that both the tube voltage and the phantom size significantly influenced the CT scan-induced linear dose-response relationship of dicentrics in human lymphocytes. Using the same phantom (standard abdomen), 80 kV CT x-rays were biologically more effective than 140 kV CT x-rays. However, it could also be determined that the applied phantom size had much more influence on the biological effectiveness. Obviously, the increasing slopes of the CT scan-induced dose response relationships of dicentrics in human lymphocytes obtained in a pediatric, a standard and an adipose abdomen have been induced by scattering effects of photons, which strongly increase with increasing phantom size.
Energy Technology Data Exchange (ETDEWEB)
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
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.; Lengsfeld, P.; Voth, M.; Schmid, E.; Pietsch, H.
2010-06-01
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.
Fisher, Aaron; Anderson, G Brooke; Peng, Roger; Leek, Jeff
2014-01-01
Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC). Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%-49.7%]) of statistically significant relationships, and 74.6% (95% CI [72.5%-76.6%]) of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1) that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2) data analysts can be trained to improve detection of statistically significant results with practice, but (3) data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/. PMID:25337457
Fisher, Aaron; Anderson, G. Brooke; Peng, Roger
2014-01-01
Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC). Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%–49.7%]) of statistically significant relationships, and 74.6% (95% CI [72.5%–76.6%]) of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1) that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2) data analysts can be trained to improve detection of statistically significant results with practice, but (3) data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/. PMID:25337457
Directory of Open Access Journals (Sweden)
Aaron Fisher
2014-10-01
Full Text Available Scatterplots are the most common way for statisticians, scientists, and the public to visually detect relationships between measured variables. At the same time, and despite widely publicized controversy, P-values remain the most commonly used measure to statistically justify relationships identified between variables. Here we measure the ability to detect statistically significant relationships from scatterplots in a randomized trial of 2,039 students in a statistics massive open online course (MOOC. Each subject was shown a random set of scatterplots and asked to visually determine if the underlying relationships were statistically significant at the P < 0.05 level. Subjects correctly classified only 47.4% (95% CI [45.1%–49.7%] of statistically significant relationships, and 74.6% (95% CI [72.5%–76.6%] of non-significant relationships. Adding visual aids such as a best fit line or scatterplot smooth increased the probability a relationship was called significant, regardless of whether the relationship was actually significant. Classification of statistically significant relationships improved on repeat attempts of the survey, although classification of non-significant relationships did not. Our results suggest: (1 that evidence-based data analysis can be used to identify weaknesses in theoretical procedures in the hands of average users, (2 data analysts can be trained to improve detection of statistically significant results with practice, but (3 data analysts have incorrect intuition about what statistically significant relationships look like, particularly for small effects. We have built a web tool for people to compare scatterplots with their corresponding p-values which is available here: http://glimmer.rstudio.com/afisher/EDA/.
The radiation dose-response relationship for control of primary breast cancer
International Nuclear Information System (INIS)
In spite of an increasing number of reports published from many institutions throughout the world the radiation dose-response characteristics of primary breast cancer remain imprecisely defined. This review, which summarises experience in over 7500 patients treated in Europe, Canada and the United States, emphasises some of the methodological problems in deriving valid conclusions concerning dose response from the seemingly abundant data presented. It draws on data from six randomised trials reported in the literature that quote local recurrence figures of primary breast cancer following controlled comparisons of segmental, simple, total and radical mastectomy with or without radiation, and from 17 series where radiation alone has been utilised or where radiation has followed wedge excision (lumpectomy). (Auth.)
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%
Dose-response effects of gamma-radiation on several growth functions of Campanularia flexuosa
International Nuclear Information System (INIS)
The present study is concerned with the dose-response effects of ionizing radiation, specifically gamma radiation, on several growth functions in the colonial hydroid Campanularia flexuosa. The growth functions monitored post-irradiation for this study include the following: (1) addition of new stolon material; (2) addition of hydranth positions to starters; (3) addition of uprights to stolons; (4) addition of hydranths to stolons post-irradiation; and (5) life-span of hydranths. Observations of certain qualitative phenomena associated with the gamma radiation are also presented. Finally, comparisons of the dose-response effects are noted, leading to some tentative conclusions concerning the nature of determination and differentiation underlying the morphogenetic events associated with these growth functions
Dose-response effects of gamma-radiation on several growth functions of Campanularia flexuosa
Energy Technology Data Exchange (ETDEWEB)
Wermuth, J.F.; Barnes, C.D.
1975-04-01
The present study is concerned with the dose-response effects of ionizing radiation, specifically gamma radiation, on several growth functions in the colonial hydroid Campanularia flexuosa. The growth functions monitored post-irradiation for this study include the following: (1) addition of new stolon material; (2) addition of hydranth positions to starters; (3) addition of uprights to stolons; (4) addition of hydranths to stolons post-irradiation; and (5) life-span of hydranths. Observations of certain qualitative phenomena associated with the gamma radiation are also presented. Finally, comparisons of the dose-response effects are noted, leading to some tentative conclusions concerning the nature of determination and differentiation underlying the morphogenetic events associated with these growth functions.
International Nuclear Information System (INIS)
Clinical benefit from dose modifying agents depends upon the effectiveness of the agents and the steepness of dose response curves for the local control of human tumors by radiotherapy. The authors have analyzed the two prospective trials and the many retrospective analyses of clinical data from the literature to determine what dose increment is needed to increase local control from 40 to 60%. This increment ranges from 3 to > 35%. Thus a dose modifying factor of at least 1.03 (to > 1.35) will be necessary for clinical detection of the benefit of a new modality, even if 135 patients are included in each arm of a trial. Two dose levels in the new treatment arm would ensure that therapeutic advantage could be assessed and would also generate prospective dose response information
Single-dose-response curves of murine gastrointestinal crypt stem cells
International Nuclear Information System (INIS)
Dose-response curves for the reproductive capacity of crypt stem cells of murine colonic, jejunal, and gastric mucosae exposed in situ to multifractionated gamma ray exposures were analyzed and single-dose-survival curves of these cells were constructed. The following conclusions were drawn: (1) The single-dose-response curves bend downward over a dose range of approximately 200 to 1500 rad; (2) cell death seems to be due to nonrepairable damage at doses less than 250 rad for colon, and 220 rad for jejunum; (3) there are 21, 110, and 140 stem cells per crypt of gastric, colonic, and jejunal mucosa, respectively; and (4) jejunal stem cells are the most radiosensitive and gastric mucosal stem cells are the most resistant
Energy Technology Data Exchange (ETDEWEB)
Shinde, S.H. [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: shs_barc@yahoo.com; Mukherjee, T. [Radiation Safety Systems Division, Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)
2007-02-15
Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10{sup -4}moldm{sup -3} and xylenol orange with 2.5x10{sup -1}moldm{sup -3} of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%.
High-resolution dose–response screening using droplet-based microfluidics
Miller, Oliver J.; Harrak, Abdeslam El; Mangeat, Thomas; Baret, Jean-Christophe; Frenz, Lucas; Debs, Bachir El; Mayot, Estelle; Samuels, Michael L; Rooney, Eamonn K.; Dieu, Pierre; Galvan, Martin; Link, Darren R.; Griffiths, Andrew D
2011-01-01
A critical early step in drug discovery is the screening of a chemical library. Typically, promising compounds are identified in a primary screen and then more fully characterized in a dose–response analysis with 7–10 data points per compound. Here, we describe a robust microfluidic approach that increases the number of data points to approximately 10,000 per compound. The system exploits Taylor–Aris dispersion to create concentration gradients, which are then segmented into picoliter microre...
Sargent, J.; Dalton, M; Beach, M.
2000-01-01
OBJECTIVE—To assess whether a dose-response relation exists between the number of cigarette promotional items (CPIs) owned by an adolescent, and smoking behaviour.?DESIGN AND SETTING—Voluntary, self administered survey of 1265 sixth through to 12th grade students (ages 10-19 years), representing 79-95% of all students attending five rural New Hampshire and Vermont public (state funded) schools in October 1996. The association between the number of CPIs owned by students and smoking behaviour ...
Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation
International Nuclear Information System (INIS)
The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.
A comparison of dose-response models for death from hematological depression
International Nuclear Information System (INIS)
Many radiation-induced lethality experiments that have been published for various mammalian species have been compiled into a database suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behavior within each experiment, etc. The data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Also, photon source energy, exposure geometry, and body weight considerations were used to select studies where the dose to hematopoietic marrow was nearly uniform, i.e., < +- 20%. The data base reflects 13 mammalian test species ranging from mouse to cattle. Some 211 studies were compiled but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to practical human exposures. Of the 105 studies, 70 were for various rodent species, and 35 were for nonrodent groups ranging from standard laboratory primates (body weight ?5 kg) to cattle (body weight 375 kg). This paper considers seven different dose-response models which are tested for validity against those 105 studies. The dose-response models included: a right-skewed extreme value, a left-skewed extreme value model, log-logistic, log-probit, logistic, probit, and Weibull models. In general, the log transformed models did not improve model performance and the extreme value models did not seem consistent with the preponderance of the data. Overall, the probit and the logistic models seemed preferable over the Weibull model. 30 refs., 8 tabs
Model-Based Meta-Analysis for Quantifying Paclitaxel Dose Response in Cancer Patients
LU, D.; Joshi, A.; LI, H.; ZHANG, N.; Ren, M M; Gao, Y.; R. Wada; Jin, J Y
2014-01-01
Model-based meta-analysis of dose response is a sophisticated method to guide dose and regimen selection. In this report, the effects of paclitaxel dose and regimen (weekly or every 3 weeks) on the efficacy and safety in cancer patients were quantified by model-based meta-analysis of 29 monotherapy trials. Logistic regression models were developed to assess the relationship between dose and objective response rate or neutropenia rate. Survival models were developed to assess the relationship ...
Dette, Holger; Biedermann, Stefanie; Zhu, Wei
2005-01-01
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...
Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation
Energy Technology Data Exchange (ETDEWEB)
Yuece, Ulkue Rabia, E-mail: ulkuyuce@hotmail.co [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Meric, Niyazi, E-mail: meric@ankara.edu.t [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Atakol, Orhan, E-mail: atakol@science.ankara.edu.t [Ankara University, Science Faculty, Department of Chemistry, 06100, Tandogan - Ankara (Turkey); Yasar, Fusun, E-mail: ab121310@adalet.gov.t [Council of Forensic Medicine, Ankara Branch, Ankara (Turkey)
2010-08-15
The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.
DEFF Research Database (Denmark)
Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels
2009-01-01
We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response re...
Dose-response relationship for breast cancer induction at radiotherapy dose
Gruber Günther; Robotka Judith; Sumila Marcin; Schneider Uwe; Mack Andreas; Besserer Jürgen
2011-01-01
Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i) the analysis of breast cancer induction after Hodgkin's disease, (ii) a cancer risk model developed for high doses including fractionation based on the linear qu...
Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships.
Blumberg, Jeffrey B; Vita, Joseph A; Chen, C-Y Oliver
2015-01-01
Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD), blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL) to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages. PMID:26633488
Basic dose response of fluorescent screen-based portal imaging device
International Nuclear Information System (INIS)
The purpose of this study is to investigate fundamental aspects of the dose response of fluorescent screen-based electronic portal imaging devices (EPIDs). We acquired scanned signal across portal planes as we varied the radiation that entered the EPID by changing the thickness and anatomy of the phantom as well as the air gap between the phantom and the EPID. In addition, we simulated the relative contribution of the scintillation light signal in the EPID system. We have shown that the dose profile across portal planes is a function of the air gap and phantom thickness. We have also found that depending on the density change within the phantom geometry, errors associated with dose response based on the EPID scan can be as high as 7%. We also found that scintillation light scattering within the EPID system is an important source of error. This study revealed and demonstrated fundamental characteristics of dose response of EPID, as relative to that of ion chambers. This study showed that EPID based on fluorescent screen cannot be an accurate dosimetry system
Energy Technology Data Exchange (ETDEWEB)
Mazzullo, M.; Bartoli, S.; Bonora, B.; Colacci, A.; Grilli, S.; Lattanzi, G.; Niero, A.; Turina, M.P. (Universita di Bologna (Italy)); Parodi, S. (Universita di Genova (Italy))
1989-07-01
The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 {times} 10{sup 7} starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was initially performed with tritium-labeled benzene, administered by IP injection. In order to exclude the possibility that part of the detected radioactivity was due to tritium incorporated into DNA from metabolic processes, {sup 14}C-benzene was then also used following a similar experimental design. By HPLC analysis, a single adduct from benzene-treated DNA was detected; adduct identification will be attempted in the near future. Linear dose-response relationship was observed within most of the range of explored doses. Linearity was particularly evident within low and very low dosages. Saturation of benzene metabolism did occur at the highest dosages for most of the assayed macromolecules and organs, especially in rat liver. This finding could be considered as indicative of the dose-response relationship of tumor induction and could be used in risk assessment.
International Nuclear Information System (INIS)
The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 x 107 starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was initially performed with tritium-labeled benzene, administered by IP injection. In order to exclude the possibility that part of the detected radioactivity was due to tritium incorporated into DNA from metabolic processes, 14C-benzene was then also used following a similar experimental design. By HPLC analysis, a single adduct from benzene-treated DNA was detected; adduct identification will be attempted in the near future. Linear dose-response relationship was observed within most of the range of explored doses. Linearity was particularly evident within low and very low dosages. Saturation of benzene metabolism did occur at the highest dosages for most of the assayed macromolecules and organs, especially in rat liver. This finding could be considered as indicative of the dose-response relationship of tumor induction and could be used in risk assessment
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.)
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)
Lagarde, Fabien; Beausoleil, Claire; Belcher, Scott M; Belzunces, Luc P; Emond, Claude; Guerbet, Michel; Rousselle, Christophe
2015-01-01
Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships with endocrine disruptors. Fifty-one experimental studies that investigated various effects associated with endocrine disruption elicited by many substances were selected. Scoring criteria were applied by adaptation of an approach previously used for identification of hormesis-type dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were categorized with this method as having a "moderate" to "high" level of plausibility for various effects. Numerous modes of action described in the literature can explain such phenomena. NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation. A stepwise decision tree was developed as a tool to standardize the analysis of NMDR relationships observed in the literature with the final aim to use these results in a Risk Assessment purpose. This decision tree was finally applied to studies focused on the effects of bisphenol A. PMID:25971433
A comparison of dose-response models for death from hematological depression in different species
International Nuclear Information System (INIS)
A database has been completed suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behaviour within each experiment, etc. Data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Photon source energy, exposure geometry, and body weight considerations were used to select studies where dose to hematopoietic tissue was approximately uniform. The database reflects 13 mammalian species ranging in size from mouse to cattle. Some 211 studies were compiled, but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to human exposures. Of the 105 studies, 70 were for rodent species, 35 for non-rodent groups ranging from standard laboratory primates (body weight ? 5 kg) to cattle (body weight ? 375 kg). Seven different dose-response models are tested for validity against the 105 studies. In general, log transformation models did not improve model performance and extreme value models did not seem consistent with the preponderance of the data. Probit and the logistic models seemed preferable over the Weibull model. (author)
Hazard-function method of resolving radiation dose-response curves
International Nuclear Information System (INIS)
A method of determining radiation dose-response relationships is presented which does not require combining into the same group members that are affected by different doses. The method is based on hazard theory and is referred to as the hazard-function method or hazard method. The hazard method is employed to resolve dose-response curves for the induction of injury sufficient to cause early mortality from pulmonary injury (mostly from radiation pneumonitis and pulmonary fibrosis) in beagle dogs, after inhalation of relatively insoluble forms of 90Y, 91Y, 144Ce or 90Sr and after inhalation of 239Pu02. The dose-response curves appear linear over a large range of doses and appear curvilinear at relatively low doses in some cases. It is demonstrated that the distribution of doses that produce injury to the lung sufficient to cause early mortality is related to the effective half-life of the radioactive material in the lung. The efficiency of low LET radioactive materials in inducing lethal pulmonary injury is shown to decrease as the effective half-life of the material in the lung increases. Dose-RBE relationships are presented and a method of correcting for wasted dose is discussed. (author)
Directory of Open Access Journals (Sweden)
Larsen Peter E
2012-06-01
Full Text Available Abstract Background Background: Deep RNA sequencing, the application of Next Generation sequencing technology to generate a comprehensive profile of the message RNA present in a set of biological samples, provides unprecedented resolution into the molecular foundations of biological processes. By aligning short read RNA sequence data to a set of gene models, expression patterns for all of the genes and gene variants in a biological sample can be calculated. However, accurate determination of gene model expression from deep RNA sequencing is hindered by the presence of ambiguously aligning short read sequences. Findings BowStrap, a program for implementing the sequence alignment tool ‘Bowtie’ in a bootstrap-style approach, accommodates multiply-aligning short read sequences and reports gene model expression as an averaged aligned reads per Kb of gene model sequence per million aligned deep RNA sequence reads with a confidence interval, suitable for calculating statistical significance of presence/absence of detected gene model expression. BowStrap v1.0 was validated against a simulated metatranscriptome. Results were compared with two alternate ‘Bowtie’-based calculations of gene model expression. BowStrap is better at accurately identifying expressed gene models in a dataset and provides a more accurate estimate of gene model expression level than methods that do not incorporate a boot-strap style approach. Conclusions BowStrap v1.0 is superior in ability to detect significant gene model expression and calculate accurate determination of gene model expression levels compared to other alignment-based methods of determining patterns of gene expression. BowStrap v1.0 also can utilize multiple processors as has decreased run time compared to the previous version, BowStrap 0.5. We anticipate that BowStrap will be a highly useful addition to the available set of Next Generation RNA sequence analysis tools.
