WorldWideScience

Sample records for statistically significant dose-response

  1. Statistical and low dose response

    International Nuclear Information System (INIS)

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

  2. DOSE-RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY: III. STATISTICAL MODELS

    Science.gov (United States)

    Although quantitative modeling has been central to cancer risk assessment for years, the concept of dose-response modeling for developmental effects is relatively new. Recently, statistical models appropriate for developmental toxicity testing have been developed and applied (Rai...

  3. Statistical modeling of dose-response relationships in clinical trials--a case study.

    Science.gov (United States)

    Holmgren, E B; Koch, G G

    1997-05-01

    This paper presents a model-based assessment of the relationship between the dose of a test treatment and response. The data set used in the analysis describes the results of two clinical trials that were designed to assess the dose-response relationship of a test treatment. The models described in the paper are fit using weighted regression as implemented by the SAS procedure CATMOD. Relationships between weighted regression and other similar procedures are discussed. PMID:9136071

  4. Design, statistical analysis and sample size calculation of dose response study of telmisartan and hydrochlorothiazide.

    Science.gov (United States)

    Horie, Yoshiharu; Higaki, Jitsuo; Takeuchi, Masahiro

    2007-09-01

    Many patients with hypertension take some antihypertensive drugs with complementary mechanisms of action to lower their blood pressure and achieve the therapeutic goals reducing the risk of cardiovascular events. Telmisartan, angiotensin II receptor blocker, and hydrochlorothiazide, diuretic are two antihypertensive drugs that have a well-recognized clinical efficacy. Their combination is expected to be one of the most appropriate therapies for hypertensive patients. However there is no information to show the effective dose combination of two drugs for the Japanese patients with mild to moderate hypertension. Therefore, the prospective, randomized, double-blinded study was planed for showing the dose response surface of two components. The 3 by 3 factorial design was applied for this purpose and the approach for calculating sample size was proposed. This study was registered with ClinicalTrial.gov (NCT00153049). PMID:17389151

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

    OpenAIRE

    Jansen, J. J. P.; Burdorf, A.

    2003-01-01

    BACKGROUND: In epidemiological studies on physical workloads and back complaints, among the important features in modelling dose-response relations are the measurement strategy of the exposure and the nature of the dose-response relation that is assumed. AIM: To evaluate the effect of these two features on the strength of the dose-response relation between physical load and severe low back pain. METHODS: The study population consisted of 7...

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

    Science.gov (United States)

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

    2005-09-01

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

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

    International Nuclear Information System (INIS)

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

  8. Self-play: statistical significance

    OpenAIRE

    Haworth, Guy Mccrossan

    2003-01-01

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

  9. Statistical significance of quantitative PCR

    OpenAIRE

    Mazza Christian; Perseguers Sébastien; McNair Alan; Karlen Yann; Mermod Nicolas

    2008-01-01

    Abstract Background PCR has the potential to detect and precisely quantify specific DNA sequences, but it is not yet often used as a fully quantitative method. A number of data collection and processing strategies have been described for the implementation of quantitative PCR. However, they can be experimentally cumbersome, their relative performances have not been evaluated systematically, and they often remain poorly validated statistically and/or experimentally. In this study, we evaluated...

  10. Mining Statistically Significant Substrings using the Chi-Square Statistic

    OpenAIRE

    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...

  11. Detection of entanglement with high statistical significance

    International Nuclear Information System (INIS)

    Full text: A witness operator is an observable which allows to verify whether a given state is entangled. In a typical experiment, only a limited number of copies of the entangled state is available for this task. In order to detect entanglement with high certainty, it is therefore of advantage to decrease the statistical error involved in the measurement of the witness. We demonstrate that the variance of a witness operator can always be minimized for a given state by adding a positive operator. Apart from witness operators, we also consider Bell-like inequalities and present an example in which an inequality with lower violation leads to a higher statistical significance. (author)

  12. Finding statistically significant communities in networks

    CERN Document Server

    Lancichinetti, Andrea; Ramasco, Jose' Javier; Fortunato, Santo

    2010-01-01

    Community structure is one of the main structural features of networks, revealing both their internal organization and the similarity of their elementary units. Despite the large variety of methods proposed to detect communities in graphs, there is a big need for multi-purpose techniques, able to handle different types of datasets and the subtleties of community structure. In this paper we present OSLOM (Order Statistics Local Optimization Method), the first method capable to detect clusters in networks accounting for edge directions, edge weights, overlapping communities, hierarchies and community dynamics. It is based on the local optimization of a fitness function expressing the statistical significance of clusters with respect to random fluctuations, which is estimated with tools of Extreme and Order Statistics. OSLOM can be used alone or as a refinement procedure of partitions/covers delivered by other techniques. We have also implemented sequential algorithms combining OSLOM with other fast techniques, ...

  13. Nonlinearity of dose responses in thermoluminescence dosimetry

    International Nuclear Information System (INIS)

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

  14. On the statistical significance of climate trends

    Science.gov (United States)

    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.

  15. The Significant Digit Law in Statistical Physics

    CERN Document Server

    Shao, Lijing; 10.1016/j.physa.2010.04.021

    2010-01-01

    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 the Benford distribution with respect to the temperature of the system, while the BE distribution conforms to it exactly whatever the temperature is. Thus the Benford's law seems to present a general pattern for physical statistics and might be even more fundamental and profound in nature. Furthermore, various elegant properties of Benford's law, especially the mantissa distribution of data sets, are discussed.

  16. The significant digit law in statistical physics

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

  18. Social significance of community structure: Statistical view

    CERN Document Server

    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...

  19. 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

  20. Mahalanobis distance and variable selection to optimize dose response

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  2. A Statistical Significance Simulation Study for the General Scientist

    CERN Document Server

    Levman, Jacob

    2011-01-01

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

  3. Caveats for using statistical significance tests in research assessments

    CERN Document Server

    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...

  4. Dose-Response Calculator for ArcGIS

    Science.gov (United States)

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

    2011-01-01

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

  5. Implicit dose-response curves.

    Science.gov (United States)

    Pérez Millán, Mercedes; Dickenstein, Alicia

    2014-07-10

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

  6. BUMP: a FORTRAN program for identifying dose-response curves subject to downturns.

    Science.gov (United States)

    Simpson, D G; Dallal, G E

    1989-02-01

    BUMP is a FORTRAN implementation of a modified Jonckheere-Terpstra test, proposed by Simpson and Margolin, to test nonparametrically for a dose-response curve when a downturn is possible at high doses. The Jonckheere-Terpstra statistic is commonly used to test for increasing or decreasing trends in dose-response relationships. In many experimental settings, however, a test agent has more than one effect, and a "bump"-shaped dose-response can occur. For instance, increasing the concentration of a certain nutrient on a petri dish may increase the growth rate at low doses yet decrease the growth rate at high doses because of toxicity. The modified test allows one to assess the significance of the initial increase in the dose-response curve and yet to minimize the effect on the conclusions of any downturn at higher doses. A complete system which operates directly on SYSTAT/MYSTAT files is available for the IBM-PC and compatibles; it includes a utility which converts ASCII data files to the SYSTAT/MYSTAT format. The FORTRAN 77 source code is available for those who would like to run BUMP on other machines. PMID:2914424

  7. 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.

  8. Formaldehyde dose-response in healthy nonsmokers

    Energy Technology Data Exchange (ETDEWEB)

    Kulle, T.J.; Sauder, L.R.; Hebel, J.R.; Green, D.J.; Chatham, M.D.

    1987-08-01

    Industrial, commercial, and domestic levels of formaldehydes exposure range from <0.1 to >5.0 ppm. Irritation of the eyes and upper respiratory tract predominate, and bronchoconstriction is described in case reports. However, pulmonary function and irritant symptoms together have not been assessed over a range of HCHO concentrations in a controlled environment. The authors investigated dose response in both symptoms and pulmonary function associated with 3-h exposures to 0.0-3.0 ppm HCHO in a controlled environmental chamber. Ten subjects were randomly exposed to 0.0, 0.5, 1.0, and 2.0 ppm HCHO at rest plus 2.0 ppm HCHO with exercise and nine additional subjects were randomly exposed to 0.0, 1.0, 2.0, and 3.0 ppm HCHO at rest plus 2.0 ppm HCHO with exercise. Significant dose-response relationships in odor and eye irritation were observed (p < 0.05). Nasal flow resistance was increased at 3.0 ppm (p < 0.01), but not at 2.0 ppm HCHO. There were no significant decrements in pulmonary function (FVC, FEV/sub 1/, FEF/sub 25-75%/, SGaw) or increases in bronchial reactivity to methacholine (log PD/sub 35SGaw/) with exposure to 0.5-3.0 ppm HCHO at rest or to 2.0 ppm HCHO with exercise.

  9. Computer Simulation of Quantal Dose-Response Relationships.

    Science.gov (United States)

    McGilliard, Kip L.

    1985-01-01

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

  10. SIGNIFICANCE OF STATISTICS IN HEALTH SCIENCES IN RURAL AREA

    OpenAIRE

    Reetu Malhotra, Vandana Singh

    2012-01-01

    The present article is aimed at significance ofstatistics in growing health science industries. Health andstatistics are essential tools in demography; health care, medicalprofession and community services. Statistics plays verysignificant role to describe what is normal and healthy inpopulation and to find limits of normality in variables, such asweight and pulse rate, sex and haemoglobin, age andmenstruation cycle etc. Statistics in health sciences willarticulates leading causes of death, s...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

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

    International Nuclear Information System (INIS)

    Purpose: To assess the shape of the dose–response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy?1 of 0.082 (95% CI 0.031–0.140), and ischemic heart disease, with an excess relative risk Gy?1 of 0.102 (95% CI 0.039–0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose–response. There were significant (p 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose–response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The by time since exposure. The consistency of the dose–response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose–exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  14. A semiparametric approach to analysing dose-response data.

    Science.gov (United States)

    Nottingham, Q J; Birch, J B

    2000-02-15

    In the analysis of a quantal dose-response experiment with grouped data, the most commonly used parametric procedure is logistic regression, commonly referred to as 'logit analysis'. The adequacy of the fit by the logistic regression curve is tested using the chi-square lack-of-fit test. If the lack-of-fit test is not significant, then the logistic model is assumed to be adequate and estimation of effective doses and confidence intervals on the effective doses can be made. When the tolerance distribution of the dose-response data is not known and cannot be assumed by the user, one can use non-parametric methods, such as kernel regression or local linear regression, to estimate the dose-response curve, effective doses and confidence intervals. This research proposes another alternative based on semi-parametric regression to analysing quantal dose-response data called model-robust quantal regression (MRQR). MRQR linearly combines the parametric and non-parametric predictions with the use of a mixing parameter. MRQR uses logistic regression as the parametric portion of the model and local linear regression as the non-parametric portion of the model. Our research has shown that the MRQR procedure can improve the fit of the dose-response curve by producing narrower confidence intervals for predictions while providing improved precision of estimates of the effective doses with respect to either logistic or local linear regression results. PMID:10649304

  15. A method for assessing the statistical significance of RNA folding.

    Science.gov (United States)

    Le, S Y; Maizel, J V

    1989-06-22

    We have developed a statistical method that is designed for analyzing potential RNA folded substructures. The statistical significance of RNA folding is assessed by the segment score. The segment score is defined as the difference between the lowest free energy calculated for the real biological sequence and the mean of the lowest free energies from random permutations of the real segment sequence, divided by the standard deviation of the random sample. This procedure was applied to the well-studied Escherichia coli 16S rRNA and potato spindle tuber viroid (PSTV) RNA. The results showed that the predictions of the locally significant secondary structures in these two molecules are in accord with the universally conserved local secondary structure elements (Gutell, Weiser & Noller, 1985, Prog. Nucl. Acid Res. molec. Biol. 32, 155-216; Riesner & Gross, 1985, A. Rev. Biochem. 54, 531-564). In addition, a statistical analysis indicated that the lowest free energies of a random sample set follow an approximately normal distribution. A reasonable size for the random sample set was determined statistically. Moreover, the statistical evaluation has been carried out using three different sets of energy rules--two sets (Salser, 1977, Cold Spring Harb. Symp. Quant Biol. 42, 985-1002; Freier, Kierzek, Jaeger, Sugimoto, Caruthers, Neilson & Turner, 1986, Proc. natn. Acad. Sci. U.S.A. 83, 9373-9377) take into account stacking energies and are based on experimental data and their computational extension (Salser, 1977)--the third set is a simplistic "unitary matrix" approach, where any base-pair is given a weight of "minus one" and an unpaired based is "zero". The Freier energy rules usually yield the strongest indication of significant folding region. However, the results derived from paired comparisons test don't provide sufficient evidence for concluding that a different set of energy rules is effective in changing the segment score level for local stem-loop structures in the 16S rRNA. PMID:2480496

  16. Signal significance in the presence of systematic and statistical uncertainties

    Science.gov (United States)

    Bityukov, S. I.; Krasnikov, N. V.

    2003-04-01

    Incorporation of uncertainties to calculations of signal significance in planned experiments is an actual task. We present a procedure of allowing for the effects of one-sided systematic errors related to nonexact knowledge of signal and background cross-sections, which affect the discovery potential of an experiment. A method is proposed for treating the statistical errors of the expected signal and background rates.

  17. Signal significance in the presence of systematic and statistical uncertainties

    Energy Technology Data Exchange (ETDEWEB)

    Bityukov, S.I. E-mail: serguei.bitioukov@cern.ch; Krasnikov, N.V

    2003-04-21

    Incorporation of uncertainties to calculations of signal significance in planned experiments is an actual task. We present a procedure of allowing for the effects of one-sided systematic errors related to nonexact knowledge of signal and background cross-sections, which affect the discovery potential of an experiment. A method is proposed for treating the statistical errors of the expected signal and background rates.0.

  18. Signal Significance in the Presence of Systematic and Statistical Uncertainties

    CERN Document Server

    Bityukov, S I

    2002-01-01

    The incorporation of uncertainties to calculations of signal significance in planned experiments is an actual task. Several approaches to this problem are discussed. We present a procedure for taking into account the systematic uncertainty related to nonexact knowledge of signal and background cross sections. A method for account of statistical uncertainties in determination of mean numbers of signal and background events is proposed. The law of conservation of unit and zero in plane ``number of events versus parameer of Poisson distribution'' is formulated.

  19. Signal significance in the presence of systematic and statistical uncertainties

    International Nuclear Information System (INIS)

    The incorporation of uncertainties to calculations of signal significance in planned experiments is an actual task. We present a procedure of taking into account the effects of one sided systematic errors related to non-exact knowledge of signal and background cross sections on the discovery potential of an experiments. A method of a treatment of statistical errors of the expected signal and background rates is proposed. The interrelation between Gamma- and Poisson distributions is demonstrated. (author)

  20. Signal significance in the presence of systematic and statistical uncertainties

    International Nuclear Information System (INIS)

    Incorporation of uncertainties to calculations of signal significance in planned experiments is an actual task. We present a procedure of allowing for the effects of one-sided systematic errors related to nonexact knowledge of signal and background cross-sections, which affect the discovery potential of an experiment. A method is proposed for treating the statistical errors of the expected signal and background rates

  1. Signal Significance in the Presence of Systematic and Statistical Uncertainties

    OpenAIRE

    Bityukov, S. I.

    2002-01-01

    The incorporation of uncertainties to calculations of signal significance in planned experiments is an actual task. Several approaches to this problem are discussed. We present a procedure for taking into account the systematic uncertainty related to nonexact knowledge of signal and background cross sections. A method of a treatment of statistical errors of the expected signal and background rates is proposed. The interrelation between Gamma- and Poisson distributions is dem...

  2. On the Atmospheric Neutrino Anomaly and its Statistical Significance

    OpenAIRE

    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...

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  6. An Efficient Rigorous Approach for Identifying Statistically Significant Frequent Itemsets

    CERN Document Server

    Kirsch, Adam; Pietracaprina, Andrea; Pucci, Geppino; Upfal, Eli; Vandin, Fabio

    2010-01-01

    As advances in technology allow for the collection, storage, and analysis of vast amounts of data, the task of screening and assessing the significance of discovered patterns is becoming a major challenge in data mining applications. In this work, we address significance in the context of frequent itemset mining. Specifically, we develop a novel methodology to identify a meaningful support threshold s* for a dataset, such that the number of itemsets with support at least s* represents a substantial deviation from what would be expected in a random dataset with the same number of transactions and the same individual item frequencies. These itemsets can then be flagged as statistically significant with a small false discovery rate. We present extensive experimental results to substantiate the effectiveness of our methodology.

  7. Large SDSS Quasar Groups and their Statistical Significance

    Science.gov (United States)

    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.

  8. The reporting of statistical significance in scientific journals: A reflexion

    Directory of Open Access Journals (Sweden)

    Jan M. Hoem

    2008-06-01

    Full Text Available Scientific journals in most empirical disciplines have regulations about how authors should report the precision of their estimates of model parameters and other model elements. Some journals that overlap fully or partly with the field of demography demand as a strict prerequisite for publication that a p-value, a confidence interval, or a standard deviation accompany any parameter estimate. I feel that this rule is sometimes applied in an overly mechanical manner. Standard deviations and p-values produced routinely by general-purpose software are taken at face value and included without questioning, and features that have too high a p-value or too large a standard deviation are too easily disregarded as being without interest because they appear not to be statistically significant. In my opinion authors should be discouraged from adhering to this practice, and flexibility rather than rigidity should be encouraged in the reporting of statistical significance. I would also encourage thoughtful rather than mechanical use of p-values, standard deviations, confidence intervals, and the like.

  9. Bayesian multimodel inference for dose-response studies

    Science.gov (United States)

    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.

  10. Large SDSS quasar groups and their statistical significance

    CERN Document Server

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

    2015-01-01

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

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

    CERN Document Server

    Chaudhari, Dipak; Laxman, Srivatsan

    2010-01-01

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

  12. Testing the Dose–Response Specification in Epidemiology: Public Health and Policy Consequences for Lead

    OpenAIRE

    Rothenberg, Stephen J.; Rothenberg, Jesse C.

    2005-01-01

    Statistical evaluation of the dose–response function in lead epidemiology is rarely attempted. Economic evaluation of health benefits of lead reduction usually assumes a linear dose–response function, regardless of the outcome measure used. We reanalyzed a previously published study, an international pooled data set combining data from seven prospective lead studies examining contemporaneous blood lead effect on IQ (intelligence quotient) of 7-year-old children (n = 1,333). We constructed...

  13. Analytical modelling of regional radiotherapy dose response of lung

    Science.gov (United States)

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

    2012-06-01

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

  14. Transmission and dose–response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens

    Science.gov (United States)

    Dose-response experiments characterize the relationship between infectious agents and their hosts. They are used to estimate the minimum e'ective infectious dose (ID50), compare between di'erent agents and quantify the e'ect of treatment regimes. The statistical analysis of dose-response data typica...

  15. Comparison of microarrays and RNA-seq for gene expression analyses of dose-response experiments.

    Science.gov (United States)

    Black, Michael B; Parks, Bethany B; Pluta, Linda; Chu, Tzu-Ming; Allen, Bruce C; Wolfinger, Russell D; Thomas, Russell S

    2014-02-01

    Relative to microarrays, RNA-seq has been reported to offer higher precision estimates of transcript abundance, a greater dynamic range, and detection of novel transcripts. However, previous comparisons of the 2 technologies have not covered dose-response experiments that are relevant to toxicology. Male F344 rats were exposed for 13 weeks to 5 doses of bromobenzene, and liver gene expression was measured using both microarrays and RNA-seq. Multiple normalization methods were evaluated for each technology, and gene expression changes were statistically analyzed using both analysis of variance and benchmark dose (BMD). Fold-change values were highly correlated between the 2 technologies, whereas the -log p values showed lower correlation. RNA-seq detected fewer statistically significant genes at lower doses, but more significant genes based on fold change except when a negative binomial transformation was applied. Overlap in genes significant by both p value and fold change was approximately 30%-40%. Random sampling of the RNA-seq data showed an equivalent number of differentially expressed genes compared with microarrays at ~5 million reads. Quantitative RT-PCR of differentially expressed genes uniquely identified by each technology showed a high degree of confirmation when both fold change and p value were considered. The mean dose-response expression of each gene was highly correlated between technologies, whereas estimates of sample variability and gene-based BMD values showed lower correlation. Differences in BMD estimates and statistical significance may be due, in part, to differences in the dynamic range of each technology and the degree to which normalization corrects genes at either end of the scale. PMID:24194394

  16. Inhalation Anthrax: Dose Response and Risk Analysis

    OpenAIRE

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

    2008-01-01

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

  17. Modeling of dose-response relationships.

    OpenAIRE

    Altshuler, B.

    1981-01-01

    The main dose-response models for chronic toxicity are considered. For dichotomous response, the log probit, multi-hit, and multistage models are presented. For time-to-occurrence response, the log-normal and three variations of multistage models are presented. Finally, the Cornfield hockey-stick model is considered, and, for low-dose extrapolation, it is suggested that response be taken to be proportional to dose and to a power of time determined by background response.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. A study of dose-response relationship between tobacco habits and oral leukoplakia.

    OpenAIRE

    Gupta, P. C.

    1984-01-01

    In a house-to-house survey in Ernakulam district, Kerala, India, 12,213 tobacco users were interviewed about the details of their tobacco usage and examined for the presence of leukoplakia. The frequency of tobacco habit was associated with the prevalence of leukoplakia indicating a positive dose-response relationship. The dose-response relationship remained significant, taking age, sex, and the type of tobacco habit into account. After adjusting for all these variables jointly the associatio...

  20. Dose-response relations from epidemiological studies

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  2. Statistically significant data base of rock properties for geothermal use

    Science.gov (United States)

    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.

  3. Dose response relationship in anti-stress gene regulatory networks.

    Science.gov (United States)

    Zhang, Qiang; Andersen, Melvin E

    2007-03-01

    To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products) in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear) depends on changes in the specific values of local response coefficients (gains) distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear, and depending on the level of local gains, presence of gain-changing events, and degree of feedforward gene activation, this region can appear as superlinear, sublinear, or even J-shaped. The general dose response transition proposed here was further examined in a complex anti-electrophilic stress pathway, which involves multiple genes, enzymes, and metabolic reactions. This work would help biologists and especially toxicologists to better assess and predict the cellular impact brought about by biological stressors. PMID:17335342

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

    Science.gov (United States)

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

    2012-01-01

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

  5. Controlled Optimal Design Program for the Logit Dose Response Model

    OpenAIRE

    Jiaqiao Hu; Wei Zhu; Yi Su; Weng Kee Wong

    2010-01-01

    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 soft...

  6. Dose-response relationships for carcinogens: a review.

    OpenAIRE

    Zeise, L.; Wilson, R.; Crouch, E. A.

    1987-01-01

    We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinea...

  7. Quantification of Hormesis in Anticancer-Agent Dose-Responses

    OpenAIRE

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

    2009-01-01

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

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

    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.

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

    International Nuclear Information System (INIS)

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

  10. DOSE-RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY III. STATISTICAL MODELS

    Science.gov (United States)

    Although quantitative modeling has been central to cancer risk assessment for years, the concept of do@e-response modeling for developmental effects is relatively new. he benchmark dose (BMD) approach has been proposed for use with developmental (as well as other noncancer) endpo...

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Mukherjee, T.; Shinde, Santosh H.

    2010-01-01

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

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

    Science.gov (United States)

    Xu, Kuan-Man

    2006-01-01

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

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

    Science.gov (United States)

    Conolly, Rory B; Gaylor, David W; Lutz, Werner K

    2005-09-01

    Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism, (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health. PMID:15996697

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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:…

  17. Duration of Exposure and the Dose-Response Model of PTSD

    Science.gov (United States)

    Kaysen, Debra; Rosen, Gerald; Bowman, Marilyn; Resick, Patricia A.

    2010-01-01

    A dose-response model underlies posttraumatic stress disorder (PTSD) and posits a relationship between event magnitude and clinical outcome. The present study examines whether one index of event magnitude--duration of exposure--contributes to risk of PTSD among female victims of sexual assault. Findings support a small but significant contribution…

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

    DEFF Research Database (Denmark)

    Engsted, Tom

    2009-01-01

    I comment on the controversy between McCloskey & Ziliak and Hoover & Siegler on statistical versus economic significance, in the March 2008 issue of the Journal of Economic Methodology. I argue that while McCloskey & Ziliak are right in emphasizing 'real error', i.e. non-sampling error that cannot be eliminated through specification testing, they fail to acknowledge those areas in economics, e.g. rational expectations macroeconomics and asset pricing, where researchers clearly distinguish between statistical and economic significance and where statistical testing plays a relatively minor role in model evaluation. In these areas models are treated as inherently misspecified and, consequently, are evaluated empirically by other methods than statistical tests. I also criticise McCloskey & Ziliak for their strong focus on the size of parameter estimates while neglecting the important question of how to obtain reliable estimates, and I argue that significance tests are useful tools in those cases where a statistical model serves as input in the quantification of an economic model. Finally, I provide a specific example from economics - asset return predictability - where the distinction between statistical and economic significance is well appreciated, but which also shows how statistical tests have contributed to our substantive economic understanding.

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

    Scientific Electronic Library Online (English)

    Lee-Ann C., Hayek; W. Ronald, Heyer.

    2005-03-01

    Full Text Available SciELO Brazil | Language: English Abstract in portuguese 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.

  20. Dose-Response Relationship Between Serum 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Diabetes Mellitus: A Meta-Analysis.

    Science.gov (United States)

    Goodman, Michael; Narayan, K M Venkat; Flanders, Dana; Chang, Ellen T; Adami, Hans-Olov; Boffetta, Paolo; Mandel, Jack S

    2015-03-15

    We systematically evaluated studies published through May 2014 in which investigators assessed the dose-response relationship between serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the occurrence of diabetes mellitus (DM), and we investigated the extent and sources of interstudy heterogeneity. The dose-response relationship between serum TCDD and DM across studies was examined using 2 dependent variables: an exposure level-specific proportion of persons with DM and a corresponding natural log-transformed ratio measure of the association between TCDD and DM. Regression slopes for each dependent variable were obtained for each study and included in a random-effects meta-analysis. Sensitivity analyses were used to assess the influence of inclusion and exclusion decisions, and sources of heterogeneity were explored using meta-regression models and a series of subanalyses. None of the summary estimates in the main models or in the sensitivity analyses indicated a statistically significant association. We found a pronounced dichotomy: a positive dose-response in cross-sectional studies of populations with low-level TCDD exposures (serum concentrations <10 pg/g lipid) and heterogeneous, but on balance null, results for prospective studies of persons with high prediagnosis TCDD body burdens. Considering the discrepancy of results for low current versus high past TCDD levels, the available data do not indicate that increasing TCDD exposure is associated with an increased risk of DM. PMID:25731889

  1. The analysis of dose-response curves--a practical approach.

    OpenAIRE

    Jackson, S. H.; Jamieson, M. J.; Johnston, A.; Shepherd, A. M.