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
Bornmann, Lutz; Leydesdorff, Loet
2013-01-01
Using the InCites tool of Thomson Reuters, this study compares normalized citation impact values calculated for China, Japan, France, Germany, United States, and the UK throughout the time period from 1981 to 2010. InCites offers a unique opportunity to study the normalized citation impacts of countries using (i) a long publication window (1981 to 2010), (ii) a differentiation in (broad or more narrow) subject areas, and (iii) allowing for the use of statistical procedures in order to obtain an insightful investigation of national citation trends across the years. Using four broad categories, our results show significantly increasing trends in citation impact values for France, the UK, and especially Germany across the last thirty years in all areas. The citation impact of papers from China is still at a relatively low level (mostly below the world average), but the country follows an increasing trend line. The USA exhibits a stable pattern of high citation impact values across the years. With small impact differences between the publication years, the US trend is increasing in engineering and technology but decreasing in medical and health sciences as well as in agricultural sciences. Similar to the USA, Japan follows increasing as well as decreasing trends in different subject areas, but the variability across the years is small. In most of the years, papers from Japan perform below or approximately at the world average in each subject area. PMID:23418600
International Nuclear Information System (INIS)
The relation between lung cancer risk and radon exposure has been clearly established, especially from the studies on uranium miner cohorts. But the association between radon exposure and extrapulmonary cancers and non-cancer diseases remains not well known. Moreover, the health risks associated with the other mining-related ionizing radiation exposures are still under consideration. The aim of this thesis is to contribute to the estimation of the radio-induced health risks at low-doses through the analysis of the kidney cancer and Circulatory System Disease (CSD) mortality risks among uranium miners. Kidney cancer mortality risk analyses were performed from the French cohort of uranium miners (n=5086; follow-up period: 1946-2007), the post-55 cohort (n=3,377; follow-up period: 1957-2007) and the German cohort of the Wismut (n=58,986; follow-up period: 1946-2003) which included 24, 11 and 174 deaths from kidney cancer, respectively. The exposures to radon and its short-lived progeny (expressed in Working Level Month WLM), to uranium ore dust (kBqh.m-3) and to external gamma rays (mSv) were estimated for each miners and the equivalent kidney dose was calculated. The dose-response relation was refined considering two responses: the instantaneous risk of kidney cancer mortality (corresponding to the classical analysis, Cause specific Hazard Ratio (CSHR) estimated with the Cox model) and its occurrence probability during the followup (Sub-distribution Hazard Ratio (SHR) estimated with the Fine and Gray model). An excess of kidney cancer mortality was observed only in the French cohort (SMR = 1.62 CI95%[1.04; 2.41]). In the Wismut cohort, a decrease of the kidney cancer mortality was observed (0.89 [0.78; 0.99]). For these three cohorts, the occupational radiological exposures (or the equivalent kidney dose) were significantly associated neither with the risk of kidney cancer mortality (e.g. CSHRWismut-radon/100 WLM=1.023 [0.993; 1.053]), nor with its occurrence probability during the follow-up (e.g. SHRWismut-radon /100 WLM=1.012 [0.983; 1.042]). CSD mortality risk analyses in the French cohort showed a significant increase of the risks of mortality from CSD (n=442, CSHR/100 WLM=1.11 [1.01; 1.22]) and from Cerebrovascular Disease (MCeV, n=105, CSHR/100 WLM=1.25 [1.09; 1.43]) with radon exposure. A case-control study nested in the French cohort was set up to collect the information related to CSD risk factors (overweight, hypertension, diabetes...) from the medical records of 313 miners (76 deaths from CSD (including 26 from Ischemic Heart Disease (IHD) and 16 from MCeV) and 237 controls). For the three radiological exposures, the exposure-risk relation was analyzed in a pseudo-cohort (n=1,644 pseudo-individuals, obtained from the weighting of the observations by their inverse selection probability) with the Cox model, adjusted for the CSD risk factors. The association between the radiological exposure and the risk of mortality from CSD, IHD or MCeV was not significant (e.g. CSHRCSD-radon/100 WLM=1.43 [0.71; 2.87]). The adjustment for CSD risk factors did not substantially change the exposure-risk relation. The lack of a significant dose-response relation suggests that the excess of kidney cancer mortality among the French uranium miners may be induced by other risk factors, unavailable for this study. The small change of the coefficients observed after adjustment for CSD risk factors in the nested case-control study supports the assumption of the existence of the MCeV mortality risk increase associated with radon exposure in the French cohort of uranium miners. Future analyses based on further follow-up updates should allow to confirm or not these results. (author)
Hayslett, H T
1991-01-01
Statistics covers the basic principles of Statistics. The book starts by tackling the importance and the two kinds of statistics; the presentation of sample data; the definition, illustration and explanation of several measures of location; and the measures of variation. The text then discusses elementary probability, the normal distribution and the normal approximation to the binomial. Testing of statistical hypotheses and tests of hypotheses about the theoretical proportion of successes in a binomial population and about the theoretical mean of a normal population are explained. The text the
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. I-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 fishInduction 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.
International Nuclear Information System (INIS)
The dose-response relationship of ionizing radiation and its stochastic effects has been thought to be linear without any thresholds for a long time. The basic data for this model was obtained from mutational assays using germ cells of male fruit fly Drosophila melanogaster. However, cancer-causing activity should be examined more appropriately in somatic cells than in germ cells. In this paper, we examined the dose-response relationship of X-ray irradiation and somatic mutation in drosophila, and found a threshold at approximately 1 Gy in the DNA repair proficient flies. In the repair deficient siblings, the threshold was smaller and the inclination of the dose-response curve was five times steeper. These results suggest that the dose-response relationship between X-ray irradiation and somatic mutation has a threshold, and that the DNA repair function contributes to its formation. (author)
Acute dose-response studies in bronchial asthma with a new corticosteroid, budesonide.
Ellul-Micallef, R.; Johansson, S A
1983-01-01
1 Budesonide is an epimeric mixture of a new synthetic non-halogenated glucocorticoid (16 alpha, 17 alpha,-(22R,S)-prophylmethylenedioxypregna-1,4-diene-11/3,21-diol-3, 20-dione). 2 Acute dose response studies with three different inhaled doses of budesonide, have been carried out in a group of 12 chronic asthmatic patients. 3 The lowest dose (100 micrograms) of inhaled budesonide produced a more marked effect in relieving airflow obstruction, than a much larger (1600 micrograms) oral dose of...
Gamboa, T; Neuparth, N.; Ribeiro da Silva, I; Rosado-Pinto, J; Rendas, AB
1997-01-01
To determine whether the slope of a maximal bronchial challenge test (in which FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single maximal bronchial challenge test with methacholin(dose range: 0.097–30.08 umol) by the dosimeter method. Maximal dose-response curves were included according to the following criteria: (1) at least one more dose beyond a FEV1 ù 20%; and (2) a MFEV1 ù 50%. P...
Mazzullo, M; Bartoli, S; Bonora, B; Colacci, A.; Grilli, S; Lattanzi, G.; Niero, A; Turina, M P; Parodi, S.
1989-01-01
The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 x 10(7) starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was initially performed with tritium-labeled benzene, administered by IP injection. In order to exclude the possibility that part of the detected radioactivity was due to tritium inco...
Dose-response of strengthening exercise for treatment of severe neck pain in women
DEFF Research Database (Denmark)
Andersen, Christoffer H; Andersen, Lars Louis
2013-01-01
Specific strength training is shown relieves neck pain in office workers. The purpose of this study is to evaluate the effectiveness of specific strength training in women with severe neck pain and to analyze the dose-response relationship between training adherence and pain reduction. 118 untrained women with severe neck pain (>30 mm VAS pain) were included from a larger study, in which the subjects were randomized to 20-weeks specific strength training for the neck/shoulders or to a control group. In the intention-to-treat analysis, the training group experienced greater pain relief than the control group (p
Dose-response of strengthening exercise for treatment of severe neck pain in women
DEFF Research Database (Denmark)
Andersen, Christoffer H; Andersen, Lars Louis; Pedersen, Mogens T; Mortensen, Peter; Karstad, Kristina; Mortensen, Ole S; Zebis, Mette Kreutzfeldt; Sjøgaard, Gisela
2013-01-01
Specific strength training is shown relieves neck pain in office workers. The purpose of this study is to evaluate the effectiveness of specific strength training in women with severe neck pain and to analyze the dose-response relationship between training adherence and pain reduction. 118 untrained women with severe neck pain (>30 mm VAS pain) were included from a larger study, in which the subjects were randomized to 20-weeks specific strength training for the neck/shoulders or to a control gr...
Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms
DEFF Research Database (Denmark)
Urbain, Paul; Jakobsen, Jette
2015-01-01
The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 ?g/g up to 3.9 ± 0.8 ?g/g dry weight (DW). At the subsequent two measurement...
Chang, Cheng-Fu; Wai, Ka-Man; Patterton, Hugh G
2004-01-01
Physical clusters of co-regulated, but apparently functionally unrelated, genes are present in many genomes. Despite the important implication that the genomic environment contributes appreciably to the regulation of gene expression, no simple statistical method has been described to identify physical clusters of co-regulated genes. Here we report the development of a model that allows the direct calculation of the significance of such clusters. We have implemented the derived statistical rel...
DEFF Research Database (Denmark)
Lorenzen, Ellen; Einer-Jensen, Katja
2000-01-01
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.
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.
DEFF Research Database (Denmark)
Larsen, C.N.; Nielsen, S.
2006-01-01
Objective: This study was performed to investigate the dose-response effects of supplementation with Bifidobacterium animalis subsp lactis (BB-12) and Lactobacillus paracasei subsp paracasei (CRL-431) on blood lipids, recovery from feces and bowel habits. Changes of the fecal microflora was analyzed in the 10(10) CFU/day probiotic and placebo group. Design: The study was designed as a randomized, placebo-controlled, double-blinded, parallel dose-response study. Subjects: Healthy young adults (18 - 40 years) were recruited by advertising in local newspapers. Of the 75 persons enrolled, 71 ( 46 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.
High-resolution dose–response screening using droplet-based microfluidics
Miller, Oliver J.; Harrak, Abdeslam El; Mangeat, Thomas; Baret, Jean-Christophe; Frenz, Lucas; Debs, Bachir El; Mayot, Estelle; Samuels, Michael L.; Rooney, Eamonn K.; Dieu, Pierre; Galvan, Martin; Link, Darren R.; Griffiths, Andrew D.
2012-01-01
A critical early step in drug discovery is the screening of a chemical library. Typically, promising compounds are identified in a primary screen and then more fully characterized in a dose–response analysis with 7–10 data points per compound. Here, we describe a robust microfluidic approach that increases the number of data points to approximately 10,000 per compound. The system exploits Taylor–Aris dispersion to create concentration gradients, which are then segmented into picoliter microreactors by droplet-based microfluidics. The large number of data points results in IC50 values that are highly precise (± 2.40% at 95% confidence) and highly reproducible (CV = 2.45%, n = 16). In addition, the high resolution of the data reveals complex dose–response relationships unambiguously. We used this system to screen a chemical library of 704 compounds against protein tyrosine phosphatase 1B, a diabetes, obesity, and cancer target. We identified a number of novel inhibitors, the most potent being sodium cefsulodine, which has an IC50 of 27 ± 0.83 ?M. PMID:22203966
High-resolution dose-response screening using droplet-based microfluidics.
Miller, Oliver J; El Harrak, Abdeslam; Mangeat, Thomas; Baret, Jean-Christophe; Frenz, Lucas; El Debs, Bachir; Mayot, Estelle; Samuels, Michael L; Rooney, Eamonn K; Dieu, Pierre; Galvan, Martin; Link, Darren R; Griffiths, Andrew D
2012-01-10
A critical early step in drug discovery is the screening of a chemical library. Typically, promising compounds are identified in a primary screen and then more fully characterized in a dose-response analysis with 7-10 data points per compound. Here, we describe a robust microfluidic approach that increases the number of data points to approximately 10,000 per compound. The system exploits Taylor-Aris dispersion to create concentration gradients, which are then segmented into picoliter microreactors by droplet-based microfluidics. The large number of data points results in IC(50) values that are highly precise (± 2.40% at 95% confidence) and highly reproducible (CV = 2.45%, n = 16). In addition, the high resolution of the data reveals complex dose-response relationships unambiguously. We used this system to screen a chemical library of 704 compounds against protein tyrosine phosphatase 1B, a diabetes, obesity, and cancer target. We identified a number of novel inhibitors, the most potent being sodium cefsulodine, which has an IC(50) of 27 ± 0.83 ?M. PMID:22203966
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.
International Nuclear Information System (INIS)
Establishing in-vitro dose calibration curves is important for reconstruction of radiation dose in the exposed individuals. The aim of this pioneering work in Thailand was to generate dose-response curves using conventional biological dosimetry: dicentric chromosome assay (DCA) and premature chromosome condensation (PCC) assay. The peripheral blood lymphocytes were irradiated with 137Cs at a dose rate of 0.652 Gy/min to doses of 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy for DCA technique, and 5, 10, 15, 20 and 25 Gy for PCC technique. The blood samples were cultured and processed following the standard procedure given by the IAEA with slight modifications. At least 500-1,000 metaphases or 100 dicentrics/ PCC rings were analyzed using an automated metaphase finder system. The yield of dicentrics with dose was fitted to a linear quadratic model using Chromosome Aberration Calculation Software (CABAS, version 2.0), whereas the dose-response curve of PCC rings was fitted to a linear relationship. These curves will be useful for in-vitro dose reconstruction and can support the preparedness for radiological emergency in the country.
International Nuclear Information System (INIS)
The carcinogenic effects of high levels of ionizing radiation are better understood than those of any other environmental agent. However, the somatic risk from low doses is highly disputed. The uncertainties stem from the fact that due to a multitude of confounding factors a direct estimation of small risks requires impracticably large samples. Therefore, risk estimates for low doses have to be derived indirectly by extrapolation from high-exposure data and are heavily dependent on assumptions about the shape of the dose-response curve. Although radiobiological theories tested mostly on in vitro systems predict a quadratic term in the dose-response equation, which should dominate the shape of the curve at least for sparsely ionizing radiation, the epidemiological data available are not yet sufficient to exclude the possibility of a purely linear relationship. In some cases, apparent thresholds may result from latent periods inversely related to dose. Besides depending on the quality of the radiation, the shape also seems to differ with the type of cancer induced. The huge epidemiological data base on atomic bomb survivors, irradiated patients, miners, and other exposed groups can most consistently be fitted to a linear quadratic model. For lung cancer in miners resulting from high linear energy transfer alpha radiation and for female breast cancer, the linear component seems to be dominant
International Nuclear Information System (INIS)
The background and some results of initial applications of a new model of time-dose response of tumors as well as fast-renewing normal tissues to fractionated radiation therapy are presented. Both the linear-quadratic and the single-hit/single-target, single-hit/multi-target model may be used for the single-dose survival of both the viable stem cells and the clonogenic tumor cells. Normal tissue tolerance is expressed as a minimum acceptable level of normal tissue functionality, due to insufficient production of replacement cells, which in turn is caused by radiation-induced depletion of the viable stem cell population. A logistic function describes the homeostatically controlled inter-fraction and post-treatment normal tissue stem cell repopulation. The onset of stem cell repopulation may be delayed, and the doubling rate of clonogenic tumor cells may increase, upon the onset of treatment. Criteria for the selection of acceptable parameter values for normal tissue as well as tumors are described. An interactive Fortran77 program has been developed to assist in the search for acceptable parameter values, the simulation of the time-dose response of normal tissues and tumors to conventional clinical fractionation schemes and the exploration of alternative schedules, including hyperfractionation. Some provisional results are presented. 29 refs.; 11 figs.; 2 tabs
Neutron dose response of tradescantia stamen hair pink mutations and RBE
Energy Technology Data Exchange (ETDEWEB)
Kim, Jin Kyu; Kim, Won Rok [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)
1998-03-01
Dose response for one of biological end-points (gene mutation) in somatic cells of tradescantia 4430 clones were studied using neutrons coming out of a californium-252 isotopic source. And the Relative Biological Effectiveness (RBE) of neutrons in relation to X-ray in the induction of TSH pink mutations was assessed. Inflorescences were irradiated with X-ray from X-ray generator and neutrons from {sup 252}Cf source. Irradiated cuttings were incubated with aeration in nutrient solution under the controlled condition. For more than 4 weeks after irradiation cell mutations were scored. Pink mutation frequencies were calculated from the pooled data for the peak interval (days 6 to 13 post-irradiation). Somatic cell mutations in TSH showed linear dose response relationships in the range of neutron doses available for the experiment. The RBE values estimated for neutrons in relation to X-rays were in the range 3.1 to 6.8, which were much lower than normally recognized value.
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
Non-linear dose response of a few plant taxa to acute gamma radiation
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Micronuclei induction serves as an essential biomarker of radiation stress in a living system, and the simplicity of its detection technique has made it a widely used indicator of radiation damage. The present study was conducted to reveal the cytological dose-response of a few plant taxa, viz., Allium cepa var. aggregatum Linn., Allium sativum Linn., Chlorophytum comosum (Thunb.) Jacques and Eichhornia crassipes (Mart.) Solms, to low LET gamma radiation with special emphasis on the pattern of micronuclei induced across low and high dose regimes. A tri-phasic non-linear dose-response pattern was observed in the four taxa studied, characterized by a low dose linear segment, a plateau and a high dose linear segment. Despite a similar response trend, the critical doses where the phase transitions occurred varied amongst the plant taxa, giving an indication to their relative radiosensitivities. E. crassipes and A. sativum, with their lower critical doses for slope modifications of phase transitions, were concluded as being more radiosensitive as compared to C. comosum and A. cepa, which had relatively higher critical doses. (author)
Rabin, B.; Joseph, J.; Shukitt-Hale, B.
Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation- induced disruption of dopaminergic function disrupts a variety of behaviors that are dependent upon the integrity of the dopaminergic system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, spatial learning and memory (Morris water maze), and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current presentation will review the data relevant to the degree to which these characteristics are in fact common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. Supported by N.A.S.A. Grant NAG9-1190.
The nickel dose–response relationship by filaggrin genotype (FLG)
DEFF Research Database (Denmark)
Ross-Hansen, Katrine; Johansen, Jeanne D
2014-01-01
BACKGROUND: On skin contact, nickel accumulates in the stratum corneum, where it is probably bound to proteins and amino acids. One probable contributor is filaggrin, which binds nickel avidly. Filaggrin gene (FLG) null mutations lead to a complete lack of filaggrin production from the affected allele, and have been associated with an increased risk of nickel contact sensitization in German and Danish adults. OBJECTIVES: To investigate whether the experimental nickel elicitation threshold level differed between heterozygous FLG mutation and non-mutation carriers. METHOD: Thirteen nickel-sensitized female patients, seven heterozygous mutation carriers and six non-mutation carriers (genotyped for R501X, 2282del4, or R2447X), were patch tested and performed a repeated open application test (ROAT) with a nickel sulfate dilution series. Logistic threshold dose-response analyses were used to test for differences between the two groups. RESULTS: No difference was found in the dose-response relationship between FLG mutation and non-mutation carriers. CONCLUSIONS: On the basis of this small patient study, it appears that the elicitation threshold level for nickel is independent of FLG null mutation single-allele carrier status.
Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis
DEFF Research Database (Denmark)
Trauelsen, Anne Marie; Bendall, Sarah
2015-01-01
BACKGROUND: Reviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk of psychosis have not been consistently found. The current study aimed to explore adversity specificity and dose-response effects of adversities on risk of psychosis. METHOD: Participants were 101 persons with first-episode psychosis (FEP) diagnosed with ICD-10 F20 - F29 (except F21) and 101 non-clinical control persons matched by gender, age and parents' socio-economic status. Assessment included the Childhood Trauma Questionnaire and parts of the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Eighty-nine percent of the FEP group reported one or more adversities compared to 37% of the control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all p<0.01). The risk of psychosis increased two and a half times for each additional adversity. All associations between specific adversities and psychosis decreased when they were adjusted for other adversities. CONCLUSION: Our findings suggest that there is a large shared effect of adversities on the risk of psychosis. Contrary to the call for further research into specific adversities, we suggest a search for mechanisms in the shared effects of traumatization. Clinical implications are thorough assessment of adversities and their possible effects.
Biological dosimetry in radiation accidents. Dose-response curve by chromosomal aberrations analysis
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The aim of this paper is to obtain a dose-response relationship for chromosomal aberrations induced in human lymphocytes after in vitro irradiation. Peripheral blood samples of 7 different donors were used. The blood irradiation was done with Cs137 gamma-rays at different doses: 0.0, 0.05, 0.1, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0 and 3.0 Gy. Lymphocyte cultures were established and maintain for 48 hours at 370C in CO2 incubator for chromosomal aberration analysis. The dose response relationship has been established based on dysenteric and ring chromosomes yield. The relationship can be described by the following equation: Y = 0.0274D + 0.0251 D2, where (Y) = dysenteric and ring chromosomes yield, (D) = radiation dose obtained. EXCEL software was established for calculation of the received dose by using this equation, as a whole body equivalent dose acute irradiation
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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
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For the year 1999 and 2000, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy Review appear in more detail from the publication Energiatilastot - Energy Statistics issued annually, which also includes historical time series over a longer period (see e.g., Energiatilastot 1998, Statistics Finland, Helsinki 1999, ISSN 0785-3165). The inside of the Review's back cover shows the energy units and the conversion coefficients used for them. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in the volume of GNP and energy consumption, Changes in the volume of GNP and electricity, Coal consumption, Natural gas consumption, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices for heat production, Fuel prices for electricity production, Carbon dioxide emissions, Total energy consumption by source and CO2-emissions, Electricity supply, Energy imports by country of origin in January-March 2000, Energy exports by recipient country in January-March 2000, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Average electricity price by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes and precautionary stock fees on oil products
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Kinetic models of thermoluminescence (TL) dose response have recently been proposed which propose to solve the long-standing conundrumconcerning the dependence of the TL dose response on ionization density. Many TL materials exhibit an initially linear dose response over several decades of dose which then turns supralinear before entering into saturation. LiF:Mg,Ti is perhaps the most outstanding and widely studied example. The dose response of the major dosimetric glow peak is strictly linear from the lowest level of dose measurable of ~10-4 Gy to ~ 1 Gy and then turns supralinear reaching maximum values of the normalized TL dose response f(D) of 3-5 at levels of dose between 300 -500 Gy .This behaviour coupled with the dependence of the supralinearity on particle type and energy (i.e., on ionization density) has presented a formidable challenge to conventional kinetic theories of dose response. It has been gradually recognized over the past decade that this behaviour in LiF:Mg,Ti requires both nanodosimetric input coupled with a mixture of both localized and delocalized recombination mechanisms. This due to the complex nature of the trapping structure giving rise to the TL. Following irradiation the trapping center (TC)- luminescent center (LC) can be populated by a locally trapped electron-hole (e-h) or an electron (e) only. The former giving rise to geminate (localized) recombination the latter to mainly delocalized recombination via charge transfer migration in the conduction band. The relative concentrations of these configurations are dependent on ionization density. In this paper we present the latest developments in which we attempt to simulate the linear/supralinear dose response, the dependence of the supralinearity on electron energy and the shape of composite glow peak 5 as a function of electron energy. In order to predict all three characteristics the simulations require the incorporation of band tail states allowing semi-localized recombination from the e-only configuration
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Life shortening was investigated in both sexes of the B6CF1 (C57BL/6 x BALB/c) mouse exposed to fission neutrons and 60Co gamma rays. Three basic exposure patterns for both neutrons and gamma rays were compared: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. Ten different dose-response models were fitted to the data for animals exposed to neutrons. The response variable used for all dose-response modeling was mean after-survival. A simple linear model adequately described the response to neutrons for females and males at doses less than or equal to 80 cGy. At higher neutron dose levels a linear-quadratic equation was required to describe the life-shortening response. An effect of exposure pattern was observed prior to the detection of curvature in the dose response for neutrons and emerged as a potentially significant factor at neutron doses in the range of 40-60 cGy. Augmentation of neutron injury with dose protraction was observed in both sexes and began at doses as low as 60 cGy. The life-shortening response for all animals exposed to gamma rays (22-1918 cGy) was linear and inversely dependent upon the protraction period (1 day, 24 weeks, 60 weeks). Depending on the exposure pattern used for the gamma-ray baseline, relative biological effectiveness (RBE) values ranged from 6 to 43. Augmentation, because it occurred only at higher levels of neutron exposure, had no influence on the estimation of RBEm
Zhou, Quan; Luo, Mei-Ling; Li, Hui; Li, Min; Zhou, Jian-Guo
2015-01-01
This is a dose-response (DR) meta-analysis to evaluate the association of coffee consumption on endometrial cancer (EC) risk. A total 1,534,039 participants from 13 published articles were added in this meta-analysis. The RR of total coffee consumption and EC were 0.80 (95% CI: 0.74-0.86). A stronger association between coffee intake and EC incidence was found in patients who were never treated with hormones, 0.60 (95% CI: 0.50-0.72), and subjects with a BMI ?25?kg/m(2), 0.57 (95% CI: 0.46-0.71). The overall RRs for caffeinated and decaffeinated coffee were 0.66 (95% CI: 0.52-0.84) and 0.77 (95% CI: 0.63-0.94), respectively. A linear DR relationship was seen in coffee, caffeinated coffee, decaffeinated coffee and caffeine intake. The EC risk decreased by 5% for every 1 cup per day of coffee intake, 7% for every 1 cup per day of caffeinated coffee intake, 4% for every 1 cup per day of decaffeinated intake of coffee, and 4% for every 100?mg of caffeine intake per day. In conclusion, coffee and intake of caffeine might significantly reduce the incidence of EC, and these effects may be modified by BMI and history of hormone therapy. PMID:26302813
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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
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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
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.
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For the year 2003 and 2004, the figures shown in the tables of the Energy Review are partly preliminary. The annual statistics of the Energy Review also includes historical time-series over a longer period (see e.g. Energiatilastot, Statistics Finland, Helsinki 2003, ISSN 0785-3165). The applied energy units and conversion coefficients are shown in the inside back cover of the Review. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in GDP, energy consumption and electricity consumption, Carbon dioxide emissions from fossile fuels use, Coal consumption, Consumption of natural gas, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices in heat production, Fuel prices in electricity production, Price of electricity by type of consumer, Average monthly spot prices at the Nord pool power exchange, Total energy consumption by source and CO2-emissions, Supplies and total consumption of electricity GWh, Energy imports by country of origin in January-March 2004, Energy exports by recipient country in January-March 2004, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Price of natural gas by type of consumer, Price of electricity by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Excise taxes, precautionary stock fees on oil pollution fees
DEFF Research Database (Denmark)
Jakobsen, Janus Christian; Gluud, Christian
2014-01-01
BACKGROUND: Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore, 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.
DEFF Research Database (Denmark)
Jakobsen, Janus Christian; Gluud, Christian
2014-01-01
BACKGROUND: Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore, 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.
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We have developed an improved applicator with a balloon being attached in order to keep a certain interval between the mucosal membrane and sources. The balloon was 15 mm in a diameter and further prepared applicators equipped with three balloons serially inside. We investigated dose-response relationship for external beam irradiation and intracavitary irradiation with this applicator. Local control radiation-induced esophageal ulcer, and fibrotic stenosis were analyzed. Seventy patients with esophageal carcinoma received 40 Gy or more of external beam followed by 12 Gy or more of intracavitary irradiation. A dose reference point was 12.5 mm from Co-60 sources. Intracavitary irradiation was given 3-5 session in 2 weeks. A dose of brachytherapy was 12 Gy/3 fractions or 16 Gy/4 fr in group A, 16 Gy/4 fr or 20 Gy/5 fr in group B, 15 Gy/3 fr or 20 Gy/4 fr in group C and 18 Gy/3 fr or 24 Gy/4 fr in group D. Two-year local control rate was 35.9% in group A, 44.0% in group B, 31.1% in group C and 50.9% in group D. It was statistically insignificant. When 50.4 Gy or less of external beam was given to T1 or 2 lesion, 2-year local control rate was 74% in patients treated with brachytherapy of 18 Gy or more and 42% in patients treated with that of less than 18 Gy (generalized Wilcoxon: P=0.0395). Radiation-induced esophageal ulcers and fibrotic stenosis were not rare in group D. Radiation-ulcers were more common in group B or C compared to group A. Total dose of intracavitary irto group A. Total dose of intracavitary irradiation should be less than 20 Gy. We recommend 50 Gy of external beam followed by 16 Gy/4 fr/2 w of intracavitary irradiation. We need to evaluate an accurate distance between the balloon surface and the mucosa with CT scan. A more sophisticated dose escalation study is now in progress. (author)We have developed an improved applicator with a balloon being attached in order to keep a certain interval between the mucosal membrane and sources. The balloon was 15 mm in a diameter and further prepared applicators equipped with three balloons serially inside. We investigated dose-response relationship for external beam irradiation and intracavitary irradiation with this applicator. Local control radiation-induced esophageal ulcer, and fibrotic stenosis were analyzed. Seventy patients with esophageal carcinoma received 40 Gy or more of external beam followed by 12 Gy or more of intracavitary irradiation. A dose reference point was 12.5 mm from Co-60 sources. Intracavitary irradiation was given 3-5 session in 2 weeks. A dose of brachytherapy was 12 Gy/3 fractions or 16 Gy/4 fr in group A, 16 Gy/4 fr or 20 Gy/5 fr in group B, 15 Gy/3 fr or 20 Gy/4 fr in group C and 18 Gy/3 fr or 24 Gy/4 fr in group D. Two-year local control rate was 35.9% in group A, 44.0% in group B, 31.1% in group C and 50.9% in group D. It was statistically insignificant. When 50.4 Gy or less of external beam was given to T1 or 2 lesion, 2-year local control rate was 74% in patients treated with brachytherapy of 18 Gy or more and 42% in patients treated with that of less than 18 Gy (generalized Wilcoxon: P=0.0395). Radiation-induced esophageal ulcers and fibrotic stenosis were not rare in group D. Radiation-ulcers were more common in group B or C compared to group A. Total dose of intracavitary i
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Hossain Mostaque
2011-07-01
Full Text Available Abstract Background Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. Methods A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS. The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP, aspartate transaminase (AST and alanine transaminase (ALT were then assayed. Results Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails, the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics. Conclusions The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a novel exposure- and dose- response relationship between arsenic exposure metrics and serum hepatic enzyme activity. Elevated serum hepatic enzyme activities in the higher exposure gradients provided new insights into arsenic-induced liver toxicity that might be helpful for the early prognosis of arsenic-induced liver diseases.
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Experiments were performed with several plant species in natural environments as well in a greenhouse and/or tissue culture facilities to establish dose-response functions of plant responses to simulated acidic rain in order to determine environmental risk assessments to ambient levels of acidic rain. Response functions of foliar injury, biomass of leaves and seed of soybean and pinto beans, root yields of radishes and garden beets, and reproduction of bracken fern are considered. The dose-response function of soybean seed yields with the hydrogen ion concentration of simulated acidic rainfalls was expressed by the equation y = 21.06-1.01 log x where y = seed yield in grams per plant and x = the hydrogen concentration if ?eq l-1. The correlation coefficient of this relationship was -0.90. A similar dose-response function was generated for percent fertilization of ferns in a forest understory. When percent fertilization is plotted on logarithmic scale with hydrogen ion concentration of the simulated rain solution, the Y intercept is 51.18, slope -0.041 with a correlation coefficient of -0.98. Other dose-response functions were generated that assist in a general knowledge as to which plant species and which physiological processes are most impacted by acidic precipitation. Some responses did not produce convenient dose-response relationships. In such cases the responses may be altered by other environmental factors or there may be no differences among treatment means
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The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1-84 d after irradiation with minimal changes after 4-8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0-20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD). (authors)
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The minimum detectable dose (MDD) limit was examined in four different ways for groups of LiF:Mg,Ti thermoluminescent dosimeters, and two ways for CaF2:Dy, CaF2:Tm, CaF2:Mn, and CaSO4:Dy dosimeters. All types were irradiated and read out at dose intervals from 8.8 ?Gy to 6.6 mGy. Dose response linearity was never lost even for the lowest dose tested. As an ideal MDD, the signal arising from a zero applied dose readout was compared to calibration from true doses, resulting in signal corresponding to 0.04-0.1 ?Gy. The effects of fading and high ambient radon exposure on the MDD were examined. (author)
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This presentation lists gross and histologic changes produced by irradiation of the skin that have been quantified. It examines available cell kinetic radiobiological and morphological variables to identify interactions that occur between component populations. The dose response data of the hair and epidermal, fibrocytic, and endothelial cell populations are examined and a rank ordering is attempted. The contribution of the radiosensitivity of these populations to defining the dose tolerance of the skin is discussed. Future clinical needs are considered. The intent is to quantify or define tissue population changes in the irradiated skin so that the data may serve as guidelines to aid the radiation therapist to select therapy schedules that preserve skin function while improving cancer control
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In the completed 226Ra portion of a 30-year-long experiment to determine the relative radiotoxicity of injected 226Ra and 239Pu, 42 of 116 animals injected with 226Ra developed 63 bone sarcomas; none were observed in 44 controls. Average alpha plus beta dose to the skeleton to death was calculated on the basis of mathematical functions developed from sequential measurements of radium and radon retention in each dog. Bone sarcomas were identified radiographically or clinically, with subsequent histopathological confirmation and classification. Most primary bone tumors were classified as osteosarcomas if osteoid arose from a malignant stroma. The dose-response curve over the six lowest injected dose levels fits well to a linear, no-threshold, least squares fit, through a control incidence of 0.8%, and with a slope of 0.042% incidence per rad. 19 refs., 5 figs., 2 tabs
Study on the dose-response relation of premature chromosome condensation induced by Okadaic acid
International Nuclear Information System (INIS)
In order to study the effect-dosage relationship between the PCC induced by Okadaic acid and the IR dosages, human peripheral blood in vitro was irradiated by X-rays at different doses (0, 0.5, 1.0, 2.0, 3.0, 5.0Gy) cultivated for 48 hours and added with Okadaic acid two hours before the end of culture. Chromosome aberrations frequencies was analyzed and compared with that induced by the conventional chromosome assay and their dose-response curves were fitted. The results show that the mitotic index of the PCC induced by Okadaic acid is higher than that of the conventional chromosome assay. And the fragment rate of chromosome condensation induced by Okadaic acid has a favorable linearity relationship with external radiation doses. (authors)
Iskandar, S M; Elias, S; Jumiah, H; Asri, M T M; Masrianis, A; Ab Rahman, M Z; Taiman, K; Abdul Rashid, M Y
2004-05-01
The radiation-response characteristics of polymetharylic acid gel dosimeter prepared with different concentrations of monomer and cross-linker is described in these studies. The dosimeters were prepared under the hypoxic condition in a glove box and were then irradiated with gamma-rays produced by Co-60 radionuclide that was generated at 1.25MeV energy. The irradiation took place at different doses ranged from 0Gy to 19Gy. Due to the radiation activities, chain-reaction polymerisation processes had taken place in the formation of polymethacrylic acid (PMAA) gel, which cause the dose response mechanism increased in the NMR relaxation rates of protons. It has been observed that for higher concentration of monomer and cross-linker, the polymerization rate was increased. PMID:15468893
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Kinetic model simulations of charge carrier transport following irradiation of LiF:Mg,Ti (TLD-100) including Fluorine vacancy/F center creation by the radiation and dose-dependent vacancy-interstitial recombination are presented which describe the experimentally measured linear/exponentially saturating optical absorption dose response of the electron trapping centers at 4.0 eV, 4.77 eV, 5.08 eV (F band) and 5.45 eV. Linear/exponentially saturating dose response is commonly observed for centers which are not created by the radiation. The creation of Fluorine vacancies by the radiation could therefore be expected to lead to a supralinear dose response of the F center before the onset of saturation. Nonetheless, the dose response is linear from 10 Gy to 500 Gy and can be fitted with a dose-filling constant ? = 6.1 · 10?5 Gy?1 corresponding to a 5% and 25% decrease from linearity at 103 Gy and 5 · 103 Gy respectively. The model attempts to resolve a central question concerning the mechanisms leading to the linear/exponentially saturating dose response of the F band even though Fluorine vacancies are being continuously created during the irradiation. The electron-trapping characteristics of the created vacancies are assumed to differ somewhat from the vacancies originally present in un-irradiated samples due to differences in their immediate environment. Vacancy-interstitial recombination for separation distances less than a critical distance, dc is demonstrated to be significant for D > 500 Gy (dc = 36 Å) and is an important mechanism contributing to the F center saturation at high dose-levels. The kinetic model accurately simulates the experimentally observed F center dose response over the entire investigated dose range of 10–105 Gy under the following conditions: (i) The concentration of vacancies initially present is unexpectedly high at ?1023 m?3, possibly due to the highly doped, non-crystalline and hot-pressed nature of the LiF:Mg,Ti samples. (ii) The transition probability, An4o, for electron capture into the initially-present vacancies is ?40 times greater than An4, the transition probability for the radiation-created vacancies. These two factors marginalize the effect of the created vacancies at low dose resulting in a linear dose response
Epidemiological methods for assessing dose-response and dose-effect relationships
DEFF Research Database (Denmark)
Kjellström, Tord; Grandjean, Philippe
2007-01-01
Description Handbook of the Toxicology of Metals is the standard reference work for physicians, toxicologists and engineers in the field of environmental and occupational health. This new edition is a comprehensive review of the effects on biological systems from metallic elements and their compounds. An entirely new structure and illustrations represent the vast array of advancements made since the last edition. Special emphasis has been placed on the toxic effects in humans with chapters on the diagnosis, treatment and prevention of metal poisoning. This up-to-date reference provides easy access to a broad range of basic toxicological data and also gives a general introduction to the toxicology of metallic compounds. Audience Toxicologists, physicians, and engineers in the fields of environmental and occupational health as well as libraries in these disciplines. Will also be a useful reference for governmental regulatory agencies and public health officers. Contents Introduction - General Considerations and International Perspectives General Chemistry, Sampling, Analytical Methods and Speciation Routes of Exposure, Dose, and Metabolism of Metals Biological Monitoring and Biomarkers Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity General Considerations of Dose-Effect and Dose-Response Relationships Interactions in Metal Toxicology Epidemiological Methods for Assessing Dose-Response and Dose-Effect Relationships Essential Metals: Assessing Risks from Deficiency and Toxicity Carcinogenicity of Metal Compounds Immunotoxicology of Metals Reproductive and Developmental Toxicity of Metals Ecotoxicology of Metals - Sources, Transport, and Effects in the Ecosystem Risk Assessment Diagnosis and Treatment of Metal Poisoning - General Aspects Principles for Prevention of the Toxic Effects of Metals Aluminum Antimony Arsenic Barium Beryllium Bismuth Cadmium Chromium Cobalt Copper Gallium and Semiconductor Compounds Germanium Indium Iron Lead Manganese Mercury Molybdenum Nickel Palladium Platinum Selenium Silver Tellurium Thallium Tin Titanium Tungsten Uranium Vanadium Zinc
DEFF Research Database (Denmark)
Christensen, Erik R.; Kusk, Kresten Ole
2009-01-01
We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4-4-(trifluoromethyl)phenoxy-phenol) with ranges of representative slopes at 50% response (0.54-2.62) and EC50s (2.20-357 mg/L) were selected. Reference EC50s and EC10s with 95% confidence limits using probit or Weibull models are calculated by nonlinear regression on the whole dataset using a dose - response regression program with variance weighting and proper inverse estimation. The Weibull model provides the best fit to the data for all four chemicals. Predicted EC10s (95% confidence limits) from our derived equations are quite accurate; for example, with 4-4-(trifluoromethyl)phenoxy-phenol and the probit model, we obtain 1.40 (1.22-1.61) mg/L versus 1.40 (1.20-1.64) mg/L obtained from the nonlinear regression program. The main advantage of the approach is that EC10 or ECx (where x = 1 - 99) can be predicted from well-determined responses around EC20 to EC80 without experimental data in the low- or high-response range. Problems with the estimation of confidence interval for EClow,x (concentration predicted to cause x% inhibition) from algal growth inhibition also are addressed. Large confidence intervals may be the result of experimental error and lack of a well-defined reference response value.
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.