    1987-01-01

    The rationale for the objective assessment of dose-response curves (DRCs) is presented. Using data derived from isoprenaline/heart rate responses studies, two new statistical methods of objectively defining the terminal linear segment of an incomplete DRC are presented. Using data derived from phenylephrine/diastolic blood pressure response studies, the parallel shift quadratic model of Sumner et al. (1982) has been extended to include a measure of the suitability of the quadratic model for e...

  2. Model for dose-response with alternative change of sign

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

    Christensen, Hanne Risager; Larsen, C.N.

    2006-01-01

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

  4. Cardiac dose-response relationships of oral and intravenous pindolol

    OpenAIRE

    Carruthers, S. George

    1982-01-01

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

  5. Dose-response relationship in multistage carcinogenesis: promoters.

    OpenAIRE

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

    1994-01-01

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

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

    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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    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.

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

    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.

  11. Statistical significance testing with mahalanobis distance for thresholds estimated from constant stimuli method.

    Science.gov (United States)

    Nagai, Takehiro; Hoshino, Takahiro; Uchikawa, Keiji

    2011-01-01

    The t-test and the analysis of variance are commonly used as statistical significance testing methods. However, they cannot assess the significance of differences between thresholds within individual observers estimated from the constant stimuli method; these thresholds are not defined as averages of samples, but they are rather defined as functions of parameters of psychometric functions fitted to participants' responses. Moreover, the statistics necessary for these statistical testing methods cannot be derived. In this paper, we propose a new statistical testing method to assess the statistical significance of differences between thresholds estimated from the constant stimuli method. The new method can assess not only threshold differences but also main effects and interactions in multifactor experiments, exploiting the asymptotic normality of maximum likelihood estimators and the characteristics of multivariate normal distributions. This proposed method could be used in similar cases to the analysis of variance for thresholds estimated from the adjustment method and the staircase method. Finally, we present some data on simulations in which we tested assumptions, power and type I error of the proposed method. PMID:21864453

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

    OpenAIRE

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

    1980-01-01

    Dose-response curves have been computed for 5 tumour sites of the head and neck region, using 2 regression models. In agreement with clinical observation, a significant increase has been found from moderate to high control rates with modest dose increases for exophytic tumours (T1 + T2 retromolar trigone-anterior faucial pillar and T2 + T3 supraglottic larynx). Further significant increases in local control after modest dose increases are not obtained when the control rate is already high and...

  13. Theory of thermoluminescence gamma dose response: The unified interaction model

    Science.gov (United States)

    Horowitz, Y. S.

    2001-09-01

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

  14. Theory of thermoluminescence gamma dose response: The unified interaction model

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Huang Xiaoqiu; Agrawal Ankit

    2009-01-01

    Abstract Background Accurate estimation of statistical significance of a pairwise alignment is an important problem in sequence comparison. Recently, a comparative study of pairwise statistical significance with database statistical significance was conducted. In this paper, we extend the earlier work on pairwise statistical significance by incorporating with it the use of multiple parameter sets. Results Results for a knowledge discovery application of homology detection reveal that using mu...

  16. Kinetic modeling of optical absorption dose response in TLD-100

    International Nuclear Information System (INIS)

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

  17. Statistical significance threshold criteria for analysis of microarray gene expression data.

    Science.gov (United States)

    Cheng, Cheng; Pounds, Stanley B; Boyett, James M; Pei, Deqing; Kuo, Mei-Ling; Roussel, Martine F

    2004-01-01

    The methodological advancement in microarray data analysis on the basis of false discovery rate (FDR) control, such as the q-value plots, allows the investigator to examine the FDR from several perspectives. However, when FDR control at the "customary" levels 0.01, 0.05, or 0.1 does not provide fruitful findings, there is little guidance for making the trade off between the significance threshold and the FDR level by sound statistical or biological considerations. Thus, meaningful statistical significance criteria that complement the existing FDR methods for large-scale multiple tests are desirable. Three statistical significance criteria, the profile information criterion, the total error proportion, and the guide-gene driven selection, are developed in this research. The first two are general significance threshold criteria for large-scale multiple tests; the profile information criterion is related to the recent theoretical studies of the connection between FDR control and minimax estimation, and the total error proportion is closely related to the asymptotic properties of FDR control in terms of the total error risk. The guide-gene driven selection is an approach to combining statistical significance and the existing biological knowledge of the study at hand. Error properties of these criteria are investigated theoretically and by simulation. The proposed methods are illustrated and compared using an example of genomic screening for novel Arf gene targets. Operating characteristics of q-value and the proposed significance threshold criteria are investigated and compared in a simulation study that employs a model mimicking a gene regulatory pathway. A guideline for using these criteria is provided. Splus/R code is available from the corresponding author upon request. PMID:16646816

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

    CERN Document Server

    Boger, J; Cumming, J B

    2000-01-01

    It has been suggested by various authors that a significant anticorrelation exists between the Homestake solar neutrino data and the sunspot cycle. Some of these claims rest on smoothing the data by taking running averages, a method that has recently undergone criticism. We demonstrate that no significant anticorrelation can be found in the Homestake, data, or in standard 2- and 4-point averages of that data. However, when 3-, 5-, and 7-point running averages are taken, an anticorrelation seems to emerge whose significance grows as the number of points in the average increases. Our analysis indicates that the apparently high significance of these anticorrelations is an artifact of the failure to consider the loss of independence introduced in the running average process. When this is considered, the significance is reduced to that of the unaveraged data. Furthermore, when evaluated via parametric subsampling, no statistically significant anticorrelation is found. We conclude that the Homestake data can not be...

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

    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 subgroup and sensitivity analyses (see step 6). (3) To take account of problems with multiplicity adjust the thresholds for significance according to the number of primary outcomes. (4) Calculate required information sizes (? the a priori required number of participants for a meta-analysis to be conclusive) for all outcomes and analyse each outcome with trial sequential analysis. Report whether the trial sequential monitoring boundaries for benefit, harm, or futility are crossed. (5) Calculate Bayes factors for all primary outcomes. (6) Use subgroup analyses and sensitivity analyses to assess the potential impact of bias on the review results. (7) Assess the risk of publication bias. (8) Assess the clinical significance of the statistically significant review results. CONCLUSIONS: If followed, the proposed eight-step procedure will increase the validity of assessments of intervention effects in systematic reviews of randomised clinical trials.

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Fernández-Somoano Ana; Suárez-Gil Patricio; Silva-Ayçaguer Luis

    2010-01-01

    Abstract Background The null hypothesis significance test (NHST) is the most frequently used statistical method, although its inferential validity has been widely criticized since its introduction. In 1988, the International Committee of Medical Journal Editors (ICMJE) warned against sole reliance on NHST to substantiate study conclusions and suggested supplementary use of confidence intervals (CI). Our objective was to evaluate the extent and quality in the use of NHST and CI, both in Englis...

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

    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.

  3. Evidence for t bar t production at the Tevatron: Statistical significance and cross section

    International Nuclear Information System (INIS)

    We summarize here the results of the ''counting experiments'' by the CDF Collaboration in the search of t bar t production in p bar p collisions at ?s = 1800 TeV at the Tevatron. We analyze their statistical significance by calculating the probability that the observed excess is a fluctuation of the expected backgrounds, and assuming the excess is from top events, extract a measurement of the t bar t production cross-section

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

    OpenAIRE

    Baldi, Pierre; Nasr, Ramzi

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Falgreen, Steffen; 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.

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

    International Nuclear Information System (INIS)

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

  7. The Effect of Ongoing Exposure Dynamics in Dose Response Relationships

    OpenAIRE

    Pujol, Josep M.; Eisenberg, Joseph E.; Haas, Charles N.; Koopman, James S.

    2009-01-01

    Characterizing infectivity as a function of pathogen dose is integral to microbial risk assessment. Dose-response experiments usually administer doses to subjects at one time. Phenomenological models of the resulting data, such as the exponential and the Beta-Poisson models, ignore dose timing and assume independent risks from each pathogen. Real world exposure to pathogens, however, ...

  8. A Framework for "Fit for Purpose" Dose Response Assessment

    Science.gov (United States)

    The NRC report Science and Decisions: Advancing Risk Assessment made several recommendations to improve chemical risk assessment, with a focus on in-depth chronic dose-response assessments conducted by the U.S. Environmental Protection Agency. The recommendations addressed two ...

  9. Corresponding dose response of radiographic film with layered Gafchromic film

    International Nuclear Information System (INIS)

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

  10. Estimating the dose-response function through the GLM approach

    OpenAIRE

    Guardabascio, Barbara; Ventura, Marco

    2013-01-01

    This paper revises the estimation of the dose-response function as in Hirano and Imbens (2004) by proposing a flexible way to estimate the generalized propensity score when the treatment variable is not necessarily normally distributed. We also provide a set of programs that accomplish this task by using the GLM in the first step of the computation.

  11. Dose response curves for organ function or cell survival

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  13. 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, 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.

  14. External beam radiotherapy dose response of prostate cancer

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    La Piana GE

    2011-07-01

    Full Text Available Giuseppe Emanuele La Piana¹, Luciano Corda², Enrica Bertella¹, Luigi Taranto Montemurro¹, Laura Pini¹, Claudio Tantucci¹¹Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, ²Prima Divisione di Medicina Interna, Spedali Civili, Brescia, ItalyBackground: Use of short-acting ß2-agonists in chronic obstructive pulmonary disease (COPD during treatment with long-acting ß2-agonists is recommended as needed, but its effectiveness is unclear. The purpose of this study was to assess the additional bronchodilating effect of increasing doses of salbutamol during acute and chronic treatment with formoterol in patients with COPD.Methods: Ten patients with COPD underwent a dose-response curve to salbutamol (until 800 µg of cumulative dose after a 1-week washout (baseline, 8 hours after the first administration of formoterol 12 µg (day 1, and after a 12-week and 24-week period of treatment with formoterol (12 µg twice daily by dry powder inhaler. Peak expiratory flow, forced expiratory volume in one second (FEV1, forced vital capacity, and inspiratory capacity were measured at the different periods of treatment and at different steps of the dose-response curve.Results: Despite acute or chronic administration of formoterol, maximal values of peak expiratory flow, FEV1, and forced vital capacity after 800 µg of salbutamol were unchanged compared with baseline. The baseline FEV1 dose-response curve was steeper than that at day 1, week 12, or week 24 (P < 0.0001. Within each dose-response curve, FEV1 was different only at baseline and at day 1 (P < 0.001, when FEV1 was still greater at 800 µg than at 0 µg (P < 0.02. In contrast, the forced vital capacity dose-response curves were similar at the different periods, while within each dose-response curve, forced vital capacity was different in all instances (P < 0.001, always being higher at 800 µg than at 0 µg (P < 0.05.Conclusion: In patients with stable COPD, the maximal effect of salbutamol on peak expiratory flow, FEV1, and forced vital capacity was unchanged after either acute or chronic treatment with formoterol. With increasing doses of salbutamol, FEV1 increased only after acute administration of formoterol. Forced vital capacity also significantly improved during long-term treatment with formoterol.Keywords: chronic obstructive pulmonary disease, salbutamol, formoterol, long-acting ß2-agonists

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

    Science.gov (United States)

    Piai, Vitória; Dahlslätt, Kristoffer; Maris, Eric

    2015-03-01

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

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

    International Nuclear Information System (INIS)

    A relatively new subject for probabilistic safety methodology is statistical analysis of trends in observed failures and other safety indicators reflecting ageing or learning in operational and maintenance experience at industrial facilities. Random variations of the indicators can mask real changes or cause false alarms. Methodology is proposed for testing statistical significance of apparent trends in safety indicators. Improved methods are developed for detecting both monotonic and non-monotonic trends, some demonstrated by simulation studies and real examples to be more powerful than those known so far. An effective way to use standard trend tests with transformed data for testing exponentiality of data is also demonstrated and found superior to a well-known Lilliefors' goodness-of-fit test

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Berg, Andreas; Bayreder, Christian; Georg, Dietmar; Bankamp, Achim; Wolber, Gerd

    2009-05-01

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

  1. Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness

    Science.gov (United States)

    Cajochen, C.; Zeitzer, J. M.; Czeisler, C. A.; Dijk, D. J.

    2000-01-01

    Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to response as assessed by a reduction in the incidence of slow-eye movements, a reduction of EEG activity in the theta-alpha frequencies (power density in the 5-9 Hz range) as well as a reduction in self-reported sleepiness. This alerting response was positively correlated with the degree of melatonin suppression by light. In accordance with the dose response function for circadian resetting and melatonin suppression, the responses of all three indices of alertness to variations in illuminance were consistent with a logistic dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

  2. Quantitative approaches for assessing dose-response relationships in genetic toxicology studies.

    Science.gov (United States)

    Gollapudi, B B; Johnson, G E; Hernandez, L G; Pottenger, L H; Dearfield, K L; Jeffrey, A M; Julien, E; Kim, J H; Lovell, D P; Macgregor, J T; Moore, M M; van Benthem, J; White, P A; Zeiger, E; Thybaud, V

    2013-01-01

    Genetic toxicology studies are required for the safety assessment of chemicals. Data from these studies have historically been interpreted in a qualitative, dichotomous "yes" or "no" manner without analysis of dose-response relationships. This article is based upon the work of an international multi-sector group that examined how quantitative dose-response relationships for in vitro and in vivo genetic toxicology data might be used to improve human risk assessment. The group examined three quantitative approaches for analyzing dose-response curves and deriving point-of-departure (POD) metrics (i.e., the no-observed-genotoxic-effect-level (NOGEL), the threshold effect level (Td), and the benchmark dose (BMD)), using data for the induction of micronuclei and gene mutations by methyl methanesulfonate or ethyl methanesulfonate in vitro and in vivo. These results suggest that the POD descriptors obtained using the different approaches are within the same order of magnitude, with more variability observed for the in vivo assays. The different approaches were found to be complementary as each has advantages and limitations. The results further indicate that the lower confidence limit of a benchmark response rate of 10% (BMDL(10) ) could be considered a satisfactory POD when analyzing genotoxicity data using the BMD approach. The models described permit the identification of POD values that could be combined with mode of action analysis to determine whether exposure(s) below a particular level constitutes a significant human risk. Subsequent analyses will expand the number of substances and endpoints investigated, and continue to evaluate the utility of quantitative approaches for analysis of genetic toxicity dose-response data. PMID:22987251

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

    Directory of Open Access Journals (Sweden)

    Cardozo Linda

    2010-08-01

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

  4. Model Averaging Software for Dichotomous Dose Response Risk Estimation

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  6. Mesothelioma dose response following intraperitoneal injection of mineral fibres.

    OpenAIRE

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

    1991-01-01

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

  7. Dose-response curves and their modification by specific mechanisms

    International Nuclear Information System (INIS)

    Three types of mechanisms are discussed that can contribute to the yield of radiation induced cancer. The relative contribution of each mechanism depends heavily on the tumor type in question. It is suggested that the most fruitful approach to the study of the biology of radiation carcinogenesis is a continued consideration of the mechanisms involved relative to the dose response curves observed (U.S.)

  8. Dose response in the tetrazolium test for skin carcinogenicity.

    OpenAIRE

    Iversen, O. H.

    1980-01-01

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

  9. Gastrointestinal arrhythmias are associated with statistically significant fluctuations in systemic information dimension

    International Nuclear Information System (INIS)

    Although cardiac arrhythmias have been studied extensively, little is known about arrhythmic phenomena in the gastrointestinal (GI) system. In this study, we demonstrate for the first time that the onset of GI arrhythmias is associated with statistically significant fluctuations in the information dimension of the associated systems. We induced gastric and intestinal arrhythmias in pigs using surgical stomach division and mesenteric artery ligation, respectively. Both conditions lead to a decreased supply of blood to the GI tract, which is associated in humans with various potentially lethal conditions including chronic mesenteric ischemia, whose mortality rate is over 60%. During our experiments, we recorded simultaneous magnetocardiographic, magnetogastrographic and magnetoenterographic signals and concluded that, when GI circulation is compromised, the information dimensionality of the system fluctuates significantly. In conclusion, dimensionality may be an important diagnostic factor for the characterization of arrhythmias in the context of GI pathophysiology. (note)

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

    Directory of Open Access Journals (Sweden)

    Zakaria M. Sawan

    2011-05-01

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

  11. A framework for fit-for-purpose dose response assessment.

    Science.gov (United States)

    Bette Meek, M E; Bolger, Michael; Bus, James S; Christopher, John; Conolly, Rory B; Lewis, R Jeffrey; Paolini, Gregory M; Schoeny, Rita; Haber, Lynne T; Rosenstein, Amy B; Dourson, Michael L

    2013-07-01

    The NRC report Science and Decisions: Advancing Risk Assessment made several recommendations to improve chemical risk assessment, with a focus on in-depth chronic dose-response assessments conducted by the U.S. Environmental Protection Agency. The recommendations addressed two broad elements: improving technical analysis and utility for decision making. To advance the discussions in the NRC report, in three multi-stakeholder workshops organized by the Alliance for Risk Assessment, available and evolving risk assessment methodologies were considered through the development and application of case studies. A key product was a framework (http://www.allianceforrisk.org/Workshop/Framework/ProblemFormulation.html) to guide risk assessors and managers to various dose-response assessment methods relevant to a range of decision contexts ranging from priority setting to full assessment, as illustrated by case studies. It is designed to facilitate selection of appropriate methodology for a variety of problem formulations and includes a variety of methods with supporting case studies, for areas flagged specifically by the NRC committee for consideration--e.g., susceptible sub-populations, population variability and background. The framewok contributes to organization and communication about methodologies for incorporating increasingly biologically informed and chemical specific knowledge into dose-response analysis, which is considered critical in evolving fit-for-purpose assessment to address relevant problem formulations. PMID:23567188

  12. Controlled Optimal Design Program for the Logit Dose Response Model

    Directory of Open Access Journals (Sweden)

    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.

  13. External beam radiotherapy dose-response of prostate cancer

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    CERN Document Server

    Zhang, Pan

    2014-01-01

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

  16. Neuropsychological prediction of conversion to dementia from questionable dementia: statistically significant but not yet clinically useful

    Science.gov (United States)

    Tian, J; Bucks, R; Haworth, J; Wilcock, G

    2003-01-01

    Background: Verbal memory impairment, one of the earliest signs of Alzheimer's disease (AD), may help identify people with cognitive impairment, insufficient for a diagnosis of dementia (questionable dementia: QD), at risk of developing AD. Other cognitive parameters have been found that may indicate which people with QD will go on to develop dementia. Nevertheless, some researchers have reported only partial success in differentiating between mild AD and age related cognitive impairment. Objectives: To discover if there are early, pre-clinical cognitive markers that could help identify patients attending our memory clinic who were at risk of developing dementia. Methods: Multidisciplinary assessment of a consecutive sample of 195 patients with QD seen in a National Health Service hospital outpatient clinic; 135 seen for a mean follow up of 24.5 months. Results: Conversion rate to dementia was 27.4% (37 of 135). A diagnosis of probable or possible AD was made in 15.6% (21 of 135) of cases. Despite statistically significant differences in some cognitive tasks between those who did and those who did not go on to dement, Cox regression analyses failed to improve prediction rates markedly above base rates and were unstable. Conclusion: A large number of studies claim good prediction of conversion to dementia using cognitive test scores. Although this study produced similarly good sensitivity and specificity values, proper consideration of the statistical analyses and their clinical significance suggested that these prediction methods are currently too imprecise for clinical use. Use of cognitive indicators combined with neuroradiological, neuropathological, and genetic factors for predicting conversion to dementia might prove more reliable but may be beyond the scope of many geriatric services. PMID:12640057

  17. SU-E-J-51: Dose Response of Common Solid State Detectors in Homogeneous Transverse and Longitudinal Magnetic Fields

    International Nuclear Information System (INIS)

    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

  18. SDRS—an algorithm for analyzing large-scale dose–response data

    OpenAIRE

    Ji, Rui-ru; Siemers, Nathan O.; Lei, Ming; Schweizer, Liang; Bruccoleri, Robert E.

    2011-01-01

    Summary: Dose–response information is critical to understanding drug effects, yet analytical methods for dose–response assays cannot cope with the dimensionality of large-scale screening data such as the microarray profiling data. To overcome this limitation, we developed and implemented the Sigmoidal Dose Response Search (SDRS) algorithm, a grid search-based method designed to handle large-scale dose–response data. This method not only calculates the pharmacological parameters for ever...

  19. The Radiation Dose-Response of the Human Spinal Cord

    International Nuclear Information System (INIS)

    Purpose: To characterize the radiation dose-response of the human spinal cord. Methods and Materials: Because no single institution has sufficient data to establish a dose-response function for the human spinal cord, published reports were combined. Requisite data were dose and fractionation, number of patients at risk, number of myelopathy cases, and survival experience of the population. Eight data points for cervical myelopathy were obtained from five reports. Using maximum likelihood estimation correcting for the survival experience of the population, estimates were obtained for the median tolerance dose, slope parameter, and ?/? ratio in a logistic dose-response function. An adequate fit to thoracic data was not possible. Hyperbaric oxygen treatments involving the cervical cord were also analyzed. Results: The estimate of the median tolerance dose (cervical cord) was 69.4 Gy (95% confidence interval, 66.4-72.6). The ?/? = 0.87 Gy. At 45 Gy, the (extrapolated) probability of myelopathy is 0.03%; and at 50 Gy, 0.2%. The dose for a 5% myelopathy rate is 59.3 Gy. Graphical analysis indicates that the sensitivity of the thoracic cord is less than that of the cervical cord. There appears to be a sensitizing effect from hyperbaric oxygen treatment. Conclusions: The estimate of ?/? is smaller than usually quoted, but values this small were found in some studies. Using ?/? = 0.87 Gy, one would expect a considerable advantage by decreasing the dose/fraction to lesscreasing the dose/fraction to less than 2 Gy. These results were obtained from only single fractions/day and should not be applied uncritically to hyperfractionation

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

    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.

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

    CERN Document Server

    Atrio-Barandela, F

    2013-01-01

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

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

    Science.gov (United States)

    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",…

  3. 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

  4. Dose response of oral timolol combined with adrenaline.

    OpenAIRE

    Ohrstro?m, 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...

  5. Mutans Streptococci Dose Response to Xylitol Chewing Gum

    OpenAIRE

    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...

  6. External beam radiotherapy for painful osseous metastases: pooled data dose response analysis

    International Nuclear Information System (INIS)

    Purpose: Although the effectiveness of external beam irradiation in palliation of pain from osseous metastases is well established, the optimal fractionation schedule has not been determined. Clinical studies to date have failed to demonstrate an advantage for higher doses. To further address this issue, we conducted a pooled dose response analysis using data from published Phase III clinical trials. Methods and Materials: Complete response (CR) was used as an endpoint because it was felt to be least susceptible to inconsistencies in assessment.The biological effective dose (BED) was calculated for each schedule using the linear-quadratic model and an ?/? of 10. Using SAS version 6.12, the data were fitted using a weighted linear regression, a logistic model, and the spline technique. Finally, BED was categorized, and odds ratios for each level were calculated. Results: CR was assessed early and late in 383 and 1,007 patients, respectively. Linear regression on the early-response data yielded a poor fit and a nonsignificant dose coefficient. With the late-response data, there was an excellent fit (R-square = 0.842) and a highly significant dose coefficient (p = 0.0002). Fitting early CR to a logistic model, we could not establish a significant dose response relationship. However, with the late-response data there was an excellent fit and the dose coefficient was significantly different from zero (0.017 ± 0.00524; p = 0.0012). Application of the spline technique or Application of the spline technique or removal of an outlier resulted in an improved fit (p 0.048 and p = 0.0001, respectively). Using BED of < 14.4 Gy as a reference level, the odds ratios for late CR were 2.29-3.32 (BED of 19.5-51.4 Gy, respectively). Conclusion: Our results demonstrate a clear dose-response for pain relief. Further testing of high intensity regiments is warranted

  7. [18F]-FDG uptake dose–response correlates with radiation pneumonitis in lung cancer patients

    International Nuclear Information System (INIS)

    Purpose: To quantify the post-radiotherapy 2-[18F]-fluoro-2-deoxyglucose (FDG) pulmonary uptake dose–response in lung cancer patients and determine its relationship with radiation pneumonitis symptoms. Methods and materials: The data from 24 patients treated for lung cancer with thoracic radiotherapy who received restaging PET/CT imaging between 4 and 12 weeks after radiotherapy completion were evaluated. Their radiation dose distribution was registered with the post-treatment restaging PET/CT. Using histogram analysis, the voxel average FDG-PET uptake vs. radiation dose was obtained for each case and linear regression was performed. The resulting slope, the pulmonary metabolic radiation response (PMRR), was used to characterize the dose–response. The Common Toxicity Criteria version 3 was used to score clinical pulmonary toxicity symptoms. Receiver operating characteristic (ROC) curves were used to determine the level of FDG uptake vs. dose, MLD, V5, V10, V20, and V30 that can best predict symptomatic and asymptomatic patients. Results: The median time between radiotherapy completion and FDG-PET imaging was 59 days (range, 26–70 days). The median of the mean SUV from lung that received 0–5 Gy was 1.00 (range, 0.37–1.48), 5–10 Gy was 1.01 (range, 0.37–1.77), 10–20 Gy was 1.04 (0.42–1.53), and >20 Gy was 1.29 (range, 0.41–8.01). Using the dose range of 0 Gy to the maximum dose minus 10 Gy, hieraose minus 10 Gy, hierarchical linear regression model of the radiation dose and normalized FDG uptake per case found an adequate fit with the linear model. Pneumonitis scores were: Grade 0 for 13, Grade 1 for 5, Grade 2 for 6, and Grade 3, 4 or 5 for none. Using a PMRR threshold of 0.017 yields an associated true positive rate of 0.67 and false positive rate of 0.15 with average error of 30%. A V5 threshold of 57.6 gives an associated true positive rate of 0.67 and false positive rate of 0.05 with a 20% average error. Conclusion: The metabolic radiation pneumonitis dose–response was evaluated from post-treatment FDG-PET/CT imaging. Statistical modeling found a linear relationship. The FDG uptake dose–response and V5 correlated with symptomatic radiation pneumonitis.

  8. 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

  9. 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

  10. Some hybrid models applicable to dose-response relationships

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Scalable detection of statistically significant communities and hierarchies, using message passing for modularity.

    Science.gov (United States)

    Zhang, Pan; Moore, Cristopher

    2014-12-23

    Modularity is a popular measure of community structure. However, maximizing the modularity can lead to many competing partitions, with almost the same modularity, that are poorly correlated with each other. It can also produce illusory ''communities'' in random graphs where none exist. We address this problem by using the modularity as a Hamiltonian at finite temperature and using an efficient belief propagation algorithm to obtain the consensus of many partitions with high modularity, rather than looking for a single partition that maximizes it. We show analytically and numerically that the proposed algorithm works all of the way down to the detectability transition in networks generated by the stochastic block model. It also performs well on real-world networks, revealing large communities in some networks where previous work has claimed no communities exist. Finally we show that by applying our algorithm recursively, subdividing communities until no statistically significant subcommunities can be found, we can detect hierarchical structure in real-world networks more efficiently than previous methods. PMID:25489096

  14. Introduction of a new critical p value correction method for statistical significance analysis of metabonomics data.

    Science.gov (United States)

    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

  15. Using Socially Significant Examples To Contextualize Probability, Data Analysis, and Statistics for Pre-service Teachers.

    Science.gov (United States)

    Mathews, Susann

    2000-01-01

    Presents some examples illustrating the importance of probability, data analysis, and statistics for the preservice mathematics teacher, and suggests ways of teaching these topics. (Contains 13 references.) (ASK)

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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)

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

    International Nuclear Information System (INIS)

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

  19. Accounting for shared and unshared dosimetric uncertainties in the dose response for ultrasound-detected thyroid nodules after exposure to radioactive fallout.

    Science.gov (United States)

    Land, Charles E; Kwon, Deukwoo; Hoffman, F Owen; Moroz, Brian; Drozdovitch, Vladimir; Bouville, André; Beck, Harold; Luckyanov, Nicholas; Weinstock, Robert M; Simon, Steven L

    2015-02-01

    Dosimetic uncertainties, particularly those that are shared among subgroups of a study population, can bias, distort or reduce the slope or significance of a dose response. Exposure estimates in studies of health risks from environmental radiation exposures are generally highly uncertain and thus, susceptible to these methodological limitations. An analysis was published in 2008 concerning radiation-related thyroid nodule prevalence in a study population of 2,994 villagers under the age of 21 years old between August 1949 and September 1962 and who lived downwind from the Semipalatinsk Nuclear Test Site in Kazakhstan. This dose-response analysis identified a statistically significant association between thyroid nodule prevalence and reconstructed doses of fallout-related internal and external radiation to the thyroid gland; however, the effects of dosimetric uncertainty were not evaluated since the doses were simple point "best estimates". In this work, we revised the 2008 study by a comprehensive treatment of dosimetric uncertainties. Our present analysis improves upon the previous study, specifically by accounting for shared and unshared uncertainties in dose estimation and risk analysis, and differs from the 2008 analysis in the following ways: 1. The study population size was reduced from 2,994 to 2,376 subjects, removing 618 persons with uncertain residence histories; 2. Simulation of multiple population dose sets (vectors) was performed using a two-dimensional Monte Carlo dose estimation method; and 3. A Bayesian model averaging approach was employed for evaluating the dose response, explicitly accounting for large and complex uncertainty in dose estimation. The results were compared against conventional regression techniques. The Bayesian approach utilizes 5,000 independent realizations of population dose vectors, each of which corresponds to a set of conditional individual median internal and external doses for the 2,376 subjects. These 5,000 population dose vectors reflect uncertainties in dosimetric parameters, partly shared and partly independent, among individual members of the study population. Risk estimates for thyroid nodules from internal irradiation were higher than those published in 2008, which results, to the best of our knowledge, from explicitly accounting for dose uncertainty. In contrast to earlier findings, the use of Bayesian methods led to the conclusion that the biological effectiveness for internal and external dose was similar. Estimates of excess relative risk per unit dose (ERR/Gy) for males (177 thyroid nodule cases) were almost 30 times those for females (571 cases) and were similar to those reported for thyroid cancers related to childhood exposures to external and internal sources in other studies. For confirmed cases of papillary thyroid cancers (3 in males, 18 in females), the ERR/Gy was also comparable to risk estimates from other studies, but not significantly different from zero. These findings represent the first reported dose response for a radiation epidemiologic study considering all known sources of shared and unshared errors in dose estimation and using a Bayesian model averaging (BMA) method for analysis of the dose response. PMID:25574587

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

    International Nuclear Information System (INIS)

    In order to make correct predictions of the second moment of statistical nuclear variables, such as the number of fissions and the number of thermalized neutrons, the dependence of the energy distribution of the source particles on their number should be considered. It has been pointed out recently that neglecting this number dependence in accelerator driven systems might result in bad estimates of the second moment, and this paper contains qualitative and quantitative estimates of the size of these efforts. We walk towards the requested results in two steps. First, models of the number dependent energy distributions of the neutrons that are ejected in the spallation reactions are constructed, both by simple assumptions and by extracting energy distributions of spallation neutrons from a high-energy particle transport code. Then, the second moment of nuclear variables in a sub-critical reactor, into which spallation neutrons are injected, is calculated. The results from second moment calculations using number dependent energy distributions for the source neutrons are compared to those where only the average energy distribution is used. Two physical models are employed to simulate the neutron transport in the reactor. One is analytical, treating only slowing down of neutrons by elastic scattering in the core material. For this model, equations are written down and solved for the second moment of thermalized neutrons that include the distribution of energy of the spallation neutrons. The other model utilizes Monte Carlo methods for tracking the source neutrons as they travel inside the reactor material. Fast and thermal fission reactions are considered, as well as neutron capture and elastic scattering, and the second moment of the number of fissions, the number of neutrons that leaked out of the system, etc. are calculated. Both models use a cylindrical core with a homogenous mixture of core material. Our results indicate that the number dependence of the energy distribution of the spallation neutrons leads to second moments that differ significantly from the ones calculated with the average energy distribution only. With the most realistic model of the energy distributions, the second moment of the number of fissions was underestimated with 12-16%

  1. Are Patterns in Paleo-Hurricane Landfalls Significant? Statistical Comparisons with Modeled Hurricane Climatology

    Science.gov (United States)

    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.

  2. The use of mode of action information in risk assessment: quantitative key events/dose-response framework for modeling the dose-response for key events.

    Science.gov (United States)

    Simon, Ted W; Simons, S Stoney; Preston, R Julian; Boobis, Alan R; Cohen, Samuel M; Doerrer, Nancy G; Fenner-Crisp, Penelope A; McMullin, Tami S; McQueen, Charlene A; Rowlands, J Craig

    2014-08-01

    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. PMID:25070415

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

    Science.gov (United States)

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

    2015-02-01

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10g/kg DEG and blood, kidney and liver tissues were collected at 48h. Both rat strains treated with 10g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10g/kg DEG, but no DGA was present at 2 or 5g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. PMID:25545985

  4. Reliability of the ADI-R for the single case-part II: clinical versus statistical significance.

    Science.gov (United States)

    Cicchetti, Domenic V; Lord, Catherine; Koenig, Kathy; Klin, Ami; Volkmar, Fred R

    2014-12-01

    In an earlier investigation, the authors assessed the reliability of the ADI-R when multiple clinicians evaluated a single case, here a female 3 year old toddler suspected of having an autism spectrum disorder (Cicchetti et al. in J Autism Dev Disord 38:764-770, 2008). Applying the clinical criteria of Cicchetti and Sparrow (Am J Men Def 86:127-137, 1981); and those of Cicchetti et al. (Child Neuropsychol 126-137, 1995): 74 % of the ADI-R items showed 100 % agreement; 6 % showed excellent agreement; 7 % showed good agreement; 3 % manifested average agreement; and the remaining 10 % evidenced poor agreement. In this follow-up investigation, the authors described and applied a novel method for determining levels of statistical significance of the reliability coefficients obtained in the earlier investigation. It is based upon a modification of the Z test for comparing a given level of inter-examiner reliability with a lower limit value of 70 % (Dixon and Massey in Introduction to statistical analysis. McGraw-Hill, New York, 1957). Results indicated that every item producing a clinically acceptable level of inter-examiner reliability was also statistically significant. However, the reverse was not true, since a number of the items with statistically significant reliability levels did not reach levels of agreement that were clinically meaningful. This indicated that clinical significance was an accurate marker of statistical significance. The generalization of these findings to other areas of diagnostic interest and importance is also examined. PMID:24996869

  5. Linear dose response curves in fungi and tradescantia

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Highlights: ? We describe an exposure–dose–response approach for assessing cadmium exposure in Anadara trapezia. ? Accumulated cadmium was detoxified in metallothionein like proteins or as active metal in mitochondria. ? Increased cadmium dose resulted in a reduction in total antioxidant capacity, decreased lysosomal stability and genotoxic damage. ? 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 ?g/g and 50 ?g/g dry mass) for 56 days. A. trapezia reached an equilibrium cadmium tissue concentration (13 ?g/g and 25 ?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 cin 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    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 – t...

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

    OpenAIRE

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

    2010-01-01

    We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program’s performance in reproducing the actual values that were use...

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

    OpenAIRE

    Sadreyev Ruslan I; Grishin Nick V

    2004-01-01

    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 ...

  13. Dose-response patterns of Radix Glycyrrhizae in Shanghan Lun

    Directory of Open Access Journals (Sweden)

    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.

  14. Mutans streptococci dose response to xylitol chewing gum.

    Science.gov (United States)

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

    2006-02-01

    Xylitol is promoted in caries-preventive strategies, yet its effective dose range is unclear. This study determined the dose-response of mutans streptococci in plaque and unstimulated saliva to xylitol gum. Participants (n = 132) were randomized: controls (G1) (sorbitol/maltitol), or combinations giving xylitol 3.44 g/day (G2), 6.88 g/day (G3), or 10.32 g/day (G4). Groups chewed 3 pellets/4 times/d. Samples were taken at baseline, 5 wks, and 6 mos, and were cultured on modified Mitis Salivarius agar for mutans streptococci and on blood agar for total culturable flora. At 5 wks, mutans streptococci levels in plaque were 10x lower than baseline in G3 and G4 (P = 0.007/0.003). There were no differences in saliva. At 6 mos, mutans streptococci in plaque for G3 and G4 remained 10x lower than baseline (P = 0.007/0.04). Saliva for G3 and G4 was lower than baseline by 8 to 9x (P = 0.011/0.038). Xylitol at 6.44 g/day and 10.32 g/day reduces mutans streptococci in plaque at 5 wks, and in plaque and unstimulated saliva at 6 mos. A plateau effect is suggested between 6.44 g and 10.32 g xylitol/day. PMID:16434738

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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.

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

    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.

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

    International Nuclear Information System (INIS)

    Purpose: To better define the appropriate dose for individual prostate cancer patients treated with three-dimensional conformal radiation therapy (3D CRT). Methods and Materials: Six hundred eighteen patients treated with 3D CRT between 4/89 and 4/97 with a median follow-up of 53 months are the subject of this study. The bNED outcomes were assessed by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. The patients were grouped into three groups by prostate-specific antigen (PSA) level (<10 ng/ml, 10-19.9 ng/ml, and 20+ ng/ml) and further subgrouped into six subgroups by favorable (T1, 2A and Gleason score ?6 and no perineural invasion) and unfavorable characteristics (one or more of T2B, T3, Gleason 7-10, perineural invasion). Dose comparisons for bNED studies were made for each of the six subgroups by dividing patients at 76 Gy for all subgroups except the favorable <10 ng/ml subgroup, which was divided at 72.5 Gy. Five-year bNED rates were compared for the median dose of each dose comparison subgroup. Dose response functions were plotted based on 5-year bNED rates for the six patient groupings, with the data from each of the six subgroups divided into three dose groups. The 5-year bNED rate was also estimated using the dose response function and compares 73 Gy with 78 Gy. Results: Dose comparisons show a significant difference in 5-year bNED rates for three of the six subgroups but not for the favorable <10 ng/ml, the favorable 10-19.9vorable <10 ng/ml, the favorable 10-19.9 ng/ml, or the unfavorable ?20 ng/ml subgroups. The significant differences ranged from 22% to 40% improvement in 5-year bNED with higher dose. Dose response functions show significant differences in 5-year bNED rates comparing 73 Gy and 78 Gy for four of the six subgroups. Again, no difference was observed for the favorable <10 ng/ml group or the unfavorable ?20 ng/ml group. The significant differences observed in 5-year bNED ranged from 15% to 43%. Conclusions: Dose response varies by patient subgroup, and appropriate dose can be estimated for up to six subdivisions of prostate cancer patients. The appropriate use of high dose with 3D CRT results in 5-year cure rates that equal or exceed other treatments. The national practice must be upgraded to allow the safe administration of 75-80 Gy with 3D CRT

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

    International Nuclear Information System (INIS)

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

  20. Beetroot juice and exercise: pharmacodynamic and dose-response relationships.

    Science.gov (United States)

    Wylie, Lee J; Kelly, James; Bailey, Stephen J; Blackwell, Jamie R; Skiba, Philip F; Winyard, Paul G; Jeukendrup, Asker E; Vanhatalo, Anni; Jones, Andrew M

    2013-08-01

    Dietary supplementation with beetroot juice (BR), containing approximately 5-8 mmol inorganic nitrate (NO3(-)), increases plasma nitrite concentration ([NO2(-)]), reduces blood pressure, and may positively influence the physiological responses to exercise. However, the dose-response relationship between the volume of BR ingested and the physiological effects invoked has not been investigated. In a balanced crossover design, 10 healthy men ingested 70, 140, or 280 ml concentrated BR (containing 4.2, 8.4, and 16.8 mmol NO3(-), respectively) or no supplement to establish the effects of BR on resting plasma [NO3(-)] and [NO2(-)] over 24 h. Subsequently, on six separate occasions, 10 subjects completed moderate-intensity and severe-intensity cycle exercise tests, 2.5 h postingestion of 70, 140, and 280 ml BR or NO3(-)-depleted BR as placebo (PL). Following acute BR ingestion, plasma [NO2(-)] increased in a dose-dependent manner, with the peak changes occurring at approximately 2-3 h. Compared with PL, 70 ml BR did not alter the physiological responses to exercise. However, 140 and 280 ml BR reduced the steady-state oxygen (O2) uptake during moderate-intensity exercise by 1.7% (P = 0.06) and 3.0% (P < 0.05), whereas time-to-task failure was extended by 14% and 12% (both P < 0.05), respectively, compared with PL. The results indicate that whereas plasma [NO2(-)] and the O2 cost of moderate-intensity exercise are altered dose dependently with NO3(-)-rich BR, there is no additional improvement in exercise tolerance after ingesting BR containing 16.8 compared with 8.4 mmol NO3(-). These findings have important implications for the use of BR to enhance cardiovascular health and exercise performance in young adults. PMID:23640589

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

    International Nuclear Information System (INIS)

    Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 ?g/kg I to the base diet (?25 ?g I/kg chow) to produce 5 nominal I levels, ranging from excess (basal + added I, Treatment 1: 1000 ?g I/kg chow) to deficient (Treatment 5: 25 ?g I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation.

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2006-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-21

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

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

    Science.gov (United States)

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

    2014-07-01

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

  8. Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study.

    Science.gov (United States)

    Ouwehand, Arthur C; DongLian, Cai; Weijian, Xu; Stewart, Morgan; Ni, Jiayi; Stewart, Tad; Miller, Larry E

    2014-01-16

    Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU(®) Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n=503) were randomized among three study groups: HOWARU(®) Restore probiotic 1.70×10(10) CFU (high-dose, n=168), HOWARU(®) Restore probiotic 4.17×10(9) CFU (low-dose, n=168), or placebo (n=167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p=0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p=0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients. PMID:24291194

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-05-01

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

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

    OpenAIRE

    Sawan, Zakaria M.

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2009-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Taylor, Anne M; Maher, William A

    2012-03-01

    The relationship between cadmium exposure dose and response was investigated in Anadara trapezia exposed to cadmium spiked sediment (10 ?g/g and 50 ?g/g dry mass) for 56 days. A. trapezia reached an equilibrium cadmium tissue concentration (13 ?g/g and 25 ?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. PMID:22014600

  17. Exposure-dose-response of Anadara trapezia to metal contaminated estuarine sediments: 3. Selenium spiked sediments.

    Science.gov (United States)

    Taylor, Anne M; Maher, William A

    2012-11-15

    Selenium enters near shore marine environments from the activities of coal-fired power stations. Although selenium is an essential element, at elevated concentrations it can cause genotoxic damage. The relationship between selenium exposure dose and response was investigated in Anadara trapezia exposed to selenium spiked sediment (5 ?g/g and 20 ?g/g dry mass) for 56 days. A. trapezia reached an equilibrium selenium tissue concentration (2 ?g/g and 10 ?g/g respectively) by day 42. Gills had significantly more selenium than the hepatopancreas and haemolymph. Between 12 and 21% of accumulated selenium in the gill and hepatopancreas was detoxified and in the metal rich granule. Most of the biologically active selenium in both tissues was in the mitochondrial fraction. Glutathione peroxidase activity and mean total glutathione concentrations for selenium exposed organisms were not significantly different to controls. The ratio of reduced to oxidised glutathione and the total antioxidant capacity were significantly reduced in selenium exposed organisms compared to control organisms. Increased selenium exposure resulted in significant increases in lipid peroxidation, lysosomal destabilisation and an increased frequency of micronuclei. A significant exposure-dose-response relationship for A. trapezia exposed to selenium enriched sediments indicates that elevated sediment selenium concentrations can increased biologically active selenium burdens and cause impairment of cellular processes and cell integrity. PMID:22963858

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Russell Steven

    2010-06-01

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

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

    International Nuclear Information System (INIS)

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

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

    CERN Document Server

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, B.L.

    1987-05-01

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

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

    Science.gov (United States)

    Casati, Michele

    2014-05-01

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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Buchanan, R. L.; Havelaar, A. H.; Smith, M. A.; Whiting, R. C.; Julien, Elizabeth

    2009-01-01

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

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

    OpenAIRE

    Cardozo Linda; Khullar Vik; El-Tahtawy Ahmed; Guan Zhonghong; Malhotra Bimal; Staskin David

    2010-01-01

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

  7. The acute radiation dose-response mortality function and accident dosimetry

    International Nuclear Information System (INIS)

    Recent determinations of the dose-response function correlating acute whole-body radiation dose with expected incidence of early mortality are reviewed. Methodologies are compared, and an updated dose-response function is nominated. The incertainity in this functions is shown to have important implications with regard to the accuracy neccessary in accident dosimetry for useful mortality prognosis. 11 refs., 2 tabs., 6 figs

  8. Dose-response study of spinal hyperbaric ropivacaine for cesarean section

    OpenAIRE

    Chen, Xin-zhong; Chen, Hong; Lou, Ai-fei; Lu?, Chang-cheng

    2006-01-01

    Background: Spinal hyperbaric ropivacaine may produce more predictable and reliable anesthesia than plain ropivacaine for cesarean section. The dose-response relation for spinal hyperbaric ropivacaine is undetermined. This double-blind, randomized, dose-response study determined the ED50 (50% effective dose) and ED95 (95% effective dose) of spinal hyperbaric ropivacaine for cesarean section anesthesia. Methods: Sixty parturients undergoing elective cesarean section delivery with use of combin...

  9. The shape of the dose-response curve and the saturation of the Elkind repair

    International Nuclear Information System (INIS)

    The authors propose a model for the maximum repair factor which is independent of the saturation effect of the maximum Elkind repair, and present experimental dose-response curves for the survival rates of V-79 cells for comparison. It is pointed out that the parabolic shape of the dose-response curve makes it possible to explain the progressive weakening of the CFU of the surviving cells which goes on with increasing dose. (U.K.)

  10. Use of Tests of Statistical Significance and Other Analytic Choices in a School Psychology Journal: Review of Practices and Suggested Alternatives.

    Science.gov (United States)

    Snyder, Patricia A.; Thompson, Bruce

    The use of tests of statistical significance was explored, first by reviewing some criticisms of contemporary practice in the use of statistical tests as reflected in a series of articles in the "American Psychologist" and in the appointment of a "Task Force on Statistical Inference" by the American Psychological Association (APA) to consider…

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2009-12-01

    In support of the U.S. Tox21 program, we have developed a simple and chemically intuitive model we call weighted feature significance (WFS) to predict the toxicological activity of compounds, based on the statistical enrichment of structural features in toxic compounds. We trained and tested the model on the following: (1) data from quantitative high-throughput screening cytotoxicity and caspase activation assays conducted at the National Institutes of Health Chemical Genomics Center, (2) data from Salmonella typhimurium reverse mutagenicity assays conducted by the U.S. National Toxicology Program, and (3) hepatotoxicity data published in the Registry of Toxic Effects of Chemical Substances. Enrichments of structural features in toxic compounds are evaluated for their statistical significance and compiled into a simple additive model of toxicity and then used to score new compounds for potential toxicity. The predictive power of the model for cytotoxicity was validated using an independent set of compounds from the U.S. Environmental Protection Agency tested also at the National Institutes of Health Chemical Genomics Center. We compared the performance of our WFS approach with classical classification methods such as Naive Bayesian clustering and support vector machines. In most test cases, WFS showed similar or slightly better predictive power, especially in the prediction of hepatotoxic compounds, where WFS appeared to have the best performance among the three methods. The new algorithm has the important advantages of simplicity, power, interpretability, and ease of implementation. PMID:19805409

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

    CERN Document Server

    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...

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

    Directory of Open Access Journals (Sweden)

    Peter Waylen

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    E. M. Dunne

    2012-06-01

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

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

    Science.gov (United States)

    Taylor, Anne M; Maher, William A

    2014-11-01

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

  17. The exercise dose response: key lessons from the past

    Science.gov (United States)

    Marcas M Bamman (University of Alabama at Birmingham Physiology and Biophysics)

    2007-12-26

    This essay looks at the historical significance of an APS classic paper that is freely available online: Fitts RH, Booth FW, Winder WW, Holloszy JO. Skeletal muscle respiratory capacity, endurance, and glycogen utilization.

  18. Low dose response analysis through a cytogenetic end-point

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

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

    2008-01-01

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

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

    International Nuclear Information System (INIS)

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

  2. Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study.

    Science.gov (United States)

    Miyauchi, Akimitsu; Matsumoto, Toshio; Shigeta, Hirofumi; Tsujimoto, Mika; Thiebaud, Daniel; Nakamura, Toshitaka

    2008-01-01

    The dose-response efficacy and safety with three doses of teriparatide and placebo was assessed, using once-daily subcutaneous injections for 24 weeks, in Japanese postmenopausal women with osteoporosis at high risk of fracture for reasons of preexisting fracture(s), advanced age, and/or low bone mineral density (BMD). In this multicenter, randomized, placebo-controlled study, 159 subjects were randomized and 154 subjects were included for analysis. Teriparatide (10-microg, 20-microg, and 40-microg doses) showed a statistically significant increase with increasing treatment dose as assessed by the percent change of lumbar spine BMD from baseline to endpoint using Williams' test when compared with placebo (P Rapid and sustained increases in bone formation markers [type I procollagen N-terminal propeptide (PINP), type I procollagen C-terminal propeptide (PICP), and bone-specific alkaline phosphatase (BAP)], followed by late increases in a bone resorption marker [type I collagen cross-linked C-telopeptide (CTX)], were observed for the teriparatide treatment groups (20-microg, 40-microg), suggesting a persistent, positive, balanced anabolic effect of teriparatide. Optimal adherence was achieved by this daily self-injection treatment. Regarding safety, most of the adverse events were mild to moderate in severity. No study drug-or study procedure-related serious adverse events were reported during the treatment period. These results observed in Japanese patients may support the observation that teriparatide stimulates bone formation in patients with osteoporosis at a high risk of fracture. PMID:18979163

  3. Dose-response algorithms for water-borne Pseudomonas aeruginosa folliculitis.

    Science.gov (United States)

    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

  4. Statistical Methods for Selecting Maximum Effective Dose and Evaluating Treatment Effect When DoseResponse is Monotonic

    OpenAIRE

    Kong, Maiying; Rai, Shesh N.; Bolli, Roberto

    2014-01-01

    The maximum effective dose (MaxED) is an important quantity for therapeutic drugs. The MaxED for therapeutic drugs is defined as the dose above which no improvement in efficacy is obtained. In this article, we propose two experimental designs and analytic methods (one single-stage design and one two-stage design) to select the MaxED among several fixed doses and to compare the therapeutic effect of the selected MaxED with a control. The selection of MaxED is based on the iso...

  5. A resource conservative procedure for comparison of dose-response relationships

    Science.gov (United States)

    Link, W.A.; Hill, E.F.; Hines, J.E.; Henry, P.F.P.

    1996-01-01

    The evaluation of effects of toxicants on a wildlife community can be complicated by varying responses among the community's constituent populations. Even within populations, considerable variability in dose-response relations may result from different avenues of exposure to the toxicant. Full scale investigations of the dose-response relations among a variety of species and avenues of exposure can therefore be prohibitively expensive, whether this expense is measured by the number of experimental animals needed, by the human resources committed to the study, or by laboratory expenses. We propose an abbreviated protocol for investigations of multiple dose-response relations that is designed to limit these expenses. The protocol begins with the judicious choice of a baseline dose-response relation to be estimated by a full scale study involving a minimum of 5 doses levels, with 10 subjects per dose level. This relation is then used as the basis for rapid screening of subsequent dose-response relations, which are compared to the baseline relation by testing for differences in the median effective dosages. These secondary studies can consist of as few as 14 animals exposed to the estimated LC50 from the baseline study. We describe MS-DOS compatible software available from the authors which can be used to analyze these data.