Dose-response relationship for breast cancer induction at radiotherapy dose
Directory of Open Access Journals (Sweden)
Gruber Günther
2011-06-01
Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an ?/? = 3 Gy were ? = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.
Origin of the linearity no threshold (LNT) dose-response concept.
Calabrese, Edward J
2013-09-01
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
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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
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.
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
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
Elen, Ken; Van den Rul, Heidi; Hardy, An; Van Bael, Marlies K.; D'Haen, Jan; Peeters, Roos; Franco, Dirk; Mullens, Jules
2009-02-01
In this paper a 28-4 fractional factorial design of experiments is applied to identify the important parameters that affect the average diameter of ZnO rods, synthesized by means of a hydrothermal procedure. A water-based Zn2+ precursor is used for the formation of one-dimensional ZnO particles, without the presence of an organic additive. Results indicate that, at the investigated levels, four of the parameters have a significant effect on the mean diameter. These are the temperature, the heating rate, stirring and an ultrasonic pre-treatment of the precursor solution. Experiments carried out with zinc acetate and zinc chloride do not show a significant difference in rod diameter. Other parameters that do not show a significant effect are the concentration of Zn2+, the molar ratio between the hydroxyl and the zinc ions, and the reaction time. Interactions are observed between stirring and an ultrasonic pre-treatment and between the zinc concentration and the OH:Zn ratio. By fixing the significant factors at their optimal value it is possible to decrease the mean diameter. The particles are characterized by means of x-ray diffraction (XRD) and transmission electron microscopy (TEM).
International Nuclear Information System (INIS)
In this paper a 28-4 fractional factorial design of experiments is applied to identify the important parameters that affect the average diameter of ZnO rods, synthesized by means of a hydrothermal procedure. A water-based Zn2+ precursor is used for the formation of one-dimensional ZnO particles, without the presence of an organic additive. Results indicate that, at the investigated levels, four of the parameters have a significant effect on the mean diameter. These are the temperature, the heating rate, stirring and an ultrasonic pre-treatment of the precursor solution. Experiments carried out with zinc acetate and zinc chloride do not show a significant difference in rod diameter. Other parameters that do not show a significant effect are the concentration of Zn2+, the molar ratio between the hydroxyl and the zinc ions, and the reaction time. Interactions are observed between stirring and an ultrasonic pre-treatment and between the zinc concentration and the OH:Zn ratio. By fixing the significant factors at their optimal value it is possible to decrease the mean diameter. The particles are characterized by means of x-ray diffraction (XRD) and transmission electron microscopy (TEM).
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
de Jong, Nynke; Verkaik-Kloosterman, Janneke; Verhagen, Hans; Boshuizen, Hendriek C; Bokkers, Bas; Hoekstra, Jeljer
2013-04-01
If a diet, food or food constituent is recognised to have both health benefits and health risks, the benefits have to be compared with the risks to develop coherent scientific evidence-based dietary advice. This means that both risk and benefit assessment should follow a similar paradigm and that benefits and risks are expressed in a common currency. Dose-response functions are vital for that purpose. However, the construction of these functions is often of second interest in the currently available (epidemiological) literature. In order to bring forward the potential of epidemiological studies for the construction of the dose-response functions for benefit-risk purposes, the scientific (nutrition and health) community is asked to expand on their data presentation, either by presenting more detailed data focusing on dose-response necessities, and/or by sharing primary data. PMID:22902968
Directory of Open Access Journals (Sweden)
K Montazeri
2005-03-01
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.
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
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Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu
2005-12-15
This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology.
Scientific Electronic Library Online (English)
Rebeca Lima, AFONSO; Juliano Pelim, PESSAN; Bruna Babler, IGREJA; Camila Fernandes, CANTAGALLO; Marcelle, DANELON; Alberto Carlos Botazzo, DELBEM.
2013-12-01
Full Text Available No in situ protocol has assessed the dose-response effects of fluoride dentifrices involving low-fluoride formulations. Objective: To assess the ability of an in situ remineralization model in determining dose-response effects of dentifrices containing low fluoride concentrations ([F]) on bovine [...] enamel. Material and Methods: Volunteers wore palatal appliances containing demineralized enamel blocks and brushed their teeth and devices with the dentifrices supplied (double-blind, crossover protocol) separately for 3 and 7 days. Surface hardness (SH), integrated subsurface hardness (?KHN) and [F] in enamel were determined. Data were analyzed by ANOVA, Tukey's test and Pearson's correlation (p
DEFF Research Database (Denmark)
Christiansen, E; Goldney, R D; Beautrai, A L; Agerbo, E
2011-01-01
There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 ...
DEFF Research Database (Denmark)
Christiansen, Erik; Goldney, R; Beautrai, A; Agerbo, Esben
2011-01-01
BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among ...
Leka, K. D.; Barnes, G.
2007-02-01
Statistical tests based on linear discriminant analysis are applied to numerous photospheric magnetic parameters, continuing toward the goal of identifying properties important for the production of solar flares. For this study, the vector field data are University of Hawai`i Imaging Vector Magnetograph daily magnetograms obtained between 2001 and 2004. Over 1200 separate magnetograms of 496 numbered active regions comprise the data set. At the soft X-ray C1.0 level, 359 magnetograms are considered ``flare productive'' in the 24 hr postobservation. Considering multiple photospheric variables simultaneously indicates that combinations of only a few familiar variables encompass the majority of the predictive power available. However, the choice of which few variables is not unique, due to strong correlations among photospheric quantities such as total magnetic flux and total vertical current, two of the most powerful predictors. The best discriminant functions result from combining one of these with additional uncorrelated variables, such as measures of the magnetic shear, and successfully classify over 80% of the regions. By comparison, a success rate of approximately 70% is achieved by simply classifying all regions as ``flare quiet.'' Redefining ``flare-productive'' at the M1.0 level, parameterizations of excess photospheric magnetic energy outperform other variables. However, the uniform flare-quiet classification rate is approximately 90%, while incorporating photospheric magnetic field information results in at most a 93% success rate. Using nonparametric discriminant analysis, we demonstrate that the results are quite robust. Thus, we conclude that the state of the photospheric magnetic field at any given time has limited bearing on whether that region will be flare productive.
Desneux, N; Rafalimanana, H; Kaiser, L
2004-02-01
Neurotoxic insecticides are widely used for crop protection and behavioural perturbations can be expected in surviving beneficial insects, including parasitoids of pest insects. The present study aims to investigate the relationship between the dose of insecticide parasitoids have been exposed to, and the subsequent ability of these parasitoids to respond to host-related cues. A four-armed olfactometer, a design widely used to observe orientation responses in various insects and parasitoids in particular, was chosen to investigate the dose-response relationship. The species studied was Aphidius ervi, a relatively generalist parasitoid of aphids, and commercialised for biological control and integrated pest management. Active ingredients with similar and different modes of action on the nervous system were compared: a pyrethroid (lambda-cyhalothrin), an organophosphate (chlorpyrifos), a carbamate (pirimicarb) and a carbamyltriazole (triazamate). Adult females were exposed to dry residues on glass for 24 h. LD50 were calculated and predicted a high risk of mortality at the field application rate. The effect of five increasing residual doses of each active ingredient was tested on responses to plant-host odour in the olfactometer, from sublethal doses to LD50, and up to LD70 for some products. It appeared that none of the doses of lambda-cyhalothrin, chlorpyriphos and pirimicarb had any effect on A. ervi responses to the odour from the aphid-infested plant (Myzus persicae on oilseed rape). But for triazamate, a significant dose-behavioural response was quantified and attraction to the odour was no longer significant in females surviving the LD50. The possible explanations for the presence or absence of effect, depending on the insecticide are discussed. PMID:14599507
Gaonkar, Bilwaj; Davatzikos, Christos
2013-09-01
Multivariate pattern analysis (MVPA) methods such as support vector machines (SVMs) have been increasingly applied to fMRI and sMRI analyses, enabling the detection of distinctive imaging patterns. However, identifying brain regions that significantly contribute to the classification/group separation requires computationally expensive permutation testing. In this paper we show that the results of SVM-permutation testing can be analytically approximated. This approximation leads to more than a thousandfold speedup of the permutation testing procedure, thereby rendering it feasible to perform such tests on standard computers. The speedup achieved makes SVM based group difference analysis competitive with standard univariate group difference analysis methods. PMID:23583748
Mark Burden, Adrian; Lewis, Sandra Elizabeth; Willcox, Emma
2014-12-01
Numerous ways exist to process raw electromyograms (EMGs). However, the effect of altering processing methods on peak and mean EMG has seldom been investigated. The aim of this study was to investigate the effect of using different root mean square (RMS) window lengths and overlaps on the amplitude, reliability and inter-individual variability of gluteus maximus EMGs recorded during the clam exercise, and on the statistical significance and clinical relevance of amplitude differences between two exercise conditions. Mean and peak RMS of 10 repetitions from 17 participants were obtained using processing window lengths of 0.01, 0.15, 0.2, 0.25 and 1 s, with no overlap and overlaps of 25, 50 and 75% of window length. The effect of manipulating window length on reliability and inter-individual variability was greater for peak EMG (coefficient of variation [CV] <9%) than for mean EMG (CV <3%), with the 1 s window generally displaying the lowest variability. As a consequence, neither statistical significance nor clinical relevance (effect size [ES]) of mean EMG was affected by manipulation of window length. Statistical significance of peak EMG was more sensitive to changes in window length, with lower p-values generally being recorded for the 1 s window. As use of different window lengths has a greater effect on variability and statistical significance of the peak EMG, then clinicians should use the mean EMG. They should also be aware that use of different numbers of exercise repetitions and participants can have a greater effect on EMG parameters than length of processing window. PMID:24985956
Bornmann, Lutz; Leydesdorff, Loet
2011-01-01
The methods presented in this paper allow for a statistical analysis revealing centers of excellence around the world using programs that are freely available. Based on Web of Science data, field-specific excellence can be identified in cities where highly-cited papers were published significantly. Compared to the mapping approaches published hitherto, our approach is more analytically oriented by allowing the assessment of an observed number of excellent papers for a city (...
Engelbrecht, C. A.; Frescura, F. A. M.; Frank, B. S.
2009-01-01
We have used Lomb-Scargle periodogram analysis and Monte Carlo significance tests to detect periodicities above the 3-sigma level in the Beta Cephei stars V400 Car, V401 Car, V403 Car and V405 Car. These methods produce six previously unreported periodicities in the expected frequency range of excited pulsations: one in V400 Car, three in V401 Car, one in V403 Car and one in V405 Car. One of these six frequencies is significant above the 4-sigma level. We provide statistical...
Linearization of dose–response curve of the radiochromic film dosimetry system
International Nuclear Information System (INIS)
Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose–response curve of the radiochromic film dosimetry system. Methods: Functional form [?= (?1)·netOD(2/3)/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC™ film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R2 values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC™ EBT3 film model are well within ±2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%/3 mm for an IMRT QA plan and 3%/2 mm for a brachytherapy QA plan are passing 95% gamma function points. Conclusions: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.
DEFF Research Database (Denmark)
Olsson, C; Thor, M
2014-01-01
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.
Linearization of dose-response curve of the radiochromic film dosimetry system
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Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad; DeBlois, Francois; Seuntjens, Jan; Chan, Maria F.; Lewis, Dave [Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Executive Administration for Radiation Protection and Safety Medical Devices Sector, Saudi Food and Drug Authority, Riyadh, Kingdom of Saudi Arabia 13312 (Saudi Arabia); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center Basking Ridge, New Jersey 07920 (United States); Ashland Inc., Wayne, New Jersey 07470 (United States)
2012-08-15
Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also 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.
International Nuclear Information System (INIS)
At therapeutic doses, acetaminophen (APAP) is a safe and effective analgesic. However, overdose of APAP is the principal cause of acute liver failure in the West. Binding of the reactive metabolite of APAP (NAPQI) to proteins is thought to be the initiating event in the mechanism of hepatotoxicity. Early work suggested that APAP-protein binding could not occur without glutathione (GSH) depletion, and likely only at toxic doses. Moreover, it was found that protein-derived APAP-cysteine could only be detected in serum after the onset of liver injury. On this basis, it was recently proposed that serum APAP-cysteine could be used as diagnostic marker of APAP overdose. However, comprehensive dose–response and time course studies have not yet been done. Furthermore, the effects of co-morbidities on this parameter have not been investigated. We treated groups of mice with APAP at multiple doses and measured liver GSH and both liver and plasma APAP-protein adducts at various timepoints. Our results show that protein binding can occur without much loss of GSH. Importantly, the data confirm earlier work that showed that protein-derived APAP-cysteine can appear in plasma without liver injury. Experiments performed in vitro suggest that this may involve multiple mechanisms, including secretion of adducted proteins and diffusion of NAPQI directly into plasma. Induction of liver necrosis through ischemia–reperfusion significantly increased the plasma concentration of protein-derived APAP-cysteine after a subtoxic dose of APAP. While our data generally support the measurement of serum APAP-protein adducts in the clinic, caution is suggested in the interpretation of this parameter. - Highlights: • Extensive GSH depletion is not required for APAP-protein binding in the liver. • APAP-protein adducts appear in plasma at subtoxic doses. • Proteins are adducted in the cell and secreted out. • Coincidental liver injury increases plasma APAP-protein adducts at subtoxic doses. • Plasma APAP-protein adducts are diagnostically useful, but interpret with care
SnET2 for the treatment of vascular disease: dose/response study in New Zealand white (NZW) rabbits
Narciso, Hugh L., Jr.; Anderson, Steven C.; DeHoratius, Sandra L.; Guerrero, Jan; Wang, T.; Spears, J. Richard
1995-05-01
Tin ethyl etiopurpurin, SnET2, is presently undergoing clinical trials for the treatment of cutaneous cancers and AIDS related Kaposi's sarcoma. Extensive pre-clinical work has been performed investigating the uptake, localization, and retention of SnET2 in catheter induced atheromatous plaques in New Zealand White (NZW) rabbits and juvenile female swine. The ultimate goal is to employ SnET2 for the prevention of intimal hyperplasia following various forms of angioplasty, thus enabling the prevention of a significant cause of restenosis. To that end, a dose/response study was undertaken to investigate the effect of varying total light dose (200, 100, and 50 J/cm2) and light dose rate (637, 318, 159 mW/cm2) during SnET2-Photodynamic Therapy, SnET2-PDT, of catheter induced plaque in a NZW rabbit iliac artery model. The SnET2 dose was held constant at 1.0 mg/kg b.w. and light was delivered intraluminally via a guidewire compatible light diffusing balloon catheter. The greatest light dose of those tested without inducing thermal damage was found to be 318 mW/cm2 while the total light dose of 50 J/cm2 produced PDT effect which was limited to the neo-intima. A relatively substantial total light dose of 200 J/cm2 was shown to produce a transmural PDT effect. This study demonstrated that the depth of PDT effect can be modulated by varying the total light dose.
Wang, Yun-Liang; Wang, Yu-Tong; Li, Jin-Feng; Zhang, Yu-Zheng; Yin, Hong-Lei; Han, Bing
2015-01-01
Background A number of epidemiologic studies examining the relationship between body mass index (BMI) and the future occurrence of Parkinson’s disease (PD) reported largely inconsistent findings. We conducted a dose-response meta-analysis of prospective studies to clarify this association. Methods Eligible prospective studies were identified by a search of PubMed and by checking the references of related publications. The generalized least squares trend estimation was employed to compute study-specific relative risks (RR) and 95% confidence intervals (CI) for an increase in BMI of 5 kg/m2, and the random-effects model was used to compute summary RR and 95% CI. Results A total of 10 prospective studies were included in the final analysis. An increase in BMI of 5 kg/m2 was not associated with PD risk, with a summary RR of 1.00 (95% CI = 0.89-1.12). Results of subgroup analysis found similar results except for a week positive association in studies that adjusted for alcohol consumption (RR = 1.13, 95% CI = 0.99-1.29), and a week inverse association in studies that did not (RR = 0.90, 95% CI = 0.78-1.04). In a separate meta-analysis, no significant association between overweight (25 kg/m2 ? BMI ?29.9 kg/m2), obesity (BMI?30 kg/m2) or excess weight (BMI?25 kg/m2) and PD risk was observed. Conclusion This meta-analysis does not support the notion that higher BMI materially increases PD risk. However, a week positive BMI-PD association that may be masked by confounders still cannot be excluded, and future prospective studies with a good control for potential confounding factors are needed. PMID:26121579
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Chronic drinking water exposure to inorganic arsenic and its metabolites increases tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, we characterized gene expression profiles from analysis of K6/ODC mice administered 0, 0.05, 0.25, 1.0 and 10 ppm sodium arsenite in their drinking water for 4 weeks. Following exposure, total RNA was isolated from mouse skin and processed to biotin-labeled cRNA for microarray analyses. Skin gene expression was analyzed with Affymetrix Mouse Genome 430A 2.0 GeneChips (registered) , and pathway analysis was conducted with DAVID (NIH), Ingenuity (registered) Systems and MetaCore's GeneGo. Differential expression of several key genes was verified through qPCR. Only the highest dose (10 ppm) resulted in significantly altered KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, including MAPK, regulation of actin cytoskeleton, Wnt, Jak-Stat, Tight junction, Toll-like, phosphatidylinositol and insulin signaling pathways. Approximately 20 genes exhibited a dose response, including several genes known to be associated with carcinogenesis or tumor progression including cyclin D1, CLIC4, Ephrin A1, STAT3 and DNA methyltransferase 3a. Although transcription changes in all identified genes have not previously been linked to arsenic carcinogenesis, their association with carcinogenesis in other systems suggests that these genes may play a role in the early stages of arsenic-induced skin carcinogenesis and can be considered potential biomarkers
Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.
2011-01-01
The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.
Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships
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Thompson Sally
2010-11-01
Full Text Available Abstract Background To compare the efficacy of pregabalin and gabapentin at comparable effective dose levels in patients with refractory partial epilepsy. Methods Eight randomized placebo controlled trials investigating the efficacy of pregabalin (4 studies and gabapentin (4 studies over 12 weeks were identified with a systematic literature search. The endpoints of interest were "responder rate" (where response was defined as at least a 50% reduction from baseline in the number of seizures and "change from baseline in seizure-free days over the last 28 days (SFD". Results of all trials were analyzed using an indirect comparison approach with placebo as the common comparator. The base-case analysis used the intention-to-treat last observation carried forward method. Two sensitivity analyses were conducted among completer and responder populations. Results The base-case analysis revealed statistically significant differences in response rate in favor of pregabalin 300 mg versus gabapentin 1200 mg (odds ratio, 1.82; 95% confidence interval, 1.02, 3.25 and pregabalin 600 mg versus gabapentin 1800 mg (odds ratio, 2.52; 95% confidence interval, 1.21, 5.27. Both sensitivity analyses supported the findings of the base-case analysis, although statistical significance was not demonstrated. All dose levels of pregabalin (150 mg to 600 mg were more efficacious than corresponding dosages of gabapentin (900 mg to 2400 mg in terms of SFD over the last 28 days. Conclusion In patients with refractory partial epilepsy, pregabalin is likely to be more effective than gabapentin at comparable effective doses, based on clinical response and the number of SFD.
Murphy, C C; Burnett, C A M; Spry, P G D; Broadway, D C; Diamond, J P
2003-01-01
Background/aims: Transscleral diode laser cyclophotocoagulation (“cyclodiode”) is widely used to treat refractory glaucoma. The main aims of this study were to investigate the dose-response relation of cyclodiode and to evaluate possible predictive factors that would help establish optimum treatment parameters.
Shi, Yun; Li, Tingting; Wang, Ying; Zhou, Lingling; Qin, Qin; Yin, Jieyun; Wei, Sheng; Liu, Li; Nie, Shaofa
2015-01-01
Controversial results of the association between household physical activity and cancer risk were reported among previous epidemiological studies. We conducted a meta-analysis to investigate the relationship of household physical activity and cancer risk quantitatively, especially in dose-response manner. PubMed, Embase, Web of science and the Cochrane Library were searched for cohort or case-control studies that examined the association between household physical activity and cancer risks. Random-effect models were conducted to estimate the summary relative risks (RRs), nonlinear or linear dose-response meta-analyses were performed to estimate the trend from the correlated log RR estimates across levels of household physical activity quantitatively. Totally, 30 studies including 41 comparisons met the inclusion criteria. Total cancer risks were reduced 16% among the people with highest household physical activity compared to those with lowest household physical activity (RR?=?0.84, 95% CI?=?0.76-0.93). The dose-response analyses indicated an inverse linear association between household physical activity and cancer risk. The relative risk was 0.98 (95% CI?=?0.97-1.00) for per additional 10 MET-hours/week and it was 0.99 (95% CI?=?0.98-0.99) for per 1?hour/week increase. These findings provide quantitative data supporting household physical activity is associated with decreased cancer risk in dose-response effect. PMID:26443426
Experiments were conducted to determine 1) dose response of glyphosate-resistant (GR) and –susceptible (non-GR) soybean [Glycine max (L.) Merr.] and canola (Brassica napus L.) to glyphosate, 2) if differential metabolism of glyphosate to aminomethylphosphonic acid (AMPA) is the underlying mechanism ...
Shi, Yun; Li, Tingting; Wang, Ying; Zhou, Lingling; Qin, Qin; Yin, Jieyun; Wei, Sheng; Liu, Li; Nie, Shaofa
2015-01-01
Controversial results of the association between household physical activity and cancer risk were reported among previous epidemiological studies. We conducted a meta-analysis to investigate the relationship of household physical activity and cancer risk quantitatively, especially in dose-response manner. PubMed, Embase, Web of science and the Cochrane Library were searched for cohort or case-control studies that examined the association between household physical activity and cancer risks. Random–effect models were conducted to estimate the summary relative risks (RRs), nonlinear or linear dose–response meta-analyses were performed to estimate the trend from the correlated log RR estimates across levels of household physical activity quantitatively. Totally, 30 studies including 41 comparisons met the inclusion criteria. Total cancer risks were reduced 16% among the people with highest household physical activity compared to those with lowest household physical activity (RR?=?0.84, 95% CI?=?0.76–0.93). The dose-response analyses indicated an inverse linear association between household physical activity and cancer risk. The relative risk was 0.98 (95% CI?=?0.97–1.00) for per additional 10 MET-hours/week and it was 0.99 (95% CI?=?0.98–0.99) for per 1?hour/week increase. These findings provide quantitative data supporting household physical activity is associated with decreased cancer risk in dose-response effect. PMID:26443426
Howie, Erin K.; Schatz, Jeffrey; Pate, Russell R.
2015-01-01
Purpose: The purpose of this study was to determine the acute dose-response relationship of classroom exercise breaks with executive function and math performance in 9- to 12-year-old children by comparing 5-min, 10-min, or 20-min classroom exercise breaks to 10 min of sedentary classroom activity. Method: This study used a within-subjects…
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Highlights: • Mice received either a range of 18F-FDG activities or whole body X-ray doses. • Blood samples were collected at 24 and 43 h for MN-RET and QPCR analysis. • Regression analysis showed that both types of exposure produced a linear response. • BM doses of 33 mGy (18F-FDG) and 25 mGy X-rays were significantly higher than controls. • No significant difference between internal (18F-FDG) and external (X-ray) was found. - Abstract: The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3–5 mice were randomly assigned to 10 groups, each receiving either a different activity of 18F-FDG: 0–37 MBq or whole body irradiated with corresponding doses of 0–300 mGy X-rays. Blood samples were collected at 24 h and at 43 h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of 18F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43 mGy and above for internal 18F-FDG exposure and to 25 mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P < 0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R2 of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose–responses at 24 h for Bbc3 and Cdkn1 were similar for 18F-FDG and X-ray exposures, with significant modifications occurring for doses over 300 mGy for Bbc3 and at the lower dose of 150 mGy for Cdkn1a. Both leucocyte gene expression and quantification of MN-RET are highly sensitive biomarkers for reliable estimation of the low doses delivered in vivo to, respectively, blood and bone marrow, following 18F-FDG PET
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Manning, Grainne [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom); Taylor, Kristina [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON (Canada); Finnon, Paul [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom); Lemon, Jennifer A.; Boreham, Douglas R. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON (Canada); Badie, Christophe, E-mail: christophe.badie@phe.gov.uk [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom)
2014-12-15
Highlights: • Mice received either a range of {sup 18}F-FDG activities or whole body X-ray doses. • Blood samples were collected at 24 and 43 h for MN-RET and QPCR analysis. • Regression analysis showed that both types of exposure produced a linear response. • BM doses of 33 mGy ({sup 18}F-FDG) and 25 mGy X-rays were significantly higher than controls. • No significant difference between internal ({sup 18}F-FDG) and external (X-ray) was found. - Abstract: The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 ({sup 18}F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3–5 mice were randomly assigned to 10 groups, each receiving either a different activity of {sup 18}F-FDG: 0–37 MBq or whole body irradiated with corresponding doses of 0–300 mGy X-rays. Blood samples were collected at 24 h and at 43 h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of {sup 18}F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43 mGy and above for internal {sup 18}F-FDG exposure and to 25 mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P < 0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R{sup 2} of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose–responses at 24 h for Bbc3 and Cdkn1 were similar for {sup 18}F-FDG and X-ray exposures, with significant modifications occurring for doses over 300 mGy for Bbc3 and at the lower dose of 150 mGy for Cdkn1a. Both leucocyte gene expression and quantification of MN-RET are highly sensitive biomarkers for reliable estimation of the low doses delivered in vivo to, respectively, blood and bone marrow, following {sup 18}F-FDG PET.
Dose-response relationships for female radium dial workers: A new look
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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
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Five hundred seventy-four patients with prostate cancer treated by external beam radiation therapy in the United States in 1973 to 1975 have been analyzed comparing radiation dose with in-field recurrence. Dose-response effects are observed for all cases and T-2 and T-3 tumors, but not for T-0, T-1 and T-4 tumors. For doses calculated at the center of the prostate, these observations suggest optimal control is obtained at no more than 6000 rad for T-0 and T-1 tumors; 6000-6500 rad for T-2 tumors; 6500-7000 rad for T-3 tumors; and that greater than 7000 rad is required only for T-4 tumors. The paraprostatic dose calculated at a point 4 cm lateral to the center of the prostate also shows a correlation of dose with infield failure for all cases. These data suggest that for T-2 and T-3 cancers, extension in the periprostatic region must be treated. A comparison of central dose vs. stage indicates institutional policy rather than cancer volume determines the radiation dose used in treating prostate cancer. A change in institutional policies to treat with optimal doses as indicated by this study would result in an overall increase in local control and a decrease in complications
Directory of Open Access Journals (Sweden)
Claussen CM
2014-02-01
Full Text Available Catherine M Claussen, Nachum Dafny Department of Neurobiology and Anatomy, University of Texas Health Science Center Medical School at Houston, Houston, TX, USA Abstract: The prefrontal cortex (PFC is part of the collective structures known as the motive circuit. The PFC acts to enhance higher cognitive functions as well as mediate the effects of psychostimulants. Previous literature shows the importance of PFC neuronal adaptation in response to acute and chronic psychostimulant exposure. The PFC receives input from other motive circuit structures, including the ventral tegmental area, which mediates and facilitates the rewarding effects of psychostimulant exposure. PFC neuronal and locomotor activity from freely behaving rats previously implanted with permanent semimicroelectrodes were recorded concomitantly using a telemetric (wireless recording system. Methylphenidate (MPD is used as a leading treatment for behavioral disorders and more recently as a cognitive enhancer. Therefore, the property of MPD dose response on PFC neuronal activity was investigated. The results indicate that MPD modulates PFC neuronal activity and behavioral activity in a dose-dependent manner. PFC neuronal responses to 0.6 mg/kg elicited mainly a decrease in PFC neuronal activity, while higher MPD doses (2.5 and 10.0 mg/kg elicited mainly increased neuronal activity in response to MPD. The correlation between MPD effects on PFC neuronal activity and animal behavior is discussed. Keywords: prefrontal cortex, Ritalin, behavior, neuronal, acute
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)
New flux based dose-response relationships for ozone for European forest tree species.
Büker, P; Feng, Z; Uddling, J; Briolat, A; Alonso, R; Braun, S; Elvira, S; Gerosa, G; Karlsson, P E; Le Thiec, D; Marzuoli, R; Mills, G; Oksanen, E; Wieser, G; Wilkinson, M; Emberson, L D
2015-11-01
To derive O3 dose-response relationships (DRR) for five European forest trees species and broadleaf deciduous and needleleaf tree plant functional types (PFTs), phytotoxic O3 doses (PODy) were related to biomass reductions. PODy was calculated using a stomatal flux model with a range of cut-off thresholds (y) indicative of varying detoxification capacities. Linear regression analysis showed that DRR for PFT and individual tree species differed in their robustness. A simplified parameterisation of the flux model was tested and showed that for most non-Mediterranean tree species, this simplified model led to similarly robust DRR as compared to a species- and climate region-specific parameterisation. Experimentally induced soil water stress was not found to substantially reduce PODy, mainly due to the short duration of soil water stress periods. This study validates the stomatal O3 flux concept and represents a step forward in predicting O3 damage to forests in a spatially and temporally varying climate. PMID:26164201
Using plant biomonitors and flux modelling to develop O3 dose-response relationships in Catalonia
International Nuclear Information System (INIS)
We used tobacco Bel-W3 biomonitoring data and ozone flux modelling (WINDEP model) with the aim of developing the absorbed dose-response relationship, and comparing this approach with the most commonly used AOT40 (the sum of hourly ozone concentrations above a cut-off of 40 ppb during daylight hours, when global radiation exceeds 50 W m-2) in the estimation of exposure-damage curves. Leaf damage values were more related to OAD15days,potential (potential ozone absorbed dose calculated over 15 consecutive days) than to AOT40 in all the studied stations. An OAD15days,potential of 180 mg m-2 was found to be the threshold for damage to the most sensitive species in this region under well watered conditions. The results show the applicability of the flux approach for risk assessment at the local scale, the improvement of the ozone damage estimation when the potential absorbed dose is modelled and used instead of just the ozone exposure, and finally, the possibilities opened by the use of biomonitoring networks. - Modelling of biomonitors ozone absorbed dose improves damage estimation in comparison with exposure indices such as AOT40
International Nuclear Information System (INIS)
In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of 60Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment
Dose responses in a normoxic polymethacrylic acid gel dosimeter using optimal CT scanning parameters
Energy Technology Data Exchange (ETDEWEB)
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
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%.
Digitoxin medication and cancer; case control and internal dose-response studies
International Nuclear Information System (INIS)
Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease.These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents
Galanos, Irene; Rokos, Demetrius
2006-12-01
A map indicating zones related to groundwater on the mountainous terrain of the island of Naxos, Greece, was produced, using statistics, remote sensing and geographic information system (GIS) techniques. Naxos mainly consists of polydeformed and polymetamorphosed crystalline formations where groundwater is restricted to secondary porosity; its movement is erratic and occurs along lithological contacts, solution openings, faults and fractures. As in the most central Aegean islands, water in Naxos is a scarce commodity. Many dry holes have been drilled. It is known that in areas of such geology, linear features may play a significant role in their hydrogeological regime. Various lineaments’ directional properties were calculated and statistically tested against collected spring data using GIS techniques in an attempt to evaluate the hydrogeological significance of remotely sensed lineaments. Based on the results achieved, a map was prepared to contribute to conventional ground surveys in the selection of drilling sites. The reliability of the map was tested with existing borehole data. The results obtained encourage the use of statistical analysis on remotely sensed lineaments for groundwater targeting studies in crystalline mountainous areas.
Directory of Open Access Journals (Sweden)
Liosi Giulia Maria
2015-09-01
Full Text Available The Fricke xylenol orange (FX gel system is a chemical dosimeter characterized by good sensitivity, linear dose response, tissue equivalence, no toxicity, easy preparation, reproducibility and low cost. Thanks to the presence of the gelatinous matrix, the system is particularly suitable to perform reliable 3D mapping of the absorbed dose spatial distribution via magnetic resonance imaging (MRI or optical techniques. The aim of this work is to study in a systematic way the influence of the pre-irradiation storage procedure upon sensitivity, dose response stability and lifetime of use of a FX gel system made with gelatin from porcine skin subjected to homogeneous irradiation. For this purpose, different pre-irradiation storage procedures, in terms of temperature and duration of each storage step, were investigated. In order to evaluate the dose response stability, the optical analyses of the samples were performed up to 6 hours after irradiation. Moreover, the samples were irradiated at time intervals of 24 hours for up to 7 days after preparation in order to evaluate the system lifetime of use. Regardless of their thermal and temporal life, the samples show linear dose responses in the investigated dose range (3-24 Gy and an increase of sensitivity with the time elapsed between preparation and irradiation. Among the three pre-irradiation storage procedures considered here, a procedure that provides the best dose response stability and lifetime of use was identified and recommended for further use. The analyzed dosimetric system possesses good properties that make it promising for medical application, particularly concerning the evaluation of pre-treatment plan quality assurance within the conformational external beam radiotherapy
Directory of Open Access Journals (Sweden)
Tamrakar Sushil B
2012-03-01
Full Text Available Abstract Background Rickettsia typhi (R. mooseri is the causative agent of murine typhus. It is one of the most widely distributed flea-borne diseases with a relatively mild febrile initial illness with six to 14 days of incubation period. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through fleabites or via contact with infected feces. This paper develops dose-response models of different routes of exposure for typhus in rodents. Methods Data from published articles were analyzed using parametric dose-response relationship models. Dose-response relationships were fit to data using the method of maximum likelihood estimation (MLE. Results Dose-response models quantifying the effects of different ages of rats and time post inoculation in BALB/c mice were analyzed in the study. Both the adult rats (inoculated intradermally and newborn rats (inoculated subcutaneously were best fit by exponential models and both distributions could be described by a single dose-response relationship. The BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The time post inoculation analysis showed that there was a definite time and response relationship existed in this case. Conclusions Intradermally or subcutaneously inoculated rats (adult and newborn models suggest that less than 1 plaque-forming unit (PFU (1.33 to 0.38 in 95% confidence limits of the pathogen is enough to seroconvert 50% of the exposed population on average. For the BALB/c mouse time post inoculation model, an average dose of 0.28 plaque-forming units (PFU (0.75 to 0.11 in 95% confidence limits will seroconvert 50% of the exposed mice.
Ferraresi, Cleber; Dos Santos, Ricardo Vinicius; Marques, Guilherme; Zangrande, Marcelo; Leonaldo, Roberley; Hamblin, Michael R; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio
2015-05-01
Low-level laser (light) therapy (LLLT) has been applied over skeletal muscles before intense exercise (muscular pre-conditioning) in order to reduce fatigue and muscle damage (measured by creatine kinase, CK) in clinical trials. However, previous exercise protocols do not exactly simulate the real muscle demand required in sports. For this reason, the aim of this randomized and double-blind placebo-controlled trial was to investigate whether light-emitting diode therapy (LEDT) applied over the quadriceps femoris muscles, hamstrings, and triceps surae of volleyball players before official matches could prevent muscle damage (CK) with a dose response, establishing a therapeutic window. A professional male volleyball team (12 athletes) was enrolled in this study, and LEDT was applied before 4 matches during a national championship. LEDT used an array of 200 light-emitting diodes (LEDs) arranged in 25 clusters of 4 infrared LEDs (850?±?20 nm; 130 mW) and 25 clusters of 4 red LEDs (630?±?10 nm; 80 mW). Athletes were randomized to receive one of four different total doses over each muscle group in a double-blind protocol: 105 J (20 s), 210 J (40 s), 315 J (60 s), and placebo (no light for 30 s). CK in blood was assessed 1 h before and 24 h after each match. LEDT at 210 J avoided significant increases in CK (+10 %; P?=?0.993) as well as 315 J (+31 %, P?=?0.407). Placebo (0 J) allowed a significant increase in CK (+53 %; P?=?0.012) as well as LEDT at 105 J (+59 %; P?=?0.001). LEDT prevented significant increases of CK in blood in athletes when applied before official matches with a light dose response of 210-315 J, suggesting athletes might consider applying LEDT before competition. PMID:25722067
International Nuclear Information System (INIS)
Ionizing radiation (IR) induces single strand breaks, double strand breaks (DSB), base damages in human cell. Double strand breaks are the most deleterious and if not repaired may lead to genomic instability and cell death. DSB can be repaired through Non-Homologous End Joining (NHEJ) pathway in resting lymphocytes. In the present study, radiation induced NHEJ genes and proteins were studied in resting Peripheral Blood Mononuclear Cells (PBMC) exposed to various doses of gamma radiation. Dose response, time point kinetics and adaptive response studies were conducted in irradiated PBMC and various end points such as DNA damage quantitation, transcription and protein expression profile were studied. Venous blood samples were collected from 20 random, normal, and healthy donors with written informed consent. PBMC was separated and irradiated with various doses between 0.1 Gy to 2.0 Gy (60Co-? source) for dose response study. Repair kinetics of DNA damage and time point changes in expression of genes and proteins were studied in post-irradiated PBMC at 2.0 Gy at various time points up to 240 min. Adaptive response study was conducted with a priming dose of 0.1 Gy followed by a challenging dose of 2.0 Gy after 4 h incubation. Our results revealed that significant increase in DNA double strand breaks at higher doses. Both slow and fast repair kinetics were observed among the donors. DNA double strand break recognizing Ku proteins (Ku70 and Ku80), XLF and Ligase IV were significantly up regulated at transcript as well as protein expression level, indicating the active role of NHEJ pathway in repairing and rejoining DNA DSBs. Radio-adaptive study also showed significant up regulation of Ku70, Ku80, DNA-PKcs, XRCC4 and Ligase IV suggesting the involvement of NHEJ proteins in radio-adaptive response in human PBMC at G0/G1, which has important implications to human health. (author)
The H-ARS Dose Response Relationship (DRR): Validation and Variables.
Plett, P Artur; Sampson, Carol H; Chua, Hui Lin; Jackson, William; Vemula, Sasidhar; Sellamuthu, Rajendran; Fisher, Alexa; Feng, Hailin; Wu, Tong; MacVittie, Thomas J; Orschell, Christie M
2015-11-01
Manipulations of lethally-irradiated animals, such as for administration of pharmaceuticals, blood sampling, or other laboratory procedures, have the potential to induce stress effects that may negatively affect morbidity and mortality. To investigate this in a murine model of the hematopoietic acute radiation syndrome, 20 individual survival efficacy studies were grouped based on the severity of the administration (Admn) schedules of their medical countermeasure (MCM) into Admn 1 (no injections), Admn 2 (1-3 injections), or Admn 3 (29 injections or 6-9 oral gavages). Radiation doses ranged from LD30/30 to LD95/30. Thirty-day survival of vehicle controls in each group was used to construct radiation dose lethality response relationship (DRR) probit plots, which were compared statistically to the original DRR from which all LDXX/30 for the studies were obtained. The slope of the Admn 3 probit was found to be significantly steeper (5.190) than that of the original DRR (2.842) or Admn 2 (2.009), which were not significantly different. The LD50/30 for Admn 3 (8.43 Gy) was less than that of the original DRR (8.53 Gy, p impact survival and that dosing regimens should be considered when constructing DRR to use in survival studies. PMID:26425900
[Exercise-induced asthma in children and oral terbutaline. A dose-response relationship study].