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

    International Nuclear Information System (INIS)

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

  7. Double-blind evaluation of the dose-response relationship of amlodipine in essential hypertension.

    Science.gov (United States)

    Mehta, J L; Lopez, L M; Vlachakis, N D; Gradman, A H; Nash, D T; O'Connell, M T; Garland, W T; Pickering, B I

    1993-06-01

    To determine the dose-response efficacy of once-daily administration of placebo or a new long-acting calcium channel blocker amlodipine in patients with mild to moderate hypertension, a randomized, multicenter, placebo-controlled, double-blind trial was conducted. The study included 210 patients with diastolic hypertension (blood pressure 95 to 114 mm Hg) without major hematologic, renal, hepatic, cardiac, or endocrine abnormalities. After a 4-week single-blind placebo run-in period, patients were given placebo or amlodipine (1.25, 2.5, 5, or 10 mg) daily for 4 weeks. To assess the antihypertensive effect of amlodipine over a 24-hour period, blood pressure and pulse rate at weeks 0 and 4 were recorded for 12 hours after the dose and then again at 24 hours. At the end of the study patients treated with all doses of amlodipine greater than 1.25 mg daily had significantly reduced diastolic blood pressure in both supine and standing than 1.25 mg daily had significantly reduced diastolic blood pressure in both supine and standing positions. Amlodipine, 1.25 mg daily, was also associated with a decrease in standing diastolic blood pressure. Response to treatment was greater in all amlodipine-treated patients than in those receiving placebo. Pulse rate in both the supine and standing positions was not significantly affected by amlodipine. At doses of 2.5, 5.0, or 10.0 mg daily, amlodipine maintained blood pressure below values obtained with placebo throughout the 24-hour period. Treatment with amlodipine was well tolerated and the incidence of side effects was low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8498314

  8. Exposure-dose-response of Anadara trapezia to metal contaminated estuarine sediments. 2. Lead spiked sediments.

    Science.gov (United States)

    Taylor, Anne M; Maher, William A

    2012-07-15

    The composition of near shore marine environments is increasingly being altered by contaminants from human activities. The ability of lead, which has no known biological function, to mimic biologically essential metals makes it one of the most toxic to marine biota. The relationship between lead exposure, dose and response was investigated in Anadara trapezia exposed for 56 days to lead spiked sediment (100 and 300 ?g/g dry mass). Lead tissue concentrations of the 300 ?g/g exposed A. trapezia doubled in the last 2 weeks of exposure with final lead tissue concentrations of exposed organisms of 1 and 12 ?g/g, respectively. Tissue lead accumulation of exposed organisms followed the pattern haemolymph>gill>hepatopancreas during much of the 56 day exposure. Between 30 and 69% of accumulated lead in the gill and hepatopancreas was detoxified and fairly evenly distributed between the metal rich granule and the metallothionein like protein fractions. Approximately half of the biologically active lead in both tissues was in the mitochondrial fraction which showed increased cytochrome c oxidase activity in lead exposed organisms. There was a reduction in GPx activity, an associated increase in total glutathione concentrations and reduced GSH:GSSG ratios due to a build up of oxidised glutathione. These changes in the glutathione pathway were reflected in the total antioxidant capacity of lead exposed A. trapezia which were significantly reduced compared to control organisms. Increased lead exposure significantly increased lipid peroxidation, lysosomal destabilisation and frequency of micronuclei. A significant exposure-dose-response relationship for A. trapezia exposed to lead enriched sediments indicates that elevated sediment lead concentrations have the potential to increase biologically active lead burdens and impair the antioxidant reduction capacity leading to a series of associated effects from lipid peroxidation to cellular perturbation and genotoxic damage. PMID:22466358

  9. Dose-response relationship for induction of solid tumors in female B6C3F1 mice irradiated neonatally with a single dose of gamma rays

    International Nuclear Information System (INIS)

    Our previous studies showed that mice during infancy are highly susceptible to the induction of several types of solid tumors. The present study was designed to elucidate the dose-response relationships for induction of solid tumors after exposure to 0.48-5.70 Gy of 137Cs gamma rays in the neonatal period in female mice. A total of 2988 mice were allowed to live out their life span under a specific pathogen free condition and life time incidences of liver, pituitary, ovarian, lung and bone tumors were recorded. The dose-response curves for liver, pituitary, ovarian and lung tumors were convex upward in the dose range examined, and were composed of three parts: an initial rapid increase of incidence at doses below 1 Gy, a gradual increase to the highest incidence, and a decrease in incidence with increasing dose in the higher dose range. The dose which induces neoplasm at the highest incidence seemed to be different for each type of solid tumor. The shape of the dose-response curve for induction of bone tumors was quite different from that for other solid tumors; the initial slope of the curve was concave upward. Dose-response relationships were analyzed using a model that allows for tumorigenic effect, inactivation of potentially tumorigenic cells and competing risks. The results showed that the tumorigenic effect was proportional to the dose of gamma rays for induction of liver, pituitary, ovarian and lung tumors; whereas the tumorigenic effect for bone tuwhereas the tumorigenic effect for bone tumors was proportional to the square of the dose. A significant increase in incidence was also found for gastrointestinal tumors, kidney tumors, adrenal tumors and hemangiomas of spleen, although dose-response relationships could not be analyzed. (author)

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

    CERN Document Server

    Østvand, Lene; Rypdal, Martin

    2013-01-01

    Various interpretations of the notion of a trend in the context of global warming are discussed, contrasting the difference between viewing a trend as the deterministic response to an external forcing and viewing it as a slow variation which can be separated from the background spectral continuum of long-range persistent climate noise. The emphasis in this paper is on the latter notion, and a general scheme is presented for testing a multi-parameter trend model against a null hypothesis which models the observed climate record as an autocorrelated noise. The scheme is employed to the instrumental global sea-surface temperature record and the global land-temperature record. A trend model comprising a linear plus an oscillatory trend with period of approximately 60 yr, and the statistical significance of the trends, are tested against three different null models: first-order autoregressive process, fractional Gaussian noise, and fractional Brownian motion. The linear trend is significant in all cases, but the o...

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

    Science.gov (United States)

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

    2013-01-01

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

  12. Bovine Staphylococcus aureus: dose response to iodine and chlorhexidine and effect of iodine challenge on antibiotic susceptibility.

    Science.gov (United States)

    Azizoglu, Reha Onur; Lyman, Roberta; Anderson, Kevin L

    2013-02-01

    Staphylococcus aureus is a gram-positive organism that is frequently associated with clinical or subclinical mastitis. The use of germicidal teat dips is one of the measures taken by the dairy industry to control mastitis. Iodine and chlorhexidine compounds are commonly used disinfectants in teat dips. We determined the minimum inhibitory concentrations (MIC) of iodine for 37 isolates of Staph. aureus and observed variations in MIC. Seven of these Staph. aureus isolates were selected as genotype group representatives based on their pulsed-field gel electrophoresis patterns. Dose responses against iodine and chlorhexidine were determined for the 7 genotype group representatives. The response of these isolates to iodine varied significantly, whereas all isolates were susceptible to chlorhexidine, even at concentrations as low as 0.0002%. We also evaluated whether exposure of Staph. aureus to sublethal levels of iodine influenced subsequent antibiotic susceptibility. No differences in antibiotic susceptibility of Staph. aureus were observed among cultures grown in brain heart infusion broth with and without supplemental iodine. The observed variation in iodine dose responses of Staph. aureus may have implications for the occurrence of Staph. aureus mastitis on dairy farms. PMID:23261384

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

    OpenAIRE

    Little, M. P.; Muirhead, C. R.

    1997-01-01

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

  14. Dose response of Cryptosporidium parvum in outbred neonatal CD-1 mice.

    OpenAIRE

    Finch, G. R.; Daniels, C. W.; Black, E. K.; Schaefer, F. W.; Belosevic, M.

    1993-01-01

    Cryptosporidium parvum infectivity in a neonatal CD-1 mouse model was used to determine the dose needed to infect 50% of the population. The 50% infective dose was estimated to be 79 oocysts. It was observed that a mean oral inoculum of 23 oocysts produced infection in 2 of 25 neonatal mice 7 days postinoculation. All animals became infected when the mean oral dose exceeded 310 oocysts per animal. The dose response of C. parvum was modeled with a logit dose-response model suitable for use in ...

  15. Quantitative mechanistically based dose-response modeling with endocrine-active compounds.

    OpenAIRE

    Andersen, M. E.; Conolly, R. B.; Faustman, E. M.; Kavlock, R. J.; Portier, C. J.; Sheehan, D. M.; Wier, P. J.; Ziese, L.

    1999-01-01

    A wide range of toxicity test methods is used or is being developed for assessing the impact of endocrine-active compounds (EACs) on human health. Interpretation of these data and their quantitative use in human and ecologic risk assessment will be enhanced by the availability of mechanistically based dose-response (MBDR) models to assist low-dose, interspecies, and (italic)in vitro(/italic) to (italic)in vivo(/italic) extrapolations. A quantitative dose-response modeling work group examined ...

  16. Chicken anti-rat lymphocyte globulin: dose response study and determination of strain-specific alloantibody.

    Science.gov (United States)

    Morris, R E

    1979-08-01

    Chicken anti-rat lymphocyte globulin (CARLG) is a new and uniquely specific immunosuppressant for which the mechanisms of immunosuppressive action are not yet known. This study defines its in vivo therapeutic dose range and in vitro allospecificity. A dose response study, using CARLG or normal chicken globulin (NCG), as the sole immunosuppressant, was conducted in Lewis (Ag-B1) recipients of Buffalo (Ag-B6) rat cardiac allografts. Groups of Lewis recipients were treated with 175 mg of NCG per kg or 30, 100, 175, or 300 mg of CARLG per kg for the first 8 post-transplant days. Doses of 175 and 300 mg of CARLG per kg resulted in significantly longer (P less than 0.01) prolongation of graft survival than doses of 30 and 100 mg of CARLG per kg, which were not significantly different (P less than 0.05) in their ability to prolong graft survival than a dose of 175 mg of NCG per kg. In vitro and in vivo absorption studies revealed that CARLG does not contain strain-specific alloantibody. When Lewis lymphoid cells were used to absorb, in vitro, a batch of CARLG produced with Brown Norway (Ag-B3) lymphoid cells as immunogen, all antibody activity toward Brown Norway cells as quantitated by a two-stage lymphocytotoxicity assay was completely removed. In another experiment, a preparation of CARLG, produced using Buffalo lymphoid cells as immunogen, underwent in vivo absorption as a result of i.v. injection into Lewis rats. Serum levels of CARLG-binding activity to Lewis or Buffalo lymphoid cells were quantitated in vitro at intervals after injection by an isotopic antiglobulin assay. Lewis rat tissues were able to remove completely serum CARLG-binding activity toward Buffalo antigens. A mechanism of action for CARLG derived from these observations is proposed and discussed. PMID:384623

  17. Dose-response relationships for female radium dial workers

    International Nuclear Information System (INIS)

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

  18. 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transforma...

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

    International Nuclear Information System (INIS)

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

  4. An evaluation of the dose-response relationship of fluoride injury to Gladiolus

    Science.gov (United States)

    Coulter, C. Thomas; Pack, Merrill R.; Sulzbach, Charles W.

    Experiments were conducted with Gladiolus to evaluate the dose-response relationship of F - injury to plants. In two experiments (Group I), plants were intermittently exposed to HF in different patterns of period length and frequency (24-384 h) with the mean HF concentrations and cumulative doses (concentration x duration) being similar among the treatments in each experiment. In another series of experiments (Group II), plants were continuously exposed to similar HF doses applied in widely different combinations of concentration (3-86 ?g F m -3) and duration (384-12 h). Leaf necrosis, as a percentage of the total leaf area of the plant, was used as the index of F - injury, and to facilitate its estimation, a mathematical model was developed relating lineal distance from the leaf tip to the area of the corresponding part of the leaf. In one of the Group I experiments (at 2.0 ?g F m -3) no significant differences in response were found between treatments. In the other experiment (at 2.9 ?g F m -3) less foliar necrosis was produced by the shorter duration, more frequent exposure treatments than by longer, less frequent exposures, inferring some degree of recovery for plants under the former conditions. In the Group II experiments no consistent relationship was found between the amount of foliar necrosis and the HF treatment concentration or duration. The range of responses in both Groups of experiments was much less than the range of the exposure conditions, which indicates a much closer relationship of F - injury to exposure dose than to the concentration, duration, or frequency of exposure.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-31

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

  7. Mechanistic interpretation of radiation dose-response relationship for subclinical metastasis

    International Nuclear Information System (INIS)

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

  8. Dopamine natriuresis in salt-repleted, water-loaded humans : a dose-response study

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Olsen, M H

    1997-01-01

    The purpose of the present study was to define the dose-response relationship between exogenous dopamine and systemic haemodynamics, renal haemodynamics, and renal excretory function at infusion rates in the range 0 to 12.5 microg kg(-1) min(-1) in normal volunteers.

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

    Science.gov (United States)

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

    2003-01-01

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

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

    Science.gov (United States)

    Steinman, Kenneth J.; Ferketich, Amy K.; Sahr, Timothy

    2008-01-01

    This article addresses two inconsistent findings in the literature on adolescent religious activity (RA) and substance use: whether a dose-response relationship characterizes the association of these variables, and whether the association varies by grade, gender, ethnicity, family structure, school type, and type of substance. Multinomial logistic…

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

    Science.gov (United States)

    Rankinen, Tuomo; Bouchard, Claude

    2002-01-01

    This paper categorizes the many benefits of physical activity, offering information concerning the type of dose necessary to get that benefit. In 2000, Health Canada and the United States Centers for Disease Control and Prevention, along with other agencies, sponsored a symposium to determine whether there was a dose-response relationship between…

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

    International Nuclear Information System (INIS)

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

  13. 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

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

    DEFF Research Database (Denmark)

    Torekov, Signe SØrensen; Kipnes, M S

    2011-01-01

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

  15. Toxicokinetics to identify nonlinearities in dose-response and implications for risk assessment

    Science.gov (United States)

    For presentation at the 45th Annual Symposium of the Society of Toxicology of Canada. The meeting will be held on 4-5 December 2013 at the Ottawa Convention Centre. Toxicokinetics to identify nonlinearities in dose-response and implications for risk assessment. Rory Conolly, Offi...

  16. Dose-response measurement in gel dosimeter using various imaging modalities

    Science.gov (United States)

    Fujibuchi, T.; Kawamura, H.; Yamanashi, K.; Hiroki, A.; Yamashita, S.; Taguchi, M.; Sato, Y.; Mimura, K.; Ushiba, H.; Okihara, T.

    2013-06-01

    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.

  17. Statistics

    CERN Document Server

    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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-15

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

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

    International Nuclear Information System (INIS)

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

  1. Dose-response relation between exposure to two types of hand-arm vibration and sensorineural perception of vibration.

    Science.gov (United States)

    Virokannas, H

    1995-01-01

    OBJECTIVES--31 railway workers and 32 lumberjacks were examined to compare the dose-response relation between the exposure to two types of hand-arm vibration and the sensory disturbances in peripheral nerves as evaluated by the vibration perception thresholds (VPTs). METHODS--Clinical examinations were carried out that included measurements of the VPTs, and electroneuromyography (ENMG), and an inquiry to confirm the use of vibrating tools. Diseases of the central nervous system and neuropathies were checked by inquiry and a clinical examination, diabetes was excluded by a blood sample analysis, and the subjects with carpal tunnel syndrome confirmed with ENMG were excluded from the study. RESULTS--Lifetime use of hand held tamping machines (railway workers) and chain saws (lumberjacks) had a significant correlation with the VPTs at frequencies from 32 to 500 Hz. The increase of the VPTs (250 Hz) in relation to use of vibrating tools was 1.8-fold higher on average in the whole group and 2.3-fold higher in the young (< 45) railway workers who had used hand held tamping machines, than in the corresponding groups of lumberjacks, who had used chain saws, whereas the frequency weighted acceleration of vibration in tamping machines was fourfold. CONCLUSION--There was a significant dose-response relation between the exposure to hand-arm vibration and the VPTs. The VPTs as a function of the frequency weighted acceleration of vibration and the exposure to vibration gave promising results for assessment of the risk of damage to sensory nerves induced by vibration. PMID:7795756

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

    OpenAIRE

    Mukherjee, T.; Shinde, Santosh H.

    2011-01-01

    Glycine dosimeter based on spectrophotometric read-out method has great potential for gamma dosimetry in low dose applications of radiation processing. However, external factors such as relative humidity, dose rate, and dose fractionation, may have a profound effect on its gamma dose response Influence of these factors on the gamma dose response of glycine dosimeter was studied in the present work.

  3. Temperature dependence of the dose response for a solid-state radiochromic dosimeter during irradiation and storage

    DEFF Research Database (Denmark)

    Skyt, Peter S; Balling, Peter

    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.

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

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

    OpenAIRE

    Wang, Hong-qiang; Tsai, Chung-jui

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    The present study compared the dose-response curves for the frequency of apoptosis in mouse hippocampal dentate gyrus (DG) and intestinal crypt using whole-body gamma irradiation. The incidence of gamma-ray-induced apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labelling (TUNEL) method. TUNEL-positive apoptotic nuclei in the DG and intestinal crypt were increased in a dose-dependent pattern (0-2 Gy). The dose-response curves were linear-quadratic, with a significant relationship between the appearance of apoptosis and irradiation dose. The slopes of the dose-response curves in the DG were much steeper (?5-6-fold) than those in the intestinal crypt within the range of 0-1 Gy exposure. Hippocampal DG might be a more effective and sensitive evaluation structure than the intestinal crypt to estimate the degree of radiation exposure in damaged organs of adult mice exposed to low irradiation dose. copy; The Author 2011. Published by Oxford Univ. Press. All rights reserved. (authors)

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

    International Nuclear Information System (INIS)

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

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

    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%.

  9. 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

  10. Dose response of artificial irradiation of fluvial sediment sample for ESR dating

    International Nuclear Information System (INIS)

    ESR dating samples need be irradiated to obtain dose response curve and the equivalent dose. The artificial dose rate is about 1 x 10-1-1 x 102 Gy/min, whereas the natural dose rate is about 3 Gy/ka. Therefore, one must be sure whether the much higher artificial dose rate is suitable for the ESR dating study. In this paper, we use different artificial dose rate to irradiate the same fluvial sample and measure the quartz Al centre ESR signal under the same conditions. The dose response curves are compared, in an attempt to gain a preliminary knowledge on that problem and build a good foundation for our ESR dating studies on fluvial samples. (authors)

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

    International Nuclear Information System (INIS)

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

  12. Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study.

    Science.gov (United States)

    Raskob, Gary; Cohen, Alexander T; Eriksson, Bengt I; Puskas, David; Shi, Minggao; Bocanegra, Tomas; Weitz, Jeffrey I

    2010-09-01

    Edoxaban is a new oral direct factor Xa inhibitor. The purpose of this study was to evaluate the efficacy and safety of different doses of edoxaban for the prevention of venous thromboembolism (VTE) in patients undergoing elective total hip replacement. A total of 903 patients were randomised to oral edoxaban 15, 30, 60 or 90 mg once daily or subcutaneous dalteparin once daily (initial dose 2,500 IU, subsequent doses 5,000 IU). Both drugs were begun 6-8 hours postoperatively and continued for 7-10 days, when bilateral venography was performed. The primary efficacy endpoint was the incidence of total VTE, which included proximal and/or distal deep-vein thrombosis (DVT) by venography or symptomatic, objectively confirmed DVT or pulmonary embolism during the treatment period. The primary safety outcome was the incidence of the composite of major and clinically relevant non-major bleeding. All venograms and bleeding events were reviewed by a central independent adjudication committee blinded as to treatment allocation. Of the 903 patients randomised, 776 were evaluable for the primary efficacy analysis. The incidences of VTE were 28.2%, 21.2%, 15.2%, and 10.6% in patients receiving edoxaban 15, 30, 60 and 90 mg, respectively, compared with 43.8% in the dalteparin group (p<0.005 ). There was a statistically significant (p<0.001) dose-response for efficacy across the edoxaban dose groups for total VTE and for major VTE. The incidence of clinically relevant bleeding was low and similar across the groups. Oral edoxaban once daily is effective for preventing VTE after total hip replacement. PMID:20589317

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

    OpenAIRE

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

    2011-01-01

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

  14. Improved dose response modeling for normal tissue damage and therapy optimization

    OpenAIRE

    Adamus-go?rka, Magdalena

    2008-01-01

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

  15. Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study.

    OpenAIRE

    Oort, Fv; Melse-boonstra, A.; Brouwer, Ia; Clarke, R.; West, Ce; Katan, Mb; Verhoef, P.

    2003-01-01

    Background: Elevated homocysteine concentrations, a likely risk factor for cardiovascular disease, can be lowered effectively with folic acid. The minimum dose of folic acid required for maximal reduction of homocysteine concentrations is not yet known reliably. Objective: We aimed to determine the lowest folic acid dose that decreases plasma homocysteine concentrations adequately in healthy older adults. Design: A dose-response trial with a randomized, double-blind, parallel-group, place...

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

    OpenAIRE

    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...

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

    OpenAIRE

    Englund Erling; Malker Hans; Wiesinger Birgitta; Wänman Anders

    2009-01-01

    Abstract Background The aim of this study was to test whether a reciprocal dose-response relation exists between frequency/severity of spinal pain and temporomandibular disorders (TMD). Methods A total of 616 subjects with varying severity of spinal pain or no spinal pain completed a questionnaire focusing on symptoms in the jaw, head and spinal region. A subset of the population (n = 266) were sampled regardless of presence or absence of spinal pain. We used two different designs, one with f...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-02-01

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

  19. Results of animal studies suggest a nonlinear dose-response relationship for benzene effects.

    OpenAIRE

    Parodi, S.; Lutz, W. K.; Colacci, A.; Mazzullo, M.; Taningher, M.; Grilli, S.

    1989-01-01

    Considering the very large industrial usage of benzene, studies in risk assessment aimed at the evaluation of carcinogenic risk at low levels of exposure are important. Animal data can offer indications about what could happen in humans and provide more diverse information than epidemiological data with respect to dose-response consideration. We have considered experiments investigating metabolism, short-term genotoxicity tests, DNA adduct formation, and carcinogenicity long-term tests. Accor...

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

    International Nuclear Information System (INIS)

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

  1. A note on the shape of shouldered dose-response curves

    International Nuclear Information System (INIS)

    Consideration is given to four alternative proposals for target-theoretical models, and their applications to radiobiological dose-response curves. One aim is the clarification of the mechanisms of stochastic effects, and the association between chromosomal aberrations and cell killing is discussed in terms of the models. Hypothetical survival curves are used to show the conditions under which a differentiation between the models might be possible. (U.K.)

  2. 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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2003-01-01

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

  5. 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)

  6. 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)

  7. 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.)

  8. Statistics

    International Nuclear Information System (INIS)

    For the years 2004 and 2005 the figures shown in the tables of Energy Review are partly preliminary. The annual statistics published in Energy Review are presented in more detail in a publication called Energy Statistics that comes out yearly. Energy Statistics also includes historical time-series over a longer period of time (see e.g. Energy Statistics, Statistics Finland, Helsinki 2004.) The applied energy units and conversion coefficients are shown in the 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-June 2003, Energy exports by recipient country in January-June 2003, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Price of natural gas by type of consumer, Price of electricity by type of consumer, Price of district heating by type of consumeice 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, precautionary stock fees and oil pollution fees

  9. Statistics

    International Nuclear Information System (INIS)

    A few reports given on the occasion of the Unichal congress in Paris are evaluated which deal with the state and development of district heating in Yugoslavia and the FRG. Furthermore, some key values from the annual statistics of the Swedish District Heating Association are derived and their values are analyzed with regard to a general declarative statement. (GG/LH)

  10. Statistics

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Jirasek, A.; Hilts, M.; Berman, A.; McAuley, K. B.

    2009-02-01

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Ioan Catalin VLAD

    2012-11-01

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

  14. Statistics

    International Nuclear Information System (INIS)

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

  15. The thresholds for statistical and clinical significance - a five-step procedure for evaluation 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.

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

    Science.gov (United States)

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

    2014-08-15

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

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

    Science.gov (United States)

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

    2013-09-12

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

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

    Science.gov (United States)

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

    2014-10-01

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

  19. Dose-response models and methods of risk prediction and causation estimation

    International Nuclear Information System (INIS)

    Dose-response models are mathematical expressions that describe the relationship between absorbed dose and radiogenic effects. The limited quality and quantity of human dose-response data make it necessary to use fairly simplistic models. Most current low-LET data support the linear-quadratic model in which radiogenic effects are linearly dependent at low doses and then become quadratically curved at higher doses. Some types of effects never exhibit a quadratic component, remaining linear over a wide range of absorbed dose. Future progress in developing more refined dose-response models is more likely to come from a better understanding of the fundamentals of radiation carcinogenesis rather than better data or better curve-fitting techniques. The risk of radiation injury is a prospective estimation of the probability that some harm will result in the future as a consequence of having been irradiated. Quantitative risk estimates for the carcinogenic, genetic, and fetal effects of low level radiation that have been determined by national and international organizations are of the order of magnitude of one chance fatality in 10,000/rem. Causation estimation is the retrospective analysis of the probability that cancer observed in an irradiated individual was caused by radiation as opposed to some other agent. Depending on the dose type of cancer, gender, age at time of irradiation, and time since irradiation, the probability of causation can range from 0% to 100%. Methodsusation can range from 0% to 100%. Methods for calculation of the probability of causation for certain types of cancer and irradiation circumstances have been developed recently by the National Institutes of Health

  20. Sex defines the age dependence of endogenous ACTH-cortisol dose responsiveness

    OpenAIRE

    Keenan, Daniel M.; Roelfsema, Ferdinand; Carroll, Bernard J.; Iranmanesh, Ali; Veldhuis, Johannes D.

    2009-01-01

    Sex influences adrenal glucocorticoid responses to ACTH in experimental animals. Whether similar sex differences operate in humans is unknown. To test this notion, we estimated ACTH-cortisol dose-response properties analytically in 48 healthy adults (n = 22 women, n = 26 men), ages 18–77 yr, body mass index (BMI) 18–32 kg/m2, previously studied at two medical centers. Plasma ACTH and cortisol concentrations were measured every 10 min for 24 h. The 145 sample pairs were used in each subjec...

  1. Methacholine Dose-Response Slopes from Maximal Bronchial Challenge Tests in Asthmatic Children: Methodological Aspects

    OpenAIRE

    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...

  2. Dose-Response Model for Listeria monocytogenes-Induced Stillbirths in Nonhuman Primates? †

    OpenAIRE

    Smith, Mary Alice; Takeuchi, Kazue; Anderson, Gary; Ware, Glenn O.; Mcclure, Harold M.; Raybourne, Richard B.; Mytle, Nutan; Doyle, Michael P.

    2007-01-01

    A dose-response model using rhesus monkeys as a surrogate for pregnant women indicates that oral exposure to 107 CFU of Listeria monocytogenes results in about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a single dose of 102 to 1010 CFU of L. monocytogenes had stillbirths. A log-logistic model predicts a dose affecting 50% of animals at 107 CFU, comparable to an estimated 106 CFU based on an outbreak among pregnant women but much less than the extrapolated estimate (1...

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Baeck, S.A.J.; Lepage, M.; Baldock, C. E-mail: c.baldock@qut.edu.au

    2002-06-01

    The relationship between the radiation absorbed dose and the NMR longitudinal and transversal relaxation rates, R{sub 1} and R{sub 2}, respectively, of a ceric sulphate dosimeter was examined. By adding copper sulphate, the R{sub 1} and R{sub 2} dose-responses were found to be linear up to 60 kGy with dose sensitivities of 13x10{sup -6} and 15x10{sup -6} s{sup -1} Gy{sup -1}, respectively. There is thus the potential for a three-dimensional ceric dosimeter for high dose applications, provided a suitable gelling substance is used.