Hertz, B; Fuglsang, G; Holm, E B
1994-09-26
We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate in 17 asthmatic children aged 6-12 years (mean 9 years). Placebo, 2, 4, and 6 mg terbutaline were given b.i.d. for 14 days in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline/day, respectively. A small but statistically significant dose-related increase was seen in morning and evening peak expiratory flow (PEF) recordings. It is concluded that continuous treatment, even with high doses or oral terbutaline, does not offer clinically useful protection against exercise-induced asthma. PMID:7985255
Poppinga, D.; Meyners, J.; Delfs, B.; Muru, A.; Harder, D.; Poppe, B.; Looe, HK
2015-12-01
This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585–607). In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x)??=??K(x)?????D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation. The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585–607). They are typical for the perturbation of the secondary electron field by a detector with enhanced electron density compared with the surrounding water. In the cases of the scintillation detector and the small ionization chamber, the negative curve portions of K(x) practically vanish. It is planned to use the measured functions K(x) and K(r) to deconvolve clinical narrow-beam signal profiles and to correct the output factor values obtained with various high-resolution detectors.
Energy Technology Data Exchange (ETDEWEB)
Yorozu, Atsunori; Dokiya, Takushi; Ogita, Mikio [National Second Hospital of Tokyo (Japan); Kuribayashi, Tohru
1996-08-01
We have developed an improved applicator with a balloon being attached in order to keep a certain interval between the mucosal membrane and sources. The balloon was 15 mm in a diameter and further prepared applicators equipped with three balloons serially inside. We investigated dose-response relationship for external beam irradiation and intracavitary irradiation with this applicator. Local control radiation-induced esophageal ulcer, and fibrotic stenosis were analyzed. Seventy patients with esophageal carcinoma received 40 Gy or more of external beam followed by 12 Gy or more of intracavitary irradiation. A dose reference point was 12.5 mm from Co-60 sources. Intracavitary irradiation was given 3-5 session in 2 weeks. A dose of brachytherapy was 12 Gy/3 fractions or 16 Gy/4 fr in group A, 16 Gy/4 fr or 20 Gy/5 fr in group B, 15 Gy/3 fr or 20 Gy/4 fr in group C and 18 Gy/3 fr or 24 Gy/4 fr in group D. Two-year local control rate was 35.9% in group A, 44.0% in group B, 31.1% in group C and 50.9% in group D. It was statistically insignificant. When 50.4 Gy or less of external beam was given to T1 or 2 lesion, 2-year local control rate was 74% in patients treated with brachytherapy of 18 Gy or more and 42% in patients treated with that of less than 18 Gy (generalized Wilcoxon: P=0.0395). Radiation-induced esophageal ulcers and fibrotic stenosis were not rare in group D. Radiation-ulcers were more common in group B or C compared to group A. Total dose of intracavitary irradiation should be less than 20 Gy. We recommend 50 Gy of external beam followed by 16 Gy/4 fr/2 w of intracavitary irradiation. We need to evaluate an accurate distance between the balloon surface and the mucosa with CT scan. A more sophisticated dose escalation study is now in progress. (author)
Directory of Open Access Journals (Sweden)
Karen Larwin
2014-02-01
Full Text Available The present study examined students' statistics-related self-efficacy, as measured with the current statistics self-efficacy (CSSE inventory developed by Finney and Schraw (2003. Structural equation modeling was used to check the confirmatory factor analysis of the one-dimensional factor of CSSE. Once confirmed, this factor was used to test whether a significant link to prior mathematics experiences exists. Additionally a new post-structural equation modeling (SEM application was employed to compute error-free latent variable score for CSSE in an effort to examine the ancillary effects of gender, age, ethnicity, department, degree level, hours completed, expected course grade, number of college-level math classes, current GPA on students' CSSE scores. Results support the one-dimensional construct and as expected, the model demonstrated a significant link between CSSE scores and prior mathematics experiences to CSSE. Additionally the students' department, expected grade, and number of prior math classes were found to have a significant effect on student's CSSE scores.
Henderson, Katherine; Buchholz, Annick; Obeid, Nicole; Mossiere, Annik; Maras, Danijela; Norris, Mark; Harrison, Megan; Feder, Stephen; Spettigue, Wendy
2014-01-01
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
Shamloo-Dashtpagerdi, Roohollah; Razi, Hooman; Aliakbari, Massumeh; Lindlöf, Angelica; Ebrahimi, Mahdi; Ebrahimie, Esmaeil
2015-01-01
Cis regulatory elements (CREs), located within promoter regions, play a significant role in the blueprint for transcriptional regulation of genes. There is a growing interest to study the combinatorial nature of CREs including presence or absence of CREs, the number of occurrences of each CRE, as well as of their order and location relative to their target genes. Comparative promoter analysis has been shown to be a reliable strategy to test the significance of each component of promoter architecture. However, it remains unclear what level of difference in the number of occurrences of each CRE is of statistical significance in order to explain different expression patterns of two genes. In this study, we present a novel statistical approach for pairwise comparison of promoters of Arabidopsis genes in the context of number of occurrences of each CRE within the promoters. First, using the sample of 1000 Arabidopsis promoters, the results of the goodness of fit test and non-parametric analysis revealed that the number of occurrences of CREs in a promoter sequence is Poisson distributed. As a promoter sequence contained functional and non-functional CREs, we addressed the issue of the statistical distribution of functional CREs by analyzing the ChIP-seq datasets. The results showed that the number of occurrences of functional CREs over the genomic regions was determined as being Poisson distributed. In accordance with the obtained distribution of CREs occurrences, we suggested the Audic and Claverie (AC) test to compare two promoters based on the number of occurrences for the CREs. Superiority of the AC test over Chi-square (2×2) and Fisher's exact tests was also shown, as the AC test was able to detect a higher number of significant CREs. The two case studies on the Arabidopsis genes were performed in order to biologically verify the pairwise test for promoter comparison. Consequently, a number of CREs with significantly different occurrences was identified between the promoters. The results of the pairwise comparative analysis together with the expression data for the studied genes revealed the biological significance of the identified CREs. PMID:25303887
DEFF Research Database (Denmark)
Schweiger, P.F.; Jakobsen, I.
1998-01-01
The effect of the fungicides carbendazim, fenpropimorph and propiconazole and of the insecticide dimethoate on plant P uptake via external hyphae of arbuscular mycorrhizal (AM) fungi was examined. Mycorrhizal plants were grown in a two-compartment system where a root-free hyphal compartment was separated from the main root compartment by nylon mesh. After 5 weeks of plant growth external hyphae of the AM fungi had spread throughout the hyphal compartment. At this time aqueous solutions of both P-32 and pesticide were added to the hyphal compartment. Resulting soil pesticide concentrations covered a wide range with the aim of describing the dose-response relationships between pesticide concentration and hyphal P uptake. Plants were harvested 6d after pesticide application. The amount of P-32 taken up into the plant was measured as was hyphal length in the hyphal compartment. Carbendazim had the most negative effect, with concentrations above 0.006 mu g g(-1) leading to a sharp decrease in hyphal P uptake. Concentrations above 0.1 mu g g-l almost completely inhibited hyphal P uptake. This concentration is lower than the expected field concentration following carbendazim application at the recommended field rate. Hyphal P uptake was also negatively affected by propiconazole but only at concentrations above 1 mu g g(-1). This corresponds to an expected field concentration of propiconazole after application of 10 times the recommended field dosage. Fenpropimorph and dimethoate had no negative effects on hyphal P uptake even when applied at concentrations of 125 or 46 mu g g(-1) respectively. These concentrations are equivalent to expected field concentrations following pesticide applications at 100 times the recommended field rate. (C) 1998 Elsevier Science Ltd. All rights reserved.
Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme
International Nuclear Information System (INIS)
Purpose: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125I implant boost after external beam radiotherapy. Methods and Materials: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analyses of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. Results: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm3 of normal brain. Conclusion: Although higher minimum brachytherapy tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy boost dose of 45-50 Gy in conjunction with convectional external beam radiotherapy, and reoperation for symptomatic necrosis.
Dose-response relationship of octylphenol and radiation evaluated by tradescantia-micronucleus assay
Energy Technology Data Exchange (ETDEWEB)
Kim, J. K.; Cheon, K. J.; Lee, B. H. [KAERI, Taejon (Korea, Republic of); Shin, H. S.; Lee, J. H. [Chungnam National Univ., Taejon (Korea, Republic of)
2002-05-01
Many kinds of synthetic chemicals have been being used for various purposes. Some of them are called 'Endocrine Disruptor's because they can disturb the endocrine system of organisms. Presently no technique is established for the quantitative assessment of biological risk of the environmental hormones. The pollen mother cells (PMC) of Tradescantia are very sensitive to chemical toxicants or ionizing radiation, and thus can be used as a biological end-point assessing their effect. Micronucleus frequencies in PMC showed a good dose- and concentration-response relationship for radiation, bisphenol A and octylphenol. A parallel series of experiment using five increasing doses of gamma-ray at 10, 20, 30, 40 and 50 cGy was conducted. The MCN frequencies of 12.0, 25.2, 41.7, 76 and 83 MCN/100 tetrads were observed from each of the increasing gamma-ray dosage groups, respectively. Lenear regression analysis of the gamma-ray data MCN frequencies yielded a correlation coefficient of 0.95. the MCN frequencies in pollen mother cells treated with bisphenol a and octylphenol showed dose-response relationship in a concentration of 0, 1, 2, 4 {mu}M and 0, 4, 10, 20 {mu}M. the MCN frequency for the bisphenol a and octylphenol group yields 2.33, 8.06, 12.7 and 19.6 MCN/100 tetrads for the bisphenol a and 2.33, 2.33, 11.47, 17.6 MCN/100 tetrads for the octylphenol. The MCN frequency of the control was 2.33 MCN/100 tetrads. It is known from the result that Trad-MCN assay can be an excellent tool for detection of biological risk due to environmental toxicants or synthetic chemicals.
Dose-response relationship of octylphenol and radiation evaluated by tradescantia-micronucleus assay
International Nuclear Information System (INIS)
Many kinds of synthetic chemicals have been being used for various purposes. Some of them are called 'Endocrine Disruptor's because they can disturb the endocrine system of organisms. Presently no technique is established for the quantitative assessment of biological risk of the environmental hormones. The pollen mother cells (PMC) of Tradescantia are very sensitive to chemical toxicants or ionizing radiation, and thus can be used as a biological end-point assessing their effect. Micronucleus frequencies in PMC showed a good dose- and concentration-response relationship for radiation, bisphenol A and octylphenol. A parallel series of experiment using five increasing doses of gamma-ray at 10, 20, 30, 40 and 50 cGy was conducted. The MCN frequencies of 12.0, 25.2, 41.7, 76 and 83 MCN/100 tetrads were observed from each of the increasing gamma-ray dosage groups, respectively. Lenear regression analysis of the gamma-ray data MCN frequencies yielded a correlation coefficient of 0.95. the MCN frequencies in pollen mother cells treated with bisphenol a and octylphenol showed dose-response relationship in a concentration of 0, 1, 2, 4 ?M and 0, 4, 10, 20 ?M. the MCN frequency for the bisphenol a and octylphenol group yields 2.33, 8.06, 12.7 and 19.6 MCN/100 tetrads for the bisphenol a and 2.33, 2.33, 11.47, 17.6 MCN/100 tetrads for the octylphenol. The MCN frequency of the control was 2.33 MCN/100 tetrads. It is known from the result that Trad-MCN assay can be an excellent tool for detection of biological risk due to environmental toxicants or synthetic chemicals
Dose-response-time modelling: Second-generation turnover model with integral feedback control.
Andersson, Robert; Jirstrand, Mats; Peletier, Lambertus; Chappell, Michael J; Evans, Neil D; Gabrielsson, Johan
2016-01-01
This study presents a dose-response-time (DRT) analysis based on a large preclinical biomarker dataset on the interaction between nicotinic acid (NiAc) and free fatty acids (FFA). Data were collected from studies that examined different rates, routes, and modes of NiAc provocations on the FFA time course. All information regarding the exposure to NiAc was excluded in order to demonstrate the utility of a DRT model. Special emphasis was placed on the selection process of the biophase model. An inhibitory Imax-model, driven by the biophase amount, acted on the turnover rate of FFA. A second generation NiAc/FFA model, which encompasses integral (slow buildup of tolerance - an extension of the previously used NiAc/FFA turnover models) and moderator (rapid and oscillatory) feedback control, was simultaneously fitted to all time courses in normal rats. The integral feedback control managed to capture an observed 90% adaptation (i.e., almost a full return to baseline) when 10 days constant-rate infusion protocols of NiAc were used. The half-life of the adaptation process had a 90% prediction interval between 3.5-12 in the present population. The pharmacodynamic parameter estimates were highly consistent when compared to an exposure-driven analysis, partly validating the DRT modelling approach and suggesting the potential of DRT analysis in areas where exposure data are not attainable. Finally, new numerical algorithms, which rely on sensitivity equations to robustly and efficiently compute the gradients in the parameter optimization, were successfully used for the mixed-effects approach in the parameter estimation. PMID:26529383
Somatic cell genetics of uranium miners and plutonium workers. A biological dose-response indicator
International Nuclear Information System (INIS)
Two populations of underground uranium miners and plutonium workers work in the state of Colorado, United States of America. We have explored the prevalence of structural chromosome aberrations in peripheral blood lymphocytes as a possible biological indicator of absorbed radiation late-effects in these populations. The uranium miners are divided into four exposure groups expressed in Working Level Months (WLM), the plutonium workers into six groups with estimated 239Pu burdens expressed in nCi. Comparison of chromosome aberration frequency data between controls, miners, and plutonium workers demonstrate: (1) a cytogenetic response to occupational ionizing radiation at low estimated doses; and (2) an increasing monotonic dose-response in the prevalence of complex (all exchange) or total aberrations in all exposure groups in these populations. We also compared trends in the prevalence of aberrations per exposure unit (WLM and nCi) in each exposure subgroup for each population. In the uranium miners, the effects per WLM seem to decrease monotonically with increasing dose, whereas in the Pu workers the change per nCi appears abrupt, with all exposure groups over 1.3 nCi (minimum detectable level) having essentially similar rates. The calculations of aberrations per respective current maximum permissible dose (120 WLM and 40 nCi) for the two populations yield 4.8 X 10-2/100 cells for uranium miners and 90.6 X 10-2/100 cells for Pu workers. Factors which may have influenced this apparent 20-fold increase in the effectiveness of plutonium in the production of complex aberrations (9-fold increase in total aberrations) are discussed. (author)
Dose-response and ghosting effects of an amorphous silicon electronic portal imaging device
International Nuclear Information System (INIS)
The purpose of this study was to investigate the dose-response characteristics, including ghosting effects, of an amorphous silicon-based electronic portal imaging device (a-Si EPID) under clinical conditions. EPID measurements were performed using one prototype and two commercial a-Si detectors on two linear accelerators: one with 4 and 6 MV and the other with 8 and 18 MV x-ray beams. First, the EPID signal and ionization chamber measurements in a mini-phantom were compared to determine the amount of buildup required for EPID dosimetry. Subsequently, EPID signal characteristics were studied as a function of dose per pulse, pulse repetition frequency (PRF) and total dose, as well as the effects of ghosting. There was an over-response of the EPID signal compared to the ionization chamber of up to 18%, with no additional buildup layer over an air gap range of 10 to 60 cm. The addition of a 2.5 mm thick copper plate sufficiently reduced this over-response to within 1% at clinically relevant patient-detector air gaps (>40 cm). The response of the EPIDs varied by up to 8% over a large range of dose per pulse values, PRF values and number of monitor units. The EPID response showed an under-response at shorter beam times due to ghosting effects, which depended on the number of exposure frames for a fixed frame acquisition rate. With an appropriate build-up layer and corrections for dose per pulse, PRF and ghosting, the variation in the a-Si EPID response can be reduced to well within ±1%
Nabel, Moritz; Bueno Piaz Barbosa, Daniela; Horsch, David; Jablonowski, Nicolai David
2014-05-01
The global demand for energy security and the mitigation of climate change are the main drivers pushing energy-plant production in Germany. However, the cultivation of these plants can cause land use conflicts since agricultural soil is mostly used for plant production. A sustainable alternative to the conventional cultivation of food-based energy-crops is the cultivation of special adopted energy-plants on marginal lands. To further increase the sustainability of energy-plant cultivation systems the dependency on synthetic fertilizers needs to be reduced via closed nutrient loops. In the presented study the energy-plant Sida hermaphrodita (Malvaceae) will be used to evaluate the potential to grow this high potential energy-crop on a marginal sandy soil in combination with fertilization via digestate from biogas production. With this dose-response experiment we will further identify an optimum dose, which will be compared to equivalent doses of NPK-fertilizer. Further, lethal doses and deficiency doses will be observed. Two weeks old Sida seedlings were transplanted to 1L pots and fertilized with six doses of digestate (equivalent to a field application of 5, 10, 20, 40, 80, 160t/ha) and three equivalent doses of NPK-fertilizer. Control plants were left untreated. Sida plants will grow for 45 days under greenhouse conditions. We hypothesize that the nutrient status of the marginal soil can be increased and maintained by defined digestate applications, compared to control plants suffering of nutrient deficiency due to the low nutrient status in the marginal substrate. The dose of 40t/ha is expected to give a maximum biomass yield without causing toxicity symptoms. Results shall be used as basis for further experiments on the field scale in a field trial that was set up to investigate sustainable production systems for energy crop production under marginal soil conditions.
International Nuclear Information System (INIS)
It is demonstrated that the method of data analysis, i.e., the method of the phenomenological/theoretical interpretation of dose response data, can greatly influence the estimation of the onset of deviation from dose response linearity of the high temperature thermoluminescence in LiF:Mg,Ti (TLD-100).