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

    Science.gov (United States)

    Bäck, S A J; Lepage, M; Baldock, C

    2002-06-01

    The relationship between the radiation absorbed dose and the NMR longitudinal and transversal relaxation rates, R1 and R2, respectively, of a ceric sulphate dosimeter was examined. By adding copper sulphate, the R1 and R2 dose-responses were found to be linear up to 60 kGy with dose sensitivities of 13 x 10(-6) and 15 x 10(-6) s(-1) Gy(-1) , respectively. There is thus the potential for a three-dimensional ceric dosimeter for high dose applications, provided a suitable gelling substance is used. PMID:12102349

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

    Science.gov (United States)

    Byers, John A

    2013-08-01

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

  7. Influence of polarity on dose-response relationships of intrathecal opioids in rats.

    Science.gov (United States)

    Plummer, J L; Cmielewski, P L; Reynolds, G D; Gourlay, G K; Cherry, D A

    1990-03-01

    Dose-response curves were constructed for intrathecal morphine (M), oxymorphone (OM), hydromorphone (HM), diamorphine (DM), 14-hydroxydihydromorphine (OHM), oxycodone (OC), hydrocodone (HC) and fentanyl (F). Intrathecal catheters were placed in 69 rats under halothane/N2O anaesthesia. After recovery, baseline hot plate and tail flick latencies were measured, and a dose of opioid was given. Hot plate and tail flick latencies were assessed at 5, 15, 30, 60, 90, 120 min and then hourly until they returned to within 25% of baseline. Response latencies were converted to per cent of maximum possible effect (% MPE) and the area under the % MPE X time curve was taken as the response. This measure includes information about both potency and duration of action. Each rat received 3 opioids and saline at intervals of 2-3 days. On a fifth occasion, the animal's first treatment was repeated. Each opioid was studied over an 8-fold dose range. Results of both hot plate and tail flick were best described by a model including log(dose), a component due to development of tolerance over the 5 experimental days, and an among-rat variation term. In the hot plate test, doses equieffective in producing a response (AUC) over the dose range studied were in the order OHM less than OM less than HM less than M less than F less than DM less than HC less than OC. Slopes of the log(dose)-response curves were similar for all drugs except OHM, which had a steeper slope. A model is proposed in which hot plate and tail flick latencies are prolonged while CSF concentrations of a drug are above its minimum effective concentration, and drug is cleared from the CSF by a first-order process, possibly uptake into the spinal cord and removal via the blood. This model predicts that log(dose)-response curves will be linear, as was observed, with slopes inversely proportional to the rate constant for clearance from CSF. According to this model the steeper slope of the OHM log(dose)-response may be interpreted as indicating slower clearance from CSF. OHM has the lowest octanol/pH 7.4 buffer distribution coefficient (0.34) of all opioids studied, possibly leading to a lower rate of uptake into the spinal cord. PMID:2326098

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

    OpenAIRE

    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...

  9. Dose-response relationships with respect to micronuclear test indices after neutron-irradiation

    International Nuclear Information System (INIS)

    It was shown by method of cytokinetic blocking that with neutron irradiation of human lymphocyte culture (mean energy of 0.85 MeV, doses of 0.05 to Gy) the dose-response relationship, with respect to the share of binuclear-cells with micronuclei in binuclear cells, was of a multiphase nature with a more or less manifest plateau within the dose-range from 0.5 to 1.0 Gy. Both micronuclear tests may be used for indicating the degree of radiation injury to the organism caused by neutrons of the above-mentioned energy and doses of 0.05-0.5 Gy

  10. 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

  11. Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies

    OpenAIRE

    Rong, Ying; Chen, Li; Zhu, Tingting; Song, Yadong; Yu, Miao; Shan, Zhilei; Sands, Amanda Lee Prouty; Hu, Frank B.; Liu, Liegang

    2013-01-01

    Objective: To investigate and quantify the potential dose-response association between egg consumption and risk of coronary heart disease and stroke. Design: Dose-response meta-analysis of prospective cohort studies. Data sources PubMed and Embase prior to June 2012 and references of relevant original papers and review articles. Eligibility criteria for selecting studies Prospective cohort studies with relative risks and 95% confidence intervals of coronary heart disease or stroke for three o...

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

    Directory of Open Access Journals (Sweden)

    T. Mukherjee

    2011-07-01

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

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

    Science.gov (United States)

    Campbell, Janice M.

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

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

    OpenAIRE

    Dropkin Greg

    2007-01-01

    Abstract Background Analyses of Japanese A-bomb survivors' cancer mortality risks are used to establish recommended annual dose limits, currently set at 1 mSv (public) and 20 mSv (occupational). Do radiation doses below 20 mSv have significant impact on cancer mortality in Japanese A-bomb survivors, and is the dose-response linear? Methods I analyse stomach, liver, lung, colon, uterus, and all-solid cancer mortality in the 0 – 20 mSv colon dose subcohort of the 1950–90 (grouped) mortality...

  15. Off-axis dose response characteristics of an amorphous silicon electronic portal imaging device

    International Nuclear Information System (INIS)

    Amorphous silicon (a-Si) electronic portal imaging devices (EPIDs) have typically been calibrated to dose at central axis (CAX). Division of acquired images by the flood-field (FF) image that corrects for pixel sensitivity variation as well as open field energy-dependent off-axis response variation should result in a flat EPID response over the entire matrix for the same field size. While the beam profile can be reintroduced to the image by an additional correction matrix, the CAX EPID response to dose calibration factor is assumed to apply to all pixels in the detector. The aim of this work was to investigate the dose response of the Varian aS500 amorphous silicon detector across the entire detector area. First it was established that the EPID response across the panel became stable (within ?0.2%) for MU settings greater than ?200 MU. The EPID was then FF calibrated with a high MU setting of ?400 for all subsequent experiments. Whole detector images with varying MU settings from 2-500 were then acquired for two dose rates (300 and 600 MU/min) for 6 MV photons for two EPIDs. The FF corrected EPID response was approximately flat or uniform across the detector for greater than 100 MU delivered (within 0.5%). However, the off-axis EPID response was greater than the CAX response for small MU irradiations, giving a raised EPID profile. Up to 5% increase in response at 20 cm off-axis compared to CAX was found for very small MU settings for one EPID, while it was withings for one EPID, while it was within 2% for the second (newer) EPID. Off-axis response nonuniformities attributed to detector damage were also found for the older EPID. Similar results were obtained with the EPID at 18 MV energy and operating in asynchronous mode (acquisition not synchronized with beam pulses), however the profiles were flatter and more irregular for the small MU irradiations. By moving the detector laterally and repeating the experiments, the increase in response off-axis was found to depend on the pixel position relative to the beam CAX. When the beam was heavily filtered by a phantom the off-axis response variation was reduced markedly to within 0.5% for all MU settings. Independent measurements of off-axis point doses with ion chamber did not show any change in off-axis factor with MUs. Measurements of beam quality (TMR20-10) for MU settings of 2, 5, and 100 at central axis and at 15 cm off-axis could not explain the effect. The response change is unlikely to be significant for clinical IMRT verification with this imaging/acclerator system where MUs are of the order of 100-300, provided the detector does not exhibit radiation damage artifacts

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

    Science.gov (United States)

    Kuang, Dan; Zhang, Wangzhen; Deng, Qifei; Zhang, Xiao; Huang, Kun; Guan, Lei; Hu, Die; Wu, Tangchun; Guo, Huan

    2013-07-01

    Polycyclic aromatic hydrocarbons (PAHs) are known to induce reactive oxygen species and oxidative stress, but the dose-response relationships between exposure to PAHs and oxidative stress levels have not been established. In this study, we recruited 1333 male coke oven workers, monitored the levels of environmental PAHs, and measured internal PAH exposure biomarkers including 12 urinary PAH metabolites and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, as well as the two oxidative biomarkers urinary 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2? (8-iso-PGF2?). We found that the total concentration of urinary PAH metabolites and plasma BPDE-Alb adducts were both significantly associated with increased 8-OHdG and 8-iso-PGF2? in both smokers and nonsmokers (all p hydroxypyrene has a significant positive association with both 8-OHdG and 8-iso-PGF2? after a Bonferroni correction (p hydroxypyrene is a useful biomarker for evaluating total PAHs exposure and assessing oxidative damage in coke oven workers. PMID:23745771

  17. 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.

  18. Dose-response relationship for the pharmacokinetic interaction of grapefruit juice with dextromethorphan investigated by human urinary metabolite profiles.

    Science.gov (United States)

    Strauch, Katja; Lutz, Ursula; Bittner, Nataly; Lutz, Werner K

    2009-08-01

    Grapefruit juice (GFJ) has been shown to affect the pharmacokinetics of a large number of drugs, essentially by inhibition of efflux transporters and CYP3A4 monooxygenase in the small intestine. The GFJ dose usually used in human studies was one glass single-strength (1x). Information on a respective dose-response relationship is not available. We investigated the effect of GFJ of different concentration (0.25 x, 0.5x, 1x, 2x) dosed in biweekly intervals in 19 volunteers. Components considered responsible for drug interactions, naringin, naringenin, bergamottin, and 6',7'-dihydroxybergamottin were determined by LC-tandem mass spectrometry. Immediately after ingestion of GFJ, participants took an aqueous solution of dextromethorphan (DEX) as probe drug. Urine was collected in two sampling periods, 0-2 and 2-4h, and excreted amounts of DEX and five metabolites associated with CYP3A4 and/or CYP2D6 enzyme activity were determined. Effects of GFJ were analyzed by the Wilcoxon matched-pairs signed-rank test against an average of four water control experiments. Two effects were highly significant: (i) a delay of total metabolite excretion in the first 2h and (ii) an inhibition of the CYP3A4-dependent metabolic pathways. Effect magnitude and significance levels were dose-dependent and indicated 200 ml 1x GFJ as "lowest observed effect level" LOEL. PMID:19445995

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

    International Nuclear Information System (INIS)

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

  20. The dose-response relationships for tumor induction after high-LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Covelli, V.; Coppola, M.; Di Majo, V.; Rebessi, S. (ENEA, Casaccia (Italy). Centro Ricerche Energia)

    1991-12-01

    This paper presents a review of several studies conducted in our laboratory to examine the carcinogenic effects in mice of high-LET radiation, and for comparison of low-LET reference radiation. For some specific end-points the following conclusions can be formulated: (1) the dose-response curves for myeloid leukemia and malignant lymphoma can be interpreted in terms of induction and inactivation; in particular, the data confirmed that a linear depenence of the induction on dose is adequate to describe the response to fission neutrons, while a pure quadratic dependence is consistent with the experimental data for low-LET radiation; (2) in the liver, a marked age-dependence was demonstrated for radiation-induced tumors with a much higher susceptability in young than in old mice; also for these tumors the dose-effect curves can be described by a linear and a quadratic relationships for high- and low-LET radiation, respectively; (3) data on ovarian tumor induction suggested threshold-like dose responses; these peculiar shapes as well as the absence of a clear radiation quality dependence of the curves are difficult findings to explain using a simple model of radiation action, and they might better be related to a non-stochastic effect of hormonal imbalance following irradiation. (author).

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

    Science.gov (United States)

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

    2003-01-01

    Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the allelochemical effects. The model is compared with experimental data for the response of lettuce seedling growth to Centaurepensin, the olfactory response of weevil larvae to alpha-terpineol, and the responses of annual ryegrass (Lolium multiflorum Lam.), creeping red fescue (Festuca rubra L., cv. Ensylva), Kentucky bluegrass (Poa pratensis L., cv. Kenblue), perennial ryegrass (L. perenne L., cv. Manhattan), and Rebel tall fescue (F. arundinacea Schreb) seedling growth to leachates of Rebel and Kentucky 31 tall fescue. The results show that the model gives a good description to observations and can be used to fit a wide range of dose responses. Assessments of the effects of leachates of Rebel and Kentucky 31 tall fescue clearly differentiate the properties of the allelopathic sources and the relative sensitivities of indicators such as the length of root and leaf. PMID:19330111

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

    International Nuclear Information System (INIS)

    The International Atomic Energy Agency hosted a two day Symposium from 2-3 December 1974 at its Headquarters, organized by the 'International Academy for Environmental Safety and the Forum fur Wissenschaft, Wirtschaft und Politik' on the subject 'Scientific Basis for the Establishment of Threshold. Levels and Dose Response Relationships of Carcinogenesis'. Following an introductory paper by the Radiation Biology Section of the Agency on 'Radiation Carcinogenesis - Dose Response Relationship, Threshold and Risk Estimates', a series of papers dealt with this problem in chemical carcinogenesis.It was suggested that more experiments should be done using non-human primates for tests of carcinogens, especially chemicals. Preliminary experiments using monkeys with a potent carcinogen - nitrosoamine - indicate that there could possibly be a dose where no effect can be observed during the 5 year period of study. It was also pointed out that the overall cost/benefit and risk/ benefit relationships should be taken into consideration in determining limits for chemicals which are potentially carcinogenic but are used routinely by the public and industries; these considerations have been weighed in setting exposure limits for radiation

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

    Science.gov (United States)

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

    2004-01-01

    Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  4. Ceruletide intravenous dose-response study by a simplified scintigraphic technique

    International Nuclear Information System (INIS)

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

  5. Dose-Response Curves of Mouse Jejunal Crypt Cells by Multifrationated Irradiation

    International Nuclear Information System (INIS)

    Using as assay for jejunal crypt stem cell survival, dose-response curves for the reproductive capacity of crypt stem cells mouse jejunum exposed to multifractionated gamma-ray irradiation(single, 2, 3, 4, 5, 6, 7, 8, 10,12, and 16 fractions) were analyzed and single-dose survival curve of these cells was constructed. The following conclusion were drawn: 1) Survival curves for higher numbers of dose fractions were displaced to higher dose, and characterized by increasingly shallower slopes. 2) The single-dose survival curve had broad shoulder, Dq=460 cGy, remaining near-exponential over initial dose range 0 to 300 cGy, with initial slope 1Do=474 cGy 3) At fractionated dose in the range of 180 to 450 cGy, the average recovered dose per fraction interval was approximately 50% of the dose per fraction. 4) The value of a/b ratio by using of linear regression analysis for the reciprocal dose plots was 8.3 Gy which lied in the range of 6-14 Gy for early-reacting tissues. 5) The linear-quadratic model for dose-response formula offers valid approximations for all doses to be used in radiotherapy, only two parameters to be determined, and considerable convenience in practical applications

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  8. Dose-response relationship for elective neck irradiation of head and neck cancer - facts and controversies

    International Nuclear Information System (INIS)

    The aim of this study is to assign dose-response relationship for subclinical neck metastases of squamous cell head and neck cancer based on extensive survey of 24 data sets collected from the literature. Neck relapse rates (NRR) without and after elective (ENI) or preoperative irradiation were estimated for each site and stage of primary tumor and the reduction in neck relapse rate was calculated. An average NRR without ENI was 22% (12-35% ) and only 2.5% (0-1 0%) after the ENI with total dose of 46- 50 Gy which gives high reduction rate in the risk of neck recurrences being on the average 89% and 42% (0-46%) after preoperative irradiation using 22-30 Gy. Dose response curve for elective and preoperative irradiation have shown that 50 Gy in 2 Gy fraction reduces the incidence of neck relapses in the NO patients by more than 90% and only by less than 50% after total doses lower than 30 Gy. No correlation between the risk of neck metastases without ENI and the reduction in neck relapses after ENI was found. (authors)

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

    Science.gov (United States)

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

    2014-01-01

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

  10. 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.

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

    International Nuclear Information System (INIS)

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

  12. Dietary balanced protein in broiler chickens. 1. A flexible and practical tool to predict dose-response curves.

    Science.gov (United States)

    Eits, R M; Kwakkel, R P; Verstegen, M W A; Den Hartog, L A

    2005-06-01

    An empirical model of exponential form was developed, different versions of which can be used to predict growth rate, feed conversion and carcase and breast meat yield of broiler chickens as a function of dietary balanced protein (DBP) content. The model was developed to support decision-making by nutritionists. The model helps in determining DBP contents that maximise profit. The model avoids the practical disadvantages of existing methods. In contrast with mechanistic models, only data that are generally known by broiler nutritionists are required as input. Compared with predictions derived from one or a few feeding trials, the model predictions are more accurate (because the model was derived from many data-sets) and more flexible (because a description of the type of broiler was included as input for the model). Broiler response studies from the literature and the Nutreco Poultry and Rabbit Research Centre (27 data-sets in total) were used in the model development to select significant variables, to quantify the parameters and to evaluate the accuracy of the predictions. Input variables were DBP content, maximum performance level, age, year (indicating genetic potential) and sex. The model, including the assumption that the shape of the dose-response curves to DBP content is independent of broiler and feed characteristics, gave an accurate simulation of growth rate, feed conversion and breast meat for nearly all data-sets. Effects of DBP content on carcase yield were relatively small, except for carcases without skin and skin fat. PMID:16050183

  13. Some implications of linear-quadratic-linear radiation dose-response with regard to hypofractionation

    International Nuclear Information System (INIS)

    Recent technological advances enable radiation therapy to be delivered in a highly conformal manner to targets located almost anywhere in the body. This capability has renewed the clinical interest in hypofractionation wherein the tumor is delivered a few fractions of very large dose per fraction. Extrapolating clinical experience from conventional regimens to fractions of high dose is important to designing hypofractionated treatments. The concept of biologically effective dose (BED) based on the linear-quadratic (LQ) formulation e-(?D+?D2) is a useful tool for intercomparing conventional fractionations but may be hampered if the value of ?/? is dose range dependent and/or when extrapolating to fractions of high dose because the LQ curve bends continuously on the log-linear plot. This does not coincide with what is observed experimentally in many clonogenic cell survival studies at high dose wherein radiation dose-response relationships more closely approximate a straight line. Intercomparison of conventional fractionations with hypofractionated regimens may benefit from BED calculations which instead use a dose range independent linear-quadratic-linear (LQ-L) formulation which better fits the experimental data across a wider range of dose. The dosimetric implications of LQ-L are explored using a simple model which requires only the specification of a dose DT at which the LQ curve transitions to final linearity and the logee cell kill per Gy in the final linear portion of the survival curve at high dose. It is shown that the line tangent to the LQ curve at transition dose DT can often be used to approximate the final slope of the dose response curve. When DT=2?/? Gy, the line tangent to the LQ curve at DT intersects the e-?D and e-?D2 curves at dose ?/? Gy and also closely fits the linear response in the high dose region of some classic in vitro cell survival curves for which the value of ?/? is low. It is hypothesized that DT will increase as the magnitude of ?/? increases. Examples are presented illustrating how to recognize LQ-L behavior in multifraction isoeffect studies of late responses such as spinal cord and lung. When planning hypofractionated regimens involving reactions with low ?/?, recognizing LQ-L behavior could be important because the dose-response is likely to transition to final linearity within the contemplated range of hypofractional doses

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Meta-analysis of dioxin cancer dose response for three occupational cohorts.

    OpenAIRE

    Crump, Kenny S.; Canady, Richard; Kogevinas, Manolis

    2003-01-01

    This article presents a meta analysis of data from three cohorts occupationally exposed to TCDD and related compounds. A statistically significant (p = 0.02) trend was found in total cancer mortality with increasing dioxin exposure. The trend tests show an increase in total cancer at cumulative TEQ (unit of measurement for TCDD-like compounds that is defined as the amount of TCDD that would produce the same toxicity as a mixture of TCDD-like compounds) serum levels that would result from life...

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

    International Nuclear Information System (INIS)

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

  18. Dose response linearity and practical factors influencing minimum detectable dose for various thermoluminescent detector types

    International Nuclear Information System (INIS)

    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)

  19. Dose-response model for Listeria monocytogenes-induced stillbirths in nonhuman primates.

    Science.gov (United States)

    Smith, Mary Alice; Takeuchi, Kazue; Anderson, Gary; Ware, Glenn O; McClure, Harold M; Raybourne, Richard B; Mytle, Nutan; Doyle, Michael P

    2008-02-01

    A dose-response model using rhesus monkeys as a surrogate for pregnant women indicates that oral exposure to 10(7) CFU of Listeria monocytogenes results in about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a single dose of 10(2) to 10(10) CFU of L. monocytogenes had stillbirths. A log-logistic model predicts a dose affecting 50% of animals at 10(7) CFU, comparable to an estimated 10(6) CFU based on an outbreak among pregnant women but much less than the extrapolated estimate (10(13) CFU) from the FDA-U.S. Department of Agriculture-CDC risk assessment using an exponential curve based on mouse data. Exposure and etiology of the disease are the same in humans and primates but not in mice. This information will aid in risk assessment, assist policy makers, and provide a model for mechanistic studies of L. monocytogenes-induced stillbirths. PMID:18070908

  20. Dose-response of electromagnetic field-enhanced ornithine decarboxylase activity.

    Science.gov (United States)

    Mullins, J M; Penafiel, L M; Juutilainen, J; Litovitz, T A

    1999-02-01

    Alteration of ODC activity in animals or cultured cells exposed to extremely low frequency electromagnetic fields, or to modulated microwave fields, has been documented by several laboratories. However, an evaluation of the dose-response relationship in these experiments has not been done. We examined ODC activity in L929 fibroblasts exposed for 4 h to 60 Hz magnetic fields of different amplitudes. Our results show a clear threshold response which could be fitted to a sigmoidal function, with the 50% point occurring at approximately 5 microT. This sigmoidal response is characteristic of biological responses which are governed by ligand-receptor binding, and has been previously observed in the incidence of magnetic-field induced morphological abnormalities in chick embryos. The implications of this study are discussed in terms of environmental exposures to EM fields. PMID:10228587

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  4. Defining a dose-response relationship for prostate external beam radiotherapy

    International Nuclear Information System (INIS)

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

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

    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.

  6. 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

  7. Dose-responsive insulin regulation of glucose transport in human skeletal muscle.

    Science.gov (United States)

    Pencek, R Richard; Bertoldo, Alessandra; Price, Julie; Kelley, Carol; Cobelli, Claudio; Kelley, David E

    2006-06-01

    Glucose transport is regarded as the principal rate control step governing insulin-stimulated glucose utilization by skeletal muscle. To assess this step in human skeletal muscle, quantitative PET imaging of skeletal muscle was performed using 3-O-methyl-[11C]glucose (3-[11C]OMG) in healthy volunteers during a two-step insulin infusion [n = 8; 30 and 120 mU.min(-1).m(-2), low (LO) and high (HI)] and during basal conditions (n = 8). Positron emission tomography images were coregistered with MRI to assess 3-[11C]OMG activity in regions of interest placed on oxidative (soleus) compared with glycolytic (tibialis anterior) muscle. Insulin dose-responsive increases of 3-[11C]OMG activity in muscle were observed (P < 0.01). Tissue activity was greater in soleus than in tibialis anterior (P < 0.05). Spectral analysis identified that two mathematical components interacted to shape tissue activity curves. These two components were interpreted physiologically as likely representing the kinetics of 3-[11C]OMG delivery from plasma to tissue and the kinetics of bidirectional glucose transport. During low compared with basal, there was a sixfold increase in k3, the rate constant attributed to inward glucose transport, and another threefold increase during HI (0.012 +/- 0.003, 0.070 +/- 0.014, 0.272 +/- 0.059 min(-1), P < 0.001). Values for k3 were similar in soleus and tibialis anterior, suggesting similar kinetics for transport, but compartmental modeling indicated a higher value in soleus for k1, denoting higher rates of 3-[11C]OMG delivery to soleus than to tibialis anterior. In summary, in healthy volunteers there is robust dose-responsive insulin stimulation of glucose transport in skeletal muscle. PMID:16390860

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-01-01

    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.

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

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines

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

    Directory of Open Access Journals (Sweden)

    Ramesh Chandra Tiwari

    2014-08-01

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

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology

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

    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

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

    Science.gov (United States)

    Kemmler, W; von Stengel, S

    2014-06-01

    The purpose of this study was to determine the long-term dose-response relationship of exercise frequency on areal bone mineral density (aBMD) in early post-menopausal women with osteopenia. Based on the 12-year results of the consequently supervised exercise group (EG) of the Erlangen Fitness and Osteoporosis Prevention Study, we retrospectively structured two exercise groups according to the overall exercise frequency. Changes in aBMD at lumbar spine and proximal femur as assessed by dual-energy x-ray absorptiometry technique were compared between a low-frequency exercise group (LEF-EG, n = 16) with 1.5-high-frequency exercise group (HEF-EG, n = 25) with ? 2-3.5 sessions/week. Changes in aBMD at the lumbar spine and proximal femur were significantly more favorable in the HEF-EG compared with the LEF-EG; lumbar spine: (mean value ± standard deviation) 1.1 ± 4.7% vs -4.1 ± 3.0%; P = 0.001, ES: d'?= 1.26; total hip: -4.4 ± 3.9% vs -6.7 ± 3.5%, P = 0.045, ES: d' = 0.70). BMD results of the LEF-EG did not significantly differ from the data of the non-training control group (lumbar spine: -4.4 ± 5.2%, total hip: -6.9 ± 5.0%). Although this result might not be generalizable across all exercise types and cohorts, it indicates that to impact bone, an overall exercise frequency of at least 2 sessions/week may be crucial, even if exercise is applied with high intensity/impact. PMID:23190199

  18. Quantitative models of the dose-response and time course of inhalational anthrax in humans.

    Science.gov (United States)

    Toth, Damon J A; Gundlapalli, Adi V; Schell, Wiley A; Bulmahn, Kenneth; Walton, Thomas E; Woods, Christopher W; Coghill, Catherine; Gallegos, Frank; Samore, Matthew H; Adler, Frederick R

    2013-08-01

    Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure-Infection-Symptomatic illness-Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID50) of 11,000 spores (95% confidence interval 7,200-17,000), ID10 of 1,700 (1,100-2,600), and ID1 of 160 (100-250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7-13.1) for exposure to ID50, 11.8 days (9.5-15.0) for ID10, and 12.1 days (9.9-15.3) for ID1. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses. PMID:24058320

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

    Science.gov (United States)

    Chappelli, Lori J.; Cucinotta, Francis A.

    2010-01-01

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

  20. 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.

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

    Science.gov (United States)

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

    2014-07-21

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. [Estimation of the zinc requirement for broilers using their ability for selective zinc absorption and by dose-response relations].

    Science.gov (United States)

    Steinruck, U; Kirchgessner, M

    1993-01-01

    Broiler chicks are able to select an adequate dietary Zn-concentration in choice-feeding. The zinc requirement should be ascertained by this method of self-selection. 72 day-old chicks were divided into 9 groups and were kept over 5 weeks in individual cages. By gradually supplementing ZnSO4.7H2O to a semisynthetic basal diet with isolated soybean protein 5 diets were made with Zn-concentrations of 14, 22, 30, 38 and 50 ppm, which respectively were fed to one group. The four other groups had to choose between two rations: 14/38; 14/50; 22/38; 22/50. Selective zinc intake was represented by a significant increase of dietary zinc concentration compared to random selection (mean of both diets). Feed intake, zinc intake and weight gain were measured daily and the end total feed consumption, live weight, feed conversion rate, plasma-zinc concentration and plasma-zinc binding capacity at the end of the experiment. In comparison optimal dietary zinc levels were estimated by dose-response relations, both by sigmoid growth curves and by broken-line model. With 30 ppm Zn chickens reached a high fattening level with daily weight gains of 60 g. Feed intake and growth rate were markedly reduced at a dosage of 14 and 22 ppm Zn, feed conversion rate was tendentially decreased below a level of about 34 ppm, whereas above zinc binding capacity reached a plateau. Birds self-selected a dietary zinc level of 32 ppm, which were adequate for the criteria feed intake and weight gains. Zinc requirements of about 40 ppm were assessed by conventional methods. PMID:8512447

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

  8. Adaptive response to hydrogen peroxide in yeast: induction, time course, and relationship to dose-response models.

    Science.gov (United States)

    Hoffmann, George R; Moczula, Andrew V; Laterza, Amanda M; Macneil, Lindsey K; Tartaglione, Jason P

    2013-07-01

    The assay for trp5 gene conversion and ilv1-92 reversion in Saccharomyces cerevisiae strain D7 was used to characterize the induction of an adaptive response by hydrogen peroxide (H(2)O(2)). Effects of a small priming dose on the genotoxic effects of a larger challenge dose were measured in exponential cultures and in early stationary phase. An adaptive response, indicated by smaller convertant and revertant frequencies after the priming dose, occurred at lower priming and challenge doses in young, well-aerated cultures. Closely spaced priming doses from 0.000975 to 2 mM, followed by a 1 mM challenge, showed that the induction of the adaptive response is biphasic. In exponential cultures it was maximal with a priming dose of 0.125-0.25 mM. Very small priming doses were insufficient to induce the adaptive response, whereas higher doses contributed to damage. A significant adaptive response was detected when the challenge dose was administered 10-20 min after the priming exposure. It was fully expressed within 45 min, and the yeast began to return to the nonadapted state after 4-6 hr. Because of the similarity of the biphasic induction to hormetic curves and the proposal that adaptive responses are a manifestation of hormesis, we evaluated whether the low doses of H(2)O(2) that induce the adaptive response show a clear hormetic response without a subsequent challenge dose. Hormesis was not evident, but there was an apparent threshold for genotoxicity at or slightly below 0.125 mM. The results are discussed with respect to linear, threshold, and hormesis dose-response models. PMID:23740476

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

    International Nuclear Information System (INIS)

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

  10. Critical reevaluation of the dose-response relationships for carcinogenic effects of low-level ionizing radiation

    International Nuclear Information System (INIS)

    In recent decades, it has been customary, for radiation protection purposes, to assume that the overall risk of radiation-induced cancer increases as a linear-nonthreshold function of the dose. The existing data do not exclude the existence of a threshold, however, and the dose-response relationship is known to vary, depending on the type of cancer in queation, the dose, dose rate, and LET of the radiation, the age, sex, and physiological state of the exposed individuals, and other variables, including the potential influence of adaptive responses and bystander effects at low doses. In light of advncing knowledge, therefore, the dose-response relationship for carcinogenic effects of low-level radiation has been reevaluated periodically by the National Council on Radiation Protection and Measurements, the International Commission of Radiological Protection, the United Nations Scientific Committee on the Effects of Atomic Radiation, the U.S. National Academy of Sciences, and other organizations. The most recent such reviews have generally found the weight of evidence to suggest that lesions which are precursors to cancer (i.e., mutations and chromosome aberrations), and certain types of cancer as well, may increase in frequency linearly with the dose in the low-dose domain. On this basis, it is concluded that no alternative dose-response model for the carcinogenic effects of low-level radiation is more plausible than the linear-nonthreshold model, although other dose-renonthreshold model, although other dose-response relationships cannot be excluded. (authors)

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

    Science.gov (United States)

    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 ...

  12. Empirical evaluation of sufficient similarity in dose-response for environmental risk assessment of a mixture of 11 pyrethroids.

    Science.gov (United States)

    Chemical mixtures in the environment are often the result of a dynamic process. When dose-response data are available on random samples throughout the process, equivalence testing can be used to determine whether the mixtures are sufficiently similar based on a pre-specified biol...

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

    International Nuclear Information System (INIS)

    The determination of the dose-response curve is a crucial step to use the Micronucleus assay in Lymphocytes as a biological dosimeters. The most widely used fitting function is the linear-quadratic function. The coefficients are fitted by calibration data provided by irradiations of blood from healthy donors. In our case we performed the calibration curve corresponding to gamma radiation from Cesium-137 (660 keV). Doses ranged from 0 to 16 Gy. The fitting procedure used was the iteratively re weighted least square algorithm implemented in a Matlab routine. The results of the analysis of our data show that the dose-effect curve does not follow a linear-quadratic curve at high radiation doses, diminishing the quadratic parameters as dose increases. This can be interpreted as a micronucleus saturation effect beyond a certain dose level. We conclude that the MN assay with lymphocytes can be well characterized as a biological dosimeters up to a maximum dose of 4.5 Gy. (Author)

  14. A two phase dose-response relationship at low dose rates

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    The use of computer graphics in conjunction with three-dimensional models of dose-response relationships for chronic exposure to ionizing radiation dramaticly clarifies the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. As an example, the functionally injurious and carcinogenic responses after systemic uptake of Ra-226 by beagles, mice and people with consequent alpha particle irradiation of the bone are represented by three-dimensional dose-rate/time/response surfaces that demonstrate the contributions with the passage of time of the competing deleterious responses. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each effect. Radiation bone injury predominates at high dose rates and bone cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for bone cancer induction. Risk assessment is benefited by the insights that become apparent with these three-dimensional models. The improved conceptualization afforded by them contributes to planning and evaluating epidemiological analyses and experimental studies

  16. Linear dose-response relationships after prolonged expression times in V-79 Chinese hamster cells

    International Nuclear Information System (INIS)

    The expression time for induced mutants resistant to 6-thioguanine, in V-79 Chinese hamster cells, was determined by respreading the cells in the selective medium at various times after treatment. The length of the expression time for mutants induced by X-rays, ethyl methane sulphonate and ultraviolet irradiation was dose dependent. For the highest dose used this was 7 to 8 days, beyond which there was no further change in mutant frequency. The dose-response relationship of these agents does not appear to deviate from linearity; this permits the calculation of mutation rate per unit dose. For X-rays, this value was 1.35 x 10-7 per rad per locus, for ethyl methane sulphonate, 2.2 x 10-2 per mole per locus and for ultraviolet irradiation, 6.3 x 10-6 per erg per mm2 per locus. The effectiveness of the 3 different mutagens for the induction of mutations was compared by calculating the increase in mutant frequency per unit of decrease in survival (D0). These increments in frequency were: 5.6 x 10-5 for X-rays, 69.5 x 10-5 for ethyl methane sulphonate and 16.6 x 10-5 for ultraviolet irradiation

  17. Component resolved OSL dose response and sensitization of various sedimentary quartz samples

    International Nuclear Information System (INIS)

    The structure of the linearly modulated optically stimulated luminescence (LM-OSL) signal was studied for four sedimentary quartz samples, collected from different sites around Istanbul, Turkey. Applying a computerized deconvolution analysis to the LM-OSL curves, at least six individual components of first-order kinetics were identified and photoionization cross-section of each component was evaluated. The OSL dose-response curve of each component for each quartz sample was obtained, showing a remarkable differentiation from component to component. The behavior of a highly dosed sample to successive LM-OSL measurements was also studied showing a stable recuperation signal in the position of the 'slow' and 'medium' components and high resistance to OSL bleaching of the 'slow' component. The individual sensitivity of each component as a function of the activation temperature was obtained. The sensitivity of each component was normalized over the respective sensitivity of the glow-peak at 110 deg. C of quartz in order to investigate the ability of the 110 deg. C glow-peak to act as a correction factor for all components of the LM-OSL curves examined

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

    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

  19. Dose response for rat skin tumors induced by single and split doses of argon ions

    International Nuclear Information System (INIS)

    Skin and other organs are capable of repairing part of the damage that eventually leads to induction of tumors if the radiation is low LET. With the availability of the argon-ion beam at the Bevalac facility at LBL, it became feasible to study repair or recovery at the LET of maximum biological effectiveness. The existence of extensive data on the dose-response curve for tumor induction in rat skin made this an ideal system for studying the RBE and repair at high-LET values in a specific organ where whole body irradiation can be avoided. Tumors began to appear by about 10 weeks in the higher dose groups and continued to appear more or less steadily until the end of the experiment at 99 weeks when overall survival was about 70%. Similarly, when the dose was fractionated the tumors began to appear at 10 weeks and continued to appear throughout the experiment at both doses. The fractionated exposures, rather than reducing the yield of tumors as for fractionated electron radiation, actually produced a slight increase in tumor yield

  20. 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)

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

    International Nuclear Information System (INIS)

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

  2. Effect of composition interactions on the dose response of an N-isopropylacrylamide gel dosimeter.

    Science.gov (United States)

    Chang, Yuan-Jen; Hsieh, Bor-Tsung

    2012-01-01

    In this study, a two-level full factorial design was used to identify the effects of the interactions between compositions in an N-isopropylacrylamide (NIPAM) gel dosimeter involving the following variables: (A) gelatin, (B) NIPAM, (C) the crosslinker N, N'-methylene-bis-acrylamide (Bis), and (D) the antioxidant tetrakis (hydroxymethyl) phosphonium chloride (THPC). The dose range was from 0 Gy to 5 Gy. Optical computed tomography was used to scan the polymer gel dosimeter. Each component was set to two levels for all four variables, including (A) 4% and 6%, (B) 4% and 6%, (C) 2% and 4%, as well as (D) 5 and 15 mM. Response surface methodology and a central composite design were adopted for the quantitative investigation of the respective interaction effects on the dose response curve of the gel. The results showed that the contributions of the interaction effects, i.e., AB (6.22%), AC (8.38%), AD (7.74%), BC (9.44%), ABC (18.24%), BCD (12.66%), and ABCD (13.4%), were greater than those of the four main effects, accounting for over 76.08% of the total variability. These results also indicated that the NIPAM gel recipe with the highest sensitivity was at 40%C (mass fraction of Bis). PMID:23077487

  3. dose-response functions and mapping of risk for materials in urban polluted atmosphere

    Science.gov (United States)

    Laurans, E.; Ausset, P.; Chabas, A.; Lefevre, R.-A.

    2003-04-01

    The French field test-site of the United-Nations International Co-operative Programme "Influence of Atmospheric Pollution on Materials, including Historic and Cultural Monuments" (ICP-Materials) located at the top of the Saint-Eustache Church in a pedestrian area in the center of Paris allows to expose various materials (stone, glass, metals, polymers...) and to measure simultaneously the atmospheric parameters (gases, particles, rain, temperature, relative humidity, time of wetness...). The dose-response functions are calculated from the doses recorded on the 30 test-sites of the ICP-Materials network and from the responses analyzed on exposed samples. The critical or acceptable levels and loads are then determined and illustrated by means of mapping. The map of risk for Portland limestone, on the entire French territory and only on Ile-de-France are then given. In conclusion, an improvement of the method is proposed for stone: the mapping of the risk has no meaning except for the area of utilization. Nevertheless, the map of risk for entire Europe concerning materials universally used, like Carrara marble, Portland cement based mortars and Si-Ca-Na modern glass are of better utility.

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

    International Nuclear Information System (INIS)

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

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

    Scientific Electronic Library Online (English)

    Madelaine, Sarria Castro; Luis Carlos, Silva Ayçaguer.

    2004-05-01

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

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

    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.

  7. Light-emitting diode therapy (LEDT) before matches prevents increase in creatine kinase with a light dose response in volleyball players.

    Science.gov (United States)

    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

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

    Scientific Electronic Library Online (English)

    Suzana Alves de, Moraes; José Maria Pacheco de, Souza.

    1996-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Suzana Alves de Moraes

    1996-10-01

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

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

    Scientific Electronic Library Online (English)

    Suzana Alves de, Moraes; José Maria Pacheco de, Souza.

    1996-10-01

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

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

    International Nuclear Information System (INIS)

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

  12. Dose-response relationship of ?-ray-induced reciprocal translocations at low doses in spermatogonia of the crab-eating monkey (Macaca fascicularis)

    International Nuclear Information System (INIS)

    The yield of translocations induced by acute ?-irradiation at low doses in the crab-eating monkey's (Macaca fascicularis) spermatogonia was examined. Over the low dose range from 0 to 1 Gy, the dose-response relationship for translocation yield was a linear one. To estimate the sensitivity to the induction of translocations in the crab-eating monkey's spermatogonia, the slope of the regression line was compared with those in other mammalian species. Consequently, over the low dose range below 1 Gy, the sensitivity of the crab-eating monkey's spermatogonia to translocation induction was similar to several mammalian species, the mouse, Chinese hamster, and the rabbit, but significantly higher than that of the rhesus monkey and lower than that of the marmoset. (Auth.)

  13. Fifteen-year follow-up of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition depressive disorders: the prognostic significance of psychotic features.

    Science.gov (United States)

    Jäger, Markus; Bottlender, Ronald; Strauss, Anton; Möller, Hans-Jürgen

    2005-01-01

    Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), after Kraepelin's original description of "manic-depressive insanity," embodied a broad concept of affective disorders including mood-congruent and mood-incongruent psychotic features. Controversial results have been reported about the prognostic significance of psychotic symptoms in depressive disorders challenging this broad concept of affective disorders. One hundred seventeen inpatients first hospitalized in 1980 to 1982 who retrospectively fulfilled the DSM-IV criteria for depressive disorders with mood-congruent or mood-incongruent psychotic features (n = 20), nonpsychotic depressive disorders (n = 33), or schizophrenia (n = 64) were followed up 15 years after their first hospitalization. Global functioning was recorded with the Global Assessment Scale; the clinical picture at follow-up was assessed using the Hamilton Rating Scale for Depression, the Positive and Negative Syndrome Scale, and the Scale for the Assessment of Negative Symptoms. With respect to global functioning, clinical picture, and social impairment at follow-up, depressive disorders with psychotic features were similar to those without, but markedly different from schizophrenia. However, patients with psychotic depressive disorders experienced more rehospitalizations than those with nonpsychotic ones. The findings indicating low prognostic significance of psychotic symptoms in depressive disorders are in line with the broad concept of affective disorders in DSM-IV. PMID:16122531

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Spigset Olav

    2001-08-01

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

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

    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.

  17. Integrating in vitro sensitivity and dose-response slope is predictive of clinical response to ABL kinase inhibitors in chronic myeloid leukemia

    OpenAIRE

    Vainstein, Vladimir; Eide, Christopher A.; O’hare, Thomas; Shukron, Ofir; Druker, Brian J.

    2013-01-01

    Decreased in vitro dose-response slope tracks with resistance BCR-ABL mutants to ABL tyrosine kinase inhibitors.Integrating in vitro dose-response slope, the IC50 of various BCR-ABL mutants, and clinical PK data can predict CML patients’ response to TKIs.

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

    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).

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

    Science.gov (United States)

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

    2003-01-01

    OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). CONCLUSIONS: Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation, it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults. Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign. Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses, but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions. This suggests that sleep debt is perhaps best understood as resulting in additional wakefulness that has a neurobiological "cost" which accumulates over time.

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

    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.

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

    International Nuclear Information System (INIS)

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

  2. Gamma-ray dose response of ESR signals in tooth enamel of cows and mice in comparison with human teeth

    Energy Technology Data Exchange (ETDEWEB)

    Toyoda, Shin E-mail: toyoda@dap.ous.ac.jp; Tanizawa, Honami; Romanyukha, A.A.; Miyazawa, Chuzou; Hoshi, Masaharu; Ueda, Yuji; Nitta, Yumiko

    2003-10-01

    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.

  3. Gamma-ray dose response of ESR signals in tooth enamel of cows and mice in comparison with human teeth

    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

  4. IRSL dating of K-feldspars: Modelling natural dose response curves to deal with anomalous fading and trap competition

    International Nuclear Information System (INIS)

    We recently proposed a model that reconstructs the natural dose response curve for K-rich feldspars, using laboratory fading measurements and dose response as input parameters. The model is based on the relationship between recombination centre density and trap lifetime. In this study we test the working of the model by comparing modelled feldspar ages with known quartz OSL ages of the same samples and with anomalous fading-corrected feldspar ages. The modelled feldspar ages are in good agreement with quartz OSL ages and corrected feldspar ages, opening possibilities for future use of the model on samples without independent age constraints. Furthermore, we investigate the effects of trap competition on the build-up of IRSL signal using two new variations of the model. Results show that incorporating trap competition into the model reduces the agreement between feldspar IRSL ages and quartz OSL ages.

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

    OpenAIRE

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

    2010-01-01

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

  6. Radiotherapy dose–response analysis for diffuse large B-cell lymphoma with a complete response to chemotherapy

    OpenAIRE

    Dorth Jennifer A; Prosnitz Leonard R; Broadwater Gloria; Beaven Anne W; Kelsey Chris R

    2012-01-01

    Abstract Objective To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Methods Patients with stage I-IV DLBCL treated from 1995–2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered...

  7. A dynamic dose–response model to account for exposure patterns in risk assessment: a case study in inhalation anthrax

    OpenAIRE

    Mayer, Bryan T.; Koopman, James S.; Ionides, Edward L.; Pujol, Josep M.; Eisenberg, Joseph N. S.

    2010-01-01

    The most commonly used dose–response models implicitly assume that accumulation of dose is a time-independent process where each pathogen has a fixed risk of initiating infection. Immune particle neutralization of pathogens, however, may create strong time dependence; i.e. temporally clustered pathogens have a better chance of overwhelming the immune particles than pathogen exposures that occur at lower levels for longer periods of time. In environmental transmission systems, we expect diff...

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

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, E.S.; Fix, J.J.

    1996-08-01

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

  9. Dose-response in an outbreak of non-bacterial food poisoning traced to a mixed seafood cocktail.

    OpenAIRE

    Gray, S. F.; Evans, M. R.

    1993-01-01

    An outbreak of non-bacterial food poisoning presumed due to small round, structured viruses (SRSV) occurred at a national conference. A detailed postal survey of all conference attenders was carried out to ascertain the cause of the outbreak and 355 questionnaires were returned. Univariate analysis showed that mussels in the seafood cocktail were the likely vehicle of infection. A dose-response relationship between the amount of seafood cocktail consumed and the risk of illness was demonstrat...

  10. Dose-response relation between exposure to two types of hand-arm vibration and sensorineural perception of vibration.

    OpenAIRE

    Virokannas, H.

    1995-01-01

    OBJECTIVES--31 railway workers and 32 lumberjacks were examined to compare the dose-response relation between the exposure to two types of hand-arm vibration and the sensory disturbances in peripheral nerves as evaluated by the vibration perception thresholds (VPTs). METHODS--Clinical examinations were carried out that included measurements of the VPTs, and electroneuromyography (ENMG), and an inquiry to confirm the use of vibrating tools. Diseases of the central nervous system and neuropathi...

  11. Universality of J-Shaped and U-Shaped Dose-Response Relations as Emergent Properties of Stochastic Transition Systems

    OpenAIRE

    Cox, Louis Anthony

    2006-01-01

    Dose-response data for many chemical carcinogens exhibit multiple apparent concentration thresholds. A relatively small increase in exposure concentration near such a threshold disproportionately increases incidence of a specific tumor type. Yet, many common mathematical models of carcinogenesis do not predict such threshold-like behavior when model parameters (e.g., describing cell transition rates) increase smoothly with dose, as often seems biologically plausible. For example, commonly use...

  12. Randomized controlled trial of 2 prenatal iron supplements: is there a dose-response relation with maternal hemoglobin?

    OpenAIRE

    Roberfroid, D.; Huybregts, L.; Habicht, J. P.; Lanou, H.; Henry, M. C.; Meda, N.; D Alessandro, U.; Kolsteren, P.

    2011-01-01

    BACKGROUND: The most appropriate dose of iron to prevent maternal anemia is still unclear. OBJECTIVE: We assessed the dose-response relation between maternal hemoglobin and 2 prenatal iron supplements. DESIGN: An intention-to-treat, double-blind, randomized controlled trial compared 30 mg Fe + folic acid and 13 other micronutrients (UNIMMAP; UNICEF/WHO/UNU multiple micronutrient supplement for pregnant and lactating women) with 60 mg Fe + folic acid (IFA) only in rural Burkina Faso. Home visi...

  13. Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat

    Science.gov (United States)

    Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat M.F. Hughes1, D.G. Ross1, J.M. Starr1, E.J. Scollon1,2, M.J. Wolansky1,3, K.M. Crofton1, M.J. DeVito1,4 1U.S. EPA, ORD, Research Triangle Park, NC, 2U.S. EPA,...

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

    International Nuclear Information System (INIS)

    Studies of the dose response of the spermatogonial stem cells in the rhesus monkey were performed at intervals of 130 and 160 days after graded doses of X irradiation. The D0 of the spermatogonial stem cells was established using the total numbers of the type A spermatogonia that were present at 130 and 160 days after irradiation and was found to be 1.07 Gy; the 95% confidence interval was 0.90-1.34 Gy

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

    Science.gov (United States)

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

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert ?-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6?7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA. PMID:24293226

  16. Computational systems biology and dose-response modeling in relation to new directions in toxicity testing.

    Science.gov (United States)

    Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B

    2010-02-01

    The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell biology has advanced rapidly with increasing availability of new data and powerful simulation techniques, a quantitative orientation is still lacking in life sciences education to make efficient use of these new tools to implement the new toxicity testing paradigm. A revamped undergraduate curriculum in the biological sciences including compulsory courses in mathematics and analysis of dynamical systems is required to address this gap. In parallel, dissemination of computational systems biology techniques and other analytical tools among practicing toxicologists and risk assessment professionals will help accelerate implementation of the new toxicity testing vision. PMID:20574901

  17. Workshop report: identifying key issues underpinning the selection of linear or non-linear dose-response extrapolation for human health risk assessment of systemic toxicants.

    Science.gov (United States)

    Pottenger, Lynn H; Becker, Richard A; Moran, Elizabeth J; Swenberg, James A

    2011-04-01

    The report of an Expert Panel convened by the National Research Council (NRC) of the National Academy of Sciences (NAS), entitled Science and Decisions: Advancing Risk Assessment (National Research Council, 2009a), includes a recommendation to use, as a default approach, low-dose linear extrapolation for systemic toxicity. This recommendation represents a significant departure from long-standing risk assessment practices for non-cancer toxicity, where the most appropriate No Observed Adverse Effect Level (NOAEL) or Benchmark Dose (BMD) of the critical effect in the key study is selected, and then a "safe exposure" level is derived by applying uncertainty factors to account for dataset completeness, potential greater sensitivity of humans when compared with experimental animals, and for potential variability of sensitivity in humans. A workshop was held to "frame" issues raised by the NAS report that needed further study. Workshop objectives included the following: (1) identify the issues raised by the 2009 NRC report and discuss the extent to which existing science may (or may not) align with the NAS analyses and recommendations, and (2) identify/develop possible actions to assist in advancing deeper and broader considerations of some of the critical issues presented by the 2009 NAS Panel. Experts invited to this "Framing" Workshop encompassed a full spectrum of toxicology and risk assessment disciplines; in particular, expertise in molecular interactions and dose-response of biological systems were well represented. The recommendations developed at this Framing Workshop provide specific ideas on possible further steps to facilitate deeper and broader consideration of the issues underpinning dose-response extrapolation in the risk assessment of systemic toxicants. PMID:21256913

  18. Nonlinearity and thresholds in dose-response relationships for carcinogenicity due to sampling variation, logarithmic dose scaling, or small differences in individual susceptibility

    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 spnts 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

  19. Nonlinearity and thresholds in dose-response relationships for carcinogenicity due to sampling variation, logarithmic dose scaling, or small differences in individual susceptibility.

    Science.gov (United States)

    Lutz, W K; Gaylor, D W; Conolly, R B; Lutz, R W

    2005-09-01

    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. PMID:15982698

  20. Dose-response relationship for induction of ovarian tumors in mice irradiated during prenatal, early postnatal and elder periods

    International Nuclear Information System (INIS)

    Female B6C3F1 mice were irradiated at day 17 prenatal period, day 0, 7, 35, 105, 240, 365 and 550 postnatal period with doses of 0.10 to 5.70 Gy gamma rays from 137Cs. All mice were allowed to live through their entire life spans under a specific-pathogen free condition. The excess relative risk for prevalence at the time of death of ovarian tumors was used as a comprehensive measure of radiation effect. The excess relative risks at 1 Gy were estimated for all irradiated groups based on the dose-response relationships and compared to each other. A marked increase in susceptibility was found during the age between day 17 prenatal and day 0 postnatal period. A drastic decrease in susceptibility was observed during the period between day 105 and day 240. The shape of the dose-response curve was downward concave in mice irradiated at day 0, 7, 35 or 105 postnatal period, whereas, the downward curvature of dose-response was not observed in mice irradiated at day 17 prenatal period, day 240, 365 or 550 postnatal period. It has become obvious that mice of the early postnatal, pre-puberty and young adult periods are highly susceptible to induction of ovarian tumors by gamma rays. (author)

  1. Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation (NCRP Report No 136)

    International Nuclear Information System (INIS)

    National Council on Radiation Protection and Measurements MD: NCRP (2001) 287 pp, $50.00 Lively debate continues on the nature of the dose-response relationship for the excess risk of cancer following exposure to ionising radiation at low doses and/or low dose rates. Clearly, these are the exposure conditions of principal importance to radiological protection. Presently, for the purposes of radiological protection, the assumption is made that the underlying dose-response relationship is linear-quadratic with no threshold, and that in the low dose and/or low dose rate region this curve can be approximated by a straight line with a gradient half that of the linear relationship which (for cancers other than leukaemia) is appropriate for moderate to high doses received at high dose rates. This, in essence, is the 'linear-nonthreshold (LNT) dose-response model' referred to in the title of NCRP Report No 136. The report begins by examining the way in which radiation energy is deposited in cells. It concludes that at low doses and low dose rates the relevant biological damage would be produced by a 'single hit' because of the spatial and temporal sparseness of the events causing the damage. Since cancer is considered to be monoclonal (single cell) in origin, this suggests that the dose-response is linear at low doses with no threshold. However, it is possible that the whole organism may be more capable of repairing damage at low doses and low dose rates, whic h would modify s and low dose rates, whic h would modify the dose-response to a sub-linear curve. The extent of such modification, if it exists, is unknown as is whether it could be 100% effective as implied by a threshold in the dose-response at some non-zero dose. The evidence for the modification of the dose-response curve at low doses is considered in the report in four chapters dealing with various biological manifestations of the fundamental damage caused by ionising radiation. The chapter on DNA repair and processing concludes that it is likely that exposure of humans to low doses and low dose rates does result in permanent alterations in DNA sequences, which points away from a threshold. However, many steps are required between these events and clinical cancer and it is not known how this progression might differ after low dose irradiation. The next chapter discusses radiation-induced mutations. All types of mutations commonly seen in human cancers can be induced by ionising radiation. There is no direct evidence for a threshold in the dose-response obtained from in vitro studies. Genomic instability may contribute to radiation-induced carcinogenesis and produce a non-linear dose-response, but insufficient is known about this process at the moment. The misrepair of DNA lesions can also give rise to chromosome aberrations and this is considered in the next chapter. While the existing data do not exclude the possibility that a threshold for the induction of chromosome aberrations may exist in the mSv dose range, there is no body of data supporting such a possibility nor would such a threshold be consistent with current understanding of the mechanisms of chromosome aberration formation at low doses. Oncogenic transformation in vitro and genomic instability are considered in the following chapter. The dose-response curve for neoplastic transformation is complex in shape and subject to variation depending upon the particular cells and experimental conditions under investigation. The report identifies the principal research need as being the development of transformation assays based on human cells. The experimental findings concerning carcinogenic effects in laboratory animals (next chapter) permit few generalisations concerning the shapes of the dose-response curves. The variations in the dose-response relationships for different cancers point to differences in causal mechanisms which are not yet understood. However, it is clear that cancer induction in vivo is a multi-stage process. The epidemiological evidence for carcinogenic effects in human populations is consider

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

    International Nuclear Information System (INIS)

    Background: The bioeffect of a physical dose depends on the nature of the tissue, fractionation scheme, dose rate and treatment time. Certainly, experienced radiotherapists are convinced of the existence of patient-to-patient variability in normal tissue response to radiotherapy for malignant tumours. The absorbed dose needs to be translated into a bioeffect dose, which takes into account treatment variables and the radiobiological characteristics of the relevant tissue. Various bioeffect models such as NSD, CRE, TDF and BED have been proposed to predict the biological effect of radiotherapy treatments. Aim: This study was aimed at deriving tolerance bioeffect dose values for normal tissue complication rate. Materials/Methods: Compiled clinical data of time dose fractionation schedules and incidence of erythema, desquamation and telangiectasia were used for the present analysis. Results: For erythema and desquamation the radiation dose varied from 23.9 to 55.1 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 40 days. For telangiectasia (score .1 at 3 years) the radiation dose varied from 25.8 to 55.1 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 40 days. For telangiectasia (score .2 at 5 years) the radiation dose varied from 25.8 to 63.0 Gy in 04 to 50 fractions (dose per fraction 1.1 to 7.3 Gy) in 11 to 68 days. For telangiectasia (score .1, .2, .3, .4 at 10 years) the radiation dose varied from 25.8 to 63.0 Gy in 04 to 35 fraaried from 25.8 to 63.0 Gy in 04 to 35 fractions (dose per fraction 1.7 to 7.3 Gy) in 22 to 68 days. TDF and LQF values for erythema, desquamation and telangiectasia were evaluated with a/b values of 7.5 Gy, 11.2 Gy and 2.8 Gy respectively. TDF and LQF had a statistically significant correlation with probability of erythema, desquamation and telangiectasia (p<0.001). Conclusions: TDF and LQF values should be limited to 60 and 86 Gy in order to limit the probability of telangiectasia. (authors)

  3. Hand-arm vibration syndrome and dose-response relation for vibration induced white finger among quarry drillers and stonecarvers. Italian Study Group on Physical Hazards in the Stone Industry.