International Nuclear Information System (INIS)
Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parameters of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance
Aouinti, Safa; Malouche, Dhafer; Giudicelli, Véronique; Kossida, Sofia; Lefranc, Marie-Paule
2015-01-01
The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 different IG and TR per individual). IMGT, the international ImMunoGeneTics information system (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc (Montpellier University and CNRS) to manage the huge and complex diversity of these antigen receptors. IMGT built on IMGT-ONTOLOGY concepts of identification (keywords), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT unique numbering), is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. IMGT/HighV-QUEST, the first web portal, and so far the only one, for the next generation sequencing (NGS) analysis of IG and TR, is the paradigm for immune repertoire standardized outputs and immunoprofiles of the adaptive immune responses. It provides the identification of the variable (V), diversity (D) and joining (J) genes and alleles, analysis of the V-(D)-J junction and complementarity determining region 3 (CDR3) and the characterization of the ‘IMGT clonotype (AA)’ (AA for amino acid) diversity and expression. IMGT/HighV-QUEST compares outputs of different batches, up to one million nucleotide sequencesfor the statistical module. These high throughput IG and TR repertoire immunoprofiles are of prime importance in vaccination, cancer, infectious diseases, autoimmunity and lymphoproliferative disorders, however their comparative statistical analysis still remains a challenge. We present a standardized statistical procedure to analyze IMGT/HighV-QUEST outputs for the evaluation of the significance of the IMGT clonotype (AA) diversity differences in proportions, per gene of a given group, between NGS IG and TR repertoire immunoprofiles. The procedure is generic and suitable for evaluating significance of the IMGT clonotype (AA) diversity and expression per gene, and for any IG and TR immunoprofiles of any species. PMID:26540440
Aouinti, Safa; Malouche, Dhafer; Giudicelli, Véronique; Kossida, Sofia; Lefranc, Marie-Paule
2015-01-01
The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 different IG and TR per individual). IMGT, the international ImMunoGeneTics information system (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc (Montpellier University and CNRS) to manage the huge and complex diversity of these antigen receptors. IMGT built on IMGT-ONTOLOGY concepts of identification (keywords), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT unique numbering), is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. IMGT/HighV-QUEST, the first web portal, and so far the only one, for the next generation sequencing (NGS) analysis of IG and TR, is the paradigm for immune repertoire standardized outputs and immunoprofiles of the adaptive immune responses. It provides the identification of the variable (V), diversity (D) and joining (J) genes and alleles, analysis of the V-(D)-J junction and complementarity determining region 3 (CDR3) and the characterization of the 'IMGT clonotype (AA)' (AA for amino acid) diversity and expression. IMGT/HighV-QUEST compares outputs of different batches, up to one million nucleotide sequencesfor the statistical module. These high throughput IG and TR repertoire immunoprofiles are of prime importance in vaccination, cancer, infectious diseases, autoimmunity and lymphoproliferative disorders, however their comparative statistical analysis still remains a challenge. We present a standardized statistical procedure to analyze IMGT/HighV-QUEST outputs for the evaluation of the significance of the IMGT clonotype (AA) diversity differences in proportions, per gene of a given group, between NGS IG and TR repertoire immunoprofiles. The procedure is generic and suitable for evaluating significance of the IMGT clonotype (AA) diversity and expression per gene, and for any IG and TR immunoprofiles of any species. PMID:26540440
DEFF Research Database (Denmark)
Christiansen, E; Goldney, R D
2011-01-01
There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 (0.8%) were registered as having had a suicide attempt. Twenty controls were matched to each case and a link to the offspring's biological parents was established.
International Nuclear Information System (INIS)
The ESR dose responses of the tooth enamel samples prepared from teeth of cow and mice were examined in comparison with that of human. The samples were prepared with combined procedures of mechanical and chemical treatments of teeth. The ESR dose response was extracted from the total ESR spectra of tooth enamel samples by a specially developed matrix method. The dosimetric signal was found to be increased linearly with gamma dose for all studied tooth enamel samples. The radiation sensitivity of cow tooth enamel was found to be close to that of human teeth while that of mouse teeth was about 25% lower. The present results indicate that, having high radiation sensitivity, cow and mouse teeth can be used for retrospective radiation dosimetry in low-dose level
Dose–response curve slope is a missing dimension in the analysis of HIV-1 drug resistance
Sampah, Maame Efua S.; Shen, Lin; Jilek, Benjamin L.; Siliciano, Robert F.
2011-01-01
HIV-1 drug resistance is a major clinical problem. Resistance is evaluated using in vitro assays measuring the fold change in IC50 caused by resistance mutations. Antiretroviral drugs are used at concentrations above IC50, however, and inhibition at clinical concentrations can only be predicted from IC50 if the shape of the dose–response curve is also known. Curve shape is influenced by cooperative interactions and is described mathematically by the slope parameter or Hill coefficient (m). Im...
Craciunescu, Corneliu N; Niculescu, Mihai D; Guo, Zhong; Johnson, Amy R.; Fischer, Leslie; Zeisel, Steven H.
2008-01-01
Diethanolamine (DEA) is a common ingredient of personal care products. Dermal administration of DEA diminishes hepatic stores of the essential nutrient choline and alters brain development. We previously reported that 80 mg/kg/day of DEA during pregnancy in mice reduced neurogenesis and increased apoptosis in the fetal hippocampus. This study was designed to establish the dose-response relationships for this effect of DEA. Timed-pregnant C57BL/6 mouse dams were dosed dermally from gestation d...
Energy Technology Data Exchange (ETDEWEB)
NONE
2005-07-01
This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6.
DEFF Research Database (Denmark)
Fischer, Louise Arup; Voelund, Aage; Andersen, Klaus Ejner; Menné, Torkil; Johansen, Jeanne Duus
2009-01-01
Background: Allergic contact dermatitis is common and can be prevented. The relationship between thresholds for patch tests and the repeated open application test (ROAT) is unclear. It would be desirable if patch test and ROAT data from already sensitized individuals could be used in prevention. Objectives: The aim was to develop an equation that could predict the response to an allergen in a ROAT based on the dose-response curve derived by patch testing. Materials/methods: Results from two huma...
DEFF Research Database (Denmark)
Fischer, Louise Arup; Voelund, Aage; Andersen, Klaus Ejner; Menné, Torkil; Johansen, Jeanne Duus
2009-01-01
BACKGROUND: Allergic contact dermatitis is common and can be prevented. The relationship between thresholds for patch tests and the repeated open application test (ROAT) is unclear. It would be desirable if patch test and ROAT data from already sensitized individuals could be used in prevention. OBJECTIVES: The aim was to develop an equation that could predict the response to an allergen in a ROAT based on the dose-response curve derived by patch testing. MATERIALS/METHODS: Results from two huma...
International Nuclear Information System (INIS)
This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6
Abdul R. Al-Ajlan; Syed R. Mehdi
2005-01-01
OBJECTIVES The objective of our study was to examine the effects and a dose response relationship of physical activity on plasma high density lipoprotein cholesterol (HDL-C) levels and body mass index (BMI) among Saudi men and women living in the metropolis of Riyadh, Kingdom of Saudi Arabia (KSA). METHODS The sample population of 474 Saudi men and women visiting the health centers in and around Riyadh was studied from September 2003 to February 2004. The population was classified in...
DEFF Research Database (Denmark)
Christensen, E.R.; Chen, D.; Nyholm, Niels; Kusk, Kresten Ole
2001-01-01
The joint toxicity of nonylamine and decylamine and of atrazine and decylamine was evaluated in assays with the green alga Selenastrum capricornutum based on an isobologram method. In this method, curves of constant response, isoboles, are plotted versus concentrations of two toxicants. The response parameter was growth rate based on biomass, and several response levels were used. Dose–response curves were developed for dilution series using fixed ratios between concentrations in toxic units of ...
DEFF Research Database (Denmark)
Carlsen, B C; Fischer, Louise Arup; Sosted, H; Vølund, A; Menné, T; Johansen, J D
2009-01-01
BACKGROUND: It is not known if reduced elicitation thresholds are evident among polysensitized individuals when using allergens to which the patients are already sensitized. Reduced elicitation thresholds may be an expression of increased reactivity in this patient group. OBJECTIVES: To examine and compare elicitation dose-response curves and elicitation thresholds in a polysensitized vs. a single/double-sensitized group for allergens to which the test subjects were already sensitized. PATIENTS/...
Ju, Sang-Yhun; Choi, Whan-Seok; Ock, Sun-Myeong; Kim, Chul-Min; Kim, Do-Hoon
2014-01-01
Increasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational ...
Chung, Francisco; Rubio, Julio; Gonzales, Carla; Gasco, Manuel; Gonzales, Gustavo F
2005-04-01
Lepidium meyenii (Brassicaceae) known as Maca grows exclusively between 4000 and 4500 m over the sea level in the Peruvian central Andes. The dried hypocotyls of Maca are traditionally used as food and for its supposed fertility-enhancing properties. A dose-response study was performed to determine the effect of 7 days oral administration of an aqueous lyophilized extract of Maca at 0.01-5 g/kg (corresponding to 0.022-11 g dry hypocotyls of Maca/kg) on body and different organ weights, stages of the seminiferous tubules, epididymal sperm count and motility, and serum testosterone and estradiol levels in rats. In doses up to 5 g extract/kg, no toxicity was observed. Almost all organ weights were similar in controls and in the Maca extract-treated groups. Seminal vesicles weight was significantly reduced at 0.01 and 0.10 g extract/kg. Maca increased in length of stages VII-VIII of the seminiferous tubules in a dose-response fashion, with highest response at 1.0 g/kg, while caput/corpus epididymal sperm count increased at the 1.0 g dose. Cauda epididymal sperm count, sperm motility, and serum estradiol level were not affected at any of the doses studied. Serum testosterone was lower at 0.10 g extract/kg. Low-seminal vesicle weights correlated with low-serum testosterone levels (R2=0.33; PMaca aqueous extract/kg. The present study demonstrated that Maca extract in doses up to 5 g/kg (equivalent to the intake of 770 g hypocotyls in a man of 70 kg) was safe and that higher effect on reproductive parameters was elicited with a dose of 1 g extract/kg corresponding to 2.2 g dry Maca hypocotyls/kg. PMID:15763375
International Nuclear Information System (INIS)
Nonlinear and threshold-like shapes of dose-response curves are often observed in tests for carcinogenicity. Here, we present three examples where an apparent threshold is spurious and can be misleading for low dose extrapolation and human cancer risk assessment. Case 1: For experiments that are not replicated, such as rodent bioassays for carcinogenicity, random variation can lead to misinterpretation of the result. This situation was simulated by 20 random binomial samplings of 50 animals per group, assuming a true linear dose response from 5% to 25% tumor incidence at arbitrary dose levels 0, 0.5, 1, 2, and 4. Linearity was suggested only by 8 of the 20 simulations. Four simulations did not reveal the carcinogenicity at all. Three exhibited thresholds, two showed a nonmonotonic behavior with a decrease at low dose, followed by a significant increase at high dose ('hormesis'). Case 2: Logarithmic representation of the dose axis transforms a straight line into a sublinear (up-bent) curve, which can be misinterpreted to indicate a threshold. This is most pronounced if the dose scale includes a wide low dose range. Linear regression of net tumor incidences and intersection with the dose axis results in an apparent threshold, even with an underlying true linear dose-incidence relationship. Case 3: Nonlinear shapes of dose-cancer incidence curves are rarely seen with epidemiological data in humans. The discrepancy to data in rodents may in part be explained by a wider span of individual susceptibilities for tumor induction in humans due to more diverse genetic background and modulation by co-carcinogenic lifestyle factors. Linear extrapolation of a human cancer risk could therefore be appropriate even if animal bioassays show nonlinearity
Kunutsor, Setor K; Apekey, Tanefa A; Cheung, Bernard M Y
2015-12-01
The objective of this review was to obtain a reliable estimate of the magnitude of the prospective association between gamma-glutamyltransferase (GGT) and risk of hypertension, and to characterize the nature of the dose-response relationship. We conducted a systematic review and dose-response meta-analysis of published prospective studies. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science databases up to May 2015. Study-specific relative risks (RRs) were meta-analyzed using random effects models. We examined a potential nonlinear relationship using restricted cubic splines. Of the 612 titles reviewed, we included 14 cohort studies with data on 44?582 participants and 5?270 hypertension cases. In a comparison of extreme thirds of baseline levels of GGT, RR for hypertension in pooled analysis of all 14 studies was 1.32 (95% confidence interval: 1.23-1.43). There was heterogeneity among the studies (P?GGT and hypertension risk (P for nonlinearity?=?0.37). The pooled RR of hypertension per 5?U/l increment in GGT levels was 1.08 (95% confidence interval: 1.04-1.13). Baseline circulating GGT level is associated with an increased risk of hypertension in the general population, consistent with a linear dose-response relationship. Further investigation of any potential relevance of GGT in hypertension prevention is warranted. PMID:26485462
Dose-response of x-ray-induced anaphase aberrations in the mitotic root tip chromosomes of allium
International Nuclear Information System (INIS)
A simplified Allium root mitotic chromosome aberration assay by using only the aberrant anaphases (fragments, laggards and bridges) as the end-points were developed by Rank and Nielsen (1993) for screening water soluble chemicals and complex mixtures. A dose-response curve was established by Meir et al., (1994) using a known clastogen, 4-nitroquinolene-N-oxide between the dose range of 0.1-0.5 ug/ml. In order to further validate this assay for clastogen detection, a series of X-ray dose response experiments was carried out. Allium roots were germinated in tapwater for 48 h and treated with a series of 10, 20, 30, 40, 50, 60 R (80 Kvp, 5 ma, dose rate 60 R/min) dosages. After an 18 hr recovery time, the root tips were hydrolyzed in 45% acetic and 1 N HC1 acid (9:1 ratio) solution under 50 degrees C for 5 min and stained with aceto-carmine. Each of the data points were derived from scoring 7-10 slides (15-50 anaphases/slide). The corrrelation coefficient, slope and intercept values of the dose-response curve are: 0.954, 0.515 and 1.155 respectively
Shindo, Y; Witt, E; Han, D; Packer, L
1994-04-01
There has not as yet been an integrated, comprehensive study of the responses of dermis and epidermis in vivo to a wide range of ultraviolet (UV) doses, encompassing all major antioxidants and a sensitive marker of oxidative damage. We have irradiated hairless mice with simulated solar light at doses of 2, 5, 12.5, and 25 J/cm2 combined UVA and UVB (0.8 to 10 MED) and measured enzymic and non-enzymic antioxidants as well as lipid hydroperoxides in both epidermis and dermis to elucidate the response of cutaneous antioxidant defense mechanisms to UV stress. Among the nonenzymic antioxidants two different dose-response patterns were seen. Ascorbate was rapidly depleted at doses between 0 and 5 J/cm2 but was less affected between 5 and 25 J/cm2. In contrast, glutathione, ubiquinol/one, and alpha-tocopherol levels remained approximately equal to control levels between 0 and 5 J/cm2, then decreased to varying degrees from 5 to 25 J/cm2; ubiquinol was almost completely depleted, whereas alpha-tocopherol dropped only 30%. The concentration of lipid hydroperoxides increased throughout the dose range. These results may be explained partly by direct destruction of some antioxidants by UV light, partly by the separate antioxidant functions of the compounds, and partly by recycling of some antioxidants (e.g., alpha-tocopherol) at the expense of others (e.g., ubiquinol). Even at the lowest dose (0.8 MED) lipid hydroperoxide formation was observed. Among the enzymic antioxidants, superoxide dismutase activity decreased significantly (to 63.6% of initial activity for epidermis and 51.5% for dermis at 25 J), whereas activities of glutathione peroxidase and glutathione reductase decreased slightly. Catalase activity decreased dramatically at doses above 5 J (to 11.8% of initial activity in epidermis and 27.7% in dermis at 25 J). The dramatic loss of catalase is almost entirely accounted for by direct destruction by the simulated solar light, but superoxide dismutase was unaffected by direct exposure; hence its destruction must be due to indirect effects, either mediated by free radicals or other harmful species formed upon irradiation. At low doses of UV light many components of the cutaneous antioxidant system were damaged, whereas at high doses all components were damaged and some were almost completely destroyed. PMID:8151122
Løvsletten, Ola; Rypdal, Martin; Rypdal, Kristoffer; Fredriksen, Hege-Beate
2015-04-01
We explore the statistics of instrumental surface temperature records on 5°× 5°, 2°× 2°, and equal-area grids. In particular, we compute the significance of determinstic trends against two parsimonious null models; auto-regressive processes of order 1, AR(1), and fractional Gaussian noises (fGn's). Both of these two null models contain a memory parameter which quantifies the temporal climate variability, with white noise nested in both classes of models. Estimates of the persistence parameters show significant positive serial correlation for most grid cells, with higher persistence over occeans compared to land areas. This shows that, in a trend detection framework, we need to take into account larger spurious trends than what follows from the frequently used white noise assumption. Tested against the fGn null hypothesis, we find that ~ 68% (~ 47%) of the time series have significant trends at the 5% (1%) significance level. If we assume an AR(1) null hypothesis instead, then the result is that ~ 94% (~ 88%) of the time series have significant trends at the 5% (1%) significance level. For both null models, the locations where we do not find significant trends are mostly the ENSO regions and the North-Atlantic. We try to discriminate between the two null models by means of likelihood-ratios. If we at each grid point choose the null model preferred by the model selection test, we find that ~ 82% (~ 73%) of the time series have significant trends at the 5% (1%). We conclude that there is emerging evidence of significant warming trends also at regional scales, although with a much lower signal-to-noise ratio compared to global mean temperatures. Another finding is that many temperature records are consistent with error models for internal variability that exhibit long-range dependence, whereas the temperature fluctuations of the tropical oceans are strongly influenced by the ENSO, and therefore seemingly more consistent with random processes with short-range dependence. Four different data products, HADCRUT4, NOAA mlost, GISS and Berkely Earth, are analyzed in this project, with similar results in all cases.
Maric, Marija; de Haan, Else; Hogendoorn, Sanne M; Wolters, Lidewij H; Huizenga, Hilde M
2015-03-01
Single-case experimental designs are useful methods in clinical research practice to investigate individual client progress. Their proliferation might have been hampered by methodological challenges such as the difficulty applying existing statistical procedures. In this article, we describe a data-analytic method to analyze univariate (i.e., one symptom) single-case data using the common package SPSS. This method can help the clinical researcher to investigate whether an intervention works as compared with a baseline period or another intervention type, and to determine whether symptom improvement is clinically significant. First, we describe the statistical method in a conceptual way and show how it can be implemented in SPSS. Simulation studies were performed to determine the number of observation points required per intervention phase. Second, to illustrate this method and its implications, we present a case study of an adolescent with anxiety disorders treated with cognitive-behavioral therapy techniques in an outpatient psychotherapy clinic, whose symptoms were regularly assessed before each session. We provide a description of the data analyses and results of this case study. Finally, we discuss the advantages and shortcomings of the proposed method. PMID:25645171
Pardo-Igúzquiza, Eulogio; Rodríguez-Tovar, Francisco J.
2012-12-01
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.
Asbestosis: a study of dose-response relationships in an asbestos textile factory
Berry, G.; Gilson, J. C.; Holmes, S.; Lewinsohn, H. C.; Roach, S. A.