    Science.gov (United States)

    Bovenzi, M

    1994-01-01

    OBJECTIVES--To investigate the occurrence of disorders associated with the hand arm vibration syndrome in a large population of stone workers in Italy. The dose-response relation for vibration induced white finger (VWF) was also studied. METHODS--The study population consisted of 570 quarry drillers and stonecarvers exposed to vibration and 258 control stone workers who performed only manual activity. Each subject was interviewed with health and workplace assessment questionnaires. Sensorineural and VWF disorders were staged according to the Stockholm workshop scales. Vibration was measured on a representative sample of percussive and rotary tools. The 8 h energy equivalent frequency weighted acceleration (A (8)) and lifetime vibration doses were calculated for each of the exposed stone workers. RESULTS--Sensorineural and musculoskeletal symptoms occurred more frequently in the workers exposed to vibration than in the controls, but trend statistics did not show a linear exposure-response relation for these disorders. The prevalence of VWF was found to be 30.2% in the entire group exposed to vibration. Raynaud's phenomenon was discovered in 4.3% of the controls. VWF was strongly associated with exposure to vibration and a monotonic dose-response relation was found. According to the exposure data of this study, the expected percentage of stone workers affected with VWF tends to increase roughly in proportion to the square root of A(8) (for a particular exposure period) or in proportion to the square root of the duration of exposure (for a constant magnitude of vibration). CONCLUSION--Even although limited to a specific work situation, the dose-response relation for VWF estimated in this study suggests a time dependency such that halving the years of exposure allows a doubling of the energy equivalent vibration. According to these findings, the vibration exposure levels currently under discussion within the European Community seem to represent reasonable exposure limits for the protection of workers against the harmful effects of hand transmitted vibration. PMID:7951792

  4. Dose-response relations for dicentric yields in G0 lymphocytes of man and crab-eating monkey following acute and chronic ?-irradiations

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

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

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

    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 largensitive 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

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

    International Nuclear Information System (INIS)

    Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of ?-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and ?-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y(0.5h) = 11.66D + 0.15 (R2 = 0.99), Y(5h) = 2.44D + 0.15 (R2 = 0.99), Y(8h) = 1.57D + 0.22 (R2 = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using ?-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in ?-H2AX foci kinetics after gamma- and X-irradiation in vitro.

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

    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

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

    International Nuclear Information System (INIS)

    To explore mechanism for the effect of saddle-like dose-response curve, the relationship of irradiation-vacuum stress, and irradiation-salt stress, was investigated with rice seeds irradiated to 60-560 Gy by 60Co ?-rays. The dose-response curve was simulated based on seedling height data, which showed obedient to linear-quadratic model. During germination,the irradiated rice seeds were stressed by 10-3 Pa vacuum, or by NaCl in different concentrations. After that, the dose-response curve manifested a saddle-like shape. The results indicate that while low dose irradiation could retard seedling growth synergistically with vacuum stress and salt stress, it could also induce adaptive response upon vacuum stress and salt stress. Low dose irradiation induced adaptive response upon environmental adverse factors could contribute to the mechanism for the effect of saddle-like dose-response curve. (authors)

  10. Preliminary research on dose response of LiF thermoluminescence dosimeter to irradiation of 49.3 MeV/u carbon ion beam

    International Nuclear Information System (INIS)

    LiF(Mg, Ti) thermoluminescence dosimeter (TLD) was applied to measure dose response to irradiation of 49.3 MeV/u 12C ion beam supplied by HIRFL. Moderate variance of dose-response efficiency was found when particle fluence increases from 1 x 107 to 2 x 108 /cm2. The average dose-response efficiency 57% was obtained. This phenomenon implies that LiF can be used to measure absorbed dose in a certain range of particle fluence. Moreover, the result is in a good agreement with the calculated dose-response efficiency 54% to 50 MeV/u 12C ion beam, which was predicted by the model of heavy-ion track structure at GSI, Germany

  11. Is a dose-response relationship a valid concept for the induction of leukaemia by bone-seeking ?-emitting radionuclides?

    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)

  12. Dose-response relationship for two components of the sex pheromone of lightbrown apple moth,Epiphyas postvittana (Lepidoptera: Tortricidae).

    Science.gov (United States)

    Bellas, T E; Bartell, R J

    1983-06-01

    Bioassay studies with mixtures of the two components from the sex pheromone ofE. postvittana are used to construct a dose-response surface. The surface clearly shows the existence of a response maximum and that an optimum ratio of the two components applies over a wide range of concentrations. Probit transformations of the same data are used to construct an isobologram. The isobole has a sharp minimum at a ratio for the two components close to the ratio produced by the females. PMID:24407619

  13. Evaluation of the comet assay for assessing the dose-response relationship of DNA damage induced by ionizing radiation.

    Science.gov (United States)

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

    2013-01-01

    Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by ?-ray irradiation. A clear dose-response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p irradiation (p DNA double-strand breaks and DNA repair in vitro of human lymphocytes presented a nice model, and a smooth, three-dimensional plane model was obtained when the two curves were combined. PMID:24240807

  14. 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

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

    OpenAIRE

    Sand, Salomon

    2005-01-01

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

  16. External beam radiotherapy dose response characteristics of 1127 men with prostate cancer treated in the PSA era

    International Nuclear Information System (INIS)

    Purpose: To characterize the relationship of radiotherapy dose to prostate cancer patient outcome, with an emphasis on the influence of pretreatment prognostic variables. Methods and Materials: The 1127 Stage T1-T4 prostate cancer patients examined were treated consecutively with definitive external beam radiotherapy at the University of Texas-M.D. Anderson Cancer Center from 1987 to 1997. All had a pretreatment prostate-specific antigen (PSA) level. Treatment failure was defined as two consecutive PSA elevations on follow-up. There were 994 patients treated with a four-field box throughout to 60-70 Gy after a small reduction at 46 Gy and 161 treated with a six-field conformal boost after 46 Gy to 74-78 Gy. No patient received neoadjuvant or adjuvant androgen ablation. Median follow-up was 51.8 months. Results: Patients were divided into three radiotherapy dose groups consisting of ?67 Gy (n = 500), >67-77 Gy (n = 495), and >77 Gy (n = 132). Relative to other prognostic factors, there were fewer patients treated to the highest dose level with a pretreatment PSA (PSAB) ?4 or >20 ng/ml, Stage T3/T4 disease, or a Gleason score of 2-6. Actuarial 4-year freedom from biochemical failure (bNED) rates for the entire cohort were 54%, 71%, and 77% (p 67-77 Gy was associated with improved bNED rates for all PSAB (?10 and >10), stage (T1/T2 and T3/T4), and Gleason score (2-6 and 7-10) subgroups tested. In contrast, the only prognostic group that benefited from raising dose from >67-77 Gy to >77 Gy was patients with a PSAB >10 ng/ml; although trends were noted for Stage T1/T2 and Gleason 2-6 patients. Patients with the combined features of a PSAB >10 ng/ml and Stage T1/T2 disease had 4-year bNED rates of 61% and 93% at the intermediate- and high-dose levels. A strongly significant linear association between dose (60-78 Gy) and 4-year actuarial bNED was demonstrated for patients with these intermediate-risk features. Conclusion: Prostate cancer dose response to external beam radiotherapy should be considered in the context of pretreatment prognostic factors. Our data indicate that, for favorable patients with a PSAB of ?10 ng/ml, intermediate doses of >67-77 Gy provide the same rate of control as higher doses. However, longer follow-up may reveal a benefit to dose escalation >77 Gy, even in this favorable subset. Substantial and clinically relevant enhancements in bNED were seen at all dose levels for moderate-risk patients, such as those having a PSAB >10 ng/ml and Stage T1/T2 disease. Sustained bNED was not realized for high-risk patients, even using 78 Gy; these patients may be best treated with higher doses, whole pelvic irradiation, and/or androgen ablation plus radiation

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

    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.

  18. Joint action of chemicals in algal toxicity tests: Influence of response level and dose-response regression model

    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.

  19. Radiation dose response of normal lung assessed by Cone Beam CT - A potential tool for biologically adaptive radiation therapy

    International Nuclear Information System (INIS)

    Background: Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose. Methods: A total of 665 CBCTs in 65 lung cancer patients treated with IMRT/VMAT to 60 or 66 Gy in 2 Gy fractions were analyzed. For each patient, CBCT lung density changes during the treatment course were related to the locally delivered dose. Results: A dose response is observed for the patient population at the end of the treatment course. However, the observed dose response is highly variable among patients. Density changes at 10th and 20th fraction are clearly correlated to those observed at the end of the treatment course. Conclusions: CBCT density changes in healthy lung tissue during radiotherapy correlate with the locally delivered dose and can be detected relatively early during the treatment. If these density changes are correlated to subsequent clinical toxicity this assay could form the basis for biological adaptive radiotherapy.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  2. Dose-response effect of black maca (Lepidium meyenii) in mice with memory impairment induced by ethanol.

    Science.gov (United States)

    Rubio, Julio; Yucra, Sandra; Gasco, Manuel; Gonzales, Gustavo F

    2011-10-01

    Previous studies have shown that black variety of maca has beneficial effects on learning and memory in experimental animal models. The present study aimed to determine whether the hydroalcoholic extract of black maca (BM) showed a dose-response effect in mice treated with ethanol 20% (EtOH) as a model of memory impairment. Mice were divided in the following groups: control, EtOH, ascorbic acid (AA) and 0.125, 0.25, 0.50 and 1.00?g/kg of BM plus EtOH. All treatments were orally administered for 28 days. Open field test was performed to determine locomotor activity and water Morris maze was done to determine spatial memory. Also, total polyphenol content in the hydroalcoholic extract of BM was determined (0.65?g pyrogallol/100?g). Mice treated with EtOH took more time to find the hidden platform than control during escape acquisition trials; meanwhile, AA and BM reversed the effect of EtOH. In addition, AA and BM ameliorated the deleterious effect of EtOH during the probe trial. Correlation analyses showed that the effect of BM a dose-dependent behavior. Finally, BM improved experimental memory impairment induced by ethanol in a dose-response manner due, in part, to its content of polyphenolic compounds. PMID:21780878

  3. Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol

    Directory of Open Access Journals (Sweden)

    Ruth Gallily

    2015-02-01

    Full Text Available Cannabidiol (CBD, a major constituent of Cannabis, has been shown to be a powerful anti-inflammatory and anti-anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell-shaped dose-response was observed, which limits its clinical use. In the present study, we have studied in mice the anti-inflammatory and anti-nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients. In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses. The clone 202 extract reduced zymosan-induced paw swelling and pain in mice, and prevented TNF? production in vivo. It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD. We therefore propose that Cannabis clone 202 (Avidekel extract is superior over CBD for the treatment of inflammatory conditions.

  4. Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.

    Science.gov (United States)

    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 changes in speed and travel direction judged to be avoidance responses during six of eight sessions. Following methods developed for Phase-I clinical trials in human medicine, response thresholds ranging from 94 to 164?dB re 1??Pa received sound pressure level (SPL) were fitted to Bayesian dose-response functions. Thresholds did not consistently differ by sonar frequency or whether a group had previously been exposed, with a mean SPL response threshold of 142?±?15?dB (mean ± s.d.). High levels of between- and within-individual variability were identified, indicating that thresholds depended upon other undefined contextual variables. The dose-response functions indicate that some killer whales started to avoid sonar at received SPL below thresholds assumed by the U.S. Navy. The predicted extent of habitat over which avoidance reactions occur depends upon whether whales responded to proximity or received SPL of the sonar or both, but was large enough to raise concerns about biological consequences to the whales. PMID:25234905

  5. Dose-response effects of Lepidium meyenii (Maca) aqueous extract on testicular function and weight of different organs in adult rats.

    Science.gov (United States)

    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; P<0.0001) and low-testosterone/estradiol ratio (R2=0.35; P<0.0001). Increase in epididymal sperm count was related to lengths of stages VII-VIII. Highest effect on stages VII-VIII of the seminiferous tubules was observed at 1.0 g Maca 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

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

    International Nuclear Information System (INIS)

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

  7. Dose response chemopreventive potential of allyl isothiocyanate against 7,12-dimethylbenz(a)anthracene induced mammary carcinogenesis in female Sprague-Dawley rats.

    Science.gov (United States)

    Rajakumar, Thangarasu; Pugalendhi, Pachaiappan; Thilagavathi, Subbaiyan

    2015-04-25

    The present study aimed to investigate the dose response chemopreventive potential of allyl isothiocyanate (AITC) against 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female Sprague-Dawley rats. Mammary tumor was induced by a single dose of DMBA (25mg/rat) injected subcutaneously near mammary gland. We observed reduced body weight and increased in total number of tumors, tumor incidence and tumor volume in DMBA-induced rats. We also observed decreased antioxidant status (SOD, CAT, GPX and GSH) and increased lipid peroxidation (TBARS and LOOH) in plasma and mammary tissues. Increased levels of CYP450, Cyt-b5 and decreased levels of phase II (GST and GR) biotransformation enzymes noticed in liver and mammary tissues of DMBA-induced rats. Further, increased levels of lipid profile (TC, TG, PL and FFA) and lipoprotein (LDL and VLDL) were noticed. Whereas, decreased level of HDL in plasma and decreased levels of PL and FFA in mammary tissue. Oral administration of AITC different doses (10, 20 and 40mg/kgbw) inhibited the tumor incidence and restored levels of biochemical markers. Biochemical findings are supported by histopathological studies. These results suggested that AITC at a dose of 20mg/kgbw significantly exert chemopreventive potential against DMBA-induced mammary carcinogenesis. PMID:25744308

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

    Science.gov (United States)

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

    1972-01-01

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

  9. A New Drug Combinatory Effect Prediction Algorithm on the Cancer Cell Based on Gene Expression and Dose–Response Curve

    Science.gov (United States)

    Goswami, C Pankaj; Cheng, L; Alexander, PS; Singal, A; Li, L

    2015-01-01

    Gene expression data before and after treatment with an individual drug and the IC20 of dose–response data were utilized to predict two drugs' interaction effects on a diffuse large B-cell lymphoma (DLBCL) cancer cell. A novel drug interaction scoring algorithm was developed to account for either synergistic or antagonistic effects between drug combinations. Different core gene selection schemes were investigated, which included the whole gene set, the drug-sensitive gene set, the drug-sensitive minus drug-resistant gene set, and the known drug target gene set. The prediction scores were compared with the observed drug interaction data at 6, 12, and 24 hours with a probability concordance (PC) index. The test result shows the concordance between observed and predicted drug interaction ranking reaches a PC index of 0.605. The scoring reliability and efficiency was further confirmed in five drug interaction studies published in the GEO database.

  10. Radiation alone in the treatment of cancer of the uterine cervix: Analysis of pelvic failure and dose response relationship

    International Nuclear Information System (INIS)

    This retrospective analysis involves 569 patients with invasive cancer of the uterine cervix treated with irradiation alone between 1969 and 1980. Treatment consisted of external and intracavitary irradiation and treatment policy remained consistent throughout the study interval. In early stage disease (FIGO IA, IB, and IIA), pelvic failure was 4.6%, 11.2%, and 8.2%, respectively. In late stage disease (FIGO IIB, III, and IVA), pelvic failure was 30.1%, 52.3%, and 69.2%, respectively. Further analysis revealed that total dose at point A is well correlated with pelvic control. An aggressive treatment is crucial in late stage disease in determining the probability of pelvic tumor control and survival. Methods of dose prescription, dose-response relationships, treatment philosophy and its therapeutic implications are discussed

  11. [The dose-response relationship for indices of the micronucleus test using neutron-spectra therapeutic irradiation].

    Science.gov (United States)

    Ankina, M A; Mikha?lova, G F; Filimonov, A S

    1991-01-01

    It was shown by method of cytokinetic blocking that with neutron irradiation of human lymphocyte culture (mean energy of 0.85 MeV, doses of 0.05 to 2 Gy) the dose-response relationship, with respect to the share of binuclear cells with micronuclei and the frequency of micronuclei in binuclear cells, was of a multiphase nature with a more or less manifest plateau within the dose-range from 0.5 to 1.0 Gy. Both micronuclear tests may be used for indicating the degree of radiation injury to the organism caused by neutrons of the above-mentioned energy and doses of 0.05-0.5 Gy. PMID:1887010

  12. Quantitative aspects of informed consent: considering the dose response curve when estimating quantity of information

    OpenAIRE

    Lynoe, N.; Hoeyer, K.

    2005-01-01

    Information is usually supposed to be a prerequisite for people making decisions on whether or not to participate in a clinical trial. Previously conducted studies and research ethics scandals indicate that participants have sometimes lacked important pieces of information. Over the past few decades the quantity of information believed to be adequate has increased significantly, and in some instances a new maxim seems to be in place: the more information, the better the ethics in terms of res...

  13. Dose-Responsive Gene Expression Changes in Juvenile and Adult Mummichogs (Fundulus heteroclitus) After Arsenic Exposure

    OpenAIRE

    2010-01-01

    Abstract The present study investigated arsenic's effects on mummichogs (Fundulus heteroclitus), while also examining what role that gender or exposure age might play. Adult male and female mummichogs were exposed to 172ppb, 575ppb, or 1,720ppb arsenic as sodium arsenite for 10 days immediately prior to spawning. No differences were noted in the number or viability of eggs between the groups, but there was a significant increase in deformities in 1,720ppb arsenic exposure group. To...

  14. Dose-response studies of depletion and repopulation of rat intestinal mucosal mast cells after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sedgwick, D.M.; Ferguson, A. (Western General Hospital, Edinburgh (United Kingdom))

    1994-04-01

    The effects of radiation on gut mucosal mast cells (MMC) and tissue eosinophils were examined. Groups of rats were given single doses of whole-body irradiation from 0.5 to 5 Gy. Serum rat mast cell protease II (RMCPII) concentration showed a significant dose-dependent fall after 1 Gy on day 3 and 1.5 Gy on day 7. MMC counts and tissue RMCPII values on day 7 decreased significantly by 70% after 1 Gy and were undetectable with larger doses. Rats with normal and expanded MMC populations were irradiated or given anaphylaxis. Serum RMCPII concentrations did not change after irradiation, but there was a 10-fold increase in RMCPII after anaphylaxis. Tissue eosinophils in jejunum were 50% of control at 7 days after 2 Gy, and this effect was progressively more marked with higher doses. Similar effects on MMC and eosinophils were demonstrated in ileum, ascending colon and rectum. After 4.5 Gy, repopulation of the gut with MMC did not occur until week 3-4 postirradiation and MMC counts were still 50% below those of controls at 5 weeks postirradiation. Counts of tisse eosinophils 5 weeks after 4.5 Gy irradiation had returned to control levels in jejunum but were still significantly depleted in colon. (Author).

  15. Dose-response studies of depletion and repopulation of rat intestinal mucosal mast cells after irradiation

    International Nuclear Information System (INIS)

    The effects of radiation on gut mucosal mast cells (MMC) and tissue eosinophils were examined. Groups of rats were given single doses of whole-body irradiation from 0.5 to 5 Gy. Serum rat mast cell protease II (RMCPII) concentration showed a significant dose-dependent fall after 1 Gy on day 3 and 1.5 Gy on day 7. MMC counts and tissue RMCPII values on day 7 decreased significantly by 70% after 1 Gy and were undetectable with larger doses. Rats with normal and expanded MMC populations were irradiated or given anaphylaxis. Serum RMCPII concentrations did not change after irradiation, but there was a 10-fold increase in RMCPII after anaphylaxis. Tissue eosinophils in jejunum were 50% of control at 7 days after 2 Gy, and this effect was progressively more marked with higher doses. Similar effects on MMC and eosinophils were demonstrated in ileum, ascending colon and rectum. After 4.5 Gy, repopulation of the gut with MMC did not occur until week 3-4 postirradiation and MMC counts were still 50% below those of controls at 5 weeks postirradiation. Counts of tisse eosinophils 5 weeks after 4.5 Gy irradiation had returned to control levels in jejunum but were still significantly depleted in colon. (Author)

  16. Prenatal irradiation and spatial memory in mice: investigation of dose-response relationship

    International Nuclear Information System (INIS)

    Pregnant CD1 mice were exposed on gestational day 18 to 250 kV X-rays at 0.1, 0.25, 0.35 and 0.5 Gy. The performances of 10 adult male offspring from each exposure condition were investigated on a spatial discrimination learning task in a radial arm maze. An impairment in the performance of this task was found which showed a correlation with dose. Compared with sham exposed control mice, performance was not significantly affected with irradiation at 0.1 Gy and was slightly but non-significantly reduced at 0.25 Gy. Irradiation at 0.35 Gy caused a significant impairment in performance, and exposure at 0.5 Gy resulted in a still larger impairment. The overall association between dose and behavioural impairment was best described by a linear relationship without a threshold, although at doses lower than about 0.25 Gy any impairment would appear to be too small to be detectable. (Author)

  17. Dose-response relationship of sertindole and haloperidol using the pharmacopsychometric triangle

    DEFF Research Database (Denmark)

    Bech, P; TanghØj, P

    2011-01-01

    Objective: Renewed insight into dose-related effects of sertindole and haloperidol was sought by re-analysing published data for antipsychotic effect, extrapyramidal effect, and patient wellbeing – i.e., the important pharmacopsychometric triangle domains. Method: Selected Positive and Negative Syndrome Scale (PANSS) subscales and the Simpson–Angus scale were tested for validity. Standardized effect sizes [last observation carried forward (LOCF)] at endpoint were calculated. Results: The scales were found to be valid instruments. The PANSS11 psychotic subscale showed clinically significant effect sizes for all doses of sertindole (12, 20, and 24 mg) and haloperidol (4, 8, and 16 mg). Extrapyramidal effects were evident for all doses of haloperidol, but absent for the lower doses of sertindole. The PANSS6 depression subscale, a proxy measure of quality of life, showed a clinically significant effect for sertindole 20 mg and no effect for haloperidol. Conclusion: This re-analysis confirmed the antipsychotic effect and absence of extrapyramidal effects for sertindole and, in addition, showed a clinically significant antidepressant effect. A profile for bipolar states emerged.

  18. A dose-response relationship between exposure to a large-scale HIV preventive intervention and consistent condom use with different sexual partners of female sex workers in southern India

    Directory of Open Access Journals (Sweden)

    Deering Kathleen N

    2011-12-01

    Full Text Available Abstract Background The Avahan Initiative, a large-scale HIV preventive intervention targeted to high-risk populations including female sex workers (FSWs, was initiated in 2003 in six high-prevalence states in India, including Karnataka. This study assessed if intervention exposure was associated with condom use with FSWs’ sexual partners, including a dose-response relationship. Methods Data were from a cross-sectional study (2006-07 of 775 FSWs in three districts in Karnataka. Survey methods accounted for the complex cluster sampling design. Bivariate and multivariable logistic regression was used to separately model the relationships between each of five intervention exposure variables and five outcomes for consistent condom use (CCU= always versus frequently/sometimes/never with different sex partners, including with: all clients; occasional clients; most recent repeat client; most recent non-paying partner; and the husband or cohabiting partner. Linear tests for trends were conducted for three continuous intervention exposure variables. Results FSWs reported highest CCU with all clients (81.7%; CCU was lowest with FSWs’ husband or cohabiting partner (9.6%. In multivariable analysis, the odds of CCU with all clients and with occasional clients were 6.3-fold [95% confidence intervals, CIs: 2.8-14.5] and 2.3-fold [95% CIs: 1.4-4.1] higher among FSWs contacted by intervention staff and 4.9-fold [95% CIs: 2.6-9.3] and 2.3-fold [95% CIs: 1.3-4.1] higher among those who ever observed a condom demonstration by staff, respectively, compared to those who had not. A significant dose-response relationship existed between each of these CCU outcomes and increased duration since first contacted by staff (P=0.001; P=0.006 and numbers of condom demonstrations witnessed (P=0.004; P=0.026; a dose-response relationship was also observed between condom use with all clients and number of times contacted by staff (P=0.047. Intervention exposure was not associated with higher odds of CCU with the most recent repeat client, most recent non-paying partner or with the husband or cohabiting partner. Conclusion Study findings suggest that exposure to a large-scale HIV intervention for FSWs was associated with increased CCU with commercial clients. Moreover, there were dose-response relationships between CCU with clients and increased duration since first contacted by staff, times contacted by staff and number of condom demonstrations. Additional program effort is required to increase condom use with non-commercial partners.