1979-01-01
ABSTRACT A group of 379 men who had worked at an asbestos textile factory for at least 10 years has been followed up. The prevalence of crepitations, 'possible asbestosis', certified asbestosis, small opacities in the chest radiograph and values of lung function have been related to dust levels. The type of asbestos processed was predominantly chrysotile although a substantial amount of crocidolite had also been used in the past. There was a higher prevalence of crepitations than had been observed previously at the same factory. The presence of crepitations is not a specific effect of asbestos exposure and 'possible asbestosis', a combined judgement of two physicians on whether a man had developed signs which might be attributable to early asbestosis, was preferred. Fifty per cent of men with a diagnosis of possible asbestosis were certified as suffering from asbestosis by the pneumoconiosis Medical Panel within 3-5 yr. The most reliable data relate to men first employed after 1950; 6·6% of men in this group had possible asbestosis after an average length of follow-up of 16 yr and an average exposure to 5 fibre/cm3 where the dust levels were determined by static area samplers. The forced expiratory volume and forced vital capacity declined significantly with exposure, after allowing for age and height, but there was no decline in the total lung capacity. The transfer factor also declined with exposure, but not to a statistically significant extent. The non-smokers and light smokers as a group had less crepitations, asbestosis and small opacities on the chest radiograph than heavier smokers with similar exposure. Combining dust concentrations to form the cumulative dose may not be completely satisfactory, and a family of measures was investigated which allows for elimination of dust from the lungs and includes the cumulative dose as a special case. Because the rate of elimination of dust from the lungs is unknown and cannot be estimated from the data, this approach leads to a wide range of possible interpretations of the data; for example the concentration such that possible asbestosis occurs in no more than 1% of men after 40 years' exposure could be as high as 1·1 fibres/cm3 or may have to be as low as 0·3 fibres/cm3. This range is wide because the data relate to higher dust levels, and a shorter period of follow-up. Until data are available on groups exposed to lower levels it will not be possible to assess the effects of the current standard with any certainty. However, the results of this study show that it is important to continue to reduce dust levels to values as low as possible. PMID:465379
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A comparison has been made of dicentric yields in G0 lymphocytes between man and crab-eating monkey, Macaca fascicularis, after acute and chronic ?-irradiations. With acute irradiation (49.6 rad/min) there was no significant difference between them, but for the chronic irradiation (17.1 rad/h) a significant difference was observed between the species. When the dose-response relations were fitted to the linear-quadratic model (Y = ?D + ?D2), the species-difference observed for chronic irradiation was almost entirely due to change in the value of ?. In addition, after chronic irradiation the ?-value for monkey was almost negligible, but that for man was significant. Post-irradiation incubation experiment showed that cells with dicentrics were partly eliminated during the course of chronic irradiation, because there were appreciable reductions of dicentric yields (ca. 25% for both man and monkey at 400 rad) together with mitotic indices (ca. 30% and 60% for man and monkey, respectively, at 400 rad). Accordingly, it would be reasonable to postulate that G0 repair for dicentrics other than selection mechanism must play a major role in the effects of low dose rate. It can be further suggested that G0-repair capacity for chromosal damages leading to dicentrics may be different among different primate species. (Auth.)
Given knowledge of exposure, the shape of the dose response curve is the key to predicting health risk, which in turn determines allowable levels of exposure and the associated economic costs of compliance.
Matrat, Mireille; Guida, Florence; Cénée, Sylvie; Févotte, Joelle; Carton, Matthieu; Cyr, Diane; Menvielle, Gwenn; Paget-Bailly, Sophie; Radoï, Loredana; Schmaus, Annie; Bara, Simona; Velten, Michel; Luce, Danièle; Stücker, Isabelle; The Icare Study Group
2015-01-01
Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent. PMID:26425123
Energy Technology Data Exchange (ETDEWEB)
Dean, J; Welsh, L; Gulliford, S; Harrington, K; Nutting, C [The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London (United Kingdom)
2014-06-01
Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in dose-response studies. We would like to thank the Engineering and Physical Sciences Research Council for funding. We acknowledge support from the NIHR RM/ICR Biomedical Research Centre. RayStatation was used under an evaluation agreement with RaySearch Laboratories AB.
International Nuclear Information System (INIS)
Purpose: The significant morbidity caused by radiation-induced acute oral mucositis means that studies aiming to elucidate dose-response relationships in this tissue are a high priority. However, there is currently no standardized method for delineating the mucosal structures within the oral cavity. This report describes the development of a methodology to delineate the oral mucosa accurately on CT scans in a semi-automated manner. Methods: An oral mucosa atlas for automated segmentation was constructed using the RayStation Atlas-Based Segmentation (ABS) module. A radiation oncologist manually delineated the full surface of the oral mucosa on a planning CT scan of a patient receiving radiotherapy (RT) to the head and neck region. A 3mm fixed annulus was added to incorporate the mucosal wall thickness. This structure was saved as an atlas template. ABS followed by model-based segmentation was performed on four further patients sequentially, adding each patient to the atlas. Manual editing of the automatically segmented structure was performed. A dose comparison between these contours and previously used oral cavity volume contours was performed. Results: The new approach was successful in delineating the mucosa, as assessed by an experienced radiation oncologist, when applied to a new series of patients receiving head and neck RT. Reductions in the mean doses obtained when using the new delineation approach, compared with the previously used technique, were demonstrated for all patients (median: 36.0%, range: 25.6% – 39.6%) and were of a magnitude that might be expected to be clinically significant. Differences in the maximum dose that might reasonably be expected to be clinically significant were observed for two patients. Conclusion: The method developed provides a means of obtaining the dose distribution delivered to the oral mucosa more accurately than has previously been achieved. This will enable the acquisition of high quality dosimetric data for use in dose-response studies. We would like to thank the Engineering and Physical Sciences Research Council for funding. We acknowledge support from the NIHR RM/ICR Biomedical Research Centre. RayStatation was used under an evaluation agreement with RaySearch Laboratories AB
International Nuclear Information System (INIS)
Chronic arsenic (As) poisoning has become a worldwide public health issue. Most human As exposure occurs from consumption of drinking water containing high amounts of inorganic As (iAs). In this paper, epidemiological studies conducted on the dose-response relationships between iAs exposure via the drinking water and related adverse health effects are reviewed. Before the review, the methods for evaluation of the individual As exposure are summarized and classified into two types, that is, the methods depending on As concentration of the drinking water and the methods depending on biological monitoring for As exposure; certain methods may be applied as optimum As exposure indexes to study dose-response relationship based on various As exposure situation. Chronic effects of iAs exposure via drinking water include skin lesions, neurological effects, hypertension, peripheral vascular disease, cardiovascular disease, respiratory disease, diabetes mellitus, and malignancies including skin cancer. The skin is quite sensitive to arsenic, and skin lesions are some of the most common and earliest nonmalignant effects related to chronic As exposure. The increase of prevalence in the skin lesions has been observed even at the exposure levels in the range of 0.005-0.01 mg/l As in drinking waters. Skin, lung, bladder, kidney, liver, and uterus are considered as sites As-induced malignancies, and the skin is though to be perhaps the most sensitive site. Prospective studies in large area of endemic As poisoning, like Bangladesh or China, where the rate of malignancies is expected to increase within the next several decades, will help to clarify the dose-response relationship between As exposure levels and adverse health effects with enhanced accuracy
Energy Technology Data Exchange (ETDEWEB)
Miller, J.H.; Heflich, R.H.
1980-09-01
Compounds like N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) result from the in vivo reduction of nitrate derivatives of benzo(..cap alpha..)pyrene. The dose-response relationship for survival of cloning ability in human fibroblasts exposed to N-AcO-AAF is being investigated to obtain a better understanding of the carcinogenic potential of coal-related air pollutants. A model is presented which correlates the survival of normal human fibroblasts after exposure to N-AcO-AAF with the rate of excision of carcinogen residues bound to DNA. The model predicts that the survival of normal cells, S/sub N/, is related to the survival of repair deficient cells, S/sub XPA/, by the equation 1n(S/sub N/) = 1n(S/sub XPA/) (1-f) where f is the fraction of potentially lethal damage repaired in the normal cell at a given dose of carcinogen. The rate of excision of AAF residues from the DNA of confluent human fibroblasts was measured over the same dose range as the survival studies. This information together with the dose-response relationship for survival of normal and repair deficient cells permits a determination of the mean number of adducts required to produce a potentially lethal lesion and the effective time available for repair. The model can be used to predict the mean lifetime of carcinogen residues on the DNA of partially repair deficient cells and the effect of recovery on the survival of normal cells. Extensions of the model to account for shoulders on the dose-response relationship curves are also discussed.
Dose-response relationship of {gamma}-H2AX foci induction in human lymphocytes after X-rays exposure
Energy Technology Data Exchange (ETDEWEB)
Mandina, Tania [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Roch-Lefevre, Sandrine H.; Voisin, Pascale [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France); Gonzalez, Jorge E.; Lamadrid, Ana I.; Romero, Ivonne [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Garcia, Omar, E-mail: omar@cphr.edu.cu [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Voisin, Philippe; Roy, Laurence [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France)
2011-09-15
Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of {gamma}-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and {gamma}-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y{sub (0.5h)} = 11.66D + 0.15 (R{sup 2} = 0.99), Y{sub (5h)} = 2.44D + 0.15 (R{sup 2} = 0.99), Y{sub (8h)} = 1.57D + 0.22 (R{sup 2} = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using {gamma}-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in {gamma}-H2AX foci kinetics after gamma- and X-irradiation in vitro.
International Nuclear Information System (INIS)
The paper represents an extension of previous work on the implications of various dose-response relationships in that we have now included time as a variable so that the effects of protraction of irradiation may be considered together with the time of appearance of the tumour following the irradiation. We have considered the forms of relationship for time distribution of tumours revealed experimentally, from which it appears that much data may be correlated in terms of a log-normal distribution of tumour yield following the insult. We have also noted that the median time of tumour appearance may be a function of total dose received or even on dose rate for protracted exposure. We have been able to derive numerical values from the biological literature for the parameters that characterize the log-normal distribution and use them for speculative studies of the effects of dose-response relatioships. We have assumed that the initial biological response is directly proportional to dose but that the effect is distributed in time. From this linear assumption we have continually generated non-linear dose-response relationships and apparent thresholds. We have studied the effects of varying the parameters and been able to demonstrate that some conditions lead to approximately linear responses. We have applied the methods to the study of point sources of irradiation and reviewed the experimental evidence for the time of appearance of tumours with particulate irradiation. The results tend to support our previous conclusions as to the risks associated with highly heterogeneous dose fields. (author)
DEFF Research Database (Denmark)
Larsen, Thomas; Mose, Frank Holden
2012-01-01
Nitric oxide (NO) is a ubiquitous vasodilator and an important regulator of renal sodium excretion. To further investigate the role of NO in renal sodium handling, we studied the effects of the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in a crossover dose-response study. During NO inhibition mean arterial pressure increased dose-dependently and reached a plateau after 20 minutes of infusion. On the contrary, the fractional excretion of sodium was reduced equally in all three L-NMMA doses. This indicates that sodium excretion is highly sensitive to even small changes in renal NO bioavailability in healthy human.
DEFF Research Database (Denmark)
Opstrup, Ulla Kampmann; Hoeyem, P; Mengel, A; Schmitz, O; Rungby, J; Oerskov, L; Møller, N
2011-01-01
Aim: To combat diabetic complications strict glycaemic control is desirable in type 2 diabetes, but some patients are severely insulin resistant and it is not known whether high doses of insulin are effective. This study was designed to determine the acute dose response effects of insulin in patients with type 2 diabetes and severe insulin resistance. Materials and Methods: We included 8 insulin resistant (mean insulin dose: 186 IU/d. BMI: 35) subjects with type 2 diabetes in a single-blinded, r...
International Nuclear Information System (INIS)
These calculations show that the inference is mistaken that a single 'dose' exists when a dose-response relationship is proposed for late effects following an injection of ?-particle-emitter. If the aim of a relationship is to predict an effect from a given injection of 224Ra, then it is necessary to take into account the distribution of marrow spaces in the skeleton. It is clear, however, that greater precision can be achieved only by a better understanding of the details of microdistribution of 224Ra and its daughters in bone and of the structure of bone itself. (author)
Hossain Mostaque; Sultana Papia; Rahman Mashiur; Rahman Matiar; Saud Zahangir; Ali Nurshad; Salam Kazi; Hossain Ekhtear; Fajol Abul; Karim Rezaul; Haque Abedul; Islam Khairul; Akhand Anwarul; Mandal Abul; Miyataka Hideki
2011-01-01
Abstract Background Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs) showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. Methods A tot...
DEFF Research Database (Denmark)
Larsen, C.N.; Nielsen, S.; Kaestel, P.; Brockmann, E.; Bennedsen, M.; Christensen, Hanne Risager; Eskesen, D.C.; Jacobsen, B.L.; Michaelsen, K.F.
2006-01-01
Objective: This study was performed to investigate the dose-response effects of supplementation with Bifidobacterium animalis subsp lactis (BB-12) and Lactobacillus paracasei subsp paracasei (CRL-431) on blood lipids, recovery from feces and bowel habits. Changes of the fecal microflora was analyzed in the 10(10) CFU/day probiotic and placebo group. Design: The study was designed as a randomized, placebo-controlled, double-blinded, parallel dose-response study. Subjects: Healthy young adults (18...
PSOD: an interactive Fortran program to simulate the radiation dose response of membrane populations
International Nuclear Information System (INIS)
Program PSOD was written to simulate the distribution in responses of membrane populations subjected to random radiation doses and dose rates. It computes the response (damage) according to one of three formulas selected by the user, and outputs statistical results to the terminal. It will plot simulated dose- and response-frequency distributions in two or three dimensions. Doses and dose rates are selected from the log normal distribution; other distributions can be incorporated as the need arises. A true log normal curve with defined mean and standard deviation can also be generated. The purpose of this documentation is to provide a complete operating manual for the program. A user guide is available on-line after initiating a session of PSOD. Detailed examinations of the statistical validity of various steps have been included to aid future modifications and updating
Directory of Open Access Journals (Sweden)
Singh D
2013-12-01
Full Text Available Dave Singh,1 Malcolm Boyce,2 Virginia Norris,3 Sandra E Kent,3 Jane H Bentley31University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester, Manchester, UK; 2Hammersmith Medicines Research, London, UK; 3GlaxoSmithKline, Middlesex, UKBackground: GSK2190915, a 5-lipoxygenase activating protein inhibitor, inhibits the production of cysteinyl leukotrienes and leukotriene B4 and 5-oxo-6,8,11,14-eicosatetraenoic acid. We have previously reported that GSK2190915 100 mg daily inhibits early and late asthmatic responses to inhaled allergen; the effects of lower doses have not been reported. This study assessed the dose–response effects of GSK2190915 10 mg and 50 mg on the early asthmatic response (EAR to inhaled allergen.Methods: Nineteen subjects with mild asthma and an EAR were enrolled in a randomized, double-blind, three-way crossover study of GSK2190915 10 mg, 50 mg, and placebo orally once-daily for 3 days. Allergen challenge was performed 2 hours after the third dose.Results: Compared with placebo, GSK2190915 10 mg and 50 mg caused significant, dose-dependent attenuation of the minimum forced expiratory volume at 1 second (FEV1 absolute change from baseline; mean treatment differences were 0.21 L (95% confidence interval [CI] 0.04 L, 0.38 L and 0.41 L (95% CI 0.24 L, 0.58 L, respectively. GSK2190915 50 mg was more effective than 10 mg; mean difference between treatments was 0.20 L, (95% CI 0.03 L, 0.36 L. Compared with placebo, GSK2190915 50 mg, but not 10 mg, significantly inhibited the weighted mean FEV1 absolute change from baseline.Conclusion: GSK2190915 50 mg attenuated the EAR similarly to GSK2190915 100 mg in our previous study, suggesting 50 mg is at the top of the dose–response curve. GSK2190915 10 mg is a suboptimal dose. The EAR can be used to assess the therapeutic dose of a new treatment for asthma.Keywords: GSK2190915, FLAP inhibitor, early asthmatic response
International Nuclear Information System (INIS)
Groundwater samples were collected in the Xiangjiang watershed in China from 2002 to 2008 to analyze concentrations of arsenic, cadmium, chromium, copper, iron, lead, mercury, manganese, and zinc. Spatial and seasonal trends of metal concentrations were then discussed. Combined with geostatistics, an ingestion risk assessment of metals in groundwater was performed using the dose-response assessment method and the triangulated irregular network (TIN) model. Arsenic concentration in groundwater had a larger variation from year to year, while the variations of other metal concentrations were minor. Meanwhile, As concentrations in groundwater over the period of 2002-2004 were significantly higher than that over the period of 2005-2007, indicating the improvement of groundwater quality within the later year. The hazard index (HI) in 2002 was also significantly higher than that in 2005, 2006, 2007 and 2008. Moreover, more than 80% of the study area recorded an HI of more than 1.0 for children, suggesting that some people will experience deleterious health effects from drinking groundwater in the Xiangjiang watershed. Arsenic and manganese were the largest contributors to human health risks (HHRs). This study highlights the value of long-term health risk evaluation and the importance of geographic information system (GIS) technologies in the assessment of watershed-scale human health risk.
DEFF Research Database (Denmark)
Christensen, E.R.; Chen, D.
2001-01-01
The joint toxicity of nonylamine and decylamine and of atrazine and decylamine was evaluated in assays with the green alga Selenastrum capricornutum based on an isobologram method. In this method, curves of constant response, isoboles, are plotted versus concentrations of two toxicants. The response parameter was growth rate based on biomass, and several response levels were used. Dose–response curves were developed for dilution series using fixed ratios between concentrations in toxic units of the compounds. Probit and Weibull dose–response curves were then determined by nonlinear regression. A model for isoboles for partially similar action was used when applicable. The no-effect concentration (NEC or EC0) was estimated based on a newly proposed model containing median effective concentration (EC50) and EC0 as explicit variables. Results show that nonylamine and decylamine are nearly concentration additive at EC50 and EC10 (similarity parameter l 5 0.70–0.76) and to a lesser extent at EC0. By contrast, the mixtures of atrazine and decylamine show antagonism in that atrazine acts as an antidote to decylamine. The shapes of these isoboles are independent of response level. The EC50 values (mg/L) for chemicals acting singly were 0.090 (nonylamine), 0.039 to 0.044 (decylamine), and 0.225 (atrazine). In order to determine NEC effectively, the level of inhibition must be fairly low, with observed growth rates between 0.6 and 1.0 times the average growth rate of the controls.
Al-Mayah, Adil; Moseley, Joanne; Hunter, Shannon; Brock, Kristy
2015-11-01
Biomechanical-based deformable image registration is conducted on the head and neck region. Patient specific 3D finite element models consisting of parotid glands (PG), submandibular glands (SG), tumor, vertebrae (VB), mandible, and external body are used to register pre-treatment MRI to post-treatment MR images to model the dose response using image data of five patients. The images are registered using combinations of vertebrae and mandible alignments, and surface projection of the external body as boundary conditions. In addition, the dose response is simulated by applying a new loading technique in the form of a dose-induced shrinkage using the dose-volume relationship. The dose-induced load is applied as dose-induced shrinkage of the tumor and four salivary glands. The Dice Similarity Coefficient (DSC) is calculated for the four salivary glands, and tumor to calculate the volume overlap of the structures after deformable registration. A substantial improvement in the registration is found by including the dose-induced shrinkage. The greatest registration improvement is found in the four glands where the average DSC increases from 0.53, 0.55, 0.32, and 0.37 to 0.68, 0.68, 0.51, and 0.49 in the left PG, right PG, left SG, and right SG, respectively by using bony alignment of vertebrae and mandible (M), body (B) surface projection and dose (D) (VB+M+B+D). PMID:26485227
Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.
Miller, Patrick J O; Antunes, Ricardo N; Wensveen, Paul J; Samarra, Filipa I P; Alves, Ana Catarina; Tyack, Peter L; Kvadsheim, Petter H; Kleivane, Lars; Lam, Frans-Peter A; Ainslie, Michael A; Thomas, Len
2014-02-01
Eight experimentally controlled exposures to 1-2?kHz or 6-7?kHz sonar signals were conducted with four killer whale groups. The source level and proximity of the source were increased during each exposure in order to reveal response thresholds. Detailed inspection of movements during each exposure session revealed sustained cha