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

    Science.gov (United States)

    Malin, Steven K; Solomon, Thomas P J; Blaszczak, Alecia; Finnegan, Stephen; Filion, Julianne; Kirwan, John P

    2013-11-15

    Although some studies suggest that a linear dose-response relationship exists between exercise and insulin sensitivity, the exercise dose required to enhance pancreatic ?-cell function is unknown. Thirty-five older obese adults with prediabetes underwent a progressive 12-wk supervised exercise intervention (5 days/wk for 60 min at ~85% HRmax). Insulin and C-peptide responses to an OGTT were used to define the first- and second-phase disposition index (DI; ?-cell function = glucose-stimulated insulin secretion × clamp-derived insulin sensitivity). Maximum oxygen consumption (Vo2max) and body composition (dual-energy X-ray absorptiometry and computed tomography) were also measured before and after the intervention. Exercise dose was computed using Vo2/heart-rate derived linear regression equations. Subjects expended 474.5 ± 8.8 kcal/session (2,372.5 ± 44.1 kcal/wk) during the intervention and lost ~8% body weight. Exercise increased first- and second-phase DI (P dose (DIfirst phase: r = 0.54, P Enhanced DI was also associated with increased Vo2max (DIfirst phase: r = 0.36, P = 0.04; DIsecond phase: r = 0.41, P Low baseline DI predicted an increase in DI after the intervention (DIfirst phase: r = -0.37; DIsecond phase: r = -0.41, each P dose-response manner in adults with prediabetes. Our data suggest that higher exercise doses (i.e., >2,000 kcal/wk) are necessary to enhance ?-cell function in adults with poor insulin secretion capacity. PMID:24045867

  20. Dose-Response Analysis of Factors Involved in Germination and Secondary Dormancy of Seeds of Sisymbrium officinale

    Science.gov (United States)

    Hilhorst, Henk W. M.

    1990-01-01

    The role of nitrate as a promoter of germination of Sisymbrium officinale seeds was examined in optimal light conditions. It was shown that the requirement for nitrate was absolute. This was true for all seed lots used. The probit of germination in water was log-linearly related to the level of endogenous nitrate. Preincubation at 15°C resulted in an immediate decrease in germination, whereas in 25 millimolar KNO3 the decrease was delayed. The decline of germination in water was strongly correlated with the rate at which nitrate leached from the seeds. The germination response to a range of KNO3 concentrations was followed during preincubation at 24-hour intervals. During the entire 264-hour preincubation period increasingly higher nitrate concentrations were required to maintain a response. This resulted in a right-hand shift of the dose-response curve parallel to the x axis. After 120 hours the high maximum germination level started to decline. The dose-response curves could be simulated by an equation from the receptor-occupancy theory. It is proposed that induction of secondary dormancy is a result of a decrease of the number of nitrate receptors. After 24 and 48 hours of preincubation, the nitrate-response curves were biphasic. The biphasic character could be related to the level of endogenous nitrate and to a differential requirement for nitrate of two fractions of the seed population. Similarities with the behavior of fluence-response curves after prolonged dark incubation led to the hypothesis that phytochrome and nitrate share the same site of action. PMID:16667802

  1. Dose-Response Analysis of Factors Involved in Germination and Secondary Dormancy of Seeds of Sisymbrium officinale: II. Nitrate.

    Science.gov (United States)

    Hilhorst, H W

    1990-11-01

    The role of nitrate as a promoter of germination of Sisymbrium officinale seeds was examined in optimal light conditions. It was shown that the requirement for nitrate was absolute. This was true for all seed lots used. The probit of germination in water was log-linearly related to the level of endogenous nitrate. Preincubation at 15 degrees C resulted in an immediate decrease in germination, whereas in 25 millimolar KNO(3) the decrease was delayed. The decline of germination in water was strongly correlated with the rate at which nitrate leached from the seeds. The germination response to a range of KNO(3) concentrations was followed during preincubation at 24-hour intervals. During the entire 264-hour preincubation period increasingly higher nitrate concentrations were required to maintain a response. This resulted in a right-hand shift of the dose-response curve parallel to the x axis. After 120 hours the high maximum germination level started to decline. The dose-response curves could be simulated by an equation from the receptor-occupancy theory. It is proposed that induction of secondary dormancy is a result of a decrease of the number of nitrate receptors. After 24 and 48 hours of preincubation, the nitrate-response curves were biphasic. The biphasic character could be related to the level of endogenous nitrate and to a differential requirement for nitrate of two fractions of the seed population. Similarities with the behavior of fluence-response curves after prolonged dark incubation led to the hypothesis that phytochrome and nitrate share the same site of action. PMID:16667802

  2. Dose--response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions

    Science.gov (United States)

    Kawata, T.; Durante, M.; Furusawa, Y.; George, K.; Takai, N.; Wu, H.; Cucinotta, F. A.; Dicello, J. F. (Principal Investigator)

    2001-01-01

    PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2 chromosomes following exposure to heavy ions of different LET. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55 keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions. Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type and isochromatid breaks in G2 cells were scored. RESULTS: The dose response curves for total chromatid breaks were linear regardless of radiation type. The relative biological effectiveness (RBE) showed a LET-dependent increase, peaking around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response curves for isochromatid-type breaks were linear for high-LET radiations, but linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the induction of isochromatid breaks obtained from linear components increased rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High-LET radiations are more effective at inducing isochromatid breaks, while low-LET radiations are more effective at inducing chromatid-type breaks. The densely ionizing track structures of heavy ions and the proximity of sister chromatids in G2 cells result in an increase in isochromatid breaks.

  3. Dose-response relationships for neostigmine antagonism of rocuronium-induced neuromuscular block in children and adults.

    Science.gov (United States)

    Abdulatif, M; Mowafi, H; al-Ghamdi, A; el-Sanabary, M

    1996-12-01

    Dose-response relationships for the antagonism of intermediate-acting neuromuscular blocking agents have not been evaluated previously in children. We have examined the dose-response relationships for neostigmine antagonism of 90% rocuronium-induced neuromuscular block in children and adults, during nitrous oxide-1 MAC of isoflurane anaesthesia. We studied 40 children, aged 2-10 yr, and 50 adults, aged 18-60 yr; all received a single bolus dose of rocuronium 0.6 mg kg-1 and accelerometry was used to monitor neuromuscular transmission. When the first twitch of the train-of-four (TOF) response (T1) recovered to 10% of its control (T0), one of five doses of neostigmine 0, 5, 10, 20 or 50 micrograms kg-1 was given by random allocation to each of the study groups (n = 8 children and n = 10 adults). Recovery of T1 and TOF ratio (T4/T1%) was recorded for 10 min after initial administration of neostigmine. Onset time of rocuronium-induced block was faster in children than in adults (mean 64.6 (95% confidence intervals 57.7-71.5) s vs 83.7 (70.7-96.6) s; P more rapid in children than in adults. Adequate recovery (T4/T1 of 80%) occurred in children at 4, 5 and 8 min after neostigmine 50, 20 and 10 micrograms kg-1, respectively. Adequate recovery was not produced in adults by any dose of neostigmine within 10 min. The effective doses of neostigmine required to achieve a TOF ratio of 80% (ED80) after 10 min in children and adults were, respectively, 7.10 (5.2-9.8) micrograms kg-1 and 56.56 (45.5-71.9) micrograms kg-1 (P more for adequate antagonism of a similar degree of block in adults. PMID:9014620

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

    International Nuclear Information System (INIS)

    There is increasing concern about airline crew members (about one million worldwide) are exposed to measurable neutrons doses. Historically, cytogenetic biodosimetry assays have been based on quantifying asymmetrical chromosome alterations (dicentrics, centric rings and acentric fragments) in mytogen-stimulated T-lymphocytes in their first mitosis after radiation exposure. Increased levels of chromosome damage in peripheral blood lymphocytes are a sensitive indicator of radiation exposure and they are routinely exploited for assessing radiation absorbed dose after accidental or occupational exposure. Since radiological accidents are not common, not all nations feel that it is economically justified to maintain biodosimetry competence. However, dependable access to biological dosimetry capabilities is completely critical in event of an accident. In this paper the dose-response curve was measured for the induction of chromosomal alterations in peripheral blood lymphocytes after chronic exposure in vitro to neutron-gamma mixes field. Blood was obtained from one healthy donor and exposed to two neutron-gamma mixed field from sources 241AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The evaluated absorbed doses were 0.2 Gy; 1.0 Gy and 2.5 Gy. The dicentric chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphase figures were analyzed for the presence of dicentrics by two experienced scorers after painted by giemsa 5%. Our preliminary results showed a linear dependence between radiations absorbed dose and dicentric chromosomes frequencies. Dose-response curve described in this paper will contribute to the construction of calibration curve that will be used in our laboratory for biological dosimetry. (author)

  5. Comparison of dose-responses of contact allergens using the guinea pig maximization test and the local lymph node assay.

    Science.gov (United States)

    van Och, F M; Vandebriel, R J; Prinsen, M K; De Jong, W H; Slob, W; van Loveren, H

    2001-10-30

    The guinea pig maximization test (GPMT) has been used as a method for the prediction of skin sensitizing potential for over 30 years. Besides hazard identification, risk assessment of sensitizing chemicals requires the assessment of potency. For the determination of potency based on lowest effective dose levels, dose-response studies are required. In the standard GPMT a single concentration is used for intracutaneous and topical induction and the assay provides a qualitative assessment of allergenicity. This paper presents data derived from quantitative evaluation of the sensitizing potency of chemicals in the GPMT, based on multiple concentrations. We performed the GPMT in accordance with the original procedure of Magnusson and Kligman; and included in this procedure a range of intradermal and topical concentrations for induction. Three allergens with different sensitizing potencies, diethylamine (DEA), tetramethyl thiuram disulfide (TMTD) and zinc dimethyl dithiocarbamate (ZDMC) were tested. The data obtained with this test procedure were compared to data we previously obtained using the local lymph node assay (LLNA). Both the GPMT and the LLNA showed dose response relationships for the three chemicals tested. For the chemicals tested, both tests differed in the relative potencies based on benchmark concentrations. While both tests ranked DEA as the least potent allergen, the GPMT ranked ZDMC more potent than TMTD, the reverse being found in the LLNA. The nature of the data provided in the LLNA makes it likely that benchmarks as defined with this test are more reliable than that defined in the GPMT. However, further validation with human data is necessary. PMID:11578800

  6. Assessing the Statistical Significance of the Achieved Classification Error of Classifiers Constructed using Serum Peptide Profiles, and a Prescription for Random Sampling Repeated Studies for Massive High-Throughput Genomic and Proteomic Studies

    Science.gov (United States)

    Lyons-Weiler, James; Pelikan, Richard; Zeh, Herbert J; Whitcomb, David C; Malehorn, David E; Bigbee, William L; Hauskrecht, Milos

    2007-01-01

    Peptide profiles generated using SELDI/MALDI time of flight mass spectrometry provide a promising source of patient-specific information with high potential impact on the early detection and classification of cancer and other diseases. The new profiling technology comes, however, with numerous challenges and concerns. Particularly important are concerns of reproducibility of classification results and their significance. In this work we describe a computational validation framework, called PACE (Permutation-Achieved Classification Error), that lets us assess, for a given classification model, the significance of the Achieved Classification Error (ACE) on the profile data. The framework compares the performance statistic of the classifier on true data samples and checks if these are consistent with the behavior of the classifier on the same data with randomly reassigned class labels. A statistically significant ACE increases our belief that a discriminative signal was found in the data. The advantage of PACE analysis is that it can be easily combined with any classification model and is relatively easy to interpret. PACE analysis does not protect researchers against confounding in the experimental design, or other sources of systematic or random error. We use PACE analysis to assess significance of classification results we have achieved on a number of published data sets. The results show that many of these datasets indeed possess a signal that leads to a statistically significant ACE. PMID:19305632

  7. Dose-response studies with biosynthetic human growth hormone (GH) in GH-deficient patients

    DEFF Research Database (Denmark)

    JØrgensen, J O; Flyvbjerg, A

    1988-01-01

    Increasing doses of biosynthetic human GH (R-hGH) were given sc to seven GH-deficient patients for three consecutive 14-day periods (2, 4, and 6 IU/day at 2000 h), followed by 14 days of no GH therapy. At the end of each period each patient was hospitalized for frequent blood sampling from 2000 to 1100 h the following day. A dose-dependent increase in serum GH and serum insulin-like growth factor I (IGF-I) levels occurred. However, the time course of the serum IGF-I concentrations was different on the four occasions; there was a significant fall in the evening when no therapy was given (P less than 0.01), a significant increase after injections of 2 IU R-hGH, and constant levels during treatment with 4 and 6 IU R-hGH. Plasma glucose levels were within the normal range, with a significantly lower fasting level (at 0400 h) when no GH was given. Breakfast induced a plasma glucose rise when GH was administered, but no rise without GH, and a postprandial serum insulin response that was GH dose dependent. GH therapy increased serum FFA (P less than 0.05) and blood 3-hydroxybutyrate levels, but had no effect on blood alanine or lactate or serum triglyceride and cholesterol levels. We conclude that the serum IGF-I response to GH is dose dependent, and that a GH replacement dose of 2 IU/day (equalling 1.5 IU/m2.day) is insufficient to maintain normal diurnal serum IGF-I levels. Furthermore, a GH-independent diurnal variation in serum IGF-I in these patients is suggested. This GH preparation also has diabetogenic and lipolytic actions.

  8. Dose-response relationship and dose optimization in radiotherapy of postoperative keloids

    International Nuclear Information System (INIS)

    Background and purpose: The treatment dose and fractionation dose that are considered in postoperative keloids had been reported in the previous studies. We performed retrospective analysis to elucidate the factors influencing the treatment outcome. Materials and methods: From 1979 to 1994, 194 lesions in 119 patients received postoperative radiotherapy after excision with the total dose ranging from 16 Gy/8 fr to 40 Gy/8 fr (mean: biologically effective dose (BED) 33.5 Gy). Kilo-voltage X-rays (55 or 100 kVp) or electron beams (4 or 6 MeV), including entire keloid scars, and any suture/puncture holes with a margin around the lesion were used. The median follow-up period was 36 months (range 12-164 months). Results: Symptomatic pain and itching relief were achieved in 96% and 91%, respectively. The relapse rate was 11% at 20 Gy in five fractions or higher dose, while 43% at less than 20 Gy. On the other hand, the incidence of adverse effects was significantly higher for patients receiving more than 20 Gy in five fractions. Conclusion: There was a significant correlation between the relapse rate and the total dose of irradiation, and between adverse effects and the total dose. To correlate local control and adverse effects, we proposed 20 Gy in five fractions as the optimal dose for the postoperative of keloids. A significant correlation between relapse rate and the interval time between excision and radiotherapy was not found in our current study.in our current study.

  9. From Bayes through Marginal Utility to Effect Sizes: A Guide to Understanding the Clinical and Statistical Significance of the Results of Autism Research Findings

    Science.gov (United States)

    Cicchetti, Domenic V.; Koenig, Kathy; Klin, Ami; Volkmar, Fred R.; Paul, Rhea; Sparrow, Sara

    2011-01-01

    The objectives of this report are: (a) to trace the theoretical roots of the concept clinical significance that derives from Bayesian thinking, Marginal Utility/Diminishing Returns in Economics, and the "just noticeable difference", in Psychophysics. These concepts then translated into: Effect Size (ES), strength of agreement, clinical…

  10. Dose Response Of TLDs AT Energy And Dose Ranges Applied In Clinical Radiology

    International Nuclear Information System (INIS)

    The study aimed to investigate the performance of lithium fluoride thermoluminescent dosimeters (TLD-700) to photon beams applied in clinical radiology in energy range 75 KVp to 15 MV at variable dose ranges. The study extended to evaluate the implication of sorting multiple crystals per reading on its response. Annealing and TL reading procedures were done using thermolyne furnace and Victoreen reader, respectively. Irradiation at 75 KVp X-rays was done using Philips PC 2000 diagnostic machine and Philips SLS-9 fluoroscopic RT-Simulator. Theratron 780 C, Co-60 machine, was used as a reference gamma ray beam as well as Philips SL-75 and Elekta Precise TM linear accelerators were used for irradiations at 6 and 15 MV X-rays, respectively. Perspex phantom (PMMA) was used as a medium of TLD-irradiation and 0.6 cc farmer chamber with PTW electrometer were used for the purposes of output dose rate measurements. Several experiments of irradiation and measurement were performed to evaluate the sensitivity, reproducibility, energy response and linearity of TLDs. The implication of sorting multiple crystals per data point was investigated in comparison with individual crystal measurements.TLD-700 employed in this study was selected in such a way that its sensitivity did not differ by more than ± 5% of the average. The selected crystals exhibit good homogeneity with relative sensitivity ranged between 0.99 and 1.00 and acceptable stability range9 and 1.00 and acceptable stability ranged between 3.36 and 4.42% over 5 reuse cycles of irradiation and measurements at Co-60 gamma rays. Non-significant variations were found in TLD responses at photon energy ranging 75 KVp to 15 MV. The TLDs showed good linearity over dose range 0.2-4 cGy at 75 KVp and 1-1100 cGy for Co-60 gamma rays as well as 6 and 15 MV for X-rays. The results of measuring multiple crystals per TL reading showed good linearity of TLD response with the number of sorted crystals ranged 1-8 crystals. Non-significant difference was recorded in TLD sensitivity of individual and three sorted crystals over energy range employed in this study.The results showed that TLD-700 had high sensitivity, good reproducibility, wide range linearity and non-significant variation in response over a range of energies typically used in clinical investigations. Sorting multiple crystals up to 8 per TL readout didn't affect the performance attainable with TLD-700 and exhibited good linearity with the number of crystals per reading. This sorting technique provides a simple, convenient, precise and accurate method for TLD measurements.

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

    International Nuclear Information System (INIS)

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

  12. Dose–response analysis of phthalate effects on gene expression in rat whole embryo culture

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Joshua F. [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Verhoef, Aart; Beelen, Vincent A. van; Pennings, Jeroen L.A. [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Piersma, Aldert H., E-mail: aldert.piersma@rivm.nl [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht (Netherlands)

    2012-10-01

    The rat postimplantation whole embryo culture (WEC) model serves as a potential screening tool for developmental toxicity. In this model, cultured rat embryos are exposed during early embryogenesis and evaluated for morphological effects. The integration of molecular-based markers may lead to improved objectivity, sensitivity and predictability of WEC in assessing developmental toxic properties of compounds. In this study, we investigated the concentration-dependent effects of two phthalates differing in potency, mono(2-ethylhexyl) phthalate (MEHP) and monomethyl phthalate (MMP, less toxic), on the transcriptome in WEC to examine gene expression in relation with dysmorphogenesis. MEHP was more potent than MMP in inducing gene expression changes as well as changes on morphology. MEHP induced significant enrichment of cholesterol/lipid/steroid (CLS) metabolism and apoptosis pathways which was associated with developmental toxicity. Regulation of genes within CLS metabolism pathways represented the most sensitive markers of MEHP exposure, more sensitive than classical morphological endpoints. As shown in direct comparisons with toxicogenomic in vivo studies, alterations in the regulation of CLS metabolism pathways has been previously identified to be associated with developmental toxicity due to phthalate exposure in utero. Our results support the application of WEC as a model to examine relative phthalate potency through gene expression and morphological responses. Additionally, our results further define the applicability domain of the WEC model for developmental toxicological investigations. -- Highlights: ? We examine the effect of two phthalates on gene expression and morphology in WEC. ? MEHP is more potent than MMP in inducing gene expression changes and dysmorphogenesis. ? MEHP significantly disrupts cholesterol metabolism pathways in a dose-dependent manner. ? Specific phthalate-related mechanisms in WEC are relevant to mechanisms in vivo.

  13. Dose–response analysis of phthalate effects on gene expression in rat whole embryo culture

    International Nuclear Information System (INIS)

    The rat postimplantation whole embryo culture (WEC) model serves as a potential screening tool for developmental toxicity. In this model, cultured rat embryos are exposed during early embryogenesis and evaluated for morphological effects. The integration of molecular-based markers may lead to improved objectivity, sensitivity and predictability of WEC in assessing developmental toxic properties of compounds. In this study, we investigated the concentration-dependent effects of two phthalates differing in potency, mono(2-ethylhexyl) phthalate (MEHP) and monomethyl phthalate (MMP, less toxic), on the transcriptome in WEC to examine gene expression in relation with dysmorphogenesis. MEHP was more potent than MMP in inducing gene expression changes as well as changes on morphology. MEHP induced significant enrichment of cholesterol/lipid/steroid (CLS) metabolism and apoptosis pathways which was associated with developmental toxicity. Regulation of genes within CLS metabolism pathways represented the most sensitive markers of MEHP exposure, more sensitive than classical morphological endpoints. As shown in direct comparisons with toxicogenomic in vivo studies, alterations in the regulation of CLS metabolism pathways has been previously identified to be associated with developmental toxicity due to phthalate exposure in utero. Our results support the application of WEC as a model to examine relative phthalate potency through gene expression and morphological responses. Additionally, our results further define the applicability domain of the WEC model for developmental toxicological investigations. -- Highlights: ? We examine the effect of two phthalates on gene expression and morphology in WEC. ? MEHP is more potent than MMP in inducing gene expression changes and dysmorphogenesis. ? MEHP significantly disrupts cholesterol metabolism pathways in a dose-dependent manner. ? Specific phthalate-related mechanisms in WEC are relevant to mechanisms in vivo.

  14. The High Dose Response and Functional Capability of the DT-702/Pd Lithium fluoride Thermoluminescent Dosimeter.

    Science.gov (United States)

    Lawlor, Tyler M; Talmadge, Molly D; Murray, Mark M; Nelson, Martin E; Mueller, Andrew C; Romanyukha, Alexander A; Fairchild, Gregory R; Grypp, Matthew D; Williams, Anthony S

    2015-05-01

    The United States Navy monitors the dose its radiation workers receive using the DT-702/PD thermoluminescent dosimeter, which consists of the Harshaw 8840 holder and the four-element Harshaw 8841 card. There were two main objectives of this research. In the first objective, the dosimeters were exposed to 100 Gy using electron and x-ray beams and found to respond approximately 30-40% lower than the delivered dose. No significant effect on the under-response was found when dose rate, radiation type, dosimeter position on the phantom, and dosimeter material were varied or when the card was irradiated while enclosed in its holder. Since the current naval policy is to remove from occupational use any thermoluminescent dosimeter with an accumulated deep dose equivalent of 0.05 Sv or greater, the functionality of the dosimeter was also investigated at deep dose equivalents of 0.05, 0.15, and 0.25 Sv using Co and Cs sources as the second main objective. All dosimeters were annealed following exposure and then exposed to 5.0 mSv from a Sr source. In all cases, the dosimeters responded within 3% of the delivered dose, indicating that the dosimeters remained functional as defined by naval dosimetry requirements. However, the anneal time required to clear the thermoluminescent dosimeter's reading was found to increase approximately as the cube root with the delivered dose. PMID:25811149

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

    Science.gov (United States)

    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 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 strategies for reducing noise exposure level are required to decrease the risk of occupational injury. PMID:25599757

  16. Dose-response relationships for resetting of human circadian clock by light

    Science.gov (United States)

    Boivin, D. B.; Duffy, J. F.; Kronauer, R. E.; Czeisler, C. A.

    1996-01-01

    Since the first report in unicells, studies across diverse species have demonstrated that light is a powerful synchronizer which resets, in an intensity-dependent manner, endogenous circadian pacemakers. Although it is recognized that bright light (approximately 7,000 to 13,000 lux) is an effective circadian synchronizer in humans, it is widely believed that the human circadian pacemaker is insensitive to ordinary indoor illumination (approximately 50-300 lux). It has been proposed that the relationship between the resetting effect of light and its intensity follows a compressive nonlinear function, such that exposure to lower illuminances still exerts a robust effect. We therefore undertook a series of experiments which support this hypothesis and report here that light of even relatively low intensity (approximately 180 lux) significantly phase-shifts the human circadian pacemaker. Our results clearly demonstrate that humans are much more sensitive to light than initially suspected and support the conclusion that they are not qualitatively different from other mammals in their mechanism of circadian entrainment.

  17. Plastic packaging and burn-in effects on ionizing dose response in CMOS microcircuits

    International Nuclear Information System (INIS)

    Results are reported from an investigation of the effects of packaging and burn-in on the post-irradiation performance of National Semiconductor 54AC02 Quad 2-input NOR gates. The test population was drawn from a single wafer fabricated in the National process qualified under Mil-Prf-38535 to an ionizing radiation hardness of 100 krads(Si). The test sample was divided between plastic and ceramic packages. Additionally, half of the plastic samples and half of the two ceramic samples received a 168 hour/125 C burn-in. Two irradiation schemes were used. The first followed Mil-Std-883 Method 1019.4 (dose rate = 50 rads(Si)/s). The second used a low dose rate (0.1 rads(Si)/s). AC, DC, transfer function and functional behavior were monitored throughout the tests. Significant differences among the package types and burn-in variations were noted with the plastic, burned-in components demonstrating enhanced degradation. They show the worst post-irradiation parameter values as well as very broad post-irradiation parameter distributions. Degradation is highly dependent upon dose rate and anneal conditions. Two different radiation induced leakage paths have been identified, and their characteristics have been correlated to variations in high dose rate and low dose rate circuit performance. Caution is recommended for system developers to ensure that radiation hardness characterization is performed for the same package/burn-in configuration to be used in the system to be used in the system

  18. Dose-Finding when the Target Dose Is on a Plateau of a Dose-Response Curve: Comparison of Fully Sequential Designs

    OpenAIRE

    Ivanova, Anastasia; Xiao, Changfu

    2013-01-01

    Consider the problem of estimating a dose with a certain response rate. Many multistage dose-finding designs for this problem were originally developed for oncology studies where the mean dose-response is strictly increasing in dose. In non-oncology Phase II dose-finding studies the dose-response curve often plateaus in the range of interest and there are several doses with the mean response equal to the target. In this case it is usually of interest to find the lowest of these doses since hi...

  19. The Influence of Trp53 in the Dose Response of Radiation-Induced Apoptosis, DNA Repair and Genomic Stability in Murine Haematopoietic Cells

    OpenAIRE

    Lemon, Jennifer A.; Taylor, Kristina; Verdecchia, Kyle; Phan, Nghi; Boreham, Douglas R.

    2014-01-01

    Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/? mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01–2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic in...

  20. Calcium supplementation and bone mineral accretion in Chinese adolescents aged 12-14 years: a 12-month, dose-response, randomised intervention trial.

    Science.gov (United States)

    Ma, Xiao-ming; Huang, Zhen-wu; Yang, Xiao-guang; Su, Yi-xiang

    2014-11-14

    A 12-month, dose-response, randomised, intervention trial was conducted to determine adequate Ca intake levels for Chinese adolescents by investigating the effect of Ca supplementation on bone mineral accretion. A total of 220 Han adolescents (111 girls and 109 boys) aged 12-14 years were recruited. All subjects were randomly divided into three groups. The bone mineral content (BMC) and bone mineral density (BMD) of the whole body, lumbar spine (L1-L4), left hip and femoral neck were measured by dual-energy X-ray absorptiometry. Girls in the high-Ca group (actual Ca intake: 1243 (sd 193) mg/d) exhibited greater increases in the femoral neck BMC compared with those in the low-Ca group (9·7